Datasets:

developerZoyal

/

full_drugs_data

like 0

{ALCOHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use for hand-washing to decrease bacteria on the skin, only when water is not available"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{ALCOHOL}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if irritation and redness develop"}', 'do_not_use': None, 'when_using': '{"When using this product do not get into eyes. if contact occurs, rinse eyes thoroughly with water"}', 'warnings': '{"Warnings Flammable, keep away from fire or flames For external use only When using this product do not get into eyes. if contact occurs, rinse eyes thoroughly with water Stop use and ask a doctor if irritation and redness develop Keep out of reach of children. if swallowed get medical help or contact a Poison Control Center right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{NICOTINE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use • reduces withdrawal symptoms, including nicotine craving, associated with quitting smoking"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"NICOTINE POLACRILEX"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if • mouth problems occur • persistent indigestion or severe sore throat occurs • irregular heartbeat or palpitations occur • you get symptoms of nicotine overdose such as nausea, vomiting, dizziness, diarrhea, weakness or rapid heartbeat • you have symptoms of an allergic reaction (such as difficulty breathing or rash)"}', 'do_not_use': None, 'when_using': None, 'warnings': '{Warnings}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{CHLOROXYLENOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses For hand washing to decrease bacteria on the skin."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{CHLOROXYLENOL}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings For external use only."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"TRIHEXYPHENIDYL HYDROCHLORIDE"}

{'contraindications': '{"CONTRAINDICATIONS Trihexyphenidyl HCl is contraindicated in patients with hypersensitivity to trihexyphenidyl HCl or to any of the tablet ingredients. Trihexyphenidyl HCl is also contraindicated in patients with narrow angle glaucoma. Blindness after long-term use due to narrow angle glaucoma has been reported."}', 'adverse_reactions': '{"ADVERSE REACTIONS Minor side effects, such as dryness of the mouth, blurred vision, dizziness, mild nausea or nervousness, will be experienced by 30 to 50 percent of all patients. These sensations, however, are much less troublesome with trihexyphenidyl HCl than with belladonna alkaloids and are usually less disturbing than unalleviated parkinsonism. Such reactions tend to become less pronounced, and even to disappear, as treatment continues. Even before these reactions have remitted spontaneously, they may often be controlled by careful adjustment of dosage form, amount of drug, or interval between doses. Isolated instances of suppurative parotitis secondary to excessive dryness of the mouth, skin rashes, dilatation of the colon, paralytic ileus, and certain psychiatric manifestations such as delusions, hallucinations, and paranoia, all of which may occur with any of the atropine-like drugs, have been reported rarely with trihexyphenidyl HCl. Potential side effects associated with the use of any atropine-like drugs, including trihexyphenidyl HCl, include cognitive dysfunctions, including confusion and memory impairment; constipation, drowsiness, urinary hesitancy or retention, tachycardia, dilation of the pupil, increased intraocular pressure, choreiform movements, weakness, vomiting, and headache. Exacerbation of parkinsonism with abrupt treatment withdrawal has been reported. Neuroleptic malignant syndrome with abrupt treatment withdrawal has been reported ( see WARNINGS , Neuroleptic Malignant Syndrome ). The occurrence of angle-closure glaucoma in patients receiving trihexyphenidyl HCl has been reported (blindness has been reported in some cases). Paradoxical sinus bradycardia, dry skin, and cycloplegia have been reported. In addition to adverse events seen in adults, the following adverse events have been reported in the literature in pediatric patients: hyperkinesia, psychosis, forgetfulness, weight loss, restlessness, chorea, and sleep alterations."}', 'drug_interactions': '{"Drug Interactions Cannabinoids, barbiturates, opiates, and alcohol may have additive effects with trihexyphenidyl HCl, and thus, an abuse potential exists. Concurrent use of alcohol or other CNS depressants with trihexyphenidyl HCl may cause increased sedative effects. Monoamine oxidase inhibitors and tricyclic antidepressants possessing significant anticholinergic activity may intensify the anticholinergic effects of antidyskinetic agents because of the secondary anticholinergic activities of these medications. Prophylactic administration of anticholinergic agents, such as trihexyphenidyl, as a prevention of drug-induced parkinsonism during neuroleptic therapy is not recommended. There may be an increased risk for the development of tardive dyskinesia during concomitant administration of anticholinergics and neuroleptics ( see PRECAUTIONS , General ) . The usual dose of either trihexyphenidyl or levodopa may need to be reduced during concomitant therapy, since concomitant administration may increase drug-induced involuntary movements ( see DOSAGE AND ADMINISTRATION )."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Trihexyphenidyl HCl is indicated as an adjunct in the treatment of all forms of parkinsonism (postencephalitic, arteriosclerotic, and idiopathic). It is often useful as adjuvant therapy when treating these forms of parkinsonism with levodopa. Additionally, it is indicated for the control of extrapyramidal disorders caused by central nervous system drugs such as the dibenzoxazepines, phenothiazines, thioxanthenes, and butyrophenones."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE The mean oral LD50 of trihexyphenidyl HCl has been reported to be 365 mg/kg (range, 325 to 410 mg/kg) in mice and 1660 mg/kg (1420 to 1940 mg/kg) in rats. At a dose of 40 mg/kg, dogs have exhibited emesis, restlessness followed by drowsiness, equilibrium disturbances, and mydriasis. In humans, doses up to 300 mg (5 mg/kg) have been ingested without fatalities or sequelae. However, rare cases of death associated with trihexyphenidyl overdosages taken in conjunction with other CNS-depressant agents have been reported or in patients with a compromised respiratory condition. Trihexyphenidyl blood concentrations associated with the fatalities ranged from 0.03 to 0.80 mg/l. Signs and Symptoms Overdosage with trihexyphenidyl HCl produces typical central symptoms of atropine intoxication (the central anticholinergic syndrome). Correct diagnosis depends upon recognition of the peripheral signs of parasympathetic blockade, including dilated and sluggish pupils; warm, dry skin; facial flushing; decreased secretions of the mouth, pharynx, nose, and bronchi; foul-smelling breath; elevated temperature; tachycardia, cardiac arrhythmias; decreased bowel sounds; and urinary retention. Neuropsychiatric signs such as delirium, disorientation, anxiety, hallucinations, illusions, confusion, incoherence, agitation, hyperactivity, ataxia, lip smacking and tasting movements, loss of memory, paranoia, combativeness, and seizures may be present. The condition can progress to stupor, coma, paralysis, cardiac and respiratory arrest, and death. Treatment Treatment of acute overdose involves symptomatic and supportive therapy. Gastric lavage or other methods to limit absorption should be instituted. A small dose of diazepam or a short- acting barbiturate may be administered if CNS excitation is observed. Phenothiazines are contraindicated because the toxicity may be intensified due to their antimuscarinic action, causing coma. Respiratory support, artificial respiration or vasopressor agents may be necessary. Hyperpyrexia must be reversed, fluid volume replaced and acid-balance maintained. Urinary catheterization may be necessary. It is not known if trihexyphenidyl HCl is dialyzable."}', 'active_flag': 'Y', 'generic_name': '{"TRIHEXYPHENIDYL HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Patients to be treated with trihexyphenidyl HCl should have a gonioscope evaluation prior to initiation of therapy and close monitoring of intraocular pressures. The use of anticholinergic drugs may precipitate angle closure with an increase in intraocular pressure. If blurring of vision occurs during therapy, the possibility of narrow angle glaucoma should be considered. Blindness has been reported due to aggravation of narrow angle glaucoma (see CONTRAINDICATIONS and ADVERSE REACTIONS ). Trihexyphenidyl HCl should be administered with caution in hot weather, especially when given concomitantly with other atropine-like drugs to the chronically ill, alcoholics, those who have central nervous system disease, or those who do manual labor in a hot environment. Anhidrosis may occur more readily when some disturbance of sweating already exists. If there is evidence of anhidrosis, the possibility of hyperthermia should be considered. Dosage should be decreased so that the ability to maintain body heat equilibrium via perspiration is not impaired. Severe anhidrosis and fatal hyperthermia have occurred with the use of anticholinergics under the conditions described above. Neuroleptic Malignant Syndrome A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with dose reduction or discontinuation of trihexyphenidyl. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmias). The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (eg, pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system (CNS) pathology."}', 'precautions': '{"PRECAUTIONS General Patients with cardiac, liver, or kidney disorders, or with hypertension, should be closely monitored. Since trihexyphenidyl HCl has atropine-like properties, patients on long-term treatment should be carefully monitored for untoward reactions. Since trihexyphenidyl HCl has parasympatholytic activity, it should be used with caution in patients with glaucoma, obstructive disease of the gastrointestinal or genitourinary tracts, and in elderly males with possible prostatic hypertrophy. Incipient glaucoma may be precipitated by parasympatholytic drugs such as trihexyphenidyl HCl. Tardive dyskinesia may appear in some patients on long-term therapy with antipsychotic drugs or may occur after therapy with these drugs has been discontinued. Antiparkinsonism agents do not alleviate the symptoms of tardive dyskinesia, and in some instances may aggravate them. However, parkinsonism and tardive dyskinesia often coexist in patients receiving chronic neuroleptic treatment, and anticholinergic therapy with trihexyphenidyl HCl may relieve some of these parkinsonism symptoms. Trihexyphenidyl HCl is not recommended for use in patients with tardive dyskinesia unless they have concomitant Parkinson\'s disease. Patients with arteriosclerosis or with a history of idiosyncrasy to other drugs may exhibit reactions of mental confusion, agitation, disturbed behavior, or nausea and vomiting. Such patients should be allowed to develop a tolerance through the initial administration of a small dose and gradual increase in dose until an effective level is reached. If a severe reaction should occur, administration of the drug should be discontinued for a few days and then resumed at a lower dosage. Psychiatric disturbances can result from indiscriminate use (leading to overdosage) to sustain continued euphoria. ( See DRUG ABUSE AND DEPENDENCE .) Abrupt withdrawal of treatment for parkinsonism may result in acute exacerbation of parkinsonism symptoms; therefore, abrupt withdrawal should be avoided ( see DOSAGE AND ADMINISTRATION ). Information for Patients Trihexyphenidyl HCl may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle. Patients should be cautioned about operating machinery, including automobiles, until they are reasonably certain that trihexyphenidyl HCl therapy does not adversely affect their ability to engage in such activities. Because of increased sedative effects, patients should be cautioned to avoid the use of alcohol or other CNS depressants while taking trihexyphenidyl HCl. Since this medication may increase the susceptibility to heat stroke (gastrointestinal (GI) problems, fever, heat intolerance), use with caution during hot weather. ( See WARNINGS .) Patients should be advised to report the occurrence of Gl problems, fever, or heat intolerance promptly since paralytic ileus, hyperthermia, or heat stroke may occur. If GI upset occurs, trihexyphenidyl HCl may be taken with food. Patients should have close monitoring of intraocular pressure. ( See WARNINGS .) Drug Interactions Cannabinoids, barbiturates, opiates, and alcohol may have additive effects with trihexyphenidyl HCl, and thus, an abuse potential exists. Concurrent use of alcohol or other CNS depressants with trihexyphenidyl HCl may cause increased sedative effects. Monoamine oxidase inhibitors and tricyclic antidepressants possessing significant anticholinergic activity may intensify the anticholinergic effects of antidyskinetic agents because of the secondary anticholinergic activities of these medications. Prophylactic administration of anticholinergic agents, such as trihexyphenidyl, as a prevention of drug-induced parkinsonism during neuroleptic therapy is not recommended. There may be an increased risk for the development of tardive dyskinesia during concomitant administration of anticholinergics and neuroleptics ( see PRECAUTIONS , General ) . The usual dose of either trihexyphenidyl or levodopa may need to be reduced during concomitant therapy, since concomitant administration may increase drug-induced involuntary movements ( see DOSAGE AND ADMINISTRATION ). Carcinogenesis, Mutagenesis, Impairment Of Fertility No carcinogenicity studies or adequate genotoxicity or fertility studies have been conducted for trihexyphenidyl HCl. Pregnancy TERATOGENIC EFFECTS PREGNANCY CATEGORY C Animal reproduction studies to evaluate teratogenic and embryotoxic potential have not been conducted with trihexyphenidyl HCl. It is also not known whether trihexyphenidyl HCl can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Trihexyphenidyl HCl should be given to a pregnant woman only if clearly needed. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when trihexyphenidyl HCl is administered to a nursing woman. As with other anticholinergics, trihexyphenidyl may cause suppression of lactation. Therefore, trihexyphenidyl should only be used if the expected benefit to the mother outweighs the potential risk to the infant. Pediatric Use Safety and effectiveness in pediatric patients have not been established. ( See also ADVERSE REACTIONS .) Geriatric Use Sensitivity to the actions of parasympatholytic drugs may increase with age, particularly over the age of 60; therefore, elderly patients generally should be started on low doses of trihexyphenidyl HCl and observed closely. Trihexyphenidyl HCl has been shown to cause some cognitive dysfunctions in the elderly, including confusion and memory impairment. ( See ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION .)"}', 'information_for_patients': '{"Information for Patients Trihexyphenidyl HCl may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle. Patients should be cautioned about operating machinery, including automobiles, until they are reasonably certain that trihexyphenidyl HCl therapy does not adversely affect their ability to engage in such activities. Because of increased sedative effects, patients should be cautioned to avoid the use of alcohol or other CNS depressants while taking trihexyphenidyl HCl. Since this medication may increase the susceptibility to heat stroke (gastrointestinal (GI) problems, fever, heat intolerance), use with caution during hot weather. ( See WARNINGS .) Patients should be advised to report the occurrence of Gl problems, fever, or heat intolerance promptly since paralytic ileus, hyperthermia, or heat stroke may occur. If GI upset occurs, trihexyphenidyl HCl may be taken with food. Patients should have close monitoring of intraocular pressure. ( See WARNINGS .)"}', 'pregnancy': '{"Pregnancy TERATOGENIC EFFECTS PREGNANCY CATEGORY C Animal reproduction studies to evaluate teratogenic and embryotoxic potential have not been conducted with trihexyphenidyl HCl. It is also not known whether trihexyphenidyl HCl can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Trihexyphenidyl HCl should be given to a pregnant woman only if clearly needed."}', 'pediatric_use': '{"Pediatric Use Safety and effectiveness in pediatric patients have not been established. ( See also ADVERSE REACTIONS .)"}', 'geriatric_use': '{"Geriatric Use Sensitivity to the actions of parasympatholytic drugs may increase with age, particularly over the age of 60; therefore, elderly patients generally should be started on low doses of trihexyphenidyl HCl and observed closely. Trihexyphenidyl HCl has been shown to cause some cognitive dysfunctions in the elderly, including confusion and memory impairment. ( See ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION .)"}'}

{LORATADINE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses temporarily relieves these symptoms due to hay fever or other upper respiratory allergies: runny nose itchy, watery eyes sneezing itching of the nose or throat"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{LORATADINE}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if an allergic reaction to this product occurs. Seek medical help right away."}', 'do_not_use': '{"Do not use if you have ever had an allergic reaction to this product or any of its ingredients."}', 'when_using': '{"When using this product do not take more than directed. Taking more than directed may cause drowsiness."}', 'warnings': '{"Warnings Do not use if you have ever had an allergic reaction to this product or any of its ingredients. Ask a doctor before use if you have liver or kidney disease. Your doctor should determine if you need a different dose. When using this product do not take more than directed. Taking more than directed may cause drowsiness. Stop use and ask a doctor if an allergic reaction to this product occurs. Seek medical help right away. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"DILTIAZEM HYDROCHLORIDE"}

{'contraindications': '{"CONTRAINDICATIONS Diltiazem is contraindicated in: Patients with sick sinus syndrome except in the presence of a functioning ventricular pacemaker Patients with second- or third-degree AV block except in the presence of a functioning ventricular pacemaker Patients with hypotension (less than 90 mm Hg systolic) Patients who have demonstrated hypersensitivity to the drug Patients with acute myocardial infarction and pulmonary congestion documented by x-ray on admission"}', 'adverse_reactions': '{"ADVERSE REACTIONS Serious adverse reactions have been rare in studies carried out to date, but it should be recognized that patients with impaired ventricular function and cardiac conduction abnormalities usually have been excluded. In domestic placebo-controlled angina trials, the incidence of adverse reactions reported during diltiazem therapy was not greater than that reported during placebo therapy. The following represent occurrences observed in clinical studies of angina patients. In many cases, the relationship to diltiazem has not been established. The most common occurrences from these studies, as well as their frequency of presentation, are edema (2.4%), headache (2.1%), nausea (1.9%), dizziness (1.5%), rash (1.3%), and asthenia (1.2%). In addition, the following events were reported infrequently (less than 1%): Cardiovascular: Angina, arrhythmia, AV block (first-degree), AV block (second- or third-degree – see WARNINGS , Cardiac Conduction ), bradycardia, bundle branch block, congestive heart failure, ECG abnormality, flushing, hypotension, palpitations, syncope, tachycardia, ventricular extrasystoles. Nervous System: Abnormal dreams, amnesia, depression, gait abnormality, hallucinations, insomnia, nervousness, paresthesia, personality change, somnolence, tremor. Gastrointestinal: Anorexia, constipation, diarrhea, dysgeusia, dyspepsia, mild elevations of alkaline phosphatase, SGOT, SGPT, and LDH (see WARNINGS , Acute Hepatic Injury ), thirst, vomiting, weight increase. Dermatological: Petechiae, photosensitivity, pruritus, urticaria. Other: Amblyopia, CPK elevation, dry mouth, dyspnea, epistaxis, eye irritation, hyperglycemia, hyperuricemia, impotence, muscle cramps, nasal congestion, nocturia, osteoarticular pain, polyuria, sexual difficulties, tinnitus. The following postmarketing events have been reported infrequently in patients receiving diltiazem: acute generalized exanthematous pustulosis, allergic reactions, alopecia, angioedema (including facial or periorbital edema), asystole, erythema multiforme (including Stevens-Johnson syndrome, toxic epidermal necrolysis), extrapyramidal symptoms, gingival hyperplasia, hemolytic anemia, increased bleeding time, leukopenia, photosensitivity (including lichenoid keratosis and hyperpigmentation at sun-exposed skin areas), purpura, retinopathy, myopathy, and thrombocytopenia. There have been observed cases of a generalized rash, some characterized as leukocytoclastic vasculitis. In addition, events such as myocardial infarction have been observed, which are not readily distinguishable from the natural history of the disease in these patients. A definitive cause and effect relationship between these events and diltiazem therapy cannot yet be established. Exfoliative dermatitis (proven by rechallenge) has also been reported. To report SUSPECTED ADVERSE REACTIONS, contact TEVA USA, PHARMACOVIGILANCE at 1-866-832-8537 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch."}', 'drug_interactions': '{"Drug Interactions Due to the potential for additive effects, caution and careful titration are warranted in patients receiving diltiazem concomitantly with any agents known to affect cardiac contractility and/or conduction (see WARNINGS ). Pharmacologic studies indicate that there may be additive effects in prolonging AV conduction when using beta-blockers or digitalis concomitantly with diltiazem (see WARNINGS ). As with all drugs, care should be exercised when treating patients with multiple medications. Diltiazem is both a substrate and an inhibitor of the cytochrome P-450 3A4 enzyme system. Other drugs that are specific substrates, inhibitors, or inducers of this enzyme system may have a significant impact on the efficacy and side effect profile of diltiazem. Patients taking other drugs that are substrates of CYP450 3A4, especially patients with renal and/or hepatic impairment, may require dosage adjustment when starting or stopping concomitantly administered diltiazem in order to maintain optimum therapeutic blood levels. Anesthetics: The depression of cardiac contractility, conductivity, and automaticity, as well as the vascular dilation associated with anesthetics, may be potentiated by calcium channel blockers. When used concomitantly, anesthetics and calcium blockers should be titrated carefully. Benzodiazepines: Studies showed that diltiazem increased the AUC of midazolam and triazolam by 3- to 4-fold and the C max by 2-fold, compared to placebo. The elimination half-life of midazolam and triazolam also increased (1.5- to 2.5-fold) during coadministration with diltiazem. These pharmacokinetic effects seen during diltiazem coadministration can result in increased clinical effects (e.g.,prolonged sedation) of both midazolam and triazolam. Beta-Blockers: Controlled and uncontrolled domestic studies suggest that concomitant use of diltiazem and beta-blockers is usually well tolerated. Available data are not sufficient, however, to predict the effects of concomitant treatment, particularly in patients with left ventricular dysfunction or cardiac conduction abnormalities. Administration of diltiazem concomitantly with propranolol in five normal volunteers resulted in increased propranolol levels in all subjects, and bioavailability of propranolol was increased approximately 50%. In vitro , propranolol appears to be displaced from its binding sites by diltiazem. If combination therapy is initiated or withdrawn in conjunction with propranolol, an adjustment in the propranolol dose may be warranted (see WARNINGS ). Buspirone: In nine healthy subjects, diltiazem significantly increased the mean buspirone AUC 5.5-fold and C max 4.1-fold compared to placebo. The T 1/2 and T max of buspirone were not significantly affected by diltiazem. Enhanced effects and increased toxicity of buspirone may be possible during concomitant administration with diltiazem. Subsequent dose adjustments may be necessary during coadministration, and should be based on clinical assessment. Carbamazepine: Concomitant administration of diltiazem with carbamazepine has been reported to result in elevated serum levels of carbamazepine (40% to 72% increase) resulting in toxicity in some cases. Patients receiving these drugs concurrently should be monitored for a potential drug interaction. Cimetidine: A study in six healthy volunteers has shown a significant increase in peak diltiazem plasma levels (58%) and area-under-the-curve (53%) after a 1 week course of cimetidine at 1200 mg per day and a single dose of diltiazem 60 mg. Ranitidine produced smaller, nonsignificant increases. The effect may be mediated by cimetidine\'s known inhibition of hepatic cytochrome P-450, the enzyme system responsible for the first-pass metabolism of diltiazem. Patients currently receiving diltiazem therapy should be carefully monitored for a change in pharmacological effect when initiating and discontinuing therapy with cimetidine. An adjustment in the diltiazem dose may be warranted. Clonidine: Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with diltiazem. Monitor heart rate in patients receiving concomitant diltiazem and clonidine. Cyclosporine: A pharmacokinetic interaction between diltiazem and cyclosporine has been observed during studies involving renal and cardiac transplant patients. In renal and cardiac transplant recipients, a reduction of cyclosporine trough dose ranging from 15% to 48% was necessary to maintain concentrations similar to those seen prior to the addition of diltiazem. If these agents are to be administered concurrently, cyclosporine concentrations should be monitored, especially when diltiazem therapy is initiated, adjusted, or discontinued. The effect of cyclosporine on diltiazem plasma concentrations has not been evaluated. Digitalis: Administration of diltiazem with digoxin in 24 healthy male subjects increased plasma digoxin concentrations approximately 20%. Another investigator found no increase in digoxin levels in 12 patients with coronary artery disease. Since there have been conflicting results regarding the effect of digoxin levels, it is recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing diltiazem therapy to avoid possible over- or under-digitalization (see WARNINGS ). Ivabradine: Concurrent use of diltiazem increases exposure to ivabradine and may exacerbate bradycardia and conduction disturbances. Avoid concomitant use of ivabradine and diltiazem. Quinidine: Diltiazem significantly increases the AUC (0→∞) of quinidine by 51%, T 1/2 by 36%, and decreases its CL oral by 33%. Monitoring for quinidine adverse effects may be warranted and the dose adjusted accordingly. Rifampin: Coadministration of rifampin with diltiazem lowered the diltiazem plasma concentrations to undetectable levels. Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered. Statins: Diltiazem is an inhibitor of CYP3A4 and has been shown to increase significantly the AUC of some statins. The risk of myopathy and rhabdomyolysis with statins metabolized by CYP3A4 may be increased with concomitant use of diltiazem. When possible, use a non-CYP3A4-metabolized statin together with diltiazem; otherwise, dose adjustments for both diltiazem and the statin should be considered along with close monitoring for signs and symptoms of any statin related adverse events. In a healthy volunteer cross-over study (N = 10), coadministration of a single 20 mg dose of simvastatin at the end of a 14 day regimen with 120 mg BID diltiazem SR resulted in a 5-fold increase in mean simvastatin AUC versus simvastatin alone. Subjects with increased average steady-state exposures of diltiazem showed a greater fold increase in simvastatin exposure. Computer-based simulations showed that at a daily dose of 480 mg of diltiazem, an 8- to 9-fold mean increase in simvastatin AUC can be expected. If coadministration of simvastatin with diltiazem is required, limit the daily doses of simvastatin to 10 mg and diltiazem to 240 mg. In a ten-subject randomized, open label, 4-way crossover study, coadministration of diltiazem (120 mg BID diltiazem SR for 2 weeks) with a single 20 mg dose of lovastatin resulted in 3- to 4-fold increase in mean lovastatin AUC and C max versus lovastatin alone. In the same study, there was no significant change in 20 mg single dose pravastatin AUC and C max during diltiazem coadministration. Diltiazem plasma levels were not significantly affected by lovastatin or pravastatin."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Diltiazem hydrochloride tablets USP are indicated for the management of chronic stable angina and angina due to coronary artery spasm."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE The oral LD 50 s in mice and rats range from 415 to 740 mg/kg and from 560 to 810 mg/kg, respectively. The intravenous LD 50 s in these species were 60 and 38 mg/kg, respectively. The oral LD 50 in dogs is considered to be in excess of 50 mg/kg, while lethality was seen in monkeys at 360 mg/kg. The toxic dose in man is not known. Due to extensive metabolism, blood levels after a standard dose of diltiazem can vary over tenfold, limiting the usefulness of blood levels in overdose cases. There have been reports of diltiazem overdose in amounts ranging from < 1 g to 18 g. Of cases with known outcome, most patients recovered and in cases with a fatal outcome, the majority involved multiple drug ingestion. Events observed following diltiazem overdose included bradycardia, hypotension, heart block, and cardiac failure. Most reports of overdose described some supportive medical measure and/or drug treatment. Bradycardia frequently responded favorably to atropine, as did heart block, although cardiac pacing was also frequently utilized to treat heart block. Fluids and vasopressors were used to maintain blood pressure, and in cases of cardiac failure, inotropic agents were administered. In addition, some patients received treatment with ventilatory support, gastric lavage, activated charcoal, and/or intravenous calcium. The effectiveness of intravenous calcium administration to reverse the pharmacological effects of diltiazem overdose has been inconsistent. In a few reported cases, overdose with calcium channel blockers associated with hypotension and bradycardia that was initially refractory to atropine became more responsive to atropine after the patients received intravenous calcium. In some cases intravenous calcium has been administered (1 g calcium chloride or 3 g calcium gluconate) over 5 minutes and repeated every 10 to 20 minutes as necessary. Calcium gluconate has also been administered as a continuous infusion at a rate of 2 g per hour for 10 hours. Infusions of calcium for 24 hours or more may be required. Patients should be monitored for signs of hypercalcemia. In the event of overdose or exaggerated response, appropriate supportive measures should be employed in addition to gastrointestinal decontamination. Diltiazem does not appear to be removed by peritoneal or hemodialysis. Limited data suggest that plasmapheresis or charcoal hemoperfusion may hasten diltiazem elimination following overdose. Based on the known pharmacological effects of diltiazem and/or reported clinical experiences, the following measures may be considered: Bradycardia: Administer atropine (0.6 to 1 mg). If there is no response to vagal blockade, administer isoproterenol cautiously. High-Degree AV Block: Treat as for bradycardia above. Fixed high-degree AV block should be treated with cardiac pacing. Cardiac Failure: Administer inotropic agents (isoproterenol, dopamine, or dobutamine) and diuretics. Hypotension: Vasopressors (e.g., dopamine or norepinephrine). Actual treatment and dosage should depend on the severity of the clinical situation and the judgment and experience of the treating physician."}', 'active_flag': 'Y', 'generic_name': '{"DILTIAZEM HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS 1. Cardiac Conduction: Diltiazem prolongs AV node refractory periods without significantly prolonging sinus node recovery time, except in patients with sick sinus syndrome. This effect may rarely result in abnormally slow heart rates (particularly in patients with sick sinus syndrome) or second- or third-degree AV block (six of 1243 patients for 0.48%). Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. A patient with Prinzmetal\'s angina developed periods of asystole (2 to 5 seconds) after a single dose of 60 mg of diltiazem (see ADVERSE REACTIONS ). 2. Congestive Heart Failure: Although diltiazem has a negative inotropic effect in isolated animal tissue preparations, hemodynamic studies in humans with normal ventricular function have not shown a reduction in cardiac index nor consistent negative effects on contractility (dP/dt). Experience with the use of diltiazem alone or in combination with beta-blockers in patients with impaired ventricular function is very limited. Caution should be exercised when using the drug in such patients. 3. Hypotension: Decreases in blood pressure associated with diltiazem therapy may occasionally result in symptomatic hypotension. 4. Acute Hepatic Injury: In rare instances, significant elevations in enzymes such as alkaline phosphatase, LDH, SGOT, SGPT, and other phenomena consistent with acute hepatic injury have been noted. These reactions have been reversible upon discontinuation of drug therapy. The relationship to diltiazem is uncertain in most cases, but probable in some (see PRECAUTIONS )."}', 'precautions': '{"PRECAUTIONS General Diltiazem is extensively metabolized by the liver and excreted by the kidneys and in bile. As with any drug given over prolonged periods, laboratory parameters of renal and hepatic function should be monitored at regular intervals. The drug should be used with caution in patients with impaired renal or hepatic function. In subacute and chronic dog and rat studies designed to produce toxicity, high doses of diltiazem were associated with hepatic damage. In special subacute hepatic studies, oral doses of 125 mg/kg and higher in rats were associated with histological changes in the liver, which were reversible when the drug was discontinued. In dogs, doses of 20 mg/kg were also associated with hepatic changes; however, these changes were reversible with continued dosing. Dermatological events (see ADVERSE REACTIONS ) may be transient and may disappear despite continued use of diltiazem. However, skin eruptions progressing to erythema multiforme and/or exfoliative dermatitis have also been infrequently reported. Should a dermatologic reaction persist, the drug should be discontinued. Drug Interactions Due to the potential for additive effects, caution and careful titration are warranted in patients receiving diltiazem concomitantly with any agents known to affect cardiac contractility and/or conduction (see WARNINGS ). Pharmacologic studies indicate that there may be additive effects in prolonging AV conduction when using beta-blockers or digitalis concomitantly with diltiazem (see WARNINGS ). As with all drugs, care should be exercised when treating patients with multiple medications. Diltiazem is both a substrate and an inhibitor of the cytochrome P-450 3A4 enzyme system. Other drugs that are specific substrates, inhibitors, or inducers of this enzyme system may have a significant impact on the efficacy and side effect profile of diltiazem. Patients taking other drugs that are substrates of CYP450 3A4, especially patients with renal and/or hepatic impairment, may require dosage adjustment when starting or stopping concomitantly administered diltiazem in order to maintain optimum therapeutic blood levels. Anesthetics: The depression of cardiac contractility, conductivity, and automaticity, as well as the vascular dilation associated with anesthetics, may be potentiated by calcium channel blockers. When used concomitantly, anesthetics and calcium blockers should be titrated carefully. Benzodiazepines: Studies showed that diltiazem increased the AUC of midazolam and triazolam by 3- to 4-fold and the C max by 2-fold, compared to placebo. The elimination half-life of midazolam and triazolam also increased (1.5- to 2.5-fold) during coadministration with diltiazem. These pharmacokinetic effects seen during diltiazem coadministration can result in increased clinical effects (e.g.,prolonged sedation) of both midazolam and triazolam. Beta-Blockers: Controlled and uncontrolled domestic studies suggest that concomitant use of diltiazem and beta-blockers is usually well tolerated. Available data are not sufficient, however, to predict the effects of concomitant treatment, particularly in patients with left ventricular dysfunction or cardiac conduction abnormalities. Administration of diltiazem concomitantly with propranolol in five normal volunteers resulted in increased propranolol levels in all subjects, and bioavailability of propranolol was increased approximately 50%. In vitro , propranolol appears to be displaced from its binding sites by diltiazem. If combination therapy is initiated or withdrawn in conjunction with propranolol, an adjustment in the propranolol dose may be warranted (see WARNINGS ). Buspirone: In nine healthy subjects, diltiazem significantly increased the mean buspirone AUC 5.5-fold and C max 4.1-fold compared to placebo. The T 1/2 and T max of buspirone were not significantly affected by diltiazem. Enhanced effects and increased toxicity of buspirone may be possible during concomitant administration with diltiazem. Subsequent dose adjustments may be necessary during coadministration, and should be based on clinical assessment. Carbamazepine: Concomitant administration of diltiazem with carbamazepine has been reported to result in elevated serum levels of carbamazepine (40% to 72% increase) resulting in toxicity in some cases. Patients receiving these drugs concurrently should be monitored for a potential drug interaction. Cimetidine: A study in six healthy volunteers has shown a significant increase in peak diltiazem plasma levels (58%) and area-under-the-curve (53%) after a 1 week course of cimetidine at 1200 mg per day and a single dose of diltiazem 60 mg. Ranitidine produced smaller, nonsignificant increases. The effect may be mediated by cimetidine\'s known inhibition of hepatic cytochrome P-450, the enzyme system responsible for the first-pass metabolism of diltiazem. Patients currently receiving diltiazem therapy should be carefully monitored for a change in pharmacological effect when initiating and discontinuing therapy with cimetidine. An adjustment in the diltiazem dose may be warranted. Clonidine: Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with diltiazem. Monitor heart rate in patients receiving concomitant diltiazem and clonidine. Cyclosporine: A pharmacokinetic interaction between diltiazem and cyclosporine has been observed during studies involving renal and cardiac transplant patients. In renal and cardiac transplant recipients, a reduction of cyclosporine trough dose ranging from 15% to 48% was necessary to maintain concentrations similar to those seen prior to the addition of diltiazem. If these agents are to be administered concurrently, cyclosporine concentrations should be monitored, especially when diltiazem therapy is initiated, adjusted, or discontinued. The effect of cyclosporine on diltiazem plasma concentrations has not been evaluated. Digitalis: Administration of diltiazem with digoxin in 24 healthy male subjects increased plasma digoxin concentrations approximately 20%. Another investigator found no increase in digoxin levels in 12 patients with coronary artery disease. Since there have been conflicting results regarding the effect of digoxin levels, it is recommended that digoxin levels be monitored when initiating, adjusting, and discontinuing diltiazem therapy to avoid possible over- or under-digitalization (see WARNINGS ). Ivabradine: Concurrent use of diltiazem increases exposure to ivabradine and may exacerbate bradycardia and conduction disturbances. Avoid concomitant use of ivabradine and diltiazem. Quinidine: Diltiazem significantly increases the AUC (0→∞) of quinidine by 51%, T 1/2 by 36%, and decreases its CL oral by 33%. Monitoring for quinidine adverse effects may be warranted and the dose adjusted accordingly. Rifampin: Coadministration of rifampin with diltiazem lowered the diltiazem plasma concentrations to undetectable levels. Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered. Statins: Diltiazem is an inhibitor of CYP3A4 and has been shown to increase significantly the AUC of some statins. The risk of myopathy and rhabdomyolysis with statins metabolized by CYP3A4 may be increased with concomitant use of diltiazem. When possible, use a non-CYP3A4-metabolized statin together with diltiazem; otherwise, dose adjustments for both diltiazem and the statin should be considered along with close monitoring for signs and symptoms of any statin related adverse events. In a healthy volunteer cross-over study (N = 10), coadministration of a single 20 mg dose of simvastatin at the end of a 14 day regimen with 120 mg BID diltiazem SR resulted in a 5-fold increase in mean simvastatin AUC versus simvastatin alone. Subjects with increased average steady-state exposures of diltiazem showed a greater fold increase in simvastatin exposure. Computer-based simulations showed that at a daily dose of 480 mg of diltiazem, an 8- to 9-fold mean increase in simvastatin AUC can be expected. If coadministration of simvastatin with diltiazem is required, limit the daily doses of simvastatin to 10 mg and diltiazem to 240 mg. In a ten-subject randomized, open label, 4-way crossover study, coadministration of diltiazem (120 mg BID diltiazem SR for 2 weeks) with a single 20 mg dose of lovastatin resulted in 3- to 4-fold increase in mean lovastatin AUC and C max versus lovastatin alone. In the same study, there was no significant change in 20 mg single dose pravastatin AUC and C max during diltiazem coadministration. Diltiazem plasma levels were not significantly affected by lovastatin or pravastatin. Carcinogenesis, Mutagenesis, Impairment of Fertility A 24 month study in rats and a 21 month study in mice showed no evidence of carcinogenicity. There was also no mutagenic response in in vitro bacterial tests. No intrinsic effect on fertility was observed in rats. Pregnancy Reproduction studies have been conducted in mice, rats, and rabbits. Administration of doses ranging from five to ten times greater (on a mg/kg basis) than the daily recommended therapeutic dose has resulted in embryo and fetal lethality. These doses, in some studies, have been reported to cause skeletal abnormalities. In the perinatal/postnatal studies, there was some reduction in early individual pup weights and survival rates. There was an increased incidence of stillbirths at doses of 20 times the human dose or greater. There are no well-controlled studies in pregnant women; therefore, use diltiazem in pregnant women only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers Diltiazem is excreted in human milk. One report suggests that concentrations in breast milk may approximate serum levels. If use of diltiazem is deemed essential, an alternative method of infant feeding should be instituted. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use Clinical studies of diltiazem did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Information for Patients Swallow diltiazem tablets whole; do not split, crush, or chew. The medication in diltiazem tablets is formulated to slowly release."}', 'information_for_patients': None, 'pregnancy': '{"Pregnancy Reproduction studies have been conducted in mice, rats, and rabbits. Administration of doses ranging from five to ten times greater (on a mg/kg basis) than the daily recommended therapeutic dose has resulted in embryo and fetal lethality. These doses, in some studies, have been reported to cause skeletal abnormalities. In the perinatal/postnatal studies, there was some reduction in early individual pup weights and survival rates. There was an increased incidence of stillbirths at doses of 20 times the human dose or greater. There are no well-controlled studies in pregnant women; therefore, use diltiazem in pregnant women only if the potential benefit justifies the potential risk to the fetus."}', 'pediatric_use': '{"Pediatric Use Safety and effectiveness in pediatric patients have not been established."}', 'geriatric_use': None}

{"DEXTROMETHORPHAN HYDROBROMIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses • temporarily relieves cough due to minor throat and bronchial irritation as may occur with a cold"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"DEXTROMETHORPHAN HYDROBROMIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if cough lasts for more than 7 days, comes back, or is accompanied by fever, rash, or persistent headache. A persistent cough may be a sign of a serious condition."}', 'do_not_use': '{"Do not use • if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric or emotional conditions, or Parkinson\'s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product."}', 'when_using': None, 'warnings': '{"Warnings Do not use • if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric or emotional conditions, or Parkinson\'s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product. Ask a doctor before use if you have • cough that occurs with too much phlegm (mucus) • cough that lasts or is chronic such as occurs with smoking, asthma or emphysema Stop use and ask a doctor if cough lasts for more than 7 days, comes back, or is accompanied by fever, rash, or persistent headache. A persistent cough may be a sign of a serious condition. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away. (1-800-222-1222)"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"ALMOTRIPTAN MALATE"}

{'contraindications': '{"4 CONTRAINDICATIONS • Ischemic heart disease, coronary artery vasospasm, or other significant underlying cardiovascular disease ( 4.1 ) • Cerebrovascular syndromes (e.g., history of stroke or TIA) ( 4.2 ) • Peripheral vascular disease (including ischemic bowel disease) ( 4.3 ) • Uncontrolled hypertension ( 4.4 ) • Do not use almotriptan tablets within 24 hours of an ergotamine-containing, or ergot-type medication, or of another 5-HT 1 agonist, e.g., another triptan ( 4.5 , 4.6 ) • Hemiplegic or basilar migraine ( 4.7 ) • Known hypersensitivity to almotriptan tablets ( 4.8 ) 4.1 Ischemic or Vasospastic Coronary Artery Disease, or Other Significant Underlying Cardiovascular Disease Do not use almotriptan tablets (almotriptan malate) in patients with ischemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischemia), or in patients who have symptoms or findings consistent with ischemic heart disease, coronary artery vasospasm, including Prinzmetal’s variant angina, or other significant underlying cardiovascular disease [see Warnings and Precautions (5.1) ] . 4.2 Cerebrovascular Syndromes Do not use almotriptan tablets in patients with cerebrovascular syndromes including (but not limited to) stroke of any type as well as transient ischemic attacks [see Warnings and Precautions (5.3) ] . 4.3 Peripheral Vascular Disease Do not use almotriptan tablets in patients with peripheral vascular disease including (but not limited to) ischemic bowel disease [see Warnings and Precautions (5.4) ] . 4.4 Uncontrolled Hypertension Because almotriptan may increase blood pressure, do not use almotriptan tablets in patients with uncontrolled hypertension [see Warnings and Precautions (5.7) ] . 4.5 Ergotamine-Containing and Ergot-Type Medications Do not use almotriptan tablets and ergotamine-containing or ergot-derived medications like dihydroergotamine, ergotamine tartrate, or methysergide within 24 hours of each other [see Drug Interactions (7.1) ] . 4.6 Concomitant Use with 5-HT 1 Agonists (e.g., Triptans) Almotriptan tablets and other 5-HT 1 agonists (e.g., triptans) should not be administered within 24 hours of each other [see Warnings and Precautions (5.1) and (5.2) ]. 4.7 Hemiplegic or Basilar Migraine Do not use almotriptan tablets in patients with hemiplegic or basilar migraine. 4.8 Hypersensitivity Almotriptan tablets are contraindicated in patients with known hypersensitivity to almotriptan or any of their inactive ingredients."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS Serious cardiac reactions, including myocardial infarction, have occurred following the use of almotriptan (almotriptan malate) tablets. These reactions are extremely rare and most have been reported in patients with risk factors predictive of CAD. Reactions reported in association with triptans have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation [see Contraindications (4.1) and Warnings and Precautions (5.1) ] . The following adverse reactions are discussed in more detail in other sections of the labeling: • Risk of Myocardial Ischemia and Infarction and Other Adverse Cardiac Events [see Warnings and Precautions (5.1) ] • Sensations of Pain, Tightness, Pressure in the Chest and/or Throat, Neck, and Jaw [see Warnings and Precautions (5.2) ] • Cerebrovascular Events and Fatalities [see Warnings and Precautions (5.3) ] • Other Vasospasm-Related Events, Including Peripheral Vascular Ischemia and Colonic Ischemia [see Warnings and Precautions (5.4) ] • Serotonin Syndrome [see Warnings and Precautions (5.5) ] • Increases in Blood Pressure [see Warnings and Precautions (5.7) ] Adverse events were assessed in controlled clinical trials that included 1840 adult patients who received one or two doses of almotriptan tablets and 386 adult patients who received placebo. The most common adverse reactions during treatment with almotriptan tablets were nausea, somnolence, headache, paresthesia, and dry mouth. In long-term open-label studies where patients were allowed to treat multiple attacks for up to 1 year, 5% (63 out of 1347 patients) withdrew due to adverse experiences. Adverse events were assessed in controlled clinical trials that included 362 adolescent patients who received almotriptan tablets and 172 adolescent patients who received placebo. The most common adverse reactions during treatment with almotriptan tablets were dizziness, somnolence, headache, paresthesia, nausea, and vomiting. In a long-term, open-label study where patients were allowed to treat multiple attacks for up to 1 year, 2% (10 out of 420 adolescent patients) withdrew due to adverse events. Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The most common adverse reactions (≥ 1% and greater than placebo) are: • In adults: nausea, dry mouth and paresthesia ( 6.1 ) • In adolescents: dizziness, somnolence, headache, paresthesia, nausea and vomiting ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan Pharmaceuticals Inc. at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Almotriptan Tablet Clinical Trials Adults Table 1 lists the adverse events that occurred in at least 1% of the adult patients treated with almotriptan tablets, and at an incidence greater than in patients treated with placebo, regardless of drug relationship. Table 1. Incidence of Adverse Events in Controlled Clinical Trials (Reported in at Least 1% of Adult Patients Treated with Almotriptan Tablets, and at an Incidence Greater than Placebo) System/Organ Class Adverse Event Almotriptan Tablets 6.25 mg (n = 527) % Almotriptan Tablets 12.5 mg (n = 1313) % Placebo (n = 386) % Digestive Disorders Nausea 1 2 1 Dry Mouth 1 1 0.5 Nervous System Disorders Paresthesia 1 1 0.5 The incidence of adverse events in controlled clinical trials was not affected by gender, weight, age, presence of aura, or use of prophylactic medications or oral contraceptives. There were insufficient data to assess the effect of race on the incidence of adverse events. Adolescents Table 2 lists the adverse reactions reported by 1% or more of almotriptan tablet-treated adolescents age 12 to 17 years in one placebo-controlled, double-blind clinical trial. Table 2. Adverse Reactions Reported by ≥ 1% of Adolescent Patients Treated with Almotriptan Tablets in One Placebo-Controlled, Double-Blind Clinical Trial System/Organ Class Adverse Reaction Almotriptan Tablets 6.25 mg (n = 180) % Almotriptan Tablets 12.5 mg (n = 182) % Placebo (n = 172) % Nervous System Disorders Dizziness 4 3 2 Somnolence < 1 5 2 Headache 1 2 1 Paresthesia < 1 1 < 1 Gastrointestinal Disorders Nausea 1 3 0 Vomiting 2 0 < 1 6.2 Other Adverse Reactions Observed in Almotriptan Tablet Clinical Trials In the paragraphs that follow, the frequencies of less commonly reported adverse clinical reactions are presented. The reports include adverse reactions in five adult controlled studies and one adolescent controlled study. Variability associated with adverse reaction reporting, the terminology used to describe adverse reactions, etc., limit the value of the quantitative frequency estimates provided. Reaction frequencies are calculated as the number of patients who used almotriptan tablets and reported a reaction divided by the total number of patients exposed to almotriptan tablets (n = 3047, all doses). All reported reactions are included except those already listed in the previous table, those too general to be informative, and those not reasonably associated with the use of the drug. Reactions are further classified within system organ class and enumerated in order of decreasing frequency using the following definitions: frequent adverse reactions are those occurring in 1/100 or more patients, infrequent adverse reactions are those occurring in fewer than 1/100 to 1/1000 patients, and rare adverse reactions are those occurring in fewer than 1/1000 patients. Body: Frequent: Headache. Infrequent: Abdominal cramp or pain, Asthenia, Chills, Back pain, Chest pain, Neck pain, Fatigue, and Rigid neck. Rare: Fever and Photosensitivity reaction. Cardiovascular: Infrequent: Vasodilation, Palpitations, and Tachycardia. Rare: Hypertension and Syncope. Digestive: Infrequent: Diarrhea, Vomiting, Dyspepsia, Gastroenteritis, and Increased thirst. Rare: Colitis, Gastritis, Esophageal reflux, and Increased salivation. Metabolic: Infrequent: Hyperglycemia and Increased serum creatine phosphokinase. Rare: Increased gamma glutamyl transpeptidase and Hypercholesteremia. Musculoskeletal: Infrequent: Myalgia. Rare: Arthralgia, Arthritis, Myopathy, and Muscle weakness. Nervous: Frequent: Dizziness and Somnolence. Infrequent: Tremor, Vertigo, Anxiety, Hypoesthesia, Restlessness, CNS stimulation, and Shakiness. Rare: Change in dreams, Impaired concentration, Abnormal coordination, Depressive symptoms, Euphoria, Hyperreflexia, Hypertonia, Nervousness, Neuropathy, Nightmares, Nystagmus, and Insomnia. Respiratory: Infrequent: Pharyngitis, Rhinitis, Dyspnea, Laryngismus, Sinusitis, and Bronchitis. Rare: Hyperventilation, Laryngitis, Sneezing, and Epistaxis. Skin: Infrequent: Diaphoresis, Pruritus, and Rash. Rare: Dermatitis and Erythema. Special Senses: Infrequent: Ear pain and Tinnitus. Rare: Diplopia, Dry eyes, Eye pain, Otitis media, Parosmia, Scotoma, Conjunctivitis, Eye irritation, Hyperacusis, and Taste alteration. Urogenital: Infrequent: Dysmenorrhea. 6.3 Postmarketing Experience The following adverse reactions have been identified during postapproval use of almotriptan tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders: Hypersensitivity reactions (including angioedema, anaphylactic reactions and anaphylactic shock) Psychiatric Disorders: Confusional state, Restlessness Nervous System Disorders: Hemiplegia, Hypoesthesia, Seizures Eye Disorders: Blepharospasm, Visual impairment, Vision blurred Ear and Labyrinth Disorders: Vertigo Cardiac Disorders: Acute myocardial infarction, Coronary artery vasospasm, Angina pectoris, Tachycardia Gastrointestinal Disorders: Abdominal discomfort, Abdominal pain, Abdominal pain upper, Colitis, Hypoesthesia oral, Swollen tongue Skin and Subcutaneous Tissue Disorders: Cold sweat, Erythema, Hyperhidrosis Musculoskeletal, Connective Tissue, and Bone Disorders: Arthralgia, Myalgia, Pain in extremity Reproductive System and Breast Disorders: Breast pain General Disorders: Malaise, Peripheral coldness."}', 'drug_interactions': '{"7 DRUG INTERACTIONS • Do not use almotriptan tablets and ergotamine-containing or ergot-type medications within 24 hours of each other ( 4.5 , 7.1 ) • Do not use almotriptan tablets and other 5-HT 1 agonist (e.g., triptans) within 24 hours of each other ( 4.6 , 7.2 ) • SSRI or SNRI: life-threatening serotonin syndrome reported during combined use with triptans ( 5.5 , 7.3 ) • Ketoconazole: use single dose of almotriptan tablets 6.25 mg; maximum almotriptan tablets daily dose 12.5 mg ( 7.4 ) 7.1 Ergot-Containing Drugs These drugs have been reported to cause prolonged vasospastic reactions. Because, in theory, vasospastic effects may be additive, ergotamine-containing or ergot-type medications (like dihydroergotamine, ergotamine tartrate, or methysergide) and almotriptan tablets (almotriptan malate) should not be used within 24 hours of each other [see Contraindications (4.5) ] . 7.2 5-HT 1 Agonists (e.g., Triptans) Concomitant use of other 5-HT 1 agonists (e.g., triptans) within 24 hours of treatment with almotriptan tablets is contraindicated [see Contraindications (4.6) ] . 7.3 Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors Cases of life-threatening serotonin syndrome have been reported during combined use of triptans and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) [see Warnings and Precautions (5.5) , Clinical Pharmacology (12.3) ] . 7.4 Ketoconazole and Other Potent CYP3A4 Inhibitors Co-administration of almotriptan and oral ketoconazole, a potent CYP3A4 inhibitor, resulted in an approximately 60% increase in exposure of almotriptan. Increased exposures to almotriptan may be expected when almotriptan is used concomitantly with other potent CYP3A4 inhibitors [see Clinical Pharmacology (12.3) ] . In patients concomitantly using potent CYP3A4 inhibitors, the recommended starting dose of almotriptan tablets is 6.25 mg. The maximum daily dose should not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan tablets and potent CYP3A4 inhibitors should be avoided in patients with renal or hepatic impairment [see Clinical Pharmacology (12.3) ] ."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Almotriptan tablets are a 5HT 1B/1D receptor agonist (triptan) indicated for: • Acute treatment of migraine attacks in adults with a history of migraine with or without aura ( 1.1 ) • Acute treatment of migraine headache pain in adolescents age 12 to 17 years with a history of migraine with or without aura, and who have migraine attacks usually lasting 4 hours or more ( 1.1 ) Important Limitations: • Use only after a clear diagnosis of migraine has been established ( 1.2 ) • In adolescents age 12 to 17 years, efficacy of almotriptan tablets on migraine-associated symptoms was not established ( 1.2 ) • Not intended for the prophylactic therapy of migraine ( 1.2 ) • Not indicated for the treatment of cluster headache ( 1.2 ) 1.1 Acute Treatment of Migraine Attacks Adults Almotriptan tablets (almotriptan malate) are indicated for the acute treatment of migraine attacks in patients with a history of migraine with or without aura. Adolescents Age 12 to 17 Years Almotriptan tablets are indicated for the acute treatment of migraine headache pain in patients with a history of migraine attacks with or without aura usually lasting 4 hours or more (when untreated). 1.2 Important Limitations Almotriptan tablets should only be used where a clear diagnosis of migraine has been established. If a patient has no response for the first migraine attack treated with almotriptan tablets, the diagnosis of migraine should be reconsidered before almotriptan tablets are administered to treat any subsequent attacks. In adolescents age 12 to 17 years, efficacy of almotriptan tablets on migraine-associated symptoms (nausea, photophobia, and phonophobia) was not established. Almotriptan tablets are not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine [see Contraindications (4.7) ] . Safety and effectiveness of almotriptan tablets have not been established for cluster headache which is present in an older, predominantly male population."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Serious adverse cardiac events, including acute myocardial infarction and life-threatening disturbances of cardiac rhythm ( 5.1 ) • It is strongly recommended that almotriptan tablets not be given to patients in whom unrecognized coronary artery disease (CAD) is predicted by the presence of risk factors. In very rare cases, serious cardiovascular events have been reported in association with almotriptan tablet use in the absence of known cardiovascular disease. If almotriptan tablets are considered, patients should first have a cardiovascular evaluation. If the evaluation is satisfactory, first dose should take place in a physician’s office setting ( 5.1 ) • Sensations of pain, tightness, pressure, and heaviness in the chest, throat, neck, and jaw: generally not associated with myocardial ischemia, but patients with signs or symptoms suggestive of angina should be evaluated for the presence of CAD ( 5.2 ) • Cerebrovascular events, some fatal ( 5.3 ) • Gastrointestinal ischemic events and peripheral vasospastic reactions (e.g., Raynaud’s syndrome) ( 5.4 ) • Potentially life-threatening serotonin syndrome, particularly in combination with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). Monitor patients for neurologic changes and gastrointestinal symptoms if concomitant treatment is clinically warranted ( 5.5 , 7.3 ) • Medication overuse headache: Detoxification may be necessary ( 5.6 ) • Increase in blood pressure, very rarely associated with significant clinical events ( 4.4 , 5.7 ) • Use with caution in patients with a known hypersensitivity to sulfonamides ( 5.8 ) 5.1 Risk of Myocardial Ischemia and Infarction and Other Adverse Cardiac Events Cardiac Events and Fatalities with 5-HT 1 Agonists Serious adverse cardiac events, including acute myocardial infarction, have been reported within a few hours following administration of almotriptan tablets (almotriptan malate). Life-threatening disturbances of cardiac rhythm and death have been reported within a few hours following the administration of other triptans. Considering the extent of use of triptans in patients with migraine, the incidence of these events is extremely low. Almotriptan tablets can cause coronary vasospasm; at least one of these events occurred in a patient with no cardiac history and with documented absence of coronary artery disease. Because of the close proximity of the events to use of almotriptan tablets, a causal relationship cannot be excluded. Patients who experience signs or symptoms suggestive of angina following dosing should be evaluated for the presence of coronary artery disease (CAD) or a predisposition to Prinzmetal’s variant angina before receiving additional doses of medication, and should be monitored electrocardiographically if dosing is resumed and similar symptoms recur. Premarketing Experience with Almotriptan Tablets in Adults Among the 3865 subjects/patients who received almotriptan tablets in premarketing clinical trials, one patient was hospitalized for observation after a scheduled electrocardiogram (ECG) was found to be abnormal (negative T-waves on the left leads) 48 hours after taking a single 6.25 mg dose of almotriptan. The patient, a 48-year-old female, had previously taken three other doses for earlier migraine attacks. Myocardial enzymes at the time of the abnormal ECG were normal. The patient was diagnosed as having had myocardial ischemia and that she had a family history of coronary disease. An ECG performed 2 days later was normal, as was a follow-up coronary angiography. The patient recovered without incident. Postmarketing Experience with Almotriptan Tablets in Adults Serious cardiovascular events have been reported in association with the use of almotriptan tablets. The uncontrolled nature of postmarketing surveillance, however, makes it impossible to definitively determine the proportion of the reported cases that were actually caused by almotriptan or to reliably assess causation in individual cases [see Adverse Reactions (6.3) ] . Patients with Documented Coronary Artery Disease Because of the potential of this class of compound (5-HT 1 agonists) to cause coronary vasospasm, almotriptan tablets should not be given to patients with documented ischemic or vasospastic coronary artery disease [see Contraindications (4.1) ] . Patients with Risk Factors for CAD It is strongly recommended that almotriptan tablets not be given to patients in whom unrecognized CAD is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoker, obesity, diabetes, strong family history of CAD, female with surgical or physiological menopause, or male over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or other significant underlying cardiovascular disease. The sensitivity of cardiac diagnostic procedures to detect cardiovascular disease or predisposition to coronary artery vasospasm is modest, at best. If, during the cardiovascular evaluation, the patient’s medical history, electrocardiographic or other investigations reveal findings indicative of, or consistent with, coronary artery vasospasm or myocardial ischemia, almotriptan tablets should not be administered [see Contraindications (4.1) ] . For patients with risk factors predictive of CAD, who are determined to have a satisfactory cardiovascular evaluation, it is strongly recommended that administration of the first dose of almotriptan tablets take place in the setting of a physician’s office or similar medically staffed and equipped facility unless the patient has previously received almotriptan tablets. Because cardiac ischemia can occur in the absence of clinical symptoms, consideration should be given to obtaining on the first occasion of use an ECG during the interval immediately following almotriptan tablets, in these patients with risk factors. It is recommended that patients who are intermittent long-term users of almotriptan tablets and who have or acquire risk factors predictive of CAD, as described above, undergo periodic interval cardiovascular evaluation as they continue to use almotriptan tablets. The systematic approach described above is intended to reduce the likelihood that patients with unrecognized cardiovascular disease will be inadvertently exposed to almotriptan tablets. The ability of cardiac diagnostic procedures to detect all cardiovascular diseases or predisposition to coronary artery vasospasm is modest at best. Cardiovascular events associated with triptan treatment have occurred in patients with no cardiac history and with documented absence of coronary artery disease. 5.2 Sensations of Pain, Tightness, Pressure in the Chest and/or Throat, Neck, and Jaw As with other 5-HT 1 agonists, sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw have been reported after treatment with almotriptan tablets. Because 5-HT 1 agonists may cause coronary vasospasm, patients who experience signs or symptoms suggestive of angina following dosing should be evaluated for the presence of CAD or a predisposition to Prinzmetal’s variant angina before receiving additional doses of medication, and should be monitored electrocardiographically if dosing is resumed and similar symptoms occur. Patients shown to have CAD and those with Prinzmetal’s variant angina should not receive 5-HT 1 agonists [see Contraindications (4.1) and Warnings and Precautions (5.1) ] . 5.3 Cerebrovascular Events and Fatalities Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with other triptans and some events have resulted in fatalities. In a number of cases, it appeared possible that the cerebrovascular events were primary, the triptan having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not. As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs and in migraineurs who present with atypical symptoms, care should be taken to exclude other potentially serious neurological conditions. It should be noted that patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, and transient ischemic attack) [see Contraindications (4.2) ] . 5.4 Other Vasospasm-Related Events, Including Peripheral Vascular Ischemia and Colonic Ischemia Triptans, including almotriptan tablets, may cause vasospastic reactions other than coronary artery vasospasm, such as peripheral and gastrointestinal vascular ischemia with abdominal pain and bloody diarrhea. Very rare reports of transient and permanent blindness and significant partial vision loss have been reported with the use of triptans. Visual disorders may also be part of a migraine attack. Patients who experience symptoms or signs suggestive of decreased arterial flow following the use of any triptan, such as ischemic bowel syndrome or Raynaud’s syndrome, are candidates for further evaluation [see Contraindications (4.3) ] . 5.5 Serotonin Syndrome The development of a potentially life-threatening serotonin syndrome may occur with triptans, including almotriptan tablets, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). If concomitant treatment with almotriptan tablets and an SSRI (e.g., fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram) or SNRI (e.g., venlafaxine, duloxetine) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea) [see Drug Interactions (7.3) ] . 5.6 Medication Overuse Headache Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or combination of these drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary. 5.7 Increases in Blood Pressure As with other triptans, significant elevations in systemic blood pressure have been reported on rare occasions with almotriptan tablet use in patients with and without a history of hypertension; very rarely these increases in blood pressure have been associated with significant clinical events. Almotriptan tablets are contraindicated in patients with uncontrolled hypertension [see Contraindications (4.4) ] . In normotensive healthy subjects and patients with hypertension controlled by medication, small, but clinically insignificant, increases in mean systolic (0.21 and 4.87 mm Hg, respectively) and diastolic (1.35 and 0.26 mm Hg, respectively) blood pressure relative to placebo were seen over the first 4 hours after oral administration of 12.5 mg of almotriptan. An 18% increase in mean pulmonary artery pressure was seen following dosing with another triptan in a study evaluating subjects undergoing cardiac catheterization. 5.8 Hypersensitivity to Sulfonamides Caution should be exercised when prescribing almotriptan tablets to patients with known hypersensitivity to sulfonamides. The chemical structure of almotriptan contains a sulfonyl group, which is structurally different from a sulfonamide. Cross-sensitivity to almotriptan in patients allergic to sulfonamides has not been systematically evaluated. 5.9 Impaired Hepatic or Renal Function Almotriptan tablets should be administered with caution to patients with diseases that may alter the absorption, metabolism, or excretion of drugs, such as those with impaired hepatic or renal function [see Dosage and Administration (2.2) , (2.3) and Clinical Pharmacology (12.3) ] . 5.10 Binding to Melanin-Containing Tissues When pigmented rats were given a single oral dose of 5 mg/kg of radiolabeled almotriptan, the elimination half-life of radioactivity from the eye was 22 days. This finding suggests that almotriptan and/or its metabolites may bind to melanin in the eye. Because almotriptan could accumulate in melanin-rich tissues over time, there is the possibility that it could cause toxicity in these tissues with extended use. However, no adverse retinal effects related to treatment with almotriptan were noted in a 52-week toxicity study in dogs given up to 12.5 mg/kg/day (resulting in exposure [AUC] to parent drug approximately 20 times that in humans receiving the maximum recommended human dose of 25 mg/day). Although no systematic monitoring of ophthalmologic function was undertaken in clinical trials, and no specific recommendations for ophthalmologic monitoring are offered, prescribers should be aware of the possibility of long-term ophthalmologic effects. 5.11 Corneal Opacities Three male dogs (out of a total of 14 treated) in a 52-week toxicity study of oral almotriptan developed slight corneal opacities that were noted after 51 weeks, but not after 25 weeks of treatment. The doses at which this occurred were 2 mg/kg/day, 5 mg/kg/day, and 12.5 mg/kg/day. The opacity reversed after a 4-week drug-free period in the affected dog treated with the highest dose. Systemic exposure (plasma AUC) to parent drug at 2 mg/kg/day was approximately 2.5 times the exposure in humans receiving the maximum recommended human daily dose of 25 mg. A no-effect dose was not established."}', 'overdosage': '{"10 OVERDOSAGE 10.1 Signs and Symptoms Patients and volunteers receiving single oral doses of 100 mg to 150 mg of almotriptan did not experience significant adverse events. Six additional normal volunteers received single oral doses of 200 mg without serious adverse events. During clinical trials with almotriptan tablets (almotriptan malate), one patient ingested 62.5 mg in a 5-hour period and another patient ingested 100 mg in a 38-hour period. Neither patient experienced adverse reactions. Based on the pharmacology of triptans, hypertension or other more serious cardiovascular symptoms could occur after overdosage. 10.2 Recommended Treatment There is no specific antidote to almotriptan tablets. In cases of severe intoxication, intensive care procedures are recommended, including establishing and maintaining a patent airway, ensuring adequate oxygenation and ventilation, and monitoring and support of the cardiovascular system. Clinical and electrocardiographic monitoring should be continued for at least 20 hours even if clinical symptoms are not observed. It is unknown what effect hemodialysis or peritoneal dialysis has on plasma concentrations of almotriptan."}', 'active_flag': 'Y', 'generic_name': '{ALMOTRIPTAN}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Drug Interactions: Advise patients to talk with their physician or pharmacist before taking any new medicines, including prescription and non-prescription drugs and supplements [see Contraindications (4.5) and (4.6) and Drug Interactions (7) ] . Hypersensitivity: Inform patients to tell their physician if they develop a rash, itching, or breathing difficulties after taking almotriptan tablets [see Warnings and Precautions (5.8) ] . Risk of Myocardial Ischemia and/or Infarction, Other Adverse Cardiac Events, Other Vasospasm-Related Events, and Cerebrovascular Events: Inform patients that almotriptan tablets may cause serious cardiovascular side effects such as myocardial infarction or stroke, which may result in hospitalization and even death. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, or slurring of speech, and should ask for medical advice when observing any indicative signs or symptoms. Apprise the patient of the importance of this follow-up [see Warnings and Precautions (5.1) , (5.2) , (5.3) , and (5.4) ] . Serotonin Syndrome: Caution patients about the risk of serotonin syndrome with the use of almotriptan tablets or other triptans, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) [see Warnings and Precautions (5.5) ] . Medication Overuse Headache: Inform patients that use of acute migraine drugs for 10 or more days per month may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6) ] . Pregnancy: Advise patients to notify their physician if they become pregnant during treatment or intend to become pregnant [see Use in Specific Populations (8.1) ] . Nursing Mothers: Advise patients to notify their physician if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.3) ] . Ability to Operate Machinery or Vehicles: Counsel patients that almotriptan tablets may cause dizziness, somnolence, visual disturbances, and other CNS symptoms that can interfere with driving or operating machinery. Accordingly, advise the patient not to drive, operate complex machinery, or engage in other hazardous activities until they have gained sufficient experience with almotriptan tablets to gauge whether they affect their mental or visual performance adversely."}', 'pregnancy': '{"8.1 Pregnancy Pregnancy Category C In animal studies, almotriptan produced developmental toxicity (increased embryolethality and fetal skeletal variations, and decreased offspring body weight) at doses greater than those used clinically. There are no adequate and well-controlled studies in pregnant women; therefore, almotriptan tablets (almotriptan malate) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. When almotriptan (125 mg/kg/day, 250 mg/kg/day, 500 mg/kg/day, or 1000 mg/kg/day) was administered orally to pregnant rats throughout the period of organogenesis, increased incidences of fetal skeletal variations (decreased ossification) were noted at a dose of 250 mg/kg/day or greater and an increase in embryolethality was seen at the highest dose. The no-effect dose for embryo-fetal developmental toxicity in rats (125 mg/kg/day) is approximately 100 times the maximum recommended human dose (MRHD) of 25 mg/day on a body surface area (mg/m 2 ) basis. Similar studies in pregnant rabbits conducted with almotriptan (oral doses of 5 mg/kg/day, 20 mg/kg/day, or 60 mg/kg/day) demonstrated increases in embryolethality at the highest dose. The no-effect dose for embryo-fetal developmental toxicity in rabbits (20 mg/kg/day) is approximately 15 times the MRHD on a mg/m 2 basis. When almotriptan (25 mg/kg/day, 100 mg/kg/day, or 400 mg/kg/day) was administered orally to rats throughout the periods of gestation and lactation, gestation length was increased and litter size and offspring body weight were decreased at the highest dose. The decrease in pup weight persisted throughout lactation. The no-effect dose in this study (100 mg/kg/day) is 40 times the MRHD on a mg/m 2 basis."}', 'pediatric_use': '{"8.4 Pediatric Use Safety and efficacy of almotriptan tablets in pediatric patients under the age of 12 years have not been established. The pharmacokinetics, efficacy, and safety of almotriptan tablets have been evaluated in adolescent patients, age 12 to 17 years [see Clinical Pharmacology (12.3) and Clinical Studies (14.2) ] . In a clinical study, almotriptan tablets 6.25 mg and 12.5 mg were found to be effective for the relief of migraine headache pain in adolescent patients age 12 to 17 years. Efficacy on migraine-associated symptoms (nausea, photophobia, and phonophobia) was not established. The most common adverse reactions (incidence of ≥ 1%) associated with almotriptan tablet treatment were dizziness, somnolence, headache, paresthesia, nausea, and vomiting [see Adverse Reactions (6.1) ] . The safety and tolerability profile of almotriptan tablet treatment in adolescents is similar to the profile observed in adults. Postmarketing experience with other triptans include a limited number of reports that describe pediatric patients who have experienced clinically serious adverse events that are similar in nature to those reported rarely in adults."}', 'geriatric_use': '{"8.5 Geriatric Use Clinical studies of almotriptan tablets did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently from younger subjects. Clearance of almotriptan was lower in elderly volunteers than in younger individuals, but there were no observed differences in the safety and tolerability between the two populations [see Clinical Pharmacology (12.3) ] . In general, dose selection for an elderly patient should be cautious, usually starting at the low dose, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. The recommended dose of almotriptan tablets for elderly patients with normal renal function for their age is the same as that recommended for younger adults."}'}

{"INSULIN ASPART"}

{'contraindications': '{"4 CONTRAINDICATIONS Insulin Aspart is contraindicated: • During episodes of hypoglycemia [see Warnings and Precautions ( 5.3 )] • In patients with hypersensitivity to Insulin Aspart or one of its excipients, [see Warnings and Precautions ( 5.5 )] • During episodes of hypoglycemia ( 4 ). • Hypersensitivity to Insulin Aspart or one of its excipients."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following adverse reactions are also discussed elsewhere: • Hypoglycemia [see Warnings and Precautions ( 5.3 )] • Hypoglycemia Due to Medication Errors [see Warnings and Precautions ( 5.4 )] • Hypersensitivity reactions [see Warnings and Precautions ( 5.5 )] • Hypokalemia [see Warnings and Precautions ( 5.6 )] Adverse reactions observed with Insulin Aspart include: hypoglycemia, allergic reactions, local injection site reactions, lipodystrophy, rash, and pruritus ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Pharma, Inc. at 1-800-727-6500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice. The safety of Insulin Aspart was evaluated in two treat-to-target trials of 6 months duration, conducted in patients with type 1 diabetes or type 2 diabetes [see Clinical Studies ( 14 )]. The data in Table 1 reflect the exposure of 596 patients with type 1 diabetes to Insulin Aspart in one clinical trial with a mean exposure duration to Insulin Aspart of 24 weeks. The mean age was 39 years. Fifty-one percent were male, 94% were Caucasian, 2% were Black and 4% were other races. The mean body mass index (BMI) was 25.6 kg/m 2 . The mean duration of diabetes was 15.7 years and the mean HbA 1c at baseline was 7.9%. The data in Table 2 reflect the exposure of 91 patients with type 2 diabetes to Insulin Aspart in one clinical trial with a mean exposure duration to Insulin Aspart of 24 weeks. The mean age was 57 years. Sixty-three percent were male, 76% were Caucasian, 9% were Black and 15% were other races. The mean BMI was 29.7 kg/m 2 . The mean duration of diabetes was 12.7 years and the mean HbA 1c at baseline was 8.1%. Common adverse reactions were defined as events that occurred in ≥5%, excluding hypoglycemia, of the population studied. Common adverse events that occurred at the same rate or greater for Insulin Aspart-treated patients than in comparator-treated patients during clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus (other than hypoglycemia) are listed in Table 1 and Table 2, respectively. Table 1: Adverse reactions that occurred in ≥ 5% of Type 1 Diabetes Mellitus Adult Patients treated with Insulin Aspart and at the same rate or greater on Insulin Aspart than on comparator Insulin Aspart + NPH (%) (n= 596) Regular Human Insulin + NPH (%) (n= 286) Headache 12 10 Injury accidental 11 10 Nausea 7 5 Diarrhea 5 3 Table 2: Adverse reactions that occurred in ≥ 5% of Type 2 Diabetes Mellitus Adult Patients treated with Insulin Aspart and at the same rate or greater on Insulin Aspart than on comparator Insulin Aspart + NPH (%) (n= 91) Human Regular Insulin + NPH (%) (n= 91) Hyporeflexia 11 7 Onychomycosis 10 5 Sensory disturbance 9 7 Urinary tract infection 8 7 Chest pain 5 3 Headache 5 3 Skin disorder 5 2 Abdominal pain 5 1 Sinusitis 5 1 Severe Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including Insulin Aspart . The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia in clinical trials for Insulin Aspart with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice. Severe hypoglycemia was defined as hypoglycemia associated with central nervous system symptoms and requiring the intervention of another person or hospitalization. The incidence of severe hypoglycemia in: • Adult and pediatric patients with type 1 diabetes mellitus who received subcutaneous Insulin Aspart was 17% at 24 weeks and 6% at 24 weeks, respectively [see Clinical Studies ( 14 )] . • Adult patients with type 2 diabetes mellitus who received subcutaneous Insulin Aspart was 10% at 24 weeks. • Adult and pediatric patients with type 1 diabetes mellitus, who received Insulin Aspart via continuous subcutaneous insulin infusion by external pump was 2% at 16 weeks and 10% at 16 weeks respectively. No severe hypoglycemic episodes were reported in adult patients with type 2 diabetes mellitus receiving Insulin Aspart via continuous subcutaneous insulin infusion by external pump at 16 weeks. Allergic Reactions Some patients taking insulin, including Insulin Aspart have experienced erythema, local edema, and pruritus at the site of injection. These conditions were usually self-limiting. Severe cases of generalized allergy (anaphylaxis) have been reported. Adverse Reactions Associated with Insulin Initiation and Glucose Control Intensification Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy. Lipodystrophy Administration of insulin, including Insulin Aspart, subcutaneously and via subcutaneous insulin infusion by external pump, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) in some patients [see Dosage and Administration ( 2.2 )]. Peripheral Edema Insulins, including Insulin Aspart, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy. Weight Gain Weight gain has occurred with insulins including Insulin Aspart and has been attributed to the anabolic effects of insulin and the decrease in glucosuria. 6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Insulin Aspart in the studies described below with the incidence of antibodies in other studies or to other products may be misleading. In a 6-month study with a 6-month extension in adult subjects with type 1 diabetes, 99.8% of patients who received Insulin Aspart were positive for anti-insulin antibodies (AIA) at least once during the study, including 97.2% that were positive at baseline. A total of 92.1% of patients who received Insulin Aspart were positive for anti-drug antibodies (ADA) at least once during the study, including 64.6% that were positive at baseline. In a phase 3 type 1 diabetes clinical trial of Insulin Aspart, initial increase in titers of antibodies to insulin, followed by a decrease to baseline values, was observed in regular human insulin and insulin aspart treatment groups with similar incidences. These antibodies did not cause deterioration in glycemic control or necessitate increases in insulin dose. 6.3 Post Marketing Experience The following adverse reactions have been identified during post-approval use of Insulin Aspart. Because these adverse reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Medication errors have been reported in which other insulins have been accidentally substituted for Insulin Aspart. Localized cutaneous amyloidosis at the injection site has occurred with insulin aspart. Hyperglycemia has been reported with repeated insulin injections into areas of localized cutaneous amyloidosis; hypoglycemia has been reported with a sudden change to an unaffected injection site."}', 'drug_interactions': '{"7 DRUG INTERACTIONS The table below presents clinically significant drug interactions with Insulin Aspart. Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when Insulin Aspart is concomitantly administered with these drugs. Drugs That May Decrease the Blood Glucose Lowering Effect of Insulin Aspart Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when Insulin Aspart is concomitantly administered with these drugs. Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of Insulin Aspart Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when Insulin Aspart is concomitantly administered with these drugs. Drugs That May Blunt Signs and Symptoms of Hypoglycemia Drugs: Beta-blockers, clonidine, guanethidine and reserpine Intervention: Increased frequency of glucose monitoring may be required when Insulin Aspart is concomitantly administered with these drugs. • Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and +sulfonamide antibiotics ( 7 ). • Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones ( 7 ). • Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine ( 7 ). • Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine ( 7 )."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Insulin Aspart is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus. Insulin Aspart is rapid acting human insulin analog indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus ( 1 )."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Never share a Insulin Aspart FlexPen, PenFill cartridge or PenFill cartridge device between patients, even if the needle is changed ( 5.1 ). • Hyperglycemia or hypoglycemia with changes in insulin regimen: Make changes to a patient’s insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) under close medical supervision with increased frequency of blood glucose monitoring ( 5.2 ). • Hypoglycemia: May be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, concomitantly administered glucose lowering medications, meal pattern, physical activity; and in patients with renal or hepatic impairments and hypoglycemia unawareness ( 5. 3). • Medication Errors: Accidental mix-ups between insulin products can occur. Instruct patients to check insulin labels before injection ( 5. 4). • Hypersensitivity reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, may occur. Discontinue Insulin Aspart, treat, and monitor, if indicated ( 5.5 ). • Hypokalemia: May be life-threatening. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated ( 5. 6). • Fluid retention and heart failure with concomitant use of thiazolidinediones (TZDs): Observe for signs and symptoms of heart failure; consider dosage reduction or discontinuation if heart failure occurs ( 5.7 ). • Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction: Monitor glucose and administer Insulin Aspart by subcutaneous injection if pump malfunction occurs ( 5.8 ). 5.1 Never Share a Insulin Aspart FlexPen, PenFill Cartridge, or PenFill Cartridge Device between Patients Insulin Aspart FlexPen, PenFill cartridge, and PenFill cartridge devices should never be shared between patients, even if the needle is changed. Patients using Insulin Aspart vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens. 5.2 Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions ( 5.3 )] or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions ( 6.1 , 6.3 )]. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, dosage adjustments of concomitant anti-diabetic products may be needed. 5.3 Hypoglycemia Hypoglycemia is the most common adverse reaction of all insulins, including Insulin Aspart. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions ( 7 )] , or in patients who experience recurrent hypoglycemia. Risk Factors for Hypoglycemia The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of Insulin Aspart may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature [see Clinical Pharmacology ( 12.2 )] . Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to concomitantly administered medication [see Drug Interactions ( 7 )] . Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations ( 8.6 , 8.7 )]. Risk Mitigation Strategies for Hypoglycemia Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia; increased frequency of blood glucose monitoring is recommended. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia; increased frequency of blood glucose monitoring is recommended. 5.4 Hypoglycemia Due to Medication Errors Accidental mix-ups between insulin products have been reported. To avoid medication errors between this Insulin Aspart product and other insulins, instruct patients to always check the insulin label before each injection. 5.5 Hypersensitivity Reactions Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including Insulin Aspart. If hypersensitivity reactions occur, discontinue Insulin Aspart; treat per standard of care and monitor until symptoms and signs resolve [see Adverse Reactions ( 6 )]. Insulin Aspart is contraindicated in patients who have had hypersensitivity reactions to insulin aspart or one of the excipients [see Contraindications ( 4 )]. 5.6 Hypokalemia All insulins, including Insulin Aspart, can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentration). 5.7 Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including Insulin Aspart, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered. 5.8 Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction Malfunction of the insulin pump or insulin infusion set or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Interim subcutaneous injections with Insulin Aspart may be required. Patients using continuous subcutaneous insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure [see How Supplied/Storage and Handling ( 16.2 ) and Patient Counseling Information ( 17 )] ."}', 'overdosage': '{"10 OVERDOSAGE Excess insulin administration may cause hypoglycemia and hypokalemia [see Warnings and Precautions ( 5.3 , 5.6 )] . Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately."}', 'active_flag': 'Y', 'generic_name': '{"INSULIN ASPART"}', 'route': '{INTRAVENOUS,SUBCUTANEOUS}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Never Share an Insulin Aspart FlexPen, PenFill Cartridge or PenFill Cartridge Device between Patients Advise patients that they must never share Insulin Aspart FlexPen, PenFill cartridge or PenFill cartridge devices with another person even if the needle is changed, because doing so carries a risk for transmission of blood-borne pathogens. Advise patients using Insulin Aspart vials not to share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens [see Warnings and Precautions ( 5.1 )] . Hyperglycemia or Hypoglycemia Inform patients that hypoglycemia is the most common adverse reaction with insulin. Instruct patients on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia, especially at initiation of Insulin Aspart therapy. Instruct patients on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, and skipped meals. Instruct patients on the management of hypoglycemia [see Warnings and Precautions ( 5.3 )] . Inform patients that their ability to concentrate and react may be impaired as a result of hypoglycemia. Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery. Advise patients that changes in insulin regimen can predispose to hyperglycemia or hypoglycemia and that changes in insulin regimen should be made under close medical supervision [see Warnings and Precautions ( 5.2 )] . Hypoglycemia with Medication Errors Instruct patients to always check the insulin label before each injection to avoid mix-ups between insulin products [see Warnings and Precautions ( 5.3 )] . Hypersensitivity Reactions Advise patients that hypersensitivity reactions have occurred with Insulin Aspart. Inform patients of the symptoms of hypersensitivity reactions [see Warnings and Precautions ( 5.4 )] . Patients Using Continuous Subcutaneous Insulin Pumps • Train patients in both intensive insulin therapy with multiple injections and in the function of their pump and pump accessories. • This Insulin Aspart product can be used with continuous subcutaneous insulin infusion pumps labeled for use with NOVOLOG (insulin aspart) - refer to the insulin pump user manual to see if NOVOLOG can be used. See recommended infusion sets in the insulin pump user manual. • Instruct patients to replace insulin in the reservoir at least every 7 days or according to the user manual, whichever is shorter, infusion sets and infusion set insertion sites should be changed in according to the manufacturer’s user manual. By following this schedule, patients avoid insulin degredation, infusion set occlusion, and loss of the insulin preservative. • Instruct patients to discard insulin exposed to temperatures higher than 37°C (98.6°F). • Instruct patients to inform physician and select a new site for infusion if infusion site becomes erythematous, pruritic, or thickened. • Instruct patients of the risk of rapid hyperglycemia and ketosis due to pump malfunction, infusion set occlusion, leakage, disconnection or kinking, and degraded insulin. If these problems cannot be promptly corrected, instruct patients to resume therapy with subcutaneous insulin injection and contact their physician [see Warnings and Precautions ( 5 ) and How Supplied/Storage and Handling ( 16.2 )] . • Instruct patients of the risk of hypoglycemia from pump malfunction. If these problems cannot be promptly corrected, instruct patients to resume therapy with subcutaneous insulin injection and contact their physician [see Warnings and Precautions ( 5 ) and How Supplied/Storage and Handling ( 16.2 )] . Manufactured by: Novo Nordisk Inc. 800 Scudders Mill Road Plainsboro, NJ 08536 U.S. License Number 1261 Distributed by: Novo Nordisk Pharma, Inc. Version: 3 Novo Nordisk ® , NovoLog ® , PenFill ® , Novolin ® , FlexPen ® , NovoFine ® , and NovoTwist ® are registered trademarks of Novo Nordisk A/S. Patent Information: http://novonordisk-us.com/products/product-patents.html © 2023 Novo Nordisk 1-800-727-6500"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Available information from published randomized controlled trials with insulin aspart use during the second trimester of pregnancy have not reported an association with insulin aspart and major birth defects or adverse maternal or fetal outcomes [see Data] . There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations] . In animal reproduction studies, administration of subcutaneous insulin aspart to pregnant rats and rabbits during the period of organogenesis did not cause adverse developmental effects at exposures 8-times and equal to the human subcutaneous dose of 1 unit/kg/day, respectively. Pre- and post-implantation losses and visceral/skeletal abnormalities were seen at higher exposures, which are considered secondary to maternal hypoglycemia. These effects were similar to those observed in rats administered regular human insulin [see Data] . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a periconceptional HbA 1c >7% and has been reported to be as high as 20 to 25% in women with a periconceptional HbA 1c >10%. The estimated background risk of miscarriage for the indicated population is unknown. Clinical Considerations Disease-Associated Maternal and/or Embryo-Fetal Risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Data Human Data Published data from 5 randomized controlled trials of 441 pregnant women with diabetes mellitus treated with insulin aspart during the late 2 nd trimester of pregnancy did not identify an association of insulin aspart with major birth defects or adverse maternal or fetal outcomes. However, these studies cannot definitely establish the absence of any risk because of methodological limitations, including a variable duration of treatment and small size of the majority of the trials. Animal Data Fertility, embryo-fetal and pre- and postnatal development studies have been performed with insulin aspart and regular human insulin in rats and rabbits. In a combined fertility and embryo-fetal development study in rats, insulin aspart was administered before mating, during mating, and throughout pregnancy. Further, in a pre- and postnatal development study insulin aspart was given throughout pregnancy and during lactation to rats. In an embryo-fetal development study insulin aspart was given to female rabbits during organogenesis. The effects of insulin aspart did not differ from those observed with subcutaneous regular human insulin. Insulin aspart, like human insulin, caused pre- and post-implantation losses and visceral/skeletal abnormalities in rats at a dose of 200 units/kg/day (approximately 32 times the human subcutaneous dose of 1 unit/kg/day, based on human exposure equivalents) and in rabbits at a dose of 10 units/kg/day (approximately three times the human subcutaneous dose of 1 unit/kg/day, based on human exposure equivalents). No significant effects were observed in rats at a dose of 50 units/kg/day and in rabbits at a dose of 3 units/kg/day. These doses are approximately 8 times the human subcutaneous dose of 1 unit/kg/day for rats and equal to the human subcutaneous dose of 1 unit/kg/day for rabbits, based on human exposure equivalents. The effects are considered secondary to maternal hypoglycemia."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness of Insulin Aspart to improve glycemic control have been established in pediatric patients with diabetes mellitus. Use of Insulin Aspart for this indication is supported by evidence from an adequate and well-controlled study in 283 pediatric patients with type 1 diabetes mellitus aged 6 to 18 years and from studies in adults with diabetes mellitus [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14 )] ."}', 'geriatric_use': '{"8.5 Geriatric Use Of the total number of patients (n=1,375) treated with Insulin Aspart in 3 controlled clinical studies, 2.6% (n=36) were 65 years of age or over. One-half of these patients had type 1 diabetes (18/1285) and the other half had type 2 diabetes (18/90). The HbA 1c response to Insulin Aspart, as compared to regular human insulin, did not differ by age."}'}

{FAMOTIDINE}

{'contraindications': '{"4 CONTRAINDICATIONS Famotidine tablets are contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis) to famotidine or other histamine-2 (H 2 ) receptor antagonists. History of serious hypersensitivity reactions (e.g., anaphylaxis) to famotidine or other H 2 receptor antagonists. (4)"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The most common adverse reactions are: headache, dizziness, constipation, and diarrhea. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Famotidine was studied in 7 U.S. and international placebo- and active-controlled trials in approximately 2500 patients [see Clinical Studies (14)] . A total of 1442 patients were treated with famotidine, including 302 treated with 40 mg twice daily, 456 treated with 20 mg twice daily, 461 treated with 40 mg once daily, and 396 treated with 20 mg once daily. The population was 17 to 91 years old, fairly well distributed between gender and race; however, the predominant race treated was Caucasian. The following adverse reactions occurred in greater than or equal to 1% of famotidine-treated patients: headache, dizziness and constipation. The following other adverse reactions were reported in less than 1% of patients in clinical trials: Body as a Whole: fever, asthenia, fatigue Cardiovascular: palpitations Gastrointestinal: elevated liver enzymes, vomiting, nausea, abdominal discomfort, anorexia, dry mouth Hematologic: thrombocytopenia Hypersensitivity: orbital edema, rash, conjunctival injection, bronchospasm Musculoskeletal: musculoskeletal pain, arthralgia Nervous System/Psychiatric: seizure, hallucinations, depression, anxiety, decreased libido, insomnia, somnolence Skin: pruritus, dry skin, flushing Special Senses: tinnitus, taste disorder Other: impotence 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of famotidine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular: arrhythmia, AV block, prolonged QT interval Gastrointestinal: cholestatic jaundice, hepatitis Hematologic: agranulocytosis, pancytopenia, leukopenia Hypersensitivity: anaphylaxis, angioedema, facial edema, urticaria Musculoskeletal: rhabdomyolysis, muscle cramps Nervous System/Psychiatric: confusion, agitation, paresthesia Respiratory: interstitial pneumonia Skin: toxic epidermal necrolysis/Stevens-Johnson syndrome"}', 'drug_interactions': '{"7 DRUG INTERACTIONS • Drugs Dependent on Gastric pH for Absorption : Systemic exposure of the concomitant drug may be significantly reduced leading to loss of efficacy. See full prescribing information for a list of interacting drugs. (7.1) • Tizanidine (CYP1A2) Substrate: Potential for substantial increases in blood concentrations of tizanidine resulting in hypotension, bradycardia or excessive drowsiness; avoid concomitant use, if possible. (7.2) 7.1 Drugs Dependent on Gastric pH for Absorption Famotidine can reduce the absorption of other drugs, due to its effect on reducing intragastric acidity, leading to loss of efficacy of the concomitant drug. Concomitant administration of famotidine with dasatinib, delavirdine mesylate, cefditoren, and fosamprenavir is not recommended. See the prescribing information for other drugs dependent on gastric pH for absorption for administration instructions, including atazanavir, erlotinib, ketoconazole, itraconazole, ledipasvir/sofosbuvir, nilotinib, and rilpivirine. 7.2 Tizanidine (CYP1A2 Substrate) Although not studied clinically, famotidine is considered a weak CYP1A2 inhibitor and may lead to substantial increases in blood concentrations of tizanidine, a CYP1A2 substrate. Avoid concomitant use with famotidine. If concomitant use is necessary, monitor for hypotension, bradycardia or excessive drowsiness. Refer to the full prescribing information for tizanidine."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Famotidine tablets are indicated in adult and pediatric patients 40 kg and greater for the treatment of: • active duodenal ulcer (DU). • active gastric ulcer (GU). • symptomatic nonerosive gastroesophageal reflux disease (GERD). • erosive esophagitis due to GERD, diagnosed by biopsy. Famotidine tablets are indicated in adults for the: • treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine neoplasias). • reduction of the risk of duodenal ulcer recurrence. Famotidine is a histamine-2 (H 2 ) receptor antagonist indicated (1) : In adult and pediatric patients 40 kg and greater for the treatment of: • active duodenal ulcer (DU). • active gastric ulcer. • symptomatic nonerosive gastroesophageal reflux disease (GERD). • erosive esophagitis due to GERD, diagnosed by biopsy. In adults for the: • treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine neoplasias). • reduction of the risk of DU recurrence."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Central Nervous System (CNS) Adverse Reactions : Elderly patients and patients with renal impairment at increased risk; reduce the dosage. ( 2.2 , 5.1 , 8.5 , 8.6 ) • GI Malignancy : Absence of GI symptoms does not preclude the presence of gastric malignancy; evaluate prior to initiating therapy. ( 5.2 ) 5.1 Central Nervous System Adverse Reactions Central nervous system (CNS) adverse reactions, including confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy, have been reported in elderly patients and patients with moderate and severe renal impairment treated with famotidine. Since famotidine blood levels are higher in patients with renal impairment than in patients with normal renal function, dosage adjustments are recommended in patients with renal impairment [see Dosage and Administration (2.2) , Clinical Pharmacology (12.3) ]. 5.2 Concurrent Gastric Malignancy In adults, symptomatic response to therapy with famotidine does not preclude the presence of gastric malignancy. Consider evaluation for gastric malignancy in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with famotidine."}', 'overdosage': '{"10 OVERDOSAGE The types of adverse reactions in overdosage of famotidine are similar to the adverse reactions encountered with use of recommended dosages [see Adverse Reactions (6.1) ] . In the event of overdosage, treatment should be symptomatic and supportive. Unabsorbed material should be removed from the gastrointestinal tract, the patient should be monitored, and supportive therapy should be employed. Due to low binding to plasma proteins, famotidine is eliminated by hemodialysis. There is limited experience on the usefulness of hemodialysis as a treatment for famotidine overdosage."}', 'active_flag': 'Y', 'generic_name': '{FAMOTIDINE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Central Nervous System (CNS) Adverse Reactions Advise elderly patients and those with moderate and severe renal impairment of the risk of CNS adverse reactions, including confusion, delirium, hallucinations, disorientation, agitation, seizures, and lethargy [see Warnings and Precautions (5.1) ] . Report symptoms immediately to a healthcare provider. QT Prolongation Advise patients with moderate and severe renal impairment of the risk of QT interval prolongation [see Use in Specific Populations (8.6) ] . Report new cardiac symptoms, such as palpitations, fainting and dizziness or lightheadedness immediately to a healthcare provider. Administration Advise patients: • Take famotidine tablets once daily before bedtime or twice daily in the morning and before bedtime, as recommended. • Famotidine tablets may be taken with or without food. • Famotidine tablets may be given with antacids. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad–500 038, India Repackaged by: Proficient Rx LP Thousand Oaks, CA 91320 Revised: 05/2019"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Available data with H 2 -receptor antagonists, including famotidine, in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse development effects were observed with oral administration of famotidine at doses up to approximately 243 and 122 times, respectively, the recommended human dose of 80 mg per day for the treatment of erosive esophagitis (see Data) . The estimated background risk for major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Reproductive studies have been performed in rats and rabbits at oral doses of up to 2000 and 500 mg/kg/day, respectively, and in both species at intravenous doses of up to 200 mg/kg/day, and have revealed no significant evidence of impaired fertility or harm to the fetus due to famotidine. While no direct fetotoxic effects have been observed, sporadic abortions occurring only in mothers displaying marked decreased food intake were seen in some rabbits at oral doses of 200 mg/kg/day (about 49 times the recommended human dose of 80 mg per day, based on body surface area) or higher. There are, however, no adequate or well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness of famotidine have been established in pediatric patients for the treatment of peptic ulcer disease (i.e., duodenal ulcer, gastric ulcer) and GERD (i.e., symptomatic nonerosive GERD, erosive esophagitis as diagnosed by endoscopy). The use of famotidine and the recommended dosage of famotidine in these pediatric patients is supported by evidence from adequate and well-controlled studies of famotidine in adults and published pharmacokinetic and pharmacodynamic data in pediatric patients [see Dosage and Administration (2.1) , Clinical Pharmacology (12.2, 12.3) ] . In pediatric patients, the safety and effectiveness for the treatment of pathological hypersecretory conditions and reduction of risk of duodenal ulcer recurrence have not been established. Famotidine 20 and 40 mg tablets are not recommended for use in pediatric patients weighing less than 40 kg because these tablet strengths exceed the recommended dose for these patients [see Dosage and Administration (2.1) ] . For pediatric patients weighing less than 40 kg, consider another famotidine formulation (e.g., oral suspension, lower dose tablet)."}', 'geriatric_use': '{"8.5 Geriatric Use Of the 1442 famotidine-treated patients in clinical studies, approximately 10% were 65 and older. In these studies, no overall differences in safety or effectiveness were observed between elderly and younger patients. In postmarketing experience, CNS adverse reactions have been reported in elderly patients with and without renal impairment receiving famotidine [see Warnings and Precautions (5.1) ] . Famotidine is known to be substantially excreted by the kidney, and the risk of adverse reactions to famotidine may be greater in elderly patients, particularly those with impaired renal function [see Use in Specific Populations (8.6) ] . In general, use the lowest effective dose of famotidine for an elderly patient and monitor renal function [see Dosage and Administration (2.2) ]."}'}

{"MENTHOL, UNSPECIFIED FORM"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses Relieves tingling, itching, burning, blistering, and pain associated with cold sores/fever blisters."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"MENTHOL, UNSPECIFIED FORM"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if condition worsens; or symptoms last more than 7 days or clear up and occur again"}', 'do_not_use': None, 'when_using': '{"When using this product do not get into eyes."}', 'warnings': '{"Warnings For external use only. When using this product do not get into eyes. Stop use and ask a doctor if condition worsens; or symptoms last more than 7 days or clear up and occur again Keep out of reach of children. If swallowed get medical help or contact a Poison Control Center right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"DOCUSATE SODIUM",SENNOSIDES}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses for overnight relief from occasional constipation (irregularity) generally produces bowel movement in 6 to 12 hours"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"DOCUSATE SODIUM, SENNOSIDES"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if you have rectal bleeding or fail to have a bowel movement after use of a laxative. These may indicate a serious condition."}', 'do_not_use': '{"Do not use laxative products for longer than 1 week unless directed by a doctor if you are now taking mineral oil, unless directed by a doctor"}', 'when_using': None, 'warnings': '{"Warnings Do not use laxative products for longer than 1 week unless directed by a doctor if you are now taking mineral oil, unless directed by a doctor Ask a doctor before use if you have stomach pain nausea vomiting noticed a sudden change in bowel habits that lasts over a period of 2 weeks Stop use and ask a doctor if you have rectal bleeding or fail to have a bowel movement after use of a laxative. These may indicate a serious condition. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"ICOSAPENT ETHYL"}

{'contraindications': '{"4 CONTRAINDICATIONS Icosapent ethyl capsules are contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to icosapent ethyl or any of its components. Icosapent ethyl capsules are contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to icosapent ethyl or any of its components. (4)"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following important adverse reactions are described below and elsewhere in the labeling: Atrial Fibrillation or Atrial Flutter [see Warnings and Precautions (5.1)] Potential for Allergic Reactions in Patients with Fish Allergy [see Warnings and Precautions (5.2)] Bleeding [see Warnings and Precautions (5.3)] Common adverse reactions (incidence ≥3% and ≥1% more frequent than placebo): musculoskeletal pain, peripheral edema, constipation, gout, and atrial fibrillation. (6.1) Common adverse reactions in the hypertriglyceridemia trials (incidence ≥1% more frequent than placebo): arthralgia and oropharyngeal pain. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Camber Pharmaceuticals, Inc., at 1-866-495-8330 or contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Common adverse reactions (incidence ≥3% on icosapent ethyl and ≥1% more frequent than placebo) included musculoskeletal pain, peripheral edema, constipation, gout, and atrial fibrillation. Hypertriglyceridemia Trials In two randomized, double-blind, placebo-controlled trials in patients with triglyceride levels between 200 and 2000 mg/dL treated for 12 weeks, adverse reactions reported with icosapent ethyl at an incidence ≥1% more frequent than placebo based on pooled data included arthralgia and oropharyngeal pain. 6.2 Postmarketing Experience Additional adverse reactions have been identified during post-approval use of icosapent ethyl capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Diarrhea Blood triglycerides increased Abdominal discomfort Pain in the extremities"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Increased Bleeding Risk with Anticoagulants and Antiplatelet Agents: Some published studies with omega-3 fatty acids have demonstrated prolongation of bleeding time. Monitor patients receiving icosapent ethyl and concomitant anticoagulants and/or antiplatelet agents for bleeding. (7) 7.1 Increased Bleeding Risk with Anticoagulants and Antiplatelet Agents Some published studies with omega-3 fatty acids have demonstrated prolongation of bleeding time. The prolongation of bleeding time reported in those studies has not exceeded normal limits and did not produce clinically significant bleeding episodes. Monitor patients receiving icosapent ethyl and concomitant anticoagulants and/or antiplatelet agents for bleeding."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Icosapent ethyl capsules are indicated: as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia. Limitations of Use: The effect of icosapent ethyl capsules on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined. Icosapent ethyl capsules are an ethyl ester of eicosapentaenoic acid (EPA) indicated: as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia. (1) Limitations of Use: The effect of icosapent ethyl capsules on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined. (1)"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Atrial Fibrillation/Flutter: Icosapent ethyl was associated with an increased risk of atrial fibrillation or atrial flutter requiring hospitalization in a double-blind, placebo-controlled trial. The incidence of atrial fibrillation was greater in patients with a previous history of atrial fibrillation or atrial flutter. (5.1) Potential for Allergic Reactions in Patients with Fish Allergy: Icosapent ethyl capsules contains ethyl esters of the omega-3 fatty acid, eicosapentaenoic acid (EPA), obtained from the oil of fish. It is not known whether patients with allergies to fish and/or shellfish are at increased risk of an allergic reaction to icosapent ethyl capsules. Inform patients with known hypersensitivity to fish and/or shellfish about the potential for allergic reactions and advise them to discontinue icosapent ethyl and seek medical attention if any reactions occur. (5.2) Bleeding: Icosapent ethyl was associated with an increased risk of bleeding in a double-blind, placebo-controlled trial. The incidence of bleeding was greater in patients receiving concomitant antithrombotic medications, such as aspirin, clopidogrel, or warfarin. (5.3) 5.1 Atrial Fibrillation/Flutter Icosapent ethyl is associated with an increased risk of atrial fibrillation or atrial flutter requiring hospitalization. In a double-blind, placebo-controlled trial of 8,179 subjects, adjudicated atrial fibrillation or atrial flutter requiring hospitalization for 24 or more hours occurred in 127 (3%) patients treated with icosapent ethyl compared to 84 (2%) patients receiving placebo [HR= 1.5 (95% CI 1.14, 1.98)]. The incidence of atrial fibrillation was greater in patients with a previous history of atrial fibrillation or atrial flutter. 5.2 Potential for Allergic Reactions in Patients with Fish Allergy Icosapent ethyl contains ethyl esters of the omega-3 fatty acid, eicosapentaenoic acid (EPA), obtained from the oil of fish. It is not known whether patients with allergies to fish and/or shellfish are at increased risk of an allergic reaction to icosapent ethyl. Inform patients with known hypersensitivity to fish and/or shellfish about the potential for allergic reactions to icosapent ethyl and advise them to discontinue icosapent ethyl and seek medical attention if any reactions occur. 5.3 Bleeding Icosapent ethyl is associated with an increased risk of bleeding. In a double-blind, placebo-controlled trial of 8,179 patients, 482 (12%) patients receiving icosapent ethyl experienced a bleeding event compared to 404 (10%) patients receiving placebo. Serious bleeding events occurred in 111 (3%) of patients on icosapent ethyl vs. 85 (2%) of patients receiving placebo. The incidence of bleeding was greater in patients receiving concomitant antithrombotic medications, such as aspirin, clopidogrel, or warfarin."}', 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"ICOSAPENT ETHYL"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling before starting icosapent ethyl capsules (Patient Information). Inform patients that icosapent ethyl capsules may increase their risk for atrial fibrillation or atrial flutter [see Warnings and Precautions (5.1)] . Inform patients with known hypersensitivity to fish and/or shellfish about the potential for allergic reactions to icosapent ethyl capsules and advise them to discontinue icosapent ethyl capsules and seek medical attention if any reactions occur [see Warnings and Precautions (5.2)] . Inform patients that icosapent ethyl capsules may increase their risk for bleeding, especially if they are receiving other antithrombotic agents [see Warnings and Precautions (5.3)] . Advise patients to swallow icosapent ethyl capsules whole. Do not break open, crush, dissolve, or chew icosapent ethyl capsules [see Dosage and Administration (2.2)] . Instruct patients to take icosapent ethyl capsules as prescribed. If a dose is missed, patients should take it as soon as they remember. However, if they miss one day of icosapent ethyl capsules, they should not double the dose when they take it. For more information about icosapent ethyl capsules, call Camber Pharmaceuticals, Inc. at 1-866-495-8330. Manufactured by: Ascent Pharmaceuticals, Inc. Central Islip, NY 11722 Manufactured for: Camber Pharmaceuticals, Inc. Piscataway, NJ 08854 Rev: 07/23"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary The available data from published case reports and the pharmacovigilance database on the use of icosapent ethyl in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies in pregnant rats, non-dose-related imbalances for some minor developmental findings were observed with oral administration of icosapent ethyl during organogenesis at exposures that were equivalent to the clinical exposure at the human dose of 4 g/day, based on body surface area comparisons. In a study in pregnant rabbits orally administered icosapent ethyl during organogenesis, there were no clinically relevant adverse developmental effects at exposures that were 5 times the clinical exposure, based on body surface area comparisons ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In pregnant rats given oral gavage doses of 0.3, 1 and 2 g/kg/day icosapent ethyl from gestation through organogenesis all drug treated groups had non-dose-related imbalances in visceral and skeletal findings, including 13 th reduced ribs, additional liver lobes, testes medially displaced and/or not descended, at human systemic exposures following a maximum oral dose of 4 g/day based on body surface comparisons. In a multigenerational developmental study in pregnant rats given doses of 0.3, 1, 3 g/kg/day icosapent ethyl by oral gavage from gestation day 7-17, icosapent ethyl did not affect viability in fetuses (F 1 or F 2 ). Non-dose-related imbalances in findings of absent optic nerves and unilateral testes atrophy at human exposures based on the maximum dose of 4 g/day and on body surface area comparisons. Additional variations consisting of early incisor eruption and increased percent cervical ribs were observed at the same exposures. Pups from high dose treated dams exhibited decreased copulation rates, delayed estrus, decreased implantations and decreased surviving fetuses (F2) suggesting potential multigenerational effects of icosapent ethyl at 7 times human systemic exposure following 4 g/day dose based on body surface area comparisons across species. In pregnant rabbits given oral gavage doses of 0.1, 0.3, and 1 g/kg/day icosapent ethyl from gestation through organogenesis, a decrease in body weight and food consumption was observed at the high dose of 1 g/kg/day (5 times the human exposure at the maximum dose of 4 g/day, based on body surface area comparisons). Slight increases in resorbed and dead fetuses were noted in the 1 g/kg/day group, but these were not significantly different from the control group. There were no differences between the icosapent ethyl groups and control group as to the number of corpora lutea , number of implantations, number of surviving fetuses, sex ratio, body weight of female fetuses or placental weight. There were no treatment-related malformations or skeletal anomalies. In pregnant rats given icosapent ethyl from gestation day 17 through lactation day 20 at 0.3, 1, 3 g/kg/day no adverse maternal or developmental effects were observed. However, complete litter loss (not dose-related) was noted in 2/23 litters at the low dose and 1/23 mid-dose dams by post-natal day 4 at human exposures at a maximum dose of 4 g/day, based on body surface area comparisons."}', 'pediatric_use': '{"8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established."}', 'geriatric_use': '{"8.5 Geriatric Use Of the total number of patients in well-controlled clinical studies of icosapent ethyl, 45% were 65 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger groups. Other reported clinical experience has not identified differences in responses between the elderly and younger patients."}'}

{"DEXTROMETHORPHAN HYDROBROMIDE",GUAIFENESIN}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses ■ Temporarily relieves cough due to minor throat and bronchial irritation as may occur with a common cold ■ Helps loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus ■ Helps make coughs more productive."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"DEXTROMETHORPHAN HYDROBROMIDE / GUAIFENESIN"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask doctor if ■ symptoms are accompanied by fever, rash or persistent headache ■ cough persists for more than 1 week or tends to recur. A persistent cough may be a sign of a serious condition."}', 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings Do not use ■ if you are now taking a prescription monoamine oxidase (inhiMor~MAIO) (Certain drugs for depression, psychiatric or emotional conditioners or Parkinson\'s disease)or for 2 weeks after stopping MAIO drug, If you do not know if your prescription drug contains an MAIO, ask your doctor or pharmacist before using this product."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"CINACALCET HYDROCHLORIDE"}

{'contraindications': '{"4 CONTRAINDICATIONS Cinacalcet treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range [ see Warnings and Precautions (5.1)]. Cinacalcet treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range. ( 4 , 5.1 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of labeling: Hypocalcemia [see Warnings and Precautions (5.1)] Upper Gastrointestinal Bleeding [see Warnings and Precautions (5.2)] Hypotension, Worsening Heart Failure and/or Arrhythmias [see Warnings and Precautions (5.3)] Adynamic Bone Disease [see Warnings and Precautions (5.4)] The most common adverse reactions (i.e., ≥ 25%) associated with cinacalcet were nausea and vomiting. (6) To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-ASC-RX01 (877-272-7901) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis In three double-blind, placebo-controlled clinical trials, 1126 patients with CKD on dialysis received study drug (656 cinacalcet , 470 placebo) for up to 6 months. The most frequently reported adverse reactions are listed in Table 1. Seizures were observed in 1.4% (13/910) of cinacalcet -treated patients and 0.7% (5/641) of placebo-treated patients across all completed placebo controlled trials. Table 1. Adverse Reactions with Frequency ≥ 5% in Patients on Dialysis in Short-Term Studies for up to 6 Months Event*: Placebo (n=470) (%) Cinacalcet (n=656) (%) Nausea 19 31 Vomiting 15 27 Diarrhea 20 21 Myalgia 14 15 Dizziness 8 10 Hypertension 5 7 Asthenia 4 7 Anorexia 4 6 Pain chest, Non-Cardiac 4 6 Dialysis Access Site Infection 4 5 *Included are events that were reported at a greater incidence in the cinacalcet group than in the placebo group. In a randomized, double-blind placebo controlled study of 3,883 patients with secondary HPT and CKD receiving dialysis in which patients were treated for up to 64 months (mean duration of treatment was 21 months in the cinacalcet group), the most frequently reported adverse reactions (incidence of ≥ 5% in the cinacalcet group and a difference ≥ 1% compared to placebo) are listed in Table 2. Table 2. Frequency of Adverse Reactions in Dialysis Patients Treated for up to 64 Months in a Long-Term Study1 Placebo (n=1923) Cinacalcet (n=1938) 3699 subject-years 4044 subject-years Percent of subjects reporting Adverse Reactions (%) 90.9 93.2 Nausea 15.5 29.1 Vomiting 13.7 25.6 Diarrhea 18.7 20.5 Dyspnea 11.5 13.4 Cough 9.8 11.7 Hypotension 10.5 11.6 Headache 9.6 11.5 Hypocalcemia 1.4 11.2 Muscle spasms 9.2 11.1 Abdominal pain 9.6 10.9 Abdominal pain upper 6.3 8.2 Hyperkalemia 6.1 8.1 Upper respiratory tract infection 6.3 7.6 Dyspepsia 4.6 7.4 Dizziness 4.7 7.3 Decreased appetite 3.5 5.9 Asthenia 3.8 5.4 Constipation 3.8 5.0 1 Adverse reactions that occurred in ≥ 5% frequency in the cinacalcet group and a difference ≥ 1% compared to the placebo group (Safety Analysis Set) Crude incidence rate = 100 * Total number of subjects with event/n n=Number of subjects receiving at least one dose of study drug Additional adverse reaction rates from the long-term, randomized, double-blind placebo controlled study for cinacalcet versus placebo are as follows: seizure (2.5%, 1.6%), rash (2.2%, 1.9%), hypersensitivity reactions (9.4%, 8.3%). Patients with Parathyroid Carcinoma and Primary Hyperparathyroidism The safety profile of cinacalcet in these patient populations is generally consistent with that seen in patients with CKD on dialysis. Forty six patients were treated with cinacalcet in a single arm study, 29 with Parathyroid Carcinoma and 17 with intractable pHPT. Nine (20%) of the patients withdrew from the study due to adverse events. The most frequent adverse reactions and the most frequent cause of withdrawal in these patient populations were nausea and vomiting. Severe or prolonged cases of nausea and vomiting can lead to dehydration and worsening hypercalcemia so careful monitoring of electrolytes is recommended in patients with these symptoms. Eight patients died during treatment with cinacalcet in this study, 7 with Parathyroid Carcinoma (24%) and 1 (6%) with intractable pHPT. Causes of death were cardiovascular (5 patients), multi-organ failure (1 patient), gastrointestinal hemorrhage (1 patient) and metastatic carcinoma (1 patient). Adverse events of hypocalcemia were reported in three patients (7%). Seizures were observed in 0.7% (1/140) of cinacalcet-treated patients and 0.0% (0/46) of placebo-treated patients in all clinical studies. Table 3. Adverse Reactions with Frequency ≥10% in a Single Arm, Open-Label Study in Patients with Primary Hyperparathyroidism or Parathyroid Carcinoma Cinacalcet Parathyroid Carcinoma (n=29) Intractable pHPT (n=17) Total (n=46) n (%) n (%) n (%) Number of Subjects Reporting Adverse Reactions 28 (97) 17 (100) 45 (98) Nausea 19 (66) 10 (59) 29 (63) Vomiting 15 (52) 6 (35) 21 (46) Paresthesia 4 (14) 5 (29) 9 (20) Fatigue 6 (21) 2 (12) 8 (17) Fracture 6 (21) 2 (12) 8 (17) Hypercalcemia 6 (21) 2 (12) 8 (17) Anorexia 6 (21) 1 (6) 7 (15) Asthenia 5 (17) 2 (12) 7 (15) Dehydration 7 (24) 0 (0) 7 (15) Anemia 5 (17) 1 (6) 6 (13) Arthralgia 5 (17) 1 (6) 6 (13) Constipation 3 (10) 3 (18) 6 (13) Depression 3 (10) 3 (18) 6 (13) Headache 6 (21) 0 (0) 6 (13) Infection Upper Respiratory 3 (10) 2 (12) 5 (11) Pain Limb 3 (10) 2 (12) 5 (11) n=Number of subjects receiving at least one dose of study drug. pHPT = primary hyperparathyroidism Hypocalcemia In 26-week studies of patients with secondary HPT and CKD on dialysis 66% of patients receiving cinacalcet compared with 25% of patients receiving placebo developed at least one serum calcium value less than 8.4 mg/dL, whereas, 29% of patients receiving cinacalcet compared with 11% of patients receiving placebo developed at least one serum calcium value less than 7.5 mg/dL. Less than 1% of patients in each group permanently discontinued study drug due to hypocalcemia. In a randomized, double-blind, placebo-controlled study in patients with secondary HPT and CKD receiving dialysis in which patients were treated for up to 64 months (mean duration of treatment was 21 months in the cinacalcet group), 75% of patients receiving cinacalcet compared with 29% of patients receiving placebo developed at least one serum calcium value less than 8.4 mg/dL and 33% of cinacalcet patients compared with 12% of patients receiving placebo had at least one serum calcium value less than 7.5 mg/dL. Most of the cases of severe hypocalcemia less than 7.5mg/dL (21/33=64%) occurred during the first 6 months. In this trial, 1.1% of patients receiving cinacalcet and 0.1% of patients receiving placebo permanently discontinued study drug due to hypocalcemia. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of cinacalcet. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Rash and hypersensitivity reactions (including angioedema and urticaria), and myalgia Isolated, idiosyncratic cases of hypotension, worsening heart failure, and/or arrhythmia have been reported in patients with impaired cardiac function Gastrointestinal bleeding Chondrocalcinosis pyrophosphate (acute pseudogout)"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Co-administration with a strong CYP3A4 inhibitor may increase serum levels of cinacalcet. Dose adjustment and monitoring of iPTH serum phosphorous and serum calcium may be required. ( 7.1 ) Cinacalcet is a strong inhibitor of CYP2D6. Dose adjustments may be required for concomitant medications that are predominantly metabolized by CYP2D6. ( 7.2 ) 7.1 Strong CYP3A4 Inhibitors Cinacalcet is partially metabolized by CYP3A4. Dose adjustment of cinacalcet may be required if a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole). The iPTH and serum calcium concentrations should be closely monitored in these patients [see Clinical Pharmacology (12.3)] . 7.2 CYP2D6 Substrates Cinacalcet is a strong inhibitor of CYP2D6. Dose adjustments may be required for concomitant medications that are predominantly metabolized by CYP2D6 (e.g., desipramine, metoprolol, and carvedilol) and particularly those with a narrow therapeutic index (e.g., flecainide and most tricyclic antidepressants) [see Clinical Pharmacology ( 12.3) ] ."}', 'indications_and_usage': '{"1 INDICATIONS & USAGE Cinacalcet is a positive modulator of the calcium sensing receptor indicated for: Secondary Hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis. (1.1) Limitations of Use: Cinacalcet is not indicated for use in patients with CKD who are not on dialysis. Hypercalcemia in adult patients with Parathyroid Carcinoma (PC). (1.2) Severe hypercalcemia in adult patients with primary HPT who are unable to undergo parathyroidectomy. (1.3) 1.1 Secondary Hyperparathyroidism Cinacalcet are indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis [see Clinical Studies ( 14.1 )]. Limitations of Use: Cinacalcet is not indicated for use in adult patients with CKD who are not on dialysis because of an increased risk of hypocalcemia [see Warnings and Precautions ( 5.1 )]. 1.2 Parathyroid Carcinoma Cinacalcet is indicated for the treatment of hypercalcemia in adult patients with Parathyroid Carcinoma [see Clinical Studies ( 14.2) ] . 1.3 Primary Hyperparathyroidism Cinacalcet are indicated for the treatment of severe hypercalcemia in adult patients with primary HPT who are unable to undergo parathyroidectomy [ see Clinical Studies (14.3) ]"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Hypocalcemia: Life threatening events and fatal outcomes were reported. Hypocalcemia can prolong QT interval, lower the threshold for seizures, and cause hypotension, worsening heart failure, and/or arrhythmia. Monitor serum calcium carefully for the occurrence of hypocalcemia during treatment (2.4, 5.1) Upper Gastrointestinal (GI) Bleeding: Patients with risk factors for upper GI bleeding may be at increased risk. Monitor patients and promptly evaluate and treat any suspected GI bleeding. (5.2) Hypotension, Worsening Heart Failure and/or Arrhythmias: In postmarketing safety surveillance, isolated, idiosyncratic cases of hypotension, worsening heart failure, and/or arrhythmia have been reported in patients with impaired cardiac function. (5.3) Adynamic Bone Disease: May develop if iPTH levels are suppressed below 100 pg/mL. (5.4) 5.1 Hypocalcemia Cinacalcet lowers serum calcium and can lead to hypocalcemia [see Adverse Reactions (6.1)] . Significant lowering of serum calcium can cause paresthesias, myalgias, muscle spasms, tetany, seizures, QT interval prolongation and ventricular arrhythmia. Life threatening events and fatal outcomes associated with hypocalcemia have been reported in patients treated with cinacalcet, including in pediatric patients. The safety and effectiveness of cinacalcet have not been established in pediatric patients [see Pediatric Use (8.4)]. Cinacalcet is not indicated for patients with CKD not on dialysis [see Indications and Usage (1)] . In patients with secondary HPT and CKD not on dialysis, the long term safety and efficacy of cinacalcet have not been established. Clinical studies indicate that cinacalcet-treated patients with CKD not on dialysis have an increased risk for hypocalcemia compared with cinacalcet -treated patients with CKD on dialysis, which may be due to lower baseline calcium levels. In a phase 3 study of 32 weeks duration and including 404 patients with CKD not on dialysis (302 cinacalcet, 102 placebo), in which the median dose for cinacalcet was 60 mg per day at the completion of the study, 80% of cinacalcet -treated patients experienced at least one serum calcium value < 8.4 mg/dL compared with 5% of patients receiving placebo. QT Interval Prolongation and Ventricular Arrhythmia Decreases in serum calcium can also prolong the QT interval, potentially resulting in ventricular arrhythmia. Cases of QT prolongation and ventricular arrhythmia have been reported in patients treated with cinacalcet. Patients with congenital long QT syndrome, history of QT interval prolongation, family history of long QT syndrome or sudden cardiac death, and other conditions that predispose to QT interval prolongation and ventricular arrhythmia may be at increased risk for QT interval prolongation and ventricular arrhythmias if they develop hypocalcemia due to cinacalcet. Closely monitor corrected serum calcium and QT interval in patients at risk receiving cinacalcet. Seizures In clinical studies, seizures (primarily generalized or tonic-clonic) were observed in 1.4% (43/3049) of cinacalcet-treated patients and 0.7% (5/687) of placebo-treated patients. While the basis for the reported difference in seizure rate is not clear, the threshold for seizures is lowered by significant reductions in serum calcium levels. Monitor serum calcium levels in patients with seizure disorders receiving cinacalcet. Concurrent Administration with Other Calcium-Lowering Drug Products Concurrent administration of cinacalcet with calcium-lowering drugs including other calcium-sensing receptor agonists could result in severe hypocalcemia. Closely monitor serum calcium in patients receiving cinacalcet and concomitant therapies known to lower serum calcium levels. Patient Education and Hypocalcemia Treatment Educate patients on the symptoms of hypocalcemia and advise them to contact a healthcare provider if they occur. If corrected serum calcium falls below the lower limit of normal or symptoms of hypocalcemia develop, start or increase calcium supplementation (including calcium, calcium containing phosphate binders, and/or vitamin D sterols or increases in dialysate calcium concentration). Cinacalcet dose reduction or discontinuation of cinacalcet may be necessary [see Dosage and Administration (2.2)] 5.2 Upper Gastrointestinal Bleeding Cases of gastrointestinal bleeding, mostly upper gastrointestinal bleeding, have occurred in patients using calcimimetics, including cinacalcet, from postmarketing and clinical trial sources. The exact cause of GI bleeding in these patients is unknown. Patients with risk factors for upper GI bleeding (such as known gastritis, esophagitis, ulcers or severe vomiting) may be at increased risk for GI bleeding when receiving cinacalcet treatment. Monitor patients for worsening of common GI adverse reactions of nausea and vomiting associated with cinacalcet [see Adverse Reactions (6.1)] and for signs and symptoms of GI bleeding and ulcerations during cinacalcet therapy. Promptly evaluate and treat any suspected GI bleeding. 5.3 Hypotension, Worsening Heart Failure and/or Arrhythmias In postmarketing safety surveillance, isolated, idiosyncratic cases of hypotension, worsening heart failure, and/or arrhythmia have been reported in patients with impaired cardiac function, in which a causal relationship to cinacalcet could not be completely excluded and which may be mediated by reductions in serum calcium levels [see Adverse Reactions (6.2)]. 5.4 Adynamic Bone Disease Adynamic bone disease may develop if iPTH levels are suppressed below 100 pg/mL. One clinical study evaluated bone histomorphometry in patients treated with cinacalcet for 1 year. Three patients with mild hyperparathyroid bone disease at the beginning of the study developed adynamic bone disease during treatment with cinacalcet. Two of these patients had iPTH levels below 100 pg/mL at multiple time points during the study. In three 6-month, phase 3 studies conducted in patients with CKD on dialysis, 11% of patients treated with cinacalcet had mean iPTH values below 100 pg/mL during the efficacy-assessment phase. If iPTH levels decrease below 150 pg/mL in patients treated with cinacalcet, the dose of cinacalcet and/or vitamin D sterols should be reduced or therapy discontinued."}', 'overdosage': '{"10 OVERDOSAGE Overdosage of cinacalcet may lead to hypocalcemia. In the event of overdosage, patients should be monitored for signs and symptoms of hypocalcemia and appropriate measures taken to correct serum calcium levels [see Warnings and Precautions (5.1)]. Since cinacalcet is highly protein bound, hemodialysis is not an effective treatment for overdosage of cinacalcet ."}', 'active_flag': 'Y', 'generic_name': '{CINACALCET}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Hypocalcemia: Advise patients to report symptoms of hypocalcemia, including paresthesias, myalgias, muscle spasms, and seizures, to their healthcare provider [ see Warnings and Precautions (5.1)]. Upper Gastrointestinal Bleeding: Advise patients to report any symptoms of upper gastrointestinal bleeding to their health care provider [see Warnings and Precautions (5.2)]. Heart Failure: Advise patients with heart failure that use of cinacalcet may worsen their heart failure and additional monitoring may be required [see Warnings and Precautions (5.3)]. Advise patients to report nausea and vomiting to their health care provider [see Adverse Reactions (6.1)]. Advise patients to take cinacalcet with food or shortly after a meal and to take the tablets whole and not divide them [see Dosage and Administration (2.1)]. Inform patients of the importance of regular blood tests, in order to monitor the safety and efficacy of cinacalcet therapy. All trademarks are the property of their respective owners. Manufactured by: Alkem Laboratories Ltd., INDIA. Distributed by: Ascend Laboratories, LLC Parsippany, NJ 07054 Revised: November, 2021 PT 2787-03"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Limited case reports of cinacalcet use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. In animal reproduction studies, when female rats were exposed to cinacalcet during the period of organogenesis through to weaning at 2-3 times the systemic drug levels (based on AUC) at the maximum recommended human dose (MRHD) of 180 mg/day, peripartum and early postnatal pup loss and reduced pup body weight gain were observed in the presence of maternal hypocalcemia [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In pregnant female rats given oral gavage doses of 2, 25, 50 mg/kg/day cinacalcet during gestation, no teratogenicity was observed at doses up to 50 mg/kg/day (exposure 4 times those resulting with a human oral dose of 180 mg/day based on AUC comparison). Decreased fetal body weights were observed at all doses (less than 1 to 4 times a human oral dose of 180 mg/day based on AUC comparison) in conjunction with maternal toxicity (decreased food consumption and body weight gain). In pregnant female rabbits given oral gavage doses of 2, 12, 25 mg/kg/day cinacalcet during gestation, no adverse fetal effects were observed (exposures less than with a human oral dose of 180 mg/day based on AUC comparisons). Reductions in maternal food consumption and body weight gain were seen at doses of 12 and 25 mg/kg/day. Cinacalcet has been shown to cross the placental barrier in rabbits. In pregnant rats given oral gavage doses of 5, 15, 25 mg/kg/day cinacalcet during gestation through lactation, no adverse fetal or pup (post-weaning) effects were observed at 5 mg/kg/day (exposures less than with a human therapeutic dose of 180 mg/day based on AUC comparisons). Higher doses of 15 and 25 mg/kg/day cinacalcet (exposures 2 to 3 times a human oral dose of 180 mg/day based on AUC comparisons) were accompanied by maternal signs of hypocalcemia (periparturient mortality and early postnatal pup loss), and reductions in postnatal maternal and pup body-weight gain."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and efficacy of cinacalcet have not been established in pediatric patients. The use of cinacalcet for the treatment of secondary HPT in pediatric patients with CKD on dialysis was evaluated in two randomized, controlled studies (Pediatric Study 1 and Study 2) where 47 pediatric patients aged 6 years to less than 18 years received at least one dose of cinacalcet and in one single-arm study (Pediatric Study 3) where 17 pediatric patients aged 28 days to less than 6 years received at least one dose of cinacalcet. Dosing with cinacalcet in pediatric study 1 was stopped because of a fatality in a cinacalcet- treated individual. The individual was noted to be severely hypocalcemic at the time of death. The cause of death was multifactorial and a contribution of cinacalcet to the death could not be excluded [see Warnings and Precautions (5.1) ] Study 1 was terminated and changes to cinacalcet dosing after the fatality were implemented in Pediatric Study 2 and Study 3 to minimize the risk of severe hypocalcemia. The data in Pediatric Studies 2 and 3 were insufficient to establish the safety and efficacy of cinacalcet for the treatment of secondary HPT in pediatric patients with CKD on dialysis. In aggregate, the pediatric studies did not establish a safe and effective cinacalcet dosing regimen for the pediatric population."}', 'geriatric_use': '{"8.5 Geriatric Use Of the total number of subjects (n=1136) in clinical studies of cinacalcet, 26 percent were 65 and over, and 9 percent were 75 and over. No overall differences in the safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Studies ( 14 ) and Clinical Pharmacology ( 12.3 )] ."}'}

{NICOTINE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use reduces withdrawal symptoms, including nicotine craving, associated with quitting smoking"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"NICOTINE POLACRILEX"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if mouth, teeth, or jaw problems occur irregular heartbeat or palpitations occur you get symptoms of nicotine overdose such as nausea, vomiting, dizziness, diarrhea, weakness and rapid heartbeat you have symptoms of an allergic reaction (such as difficulty breathing or rash)"}', 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings If you are pregnant or breast-feeding, only use this medicine on the advice of your health care provider. Smoking can seriously harm your child. Try to stop smoking without using any nicotine replacement medicine. This medicine is believed to be safer than smoking. However, the risks to your child from this medicine are not fully known. Ask a doctor before use if you have a sodium-restricted diet heart disease, recent heart attack, or irregular heartbeat. Nicotine can increase your heart rate. high blood pressure not controlled with medication. Nicotine can increase your blood pressure. stomach ulcer or diabetes history of seizures Ask a doctor or pharmacist before use if you are using a non-nicotine stop smoking drug taking prescription medicine for depression or asthma. Your prescription dose may need to be adjusted. Stop use and ask a doctor if mouth, teeth, or jaw problems occur irregular heartbeat or palpitations occur you get symptoms of nicotine overdose such as nausea, vomiting, dizziness, diarrhea, weakness and rapid heartbeat you have symptoms of an allergic reaction (such as difficulty breathing or rash) Keep out of reach of children and pets. Pieces of nicotine gum may have enough nicotine to make children and pets sick. Wrap used pieces of gum in paper and throw away in the trash. In case of overdose, get medical help or contact a Poison Control Center (1-800-222-1222) right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"WARFARIN SODIUM"}

{'contraindications': '{"4 CONTRAINDICATIONS Warfarin Sodium is contraindicated in: Pregnancy Warfarin sodium tablets are contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism [ see Warnings and Precautions (5.7) and Use in Specific Populations (8.1 ) ]. Warfarin sodium can cause fetal harm when administered to a pregnant woman. Warfarin sodium exposure during pregnancy causes a recognized pattern of major congenital malformations (warfarin embryopathy and fetotoxicity), fatal fetal hemorrhage, and an increased risk of spontaneous abortion and fetal mortality. If warfarin sodium is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [ see Use in Specific Populations (8.1) ]. Warfarin Sodium is contraindicated in patients with: Hemorrhagic tendencies or blood dyscrasias Recent or contemplated surgery of the central nervous system or eye, or traumatic surgery resulting in large open surfaces [ see Warnings and Precautions (5.8) ] Bleeding tendencies associated with: − Active ulceration or overt bleeding of the gastrointestinal, genitourinary, or respiratory tract− Central nervous system hemorrhage− Cerebral aneurysms, dissecting aorta− Pericarditis and pericardial effusions− Bacterial endocarditis Threatened abortion, eclampsia, and preeclampsia Unsupervised patients with conditions associated with potential high level of non-compliance Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding Hypersensitivity to warfarin or to any other components of this product (e.g., anaphylaxis) [ see Adverse Reactions (6) ] Major regional or lumbar block anesthesia Malignant hypertension Pregnancy, except in women with mechanical heart valves. ( 4 , 5.7 , 8.1 ) Hemorrhagic tendencies or blood dyscrasias. ( 4 ) Recent or contemplated surgery of the central nervous system (CNS) or eye, or traumatic surgery resulting in large open surfaces. ( 4, 5.8) Bleeding tendencies associated with certain conditions. ( 4 ) Threatened abortion, eclampsia, and preeclampsia. ( 4 ) Unsupervised patients with potential high levels of non-compliance. ( 4 ) Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding. ( 4 ) Hypersensitivity to warfarin or any component of the product. ( 4 ) Major regional or lumbar block anesthesia. ( 4 ) Malignant hypertension. ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions to warfarin sodium are discussed in greater detail in other sections of the labeling: Hemorrhage [see Boxed Warning , Warnings and Precautions (5.1) , and Overdosage (10) ] Tissue Necrosis [see Warnings and Precautions (5.2) ] Calciphylaxis [see Warnings and Precautions (5.3) ] Acute Kidney Injury [see Warnings and Precautions (5.4) ] Systemic Atheroemboli and Cholesterol Microemboli [see Warnings and Precautions (5.5) ] Limb Ischemia, Necrosis, and Gangrene in Patients with HIT and HITTS [see Warnings and Precautions (5.6) ] Other Clinical Settings with Increased Risks [see Warnings and Precautions (5.8) ] Other adverse reactions to warfarin sodium include: Immune system disorders: hypersensitivity/allergic reactions (including urticaria and anaphylactic reactions) Vascular disorders: vasculitis Hepatobiliary disorders: hepatitis, elevated liver enzymes. Cholestatic hepatitis has been associated with concomitant administration of warfarin sodium and ticlopidine. Gastrointestinal disorders: nausea, vomiting, diarrhea, taste perversion, abdominal pain, flatulence, bloating Skin disorders: rash, dermatitis (including bullous eruptions), pruritus, alopecia Respiratory disorders: tracheal or tracheobronchial calcification General disorders: chills Most common adverse reactions to warfarin sodium are fatal and nonfatal hemorrhage from any tissue or organ. (6) To report SUSPECTED ADVERSE REACTIONS, contact Rising Health, LLC at 1-833-395-6928 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch ."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Concomitant use of drugs that increase bleeding risk, antibiotics, antifungals, botanical (herbal) products, and inhibitors and inducers of CYP2C9, 1A2, or 3A4. ( 7 ) Consult labeling of all concurrently used drugs for complete information about interactions with warfarin sodium or increased risks for bleeding. (7) 7.1 General Information Drugs may interact with warfarin sodium through pharmacodynamic or pharmacokinetic mechanisms. Pharmacodynamic mechanisms for drug interactions with warfarin sodium are synergism (impaired hemostasis, reduced clotting factor synthesis), competitive antagonism (vitamin K), and alteration of the physiologic control loop for vitamin K metabolism (hereditary resistance). Pharmacokinetic mechanisms for drug interactions with warfarin sodium are mainly enzyme induction, enzyme inhibition, and reduced plasma protein binding. It is important to note that some drugs may interact by more than one mechanism. More frequent INR monitoring should be performed when starting or stopping other drugs, including botanicals, or when changing dosages of other drugs, including drugs intended for short-term use (e.g., antibiotics, antifungals, corticosteroids) [see Boxed Warning ] . Consult the labeling of all concurrently used drugs to obtain further information about interactions with warfarin sodium or adverse reactions pertaining to bleeding. 7.2 CYP450 Interactions CYP450 isozymes involved in the metabolism of warfarin include CYP2C9, 2C19, 2C8, 2C18, 1A2, and 3A4. The more potent warfarin S -enantiomer is metabolized by CYP2C9 while the R -enantiomer is metabolized by CYP1A2 and 3A4. Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the effect (increase INR) of warfarin by increasing the exposure of warfarin. Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the effect (decrease INR) of warfarin by decreasing the exposure of warfarin. Examples of inhibitors and inducers of CYP2C9, 1A2, and 3A4 are below in Table 2; however, this list should not be considered all-inclusive. Consult the labeling of all concurrently used drugs to obtain further information about CYP450 interaction potential. The CYP450 inhibition and induction potential should be considered when starting, stopping, or changing dose of concomitant medications. Closely monitor INR if a concomitant drug is a CYP2C9, 1A2, and/or 3A4 inhibitor or inducer. Table 2: Examples of CYP450 Interactions with Warfarin Enzyme Inhibitors Inducers CYP2C9 amiodarone, capecitabine, cotrimoxazole, etravirine, fluconazole, fluvastatin, fluvoxamine, metronidazole, miconazole, oxandrolone, sulfinpyrazone, tigecycline, voriconazole, zafirlukast aprepitant, bosentan, carbamazepine, phenobarbital, rifampin CYP1A2 acyclovir, allopurinol, caffeine, cimetidine, ciprofloxacin, disulfiram, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, norfloxacin, oral contraceptives, phenylpropanolamine, propafenone, propranolol, terbinafine, thiabendazole, ticlopidine, verapamil, zileuton montelukast, moricizine, omeprazole, phenobarbital, phenytoin, cigarette smoking CYP3A4 alprazolam, amiodarone, amlodipine, amprenavir, aprepitant, atorvastatin, atazanavir, bicalutamide, cilostazol, cimetidine, ciprofloxacin, clarithromycin, conivaptan, cyclosporine, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, imatinib, indinavir, isoniazid, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, nilotinib, oral contraceptives, posaconazole, ranitidine, ranolazine, ritonavir, saquinavir, telithromycin, tipranavir, voriconazole, zileuton armodafinil, amprenavir, aprepitant, bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenytoin, pioglitazone, prednisone, rifampin, rufinamide 7.3 Drugs that Increase Bleeding Risk Examples of drugs known to increase the risk of bleeding are presented in Table 3. Because bleeding risk is increased when these drugs are used concomitantly with warfarin, closely monitor patients receiving any such drug with warfarin. Table 3: Drugs that Can Increase the Risk of Bleeding Drug Class Specific Drugs Anticoagulants argatroban, dabigatran, bivalirudin, desirudin, heparin, lepirudin Antiplatelet Agents aspirin, cilostazol, clopidogrel, dipyridamole, prasugrel, ticlopidine Nonsteroidal Anti-Inflammatory Agents celecoxib, diclofenac, diflunisal, fenoprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, naproxen, oxaprozin, piroxicam, sulindac Serotonin Reuptake Inhibitors citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, venlafaxine, vilazodone 7.4 Antibiotics and Antifungals There have been reports of changes in INR in patients taking warfarin and antibiotics or antifungals, but clinical pharmacokinetic studies have not shown consistent effects of these agents on plasma concentrations of warfarin. Closely monitor INR when starting or stopping any antibiotic or antifungal in patients taking warfarin. 7.5 Botanical (Herbal) Products and Foods More frequent INR monitoring should be performed when starting or stopping botanicals. Few adequate, well-controlled studies evaluating the potential for metabolic and/or pharmacologic interactions between botanicals and warfarin sodium exist. Due to a lack of manufacturing standardization with botanical medicinal preparations, the amount of active ingredients may vary. This could further confound the ability to assess potential interactions and effects on anticoagulation. Some botanicals may cause bleeding events when taken alone (e.g., garlic and Ginkgo biloba) and may have anticoagulant, antiplatelet, and/or fibrinolytic properties. These effects would be expected to be additive to the anticoagulant effects of warfarin sodium. Conversely, some botanicals may decrease the effects of warfarin sodium (e.g., co-enzyme Q 10 , St. John’s wort, ginseng). Some botanicals and foods can interact with warfarin sodium through CYP450 interactions (e.g., echinacea, grapefruit juice, ginkgo, goldenseal, St. John’s wort). The amount of vitamin K in food may affect therapy with warfarin sodium. Advise patients taking warfarin sodium to eat a normal, balanced diet maintaining a consistent amount of vitamin K. Patients taking warfarin sodium should avoid drastic changes in dietary habits, such as eating large amounts of green leafy vegetables."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Warfarin sodium tablets are indicated for: Prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (PE). Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation (AF) and/or cardiac valve replacement. Reduction in the risk of death, recurrent myocardial infarction (MI), and thromboembolic events such as stroke or systemic embolization after myocardial infarction. Limitations of Use Warfarin sodium tablets have no direct effect on an established thrombus, nor does it reverse ischemic tissue damage. Once a thrombus has occurred, however, the goals of anticoagulant treatment are to prevent further extension of the formed clot and to prevent secondary thromboembolic complications that may result in serious and possibly fatal sequelae. Warfarin sodium tablets are vitamin K antagonist indicated for: Prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism. (1) Prophylaxis and treatment of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. (1) Reduction in the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction. (1) Limitations of Use Warfarin sodium tablets have no direct effect on an established thrombus, nor does it reverse ischemic tissue damage. (1)"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Tissue necrosis: Necrosis or gangrene of skin or other tissues can occur, with severe cases requiring debridement or amputation. Discontinue warfarin sodium and consider alternative anticoagulants if necessary. (5.2) Calciphylaxis: Fatal and serious cases have occurred. Discontinue warfarin sodium and consider alternative anticoagulation therapy. ( 5.3 ) Acute kidney injury may occur during episodes of excessive anticoagulation and hematuria. ( 5.4 ) Systemic atheroemboli and cholesterol microemboli: Some cases have progressed to necrosis or death. Discontinue warfarin sodium if such emboli occur. ( 5.5 ) Heparin-induced thrombocytopenia (HIT): Initial therapy with warfarin sodium in HIT has resulted in cases of amputation and death. Warfarin sodium may be considered after platelet count has normalized. ( 5.6) Pregnant women with mechanical heart valves: Warfarin sodium may cause fetal harm; however, the benefits may outweigh the risks.( 5.7 ) 5.1 Hemorrhage Warfarin sodium can cause major or fatal bleeding. Bleeding is more likely to occur within the first month. Risk factors for bleeding include high intensity of anticoagulation (INR >4.0), age greater than or equal to 65, history of highly variable INRs, history of gastrointestinal bleeding, hypertension, cerebrovascular disease, anemia, malignancy, trauma, renal impairment, certain genetic factors [ see Clinical Pharmacology (12.5) ], certain concomitant drugs [ see Drug Interactions (7) ], and long duration of warfarin therapy. Perform regular monitoring of INR in all treated patients. Those at high risk of bleeding may benefit from more frequent INR monitoring, careful dose adjustment to desired INR, and a shortest duration of therapy appropriate for the clinical condition. However, maintenance of INR in the therapeutic range does not eliminate the risk of bleeding. Drugs, dietary changes, and other factors affect INR levels achieved with warfarin sodium therapy. Perform more frequent INR monitoring when starting or stopping other drugs, including botanicals, or when changing dosages of other drugs [ see Drug Interactions (7) ]. Instruct patients about prevention measures to minimize risk of bleeding and to report signs and symptoms of bleeding [ see Patient Counseling Information (17) ]. 5.2 Tissue Necrosis Warfarin sodium can cause necrosis and/or gangrene of skin and other tissues, which is an uncommon but serious risk (<0.1%). Necrosis may be associated with local thrombosis and usually appears within a few days of the start of warfarin sodium therapy. In severe cases of necrosis, treatment through debridement or amputation of the affected tissue, limb, breast, or penis has been reported. Careful clinical evaluation is required to determine whether necrosis is caused by an underlying disease. Although various treatments have been attempted, no treatment for necrosis has been considered uniformly effective. Discontinue warfarin sodium therapy if necrosis occurs. Consider alternative drugs if continued anticoagulation therapy is necessary. 5.3 Calciphylaxis Warfarin sodium can cause fatal and serious calciphylaxis or calcium uremic arteriolopathy, which has been reported in patients with and without end-stage renal disease. When calciphylaxis is diagnosed in these patients, discontinue Warfarin sodium and treat calciphylaxis as appropriate. Consider alternative anticoagulation therapy. 5.4 Acute Kidney Injury In patients with altered glomerular integrity or with a history of kidney disease, acute kidney injury may occur with Warfarin sodium, possibly in relation to episodes of excessive anticoagulation and hematuria [see Use in Specific Populations (8.6 )] . More frequent monitoring of anticoagulation is advised in patients with compromised renal function. 5.5 Systemic Atheroemboli and Cholesterol Microemboli Anticoagulation therapy with warfarin sodium may enhance the release of atheromatous plaque emboli. Systemic atheroemboli and cholesterol microemboli can present with a variety of signs and symptoms depending on the site of embolization. The most commonly involved visceral organs are the kidneys followed by the pancreas, spleen, and liver. Some cases have progressed to necrosis or death. A distinct syndrome resulting from microemboli to the feet is known as “purple toes syndrome.” Discontinue warfarin sodium therapy if such phenomena are observed. Consider alternative drugs if continued anticoagulation therapy is necessary. 5.6 Limb Ischemia, Necrosis, and Gangrene in Patients with HIT and HITTS Do not use warfarin sodium as initial therapy in patients with heparin-induced thrombocytopenia (HIT) and with heparin-induced thrombocytopenia with thrombosis syndrome (HITTS). Cases of limb ischemia, necrosis, and gangrene have occurred in patients with HIT and HITTS when heparin treatment was discontinued and warfarin therapy was started or continued. In some patients, sequelae have included amputation of the involved area and/or death. Treatment with warfarin sodium may be considered after the platelet count has normalized. 5.7 Use in Pregnant Women with Mechanical Heart Valves Warfarin sodium can cause fetal harm when administered to a pregnant woman. While warfarin sodium is contraindicated during pregnancy, the potential benefits of using warfarin sodium may outweigh the risks for pregnant women with mechanical heart valves at high risk of thromboembolism. In those individual situations, the decision to initiate or continue warfarin sodium should be reviewed with the patient, taking into consideration the specific risks and benefits pertaining to the individual patient’s medical situation, as well as the most current medical guidelines. Warfarin sodium exposure during pregnancy causes a recognized pattern of major congenital malformations (warfarin embryopathy and fetotoxicity), fatal fetal hemorrhage, and an increased risk of spontaneous abortion and fetal mortality. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [ see Use in Specific Populations (8.1) ]. 5.8 Other Clinical Settings with Increased Risks In the following clinical settings, the risks of warfarin sodium therapy may be increased: Moderate to severe hepatic impairment Infectious diseases or disturbances of intestinal flora (e.g., sprue, antibiotic therapy) Use of an indwelling catheter Severe to moderate hypertension Deficiency in protein C-mediated anticoagulant response: Warfarin sodium reduces the synthesis of the naturally occurring anticoagulants, protein C and protein S. Hereditary or acquired deficiencies of protein C or its cofactor, protein S, have been associated with tissue necrosis following warfarin administration. Concomitant anticoagulation therapy with heparin for 5 to 7 days during initiation of therapy with warfarin sodium may minimize the incidence of tissue necrosis in these patients. Eye surgery: In cataract surgery, warfarin sodium use was associated with a significant increase in minor complications of sharp needle and local anesthesia block but not associated with potentially sight-threatening operative hemorrhagic complications. As warfarin sodium cessation or reduction may lead to serious thromboembolic complications, the decision to discontinue warfarin sodium before a relatively less invasive and complex eye surgery, such as lens surgery, should be based upon the risks of anticoagulant therapy weighed against the benefits. Polycythemia vera Vasculitis Diabetes mellitus 5.9 Endogenous Factors Affecting INR The following factors may be responsible for increased INR response: diarrhea, hepatic disorders, poor nutritional state, steatorrhea, or vitamin K deficiency. The following factors may be responsible for decreased INR response: increased vitamin K intake or hereditary warfarin resistance."}', 'overdosage': '{"10 OVERDOSAGE 10.1 Signs and Symptoms Bleeding (e.g., appearance of blood in stools or urine, hematuria, excessive menstrual bleeding, melena, petechiae, excessive bruising or persistent oozing from superficial injuries, unexplained fall in hemoglobin) is a manifestation of excessive anticoagulation. 10.2 Treatment The treatment of excessive anticoagulation is based on the level of the INR, the presence or absence of bleeding, and clinical circumstances. Reversal of warfarin sodium anticoagulation may be obtained by discontinuing warfarin sodium therapy and, if necessary, by administration of oral or parenteral vitamin K 1 . The use of vitamin K 1 reduces response to subsequent warfarin sodium therapy and patients may return to a pretreatment thrombotic status following the rapid reversal of a prolonged INR. Resumption of warfarin sodium administration reverses the effect of vitamin K, and a therapeutic INR can again be obtained by careful dosage adjustment. If rapid re-anticoagulation is indicated, heparin may be preferable for initial therapy. Prothrombin complex concentrate (PCC), fresh frozen plasma, or activated Factor VII treatment may be considered if the requirement to reverse the effects of warfarin sodium is urgent. A risk of hepatitis and other viral diseases is associated with the use of blood products; PCC and activated Factor VII are also associated with an increased risk of thrombosis. Therefore, these preparations should be used only in exceptional or life-threatening bleeding episodes secondary to warfarin sodium overdosage."}', 'active_flag': 'Y', 'generic_name': '{"WARFARIN SODIUM"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Instructions for Patients Advise patients to: Strictly adhere to the prescribed dosage schedule [ see Dosage and Administration ( 2.1 ) ]. If the prescribed dose of warfarin sodium is missed, take the dose as soon as possible on the same day but do not take a double dose of warfarin sodium the next day to make up for missed doses [ see Dosage and Administration (2.6 ) ]. Obtain prothrombin time tests and make regular visits to their physician or clinic to monitor therapy [ see Dosage and Administration ( 2.1 ) ]. Be aware that if therapy with warfarin sodium is discontinued, the anticoagulant effects of warfarin sodium may persist for about 2 to 5 days [ see Clinical Pharmacology ( 12.2 ) ]. Avoid any activity or sport that may result in traumatic injury [ see Use in Specific Populations ( 8.4 ) ] . And to tell their physician if they fall often as this may increase their risk for complications. Eat a normal, balanced diet to maintain a consistent intake of vitamin K. Avoid drastic changes in dietary habits, such as eating large amounts of leafy, green vegetables [ see Drug Interactions ( 7.5 ) ]. Contact their physician to report any serious illness, such as severe diarrhea, infection, or fever [see Warnings and Precautions (5) and Adverse Reactions (6)] . Immediately contact their physician when experiencing pain and discoloration of the skin (a purple bruise like rash) mostly on areas of the body with a high fat content, such as breasts, thighs, buttocks, hips and abdomen [ see Warnings and Precautions ( 5.2 ) ]. Immediately contact their physician when experiencing any unusual symptom or pain since warfarin sodium may cause small cholesterol or athero emboli. On feet it may appear as a sudden cool, painful, purple discoloration of toe(s) or forefoot [ see Warnings and Precautions ( 5.5 ) ]. Immediately contact their physician when taking warfarin sodium after any heparin formulation therapy and experiencing bloody or black stools or appearence of bruises, or bleeding [ see Warnings and Precautions ( 5.6 ) ]. To tell all of their healthcare professionals and dentists that they are taking warfarin sodium. This should be done before they have any surgery or dental procedure [ see Dosage and Administration ( 2.7 ) ]. Carry identification stating that they are taking warfarin sodium. Bleeding Risks Advise patients to: Notify their physician immediately if any unusual bleeding or symptoms occur. Signs and symptoms of bleeding include: pain, swelling or discomfort, prolonged bleeding from cuts, increased menstrual flow or vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or dark brown urine, red or tar black stools, headache, dizziness, or weakness [ see Box Warning and Warnings and Precautions ( 5.1 ) ]. Concomitant Medications and Botanicals (Herbals) Advise patients to: Not take or discontinue any other drug, including salicylates (e.g., aspirin and topical analgesics), other over-the-counter drugs, and botanical (herbal) products except on advice of your physician [ see Drug Interactions ( 7 ) ]. Pregnancy and Nursing Advise patients to: Notify their physician if they are pregnant or planning to become pregnant or considering breast feeding [ see Use in Specific Populations (8.1, 8.2 , 8.3 ) ]. Avoid warfarin sodium during pregnancy except in pregnant women with mechanical heart valves, who are at risk of thromboembolism [ see Contraindications (4 ) ]. Use effective measures to avoid pregnancy while taking warfarin sodium. This is very important because their unborn baby could be seriously harmed if they take warfarin sodium while they are pregnant [ see Use in Specific Populations (8.1 , 8.3 ) ]. Revised: 06/2018"}', 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{PARICALCITOL}

{'contraindications': '{"4 CONTRAINDICATIONS ZEMPLAR is contraindicated in patients with: Hypercalcemia [see Warnings and Precautions ( 5.1 )] Vitamin D toxicity [see Warnings and Precautions ( 5.1 )] Known hypersensitivity to paricalcitol or any of the inactive ingredients in ZEMPLAR. Hypersensitivity adverse reactions have been reported [e.g., angioedema (including laryngeal edema) and urticaria] [see Adverse Reactions ( 6.2 )] . Hypercalcemia ( 4 ) Vitamin D toxicity ( 4 ) Known hypersensitivity to paricalcitol or any inactive ingredient ( 4 )."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Hypercalcemia [see Warnings and Precautions ( 5.1 )] Adynamic Bone Disease [see Warnings and Precautions ( 5.3 )] The most common adverse reactions (> 5% and more frequent than placebo) are nausea, vomiting and edema ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Four placebo-controlled, double-blind, multicenter studies were conducted in 113 patients (51% male, 10% Caucasian, 81% African-American and 9% Hispanic, ranging in age from 18 to 90 years). Sixty-two patients were exposed to ZEMPLAR and the average dose at the end of treatment was 0.12 mcg/kg/dose with a mean number of 55 days of dosing across the studies. Discontinuation of therapy due to any adverse reaction occurred in 6.5% of patients treated with ZEMPLAR and 2.0% of patients treated with placebo. Adverse reactions occurring with greater frequency in the ZEMPLAR group and at a frequency of 2% or greater are presented in Table 3. Table 3. Adverse Reactions Occurring at a Rate of 2% or Greater in Patients with CKD on Dialysis in Four Placebo-Controlled Studies Adverse Reaction Placebo (n = 51) % ZEMPLAR (n = 62) % Nausea 8 13 Vomiting 6 8 Edema 0 7 Gastrointestinal Hemorrhage 2 5 Chills 2 5 Pyrexia 2 5 Pneumonia 0 5 Sepsis 2 5 Influenza 4 5 Arthralgia 4 5 Palpitations 0 3 Dry Mouth 2 3 Malaise 0 3 Other Adverse Reactions The following adverse reactions occurred in less than 2% of the ZEMPLAR treated patients in the above mentioned studies and in additional double-blind, active-controlled and open-label studies: Blood and Lymphatic System Disorders: Anemia, lymphadenopathy Cardiac Disorders: Arrhythmia, atrial flutter, irregular heart rate, cardiac arrest, chest discomfort, chest pain, edema peripheral Ear and Labyrinth Disorders : Ear discomfort Endocrine Disorders: Hypoparathyroidism Eye Disorders : Conjunctivitis, glaucoma, ocular hyperemia Gastrointestinal Disorders : Abdominal discomfort, constipation, diarrhea, dysphagia, gastritis, intestinal ischemia, rectal hemorrhage General Disorders: Asthenia, condition aggravated, fatigue, feeling abnormal, pain, swelling Infections: Nasopharyngitis, upper respiratory tract infection, vaginal infection Injection site reactions: Injection site extravasation, injection site pain Laboratory abnormalities: Hypercalcemia, hyperkalemia, hyperphosphatemia, hypocalcemia, increased aspartate aminotransferase, prolonged bleeding time Metabolism and Nutrition Disorders: Decreased appetite, thirst, decreased weight Musculoskeletal and Connective Tissue Disorders: Joint stiffness, muscle twitching, myalgia Neoplasms Benign, Malignant and Unspecified: Breast cancer Nervous System Disorders: Cerebrovascular accident, dizziness, dysgeusia, headache, hypoesthesia, myoclonus, paresthesia, syncope, unresponsive to stimuli, gait disturbance Psychiatric Disorders : Agitation, confusional state, delirium, insomnia, nervousness, restlessness Reproductive System and Breast Disorders : Breast pain, erectile dysfunction Respiratory, Thoracic and Mediastinal Disorders: Cough, dyspnea, orthopnea, pulmonary edema, wheezing Skin and Subcutaneous Tissue Disorders: Alopecia, blister, hirsutism, night sweats, rash pruritic, pruritus, skin burning sensation Vascular Disorders: Hypertension, hypotension 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of ZEMPLAR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Allergic reactions, such as rash, urticaria, and angioedema (including laryngeal edema) have been reported."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Table 4 includes clinically significant drug interactions with ZEMPLAR. Table 4. Clinically Significant Drug Interactions with ZEMPLAR Drugs that May Increase the risk of Hypercalcemia Clinical Impact Concomitant administration of high doses of calcium-containing preparations or other vitamin D compounds may increase the risk of hypercalcemia. Thiazide diuretics are known to induce hypercalcemia by reducing excretion of calcium in the urine. Examples Calcium-containing products, other vitamin D compounds or thiazide diuretics Intervention Monitor calcium more frequently and adjust ZEMPLAR dose as needed [see Warnings and Precautions ( 5.1 )] . Digitalis Compounds Clinical Impact ZEMPLAR can cause hypercalcemia which can potentiate the risk of digitalis toxicity. Intervention Monitor patients for signs and symptoms of digitalis toxicity and increase frequency of serum calcium monitoring when initiating or adjusting the dose of ZEMPLAR in patients receiving digitalis compounds [see Warnings and Precautions ( 5.2 )]. Strong CYP3A Inhibitors Clinical Impact ZEMPLAR is partially metabolized by CYP3A. Exposure of ZEMPLAR will increase upon coadministration with strong CYP3A inhibitors [see Clinical Pharmacology ( 12.3 )]. Examples Boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, and voriconazole Intervention If a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor, dose adjustment of ZEMPLAR may be necessary. Monitor intact PTH and serum calcium concentrations closely. Strong CYP3A Inhibitors: Co-administration with strong CYP3A inhibitors (e.g., ketoconazole) increases ZEMPLAR exposure. Dose adjustment may be necessary. Closely monitor intact PTH and serum calcium ( 2.4 , 7 )."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE ZEMPLAR is indicated for the prevention and treatment of secondary hyperparathyroidism in patients 5 years of age and older with chronic kidney disease (CKD) on dialysis. ZEMPLAR is a vitamin D analog indicated for the prevention and treatment of secondary hyperparathyroidism in patients 5 years of age and older with chronic kidney disease on dialysis ( 1 )."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Hypercalcemia: Can occur during treatment with ZEMPLAR and can lead to cardiac arrhythmias and seizures. Severe hypercalcemia may require emergency attention. The risk may be increased when ZEMPLAR is used concomitantly with high dose calcium preparations, thiazide diuretics, or vitamin D compounds. Inform patients about symptoms of hypercalcemia and monitor serum calcium prior to initiation and during treatment and adjust dose accordingly ( 2 , 5.1 ). Digitalis toxicity: Risk increases with hypercalcemia. In patients using digitalis compounds, monitor both serum calcium and patients for signs and symptoms of digitalis toxicity. Monitor more frequently when initiating or adjusting the dose of ZEMPLAR ( 5.2 ). Adynamic Bone Disease: May develop and increase risk of fractures if intact PTH levels are suppressed to abnormally low levels. Monitor intact PTH levels and adjust dose if needed ( 5.3 ). 5.1 Hypercalcemia Hypercalcemia may occur during ZEMPLAR treatment. Acute hypercalcemia may increase the risk of cardiac arrhythmias and seizures and may potentiate the effect of digitalis on the heart [see Warnings and Precautions ( 5.2 )] . Chronic hypercalcemia can lead to generalized vascular calcification and other soft-tissue calcification. Severe hypercalcemia may require emergency attention. Hypercalcemia may be exacerbated by concomitant administration of high doses of calcium-containing preparations, thiazide diuretics, or other vitamin D compounds [see Drug Interactions ( 7 )]. In addition, high intake of calcium and phosphate concomitantly with vitamin D compounds may lead to hypercalciuria and hyperphosphatemia. Patients with a history of hypercalcemia prior to initiating therapy may be at increased risk for development of hypercalcemia with ZEMPLAR. In these circumstances, frequent serum calcium monitoring and ZEMPLAR dose adjustments may be required. When initiating ZEMPLAR or adjusting ZEMPLAR dose, measure serum calcium frequently (e.g., twice weekly). Once a maintenance dose has been established, measure serum calcium at least monthly . If hypercalcemia occurs, reduce the dose or discontinue ZEMPLAR until serum calcium is normal [see Dosage and Administration ( 2.2 , 2.3 )] . Inform patients about the symptoms of elevated calcium (feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination and weight loss) and instruct them to report new or worsening symptoms when they occur. 5.2 Digitalis Toxicity ZEMPLAR can cause hypercalcemia [see Warnings and Precautions ( 5.1 )] which increases the risk of digitalis toxicity. In patients using ZEMPLAR concomitantly with digitalis compounds, monitor serum calcium and patients for signs and symptoms of digitalis toxicity. Increase the frequency of monitoring when initiating or adjusting the dose of ZEMPLAR [see Drug Interactions ( 7 )] . 5.3 Adynamic Bone Disease Adynamic bone disease with subsequent increased risk of fractures may develop if intact PTH levels are suppressed by ZEMPLAR to abnormally low levels. Monitor intact PTH levels to avoid over suppression and adjust ZEMPLAR dose, if needed [see Dosage and Administration ( 2.2 , 2.3 )] ."}', 'overdosage': '{"10 OVERDOSAGE Overdosage of ZEMPLAR may lead to hypercalcemia, hypercalciuria, and hyperphosphatemia. [see Warnings and Precautions ( 5.1 )] . The treatment of acute overdosage should consist of supportive measures and discontinuation of drug administration. Serum calcium levels should be measured until normal. Paricalcitol is not significantly removed by dialysis."}', 'active_flag': 'Y', 'generic_name': '{PARICALCITOL}', 'route': '{INTRAVENOUS}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Hypercalcemia Advise patients to contact a health care provider if they develop symptoms of elevated calcium (e.g. feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination and weight loss) [see Warnings and Precautions ( 5.1 )] . Monitoring Inform patients that they will need routine monitoring of laboratory parameters such as calcium and intact PTH while receiving ZEMPLAR. Inform patients that more frequent monitoring is necessary during the initiation of therapy, following dose changes or when potentially interacting medications are started or discontinued [see Dosage and Administration ( 2 ), Drug Interactions ( 7 )] . Drug Interactions Advise patients to inform their physician of all medications, including prescription and nonprescription drugs, and supplements they are taking. Advise patients to also inform their physician that they are receiving ZEMPLAR if a new medication is prescribed [see Drug Interactions ( 7 )] . Manufactured for AbbVie Inc. North Chicago, IL 60064, U.S.A. © 1998-2021 AbbVie Inc. 8021417 May, 2021"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Limited data with ZEMPLAR in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with chronic kidney disease in pregnancy (see Clinical Considerations ) . In animal reproduction studies, slightly increased embryofetal loss was observed in pregnant rats and rabbits administered paricalcitol intravenously during the period of organogenesis at doses 2 and 0.5 times, respectively, a human dose of 14 mcg (equivalent to 0.24 mcg/kg), based on body surface area (mcg/m 2 ). Adverse reproductive outcomes were observed at doses that caused maternal toxicity (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Chronic kidney disease in pregnancy increases the risk for maternal hypertension and preeclampsia, miscarriage, preterm delivery, polyhydramnios, still birth, and low birth weight infants. Data Animal Data Pregnant rats and rabbits were treated with paricalcitol by once-daily intravenous injection during the period of organogenesis (in rats, from gestation day (GD) 6 to 17; in rabbits, from GD 6 to 18). Rats were dosed at 0, 0.3, 1 or 3 mcg/kg/day and rabbits at 0, 0.03, 0.1 or 0.3 mcg/kg/day, representing up to 2 or 0.5 times, respectively, a human dose of 0.24 mcg/kg, based on body surface area (mcg/m 2 ). Slightly decreased fetal viability was observed in both studies at the highest doses representing 2 and 0.5 times, respectively, a human dose of 0.24 mcg/kg, in the presence of maternal toxicity (decreased body weight and food consumption). Pregnant rats were administered paricalcitol by intravenous injection three times per week at doses of 0, 0.3, 3 or 20 mcg/kg/day throughout gestation, parturition and lactation (GD 6 to lactation day (LD) 20) representing exposures up to 13 times a human dose of 0.24 mcg/kg. A small increase in stillbirths and pup deaths from parturition to LD 4 were observed at the high dose when compared to the control group (9.2% versus 3.3% in controls) at 13 times a human dose of 0.24 mcg/kg, which occurred at a maternally toxic dose known to cause hypercalcemia in rats. Surviving pups were not adversely affected; body weight gains, developmental landmarks, reflex ontogeny, learning indices, and locomotor activity were all within normal parameters. F1 reproductive capacity was unaffected."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and efficacy of ZEMPLAR for the prevention and treatment of secondary hyperparathyroidism associated with CKD have been established in pediatric patients 5 years of age and older with CKD on dialysis. Use of ZEMPLAR in pediatric patients 5 years of age and older is supported by evidence from an adequate and well-controlled study in 29 patients, 5 to 19 years of age, with CKD on hemodialysis [see Clinical Studies ( 14 )]. The safety and efficacy of ZEMPLAR have not been established in pediatric patients less than 5 years old."}', 'geriatric_use': '{"8.5 Geriatric Use Clinical studies of ZEMPLAR did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic or cardiac function, and of concomitant disease or other drug therapy."}'}

{"COCOA BUTTER","PHENYLEPHRINE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses • helps relieve the local itching and discomfort associated with hemorrhoids • temporarily relieves burning and shrinks hemorrhoidal tissue • temporarily provides a coating for relief of anorectal discomforts • temporarily protects the inflamed, irritated anorectal surface to help make bowel movements less painful"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"COCOA BUTTER, PHENYLEPHRINE HCL"}', 'route': '{RECTAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if • bleeding occurs • condition worsens or does not improve within 7 days"}', 'do_not_use': None, 'when_using': '{"When using this product do not exceed the recommended daily dosage unless directed by a doctor"}', 'warnings': '{"Warnings For rectal use only Ask a doctor before use if you have • heart disease • high blood pressure • thyroid disease • diabetes • difficulty in urination due to enlargement of the prostate gland Ask a doctor or pharmacist before use if you are presently taking a prescription drug for high blood pressure or depression. When using this product do not exceed the recommended daily dosage unless directed by a doctor Stop use and ask a doctor if • bleeding occurs • condition worsens or does not improve within 7 days If pregnant or breast feeding, ask a health professional before use."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{HYDROQUINONE}

{'contraindications': '{"CONTRAINDICATIONS People with prior history of sensitivity or allergic reaction to this product or any of its ingredients should not use it. The safety of topical hydroquinone use during pregnancy or in children (12 years and under) has not been established."}', 'adverse_reactions': '{"ADVERSE REACTIONS No systemic adverse reactions have been reported. Occasional hypersensitivity (localized contact dermatitis) may occur, in which case the product should be discontinued and physician notified immediately. To report SUSPECTED ADVERSE REACTIONS, contact Obagi Medical Products, a division of Valeant Pharmaceuticals North America LLC, at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE The gradual bleaching of hyperpigmented skin conditions such as chloasma, melasma, freckles, senile lentigines, and other unwanted areas of melanin hyperpigmentation."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{HYDROQUINONE}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS • Hydroquinone is a skin-bleaching agent, which may produce unwanted cosmetic effects if not used as directed. The physician should be familiar with the contents of this insert before prescribing or dispensing this product. • Test for skin sensitivity before using by applying a small amount to an unbroken patch of skin and check within 24 hours. Minor redness is not a contraindication, but where there is itching or vesicle formation or excessive inflammatory response, the product should be discontinued and a physician consulted. Close patient supervision is recommended. • Avoid contact with eyes, nose, mouth, and lips. In case of accidental contact, the patient should rinse thoroughly with water and contact a physician. • Sunscreen use is an essential aspect of hydroquinone therapy because even minimal sunlight exposure sustains melanocytic activity. The Obagi-C ® Rx System C-Therapy Night Cream contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people."}', 'precautions': '{"PRECAUTIONS (See WARNINGS . ) Treatment should be limited to relatively small areas of the body at one time since some patients experience a transient skin reddening and a mild burning sensation, which does not preclude treatment. Pregnancy Pregnancy Category C Animal reproduction studies have not been conducted with topical hydroquinone. It is also not known whether hydroquinone can cause fetal harm when used topically on a pregnant woman or affect reproductive capacity. It is not known to what degree, if any, topical hydroquinone is absorbed systemically. Topical hydroquinone should be used on pregnant women only when clearly indicated. Nursing Mothers It is not known whether topical hydroquinone is absorbed or excreted in human milk. Caution is advised when topical hydroquinone is used by a nursing mother. Pediatric Usage Safety and effectiveness in children, below the age of 12 years, have not been established."}', 'information_for_patients': '{"PATIENT INFORMATION For Topical Use Only Complete skin care regimen formulated with 4% hydroquinone to reduce hyperpigmentation and other essential ingredients to help address the signs of skin aging caused by photoaging. Please read this product information prior to use of the Obagi-C ® Rx System. Any questions regarding your particular skin care regimen should be directed to your physician. More information about the Obagi-C® Rx System or other Obagi systems is available at our website at www.obagi.com."}', 'pregnancy': '{"Pregnancy Pregnancy Category C Animal reproduction studies have not been conducted with topical hydroquinone. It is also not known whether hydroquinone can cause fetal harm when used topically on a pregnant woman or affect reproductive capacity. It is not known to what degree, if any, topical hydroquinone is absorbed systemically. Topical hydroquinone should be used on pregnant women only when clearly indicated."}', 'pediatric_use': '{"Pediatric Usage Safety and effectiveness in children, below the age of 12 years, have not been established."}', 'geriatric_use': None}

{"CALCIUM CARBONATE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"USE(S) relieves: acid indigestion heartburn"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"CALCIUM CARBONATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': '{"WHEN USING THIS PRODUCT do not take more than 10 tablets in a 24-hour period, or use the maximum dosage of this product for more than 2 weeks, except under the advice and supervision of a doctor."}', 'warnings': '{"WARNINGS ."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{PREGABALIN}

{'contraindications': '{"4 CONTRAINDICATIONS Pregabalin capsules are contraindicated in patients with known hypersensitivity to pregabalin or any of its components. Angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy [see Warnings and Precautions ( 5.2 )] . • Known hypersensitivity to pregabalin or any of its components. ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: • Angioedema [see Warnings and Precautions ( 5.1 )] • Hypersensitivity [see Warnings and Precautions ( 5.2 )] • Increased Risk of Adverse Reactions with Abrupt or Rapid Discontinuation [see Warnings and Precautions ( 5.3 )] • Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.4 )] • Peripheral Edema [see Warnings and Precautions ( 5.5 )] • Dizziness and Somnolence [see Warnings and Precautions ( 5.6 )] • Weight Gain [see Warnings and Precautions ( 5.7 )] • Tumorigenic Potential [see Warnings and Precautions ( 5.8 )] • Ophthalmological Effects [see Warnings and Precautions ( 5.9 )] • Creatine Kinase Elevations [see Warnings and Precautions ( 5.10 )] • Decreased Platelet Count [see Warnings and Precautions ( 5.11 )] • PR Interval Prolongation [see Warnings and Precautions ( 5.12 )] Most common adverse reactions (greater than or equal to 5% and twice placebo) in adults are dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and thinking abnormal (primarily difficulty with concentration/attention). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs Limited at 1-866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In all controlled and uncontrolled trials across various patient populations during the premarketing development of pregabalin capsules, more than 10,000 patients have received pregabalin capsules. Approximately 5,000 patients were treated for 6 months or more, over 3,100 patients were treated for 1 year or longer, and over 1,400 patients were treated for at least 2 years. Adverse Reactions Most Commonly Leading to Discontinuation in All Premarketing Controlled Clinical Studies In premarketing controlled trials of all adult populations combined, 14% of patients treated with pregabalin capsules and 7% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin capsules treatment group, the adverse reactions most frequently leading to discontinuation were dizziness (4%) and somnolence (4%). In the placebo group, 1% of patients withdrew due to dizziness and less than 1% withdrew due to somnolence. Other adverse reactions that led to discontinuation from controlled trials more frequently in the pregabalin capsules group compared to the placebo group were ataxia, confusion, asthenia, thinking abnormal, blurred vision, incoordination, and peripheral edema (1% each). Most Common Adverse Reactions in All Controlled Clinical Studies in Adults In premarketing controlled trials of all adult patient populations combined (including DPN, PHN, and adult patients with partial-onset seizures), dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and \\"thinking abnormal\\" (primarily difficulty with concentration/attention) were more commonly reported by subjects treated with pregabalin capsules than by subjects treated with placebo (greater than or equal to 5% and twice the rate of that seen in placebo). Controlled Studies with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy Adverse Reactions Leading to Discontinuation In clinical trials in adults with neuropathic pain associated with diabetic peripheral neuropathy, 9% of patients treated with pregabalin capsules and 4% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin capsules treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (3%) and somnolence (2%). In comparison, less than 1% of placebo patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring with greater frequency in the pregabalin capsules group than in the placebo group, were asthenia, confusion, and peripheral edema. Each of these events led to withdrawal in approximately 1% of patients. Most Common Adverse Reactions Table 4 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 1% of patients with neuropathic pain associated with diabetic neuropathy in the combined pregabalin capsules group for which the incidence was greater in this combined pregabalin capsules group than in the placebo group. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of \\"mild\\" or \\"moderate”. Table 4. Adverse Reaction Incidence in Controlled Trials in Neuropathic Pain Associated with Diabetic Peripheral Neuropathy Body system Preferred term 75 mg/day [N=77] % 150 mg/day [N=212] % 300 mg/day [N=321] % 600 mg/day [N=369] % All PG B* [N=979] % Placebo [N=459] % Body as a whole Asthenia 4 2 4 7 5 2 Accidental injury 5 2 2 6 4 3 Back pain 0 2 1 2 2 0 Chest pain 4 1 1 2 2 1 Face edema 0 1 1 2 1 0 Digestive system Dry mouth 3 2 5 7 5 1 Constipation 0 2 4 6 4 2 Flatulence 3 0 2 3 2 1 Metabolic and nutritional disorders Peripheral edema 4 6 9 12 9 2 Weight gain 0 4 4 6 4 0 Edema 0 2 4 2 2 0 Hypoglycemia 1 3 2 1 2 1 Nervous system Dizziness 8 9 23 29 21 5 Somnolence 4 6 13 16 12 3 Neuropathy 9 2 2 5 4 3 Ataxia 6 1 2 4 3 1 Vertigo 1 2 2 4 3 1 Confusion 0 1 2 3 2 1 Euphoria 0 0 3 2 2 0 Incoordination 1 0 2 2 2 0 Thinking abnormal † 1 0 1 3 2 0 Tremor 1 1 1 2 1 0 Abnormal gait 1 0 1 3 1 0 Amnesia 3 1 0 2 1 0 Nervousness 0 1 1 1 1 0 Respiratory system Dyspnea 3 0 2 2 2 1 Special senses Blurry vision ‡ 3 1 3 6 4 2 Abnormal vision 1 0 1 1 1 0 * PGB: pregabalin † Thinking abnormal primarily consists of events related to difficulty with concentration/attention but also includes events related to cognition and language problems and slowed thinking. ‡ Investigator term; summary level term is amblyopia Controlled Studies in Postherpetic Neuralgia Adverse Reactions Leading to Discontinuation In clinical trials in adults with postherpetic neuralgia, 14% of patients treated with pregabalin capsules and 7% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin capsules treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (4%) and somnolence (3%). In comparison, less than 1% of placebo patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring in greater frequency in the pregabalin capsules group than in the placebo group, were confusion (2%), as well as peripheral edema, asthenia, ataxia, and abnormal gait (1% each). Most Common Adverse Reactions Table 5 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 1% of patients with neuropathic pain associated with postherpetic neuralgia in the combined pregabalin capsules group for which the incidence was greater in this combined pregabalin capsules group than in the placebo group. In addition, an event is included, even if the incidence in the all pregabalin capsules group is not greater than in the placebo group, if the incidence of the event in the 600 mg/day group is more than twice that in the placebo group. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of \\"mild\\" or \\"moderate\\". Overall, 12.4% of all pregabalin-treated patients and 9.0% of all placebo-treated patients had at least one severe event while 8% of pregabalin-treated patients and 4.3% of placebo-treated patients had at least one severe treatment-related adverse event. Table 5. Adverse Reaction Incidence in Controlled Trials in Neuropathic Pain Associated with Postherpetic Neuralgia Body system Preferred term 75 mg/d [N=84] % 150 mg/d [N=302] % 300 mg/d [N=312] % 600 mg/d [N=154] % All PGB * [N=852] % Placebo [N=398] % Body as a whole Infection 14 8 6 3 7 4 Headache 5 9 5 8 7 5 Pain 5 4 5 5 5 4 Accidental injury 4 3 3 5 3 2 Flu syndrome 1 2 2 1 2 1 Face edema 0 2 1 3 2 1 Digestive system Dry mouth 7 7 6 15 8 3 Constipation 4 5 5 5 5 2 Flatulence 2 1 2 3 2 1 Vomiting 1 1 3 3 2 1 Metabolic and nutritional disorders Peripheral edema 0 8 16 16 12 4 Weight gain 1 2 5 7 4 0 Edema 0 1 2 6 2 1 Musculoskeletal system Myasthenia 1 1 1 1 1 0 Nervous system Dizziness 11 18 31 37 26 9 Somnolence 8 12 18 25 16 5 Ataxia 1 2 5 9 5 1 Abnormal gait 0 2 4 8 4 1 Confusion 1 2 3 7 3 0 Thinking abnormal † 0 2 1 6 2 2 Incoordination 2 2 1 3 2 0 Amnesia 0 1 1 4 2 0 Speech disorder 0 0 1 3 1 0 Respiratory system Bronchitis 0 1 1 3 1 1 Special senses Blurry vision ‡ 1 5 5 9 5 3 Diplopia 0 2 2 4 2 0 Abnormal vision 0 1 2 5 2 0 Eye Disorder 0 1 1 2 1 0 Urogenital System Urinary Incontinence 0 1 1 2 1 0 * PGB: pregabalin † Thinking abnormal primarily consists of events related to difficulty with concentration/attention but also includes events related to cognition and language problems and slowed thinking. ‡ Investigator term; summary level term is amblyopia Controlled Studies of Adjunctive Therapy for Partial-Onset Seizures in Adult Patients Adverse Reactions Leading to Discontinuation Approximately 15% of patients receiving pregabalin capsules and 6% of patients receiving placebo in trials of adjunctive therapy for partial-onset seizures discontinued prematurely due to adverse reactions. In the pregabalin capsules treatment group, the adverse reactions most frequently leading to discontinuation were dizziness (6%), ataxia (4%), and somnolence (3%). In comparison, less than 1% of patients in the placebo group withdrew due to each of these events. Other adverse reactions that led to discontinuation of at least 1% of patients in the pregabalin capsules group and at least twice as frequently compared to the placebo group were asthenia, diplopia, blurred vision, thinking abnormal, nausea, tremor, vertigo, headache, and confusion (which each led to withdrawal in 2% or less of patients). Most Common Adverse Reactions Table 6 lists all dose-related adverse reactions occurring in at least 2% of all pregabalin capsules-treated patients. Dose-relatedness was defined as the incidence of the adverse event in the 600 mg/day group was at least 2% greater than the rate in both the placebo and 150 mg/day groups. In these studies, 758 patients received pregabalin capsules and 294 patients received placebo for up to 12 weeks. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of \\"mild\\" or \\"moderate”. Table 6. Dose-related Adverse Reaction Incidencein ControlledTrials ofAdjunctive Therapy for Partial-Onset Seizures in Adult Patients Body System Preferred Term 150 mg/d [N = 185] % 300 mg/d [N = 90] % 600 mg/d [N = 395] % All PGB * [N = 670] † % Placebo [N = 294] % Body as a Whole Accidental Injury 7 11 10 9 5 Pain 3 2 5 4 3 Digestive System Increased Appetite 2 3 6 5 1 Dry Mouth 1 2 6 4 1 Constipation 1 1 7 4 2 Metabolic and Nutritional Disorders Weight Gain 5 7 16 12 1 Peripheral Edema 3 3 6 5 2 Nervous System Dizziness 18 31 38 32 11 Somnolence 11 18 28 22 11 Ataxia 6 10 20 15 4 Tremor 3 7 11 8 4 Thinking Abnormal ‡ 4 8 9 8 2 Amnesia 3 2 6 5 2 Speech Disorder 1 2 7 5 1 Incoordination 1 3 6 4 1 Abnormal Gait 1 3 5 4 0 Twitching 0 4 5 4 1 Confusion 1 2 5 4 2 Myoclonus 1 0 4 2 0 Special Senses Blurred Vision § 5 8 12 10 4 Diplopia 5 7 12 9 4 Abnormal Vision 3 1 5 4 1 * PGB: pregabalin † Excludes patients who received the 50 mg dose in Study E1. ‡ Thinking abnormal primarily consists of events related to difficulty with concentration/attention but also includes events related to cognition and language problems and slowed thinking. § Investigator term; summary level term is amblyopia. Controlled Studies with Fibromyalgia Adverse Reactions Leading to Discontinuation In clinical trials of patients with fibromyalgia, 19% of patients treated with pregabalin (150 mg to 600 mg/day) and 10% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (6%) and somnolence (3%). In comparison, less than 1% of placebo-treated patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring with greater frequency in the pregabalin treatment group than in the placebo treatment group, were fatigue, headache, balance disorder, and weight increased. Each of these adverse reactions led to withdrawal in approximately 1% of patients. Most Common Adverse Reactions Table 9 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 2% of patients with fibromyalgia in the ‘all pregabalin’ treatment group for which the incidence was greater than in the placebo treatment group. A majority of pregabalin-treated patients in clinical studies experienced adverse reactions with a maximum intensity of \\"mild\\" or \\"moderate\\". Table 9. Adverse Reaction Incidence in Controlled Trials in Fibromyalgia System Organ Class Preferred term 150 mg/d [N=132] % 300 mg/d [N=502] % 450 mg/d [N=505] % 600 mg/d [N=378] % All PGB * [N=1,517] % Placebo [N=505] % Ear and Labyrinth Disorders Vertigo 2 2 2 1 2 0 Eye Disorders Vision blurred 8 7 7 12 8 1 Gastrointestinal Disorders Dry mouth 7 6 9 9 8 2 Constipation 4 4 7 10 7 2 Vomiting 2 3 3 2 3 2 Flatulence 1 1 2 2 2 1 Abdominal distension 2 2 2 2 2 1 General Disorders and Administrative Site Conditions Fatigue 5 7 6 8 7 4 Edema peripheral 5 5 6 9 6 2 Chest pain 2 1 1 2 2 1 Feeling abnormal 1 3 2 2 2 0 Edema 1 2 1 2 2 1 Feeling drunk 1 2 1 2 2 0 Infections and Infestations Sinusitis 4 5 7 5 5 4 Investigations Weight increased 8 10 10 14 11 2 Metabolism and Nutrition Disorders Increased appetite 4 3 5 7 5 1 Fluid retention 2 3 3 2 2 1 Musculoskeletal and Connective Tissue Disorders Arthralgia 4 3 3 6 4 2 Muscle spasms 2 4 4 4 4 2 Back pain 2 3 4 3 3 3 Nervous System Disorders Dizziness 23 31 43 45 38 9 Somnolence 13 18 22 22 20 4 Headache 11 12 14 10 12 12 Disturbance in attention 4 4 6 6 5 1 Balance disorder 2 3 6 9 5 0 Memory impairment 1 3 4 4 3 0 Coordination abnormal 2 1 2 2 2 1 Hypoesthesia 2 2 3 2 2 1 Lethargy 2 2 1 2 2 0 Tremor 0 1 3 2 2 0 Psychiatric Disorders Euphoric Mood 2 5 6 7 6 1 Confusional state 0 2 3 4 3 0 Anxiety 2 2 2 2 2 1 Disorientation 1 0 2 1 2 0 Depression 2 2 2 2 2 2 Respiratory, Thoracic and Mediastinal Disorders Pharyngolaryngeal pain 2 1 3 3 2 2 * PGB: pregabalin Controlled Studies in Neuropathic Pain Associated with Spinal Cord Injury Adverse Reactions Leading to Discontinuation In clinical trials of adults with neuropathic pain associated with spinal cord injury, 13% of patients treated with pregabalin and 10% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the most common reasons for discontinuation due to adverse reactions were somnolence (3%) and edema (2%). In comparison, none of the placebo-treated patients withdrew due to somnolence and edema. Other reasons for discontinuation from the trials, occurring with greater frequency in the pregabalin treatment group than in the placebo treatment group, were fatigue and balance disorder. Each of these adverse reactions led to withdrawal in less than 2% of patients. Most Common Adverse Reactions Table 10 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 2% of patients for which the incidence was greater than in the placebo treatment group with neuropathic pain associated with spinal cord injury in the controlled trials. A majority of pregabalin-treated patients in clinical studies experienced adverse reactions with a maximum intensity of \\"mild\\" or \\"moderate\\". Table 10. Adverse Reaction Incidence in Controlled Trials in Neuropathic Pain Associated with Spinal Cord Injury System Organ Class Preferred term PGB* (N=182) Placebo (N=174) % % Ear and labyrinth disorders Vertigo 2.7 1.1 Eye disorders Vision blurred 6.6 1.1 Gastrointestinal disorders Dry mouth 11.0 2.9 Constipation 8.2 5.7 Nausea 4.9 4.0 Vomiting 2.7 1.1 General disorders and administration site conditions Fatigue 11.0 4.0 Edema peripheral 10.4 5.2 Edema 8.2 1.1 Pain 3.3 1.1 Infections and infestations Nasopharyngitis 8.2 4.6 Investigations Weight increased 3.3 1.1 Blood creatine phosphokinase increased 2.7 0 Musculoskeletal and connective tissue disorders Muscular weakness 4.9 1.7 Pain in extremity 3.3 2.3 Neck pain 2.7 1.1 Back pain 2.2 1.7 Joint swelling 2.2 0 Nervous system disorders Somnolence 35.7 11.5 Dizziness 20.9 6.9 Disturbance in attention 3.8 0 Memory impairment 3.3 1.1 Paresthesia 2.2 0.6 Psychiatric disorders Insomnia 3.8 2.9 Euphoric mood 2.2 0.6 Renal and urinary disorders Urinary incontinence 2.7 1.1 Skin and subcutaneous tissue disorders Decubitus ulcer 2.7 1.1 Vascular disorders Hypertension 2.2 1.1 Hypotension 2.2 0 * PGB: Pregabalin Other Adverse Reactions Observed During the Clinical Studies of Pregabalin Capsules Following is a list of treatment-emergent adverse reactions reported by patients treated with pregabalin capsules during all clinical trials. The listing does not include those events already listed in the previous tables or elsewhere in labeling, those events for which a drug cause was remote, those events which were so general as to be uninformative, and those events reported only once which did not have a substantial probability of being acutely life-threatening. Events are categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse reactions are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1,000 patients; rare reactions are those occurring in fewer than 1/1,000 patients. Events of major clinical importance are described in the Warnings and Precautions section ( 5 ). Body as a Whole – Frequent : Abdominal pain, Allergic reaction, Fever, Infrequent : Abscess, Cellulitis, Chills, Malaise, Neck rigidity, Overdose, Pelvic pain, Photosensitivity reaction, Rare : Anaphylactoid reaction, Ascites, Granuloma, Hangover effect, Intentional Injury, Retroperitoneal Fibrosis, Shock Cardiovascular System – Infrequent : Deep thrombophlebitis, Heart failure, Hypotension, Postural hypotension, Retinal vascular disorder, Syncope; Rare : ST Depressed, Ventricular Fibrillation Digestive System – Frequent : Gastroenteritis, Increased appetite; Infrequent : Cholecystitis, Cholelithiasis, Colitis, Dysphagia, Esophagitis, Gastritis, Gastrointestinal hemorrhage, Melena, Mouth ulceration, Pancreatitis, Rectal hemorrhage, Tongue edema; Rare : Aphthous stomatitis, Esophageal Ulcer, Periodontal abscess Hemic and Lymphatic System – Frequent : Ecchymosis; Infrequent : Anemia, Eosinophilia, Hypochromic anemia, Leukocytosis, Leukopenia, Lymphadenopathy, Thrombocytopenia; Rare : Myelofibrosis, Polycythemia, Prothrombin decreased, Purpura, Thrombocythemia, Alanine aminotransferase increased, Aspartate aminotransferase increased Metabolic and Nutritional Disorders – Rare : Glucose Tolerance Decreased, Urate Crystalluria Musculoskeletal System – Frequent : Arthralgia, Leg cramps, Myalgia, Myasthenia; Infrequent : Arthrosis; Rare : Chondrodystrophy, Generalized Spasm Nervous System – Frequent : Anxiety, Depersonalization, Hypertonia, Hypoesthesia, Libido decreased, Nystagmus, Paresthesia, Sedation, Stupor, Twitching; Infrequent : Abnormal dreams, Agitation, Apathy, Aphasia, Circumoral paresthesia, Dysarthria, Hallucinations, Hostility, Hyperalgesia, Hyperesthesia, Hyperkinesia, Hypokinesia, Hypotonia, Libido increased, Myoclonus, Neuralgia; Rare : Addiction, Cerebellar syndrome, Cogwheel rigidity, Coma, Delirium, Delusions, Dysautonomia, Dyskinesia, Dystonia, Encephalopathy, Extrapyramidal syndrome, Guillain-Barré syndrome, Hypalgesia, Intracranial hypertension, Manic reaction, Paranoid reaction, Peripheral neuritis, Personality disorder, Psychotic depression, Schizophrenic reaction, Sleep disorder, Torticollis, Trismus Respiratory System – Rare : Apnea, Atelectasis, Bronchiolitis, Hiccup, Laryngismus, Lung edema, Lung fibrosis, Yawn Skin and Appendages – Frequent : Pruritus, Infrequent : Alopecia, Dry skin, Eczema, Hirsutism, Skin ulcer, Urticaria, Vesiculobullous rash; Rare : Angioedema, Exfoliative dermatitis, Lichenoid dermatitis, Melanosis, Nail Disorder, Petechial rash, Purpuric rash, Pustular rash, Skin atrophy, Skin necrosis, Skin nodule, Stevens-Johnson syndrome, Subcutaneous nodule Special senses – Frequent : Conjunctivitis, Diplopia, Otitis media, Tinnitus; Infrequent : Abnormality of accommodation, Blepharitis, Dry eyes, Eye hemorrhage, Hyperacusis, Photophobia, Retinal edema, Taste loss, Taste perversion; Rare : Anisocoria, Blindness, Corneal ulcer, Exophthalmos, Extraocular palsy, Iritis, Keratitis, Keratoconjunctivitis, Miosis, Mydriasis, Night blindness, Ophthalmoplegia, Optic atrophy, Papilledema, Parosmia, Ptosis, Uveitis Urogenital System – Frequent : Anorgasmia, Impotence, Urinary frequency, Urinary incontinence; Infrequent : Abnormal ejaculation, Albuminuria, Amenorrhea, Dysmenorrhea, Dysuria, Hematuria, Kidney calculus, Leukorrhea, Menorrhagia, Metrorrhagia, Nephritis, Oliguria, Urinary retention, Urine abnormality; Rare : Acute kidney failure, Balanitis, Bladder Neoplasm, Cervicitis, Dyspareunia, Epididymitis, Female lactation, Glomerulitis, Ovarian disorder, Pyelonephritis Comparison of Gender and Race The overall adverse event profile of pregabalin was similar between women and men. There are insufficient data to support a statement regarding the distribution of adverse experience reports by race. Pediatric use information is approved for Pfizer\'s LYRICA (pregabalin) Capsules and Oral Solution products. However, due to Pfizer\'s marketing exclusivity rights, this drug product is not labeled with that pediatric information. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of pregabalin capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Nervous System Disorders – Headache Gastrointestinal Disorders – Nausea, Diarrhea Reproductive System and Breast Disorders – Gynecomastia, Breast Enlargement In addition, there are postmarketing reports of events related to reduced lower gastrointestinal tract function (e.g., intestinal obstruction, paralytic ileus, constipation) when pregabalin capsules were co-administered with medications that have the potential to produce constipation, such as opioid analgesics. There are also postmarketing reports of respiratory failure and coma in patients taking pregabalin and other CNS depressant medications."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Since pregabalin capsules are predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (less than 2% of a dose recovered in urine as metabolites), and does not bind to plasma proteins, its pharmacokinetics are unlikely to be affected by other agents through metabolic interactions or protein binding displacement. In vitro and in vivo studies showed that pregabalin capsules are unlikely to be involved in significant pharmacokinetic drug interactions. Specifically, there are no pharmacokinetic interactions between pregabalin and the following antiepileptic drugs: carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital, and topiramate. Important pharmacokinetic interactions would also not be expected to occur between pregabalin capsules and commonly used antiepileptic drugs [see Clinical Pharmacology ( 12)]. Pharmacodynamics Multiple oral doses of pregabalin capsules were co-administered with oxycodone, lorazepam, or ethanol. Although no pharmacokinetic interactions were seen, additive effects on cognitive and gross motor functioning were seen when pregabalin capsules were co-administered with these drugs. No clinically important effects on respiration were seen."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Pregabalin capsules are indicated for: • Management of neuropathic pain associated with diabetic peripheral neuropathy • Management of postherpetic neuralgia • Adjunctive therapy for the treatment of partial onset seizures in patients 17 years of age and older • Management of fibromyalgia • Management of neuropathic pain associated with spinal cord injury Pediatric use information is approved for Pfizer\'s LYRICA (pregabalin) Capsules and Oral Solution products. However, due to Pfizer\'s marketing exclusivity rights, this drug product is not labeled with that pediatric information. Pregabalin capsules are indicated for: • Neuropathic pain associated with diabetic peripheral neuropathy (DPN) ( 1 ) • Postherpetic neuralgia (PHN) ( 1 ) • Adjunctive therapy for the treatment of partial-onset seizures in patients 17 years of age and older ( 1 ) • Fibromyalgia ( 1 ) • Neuropathic pain associated with spinal cord injury ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Angioedema (e.g., swelling of the throat, head and neck) can occur, and may be associated with life-threatening respiratory compromise requiring emergency treatment. Discontinue pregabalin capsules immediately in these cases. ( 5.1 ) • Hypersensitivity reactions (e.g., hives, dyspnea, and wheezing) can occur. Discontinue pregabalin capsules immediately in these patients. ( 5.2 ) • Increased seizure frequency or other adverse reactions may occur if pregabalin capsules are rapidly discontinued. Withdraw pregabalin capsules gradually over a minimum of 1 week. ( 5.3 ) • Antiepileptic drugs, including pregabalin capsules, increase the risk of suicidal thoughts or behavior. ( 5.4 ) • Pregabalin capsules may cause peripheral edema. Exercise caution when co-administering pregabalin capsules and thiazolidinedione antidiabetic agents. ( 5.5 ) • Pregabalin capsules may cause dizziness and somnolence and impair patients’ ability to drive or operate machinery. ( 5.6 ) 5.1 Angioedema There have been postmarketing reports of angioedema in patients during initial and chronic treatment with pregabalin capsules. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). There were reports of life-threatening angioedema with respiratory compromise requiring emergency treatment. Discontinue pregabalin capsules immediately in patients with these symptoms. Exercise caution when prescribing pregabalin capsules to patients who have had a previous episode of angioedema. In addition, patients who are taking other drugs associated with angioedema (e.g., angiotensin converting enzyme inhibitors [ACE-inhibitors]) may be at increased risk of developing angioedema. 5.2 Hypersensitivity There have been postmarketing reports of hypersensitivity in patients shortly after initiation of treatment with pregabalin capsules. Adverse reactions included skin redness, blisters, hives, rash, dyspnea, and wheezing. Discontinue pregabalin capsules immediately in patients with these symptoms. 5.3 Increased Risk of Adverse Reactions with Abrupt or Rapid Discontinuation As with all antiepileptic drugs (AEDs), withdraw pregabalin capsules gradually to minimize the potential of increased seizure frequency in patients with seizure disorders. Following abrupt or rapid discontinuation of pregabalin capsules, some patients reported symptoms including insomnia, nausea, headache, anxiety, hyperhidrosis, and diarrhea. If pregabalin capsules are discontinued, taper the drug gradually over a minimum of 1 week rather than discontinue the drug abruptly. 5.4 Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including pregabalin capsules, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Table 3 shows absolute and relative risk by indication for all evaluated AEDs. Table 3. Risk by Indication for Antiepileptic Drugs in the Pooled Analysis Indication Placebo Patients with Events Per 1,000 Patients Drug Patients with Events Per 1,000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1,000 Patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing pregabalin capsules or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. 5.5 Peripheral Edema Pregabalin capsules treatment may cause peripheral edema. In short-term trials of patients without clinically significant heart or peripheral vascular disease, there was no apparent association between peripheral edema and cardiovascular complications such as hypertension or congestive heart failure. Peripheral edema was not associated with laboratory changes suggestive of deterioration in renal or hepatic function. In controlled clinical trials in adult patients, the incidence of peripheral edema was 6% in the pregabalin capsules group compared with 2% in the placebo group. In controlled clinical trials, 0.5% of pregabalin capsules patients and 0.2% placebo patients withdrew due to peripheral edema. Higher frequencies of weight gain and peripheral edema were observed in patients taking both pregabalin capsules and a thiazolidinedione antidiabetic agent compared to patients taking either drug alone. The majority of patients using thiazolidinedione antidiabetic agents in the overall safety database were participants in studies of pain associated with diabetic peripheral neuropathy. In this population, peripheral edema was reported in 3% (2/60) of patients who were using thiazolidinedione antidiabetic agents only, 8% (69/859) of patients who were treated with pregabalin capsules only, and 19% (23/120) of patients who were on both pregabalin capsules and thiazolidinedione antidiabetic agents. Similarly, weight gain was reported in 0% (0/60) of patients on thiazolidinediones only; 4% (35/859) of patients on pregabalin capsules only; and 7.5% (9/120) of patients on both drugs. As the thiazolidinedione class of antidiabetic drugs can cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, exercise caution when co-administering pregabalin capsules and these agents. Because there are limited data on congestive heart failure patients with New York Heart Association (NYHA) Class III or IV cardiac status, exercise caution when using pregabalin capsules in these patients. 5.6 Dizziness and Somnolence Pregabalin capsules may cause dizziness and somnolence. Inform patients that pregabalin capsules-related dizziness and somnolence may impair their ability to perform tasks such as driving or operating machinery [see Patient Counseling Information ( 17 )]. In the pregabalin capsules controlled trials in adult patients, dizziness was experienced by 30% of pregabalin capsules-treated patients compared to 8% of placebo-treated patients; somnolence was experienced by 23% of pregabalin capsules-treated patients compared to 8% of placebo-treated patients. Dizziness and somnolence generally began shortly after the initiation of pregabalin capsules therapy and occurred more frequently at higher doses. Dizziness and somnolence were the adverse reactions most frequently leading to withdrawal (4% each) from controlled studies. In pregabalin capsules-treated patients reporting these adverse reactions in short-term, controlled studies, dizziness persisted until the last dose in 30% and somnolence persisted until the last dose in 42% of patients [see Drug Interactions ( 7 )]. Pediatric use information is approved for Pfizer\'s LYRICA (pregabalin) Capsules and Oral Solution products. However, due to Pfizer’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. 5.7 Weight Gain Pregabalin capsules treatment may cause weight gain. In pregabalin capsules controlled clinical trials in adult patients of up to 14 weeks, a gain of 7% or more over baseline weight was observed in 9% of pregabalin capsules-treated patients and 2% of placebo-treated patients. Few patients treated with pregabalin capsules (0.3%) withdrew from controlled trials due to weight gain. Pregabalin capsules associated weight gain was related to dose and duration of exposure, but did not appear to be associated with baseline BMI, gender, or age. Weight gain was not limited to patients with edema [see Warnings and Precautions ( 5.5 )]. Although weight gain was not associated with clinically important changes in blood pressure in short-term controlled studies, the long-term cardiovascular effects of pregabalin capsules-associated weight gain are unknown. Among diabetic patients, pregabalin capsules-treated patients gained an average of 1.6 kg (range: -16 to 16 kg), compared to an average 0.3 kg (range: -10 to 9 kg) weight gain in placebo patients. In a cohort of 333 diabetic patients who received pregabalin capsules for at least 2 years, the average weight gain was 5.2 kg. While the effects of pregabalin capsules-associated weight gain on glycemic control have not been systematically assessed, in controlled and longer-term open label clinical trials with diabetic patients, pregabalin capsules treatment did not appear to be associated with loss of glycemic control (as measured by HbA 1C ). 5.8 Tumorigenic Potential In standard preclinical in vivo lifetime carcinogenicity studies of pregabalin capsules, an unexpectedly high incidence of hemangiosarcoma was identified in two different strains of mice [see Nonclinical Toxicology ( 13.1 )]. The clinical significance of this finding is unknown. Clinical experience during pregabalin capsules premarketing development provides no direct means to assess its potential for inducing tumors in humans. In clinical studies across various patient populations, comprising 6,396 patient-years of exposure in patients greater than 12 years of age, new or worsening-preexisting tumors were reported in 57 patients. Without knowledge of the background incidence and recurrence in similar populations not treated with pregabalin capsules, it is impossible to know whether the incidence seen in these cohorts is or is not affected by treatment. 5.9 Ophthalmological Effects In controlled studies in adult patients, a higher proportion of patients treated with pregabalin capsules reported blurred vision (7%) than did patients treated with placebo (2%), which resolved in a majority of cases with continued dosing. Less than 1% of patients discontinued pregabalin capsules treatment due to vision-related events (primarily blurred vision). Prospectively planned ophthalmologic testing, including visual acuity testing, formal visual field testing and dilated funduscopic examination, was performed in over 3,600 patients. In these patients, visual acuity was reduced in 7% of patients treated with pregabalin capsules, and 5% of placebo-treated patients. Visual field changes were detected in 13% of pregabalin capsules-treated, and 12% of placebo-treated patients. Funduscopic changes were observed in 2% of pregabalin capsules-treated and 2% of placebo-treated patients. Although the clinical significance of the ophthalmologic findings is unknown, inform patients to notify their physician if changes in vision occur. If visual disturbance persists, consider further assessment. Consider more frequent assessment for patients who are already routinely monitored for ocular conditions [see Patient Counseling Information ( 17 )]. 5.10 Creatine Kinase Elevations Pregabalin capsules treatment was associated with creatine kinase elevations. Mean changes in creatine kinase from baseline to the maximum value were 60 U/L for pregabalin capsules-treated patients and 28 U/L for the placebo patients. In all controlled trials in adult patients across multiple patient populations, 1.5% of patients on pregabalin capsules and 0.7% of placebo patients had a value of creatine kinase at least three times the upper limit of normal. Three pregabalin capsules-treated subjects had events reported as rhabdomyolysis in premarketing clinical trials. The relationship between these myopathy events and pregabalin capsules is not completely understood because the cases had documented factors that may have caused or contributed to these events. Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if these muscle symptoms are accompanied by malaise or fever. Discontinue treatment with pregabalin capsules if myopathy is diagnosed or suspected or if markedly elevated creatine kinase levels occur. 5.11 Decreased Platelet Count Pregabalin capsules treatment was associated with a decrease in platelet count. Pregabalin capsules-treated subjects experienced a mean maximal decrease in platelet count of 20 × 10 3 /μL, compared to 11 × 10 3 /μL in placebo patients. In the overall database of controlled trials in adult patients, 2% of placebo patients and 3% of pregabalin capsules patients experienced a potentially clinically significant decrease in platelets, defined as 20% below baseline value and less than 150 × 10 3 /μL. A single pregabalin capsules-treated subject developed severe thrombocytopenia with a platelet count less than 20 x 10 3 /μL. In randomized controlled trials, pregabalin capsules were not associated with an increase in bleeding-related adverse reactions. 5.12 PR Interval Prolongation Pregabalin capsules treatment was associated with PR interval prolongation. In analyses of clinical trial ECG data in adult patients, the mean PR interval increase was 3 to 6 msec at pregabalin capsules doses greater than or equal to 300 mg/day. This mean change difference was not associated with an increased risk of PR increase greater than or equal to 25% from baseline, an increased percentage of subjects with on-treatment PR greater than 200 msec, or an increased risk of adverse reactions of second or third degree AV block. Subgroup analyses did not identify an increased risk of PR prolongation in patients with baseline PR prolongation or in patients taking other PR prolonging medications. However, these analyses cannot be considered definitive because of the limited number of patients in these categories."}', 'overdosage': '{"10 OVERDOSAGE Signs, Symptoms and Laboratory Findings of Acute Overdosage in Humans There is limited experience with overdose of pregabalin capsules. The highest reported accidental overdose of pregabalin capsules during the clinical development program was 8000 mg, and there were no notable clinical consequences. Treatment or Management of Overdose There is no specific antidote for overdose with pregabalin capsules. If indicated, elimination of unabsorbed drug may be attempted by emesis or gastric lavage; observe usual precautions to maintain the airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient. Contact a Certified Poison Control Center for up-to-date information on the management of overdose with pregabalin capsules. Although hemodialysis has not been performed in the few known cases of overdose, it may be indicated by the patient\'s clinical state or in patients with significant renal impairment. Standard hemodialysis procedures result in significant clearance of pregabalin (approximately 50% in 4 hours)."}', 'active_flag': 'Y', 'generic_name': '{PREGABALIN}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Angioedema Advise patients that pregabalin capsules may cause angioedema, with swelling of the face, mouth (lip, gum, tongue) and neck (larynx and pharynx) that can lead to life-threatening respiratory compromise. Instruct patients to discontinue pregabalin capsules and immediately seek medical care if they experience these symptoms [see Warnings and Precautions ( 5.1)]. Hypersensitivity Advise patients that pregabalin capsules has been associated with hypersensitivity reactions such as wheezing, dyspnea, rash, hives, and blisters. Instruct patients to discontinue pregabalin capsules and immediately seek medical care if they experience these symptoms [see Warnings and Precautions ( 5.2 )]. Adverse Reactions with Abrupt or Rapid Discontinuation Advise patients to take pregabalin capsules as prescribed. Abrupt or rapid discontinuation may result in increased seizure frequency in patients with seizure disorders, and insomnia, nausea, headache, anxiety, hyperhidrosis, or diarrhea [see Warnings and Precautions ( 5.3)]. Suicidal Thinking and Behavior Patients, their caregivers, and families should be counseled that AEDs, including pregabalin capsules, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Report behaviors of concern immediately to healthcare providers [see Warnings and Precautions (5.4)]. Dizziness and Somnolence Counsel patients that pregabalin capsules may cause dizziness, somnolence, blurred vision and other CNS signs and symptoms. Accordingly, advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they have gained sufficient experience on pregabalin capsules to gauge whether or not it affects their mental, visual, and/or motor performance adversely [see Warnings and Precautions ( 5.6)]. Weight Gain and Edema Counsel patients that pregabalin capsules may cause edema and weight gain. Advise patients that concomitant treatment with pregabalin capsules and a thiazolidinedione antidiabetic agent may lead to an additive effect on edema and weight gain. For patients with preexisting cardiac conditions, this may increase the risk of heart failure [see Warnings and Precautions ( 5.5 and 5.7)]. Ophthalmological Effects Counsel patients that pregabalin capsules may cause visual disturbances. Inform patients that if changes in vision occur, they should notify their physician [see Warnings and Precautions (5.9)]. Creatine Kinase Elevations Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever [see Warnings and Precautions ( 5.10)]. CNS Depressants Inform patients who require concomitant treatment with central nervous system depressants such as opiates or benzodiazepines that they may experience additive CNS side effects, such as somnolence [see Warnings and Precautions ( 5.6) and Drug Interactions (7) ]. Alcohol Tell patients to avoid consuming alcohol while taking pregabalin capsules, as pregabalin capsules may potentiate the impairment of motor skills and sedating effects of alcohol. Missed Dose Counsel patients if they miss a dose, they should take it as soon as they remember. If it is almost time for the next dose, they should skip the missed dose and take the next dose at their regularly scheduled time. Instruct patients not to take two doses at the same time. Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to pregabalin capsules during pregnancy [see Use in Specific Populations ( 8.1)]. Lactation Advise nursing mothers that breastfeeding is not recommended during treatment with pregabalin capsules [see Use in Specific Populations ( 8.2)]. Male Fertility Inform men being treated with pregabalin capsules who plan to father a child of the potential risk of male-mediated teratogenicity. In preclinical studies in rats, pregabalin was associated with an increased risk of male-mediated teratogenicity. The clinical significance of this finding is uncertain [see Nonclinical Toxicology ( 13.1 ) and Use in Specific populations (8.3)]. Dermatopathy Instruct diabetic patients to pay particular attention to skin integrity while being treated with pregabalin capsules and to inform their healthcare provider about any sores or skin problems. Some animals treated with pregabalin developed skin ulcerations, although no increased incidence of skin lesions associated with pregabalin capsules was observed in clinical trials [see Nonclinical Toxicology ( 13.2)]. Manufactured for: Camber Pharmaceuticals, Inc. Piscataway, NJ 08854 By: HETERO TM Hetero Labs Limited Jeedimetla, Hyderabad-500055, India Revised: 07/2019"}', 'pregnancy': '{"8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to pregabalin capsules during pregnancy. To provide information regarding the effects of in utero exposure to pregabalin capsules, physicians are advised to recommend that pregnant patients taking pregabalin capsules enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/. Risk Summary There are no adequate and well-controlled studies with pregabalin capsules in pregnant women. However, in animal reproduction studies, increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity, including skeletal malformations, retarded ossification, and decreased fetal body weight were observed in the offspring of rats and rabbits given pregabalin orally during organogenesis, at doses that produced plasma pregabalin exposures (AUC) greater than or equal to 16 times human exposure at the maximum recommended dose (MRD) of 600 mg/day [see Data]. In an animal development study, lethality, growth retardation, and nervous and reproductive system functional impairment were observed in the offspring of rats given pregabalin during gestation and lactation. The no-effect dose for developmental toxicity was approximately twice the human exposure at MRD. The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. Advise pregnant women of the potential risk to a fetus. Data Animal Data When pregnant rats were given pregabalin (500 mg, 1250 mg, or 2500 mg/kg) orally throughout the period of organogenesis, incidences of specific skull alterations attributed to abnormally advanced ossification (premature fusion of the jugal and nasal sutures) were increased at greater than or equal to 1250 mg/kg, and incidences of skeletal variations and retarded ossification were increased at all doses. Fetal body weights were decreased at the highest dose. The low dose in this study was associated with a plasma exposure (AUC) approximately 17 times human exposure at the MRD of 600 mg/day. A no-effect dose for rat embryo-fetal developmental toxicity was not established. When pregnant rabbits were given pregabalin capsules (250 mg, 500 mg, or 1250 mg/kg) orally throughout the period of organogenesis, decreased fetal body weight and increased incidences of skeletal malformations, visceral variations, and retarded ossification were observed at the highest dose. The no-effect dose for developmental toxicity in rabbits (500 mg/kg) was associated with a plasma exposure approximately 16 times human exposure at the MRD. In a study in which female rats were dosed with pregabalin capsules (50 mg, 100 mg, 250 mg, 1250 mg, or 2500 mg/kg) throughout gestation and lactation, offspring growth was reduced at greater than or equal to 100 mg/kg and offspring survival was decreased at greater than or equal to 250 mg/kg. The effect on offspring survival was pronounced at doses greater than or equal to 1250 mg/kg, with 100% mortality in high-dose litters. When offspring were tested as adults, neurobehavioral abnormalities (decreased auditory startle responding) were observed at greater than or equal to 250 mg/kg and reproductive impairment (decreased fertility and litter size) was seen at 1250 mg/kg. The no-effect dose for pre- and postnatal developmental toxicity in rats (50 mg/kg) produced a plasma exposure approximately 2 times human exposure at the MRD. In the prenatal-postnatal study in rats, pregabalin prolonged gestation and induced dystocia at exposures greater than or equal to 50 times the mean human exposure (AUC (0 to 24) of 123 mcg∙hr/mL) at theMRD."}', 'pediatric_use': '{"8.4 Pediatric Use Neuropathic Pain Associated with Diabetic Peripheral Neuropathy, Postherpetic Neuralgia, and Neuropathic Pain Associated with Spinal Cord Injury Safety and effectiveness in pediatric patients have not been established. Fibromyalgia Safety and effectiveness in pediatric patients have not been established. Adjunctive Therapy for Partial-Onset Seizures Safety and effectiveness in pediatric patients below the age of 1 month have not been established. Juvenile Animal Data In studies in which pregabalin (50 mg to 500 mg/kg) was orally administered to young rats from early in the postnatal period (Postnatal Day 7) through sexual maturity, neurobehavioral abnormalities (deficits in learning and memory, altered locomotor activity, decreased auditory startle responding and habituation) and reproductive impairment (delayed sexual maturation and decreased fertility in males and females) were observed at doses greater than or equal to 50 mg/kg. The neurobehavioral changes of acoustic startle persisted at greater than or equal to 250 mg/kg and locomotor activity and water maze performance at greater than or equal to 500 mg/kg in animals tested after cessation of dosing and, thus, were considered to represent long-term effects. The low effect dose for developmental neurotoxicity and reproductive impairment in juvenile rats (50 mg/kg) was associated with a plasma pregabalin exposure (AUC) approximately equal to human exposure at the maximum recommended dose of 600 mg/day. A no-effect dose was not established. Information describing a clinical study in which efficacy was not demonstrated in patients is approved for Pfizer Inc.\'s Lyrica® (pregabalin) products. Additional pediatric use information is approved for Pfizer\'s LYRICA (pregabalin) Capsules and Oral Solution products. However, due to Pfizer’s marketing exclusivity rights, this drug product is not labeled with that pediatric information."}', 'geriatric_use': '{"8.5 Geriatric Use In controlled clinical studies of pregabalin capsules in neuropathic pain associated with diabetic peripheral neuropathy, 246 patients were 65 to 74 years of age, and 73 patients were 75 years of age or older. In controlled clinical studies of pregabalin capsules in neuropathic pain associated with postherpetic neuralgia, 282 patients were 65 to 74 years of age, and 379 patients were 75 years of age or older. In controlled clinical studies of pregabalin capsules in epilepsy, there were only 10 patients 65 to 74 years of age, and 2 patients who were 75 years of age or older. No overall differences in safety and efficacy were observed between these patients and younger patients. In controlled clinical studies of pregabalin capsules in fibromyalgia, 106 patients were 65 years of age or older. Although the adverse reaction profile was similar between the two age groups, the following neurological adverse reactions were more frequent in patients 65 years of age or older: dizziness, vision blurred, balance disorder, tremor, confusional state, coordination abnormal, and lethargy. Pregabalin capsules are known to be substantially excreted by the kidney, and the risk of toxic reactions to pregabalin capsules may be greater in patients with impaired renal function. Because pregabalin is eliminated primarily by renal excretion, adjust the dose for elderly patients with renal impairment [see Dosage and Administration (2.7)]."}'}

{ALCOHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses Hand sanitizing to decrease bacteria on skin. Recommended for repeated use. No rinsing required."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{ETHANOL}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask doctor Stop use and ask doctor if skin irritation or redness persists for more than 72 hours."}', 'do_not_use': None, 'when_using': '{"When using this product Do not swallow. If swallowed, do not induce vomiting and if individual is conscious, give large quantity of water to drink and consult a physician immediately."}', 'warnings': '{"Warnings Flammable. Keep away from fire, flame or spark. For external use only. . Do not use in the eye; if in eyes, rinse thoroughly with water."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{AMOXICILLIN}

{'contraindications': '{"4 CONTRAINDICATIONS Amoxicillin is contraindicated in patients who have experienced a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin or to other β-lactam antibacterial drugs (e.g., penicillins and cephalosporins). History of a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin or to other beta-lactams (e.g., penicillins or cephalosporins). ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: Anaphylactic reactions [ see Warnings and Precautions ( 5.1 ) ] Severe Cutaneous Adverse Reactions [ see Warnings and Precautions ( 5.2 ) ] Clostridioides difficile -Associated Diarrhea (CDAD) [ see Warnings and Precautions ( 5.3 ) ] The most common adverse reactions (greater than 1%) observed in clinical trials of Amoxicillin for Oral Suspension, USP were diarrhea, rash, vomiting, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-233-2001, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions (greater than 1%) observed in clinical trials of amoxicillin oral suspension were diarrhea, rash, vomiting, and nausea. Triple therapy: The most frequently reported adverse events for patients who received triple therapy (amoxicillin/clarithromycin/ lansoprazole) were diarrhea (7%), headache (6%), and taste perversion (5%). Dual therapy: The most frequently reported adverse events for patients who received double therapy amoxicillin/lansoprazole were diarrhea (8%) and headache (7%). For more information on adverse reactions with clarithromycin or lansoprazole, refer to the Adverse Reactions section of their package inserts. 6.2 Postmarketing Experience In addition to adverse events reported from clinical trials, the following events have been identified during postmarketing use of penicillins. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to amoxicillin. Infections and Infestations: Mucocutaneous candidiasis. Gastrointestinal: Black hairy tongue, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [ see Warnings and Precautions ( 5.3 ) ]. Immune: Hypersensitivity reactions, anaphylactic/anaphylactoid reactions (including shock), angioedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), hypersensitivity vasculitis [ see Warnings and Precautions ( 5.1 ) ]. Skin and Appendages: Rashes, pruritus, urticaria, erythema multiforme, SJS, TEN, DRESS, AGEP, exfoliative dermatitis [ see Warnings and Precautions ( 5.2 ) ]. Liver: A moderate rise in AST and/or ALT has been noted, but the significance of this finding is unknown. Hepatic dysfunction including cholestatic jaundice, hepatic cholestasis and acute cytolytic hepatitis have been reported. Renal: Crystalluria has been reported [ see Overdosage ( 10 ) ]. Hemic and Lymphatic Systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Central Nervous System: Reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, aseptic meningitis, and/or dizziness have been reported. Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) has been reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Co-administration with probenicid is not recommended. ( 7.1 ) Concomitant use of Amoxicillin for Oral Suspension, USP and oral anticoagulants may increase the prolongation of prothrombin time. ( 7.2 ) Co-administration with allopurinol increases the risk of rash. ( 7.3 ) Amoxicillin for Oral Suspension, USP may reduce the efficacy of oral contraceptives. ( 7.4 ) 7.1 Probenecid Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use of amoxicillin and probenecid may result in increased and prolonged blood levels of amoxicillin. 7.2 Oral Anticoagulants Abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been reported in patients receiving amoxicillin and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation. 7.3 Allopurinol The concurrent administration of allopurinol and amoxicillin increases the incidence of rashes in patients receiving both drugs as compared to patients receiving amoxicillin alone. It is not known whether this potentiation of rashes is due to allopurinol or the hyperuricemia present in these patients. 7.4 Oral Contraceptives Amoxicillin may affect intestinal flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives. 7.5 Other Antibacterials Chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with the bactericidal effects of penicillin. This has been demonstrated in vitro ; however, the clinical significance of this interaction is not well documented. 7.6 Effects on Laboratory Tests High urine concentrations of ampicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST ® , Benedict’s Solution, or Fehling’s Solution. Since this effect may also occur with amoxicillin, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as CLINISTIX ® ) be used. Following administration of ampicillin or amoxicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been noted."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Adults and Pediatric Patients Upper Respiratory Tract Infections of the Ear, Nose, and Throat: Amoxicillin for Oral Suspension, USP is indicated in the treatment of infections due to susceptible (ONLY β-lactamase–negative) isolates of Streptococcus species. (α-and β-hemolytic isolates only), Streptococcus pneumoniae , Staphylococcus spp., or Haemophilus influenzae . Infections of the Genitourinary Tract: Amoxicillin for Oral Suspension, USP is indicated in the treatment of infections due to susceptible (ONLY β-lactamase–negative) isolates of Escherichia coli , Proteus mirabilis , or Enterococcus faecalis . Infections of the Skin and Skin Structure: Amoxicillin for Oral Suspension, USP is indicated in the treatment of infections due to susceptible (ONLY β-lactamase–negative) isolates of Streptococcus spp. (α-and β-hemolytic isolates only), Staphylococcus spp., or E. coli . Infections of the Lower Respiratory Tract: Amoxicillin for Oral Suspension, USP is indicated in the treatment of infections due to susceptible (ONLY β-lactamase–negative) isolates of Streptococcus spp. (α-and β-hemolytic isolates only), S. pneumoniae , Staphylococcus spp., or H. influenzae . Adult Patients only Helicobacter pylori Infection and Duodenal Ulcer Disease: Triple therapy for Helicobacter pylori (H. pylori) with clarithromycin and lansoprazole: Amoxicillin for Oral Suspension, USP, in combination with clarithromycin plus lansoprazole as triple therapy, is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) to eradicate H. pylori . Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. Dual therapy for H. pylori with lansoprazole: Amoxicillin for Oral Suspension, USP, in combination with lansoprazole delayed-release capsules as dual therapy, is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected. (See the clarithromycin package insert, MICROBIOLOGY.) Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin for Oral Suspension, USP, and other antibacterial drugs, Amoxicillin for Oral Suspension, USP, should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Amoxicillin for Oral Suspension, USP is a penicillin-class antibacterial indicated for treatment of infections due to susceptible strains of designated microorganisms. ( 1 ) Adults and Pediatric Patients ( 1 ) Upper Respiratory Tract Infections of the Ear, Nose, and Throat Infections of the Genitourinary Tract Infections of the Skin and Skin Structure Infections of the Lower Respiratory Tract Adult Patients only ( 1 ) Helicobacter pylori Infection and Duodenal Ulcer Disease Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of Amoxicillin for Oral Suspension, USP and other antibacterial drugs, Amoxicillin for Oral Suspension, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Anaphylactic reactions: Serious and occasionally fatal anaphylactic reactions have been reported in patients on penicillin therapy, including amoxicillin. Discontinue Amoxicillin for Oral Suspension, USP if a reaction occurs ( 5.1 ). Severe cutaneous adverse reactions (SCAR): Monitor closely. Discontinue if rash progresses. ( 5.2 ) Clostridioides difficile -associated diarrhea (CDAD) (ranging from mild diarrhea to fatal colitis): Evaluate if diarrhea occurs. ( 5.3 ) 5.1 Anaphylactic Reactions Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy including amoxicillin. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before initiating therapy with amoxicillin, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, amoxicillin should be discontinued, and appropriate therapy instituted. 5.2 Severe Cutaneous Adverse Reactions Amoxicillin may cause severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). If patients develop skin rash they should be monitored closely, and amoxicillin discontinued if lesions progress. 5.3 Clostridioides difficile -Associated Diarrhea (CDAD) Clostridioides difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including amoxicillin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. 5.4 Development of Drug-Resistant Bacteria Prescribing amoxicillin in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. 5.5 Skin Rash in Patients with Mononucleosis A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, amoxicillin should not be administered to patients with mononucleosis. 5.6 Phenylketonurics Amoxicillin chewable tablets contain aspartame which contains phenylalanine. Each 200 mg chewable tablet contains 1.82 mg phenylalanine; each 400 mg chewable tablet contains 3.64 mg phenylalanine. The oral suspension formulations of amoxicillin do not contain phenylalanine and can be used by phenylketonurics."}', 'overdosage': '{"10 OVERDOSAGE In case of overdosage, discontinue amoxicillin, treat symptomatically, and institute supportive measures as required. A prospective study of 51 pediatric patients at a poison-control center suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms. Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxicillin 1 . Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin crystalluria. Renal impairment appears to be reversible with cessation of drug administration. High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of amoxicillin. Amoxicillin may be removed from circulation by hemodialysis."}', 'active_flag': 'Y', 'generic_name': '{AMOXICILLIN}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Administration Instructions Advise patients that amoxicillin for oral suspension may be taken every 8 hours or every 12 hours, depending on the dose prescribed. Allergic Reactions Counsel patients that amoxicillin for oral suspension contains a penicillin class drug product that can cause allergic reactions in some individuals. Severe Cutaneous Adverse Reactions (SCAR) Advise patients about the signs and symptoms of serious skin manifestations. Instruct patients to stop taking amoxicillin for oral suspension immediately and promptly report the first signs or symptoms of skin rash, mucosal lesions, or any other sign of hypersensitivity [see Warnings and Precautions ( 5.2 )] . Diarrhea Counsel patients that diarrhea is a common problem caused by antibacterial drugs which usually ends when the antibacterial drug is discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken their last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible. Antibacterial Resistance Patients should be counseled that antibacterial drugs, including amoxicillin for oral suspension, should only be used to treat or prevent bacterial infections. Antibacterial drugs do not treat viral infections (e.g., the common cold). When amoxicillin for oral suspension is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by amoxicillin for oral suspension or other antibacterial drugs in the future. Storage and Special Handling Instructions It is preferable to refrigerate amoxicillin for oral suspension, but not required. Shake oral suspensions well before each use. Keep bottle tightly closed. When dosing a child with the suspension (liquid), use a calibrated oral syringe. Be sure to rinse the calibrated oral syringe after each use. Bottles of suspension of amoxicillin may contain more liquid than required. Follow your doctor’s instructions about the amount to use and the days of treatment your child requires. Discard any unused portion of the suspension after 14 days. Phenylketonuria The oral suspensions of Amoxicillin do not contain phenylalanine and can be used by phenylketonurics. CLINITEST is a registered trademark of Miles, Inc. CLINISTIX is a registered trademark of Bayer Corporation. CLOtest is a registered trademark of Kimberly-Clark Corporation. Distributed by: Hikma Pharmaceuticals USA Inc. Berkeley Heights, NJ 07922 Manufactured by: Hikma Pharmaceuticals P.O. Box 182400 Amman 11118 – Jordan 2INAMOXU24N-E Revised November 2022"}', 'pregnancy': '{"8.1 Pregnancy Teratogenic Effects : Reproduction studies have been performed in mice and rats at doses up to 2000 mg/kg (3 and 6 times the 3 g human dose, based on body surface area). There was no evidence of harm to the fetus due to amoxicillin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, amoxicillin should be used during pregnancy only if clearly needed."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness of amoxicillin for the treatment of upper respiratory tract infections, and infections of the genitourinary tract, skin and skin structure and lower respiratory tract have been established in pediatric patients. The safety and effectiveness of amoxicillin for the treatment of H.Pylori infection have not been established in pediatric patients. Because of incompletely developed renal function in neonates and young infants, the elimination of amoxicillin may be delayed. Dosing of amoxicillin should be modified in pediatric patients 12 weeks or younger (3 months or younger) [see Dosage and Administration ( 2.3 )] ."}', 'geriatric_use': '{"8.5 Geriatric Use An analysis of clinical studies of amoxicillin was conducted to determine whether subjects aged 65 and over respond differently from younger subjects. These analyses have not identified differences in responses between the elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function."}'}

{CARBAMAZEPINE}

{'contraindications': '{"CONTRAINDICATIONS Carbamazepine extended-release tablets should not be used in patients with a history of previous bone marrow depression, hypersensitivity to the drug, or known sensitivity to any of the tricyclic compounds, such as amitriptyline, desipramine, imipramine, protriptyline, nortriptyline, etc. Likewise, on theoretical grounds its use with monoamine oxidase (MAO) inhibitors is not recommended. Before administration of carbamazepine extended-release tablets, MAO inhibitors should be discontinued for a minimum of 14 days, or longer if the clinical situation permits. Co-administration of carbamazepine and nefazodone may result in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect. Co-administration of carbamazepine with nefazodone is contraindicated."}', 'adverse_reactions': '{"ADVERSE REACTIONS If adverse reactions are of such severity that the drug must be discontinued, the physician must be aware that abrupt discontinuation of any anticonvulsant drug in a responsive epileptic patient may lead to seizures or even status epilepticus with its life-threatening hazards. The most severe adverse reactions have been observed in the hemopoietic system and skin (see BOXED WARNING ), the liver, and the cardiovascular system. The most frequently observed adverse reactions, particularly during the initial phases of therapy, are dizziness, drowsiness, unsteadiness, nausea, and vomiting. To minimize the possibility of such reactions, therapy should be initiated at the lowest dosage recommended. The following additional adverse reactions have been reported: Hemopoietic System: Aplastic anemia, agranulocytosis, pancytopenia, bone marrow depression, thrombocytopenia, leukopenia, leukocytosis, eosinophilia, acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda. Skin: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) (see BOXED WARNING ), Acute Generalized Exanthematous Pustulosis (AGEP), pruritic and erythematous rashes, urticaria, photosensitivity reactions, alterations in skin pigmentation, exfoliative dermatitis, erythema multiforme and nodosum, purpura, aggravation of disseminated lupus erythematosus, alopecia, diaphoresis, onychomadesis and hirsutism. In certain cases, discontinuation of therapy may be necessary. Cardiovascular System: Congestive heart failure, edema, aggravation of hypertension, hypotension, syncope and collapse, aggravation of coronary artery disease, arrhythmias and AV block, thrombophlebitis, thromboembolism (e.g., pulmonary embolism), and adenopathy or lymphadenopathy. Some of these cardiovascular complications have resulted in fatalities. Myocardial infarction has been associated with other tricyclic compounds. Liver: Abnormalities in liver function tests, cholestatic and hepatocellular jaundice, hepatitis, very rare cases of hepatic failure. Pancreatic: Pancreatitis. Respiratory System: Pulmonary hypersensitivity characterized by fever, dyspnea, pneumonitis, or pneumonia. Genitourinary System: Urinary frequency, acute urinary retention, oliguria with elevated blood pressure, azotemia, renal failure, and impotence. Albuminuria, glycosuria, elevated BUN, and microscopic deposits in the urine have also been reported. There have been rare reports of impaired male fertility and/or abnormal spermatogenesis. Testicular atrophy occurred in rats receiving carbamazepine orally from 4 to 52 weeks at dosage levels of 50 to 400 mg/kg/day. Additionally, rats receiving carbamazepine in the diet for 2 years at dosage levels of 25, 75, and 250 mg/kg/day had a dose-related incidence of testicular atrophy and aspermatogenesis. In dogs, it produced a brownish discoloration, presumably a metabolite, in the urinary bladder at dosage levels of 50 mg/kg and higher. Relevance of these findings to humans is unknown. Nervous System: Dizziness, drowsiness, disturbances of coordination, confusion, headache, fatigue, blurred vision, visual hallucinations, transient diplopia, oculomotor disturbances, nystagmus, speech disturbances, abnormal involuntary movements, peripheral neuritis and paresthesias, depression with agitation, talkativeness, tinnitus, hyperacusis, neuroleptic malignant syndrome. There have been reports of associated paralysis and other symptoms of cerebral arterial insufficiency, but the exact relationship of these reactions to the drug has not been established. Isolated cases of neuroleptic malignant syndrome have been reported both with and without concomitant use of psychotropic drugs. Digestive System: Nausea, vomiting, gastric distress and abdominal pain, diarrhea, constipation, anorexia, and dryness of the mouth and pharynx, including glossitis and stomatitis. Eyes: Scattered punctate cortical lens opacities, increased intraocular pressure (see WARNINGS, General ) as well as conjunctivitis, have been reported. Although a direct causal relationship has not been established, many phenothiazines and related drugs have been shown to cause eye changes. Musculoskeletal System: Aching joints and muscles, and leg cramps. Metabolism: Fever and chills. Hyponatremia (see WARNINGS, General ). Decreased levels of plasma calcium have been reported. Osteoporosis has been reported. Isolated cases of a lupus erythematosus-like syndrome have been reported. There have been occasional reports of elevated levels of cholesterol, HDL cholesterol, and triglycerides in patients taking anticonvulsants. A case of aseptic meningitis, accompanied by myoclonus and peripheral eosinophilia, has been reported in a patient taking carbamazepine in combination with other medications. The patient was successfully dechallenged, and the meningitis reappeared upon rechallenge with carbamazepine. To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch ."}', 'drug_interactions': '{"Drug Interactions There has been a report of a patient who passed an orange rubbery precipitate in his stool the day after ingesting carbamazepine suspension immediately followed by Thorazine ® solution. Subsequent testing has shown that mixing carbamazepine suspension and chlorpromazine solution (both generic and brand name) as well as carbamazepine suspension and liquid Mellaril ® , resulted in the occurrence of this precipitate. Because the extent to which this occurs with other liquid medications is not known, carbamazepine suspension should not be administered simultaneously with other liquid medicinal agents or diluents (see DOSAGE AND ADMINISTRATION ). Clinically meaningful drug interactions have occurred with concomitant medications and include (but are not limited to) the following: Agents That May Affect Carbamazepine Plasma Levels When carbamazepine is given with drugs that can increase or decrease carbamazepine levels, close monitoring of carbamazepine levels is indicated and dosage adjustment may be required. Agents That Increase Carbamazepine Levels CYP3A4 inhibitors inhibit carbamazepine metabolism and can thus increase plasma carbamazepine levels. Drugs that have been shown, or would be expected, to increase plasma carbamazepine levels include aprepitant, cimetidine, ciprofloxacin, danazol, diltiazem, macrolides (e.g., erythromycin, clarithromycin), fluoxetine, fluvoxamine, trazodone, omeprazole, oxybutynin, isoniazid, niacinamide (nicotinamide), azoles (e.g., ketoconazole, itraconazole, fluconazole, voriconazole), acetazolamide, verapamil, ticlopidine, grapefruit juice, and protease inhibitors. Human microsomal epoxide hydrolase has been identified as the enzyme responsible for the formation of the 10,11-transdiol derivative from carbamazepine-10,11 epoxide. Co-administration of inhibitors of human microsomal epoxide hydrolase may result in increased carbamazepine-10,11 epoxide plasma concentrations. Accordingly, the dosage of carbamazepine should be adjusted and/or the plasma levels monitored when used concomitantly with loxapine, quetiapine, valproic acid, or brivaracetam. Agents That Decrease Carbamazepine Levels CYP3A4 inducers can increase the rate of carbamazepine metabolism. Drugs that have been shown, or that would be expected, to decrease plasma carbamazepine levels include cisplatin, doxorubicin HCl, felbamate, fosphenytoin, rifampin, phenobarbital, phenytoin, primidone, methsuximide, theophylline, aminophylline. Effect of Carbamazepine on Plasma Levels of Concomitant Agents Decreased Levels of Concomitant Medications Carbamazepine is a potent inducer of hepatic 3A4 and is also known to be an inducer of CYP1A2, 2B6, 2C8/9/19, and may therefore reduce plasma concentrations of co-medications mainly metabolized by CYP1A2, 2B6, 2C8/9/19, and 3A4, through induction of their metabolism. When used concomitantly with carbamazepine, monitoring of concentrations or dosage adjustment of these agents may be necessary: When carbamazepine is added to aripiprazole, the aripiprazole dose should be doubled. Additional dose increases should be based on clinical evaluation. If carbamazepine is later withdrawn, the aripiprazole dose should be reduced. When carbamazepine is used with tacrolimus, monitoring of tacrolimus blood concentrations and appropriate dosage adjustments are recommended. The use of concomitant strong CYP3A4 inducers, such as carbamazepine should be avoided with temsirolimus. If patients must be co-administered carbamazepine with temsirolimus, an adjustment of temsirolimus dosage should be considered. The use of carbamazepine with lapatinib should generally be avoided. If carbamazepine is started in a patient already taking lapatinib, the dose of lapatinib should be gradually titrated up. If carbamazepine is discontinued, the lapatinib dose should be reduced. Concomitant use of carbamazepine with nefazodone results in plasma concentrations of nefazodone and its active metabolite insufficient to achieve a therapeutic effect. Co-administration of carbamazepine with nefazodone is contraindicated (see CONTRAINDICATIONS ). Monitor concentrations of valproate when carbamazepine is introduced or withdrawn in patients using valproic acid. In addition, carbamazepine causes, or would be expected to cause, decreased levels of the following drugs, for which monitoring of concentrations or dosage adjustment may be necessary: acetaminophen, albendazole, alprazolam, aprepitant, buprenorphone, bupropion, citalopram, clonazepam, clozapine, corticosteroids (e.g., prednisolone, dexamethasone), cyclosporine, dicumarol, dihydropyridine calcium channel blockers (e.g., felodipine), doxycycline, eslicarbazepine, ethosuximide, everolimus, haloperidol, imatinib, itraconazole, lamotrigine, levothyroxine, methadone, methsuximide, mianserin, midazolam, olanzapine, oral and other hormonal contraceptives, oxcarbazepine, paliperidone, phensuximide, phenytoin, praziquantel, protease inhibitors, risperidone, sertraline, sirolimus, tadalafil, theophylline, tiagabine, topiramate, tramadol, trazodone, tricyclic antidepressants (e.g., imipramine, amitriptyline, nortriptyline), valproate, warfarin, ziprasidone, zonisamide. Other Drug Interactions Cyclophosphamide is an inactive prodrug and is converted to its active metabolite in part by CYP3A. The rate of metabolism and the leukopenic activity of cyclophosphamide are reportedly increased by chronic co-administration of CYP3A4 inducers. There is a potential for increased cyclophosphamide toxicity when co-administered with carbamazepine. Concomitant administration of carbamazepine and lithium may increase the risk of neurotoxic side effects. Concomitant use of carbamazepine with olanzapine, dantrolene, or ibuprofen may increase plasma carbamazepine levels. Concomitant use of carbamazepine and isoniazid has been reported to increase isoniazid-induced hepatotoxicity. Alterations of thyroid function have been reported in combination therapy with other anticonvulsant medications. Concomitant use of carbamazepine with hormonal contraceptive products (e.g., oral, and levonorgestrel subdermal implant contraceptives) may render the contraceptives less effective because the plasma concentrations of the hormones may be decreased. Breakthrough bleeding and unintended pregnancies have been reported. Alternative or back-up methods of contraception should be considered. Resistance to the neuromuscular blocking action of the nondepolarizing neuromuscular blocking agents pancuronium, vecuronium, rocuronium and cisatracurium has occurred in patients chronically administered carbamazepine. Whether or not carbamazepine has the same effect on other non-depolarizing agents is unknown. Patients should be monitored closely for more rapid recovery from neuromuscular blockade than expected, and infusion rate requirements may be higher. Concomitant use of carbamazepine with rivaroxaban, apixaban, dabigatran, and edoxaban (direct acting oral anticoagulants) is expected to result in decreased plasma concentrations of these anticoagulants that may be insufficient to achieve the intended therapeutic effect. In general, co-administration of carbamazepine with rivaroxaban, apixaban, dabigatran, and edoxaban should be avoided."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Epilepsy Carbamazepine extended-release tablets are indicated for use as an anticonvulsant drug. Evidence supporting efficacy of carbamazepine extended-release tablets as an anticonvulsant was derived from active drug-controlled studies that enrolled patients with the following seizure types: Partial seizures with complex symptomatology (psychomotor, temporal lobe). Patients with these seizures appear to show greater improvement than those with other types. Generalized tonic-clonic seizures (grand mal). Mixed seizure patterns which include the above, or other partial or generalized seizures. Absence seizures (petit mal) do not appear to be controlled by carbamazepine extended-release tablets (see PRECAUTIONS, General ). Trigeminal Neuralgia Carbamazepine extended-release tablets are indicated in the treatment of the pain associated with true trigeminal neuralgia. Beneficial results have also been reported in glossopharyngeal neuralgia. This drug is not a simple analgesic and should not be used for the relief of trivial aches or pains."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Acute Toxicity Lowest known lethal dose: adults, 3.2 g (a 24-year-old woman died of a cardiac arrest and a 24-year-old man died of pneumonia and hypoxic encephalopathy); children, 4 g (a 14-year-old girl died of a cardiac arrest), 1.6 g (a 3-year-old girl died of aspiration pneumonia). Oral LD 50 in animals (mg/kg): mice, 1100 to 3750; rats, 3850 to 4025; rabbits, 1500 to 2680; guinea pigs, 920. Signs and Symptoms The first signs and symptoms appear after 1 to 3 hours. Neuromuscular disturbances are the most prominent. Cardiovascular disorders are generally milder, and severe cardiac complications occur only when very high doses (greater than 60 g) have been ingested. Respiration: Irregular breathing, respiratory depression. Cardiovascular System: Tachycardia, hypotension or hypertension, shock, conduction disorders. Nervous System and Muscles: Impairment of consciousness ranging in severity to deep coma. Convulsions, especially in small children. Motor restlessness, muscular twitching, tremor, athetoid movements, opisthotonos, ataxia, drowsiness, dizziness, mydriasis, nystagmus, adiadochokinesia, ballism, psychomotor disturbances, dysmetria. Initial hyperreflexia, followed by hyporeflexia. Gastrointestinal Tract: Nausea, vomiting. Kidneys and Bladder: Anuria or oliguria, urinary retention. Laboratory Findings: Isolated instances of overdosage have included leukocytosis, reduced leukocyte count, glycosuria, and acetonuria. EEG may show dysrhythmias. Combined Poisoning: When alcohol, tricyclic antidepressants, barbiturates, or hydantoins are taken at the same time, the signs and symptoms of acute poisoning with carbamazepine may be aggravated or modified. Treatment The prognosis in cases of severe poisoning is critically dependent upon prompt elimination of the drug, which may be achieved by inducing vomiting, irrigating the stomach, and by taking appropriate steps to diminish absorption. If these measures cannot be implemented without risk on the spot, the patient should be transferred at once to a hospital, while ensuring that vital functions are safeguarded. There is no specific antidote. Elimination of the Drug: Induction of vomiting. Gastric lavage. Even when more than 4 hours have elapsed following ingestion of the drug, the stomach should be repeatedly irrigated, especially if the patient has also consumed alcohol. Measures to Reduce Absorption: Activated charcoal, laxatives. Measures to Accelerate Elimination: Forced diuresis. Dialysis is indicated only in severe poisoning associated with renal failure. Replacement transfusion is indicated in severe poisoning in small children. Respiratory Depression: Keep the airways free; resort, if necessary, to endotracheal intubation, artificial respiration, and administration of oxygen. Hypotension, Shock: Keep the patient’s legs raised and administer a plasma expander. If blood pressure fails to rise despite measures taken to increase plasma volume, use of vasoactive substances should be considered. Convulsions: Diazepam or barbiturates. Warning: Diazepam or barbiturates may aggravate respiratory depression (especially in children), hypotension, and coma. However, barbiturates should not be used if drugs that inhibit monoamine oxidase have also been taken by the patient either in overdosage or in recent therapy (within 1 week). Surveillance: Respiration, cardiac function (ECG monitoring), blood pressure, body temperature, pupillary reflexes, and kidney and bladder function should be monitored for several days. Treatment of Blood Count Abnormalities: If evidence of significant bone marrow depression develops, the following recommendations are suggested: (1) stop the drug, (2) perform daily CBC, platelet, and reticulocyte counts, (3) do a bone marrow aspiration and trephine biopsy immediately and repeat with sufficient frequency to monitor recovery. Special periodic studies might be helpful as follows: (1) white cell and platelet antibodies, (2) 59 Fe-ferrokinetic studies, (3) peripheral blood cell typing, (4) cytogenetic studies on marrow and peripheral blood, (5) bone marrow culture studies for colony-forming units, (6) hemoglobin electrophoresis for A 2 and F hemoglobin, and (7) serum folic acid and B 12 levels. A fully developed aplastic anemia will require appropriate, intensive monitoring and therapy, for which specialized consultation should be sought."}', 'active_flag': 'Y', 'generic_name': '{CARBAMAZEPINE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Serious Dermatologic Reactions Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have been reported with carbamazepine treatment. The risk of these events is estimated to be about 1 to 6 per 10,000 new users in countries with mainly Caucasian populations. However, the risk in some Asian countries is estimated to be about 10 times higher. Carbamazepine should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered. SJS/TEN and HLA-B*1502 Allele Retrospective case-control studies have found that in patients of Chinese ancestry there is a strong association between the risk of developing SJS/TEN with carbamazepine treatment and the presence of an inherited variant of the HLA-B gene, HLA-B*1502. The occurrence of higher rates of these reactions in countries with higher frequencies of this allele suggests that the risk may be increased in allele-positive individuals of any ethnicity. Across Asian populations, notable variation exists in the prevalence of HLA-B*1502. Greater than 15% of the population is reported positive in Hong Kong, Thailand, Malaysia, and parts of the Philippines, compared to about 10% in Taiwan and 4% in North China. South Asians, including Indians, appear to have intermediate prevalence of HLA-B*1502, averaging 2% to 4%, but higher in some groups. HLA-B*1502 is present in less than 1% of the population in Japan and Korea. HLA-B*1502 is largely absent in individuals not of Asian origin (e.g., Caucasians, African-Americans, Hispanics, and Native Americans). Prior to initiating carbamazepine therapy, testing for HLA-B*1502 should be performed in patients with ancestry in populations in which HLA-B*1502 may be present. In deciding which patients to screen, the rates provided above for the prevalence of HLA-B*1502 may offer a rough guide, keeping in mind the limitations of these figures due to wide variability in rates even within ethnic groups, the difficulty in ascertaining ethnic ancestry, and the likelihood of mixed ancestry. Carbamazepine should not be used in patients positive for HLA-B*1502 unless the benefits clearly outweigh the risks. Tested patients who are found to be negative for the allele are thought to have a low risk of SJS/TEN (see BOXED WARNING and PRECAUTIONS, Laboratory Tests ). Over 90% of carbamazepine treated patients who will experience SJS/TEN have this reaction within the first few months of treatment. This information may be taken into consideration in determining the need for screening of genetically at-risk patients currently on carbamazepine. The HLA-B*1502 allele has not been found to predict risk of less severe adverse cutaneous reactions from carbamazepine such as maculopapular eruption (MPE) or to predict Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Chinese ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin. Consideration should be given to avoiding use of other drugs associated with SJS/TEN in HLA-B*1502 positive patients, when alternative therapies are otherwise equally acceptable. Hypersensitivity Reactions and HLA-A*3101 Allele Retrospective case-control studies in patients of European, Korean, and Japanese ancestry have found a moderate association between the risk of developing hypersensitivity reactions and the presence of HLA-A*3101, an inherited allelic variant of the HLA-A gene, in patients using carbamazepine. These hypersensitivity reactions include SJS/TEN, maculopapular eruptions, and Drug Reaction with Eosinophilia and Systemic Symptoms (see DRESS/Multiorgan hypersensitivity below). HLA-A*3101 is expected to be carried by more than 15% of patients of Japanese, Native American, Southern Indian (for example, Tamil Nadu) and some Arabic ancestry; up to about 10% in patients of Han Chinese, Korean, European, Latin American, and other Indian ancestry; and up to about 5% in African-Americans and patients of Thai, Taiwanese, and Chinese (Hong Kong) ancestry. The risks and benefits of carbamazepine therapy should be weighed before considering carbamazepine in patients known to be positive for HLA-A*3101. Application of HLA genotyping as a screening tool has important limitations and must never substitute for appropriate clinical vigilance and patient management. Many HLA-B*1502-positive and HLA-A*3101-positive patients treated with carbamazepine will not develop SJS/TEN or other hypersensitivity reactions, and these reactions can still occur infrequently in HLA-B*1502-negative and HLA-A*3101-negative patients of any ethnicity. The role of other possible factors in the development of, and morbidity from, SJS/TEN and other hypersensitivity reactions, such as antiepileptic drug (AED) dose, compliance, concomitant medications, comorbidities, and the level of dermatologic monitoring, have not been studied. Aplastic Anemia and Agranulocytosis Aplastic anemia and agranulocytosis have been reported in association with the use of carbamazepine (see BOXED WARNING ). Patients with a history of adverse hematologic reaction to any drug may be particularly at risk of bone marrow depression. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has occurred with carbamazepine. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Carbamazepine should be discontinued if an alternative etiology for the signs or symptoms cannot be established. Hypersensitivity Hypersensitivity reactions to carbamazepine have been reported in patients who previously experienced this reaction to anticonvulsants including phenytoin, primidone, and phenobarbital. If such history is present, benefits and risks should be carefully considered and, if carbamazepine is initiated, the signs and symptoms of hypersensitivity should be carefully monitored. Patients should be informed that about a third of patients who have had hypersensitivity reactions to carbamazepine also experience hypersensitivity reactions with oxcarbazepine (Trileptal ® ). Anaphylaxis and Angioedema Rare cases of anaphylaxis and angioedema involving the larynx, glottis, lips, and eyelids have been reported in patients after taking the first or subsequent doses of carbamazepine. Angioedema associated with laryngeal edema can be fatal. If a patient develops any of these reactions after treatment with carbamazepine, the drug should be discontinued and an alternative treatment started. These patients should not be rechallenged with the drug. Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including carbamazepine, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Table 1 shows absolute and relative risk by indication for all evaluated AEDs. Table 1 Risk by Indication for Antiepileptic Drugs in the Pooled Analysis Indication Placebo Patients with Events Per 1,000 Patients Drug Patients with Events Per 1,000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1,000 Patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing carbamazepine or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. General Carbamazepine has shown mild anticholinergic activity that may be associated with increased intraocular pressure; therefore, patients with increased intraocular pressure should be closely observed during therapy. Because of the relationship of the drug to other tricyclic compounds, the possibility of activation of a latent psychosis and, in elderly patients, of confusion or agitation should be borne in mind. The use of carbamazepine should be avoided in patients with a history of hepatic porphyria (e.g., acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda). Acute attacks have been reported in such patients receiving carbamazepine therapy. Carbamazepine administration has also been demonstrated to increase porphyrin precursors in rodents, a presumed mechanism for the induction of acute attacks of porphyria. As with all antiepileptic drugs, carbamazepine should be withdrawn gradually to minimize the potential of increased seizure frequency. Hyponatremia can occur as a result of treatment with carbamazepine. In many cases, the hyponatremia appears to be caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The risk of developing SIADH with carbamazepine treatment appears to be dose-related. Elderly patients and patients treated with diuretics are at greater risk of developing hyponatremia. Signs and symptoms of hyponatremia include headache, new or increased seizure frequency, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to falls. Consider discontinuing carbamazepine in patients with symptomatic hyponatremia. Usage in Pregnancy Carbamazepine can cause fetal harm when administered to a pregnant woman. Epidemiological data suggest that there may be an association between the use of carbamazepine during pregnancy and congenital malformations, including spina bifida. There have also been reports that associate carbamazepine with developmental disorders and congenital anomalies (e.g., craniofacial defects, cardiovascular malformations, and anomalies involving various body systems). Developmental delays based on neurobehavioral assessments have been reported. When treating or counseling women of childbearing potential, the prescribing physician will wish to weigh the benefits of therapy against the risks. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Retrospective case reviews suggest that, compared with monotherapy, there may be a higher prevalence of teratogenic effects associated with the use of anticonvulsants in combination therapy. Therefore, if therapy is to be continued, monotherapy may be preferable for pregnant women. In humans, trans placental passage of carbamazepine is rapid (30 to 60 minutes), and the drug is accumulated in the fetal tissues, with higher levels found in liver and kidney than in brain and lung. Carbamazepine has been shown to have adverse effects in reproduction studies in rats when given orally in dosages 10 to 25 times the maximum human daily dosage (MHDD) of 1,200 mg on a mg/kg basis or 1.5 to 4 times the MHDD on a mg/m 2 basis. In rat teratology studies, 2 of 135 offspring showed kinked ribs at 250 mg/kg and 4 of 119 offspring at 650 mg/kg showed other anomalies (cleft palate, 1; talipes, 1; anophthalmos, 2). In reproduction studies in rats, nursing offspring demonstrated a lack of weight gain and an unkempt appearance at a maternal dosage level of 200 mg/kg. Antiepileptic drugs should not be discontinued abruptly in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorder are such that removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus. Tests to detect defects using currently accepted procedures should be considered a part of routine prenatal care in childbearing women receiving carbamazepine. There have been a few cases of neonatal seizures and/or respiratory depression associated with maternal carbamazepine and other concomitant anticonvulsant drug use. A few cases of neonatal vomiting, diarrhea, and/or decreased feeding have also been reported in association with maternal carbamazepine use. These symptoms may represent a neonatal withdrawal syndrome. To provide information regarding the effects of in utero exposure to carbamazepine, physicians are advised to recommend that pregnant patients taking carbamazepine enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/."}', 'precautions': '{"PRECAUTIONS General Before initiating therapy, a detailed history and physical examination should be made. Carbamazepine should be used with caution in patients with a mixed seizure disorder that includes atypical absence seizures, since in these patients carbamazepine has been associated with increased frequency of generalized convulsions (see INDICATIONS AND USAGE ). Therapy should be prescribed only after critical benefit-to-risk appraisal in patients with a history of cardiac conduction disturbance, including second- and third-degree AV heart block; cardiac, hepatic, or renal damage; adverse hematologic or hypersensitivity reaction to other drugs, including reactions to other anticonvulsants; or interrupted courses of therapy with carbamazepine. AV heart block, including second- and third-degree block, have been reported following carbamazepine treatment. This occurred generally, but not solely, in patients with underlying EKG abnormalities or risk factors for conduction disturbances. Hepatic effects, ranging from slight elevations in liver enzymes to rare cases of hepatic failure have been reported (see ADVERSE REACTIONS and PRECAUTIONS, Laboratory Tests ). In some cases, hepatic effects may progress despite discontinuation of the drug. In addition rare instances of vanishing bile duct syndrome have been reported. This syndrome consists of a cholestatic process with a variable clinical course ranging from fulminant to indolent, involving the destruction and disappearance of the intrahepatic bile ducts. Some, but not all, cases are associated with features that overlap with other immunoallergenic syndromes such as multiorgan hypersensitivity (DRESS syndrome) and serious dermatologic reactions. As an example there has been a report of vanishing bile duct syndrome associated with Stevens-Johnson syndrome and in another case an association with fever and eosinophilia. Since a given dose of carbamazepine suspension will produce higher peak levels than the same dose given as the tablet, it is recommended that patients given the suspension be started on lower doses and increased slowly to avoid unwanted side effects (see DOSAGE AND ADMINISTRATION ). Carbamazepine suspension contains sorbitol and, therefore, should not be administered to patients with rare hereditary problems of fructose intolerance. Information for Patients Patients should be informed of the availability of a Medication Guide and they should be instructed to read the Medication Guide before taking carbamazepine. Patients should be made aware of the early toxic signs and symptoms of a potential hematologic problem, as well as dermatologic, hypersensitivity or hepatic reactions. These symptoms may include, but are not limited to, fever, sore throat, rash, ulcers in the mouth, easy bruising, lymphadenopathy and petechial or purpuric hemorrhage, and in the case of liver reactions, anorexia, nausea/vomiting, or jaundice. The patient should be advised that, because these signs and symptoms may signal a serious reaction, that they must report any occurrence immediately to a physician. In addition, the patient should be advised that these signs and symptoms should be reported even if mild or when occurring after extended use. Patients should be advised that serious skin reactions have been reported in association with carbamazepine. In the event a skin reaction should occur while taking carbamazepine, patients should consult with their physician immediately (see WARNINGS ). Patients should be advised that anaphylactic reactions and angioedema may occur during treatment with carbamazepine (see WARNINGS ). Advise patients to immediately report signs and symptoms suggesting angioedema (swelling of the face, eyes, lips, or tongue, or difficulty in swallowing or breathing) and to stop taking the drug until they have consulted with their healthcare provider. Patients, their caregivers, and families should be counseled that AEDs, including carbamazepine, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers. Carbamazepine may interact with some drugs. Therefore, patients should be advised to report to their doctors the use of any other prescription or nonprescription medications or herbal products. Caution should be exercised if alcohol is taken in combination with carbamazepine therapy, due to a possible additive sedative effect. Since dizziness and drowsiness may occur, patients should be cautioned about the hazards of operating machinery or automobiles or engaging in other potentially dangerous tasks. Patients should be encouraged to enroll in the NAAED Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see WARNINGS, Usage in Pregnancy subsection). Laboratory Tests For genetically at-risk patients (see WARNINGS ), high-resolution ‘ HLA-B*1502 typing ’ is recommended. The test is positive if either one or two HLA-B*1502 alleles are detected and negative if no HLA-B*1502 alleles are detected. Complete pretreatment blood counts, including platelets and possibly reticulocytes and serum iron, should be obtained as a baseline. If a patient in the course of treatment exhibits low or decreased white blood cell or platelet counts, the patient should be monitored closely. Discontinuation of the drug should be considered if any evidence of significant bone marrow depression develops. Baseline and periodic evaluations of liver function, particularly in patients with a history of liver disease, must be performed during treatment with this drug since liver damage may occur (see PRECAUTIONS, General and ADVERSE REACTIONS ). Carbamazepine should be discontinued, based on clinical judgment, if indicated by newly occurring or worsening clinical or laboratory evidence of liver dysfunction or hepatic damage, or in the case of active liver disease. Baseline and periodic eye examinations, including slit-lamp, funduscopy, and tonometry, are recommended since many phenothiazines and related drugs have been shown to cause eye changes. Baseline and periodic complete urinalysis and BUN determinations are recommended for patients treated with this agent because of observed renal dysfunction. Monitoring of blood levels (see CLINICAL PHARMACOLOGY ) has increased the efficacy and safety of anticonvulsants. This monitoring may be particularly useful in cases of dramatic increase in seizure frequency and for verification of compliance. In addition, measurement of drug serum levels may aid in determining the cause of toxicity when more than one medication is being used. Thyroid function tests have been reported to show decreased values with carbamazepine administered alone. Interference with some pregnancy tests has been reported. Drug Interactions There has been a report of a patient who passed an orange rubbery precipitate in his stool the day after ingesting carbamazepine suspension immediately followed by Thorazine ® solution. Subsequent testing has shown that mixing carbamazepine suspension and chlorpromazine solution (both generic and brand name) as well as carbamazepine suspension and liquid Mellaril ® , resulted in the occurrence of this precipitate. Because the extent to which this occurs with other liquid medications is not known, carbamazepine suspension should not be administered simultaneously with other liquid medicinal agents or diluents (see DOSAGE AND ADMINISTRATION ). Clinically meaningful drug interactions have occurred with concomitant medications and include (but are not limited to) the following: Agents That May Affect Carbamazepine Plasma Levels When carbamazepine is given with drugs that can increase or decrease carbamazepine levels, close monitoring of carbamazepine levels is indicated and dosage adjustment may be required. Agents That Increase Carbamazepine Levels CYP3A4 inhibitors inhibit carbamazepine metabolism and can thus increase plasma carbamazepine levels. Drugs that have been shown, or would be expected, to increase plasma carbamazepine levels include aprepitant, cimetidine, ciprofloxacin, danazol, diltiazem, macrolides (e.g., erythromycin, clarithromycin), fluoxetine, fluvoxamine, trazodone, omeprazole, oxybutynin, isoniazid, niacinamide (nicotinamide), azoles (e.g., ketoconazole, itraconazole, fluconazole, voriconazole), acetazolamide, verapamil, ticlopidine, grapefruit juice, and protease inhibitors. Human microsomal epoxide hydrolase has been identified as the enzyme responsible for the formation of the 10,11-transdiol derivative from carbamazepine-10,11 epoxide. Co-administration of inhibitors of human microsomal epoxide hydrolase may result in increased carbamazepine-10,11 epoxide plasma concentrations. Accordingly, the dosage of carbamazepine should be adjusted and/or the plasma levels monitored when used concomitantly with loxapine, quetiapine, valproic acid, or brivaracetam. Agents That Decrease Carbamazepine Levels CYP3A4 inducers can increase the rate of carbamazepine metabolism. Drugs that have been shown, or that would be expected, to decrease plasma carbamazepine levels include cisplatin, doxorubicin HCl, felbamate, fosphenytoin, rifampin, phenobarbital, phenytoin, primidone, methsuximide, theophylline, aminophylline. Effect of Carbamazepine on Plasma Levels of Concomitant Agents Decreased Levels of Concomitant Medications Carbamazepine is a potent inducer of hepatic 3A4 and is also known to be an inducer of CYP1A2, 2B6, 2C8/9/19, and may therefore reduce plasma concentrations of co-medications mainly metabolized by CYP1A2, 2B6, 2C8/9/19, and 3A4, through induction of their metabolism. When used concomitantly with carbamazepine, monitoring of concentrations or dosage adjustment of these agents may be necessary: When carbamazepine is added to aripiprazole, the aripiprazole dose should be doubled. Additional dose increases should be based on clinical evaluation. If carbamazepine is later withdrawn, the aripiprazole dose should be reduced. When carbamazepine is used with tacrolimus, monitoring of tacrolimus blood concentrations and appropriate dosage adjustments are recommended. The use of concomitant strong CYP3A4 inducers, such as carbamazepine should be avoided with temsirolimus. If patients must be co-administered carbamazepine with temsirolimus, an adjustment of temsirolimus dosage should be considered. The use of carbamazepine with lapatinib should generally be avoided. If carbamazepine is started in a patient already taking lapatinib, the dose of lapatinib should be gradually titrated up. If carbamazepine is discontinued, the lapatinib dose should be reduced. Concomitant use of carbamazepine with nefazodone results in plasma concentrations of nefazodone and its active metabolite insufficient to achieve a therapeutic effect. Co-administration of carbamazepine with nefazodone is contraindicated (see CONTRAINDICATIONS ). Monitor concentrations of valproate when carbamazepine is introduced or withdrawn in patients using valproic acid. In addition, carbamazepine causes, or would be expected to cause, decreased levels of the following drugs, for which monitoring of concentrations or dosage adjustment may be necessary: acetaminophen, albendazole, alprazolam, aprepitant, buprenorphone, bupropion, citalopram, clonazepam, clozapine, corticosteroids (e.g., prednisolone, dexamethasone), cyclosporine, dicumarol, dihydropyridine calcium channel blockers (e.g., felodipine), doxycycline, eslicarbazepine, ethosuximide, everolimus, haloperidol, imatinib, itraconazole, lamotrigine, levothyroxine, methadone, methsuximide, mianserin, midazolam, olanzapine, oral and other hormonal contraceptives, oxcarbazepine, paliperidone, phensuximide, phenytoin, praziquantel, protease inhibitors, risperidone, sertraline, sirolimus, tadalafil, theophylline, tiagabine, topiramate, tramadol, trazodone, tricyclic antidepressants (e.g., imipramine, amitriptyline, nortriptyline), valproate, warfarin, ziprasidone, zonisamide. Other Drug Interactions Cyclophosphamide is an inactive prodrug and is converted to its active metabolite in part by CYP3A. The rate of metabolism and the leukopenic activity of cyclophosphamide are reportedly increased by chronic co-administration of CYP3A4 inducers. There is a potential for increased cyclophosphamide toxicity when co-administered with carbamazepine. Concomitant administration of carbamazepine and lithium may increase the risk of neurotoxic side effects. Concomitant use of carbamazepine with olanzapine, dantrolene, or ibuprofen may increase plasma carbamazepine levels. Concomitant use of carbamazepine and isoniazid has been reported to increase isoniazid-induced hepatotoxicity. Alterations of thyroid function have been reported in combination therapy with other anticonvulsant medications. Concomitant use of carbamazepine with hormonal contraceptive products (e.g., oral, and levonorgestrel subdermal implant contraceptives) may render the contraceptives less effective because the plasma concentrations of the hormones may be decreased. Breakthrough bleeding and unintended pregnancies have been reported. Alternative or back-up methods of contraception should be considered. Resistance to the neuromuscular blocking action of the nondepolarizing neuromuscular blocking agents pancuronium, vecuronium, rocuronium and cisatracurium has occurred in patients chronically administered carbamazepine. Whether or not carbamazepine has the same effect on other non-depolarizing agents is unknown. Patients should be monitored closely for more rapid recovery from neuromuscular blockade than expected, and infusion rate requirements may be higher. Concomitant use of carbamazepine with rivaroxaban, apixaban, dabigatran, and edoxaban (direct acting oral anticoagulants) is expected to result in decreased plasma concentrations of these anticoagulants that may be insufficient to achieve the intended therapeutic effect. In general, co-administration of carbamazepine with rivaroxaban, apixaban, dabigatran, and edoxaban should be avoided. Carcinogenesis, Mutagenesis, Impairment of Fertility Carbamazepine, when administered to Sprague-Dawley rats for two years in the diet at doses of 25, 75, and 250 mg/kg/day, resulted in a dose-related increase in the incidence of hepatocellular tumors in females and of benign interstitial cell adenomas in the testes of males. Carbamazepine must, therefore, be considered to be carcinogenic in Sprague-Dawley rats. Bacterial and mammalian mutagenicity studies using carbamazepine produced negative results. The significance of these findings relative to the use of carbamazepine in humans is, at present, unknown. Usage in Pregnancy (see WARNINGS ). Labor and Delivery The effect of carbamazepine on human labor and delivery is unknown. Nursing Mothers Carbamazepine and its epoxide metabolite are transferred to breast milk. The ratio of the concentration in breast milk to that in maternal plasma is about 0.4 for carbamazepine and about 0.5 for the epoxide. The estimated doses given to the newborn during breastfeeding are in the range of 2 to 5 mg daily for carbamazepine and 1 to 2 mg daily for the epoxide. Because of the potential for serious adverse reactions in nursing infants from carbamazepine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Substantial evidence of carbamazepine’s effectiveness for use in the management of children with epilepsy (see INDICATIONS AND USAGE for specific seizure types) is derived from clinical investigations performed in adults and from studies in several in vitro systems which support the conclusion that (1) the pathogenetic mechanisms underlying seizure propagation are essentially identical in adults and children, and (2) the mechanism of action of carbamazepine in treating seizures is essentially identical in adults and children. Taken as a whole, this information supports a conclusion that the generally accepted therapeutic range of total carbamazepine in plasma (i.e., 4 to 12 mcg/mL) is the same in children and adults. The evidence assembled was primarily obtained from short-term use of carbamazepine. The safety of carbamazepine in children has been systematically studied up to 6 months. No longer-term data from clinical trials is available. Geriatric Use No systematic studies in geriatric patients have been conducted."}', 'information_for_patients': '{"Information for Patients Patients should be informed of the availability of a Medication Guide and they should be instructed to read the Medication Guide before taking carbamazepine. Patients should be made aware of the early toxic signs and symptoms of a potential hematologic problem, as well as dermatologic, hypersensitivity or hepatic reactions. These symptoms may include, but are not limited to, fever, sore throat, rash, ulcers in the mouth, easy bruising, lymphadenopathy and petechial or purpuric hemorrhage, and in the case of liver reactions, anorexia, nausea/vomiting, or jaundice. The patient should be advised that, because these signs and symptoms may signal a serious reaction, that they must report any occurrence immediately to a physician. In addition, the patient should be advised that these signs and symptoms should be reported even if mild or when occurring after extended use. Patients should be advised that serious skin reactions have been reported in association with carbamazepine. In the event a skin reaction should occur while taking carbamazepine, patients should consult with their physician immediately (see WARNINGS ). Patients should be advised that anaphylactic reactions and angioedema may occur during treatment with carbamazepine (see WARNINGS ). Advise patients to immediately report signs and symptoms suggesting angioedema (swelling of the face, eyes, lips, or tongue, or difficulty in swallowing or breathing) and to stop taking the drug until they have consulted with their healthcare provider. Patients, their caregivers, and families should be counseled that AEDs, including carbamazepine, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers. Carbamazepine may interact with some drugs. Therefore, patients should be advised to report to their doctors the use of any other prescription or nonprescription medications or herbal products. Caution should be exercised if alcohol is taken in combination with carbamazepine therapy, due to a possible additive sedative effect. Since dizziness and drowsiness may occur, patients should be cautioned about the hazards of operating machinery or automobiles or engaging in other potentially dangerous tasks. Patients should be encouraged to enroll in the NAAED Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see WARNINGS, Usage in Pregnancy subsection)."}', 'pregnancy': '{"Usage in Pregnancy (see WARNINGS )."}', 'pediatric_use': '{"Pediatric Use Substantial evidence of carbamazepine’s effectiveness for use in the management of children with epilepsy (see INDICATIONS AND USAGE for specific seizure types) is derived from clinical investigations performed in adults and from studies in several in vitro systems which support the conclusion that (1) the pathogenetic mechanisms underlying seizure propagation are essentially identical in adults and children, and (2) the mechanism of action of carbamazepine in treating seizures is essentially identical in adults and children. Taken as a whole, this information supports a conclusion that the generally accepted therapeutic range of total carbamazepine in plasma (i.e., 4 to 12 mcg/mL) is the same in children and adults. The evidence assembled was primarily obtained from short-term use of carbamazepine. The safety of carbamazepine in children has been systematically studied up to 6 months. No longer-term data from clinical trials is available."}', 'geriatric_use': '{"Geriatric Use No systematic studies in geriatric patients have been conducted."}'}

{"PROMETHAZINE HYDROCHLORIDE"}

{'contraindications': '{"CONTRAINDICATIONS Promethazine hydrochloride tablets, USP are contraindicated for use in pediatric patients less than two years of age. Promethazine hydrochloride tablets, USP are contraindicated in comatose states, and in individuals known to be hypersensitive or to have had an idiosyncratic reaction to promethazine or to other phenothiazines. Antihistamines are contraindicated for use in the treatment of lower respiratory tract symptoms including asthma."}', 'adverse_reactions': '{"ADVERSE REACTIONS Central Nervous System Drowsiness is the most prominent CNS effect of this drug. Sedation, somnolence, blurred vision, dizziness; confusion, disorientation, and extrapyramidal symptoms such as oculogyric crisis, torticollis, and tongue protrusion; lassitude, tinnitus, incoordination, fatigue, euphoria, nervousness, diplopia, insomnia, tremors, convulsive seizures, excitation, catatonic-like states, hysteria. Hallucinations have also been reported. Cardiovascular -Increased or decreased blood pressure, tachycardia, bradycardia, faintness. Dermatologic - Dermatitis, photosensitivity, urticaria. Hematologic -Leukopenia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis. Gastrointestinal -Dry mouth, nausea, vomiting, jaundice. Respiratory -Asthma, nasal stuffiness, respiratory depression (potentially fatal) and apnea (potentially fatal) (see WARNINGS-Respiratory Depression ). Other -Angioneurotic edema. Neuroleptic malignant syndrome (potentially fatal) has also been reported (see WARNINGS-Neuroleptic Malignant Syndrome ). Paradoxical Reactions Hyperexcitability and abnormal movements have been reported in patients following a single administration of promethazine hydrochloride. Consideration should be given to the discontinuation of promethazine hydrochloride and to the use of other drugs if these reactions occur. Respiratory depression, nightmares, delirium, and agitated behavior have also been reported in some of these patients."}', 'drug_interactions': '{"Drug Interactions CNS Depressants - Promethazine hydrochloride tablets, USP may increase, prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients receiving promethazine hydrochloride. When given concomitantly with promethazine hydrochloride tablets, USP the dose of barbiturates should be reduced by at least one-half, and the dose of narcotics should be reduced by one-quarter to one-half. Dosage must be individualized. Excessive amounts of promethazine hydrochloride relative to a narcotic may lead to restlessness and motor hyperactivity in the patient with pain; these symptoms usually disappear with adequate control of the pain. Epinephrine - Because of the potential for promethazine hydrochloride to reverse epinephrine\'s vasopressor effect, epinephrine should NOT be used to treat hypotension associated with promethazine hydrochloride tablets, USP overdose. Anticholinergics - Concomitant use of other agents with anticholinergic properties should be undertaken with caution. Monoamine Oxidase Inhibitors (MAOI) - Drug interactions, including an increased incidence of extrapyramidal effects, have been reported when some MAOI and phenothiazines are used concomitantly. This possibility should be considered with promethazine hydrochloride tablets, USP."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Promethazine Hydrochloride, is useful orally for. Perennial and seasonal allergic rhinitis. Vasomotor rhinitis. Allergic conjunctivitis due to inhalant allergens and foods. Mild, uncomplicated allergic skin manifestations of urticaria and angioedema. Amelioration of allergic reactions to blood or plasma. Dermographism. Anaphylactic reactions, as adjunctive therapy to epinephrine and other standard measures, after the acute manifestations have been controlled. Preoperative, postoperative, or obstetric sedation. Prevention and control of nausea and vomiting associated with certain types of anesthesia and surgery. Therapy adjunctive to meperidine or other analgesics for control of post-operative pain. Sedation in both children and adults, as well as relief of apprehension and production of light sleep from which the patient can be easily aroused. Active and prophylactic treatment of motion sickness. Antiemetic therapy in postoperative patients."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Signs and symptoms of overdosage with promethazine hydrochloride range from mild depression of the central nervous system and cardiovascular system to profound hypotension, respiratory depression, unconsciousness, and sudden death. Other reported reactions include hyperreflexia, hypertonia, ataxia, athetosis, and extensor-plantar reflexes (Babinski reflex). Stimulation may be evident, especially in children and geriatric patients. Convulsions may rarely occur. A paradoxical-type reaction has been reported in children receiving single doses of 75 mg to 125 mg orally, characterized by hyperexcitability and nightmares. Atropine-like signs and symptoms-dry mouth, fixed, dilated pupils, flushing, as well as gastrointestinal symptoms-may occur. Treatment Treatment of overdosage is essentially symptomatic and supportive. Only in cases of extreme overdosage or individual sensitivity do vital signs, including respiration, pulse, blood pressure, temperature, and EKG, need to be monitored. Activated charcoal orally or by lavage may be given, or sodium or magnesium sulfate orally as a cathartic. Attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. Diazepam may be used to control convulsions. Acidosis and electrolyte losses should be corrected. Note that any depressant effects of promethazine hydrochloride are not reversed by naloxone. Avoid analeptics which may cause convulsions. The treatment of choice for resulting hypotension is administration of intravenous fluids, accompanied by repositioning if indicated. In the event that vasopressors are considered for the management of severe hypotension which does not respond to intravenous fluids and repositioning, the administration of norepinephrine or phenylephrine should be considered. EPINEPHRINE SHOULD NOT BE USED, since its use in patients with partial adrenergic blockade may further lower the blood pressure. Extrapyramidal reactions may be treated with anticholinergic antiparkinsonian agents, diphenhydramine, or barbiturates. Oxygen may also be administered. Limited experience with dialysis indicates that it is not helpful."}', 'active_flag': 'Y', 'generic_name': '{"PROMETHAZINE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS PROMETHAZINE HYDROCHLORIDE TABLETS, USP SHOULD NOT BE USED IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE BECAUSE OF THE POTENTIAL FOR FATAL RESPIRATORY DEPRESSION. POSTMARKETING CASES OF RESPIRATORY DEPRESSION, INCLUDING FATALITIES, HAVE BEEN REPORTED WITH USE OF PROMETHAZINE HYDROCHLORIDE TABLETS, USP IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE. A WIDE RANGE OF WEIGHT-BASED DOSES OF PROMETHAZINE HYDROCHLORIDE TABLETS, USP HAVE RESULTED IN RESPIRATORY DEPRESSION IN THESE PATIENTS. CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE HYDROCHLORIDE TABLETS, USP TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER. IT IS RECOMMENDED THAT THE LOWEST EFFECTIVE DOSE OF PROMETHAZINE HYDROCHLORIDE BE USED IN PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER AND CONCOMITANT ADMINISTRATION OF OTHER DRUGS WITH RESPIRATORY DEPRESSANT EFFECTS BE AVOIDED. CNS Depression Promethazine hydrochloride tablets, USP may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine hydrochloride (see PRECAUTIONS Information for Patients and Drug Interactions ) Respiratory Depression Promethazine hydrochloride tablets, USP may lead to potentially fatal respiratory depression. Use of promethazine hydrochloride tablets, USP in patients with compromised respiratory function (e.g., COPD, sleep apnea) should be avoided. Lower Seizure Threshold Promethazine hydrochloride tablets, USP may lower seizure threshold. It should be used with caution in persons with seizure disorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, which may also affect seizure threshold. Bone-Marrow Depression Promethazine hydrochloride tablets, USP should be used with caution in patients with bone-marrow depression. Leukopenia and agranulocytosis have been reported, usually when promethazine hydrochloride has been used in association with other known marrow-toxic agents. Neuroleptic Malignant Syndrome A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with promethazine hydrochloride alone or in combination with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmias). The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology. The management of NMS should include 1) immediate discontinuation of promethazine hydrochloride, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS. Since recurrences of NMS have been reported with phenothiazines, the reintroduction of promethazine hydrochloride should be carefully considered. Use in Pediatric Patients PROMETHAZINE HYDROCHLORIDE TABLETS, USP ARE CONTRAINDICATED FOR USE IN PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE. CAUTION SHOULD BE EXERCISED WHEN ADMINISTERING PROMETHAZINE HYDROCHLORIDE TABLETS, USP TO PEDIATRIC PATIENTS 2 YEARS OF AGE AND OLDER BECAUSE OF THE POTENTIAL FOR FATAL RESPIRATORY DEPRESSION. RESPIRATORY DEPRESSION AND APNEA, SOMETIMES ASSOCIATED WITH DEATH, ARE STRONGLY ASSOCIATED WITH PROMETHAZINE PRODUCTS AND ARE NOT DIRECTLY RELATED TO INDIVIDUALIZED WEIGHT-BASED DOSING, WHICH MIGHT OTHERWISE PERMIT SAFE ADMINISTRATION. CONCOMITANT ADMINISTRATION OF PROMETHAZINE PRODUCTS WITH OTHER RESPIRATORY DEPRESSANTS HAS AN ASSOCIATION WITH RESPIRATORY DESPRESSION, AND SOMETIMES DEATH, IN PEDIATRIC PATIENTS. ANTIEMETICS ARE NOT RECOMMENDED FOR TREATMENT OF UNCOMPLICATED VOMITING IN PEDIATRIC PATIENTS, AND THEIR USE SHOULD BE LIMITED TO PROLONGED VOMITING OF KNOWN ETIOLOGY. THE EXTRAPYRAMIDAL SYMPTOMS WHICH CAN OCCUR SECONDARY TO PROMETHAZINE HYDROCHLORIDE TABLETS, USP ADMINISTRATION MAY BE CONFUSED WITH THE CNS SIGNS OF UNDIAGNOSED PRIMARY DISEASE, e.g., ENCEPHALOPATHY OR REYE\'S SYNDROME. THE USE OF PROMETHAZINE HYDROCHLORIDE TABLETS, USP SHOULD BE AVOIDED IN PEDIATRIC PATIENTS WHOSE SIGNS AND SYMPTOMS MAY SUGGEST REYE\'S SYNDROME OR OTHER HEPATIC DISEASES. Excessively large dosages of antihistamines, including promethazine hydrochloride tablets, USP in pediatric patients may cause sudden death (see OVERDOSAGE ).Hallucinations and convulsions have occurred with therapeutic doses and overdoses of promethazine hydrochloride in pediatric patients. In pediatric patients who are acutely ill associated with dehydration, there is an increased susceptibility to dystonias with the use of promethazine hydrochloride. Other Considerations Administration of promethazine hydrochloride has been associated with reported cholestatic jaundice."}', 'precautions': '{"PRECAUTIONS General Drugs having anticholinergic properties should be used with caution in patients with narrow-angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, and bladder-neck obstruction. Promethazine hydrochloride tablets, USP should be used cautiously in persons with cardiovascular disease or with impairment of liver function. Information for Patients Promethazine hydrochloride tablets, USP may cause marked drowsiness or impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. The use of alcohol or other central-nervous-system depressants such as sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers, may enhance impairment ( see WARNINGS-CNS Depression and PRECAUTIONS-Drug Interactions ). Pediatric patients should be supervised to avoid potential harm in bike riding or in other hazardous activities. Patients should be advised to report any involuntary muscle movements. Avoid prolonged exposure to the sun. Drug Interactions CNS Depressants - Promethazine hydrochloride tablets, USP may increase, prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients receiving promethazine hydrochloride. When given concomitantly with promethazine hydrochloride tablets, USP the dose of barbiturates should be reduced by at least one-half, and the dose of narcotics should be reduced by one-quarter to one-half. Dosage must be individualized. Excessive amounts of promethazine hydrochloride relative to a narcotic may lead to restlessness and motor hyperactivity in the patient with pain; these symptoms usually disappear with adequate control of the pain. Epinephrine - Because of the potential for promethazine hydrochloride to reverse epinephrine\'s vasopressor effect, epinephrine should NOT be used to treat hypotension associated with promethazine hydrochloride tablets, USP overdose. Anticholinergics - Concomitant use of other agents with anticholinergic properties should be undertaken with caution. Monoamine Oxidase Inhibitors (MAOI) - Drug interactions, including an increased incidence of extrapyramidal effects, have been reported when some MAOI and phenothiazines are used concomitantly. This possibility should be considered with promethazine hydrochloride tablets, USP. Drug/Laboratory Test Interactions The following laboratory tests may be affected in patients who are receiving therapy with promethazine hydrochloride: Pregnancy Tests Diagnostic pregnancy tests based on immunological reactions between HCG and anti-HCG may result in false-negative or false-positive interpretations. Glucose Tolerance Test An increase in blood glucose has been reported in patients receiving promethazine hydrochloride. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to assess the carcinogenic potential of promethazine, nor are there other animal or human data concerning carcinogenicity, mutagenicity, or impairment of fertility with this drug. Promethazine was nonmutagenic in the Salmonella test system of Ames. Pregnancy Teratogenic Effects - Pregnancy Category C Teratogenic effects have not been demonstrated in rat-feeding studies at doses of 6.25 and 12.5 mg/kg of promethazine hydrochloride. These doses are from approximately 2.1 to 4.2 times the maximum recommended total daily dose of promethazine for a 50-kg subject, depending upon the indication for which the drug is prescribed. Daily doses of 25 mg/kg intraperitoneally have been found to produce fetal mortality in rats. Specific studies to test the action of the drug on parturition, lactation, and development of the animal neonate were not done, but a general preliminary study in rats indicated no effect on these parameters. Although antihistamines have been found to produce fetal mortality in rodents, the pharmacological effects of histamine in the rodent do not parallel those in man. There are no adequate and well-controlled studies of promethazine hydrochloride tablets, USP in pregnant women. Promethazine hydrochloride tablets, USP should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects- Promethazine hydrochloride tablets, USP administered to a pregnant woman within two weeks of delivery may inhibit platelet aggregation in the newborn. Labor and Delivery Promethazine hydrochloride may be used alone or as an adjunct to narcotic analgesics during labor ( DOSAGE AND ADMINISTRATION ). Limited data suggest that use of promethazine hydrochloride during labor and delivery does not have an appreciable effect on the duration of labor or delivery and does not increase the risk of need for intervention in the newborn. The effect on later growth and development of the newborn is unknown (see also Error! Hyperlink reference not valid. ). Nursing Mothers It is not known whether promethazine hydrochloride is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from promethazine hydrochloride tablets, USP a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use PROMETHAZINE HYDROCHLORIDE TABLETS, USP ARE CONTRAINDICATED FOR USE IN PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE (see WARNINGS-BLACK BOX Warning and Use in Pediatric Patients ). Promethazine hydrochloride tablets, USP should be used with caution in pediatric patients 2 years of age and older (see WARNINGS-Use in Pediatric Patients ). Geriatric Use Clinical studies of promethazine hydrochloride formulations did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. Sedating drugs may cause confusion and over-sedation in the elderly; elderly patients generally should be started on low doses of promethazine hydrochloride tablets, USP and observed closely."}', 'information_for_patients': '{"Information for Patients Promethazine hydrochloride tablets, USP may cause marked drowsiness or impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. The use of alcohol or other central-nervous-system depressants such as sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers, may enhance impairment ( see WARNINGS-CNS Depression and PRECAUTIONS-Drug Interactions ). Pediatric patients should be supervised to avoid potential harm in bike riding or in other hazardous activities. Patients should be advised to report any involuntary muscle movements. Avoid prolonged exposure to the sun."}', 'pregnancy': '{"Pregnancy Teratogenic Effects - Pregnancy Category C Teratogenic effects have not been demonstrated in rat-feeding studies at doses of 6.25 and 12.5 mg/kg of promethazine hydrochloride. These doses are from approximately 2.1 to 4.2 times the maximum recommended total daily dose of promethazine for a 50-kg subject, depending upon the indication for which the drug is prescribed. Daily doses of 25 mg/kg intraperitoneally have been found to produce fetal mortality in rats. Specific studies to test the action of the drug on parturition, lactation, and development of the animal neonate were not done, but a general preliminary study in rats indicated no effect on these parameters. Although antihistamines have been found to produce fetal mortality in rodents, the pharmacological effects of histamine in the rodent do not parallel those in man. There are no adequate and well-controlled studies of promethazine hydrochloride tablets, USP in pregnant women. Promethazine hydrochloride tablets, USP should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects- Promethazine hydrochloride tablets, USP administered to a pregnant woman within two weeks of delivery may inhibit platelet aggregation in the newborn."}', 'pediatric_use': '{"Pediatric Use PROMETHAZINE HYDROCHLORIDE TABLETS, USP ARE CONTRAINDICATED FOR USE IN PEDIATRIC PATIENTS LESS THAN TWO YEARS OF AGE (see WARNINGS-BLACK BOX Warning and Use in Pediatric Patients ). Promethazine hydrochloride tablets, USP should be used with caution in pediatric patients 2 years of age and older (see WARNINGS-Use in Pediatric Patients )."}', 'geriatric_use': '{"Geriatric Use Clinical studies of promethazine hydrochloride formulations did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. Sedating drugs may cause confusion and over-sedation in the elderly; elderly patients generally should be started on low doses of promethazine hydrochloride tablets, USP and observed closely."}'}

{"PANTOPRAZOLE SODIUM"}

{'contraindications': '{"4 CONTRAINDICATIONS 1. PROTONIX is contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria [see Adverse Reactions (6) ] . 2. Proton pump inhibitors (PPIs), including PROTONIX, are contraindicated with rilpivirine-containing products [see Drug Interactions (7) ] . 3. Patients with known hypersensitivity to any component of the formulation or to substituted benzimidazoles ( 4 ) 4. Patients receiving rilpivirine-containing products ( 4 , 7 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in labeling: 1. Acute Interstitial Nephritis [see Warnings and Precautions (5.2) ] 2. Clostridium difficile- Associated Diarrhea [see Warnings and Precautions (5.3) ] 3. Bone Fracture [see Warnings and Precautions (5.4) ] 4. Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.5) ] 5. Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.6) ] 6. Hypomagnesemia [see Warnings and Precautions (5.7) ] 7. Fundic Gland Polyps [see Warnings and Precautions (5.9) ] Most common adverse reactions are: 3. For adult use (>2%): headache, diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness, and arthralgia. ( 6.1 ) 4. For pediatric use (>4%): URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience The adverse reaction profiles for PROTONIX (pantoprazole sodium) For Delayed-Release Oral Suspension and PROTONIX (pantoprazole sodium) Delayed-Release Tablets are similar. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adults Safety in nine randomized comparative US clinical trials in patients with GERD included 1,473 patients on oral PROTONIX (20 mg or 40 mg), 299 patients on an H 2 -receptor antagonist, 46 patients on another PPI, and 82 patients on placebo. The most frequently occurring adverse reactions are listed in Table 3. Table 3: Adverse Reactions Reported in Clinical Trials of Adult Patients with GERD at a Frequency of >2% PROTONIX (n=1473) % Comparators (n=345) % Placebo (n=82) % Headache 12.2 12.8 8.5 Diarrhea 8.8 9.6 4.9 Nausea 7.0 5.2 9.8 Abdominal pain 6.2 4.1 6.1 Vomiting 4.3 3.5 2.4 Flatulence 3.9 2.9 3.7 Dizziness 3.0 2.9 1.2 Arthralgia 2.8 1.4 1.2 Additional adverse reactions that were reported for PROTONIX in clinical trials with a frequency of ≤2% are listed below by body system: Body as a Whole: allergic reaction, pyrexia, photosensitivity reaction, facial edema Gastrointestinal: constipation, dry mouth, hepatitis Hematologic: leukopenia, thrombocytopenia Metabolic/Nutritional: elevated CK (creatine kinase), generalized edema, elevated triglycerides, liver enzymes elevated Musculoskeletal: myalgia Nervous: depression, vertigo Skin and Appendages: urticaria, rash, pruritus Special Senses: blurred vision Pediatric Patients Safety of PROTONIX in the treatment of EE associated with GERD was evaluated in pediatric patients ages 1 year through 16 years in three clinical trials. Safety trials involved pediatric patients with EE; however, as EE is uncommon in the pediatric population, 249 pediatric patients with endoscopically-proven or symptomatic GERD were also evaluated. All adult adverse reactions to PROTONIX are considered relevant to pediatric patients. In patients ages 1 year through 16 years, the most commonly reported (>4%) adverse reactions include: URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain. For safety information in patients less than 1 year of age see Use in Specific Populations (8.4) . Additional adverse reactions that were reported for PROTONIX in pediatric patients in clinical trials with a frequency of ≤4% are listed below by body system: Body as a Whole: allergic reaction, facial edema Gastrointestinal: constipation, flatulence, nausea Metabolic/Nutritional: elevated triglycerides, elevated liver enzymes, elevated CK (creatine kinase) Musculoskeletal: arthralgia, myalgia Nervous: dizziness, vertigo Skin and Appendages: urticaria The following adverse reactions seen in adults in clinical trials were not reported in pediatric patients in clinical trials, but are considered relevant to pediatric patients: photosensitivity reaction, dry mouth, hepatitis, thrombocytopenia, generalized edema, depression, pruritus, leukopenia, and blurred vision. Zollinger-Ellison (ZE) Syndrome In clinical studies of ZE Syndrome, adverse reactions reported in 35 patients taking PROTONIX 80 mg/day to 240 mg/day for up to 2 years were similar to those reported in adult patients with GERD. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of PROTONIX. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions are listed below by body system: Gastrointestinal Disorders: fundic gland polyps General Disorders and Administration Conditions: asthenia, fatigue, malaise Hematologic: pancytopenia, agranulocytosis Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure Immune System Disorders: anaphylaxis (including anaphylactic shock), systemic lupus erythematosus Infections and Infestations: Clostridium difficile associated diarrhea Investigations: weight changes Metabolism and Nutritional Disorders: hyponatremia, hypomagnesemia Musculoskeletal Disorders: rhabdomyolysis, bone fracture Nervous: ageusia, dysgeusia Psychiatric Disorders: hallucination, confusion, insomnia, somnolence Renal and Urinary Disorders: interstitial nephritis Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions (some fatal), including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN, some fatal), angioedema (Quincke\'s edema) and cutaneous lupus erythematosus"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with PROTONIX and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. Table 4: Clinically Relevant Interactions Affecting Drugs Co-Administered with PROTONIX and Interactions with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. 1. Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with pantoprazole may reduce antiviral effect and promote the development of drug resistance. 2. Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with pantoprazole may increase toxicity of the antiretroviral drugs . 3. There are other antiretroviral drugs which do not result in clinically relevant interactions with pantoprazole. Intervention: Rilpivirine-containing products: Concomitant use with PROTONIX is contraindicated [see Contraindications (4) ] . See prescribing information. Atazanavir: See prescribing information for atazanavir for dosing information. Nelfinavir: Avoid concomitant use with PROTONIX. See prescribing information for nelfinavir. Saquinavir: See the prescribing information for saquinavir and monitor for potential saquinavir toxicities. Other antiretrovirals: See prescribing information. Warfarin Clinical Impact: Increased INR and prothrombin time in patients receiving PPIs, including pantoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Intervention: Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin. Clopidogrel Clinical Impact: Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition [see Clinical Pharmacology (12.3) ]. Intervention: No dose adjustment of clopidogrel is necessary when administered with an approved dose of PROTONIX. Methotrexate Clinical Impact: Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [see Warnings and Precautions (5.12) ] . Intervention: A temporary withdrawal of PROTONIX may be considered in some patients receiving high-dose methotrexate. Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Impact: Pantoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity. Intervention: Mycophenolate mofetil (MMF): Co-administration of pantoprazole sodium in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH [see Clinical Pharmacology (12.3) ] . The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PROTONIX and MMF. Use PROTONIX with caution in transplant patients receiving MMF. See the prescribing information for other drugs dependent on gastric pH for absorption. Interactions with Investigations of Neuroendocrine Tumors Clinical Impact: CgA levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors [see Warnings and Precautions (5.10) , Clinical Pharmacology (12.2) ] . Intervention: Temporarily stop PROTONIX treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary. False Positive Urine Tests for THC Clinical Impact: There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs [see Warnings and Precautions (5.11) ] . Intervention: An alternative confirmatory method should be considered to verify positive results. See full prescribing information for a list of clinically important drug interactions ( 7 )"}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE PROTONIX For Delayed-Release Oral Suspension and PROTONIX Delayed-Release Tablets are indicated for: PROTONIX is a proton pump inhibitor (PPI) indicated for the following: 4. Short-Term Treatment of Erosive Esophagitis Associated with Gastroesophageal Reflux Disease (GERD) ( 1.1 ) 5. Maintenance of Healing of Erosive Esophagitis ( 1.2 ) 6. Pathological Hypersecretory Conditions Including Zollinger-Ellison (ZE) Syndrome ( 1.3 ) 1.1 Short-Term Treatment of Erosive Esophagitis Associated With Gastroesophageal Reflux Disease (GERD) PROTONIX is indicated in adults and pediatric patients five years of age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis (EE). For those adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of PROTONIX may be considered. Safety of treatment beyond 8 weeks in pediatric patients has not been established. 1.2 Maintenance of Healing of Erosive Esophagitis PROTONIX is indicated for maintenance of healing of EE and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with GERD. Controlled studies did not extend beyond 12 months. 1.3 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome PROTONIX is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison (ZE) Syndrome."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS 9. Gastric Malignancy: In adults, symptomatic response does not preclude presence of gastric malignancy. Consider additional follow-up and diagnostic testing. ( 5.1 ) 10. Acute Interstitial Nephritis : Observed in patients taking PPIs. ( 5.2 ) 11. Clostridium difficile- Associated Diarrhea : PPI therapy may be associated with increased risk of Clostridium difficile- associated diarrhea. ( 5.3 ) 12. Bone Fracture : Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. ( 5.4 ) 13. Cutaneous and Systemic Lupus Erythematosus : Mostly cutaneous; new onset or exacerbation of existing disease; discontinue PROTONIX and refer to specialist for evaluation. ( 5.5 ) 14. Cyanocobalamin (Vitamin B-12) Deficiency : Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin. ( 5.6 ) 15. Hypomagnesemia : Reported rarely with prolonged treatment with PPIs. ( 5.7 ) 16. Fundic Gland Polyps: Risk increases with long-term use, especially beyond one year. Use the shortest duration of therapy. ( 5.9 ) 5.1 Presence of Gastric Malignancy In adults, symptomatic response to therapy with PROTONIX does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy. 5.2 Acute Interstitial Nephritis Acute interstitial nephritis has been observed in patients taking PPIs including PROTONIX. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue PROTONIX if acute interstitial nephritis develops [see Contraindications (4) ]. 5.3 Clostridium difficile- Associated Diarrhea Published observational studies suggest that PPI therapy like PROTONIX may be associated with an increased risk of Clostridium difficile associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.2) ] . Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. 5.4 Bone Fracture Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2) , Adverse Reactions (6.2) ]. 5.5 Cutaneous and Systemic Lupus Erythematosus Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including pantoprazole sodium. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematous cases were CLE. The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement. Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported. Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving PROTONIX, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g. ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations. 5.6 Cyanocobalamin (Vitamin B-12) Deficiency Generally, daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (Vitamin B-12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed. 5.7 Hypomagnesemia Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, and in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2) ] . 5.8 Tumorigenicity Due to the chronic nature of GERD, there may be a potential for prolonged administration of PROTONIX. In long-term rodent studies, pantoprazole was carcinogenic and caused rare types of gastrointestinal tumors. The relevance of these findings to tumor development in humans is unknown [see Nonclinical Toxicology (13.1) ] . 5.9 Fundic Gland Polyps PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated. 5.10 Interference with Investigations for Neuroendocrine Tumors Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop PROTONIX treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary [see Clinical Pharmacology (12.2) ] . 5.11 Interference with Urine Screen for THC There have been reports of false-positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including PROTONIX [see Drug Interactions (7) ] . 5.12 Concomitant Use of PROTONIX with Methotrexate Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions (7) ]."}', 'overdosage': '{"10 OVERDOSAGE Experience in patients taking very high doses of PROTONIX (greater than 240 mg) is limited. Spontaneous post-marketing reports of overdose are generally within the known safety profile of PROTONIX. Pantoprazole is not removed by hemodialysis. In case of overdosage, treatment should be symptomatic and supportive. Single oral doses of pantoprazole at 709 mg/kg, 798 mg/kg, and 887 mg/kg were lethal to mice, rats, and dogs, respectively. The symptoms of acute toxicity were hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor. If overexposure to PROTONIX occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage."}', 'active_flag': 'Y', 'generic_name': '{"PANTOPRAZOLE SODIUM"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Gastric Malignancy Advise patients to return to their healthcare provider if they have a suboptimal response or an early symptomatic relapse [see Warnings and Precautions (5.1) ] . Acute Interstitial Nephritis Advise patients to call their healthcare provider immediately if they experience signs and/or symptoms associated with acute interstitial nephritis [see Warnings and Precautions (5.2) ] . Clostridium difficile- Associated Diarrhea Advise patients to immediately call their healthcare provider if they experience diarrhea that does not improve [see Warnings and Precautions (5.3) ] . Bone Fracture Advise patients to report any fractures, especially of the hip, wrist or spine, to their healthcare provider [see Warnings and Precautions (5.4) ] . Cutaneous and Systemic Lupus Erythematosus Advise patients to immediately call their healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus [see Warnings and Precautions (5.5) ] . Cyanocobalamin (Vitamin B-12) Deficiency Advise patients to report any clinical symptoms that may be associated with cyancobalamin deficiency to their healthcare provider if they have been receiving PROTONIX for longer than 3 years [see Warnings and Precautions (5.6) ] . Hypomagnesemia Advise patients to report any clinical symptoms that may be associated with hypomagnesemia to their healthcare provider, if they have been receiving PROTONIX for at least 3 months [see Warnings and Precautions (5.7) ] . Drug Interactions Instruct patients to inform their healthcare provider of any other medications they are currently taking, including rilpivirine-containing products [see Contraindications (4) ] digoxin [see Warnings and Precautions (5.7) ] and high dose methotrexate [see Warnings and Precautions (5.12) ] . Pregnancy Advise a pregnant woman of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1) ] . Administration • Do not split, crush, or chew PROTONIX For Delayed-Release Oral Suspension and PROTONIX Delayed-Release Tablets. • PROTONIX oral suspension packet is a fixed dose and cannot be divided to make a smaller dose. • Swallow PROTONIX Delayed-Release Tablets whole, with or without food in the stomach. • Concomitant administration of antacids does not affect the absorption of PROTONIX Delayed-Release Tablets. • Take PROTONIX For Delayed-Release Oral Suspension approximately 30 minutes before a meal. • Administer PROTONIX For Delayed-Release Oral Suspension in apple juice or applesauce, as described in the Instructions for Use. Do not administer in water, other liquids, or foods. • For patients with a nasogastric (NG) or gastrostomy tube, PROTONIX For Delayed-Release Oral Suspension can be administered with apple juice, as described in the Instructions for Use. • Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and take the next dose at the regular scheduled time. Do not take 2 doses at the same time."}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Available data from published observational studies did not demonstrate an association of major malformations or other adverse pregnancy outcomes with pantoprazole. In animal reproduction studies, no evidence of adverse development outcomes was observed with pantoprazole. Reproduction studies have been performed in rats at oral doses up to 450 mg/kg/day (about 88 times the recommended human dose) and rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose) with administration of pantoprazole during organogenesis in pregnant animals and have revealed no evidence of harm to the fetus due to pantoprazole in this study (see Data ) . A pre-and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. Oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day) were administered to pregnant females from gestation day (GD) 6 through lactation day (LD) 21. Changes in bone morphology were observed in pups exposed to pantoprazole in utero and through milk during the period of lactation as well as by oral dosing from postnatal day (PND) 4 through PND 21 [see Use in Specific Populations (8.4) ] . There were no drug-related findings in maternal animals . Advise pregnant women of the potential risk of fetal harm. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data Available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and pantoprazole use. Methodological limitations of these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. In a prospective study by the European Network of Teratology Information Services, outcomes from a group of 53 pregnant women administered median daily doses of 40 mg pantoprazole were compared to a control group of 868 pregnant women who did not take any proton pump inhibitors (PPIs). There was no difference in the rate of major malformations between women exposed to PPIs and the control group, corresponding to a Relative Risk (RR)=0.55, [95% Confidence Interval (CI) 0.08–3.95]. In a population-based retrospective cohort study covering all live births in Denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to pantoprazole in 549 live births. A meta-analysis that compared 1,530 pregnant women exposed to PPIs in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to PPIs (for major malformations OR=1.12 ([95% CI 0.86–1.45] and for spontaneous abortions OR=1.29 [95% CI 0.84–1.97]). Animal Data Reproduction studies have been performed in rats at oral pantoprazole doses up to 450 mg/kg/day (about 88 times the recommended human dose based on body surface area) and in rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose based on body surface area) with administration of pantoprazole sodium during organogenesis in pregnant animals. The studies have revealed no evidence of impaired fertility or harm to the fetus due to pantoprazole. A pre- and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. Oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day on a body surface area basis) were administered to pregnant females from gestation day (GD) 6 through lactation day (LD) 21. On postnatal day (PND 4) through PND 21, the pups were administered oral doses at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (AUC) in humans at a dose of 40 mg). There were no drug-related findings in maternal animals. During the preweaning dosing phase (PND 4 to 21) of the pups, there were increased mortality and/or moribundity and decreased body weight and body weight gain at 5 mg/kg/day (approximately equal exposures (AUC) in humans receiving the 40 mg dose) and higher doses. On PND 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (AUC) in humans at the 40 mg dose) and higher doses. The femur findings included lower total area, bone mineral content and density, periosteal and endosteal circumference, and cross-sectional moment of inertia. There were no microscopic changes in the distal femur, proximal tibia, or stifle joints. Changes in bone parameters were partially reversible following a recovery period, with findings on PND 70 limited to lower femur metaphysis cortical/subcortical bone mineral density in female pups at 5 mg/kg/day (approximately equal exposures (AUC) in humans at the 40 mg dose) and higher doses."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness of PROTONIX for short-term treatment (up to eight weeks) of EE associated with GERD have been established in pediatric patients 1 year through 16 years of age. Effectiveness for EE has not been demonstrated in patients less than 1 year of age. In addition, for patients less than 5 years of age, there is no appropriate dosage strength in an age-appropriate formulation available. Therefore, PROTONIX is indicated for the short-term treatment of EE associated with GERD for patients 5 years and older. The safety and effectiveness of PROTONIX for pediatric uses other than EE have not been established. 1 year through 16 years of age Use of PROTONIX in pediatric patients 1 year through 16 years of age for short-term treatment (up to eight weeks) of EE associated with GERD is supported by: a) extrapolation of results from adequate and well-controlled studies that supported the approval of PROTONIX for treatment of EE associated with GERD in adults, and b) safety, effectiveness, and pharmacokinetic studies performed in pediatric patients [see Clinical Studies (14.1) , Clinical Pharmacology (12.3) ] . Safety of PROTONIX in the treatment of EE associated with GERD in pediatric patients 1 through 16 years of age was evaluated in three multicenter, randomized, double-blind, parallel-treatment studies, involving 249 pediatric patients, including 8 with EE (4 patients ages 1 year to 5 years and 4 patients 5 years to 11 years). The children ages 1 year to 5 years with endoscopically diagnosed EE (defined as an endoscopic Hetzel-Dent score ≥2) were treated once daily for 8 weeks with one of two dose levels of PROTONIX (approximating 0.6 mg/kg or 1.2 mg/kg). All 4 of these patients with EE were healed (Hetzel-Dent score of 0 or 1) at 8 weeks. Because EE is uncommon in the pediatric population, predominantly pediatric patients with endoscopically-proven or symptomatic GERD were also included in these studies. Patients were treated with a range of doses of PROTONIX once daily for 8 weeks. For safety findings see Adverse Reactions (6.1) . Because these pediatric trials had no placebo, active comparator, or evidence of a dose response, the trials were inconclusive regarding the clinical benefit of PROTONIX for symptomatic GERD in the pediatric population. The effectiveness of PROTONIX for treating symptomatic GERD in pediatric patients has not been established. Although the data from the clinical trials support use of PROTONIX for the short-term treatment of EE associated with GERD in pediatric patients 1 year through 5 years, there is no commercially available dosage formulation appropriate for patients less than 5 years of age [see Dosage and Administration (2) ] . In a population pharmacokinetic analysis, clearance values in the children 1 to 5 years old with endoscopically proven GERD had a median value of 2.4 L/h. Following a 1.2 mg/kg equivalent dose (15 mg for ≤12.5 kg and 20 mg for >12.5 to <25 kg), the plasma concentrations of pantoprazole were highly variable and the median time to peak plasma concentration was 3 to 6 hours. The estimated AUC for patients 1 to 5 years old was 37% higher than for adults receiving a single 40 mg tablet, with a geometric mean AUC value of 6.8 µg∙hr/mL. Neonates to less than one year of age PROTONIX was not found to be effective in a multicenter, randomized, double-blind, placebo-controlled, treatment-withdrawal study of 129 pediatric patients 1 through 11 months of age. Patients were enrolled if they had symptomatic GERD based on medical history and had not responded to non-pharmacologic interventions for GERD for two weeks. Patients received PROTONIX daily for four weeks in an open-label phase, then patients were randomized in equal proportion to receive PROTONIX treatment or placebo for the subsequent four weeks in a double-blind manner. Efficacy was assessed by observing the time from randomization to study discontinuation due to symptom worsening during the four-week treatment-withdrawal phase. There was no statistically significant difference between PROTONIX and placebo in the rate of discontinuation. In this trial, the adverse reactions that were reported more commonly (difference of ≥4%) in the treated population compared to the placebo population were elevated CK, otitis media, rhinitis, and laryngitis. In a population pharmacokinetic analysis, the systemic exposure was higher in patients less than 1 year of age with GERD compared to adults who received a single 40 mg dose (geometric mean AUC was 103% higher in preterm infants and neonates receiving single dose of 2.5 mg of PROTONIX, and 23% higher in infants 1 through 11 months of age receiving a single dose of approximately 1.2 mg/kg). In these patients, the apparent clearance (CL/F) increased with age (median clearance: 0.6 L/hr, range: 0.03 to 3.2 L/hr). These doses resulted in pharmacodynamic effects on gastric but not esophageal pH. Following once daily dosing of 2.5 mg of PROTONIX in preterm infants and neonates, there was an increase in the mean gastric pH (from 4.3 at baseline to 5.2 at steady-state) and in the mean % time that gastric pH was > 4 (from 60% at baseline to 80% at steady-state). Following once daily dosing of approximately 1.2 mg/kg of PROTONIX in infants 1 through 11 months of age, there was an increase in the mean gastric pH (from 3.1 at baseline to 4.2 at steady-state) and in the mean % time that gastric pH was > 4 (from 32% at baseline to 60% at steady-state). However, no significant changes were observed in mean intraesophageal pH or % time that esophageal pH was <4 in either age group. Because PROTONIX was not shown to be effective in the randomized, placebo-controlled study in this age group, the use of PROTONIX for treatment of symptomatic GERD in infants less than 1 year of age is not indicated. Animal Toxicity Data In a pre- and post-natal development study in rats, the pups were administered oral doses of pantoprazole at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (AUC) in children aged 6 to 11 years at a dose of 40 mg) on postnatal day (PND 4) through PND 21, in addition to lactational exposure through milk. On PND 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (AUC) in children aged 6 to 11 years at the 40 mg dose) and higher doses. Changes in bone parameters were partially reversible following a recovery period. In neonatal/juvenile animals (rats and dogs) toxicities were similar to those observed in adult animals, including gastric alterations, decreases in red cell mass, increases in lipids, enzyme induction and hepatocellular hypertrophy. An increased incidence of eosinophilic chief cells in adult and neonatal/juvenile rats, and atrophy of chief cells in adult rats and in neonatal/juvenile dogs, was observed in the fundic mucosa of stomachs in repeated-dose studies. Full to partial recovery of these effects were noted in animals of both age groups following a recovery period."}', 'geriatric_use': '{"8.5 Geriatric Use In short-term US clinical trials, EE healing rates in the 107 elderly patients (≥65 years old) treated with PROTONIX were similar to those found in patients under the age of 65. The incidence rates of adverse reactions and laboratory abnormalities in patients aged 65 years and older were similar to those associated with patients younger than 65 years of age."}'}

{"SODIUM FLUORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Hoo Gargle Jasmine Mint Flavor Indications aids in the prevention of dental cavities"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"SODIUM FLUORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"Hoo Gargle Jasmine Mint Flavor Warning Warnings Keep out of reach of children. If more than used for rinsing is accidentally swallowed, get medical help or contact a Poison Control Center right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"NOREPINEPHRINE BITARTRATE"}

{'contraindications': '{"4 CONTRAINDICATIONS None. None."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following adverse reactions are described in greater detail in other sections: Tissue Ischemia [see Warnings and Precautions (5.1) ] Hypotension [see Warnings and Precautions (5.2) ] Cardiac Arrhythmias [see Warnings and Precautions (5.3) ] The most common adverse reactions are hypertension and bradycardia. The following adverse reactions can occur: Nervous system disorders: Anxiety, headache Respiratory disorders: Respiratory difficulty, pulmonary edema Most common adverse reactions are ischemic injury, bradycardia, anxiety, transient headache, respiratory difficulty, and extravasation necrosis at injection site. To report SUSPECTED ADVERSE REACTIONS, contact Caplin Steriles Limited at 1-866-978-6111 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types may result in hypertension. (7.1) Cyclopropane and halothane anesthetics increase cardiac autonomic irritability. (7.4) 7.1 MAO-Inhibiting Drugs Co-administration of norepinephrine bitartrate with monoamine oxidase (MAO) inhibitors or other drugs with MAO-inhibiting properties (e.g., linezolid) can cause severe, prolonged hypertension. If administration of norepinephrine bitartrate cannot be avoided in patients who recently have received any of these drugs and in whom, after discontinuation, MAO activity has not yet sufficiently recovered, monitor for hypertension. 7.2 Tricyclic Antidepressants Co-administration of norepinephrine bitartrate with tricyclic antidepressants (including amitriptyline, nortriptyline, protriptyline, clomipramine, desipramine, imipramine) can cause severe, prolonged hypertension. If administration of norepinephrine bitartrate cannot be avoided in these patients, monitor for hypertension. 7.3 Antidiabetics Norepinephrine Bitartrate can decrease insulin sensitivity and raise blood glucose. Monitor glucose and consider dosage adjustment of antidiabetic drugs. 7.4 Halogenated Anesthetics Concomitant use of norepinephrine bitartrate with halogenated anesthetics (e.g., cyclopropane, desflurane, enflurane, isoflurane, and sevoflurane) may lead to ventricular tachycardia or ventricular fibrillation. Monitor cardiac rhythm in patients receiving concomitant halogenated anesthetics."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Norepinephrine Bitartrate Injection is indicated to raise blood pressure in adult patients with severe, acute hypotension. Norepinephrine Bitartrate Injection is a catecholamine indicated for restoration of blood pressure in adult patients with acute hypotensive states."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Tissue Ischemia : Avoid extravasation of norepinephrine bitartrate injection into the tissues, as local necrosis might ensue due to the vasoconstrictive action of the drug. Infuse norepinephrine bitartrate injection into a large vein. To prevent sloughing and necrosis in areas in which extravasation has taken place, the area should be infiltrated as soon as possible with 10 mL to 15 mL of saline solution containing from 5 mg to 10 mg of an adrenergic blocking agent. (5.1) Hypotension After Abrupt Discontinuation : Sudden cessation of the infusion rate may result in marked hypotension. Reduce the norepinephrine bitartrate injection infusion rate gradually. (5.2) Cardiac Arrhythmias : Norepinephrine Bitartrate may cause arrhythmias. Monitor cardiac function in patients with underlying heart disease. (5.3) Allergic Reactions with Sulfite : Norepinephrine Bitartrate contains sodium metabisulfite. Sulfite may cause allergic-type-reactions. (5.4) 5.1 Tissue Ischemia Administration of norepinephrine bitartrate to patients who are hypotensive from hypovolemia can result in severe peripheral and visceral vasoconstriction, decreased renal perfusion and reduced urine output, tissue hypoxia, lactic acidosis, and reduced systemic blood flow despite “normal” blood pressure. Address hypovolemia prior to initiating norepinephrine bitartrate [see Dosage and Administration (2.1) ] . Avoid norepinephrine bitartrate in patients with mesenteric or peripheral vascular thrombosis, as this may increase ischemia and extend the area of infarction. Gangrene of the extremities has occurred in patients with occlusive or thrombotic vascular disease or who received prolonged or high dose infusions. Monitor for changes to the skin of the extremities in susceptible patients. Extravasation of norepinephrine bitartrate may cause necrosis and sloughing of surrounding tissue. To reduce the risk of extravasation, infuse into a large vein, check the infusion site frequently for free flow, and monitor for signs of extravasation [see Dosage and Administration (2.1) ] . Emergency Treatment of Extravasation To prevent sloughing and necrosis in areas in which extravasation has occurred, infiltrate the ischemic area as soon as possible, using a syringe with a fine hypodermic needle with 5 to 10 mg of phentolamine mesylate in 10 to 15 mL of 0.9% Sodium Chloride Injection in adults. Sympathetic blockade with phentolamine causes immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours. 5.2 Hypotension after Abrupt Discontinuation Sudden cessation of the infusion rate may result in marked hypotension. When discontinuing the infusion, gradually reduce the norepinephrine bitartrate infusion rate while expanding blood volume with intravenous fluids. 5.3 Cardiac Arrhythmias Norepinephrine Bitartrate elevates intracellular calcium concentrations and may cause arrhythmias, particularly in the setting of hypoxia or hypercarbia. Perform continuous cardiac monitoring of patients with arrhythmias. 5.4 Allergic Reactions Associated with Sulfite Norepinephrine Bitartrate contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people."}', 'overdosage': '{"10 OVERDOSAGE Overdosage with norepinephrine bitartrate may result in headache, severe hypertension, reflex bradycardia, marked increase in peripheral resistance, and decreased cardiac output. In case of overdosage, discontinue norepinephrine bitartrate until the condition of the patient stabilizes."}', 'active_flag': 'Y', 'generic_name': '{"NOREPINEPHRINE BITARTRATE"}', 'route': '{INTRAVENOUS}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Risk of Tissue Damage Advise the patient, family, or caregiver to report signs of extravasation urgently [see Warnings and Precautions (5.1) ]. Manufactured by Caplin Steriles Limited, Gummidipoondi – 601 201, INDIA. 222XXXXX"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Limited published data consisting of a small number of case reports and multiple small trials involving the use of norepinephrine in pregnant women at the time of delivery have not identified an increased risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus from hypotension associated with septic shock, myocardial infarction and stroke which are medical emergencies in pregnancy and can be fatal if left untreated. (see Clinical Considerations). In animal reproduction studies, using high doses of intravenous norepinephrine resulted in lowered maternal placental blood flow. Clinical relevance to changes in the human fetus is unknown since the average maintenance dose is ten times lower (see Data) . Increased fetal reabsorptions were observed in pregnant hamsters after receiving daily injections at approximately 2 times the maximum recommended dose on a mg/m 3 basis for four days during organogenesis (see Data) . The estimated background risk for major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 - 4% and 15 - 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypotension associated with septic shock, myocardial infarction, and stroke are medical emergencies in pregnancy which can be fatal if left untreated. Delaying treatment in pregnant women with hypotension associated with septic shock, myocardial infarction and stroke may increase the risk of maternal and fetal morbidity and mortality. Life-sustaining therapy for the pregnant woman should not be withheld due to potential concerns regarding the effects of norepinephrine on the fetus. Data Animal Data A study in pregnant sheep receiving high doses of intravenous norepinephrine (40 mcg/min, at approximately 10 times the average maintenance dose of 2 - 4 mcg/min in human, on a mg/kg basis) exhibited a significant decrease in maternal placental blood flow. Decreases in fetal oxygenation, urine and lung liquid flow were also observed. Norepinephrine administration to pregnant rats on Gestation Day 16 or 17 resulted in cataract production in rat fetuses. In hamsters, an increased number of resorptions (29.1% in study group vs. 3.4% in control group), fetal microscopic liver abnormalities and delayed skeletal ossification were observed at approximately 2 times the maximum recommended intramuscular or subcutaneous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day from Gestation Day 7 - 10)."}', 'pediatric_use': '{"8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established."}', 'geriatric_use': '{"8.5 Geriatric Use Clinical studies of norepinephrine bitartrate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Avoid administration of norepinephrine bitartrate into the veins in the leg in elderly patients [see Warnings and Precautions (5.1) ]."}'}

{"AMLODIPINE BESYLATE"}

{'contraindications': '{"4 CONTRAINDICATIONS • Known sensitivity to amlodipine ( 4 ) Amlodipine besylate tablets are contraindicated in patients with known sensitivity to amlodipine."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS Most common adverse reaction to amlodipine is edema which occurred in a dose related manner. Other adverse experiences not dose related but reported with an incidence >1.0% are fatigue, nausea, abdominal pain, and somnolence. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Unichem Pharmaceuticals (USA), Inc., at 1 866-562-4616 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Amlodipine has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials. In general, treatment with amlodipine was well-tolerated at doses up to 10 mg daily. Most adverse reactions reported during therapy with amlodipine were of mild or moderate severity. In controlled clinical trials directly comparing amlodipine (N=1730) at doses up to 10 mg to placebo (N=1250), discontinuation of amlodipine because of adverse reactions was required in only about 1.5% of patients and was not significantly different from placebo (about 1%). The most commonly reported side effects more frequent than placebo are reflected in the table below. The incidence (%) of side effects that occurred in a dose related manner are as follows: Amlodipine Placebo 2.5 mg N=275 5 mg N=296 10 mg N=268 N=520 Edema 1.8 3.0 10.8 0.6 Dizziness 1.1 3.4 3.4 1.5 Flushing 0.7 1.4 2.6 0.0 Palpitation 0.7 1.4 4.5 0.6 Other adverse reactions that were not clearly dose related but were reported with an incidence greater than 1.0% in placebo-controlled clinical trials include the following: Amlodipine (%) (N=1730) Placebo (%) (N=1250) Fatigue 4.5 2.8 Nausea 2.9 1.9 Abdominal Pain 1.6 0.3 Somnolence 1.4 0.6 For several adverse experiences that appear to be drug and dose related, there was a greater incidence in women than men associated with amlodipine treatment as shown in the following table: Amlodipine Placebo Male = % (N=1218) Female=% (N=512) Male=% (N=914) Female=% (N=336) Edema 5.6 14.6 1.4 5.1 Flushing 1.5 4.5 0.3 0.9 Palpitations 1.4 3.3 0.9 0.9 Somnolence 1.3 1.6 0.8 0.3 The following events occurred in <1% but >0.1% of patients in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship: Cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, peripheral ischemia, syncope, tachycardia, vasculitis. Central and Peripheral Nervous System: hypoesthesia, neuropathy peripheral, paresthesia, tremor, vertigo. Gastrointestinal: anorexia, constipation, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia. General: allergic reaction, asthenia, 1 back pain, hot flushes, malaise, pain, rigors, weight gain, weight decrease. Musculoskeletal System: arthralgia, arthrosis, muscle cramps, 1 myalgia. Psychiatric: sexual dysfunction (male 1 and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization. Respiratory System: dyspnea, 1 epistaxis. Skin and Appendages: angioedema, erythema multiforme, pruritus, 1 rash, 1 rash erythematous, rash maculopapular. Special Senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus. Urinary System: micturition frequency, micturition disorder, nocturia. Autonomic Nervous System: dry mouth, sweating increased. Metabolic and Nutritional: hyperglycemia, thirst. Hemopoietic: leukopenia, purpura, thrombocytopenia. 1 These events occurred in less than 1% in placebo-controlled trials, but the incidence of these side effects was between 1% and 2% in all multiple dose studies. Amlodipine therapy has not been associated with clinically significant changes in routine laboratory tests. No clinically relevant changes were noted in serum potassium, serum glucose, total triglycerides, total cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, or creatinine. In the CAMELOT and PREVENT studies [see Clinical Studies ( 14.4 )] , the adverse event profile was similar to that reported previously (see above), with the most common adverse event being peripheral edema. 6.2 Postmarketing Experience Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following postmarketing event has been reported infrequently where a causal relationship is uncertain: gynecomastia. In postmarketing experience, jaundice and hepatic enzyme elevations (mostly consistent with cholestasis or hepatitis), in some cases severe enough to require hospitalization, have been reported in association with use of amlodipine. Postmarketing reporting has also revealed a possible association between extrapyramidal disorder and amlodipine. Amlodipine has been used safely in patients with chronic obstructive pulmonary disease, well-compensated congestive heart failure, coronary artery disease, peripheral vascular disease, diabetes mellitus, and abnormal lipid profiles."}', 'drug_interactions': '{"7 DRUG INTERACTIONS • Do not exceed doses greater than 20 mg daily of simvastatin. ( 7.2 ) 7.1 Impact of Other Drugs on Amlodipine CYP3A Inhibitors Co-administration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A inhibitors to determine the need for dose adjustment [see Clinical Pharmacology ( 12.3 )] . CYP3A Inducers No information is available on the quantitative effects of CYP3A inducers on amlodipine. Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. Sildenafil Monitor for hypotension when sildenafil is co-administered with amlodipine [see Clinical Pharmacology ( 12.2 )] . 7.2 Impact of Amlodipine on Other Drugs Simvastatin Co-administration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily [see Clinical Pharmacology ( 12.3 )] . Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus is recommended and adjust the dose when appropriate [see Clinical Pharmacology ( 12.3 )] ."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Amlodipine besylate tablets are calcium channel blockers and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of: • Hypertension ( 1.1 ) • Amlodipine besylate tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. • Coronary Artery Disease ( 1.2 ) • Chronic Stable Angina • Vasospastic Angina (Prinzmetal\'s or Variant Angina) • Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction < 40% 1.1 Hypertension Amlodipine besylate tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including amlodipine besylate tablets. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program\'s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mm Hg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Amlodipine besylate tablets may be used alone or in combination with other antihypertensive agents. 1.2 Coronary Artery Disease (CAD) Chronic Stable Angina Amlodipine besylate tablets are indicated for the symptomatic treatment of chronic stable angina. Amlodipine besylate tablets may be used alone or in combination with other antianginal agents. Vasospastic Angina (Prinzmetal\'s or Variant Angina) Amlodipine besylate tablets are indicated for the treatment of confirmed or suspected vasospastic angina. Amlodipine besylate tablets may be used as monotherapy or in combination with other antianginal agents. Angiographically Documented CAD In patients with recently documented CAD by angiography and without heart failure or an ejection fraction <40%, amlodipine besylate tablets are indicated to reduce the risk of hospitalization for angina and to reduce the risk of a coronary revascularization procedure."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. However, acute hypotension is unlikely. ( 5.1 ) • Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease. ( 5.2 ) • Titrate slowly in patients with severe hepatic impairment ( 5.3 ) 5.1 Hypotension Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. Because of the gradual onset of action, acute hypotension is unlikely. 5.2 Increased Angina or Myocardial Infarction Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease. 5.3 Patients with Hepatic Failure Because amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t 1/2 ) is 56 hours in patients with impaired hepatic function, titrate slowly when administering amlodipine to patients with severe hepatic impairment."}', 'overdosage': '{"10 OVERDOSAGE Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of amlodipine is limited. Single oral doses of amlodipine maleate equivalent to 40 mg amlodipine/kg and 100 mg amlodipine/kg in mice and rats, respectively, caused deaths. Single oral amlodipine maleate doses equivalent to 4 or more mg amlodipine/kg or higher in dogs (11 or more times the maximum recommended human dose on a mg/m 2 basis) caused a marked peripheral vasodilation and hypotension. If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, provide cardiovascular support including elevation of the extremities and the judicious administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine) with attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit."}', 'active_flag': 'Y', 'generic_name': '{"AMLODIPINE BESYLATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': None, 'pregnancy': '{"8.1 Pregnancy Risk Summary The limited available data based on post-marketing reports with amlodipine use in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy [see Clinical Considerations] . In animal reproduction studies, there was no evidence of adverse developmental effects when pregnant rats and rabbits were treated orally with amlodipine maleate during organogenesis at doses approximately 10 and 20-times the maximum recommended human dose (MRHD), respectively. However for rats, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold). Amlodipine has been shown to prolong both the gestation period and the duration of labor in rats at this dose [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly. Data Animal Data No evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats and rabbits were treated orally with amlodipine maleate at doses up to 10 mg amlodipine/kg/day (approximately 10 and 20 times the MRHD based on body surface area, respectively) during their respective periods of major organogenesis. However for rats, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold)in rats receiving amlodipine maleate at a dose equivalent to 10 mg amlodipine/kg/day for 14 days before mating and throughout mating and gestation. Amlodipine maleate has been shown to prolong both the gestation period and the duration of labor in rats at this dose."}', 'pediatric_use': '{"8.4 Pediatric Use Amlodipine (2.5 to 5 mg daily) is effective in lowering blood pressure in patients 6 to 17 years [see Clinical Studies ( 14.1 )] . Effect of amlodipine on blood pressure in patients less than 6 years of age is not known."}', 'geriatric_use': '{"8.5 Geriatric Use Clinical studies of amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of amlodipine with a resulting increase of AUC of approximately 40–60%, and a lower initial dose may be required [see Dosage and Administration ( 2.1 )] ."}'}

{DUTASTERIDE}

{'contraindications': '{"4 CONTRAINDICATIONS Dutasteride capsules are contraindicated for use in: • Pregnancy. Dutasteride use is contraindicated in women who are pregnant. In animal reproduction and developmental toxicity studies, dutasteride inhibited development of male fetus external genitalia. Therefore, dutasteride may cause fetal harm when administered to a pregnant woman. [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1) ]. • Patients with previously demonstrated, clinically significant hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride or other 5 alpha-reductase inhibitors [see Adverse Reactions (6.2) ]. • Pregnancy. Dutasteride use is contraindicated in women who are pregnant. ( 4 , 5.4 , 8.1 ) • Patients with previously demonstrated, clinically significant hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride capsules or other 5 alpha-reductase inhibitors. ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The most common adverse reactions, reported in ≥1% of subjects treated with dutasteride capsules and more commonly than in subjects treated with placebo, are impotence, decreased libido, ejaculation disorders, and breast disorders. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Epic Pharma, LLC at 1-888-374-2791 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trial of another drug and may not reflect the rates observed in practice. From clinical trials with Dutasteride as monotherapy or in combination with tamsulosin: • The most common adverse reactions reported in subjects receiving dutasteride were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), and ejaculation disorders. The most common adverse reactions reported in subjects receiving combination therapy (dutasteride plus tamsulosin) were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), ejaculation disorders, and dizziness. Ejaculation disorders occurred significantly more in subjects receiving combination therapy (11%) compared with those receiving dutasteride (2%) or tamsulosin (4%) as monotherapy. • Trial withdrawal due to adverse reactions occurred in 4% of subjects receiving dutasteride, and 3% of subjects receiving placebo in placebo-controlled trials with dutasteride. The most common adverse reaction leading to trial withdrawal was impotence (1%). • In the clinical trial evaluating the combination therapy, trial withdrawal due to adverse reactions occurred in 6% of subjects receiving combination therapy (dutasteride plus tamsulosin) and 4% of subjects receiving dutasteride or tamsulosin as monotherapy. The most common adverse reaction in all treatment arms leading to trial withdrawal was erectile dysfunction (1% to 1.5%). Monotherapy Over 4,300 male subjects with BPH were randomly assigned to receive placebo or 0.5-mg daily doses of dutasteride in 3 identical 2-year, placebo-controlled, double-blind, Phase 3 treatment trials, each followed by a 2-year open-label extension. During the double-blind treatment period, 2,167 male subjects were exposed to dutasteride, including 1,772 exposed for 1 year and 1,510 exposed for 2 years. When including the open-label extensions, 1,009 male subjects were exposed to dutasteride for 3 years and 812 were exposed for 4 years. The population was aged 47 to 94 years (mean age: 66 years) and greater than 90% were white. Table 1 summarizes clinical adverse reactions reported in at least 1% of subjects receiving dutasteride and at a higher incidence than subjects receiving placebo. Table 1. Adverse Reactions Reported in ≥1% of Subjects over a 24-Month Period and More Frequently in the Group Receiving Dutasteride Capsules than the Placebo Group (Randomized, Double-blind, Placebo-Controlled Trials Pooled) by Time of Onset Adverse Reaction Adverse Reaction Time of Onset Months 0-6 Months 7-12 Months 13-18 Months 19-24 Dutasteride capsules (n) (n = 2,167) (n = 1,901) (n = 1,725) (n = 1,605) Placebo (n) (n = 2,158) (n = 1,922) (n = 1,714) (n = 1,555) Impotencea Dutasteride capsules 4.7% 1.4% 1.0% 0.8% Placebo 1.7% 1.5% 0.5% 0.9% Decreased libido a Dutasteride capsules 3.0% 0.7% 0.3% 0.3% Placebo 1.4% 0.6% 0.2% 0.1% Ejaculation disorders a Dutasteride capsules 1.4% 0.5% 0.5% 0.1% Placebo 0.5% 0.3% 0.1% 0.0% Breast disorders b Dutasteride capsules 0.5% 0.8% 1.1% 0.6% Placebo 0.2% 0.3% 0.3% 0.1% a These sexual adverse reactions are associated with dutasteride treatment (including monotherapy and combination with tamsulosin). These adverse reactions may persist after treatment discontinuation. The role of dutasteride in this persistence is unknown. b Includes breast tenderness and breast enlargement. Long-Term Treatment (Up to 4 Years) High-grade Prostate Cancer: The REDUCE trial was a randomized, double-blind, placebo-controlled trial that enrolled 8,231 men aged 50 to 75 years with a serum PSA of 2.5 ng/mL to 10 ng/mL and a negative prostate biopsy within the previous 6 months. Subjects were randomized to receive placebo (n = 4,126) or 0.5-mg daily doses of dutasteride capsules (n = 4,105) for up to 4 years. The mean age was 63 years and 91% were white. Subjects underwent protocol-mandated scheduled prostate biopsies at 2 and 4 years of treatment or had “for-cause biopsies” at non-scheduled times if clinically indicated. There was a higher incidence of Gleason score 8-10 prostate cancer in men receiving dutasteride capsules (1.0%) compared with men on placebo (0.5%) [see Indications and Usage (1.3) , Warnings and Precautions (5.2) ]. In a 7-year placebo-controlled clinical trial with another 5 alpha-reductase inhibitor (finasteride 5 mg, PROSCAR ® ), similar results for Gleason score 8-10 prostate cancer were observed (finasteride 1.8% versus placebo 1.1%). No clinical benefit has been demonstrated in patients with prostate cancer treated with dutasteride capsules. Reproductive and Breast Disorders In the 3 pivotal placebo-controlled BPH trials with dutasteride capsules, each 4 years in duration, there was no evidence of increased sexual adverse reactions (impotence, decreased libido, and ejaculation disorder) or breast disorders with increased duration of treatment. Among these 3 trials, there was 1 case of breast cancer in the dutasteride group and 1 case in the placebo group. No cases of breast cancer were reported in any treatment group in the 4-year CombAT trial or the 4-year REDUCE trial. The relationship between long-term use of dutasteride and male breast neoplasia is currently unknown. Combination with Alpha-blocker Therapy (CombAT) Over 4,800 male subjects with BPH were randomly assigned to receive 0.5-mg dutasteride capsules, 0.4-mg tamsulosin, or combination therapy (0.5-mg dutasteride capsules plus 0.4-mg tamsulosin) administered once daily in a 4-year double-blind trial. Overall, 1,623 subjects received monotherapy with dutasteride capsules; 1,611 subjects received monotherapy with tamsulosin; and 1,610 subjects received combination therapy. The population was aged 49 to 88 years (mean age: 66 years) and 88% were white. Table 2 summarizes adverse reactions reported in at least 1% of subjects in the combination group and at a higher incidence than subjects receiving monotherapy with dutasteride capsules or tamsulosin. Table 2. Adverse Reactions Reported over a 48-Month Period in ≥1% of Subjects and More Frequently in the Coadministration Therapy Group than the Groups Receiving Monotherapy with Dustateride Capsules or Tamsulosin (CombAT) by Time of Onset Adverse Reaction Adverse Reaction Time of Onset Year 1 Months 0-6 Months 7-12 Year 2 Years 3 Year 4 Combination a (n = 1,610) (n = 1,527) (n = 1,428) (n = 1,283) (n = 1,200) Dutasteride capsules (n = 1,623) (n = 1,548) (n = 1,464) (n = 1,325) (n = 1,200) Tamsulosin (n = 1,611) (n = 1,545) (n = 1,468) (n = 1,281) (n = 1,112) Ejaculation disorders b,c Combination 7.8% 1.6% 1.0% 0.5% <0.1% Dutasteride capsules 1.0% 0.5% 0.5% 0.2% 0.3% Tamsulosin 2.2% 0.5% 0.5% 0.2% 0.3% Impotence c,d Combination 5.4% 1.1% 1.8% 0.9% 0.4% Dutasteride capsules 4.0% 1.1% 1.6% 0.6% 0.3% Tamsulosin 2.6% 0.8% 1.0% 0.6% 1.1% Decreased libido c,e Combination 4.5% 0.9% 0.8% 0.2% 0.0% Dutasteride capsules 3.1% 0.7% 1.0% 0.2% 0.0% Tamsulosin 2.0% 0.6% 0.7% 0.2% <0.1% Breast disorders f Combination 1.1% 1.1% 0.8% 0.9% 0.6% Dutasteride capsules 0.9% 0.9% 1.2% 0.5% 0.7% Tamsulosin 0.4% 0.4% 0.4% 0.2% 0.0% Dizziness Combination 1.1% 0.4% 0.1% <0.1% 0.2% Dutasteride capsules 0.5% 0.3% 0.1% <0.1% <0.1% Tamsulosin 0.9% 0.5% 0.4% <0.1% 0.0% a Combination = Dutasteride capsules 0.5 mg once daily plus tamsulosin 0.4 mg once daily. b Includes anorgasmia, retrograde ejaculation, semen volume decreased, orgasmic sensation decreased, orgasm abnormal, ejaculation delayed, ejaculation disorder, ejaculation failure, and premature ejaculation. c These sexual adverse reactions are associated with dutasteride treatment (including monotherapy and combination with tamsulosin). These adverse reactions may persist after treatment discontinuation. The role of dutasteride in this persistence is unknown. d Includes erectile dysfunction and disturbance in sexual arousal. e Includes libido decreased, libido disorder, loss of libido, sexual dysfunction, and male sexual dysfunction. f Includes breast enlargement, gynecomastia, breast swelling, breast pain, breast tenderness, nipple pain, and nipple swelling. Cardiac Failure: In CombAT, after 4 years of treatment, the incidence of the composite term cardiac failure in the combination therapy group (12/1,610; 0.7%) was higher than in either monotherapy group: dutasteride capsules, 2/1,623 (0.1%) and tamsulosin, 9/1,611 (0.6%).Composite cardiac failure was also examined in a separate 4-year placebo-controlled trial evaluating dutasteride capsules in men at risk for development of prostate cancer. The incidence of cardiac failure in subjects taking dutasteride capsules was 0.6% (26/4,105) compared with 0.4% (15/4,126) in subjects on placebo. A majority of subjects with cardiac failure in both trials had co-morbidities associated with an increased risk of cardiac failure. Therefore, the clinical significance of the numerical imbalances in cardiac failure is unknown. No causal relationship between dutasteride capsules, alone or in combination with tamsulosin, and cardiac failure has been established. No imbalance was observed in the incidence of overall cardiovascular adverse events in either trial 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of dutasteride capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to dutasteride. Immune System Disorders Hypersensitivity reactions, including rash, pruritus, urticaria, localized edema, serious skin reactions, and angioedema. Neoplasms Male breast cancer. Psychiatric Disorders Depressed mood. Reproductive System and Breast Disorders Testicular pain and testicular swelling."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Use with caution in patients taking potent, chronic cytochrome P450 (CYP)3A4 enzyme inhibitors (e.g., ritonavir). ( 7 ) 7.1 Cytochrome P450 3A Inhibitors Dutasteride is extensively metabolized in humans by the CYP3A4 and CYP3A5 isoenzymes. The effect of potent CYP3A4 inhibitors on dutasteride has not been studied. Because of the potential for drug-drug interactions, use caution when prescribing dutasteride capsules to patients taking potent, chronic CYP3A4 enzyme inhibitors (e.g., ritonavir) [see Clinical Pharmacology (12.3) ]. 7.2 Alpha-adrenergic Antagonists The administration of dutasteride capsules in combination with tamsulosin or terazosin has no effect on the steady-state pharmacokinetics of either alpha-adrenergic antagonist. The effect of administration of tamsulosin or terazosin on dutasteride pharmacokinetic parameters has not been evaluated. 7.3 Calcium Channel Antagonists Coadministration of verapamil or diltiazem decreases dutasteride clearance and leads to increased exposure to dutasteride. The change in dutasteride exposure is not considered to be clinically significant. No dose adjustment is recommended [see Clinical Pharmacology (12.3) ]. 7.4 Cholestyramine Administration of a single 5-mg dose of dutasteride capsules followed 1 hour later by 12 g of cholestyramine does not affect the relative bioavailability of dutasteride [see Clinical Pharmacology (12.3) ]. 7.5 Digoxin Dutasteride capsules do not alter the steady-state pharmacokinetics of digoxin when administered concomitantly at a dose of 0.5 mg/day for 3 weeks [see Clinical Pharmacology (12.3) ]. 7.6 Warfarin Concomitant administration of dutasteride capsules 0.5 mg/day for 3 weeks with warfarin does not alter the steady-state pharmacokinetics of the S- or R-warfarin isomers or alter the effect of warfarin on prothrombin time [see Clinical Pharmacology (12.3) ]."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Dutasteride capsules is a 5 alpha-reductase inhibitor indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to: ( 1.1 ) • improve symptoms, • reduce the risk of acute urinary retention, and • reduce the risk of the need for BPH-related surgery. Dutasteride capsules in combination with the alpha-adrenergic antagonist, tamsulosin, is indicated for the treatment of symptomatic BPH in men with an enlarged prostate. (1.2) Limitations of Use: Dutasteride capsules is not approved for the prevention of prostate cancer. (1.3) 1.1 Monotherapy Dutasteride capsules are indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to: • improve symptoms, • reduce the risk of acute urinary retention (AUR), and • reduce the risk of the need for BPH-related surgery. 1.2 Combination with Alpha-adrenergic Antagonist Dutasteride capsules in combination with the alpha-adrenergic antagonist, tamsulosin, is indicated for the treatment of symptomatic BPH in men with an enlarged prostate. 1.3 Limitations of Use Dutasteride capsules are not approved for the prevention of prostate cancer."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Dutasteride capsules reduce serum prostate-specific antigen (PSA) concentration by approximately 50%. However, any confirmed increase in PSA while on dutasteride capsules may signal the presence of prostate cancer and should be evaluated, even if those values are still within the normal range for untreated men. ( 5.1 ) • Dutasteride capsules may increase the risk of high-grade prostate cancer. ( 5.2 , 6.1 ) • Prior to initiating treatment with dutasteride capsules, consideration should be given to other urological conditions that may cause similar symptoms. ( 5.3 ) • Women who are pregnant or may be pregnant should not handle dutasteride capsules due to potential risk to a male fetus. ( 5.4 , 8.1 ) • Patients should not donate blood until 6 months after their last dose of dutasteride capsules. (5.5) 5.1 Effects on Prostate-specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection In clinical trials, dutasteride reduced serum PSA concentration by approximately 50% within 3 to 6 months of treatment. This decrease was predictable over the entire range of PSA values in subjects with symptomatic BPH, although it may vary in individuals. dutasteride may also cause decreases in serum PSA in the presence of prostate cancer. To interpret serial PSAs in men taking dutasteride, a new PSA baseline should be established at least 3 months after starting treatment and PSA monitored periodically thereafter. Any confirmed increase from the lowest PSA value while on dutasteride may signal the presence of prostate cancer and should be evaluated, even if PSA levels are still within the normal range for men not taking a 5 alpha-reductase inhibitor. Noncompliance with dutasteride may also affect PSA test results. To interpret an isolated PSA value in a man treated with dutasteride for 3 months or more, the PSA value should be doubled for comparison with normal values in untreated men.The free-to-total PSA ratio (percent free PSA) remains constant, even under the influence of dutasteride. If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men receiving dutasteride, no adjustment to its value appears necessary. Coadministration of dutasteride and tamsulosin resulted in similar changes to serum PSA as dutasteride monotherapy. 5.2 Increased Risk of High-grade Prostate Cancer In men aged 50 to 75 years with a prior negative biopsy for prostate cancer and a baseline PSA between 2.5 ng/mL and 10.0 ng/mL taking dutasteride in the 4-year Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, there was an increased incidence of Gleason score 8-10 prostate cancer compared with men taking placebo (dutasteride 1.0% versus placebo 0.5%) [see Indications and Usage (1.3) , Adverse Reactions (6.1) ]. In a 7-year placebo-controlled clinical trial with another 5 alpha-reductase inhibitor (finasteride 5 mg, PROSCAR ® ), similar results for Gleason score 8-10 prostate cancer were observed (finasteride 1.8% versus placebo 1.1%). 5 alpha-reductase inhibitors may increase the risk of development of high-grade prostate cancer. Whether the effect of 5 alpha-reductase inhibitors to reduce prostate volume or trial-related factors impacted the results of these trials has not been established. 5.3 Evaluation for Other Urological Diseases Prior to initiating treatment with dutasteride, consideration should be given to other urological conditions that may cause similar symptoms. In addition, BPH and prostate cancer may coexist. 5.4 Transdermal Exposure of Dutasteride in Pregnant Women—Risk to Male Fetus Dutasteride capsules should not be handled by women who are pregnant or may be pregnant. Dutasteride can be absorbed through the skin and could result in unintended fetal exposure and potential risk to a male fetus. If a pregnant woman comes in contact with leaking dutasteride capsules, the contact area should be washed immediately with soap and water [see Use in Specific Populations (8.1) ]. Dutasteride can be absorbed through the skin based on animal studies [see Nonclinical Toxicology (13.2) ]. 5.5 Blood Donation Men being treated with dutasteride should not donate blood until at least 6 months have passed following their last dose. The purpose of this deferred period is to prevent administration of dutasteride to a pregnant female transfusion recipient. 5.6 Effect on Semen Characteristics The effects of dutasteride 0.5 mg/day on semen characteristics were evaluated in healthy men throughout 52 weeks of treatment and 24 weeks of post-treatment follow-up. At 52 weeks, compared with placebo, dutasteride treatment resulted in mean reduction in total sperm count, semen volume, and sperm motility; the effects on total sperm count were not reversible after 24 weeks of follow-up. Sperm concentration and sperm morphology were unaffected and mean values for all semen parameters remained within the normal range at all timepoints. The clinical significance of the effect of dutasteride on semen characteristics for an individual patient’s fertility is not known [see Use in Specific Populations (8.3) ]."}', 'overdosage': '{"10 OVERDOSAGE In volunteer trials, single doses of dutasteride up to 40 mg (80 times the therapeutic dose) for 7 days have been administered without significant safety concerns. In a clinical trial, daily doses of 5 mg (10 times the therapeutic dose) were administered to 60 subjects for 6 months with no additional adverse effects to those seen at therapeutic doses of 0.5 mg. There is no specific antidote for dutasteride. Therefore, in cases of suspected overdosage, symptomatic and supportive treatment should be given as appropriate, taking the long half-life of dutasteride into consideration."}', 'active_flag': 'Y', 'generic_name': '{DUTASTERIDE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). PSA Monitoring Inform patients that dutasteride capsules reduce serum PSA levels by approximately 50% within 3 to 6 months of therapy, although it may vary for each individual. For patients undergoing PSA screening, increases in PSA levels while on treatment with dutasteride capsules may signal the presence of prostate cancer and should be evaluated by a healthcare provider [see Warnings and Precautions (5.1) ]. Increased Risk of High-Grade Prostate Cancer Inform patients that there was an increase in high-grade prostate cancer in men treated with 5 alpha-reductase inhibitors (which are indicated for BPH treatment), including dutasteride capsules, compared with those treated with placebo in trials looking at the use of these drugs to reduce the risk of prostate cancer [see Indications and Usage (1.3) , Warnings and Precautions (5.2) , Adverse Reactions (6.1) ]. Transdermal Exposure of Dutasteride in Pregnant or Potentially Pregnant Women—Risk to Male Inform patients that dutasteride capsules should not be handled by women who are pregnant or may potentially be pregnant because of the potential for absorption of dutasteride and the subsequent potential risk to a developing male fetus. Dutasteride can be absorbed through the skin and could result in unintended fetal exposure. If a pregnant or potentially pregnant woman comes in contact with leaking dutasteride capsules, the contact area should be washed immediately with soap and water [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1) ]. Effects on Semen Parameters Advise men that dutasteride may affect sperm characteristics but the effect on fertility is unknown [see Warnings and Precautions (5.6) , Use in Specific Populations (8.3) ]. Blood Donation Inform men treated with dutasteride capsules that they should not donate blood until at least 6 months following their last dose to prevent pregnant women from receiving dutasteride through blood transfusion [see Warnings and Precautions (5.5) ]. Serum levels of dutasteride are detectable for 4 to 6 months after treatment ends [see Clinical Pharmacology (12.3) ]. Manufactured by: Humanwell PuraCap Pharmaceutical Wuhan, Hubei 430206, China Distributed by: Epic Pharma, LLC Laurelton, NY 11413 Rev. 04-2020-00 PI-EDUT-00"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Dutasteride is contraindicated for use in pregnancy because it may cause harm to the male fetus [see Contraindications (4) ]. Dutasteride is not indicated for use in women. Dutasteridem is a 5 alpha-reductase inhibitor that prevents conversion of testosterone to dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia. Abnormalities in the genitalia of male fetuses is an expected physiological consequence of inhibition of this conversion. These results are similar to observations in male infants with genetic 5 alpha-reductase deficiency. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. In animal reproduction studies, dutasteride inhibited normal development of external genitalia in male offspring when given to rats or rabbits during organogenesis at less than the maximum recommended human dose (MRHD) of 0.5 mg daily, in the absence of maternal toxicity. At 15 times the MRHD, prolonged pregnancy, decreased reproductive organ weights, and delayed puberty in male offspring were observed in rats, with no-effect levels less than the MRHD of 0.5 mg daily. Increased placental weights in rabbits were also observed, with no-effect levels less than the MRHD of 0.5 mg daily (see Data). Although dutasteride is secreted into human semen, the drug concentration in the human female partner is approximately 100 times less than concentrations producing abnormalities of male genitalia in animal studies (see Data). In monkeys dosed during organogenesis at blood concentrations comparable to or above levels to which a human female partner is estimated to be exposed, male offspring external genitalia was not adversely affected. No feminization occurred in male offspring of untreated female rats mated to treated male rats even though detectable blood levels of dutasteride were observed in the female rats [see Nonclinical Toxicology (13.1) ]. Data Human Data: The highest measured semen concentration of dutasteride in treated men was 14 ng/mL. Although dutasteride is detected in semen, assuming exposure of a 50-kg woman to 5 mL of semen and 100% absorption, the woman’s expected dutasteride blood concentration through semen would be about 0.0175 ng/mL. This concentration is approximately 100 times less than blood concentrations producing abnormalities of male genitalia in animal studies. Dutasteride is highly protein bound in human semen (greater than 96%), which may reduce the amount of dutasteride available for vaginal absorption. Animal Data: In an embryo-fetal development study in rats, oral administration of dutasteride at 10 times less than the MRHD of 0.5 mg daily (based on average blood levels in men) resulted in feminization of male genitalia in the fetus (decreased anogenital distance at 0.05 mg/kg/day, with a lack of a no-effect level) in the absence of maternal toxicity. In addition, nipple development, hypospadias, and distended preputial glands occurred in fetuses of dams treated at doses of 2.5 mg/kg/day or greater (approximately 15 times the MRHD). Reduced fetal body weight and associated delayed ossification in the presence of maternal toxicity (decreased body weight gain) were observed at maternal exposure approximately 15 times the MRHD (dose of 2.5 mg/kg/day or greater). An increase in stillborn pups was observed in dams treated at 30 mg/kg/day (approximately 111 times the MRHD), with a no-effect level of 12.5 mg/kg/day. In a rabbit embryo-fetal development study, doses 28 times the MRHD (doses of 30 mg/kg/day or greater), based on average blood levels in men, were administered orally on Gestation Days 7 to 29 (during organogenesis and the late period of external genitalia development). Histological evaluation of the genital papilla of fetuses revealed evidence of feminization of the male fetus as well as fused skull bones and increased placental weights at all doses in the absence of maternal toxicity. A second embryo-fetal development study in rabbits dosed throughout pregnancy (organogenesis and later period of external genitalia development [Gestation Days 6 to 29]) at 0.3 times the MRHD (doses of 0.05 mg/kg/day or greater, with no no-effect level), also produced evidence of feminization of the genitalia in male fetuses and increased placental weights at all doses in the absence of maternal toxicity. In an embryo-fetal development study, pregnant rhesus monkeys were exposed intravenously during organogenesis (Gestation Days 20 to 100) to a dutasteride blood level comparable to or above the estimated dutasteride exposure of a human female partner. Dutasteride was administered on Gestation Days 20 to 100 (during organogenesis) at doses of 400, 780, 1,325, or 2,010 ng/day (12 monkeys/group). No feminization of male external genitalia of monkey offspring was observed. Reduction of fetal adrenal weights, reduction in fetal prostate weights, and increases in fetal ovarian and testis weights were observed at the highest dose tested. Based on the highest measured semen concentration of dutasteride in treated men (14 ng/mL), these doses in the monkey represent up to 16 times the potential maximum exposure of a 50-kg human female to 5 mL of semen daily from a dutasteride-treated male, assuming 100% absorption. The dose levels (on a ng/kg basis) administered to monkeys in this study are 32 to 186 times the nominal (ng/kg) dose to which a female would potentially be exposed via the semen. It is not known whether rabbits or rhesus monkeys produce any of the major human metabolites. In an oral pre-and post-natal development study in rats, feminization of the male genitalia was observed. Decreased anogenital distance was observed at 0.05 times the MRHD and greater (0.05 mg/kg/day and greater), with a lack of a no-effect level, based on average blood levels in men as an estimation of AUC. Hypospadias and nipple development were observed at 2.5 mg/kg/day or greater (14 times the MRHD or greater, with a no-effect level at 0.05 mg/kg/day). Doses of 2.5 mg/kg/day and greater also resulted in prolonged gestation in the parental females, an increase in time to balano-preputial separation in male offspring, a decrease in time to vaginal patency for female offspring, and a decrease in prostate and seminal vesicle weights in male offspring. Increased stillbirths and decreased neonatal viability in offspring were noted at 30 mg/kg/day (102 times the MRHD in the presence of maternal toxicity [decreased body weights])."}', 'pediatric_use': '{"8.4 Pediatric Use Dutasteride is not indicated for use in pediatric patients. Safety and effectiveness in pediatric patients have not been established."}', 'geriatric_use': '{"8.5 Geriatric Use Of 2,167 male subjects treated with dutasteride capsules in 3 clinical trials, 60% were aged 65 years and older and 15% were aged 75 years and older. No overall differences in safety or efficacy were observed between these subjects and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3) ]."}'}

{"CALCIUM CARBONATE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses relieves: acid indigestion heartburn"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"CALCIUM CARBONATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': '{"When using this product do not take more than 10 tablets in a 24-hour period, or use the maximum dosage of this product for more than 2 weeks, except under the advice and supervision of a doctor."}', 'warnings': '{"Warnings Ask a doctor or pharmacist before use if you are presently taking a prescription drug. Antacids may interact with certain prescription drugs. When using this product do not take more than 10 tablets in a 24-hour period, or use the maximum dosage of this product for more than 2 weeks, except under the advice and supervision of a doctor."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"BRIMONIDINE TARTRATE"}

{'contraindications': '{"4 CONTRAINDICATIONS Brimonidine Tartrate Ophthalmic Solution, 0.2% is contraindicated in patients with hypersensitivity to brimonidine tartrate or any component of this medication. It is also contraindicated in patients receiving monoamine oxidase (MAO) inhibitor therapy. Neonates and infants (under the age of 2 years). ( 4.1 ) 4.1 Neonates and Infants (under the age of 2 years) Brimonidine tartrate ophthalmic solution, 0.2% is contraindicated in neonates and infants (under the age of 2 years) [ see Use in Specific Populations ( 8.4)] . 4.2 Hypersensitivity Reactions Brimonidine tartrate ophthalmic solution, 0.2% is contraindicated in patients who have exhibited a hypersensitivity reaction to any component of this medication in the past [ see Adverse Reactions ( 6.1 ) and ( 6.2 )]."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Potentiation of Vascular Insufficiency [ see Warnings and Precautions ( 5.1 )] Severe Cardiovascular Disease [ see Warnings and Precautions ( 5.2 )] Contamination of Topical Ophthalmic Products after Use [see Warnings and Precautions ( 5.3 )] Neonates and Infants (under the age of 2 years) [ see Contraindications ( 4.1 )] Most common adverse reactions occurring in approximately 10 to 30% of patients receiving brimonidine tartrate ophthalmic solution 0.2% included oral dryness, ocular hyperemia, burning and stinging, headache, blurring, foreign body sensation, fatigue/drowsiness, conjunctival follicles, ocular allergic reactions, and ocular pruritus. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Indoco Remedies Limited at +1-855-642-2594 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Adverse reactions occurring in approximately 10 to 30% of the subjects (in descending order): oral dryness, ocular hyperemia, burning and stinging, headache, blurring, foreign body sensation, fatigue/drowsiness, conjunctival follicles, ocular allergic reactions, and ocular pruritus. Adverse reactions occurring in approximately 3 to 9% of the subjects (in descending order): corneal staining/erosion, photophobia, eyelid erythema, ocular ache/pain, ocular dryness, tearing, upper respiratory symptoms, eyelid edema, conjunctival edema, dizziness, blepharitis, ocular irritation, gastrointestinal symptoms, asthenia, conjunctival blanching, abnormal vision and muscular pain. Adverse reactions reported < 3% of the patients: lid crusting, conjunctival hemorrhage, abnormal taste, insomnia, conjunctival discharge, depression, hypertension, anxiety, palpitations/arrhythmias, nasal dryness and syncope. 6.2 Postmarketing Experience The following reactions have been identified during postmarketing use of brimonidine tartrate ophthalmic solutions in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to brimonidine tartrate ophthalmic solutions, or a combination of these factors, include: • Bradycardia; conjunctivitis; hypersensitivity; hypotension; iritis; keratoconjunctivitis sicca; lacrimation increased; miosis; nausea; skin reactions (including erythema, eyelid pruritus, rash, and vasodilation); and tachycardia. • Apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence in infants receiving brimonidine tartrate ophthalmic solutions."}', 'drug_interactions': '{"7 DRUG INTERACTIONS • Antihypertensives/cardiac glycosides may lower blood pressure. ( 7.1 ) • Use with CNS depressants may result in an additive or potentiating effect. ( 7.2 ) • Tricyclic antidepressants may potentially blunt the hypotensive effect of systemic clonidine. ( 7.3 ) • Monoamine oxidase inhibitors may result in increased hypotension. ( 7.4 ) 7.1 Antihypertensive/Cardiac Glycosides Because brimonidine tartrate ophthalmic solution, 0.2% may reduce blood pressure, caution in using drugs such as antihypertensives and/or cardiac glycosides with brimonidine tartrate ophthalmic solution, 0.2% is advised. 7.2 CNS Depressants Although specific drug interaction studies have not been conducted with brimonidine tartrate ophthalmic solution, 0.2%, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics) should be considered. 7.3 Tricyclic Antidepressants Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of these agents with brimonidine tartrate ophthalmic solution, 0.2% in humans can lead to resulting interference with the IOP lowering effect. Caution is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines. 7.4 Monoamine Oxidase Inhibitors Monoamine oxidase (MAO) inhibitors may theoretically interfere with the metabolism of brimonidine and potentially result in an increased systemic side-effect such as hypotension. Caution is advised in patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amines."}', 'indications_and_usage': '{"1 INDICATIONS & USAGE Brimonidine tartrate ophthalmic solution, 0.2% is indicated for lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension. The IOP lowering efficacy of Brimonidine tartrate ophthalmic solution, 0.2% diminishes over time in some patients. This loss of effect appears with a variable time of onset in each patient and should be closely monitored. Brimonidine Tartrate Ophthalmic Solution, 0.2% is an alpha adrenergic agonist indicated for lowering intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Potentiation of vascular insufficiency. ( 5.1 ) 5.1 Potentiation of Vascular Insufficiency Brimonidine tartrate ophthalmic solution, 0.2% may potentiate syndromes associated with vascular insufficiency. Brimonidine tartrate ophthalmic solution, 0.2% should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension, or thromboangiitis obliterans 5.2 Severe Cardiovascular Disease Although brimonidine tartrate ophthalmic solution had minimal effect on the blood pressure of patients in clinical studies, caution should be exercised in treating patients with severe cardiovascular disease 5.3 Contamination of Topical Ophthalmic Products After Use There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface [ see Patient Counseling Information ( 17 )]. 5.4 Use with Contact Lenses The preservative in Brimonidine tartrate ophthalmic solution, 0.2%, benzalkonium chloride, may be absorbed by soft contact lenses. Patients wearing soft contact lenses should be instructed to wait at least 15 minutes after instilling Brimonidine Tartrate Ophthalmic Solution, 0.2% to insert soft contact lenses."}', 'overdosage': '{"10 OVERDOSAGE Very limited information exists on accidental ingestion of brimonidine in adults; the only adverse reaction reported to date has been hypotension. Symptoms of brimonidine overdose have been reported in neonates, infants, and children receiving brimonidine tartrate as part of medical treatment of congenital glaucoma or by accidental oral ingestion [see Use In Specific Populations (8.4)]. Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained."}', 'active_flag': 'Y', 'generic_name': '{"BRIMONIDINE TARTRATE"}', 'route': '{OPHTHALMIC}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Handling the Container Instruct patients that ocular solutions, if handled improperly or if the tip of the dispensing container contacts the eye or surrounding structures, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions [see Warnings and Precautions (5.3)]. Always replace the cap after using. If solution changes color or becomes cloudy, do not use. Do not use the product after the expiration date marked on the bottle. When to Seek Physician Advice Advise patients that if they have ocular surgery or develop an intercurrent ocular condition (e.g., trauma or infection), they should immediately seek their physician\'s advice concerning the continued use of the present multidose container. Use with Contact Lenses Advise patients that contact lenses should be removed prior to instillation of brimonidine tartrate ophthalmic solution 0.2% and may be reinserted 15 minutes following its administration. Use with Other Ophthalmic Drugs Advise patients that if more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart. Potential for Decreased Mental Alertness As with other similar medications, brimonidine tartrate ophthalmic solution 0.2% may cause fatigue and/or drowsiness in some patients. Caution patients who engage in hazardous activities of the potential for a decrease in mental alertness. Manufactured by: Indoco Remedies Limited, L-32, 33, 34, Verna Industrial Area, Verna, Goa – 403722. India. logo"}', 'pregnancy': '{"8.1 Pregnancy Pregnancy Category B: Teratogenicity studies have been performed in animals. Brimonidine tartrate was not teratogenic when given orally during gestation days 6 through 15 in rats and days 6 through 18 in rabbits. The highest doses of brimonidine tartrate in rats (2.5 mg/kg/day) and rabbits (5 mg/kg/day) achieved AUC exposure values 375-fold higher or 19-fold higher, respectively, than similar values estimated in humans treated with Brimonidine Tartrate Ophthalmic Solution, 0.2%, one drop in one eye, twice daily. There are no adequate and well-controlled studies in pregnant women; however, in animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent. Because animal reproduction studies are not always predictive of human response, brimonidine tartrate ophthalmic solution, 0.2% should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus."}', 'pediatric_use': '{"8.4 Pediatric Use Brimonidine tartrate ophthalmic solution, 0.2% is contraindicated in children under the age of 2 years [ see Contraindications ( 4.1 )]. During postmarketing surveillance, apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence have been reported in infants receiving brimonidine. The safety and effectiveness of brimonidine tartrate have not been studied in children below the age of 2 years. In a well-controlled clinical study conducted in pediatric glaucoma patients (ages 2 to 7 years) the most commonly observed adverse reactions with brimonidine tartrate ophthalmic solution, 0.2% dosed three times daily were somnolence (50 to 83% in patients ages 2 to 6 years) and decreased alertness. In pediatric patients 7 years of age (greater than 20 kg), somnolence appears to occur less frequently (25%). Approximately 16% of patients on brimonidine tartrate ophthalmic solution, 0.2% discontinued from the study due to somnolence."}', 'geriatric_use': '{"8.5 Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and other adult patients."}'}

{ALCOHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses Reduce bacteria on hands."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{ALCOHOL}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if irritation or redness develops."}', 'do_not_use': '{"Do not use on open skin wounds"}', 'when_using': '{"When using this product keep out of eyes."}', 'warnings': '{"Warnings Flammable. Keep away from source of Ignition or flame. For external use only. Do not use on open skin wounds When using this product keep out of eyes. Stop use and ask a doctor if irritation or redness develops. Keep out of reach of children. If swallowed, get medical help or contact a doctor immediately."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"OMEPRAZOLE MAGNESIUM"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use treats frequent heartburn (occurs 2 or more days a week) not intended for immediate relief of heartburn; this drug may take 1 to 4 days for full effect"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{OMEPRAZOLE}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if: your heartburn continues or worsens you need to take this product for more than 14 days you need to take more than 1 course of treatment every 4 months you get diarrhea you develop a rash or joint pain"}', 'do_not_use': '{"Do not use if you have: trouble or pain swallowing food, vomiting with blood, or bloody or black stools heartburn with lightheadedness, sweating or dizziness chest pain or shoulder pain with shortness of breath; sweating; pain spreading to arms, neck or shoulders; or lightheadedness frequent chest pain These may be signs of a serious condition. See your doctor."}', 'when_using': None, 'warnings': '{"Warnings Allergy alert: Do not use if you are allergic to omeprazole"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"MILRINONE LACTATE"}

{'contraindications': '{"CONTRAINDICATIONS Milrinone is contraindicated in patients who are hypersensitive to it. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products."}', 'adverse_reactions': '{"ADVERSE REACTIONS Cardiovascular Effects In patients receiving milrinone in Phase II and III clinical trials, ventricular arrhythmias were reported in 12.1%: Ventricular ectopic activity, 8.5%; nonsustained ventricular tachycardia, 2.8%; sustained ventricular tachycardia, 1% and ventricular fibrillation, 0.2% (2 patients experienced more than one type of arrhythmia). Holter recordings demonstrated that in some patients injection of milrinone increased ventricular ectopy, including nonsustained ventricular tachycardia. Life-threatening arrhythmias were infrequent and when present have been associated with certain underlying factors such as preexisting arrhythmias, metabolic abnormalities (e.g. hypokalemia), abnormal digoxin levels and catheter insertion. Milrinone was not shown to be arrhythmogenic in an electro physiology study. Supraventricular arrhythmias were reported in 3.8% of the patients receiving milrinone. The incidence of both supraventricular and ventricular arrhythmias has not been related to the dose or plasma milrinone concentration. Other cardio vascular adverse reactions include hypotension, 2.9% and angina/chest pain, 1.2%. In the post-marketing experience, there have been rare cases of “torsades de pointes” reported. CNS Effects Headaches, usually mild to moderate in severity, have been reported in 2.9% of patients receiving milrinone. Other Effects Other adverse reactions reported, but not definitely related to the administration of milrinone include hypokalemia, 0.6%; tremor, 0.4%; and thrombocytopenia, 0.4%. Post-Marketing Adverse Event Reports In addition to adverse events reported from clinical trials, the following events have been reported from worldwide post-marketing experience with Milrinone: Isolated spontaneous reports of bronchospasm and anaphylactic shock. Liver function test abnormalities and skin reactions such as rash. Administration site conditions: Infusion site reaction. To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma at 864-879-9994 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch ."}', 'drug_interactions': '{"Drug Interactions No untoward clinical manifestations have been observed in limited experience with patients in whom milrinone was used concurrently with the following drugs: digitalis glycosides; lidocaine, quinidine; hydralazine, prazosin; isosorbide dinitrate, nitroglycerin; chlorthalidone, furosemide, hydrochlorothiazide, spironolactone; captopril; heparin, warfarin, diazepam, insulin; and potassium supplements."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Milrinone is indicated for the short-term intravenous treatment of patients with acute decompensated heart failure. Patients receiving milrinone should be observed closely with appropriate electrocardiographic equipment. The facility for immediate treatment of potential cardiac events, which may include life-threatening ventricular arrhythmias, must be available. The majority of experience with intravenous milrinone has been in patients receiving digoxin and diuretics. There is no experience in controlled trials with infusions of milrinone for periods exceeding 48 hours."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Doses of milrinone may produce hypotension because of its vasodilator effect. If this occurs, administration of milrinone should be reduced or temporarily discontinued until the patient\'s condition stabilizes. No specific antidote is known, but general measures for circulatory support should be taken."}', 'active_flag': 'Y', 'generic_name': '{"MILRINONE LACTATE"}', 'route': '{INTRAVENOUS}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Whether given orally or by continuous or intermittent intravenous infusion, milrinone has not been shown to be safe or effective in the longer (greater than 48 hours) treatment of patients with heart failure. In a multicenter trial of 1088 patients with Class III and IV heart failure, long-term oral treatment with milrinone was associated with no improvement in symptoms and an increased risk of hospitalization and death. In this study, patients with Class IV symptoms appeared to be at particular risk of life-threatening cardiovascular reactions. There is no evidence that milrinone given by long-term continuous or intermittent infusion does not carry a similar risk. The use of milrinone both intravenously and orally has been associated with increased frequency of ventricular arrhythmias, including nonsustained ventricular tachycardia. Long-term oral use has been associated with an increased risk of sudden death. Hence, patients receiving milrinone should be observed closely with the use of continuous electrocardiographic monitoring to allow the prompt detection and management of ventricular arrhythmias."}', 'precautions': '{"PRECAUTIONS General Milrinone should not be used in patients with severe obstructive aortic or pulmonic valvular disease in lieu of surgical relief of the obstruction. Like other inotropic agents, it may aggravate outflow tract obstruction in hypertrophic subaortic stenosis. Supraventricular and ventricular arrhythmias have been observed in the high-risk population treated. In some patients, injections of milrinone and oral milrinone have been shown to increase ventricular ectopy, including nonsustained ventricular tachycardia. The potential for arrhythmia, present in congestive heart failure itself, may be increased by many drugs or combinations of drugs. Patients receiving milrinone should be closely monitored during infusion. Milrinone produces a slight shortening of AV node conduction time, indicating a potential for an increased ventricular response rate in patients with atrial flutter/fibrillation which is not controlled with digitalis therapy. During therapy with milrinone, blood pressure and heart rate should be monitored and the rate of infusion slowed or stopped in patients showing excessive decreases in blood pressure. If prior vigorous diuretic therapy is suspected to have caused significant decreases in cardiac filling pressure, milrinone should be cautiously administered with monitoring of blood pressure, heart rate, and clinical symptomatology. There is no experience in controlled trials with infusions of milrinone for periods exceeding 48 hours. Cases of infusion site reactions have been reported with intravenous milrinone therapy (see ADVERSE REACTIONS ). Consequently, careful monitoring of the infusion site should be maintained to avoid possible extravasation. Use in Acute Myocardial Infarction No clinical studies have been conducted in patients in the acute phase of post myocardial infarction. Until further clinical experience with this class of drugs is gained, milrinone is not recommended in these patients. Laboratory Tests Fluid and electrolytes: Fluid and electrolyte changes and renal function should be carefully monitored during therapy with milrinone. Improvement in cardiac output with resultant diuresis may necessitate a reduction in the dose of diuretic. Potassium loss due to excessive diuresis may predispose digitalized patients to arrhythmias. Therefore, hypokalemia should be corrected by potassium supplementation in advance of or during use of milrinone. Drug Interactions No untoward clinical manifestations have been observed in limited experience with patients in whom milrinone was used concurrently with the following drugs: digitalis glycosides; lidocaine, quinidine; hydralazine, prazosin; isosorbide dinitrate, nitroglycerin; chlorthalidone, furosemide, hydrochlorothiazide, spironolactone; captopril; heparin, warfarin, diazepam, insulin; and potassium supplements. Chemical Interactions There is an immediate chemical interaction which is evidenced by the formation of a precipitate when furosemide is injected into an intravenous line of an infusion of milrinone. Therefore, furosemide should not be administered in intravenous lines containing milrinone. Carcinogenesis , Mutagenesis , Impairment o f Fertility Twenty-four months of oral administration of milrinone to mice at doses up to 40 mg/kg/day (about 50 times the human oral therapeutic dose in a 50 kg patient) was unassociated with evidence of carcinogenic potential. Neither was there evidence of carcinogenic potential when milrinone was orally administered to rats at doses up to 5 mg/kg/day (about 6 times the human oral therapeutic dose) for twenty-four months or at 25 mg/kg/day (about 30 times the human oral therapeutic dose) for up to 18 months in males and 20 months in females. Whereas the Chinese Hamster Ovary Chromosome Aberration Assay was positive in the presence of a metabolic activation system, results from the Ames Test, the Mouse Lymphoma Assay, the Micronucleus Test, and the in vivo Rat Bone Marrow Metaphase Analysis indicated an absence of mutagenic potential. In reproductive performance studies in rats, milrinone had no effect on male or female fertility at oral doses up to 32 mg/kg/day. Animal Toxicity Oral and intravenous administration of toxic dosages of milrinone to rats and dogs resulted in myocardial degeneration/fibrosis and endocardial hemorrhage, principally affecting the left ventricular papillary muscles. Coronary vascular lesions characterized by periarterial edema and inflammation have been observed in dogs only. The myocardial/endocardial changes are similar to those produced by beta-adrenergic receptor agonists such as isoproterenol, while the vascular changes are similar to those produced by minoxidil and hydralazine. Doses within the recommended clinical dose range (up to 1.13 mg/kg/day) for congestive heart failure patients have not produced significant adverse effects in animals. Pregnancy Oral administration of milrinone to pregnant rats and rabbits during organogenesis produced no evidence of teratogenicity at dose levels up to 40 mg/kg/day and 12 mg/kg/day, respectively. Milrinone did not appear to be teratogenic when administered intravenously to pregnant rats at doses up to 3 mg/kg/day (about 2.5 times the maximum recommended clinical intravenous dose) or pregnant rabbits at doses up to 12 mg/kg/day, although an increased resorption rate was apparent at both 8 mg/kg/day and 12 mg/kg/day (intravenous) in the latter species. There are no adequate and well-controlled studies in pregnant women. Milrinone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers Caution should be exercised when milrinone is administered to nursing women, since it is not known whether it is excreted in human milk. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Use in Elderly Patients There are no special dosage recommendations for the elderly patient. Ninety percent of all patients administered milrinone in clinical studies were within the age range of 45 to 70 years, with a mean age of 61 years. Patients in all age groups demonstrated clinically and statistically significant responses. No age-related effects on the incidence of adverse reactions have been observed. Controlled pharmacokinetic studies have not disclosed any age -related effects on the distribution and elimination of milrinone."}', 'information_for_patients': None, 'pregnancy': '{"Pregnancy Oral administration of milrinone to pregnant rats and rabbits during organogenesis produced no evidence of teratogenicity at dose levels up to 40 mg/kg/day and 12 mg/kg/day, respectively. Milrinone did not appear to be teratogenic when administered intravenously to pregnant rats at doses up to 3 mg/kg/day (about 2.5 times the maximum recommended clinical intravenous dose) or pregnant rabbits at doses up to 12 mg/kg/day, although an increased resorption rate was apparent at both 8 mg/kg/day and 12 mg/kg/day (intravenous) in the latter species. There are no adequate and well-controlled studies in pregnant women. Milrinone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus."}', 'pediatric_use': '{"Pediatric Use Safety and effectiveness in pediatric patients have not been established."}', 'geriatric_use': None}

{ACETAMINOPHEN,"DEXTROMETHORPHAN HYDROBROMIDE","PHENYLEPHRINE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses • temporarily relieves common cold/flu symptoms: • cough due to minor throat and bronchial irritation • nasal congestion • minor aches and pains • sore throat • headache • fever"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"ACETAMINOPHEN, DEXTROMETHORPHAN HBR, PHENYLEPHRINE HCL"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if • you get nervous, dizzy or sleepless • pain, nasal congestion or cough gets worse or lasts more than 5 days (children) or 7 days (adults) • fever gets worse or lasts more than 3 days • redness or swelling is present • new symptoms occur • cough comes back or occurs with rash or headache that lasts. These could be signs of a serious condition."}', 'do_not_use': '{"Do not use • with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist. • if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson’s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product. • if you have ever had an allergic reaction to this product or any of its ingredients"}', 'when_using': '{"When using this product do not use more than directed"}', 'warnings': '{"Warnings Liver warning: This product contains acetaminophen. Severe liver damage may occur if • adult takes more than 4,000 mg of acetaminophen in 24 hours • child takes more than 5 doses in 24 hours • taken with other drugs containing acetaminophen • adult has 3 or more alcoholic drinks every day while using this product Allergy alert: Acetaminophen may cause severe skin reactions. Symptoms may include: • skin reddening • blisters • rash If a skin reaction occurs, stop use and seek medical help right away. Sore throat warning: If sore throat is severe, persists for more than 2 days, is accompanied or followed by fever, headache, rash, nausea, or vomiting, consult a doctor promptly. Do not use • with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist. • if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson’s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product. • if you have ever had an allergic reaction to this product or any of its ingredients Ask a doctor before use if you have • liver disease • heart disease • high blood pressure • thyroid disease • diabetes • trouble urinating due to an enlarged prostate gland • cough that occurs with too much phlegm (mucus) • persistent or chronic cough such as occurs with smoking, asthma, or emphysema Ask a doctor or pharmacist before use if you are taking the blood thinning drug warfarin When using this product do not use more than directed Stop use and ask a doctor if • you get nervous, dizzy or sleepless • pain, nasal congestion or cough gets worse or lasts more than 5 days (children) or 7 days (adults) • fever gets worse or lasts more than 3 days • redness or swelling is present • new symptoms occur • cough comes back or occurs with rash or headache that lasts. These could be signs of a serious condition. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. Overdose warning: In case of overdose, get medical help or contact a Poison Control Center right away (1-800-222-1222). Quick medical attention is critical for adults as well as for children even if you do not notice any signs or symptoms."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{LANSOPRAZOLE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use • treats frequent heartburn (occurs 2 or more days a week) • not intended for immediate relief of heartburn; this drug may take 1 to 4 days for full effect"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{LANSOPRAZOLE}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if • your heartburn continues or worsens • you need to take this product for more than 14 days • you need to take more than 1 course of treatment every 4 months • you get diarrhea • you develop a rash or joint pain"}', 'do_not_use': '{"Do not use • if you have trouble or pain swallowing food, vomiting with blood, or bloody or black stools. These may be signs of a serious condition. See your doctor."}', 'when_using': None, 'warnings': '{"Warnings Allergy alert: Do not use if you are allergic to lansoprazole Do not use • if you have trouble or pain swallowing food, vomiting with blood, or bloody or black stools. These may be signs of a serious condition. See your doctor. Ask a doctor before use if you have • liver disease • had heartburn over 3 months. This may be a sign of a more serious condition. • heartburn with lightheadedness, sweating or dizziness • chest pain or shoulder pain with shortness of breath; sweating; pain spreading to arms, neck or shoulders; or lightheadedness • frequent chest pain • frequent wheezing, particularly with heartburn • unexplained weight loss • nausea or vomiting • stomach pain Ask a doctor or pharmacist before use if you are • taking a prescription drug. Acid reducers may interact with certain prescription drugs. Stop use and ask a doctor if • your heartburn continues or worsens • you need to take this product for more than 14 days • you need to take more than 1 course of treatment every 4 months • you get diarrhea • you develop a rash or joint pain If pregnant or breast-feeding, ask a health care professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away (1-800-222-1222)."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"PANTOPRAZOLE SODIUM"}

{'contraindications': '{"4 CONTRAINDICATIONS Pantoprazole is contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria [see Adverse Reactions ( 6 )]. Proton pump inhibitors (PPIs), including Pantoprazole, are contraindicated with patients receiving rilpivirine-containing products [see Drug Interactions ( 7 )]. Patients with known hypersensitivity to any component of the formulation or to substituted benzimidazoles ( 4 ) Patients receiving rilpivirine-containing products ( 4 , 7 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in labeling: Acute Interstitial Nephritis [see Warnings and Precautions ( 5.2 )] Clostridium difficile- Associated Diarrhea [see Warnings and Precautions ( 5.3 )] Bone Fracture [see Warnings and Precautions ( 5.4 )] Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions ( 5.5 )] Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions ( 5.6 )] Hypomagnesemia [see Warnings and Precautions ( 5.7 )] Fundic Gland Polyps [see Warnings and Precautions ( 5.9 )] Most common adverse reactions are: For adult use (>2%): headache, diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness, and arthralgia. ( 6.1 ) For pediatric use (>4%): URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lannett Company, Inc. at 1-844-834-0530 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adults Safety in nine randomized comparative US clinical trials in patients with GERD included 1,473 patients on oral Pantoprazole (20 mg or 40 mg), 299 patients on an H 2 -receptor antagonist, 46 patients on another PPI, and 82 patients on placebo. The most frequently occurring adverse reactions are listed in Table 3. Table 3: Adverse Reactions Reported in Clinical Trials of Adult Patients with GERD at a Frequency of > 2% Pantoprazole (n=1473) % Comparators (n=345) % Placebo (n=82) % Headache 12.2 12.8 8.5 Diarrhea 8.8 9.6 4.9 Nausea 7.0 5.2 9.8 Abdominal pain 6.2 4.1 6.1 Vomiting 4.3 3.5 2.4 Flatulence 3.9 2.9 3.7 Dizziness 3.0 2.9 1.2 Arthralgia 2.8 1.4 1.2 Additional adverse reactions that were reported for Pantoprazole in clinical trials with a frequency of ≤ 2% are listed below by body system: Body as a Whole: allergic reaction, pyrexia, photosensitivity reaction, facial edema Gastrointestinal: constipation, dry mouth, hepatitis Hematologic: leukopenia, thrombocytopenia Metabolic/Nutritional: elevated CK (creatine kinase), generalized edema, elevated triglycerides, liver enzymes elevated Musculoskeletal: myalgia Nervous: depression, vertigo Skin and Appendages: urticaria, rash, pruritus Special Senses: blurred vision Pediatric Patients Safety of Pantoprazole in the treatment of EE associated with GERD was evaluated in pediatric patients ages 1 year through 16 years in three clinical trials. Safety trials involved pediatric patients with EE; however, as EE is uncommon in the pediatric population, 249 pediatric patients with endoscopically-proven or symptomatic GERD were also evaluated. All adult adverse reactions to Pantoprazole are considered relevant to pediatric patients. In patients ages 1 year through 16 years, the most commonly reported (> 4%) adverse reactions include: URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain. For safety information in patients less than 1 year of age see Use in Specific Populations ( 8.4 ) . Additional adverse reactions that were reported for Pantoprazole in pediatric patients in clinical trials with a frequency of ≤ 4% are listed below by body system: Body as a Whole: allergic reaction, facial edema Gastrointestinal: constipation, flatulence, nausea Metabolic/Nutritional: elevated triglycerides, elevated liver enzymes, elevated CK (creatine kinase) Musculoskeletal: arthralgia, myalgia Nervous: dizziness, vertigo Skin and Appendages: urticaria The following adverse reactions seen in adults in clinical trials were not reported in pediatric patients in clinical trials, but are considered relevant to pediatric patients: photosensitivity reaction, dry mouth, hepatitis, thrombocytopenia, generalized edema, depression, pruritus, leukopenia, and blurred vision. Zollinger-Ellison (ZE) Syndrome In clinical studies of ZE Syndrome, adverse reactions reported in 35 patients taking Pantoprazole 80 mg/day to 240 mg/day for up to 2 years were similar to those reported in adult patients with GERD. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of Pantoprazole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions are listed below by body system: Gastrointestinal Disorders: fundic gland polyps General Disorders and Administration Conditions: asthenia, fatigue, malaise Hematologic: pancytopenia, agranulocytosis Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure Immune System Disorders: anaphylaxis (including anaphylactic shock), systemic lupus erythematosus Infections and Infestations: Clostridium difficile associated diarrhea Investigations: weight changes Metabolism and Nutritional Disorders: hyponatremia, hypomagnesemia Musculoskeletal Disorders: rhabdomyolysis, bone fracture Nervous: ageusia, dysgeusia Psychiatric Disorders: hallucination, confusion, insomnia, somnolence Renal and Urinary Disorders: interstitial nephritis Skin and Subcutaneous Tissue Disorders: severe dermatologic reactions (some fatal), including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN, some fatal), angioedema (Quincke’s edema) and cutaneous lupus erythematosus"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Table 4 includes drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with Pantoprazole and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. Table 4: Clinically Relevant Interactions Affecting Drugs Co-Administered with Pantoprazole and Interactions with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with Pantoprazole may reduce antiviral effect and promote the development of drug resistance. Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with Pantoprazole may increase toxicity of the antiretroviral drugs . There are other antiretroviral drugs which do not result in clinically relevant interactions with pantoprazole sodium. Intervention: Rilpivirine-containing products: Concomitant use with Pantoprazole is contraindicated [see Contraindications ( 4 )]. See prescribing information. Atazanavir: See prescribing information for atazanavir for dosing information. Nelfinavir: Avoid concomitant use with Pantoprazole. See prescribing information for nelfinavir. Saquinavir: See the prescribing information for saquinavir and monitor for potential saquinavir toxicities. Other antiretrovirals: See prescribing information. Warfarin Clinical Impact: Increased INR and prothrombin time in patients receiving PPIs, including pantoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Intervention: Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin. Clopidogrel Clinical Impact: Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidorgrel-induced platelet inhibition [see Clinical Pharmacology ( 12.3 )]. Intervention: No dose adjustment of clopidogrel is necessary when administered with an approved does of Pantoprazole. Methotrexate Clinical Impact: Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [see Warnings and Precautions ( 5.12 )]. Intervention: A temporary withdrawal of Pantoprazole may be considered in some patients receiving high-dose methotrexate. Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Impact: Pantoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity. Intervention: Mycophenolate mofetil (MMF): Co-administration of pantoprazole sodium in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH [see Clinical Pharmacology ( 12.3 )]. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving Pantoprazole and MMF. Use Pantoprazole with caution in transplant patients receiving MMF. See the prescribing information for other drugs dependent on gastric pH for absorption. Interactions with Investigation of Neuroendocrine Tumors Clinical Impact: CgA levels increase secondary PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors [see Warnings and Precautions ( 5.10 ), Clinical Pharmacology ( 12.2 )] Intervention: Temporarily stop Pantoprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary. False Positive Urine Tests for THC Clinical Impact: There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs [see Warnings and Precautions ( 5.11 )]. Intervention: An alternative confirmatory method should be considered to verify positive results. See full prescribing information for a list of clinically important drug interactions ( 7 )"}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Pantoprazole Sodium Delayed-Release Tablets, USP are indicated for: Pantoprazole is a proton pump inhibitor (PPI) indicated for the following: Short-Term Treatment of Erosive Esophagitis Associated with Gastroesophageal Reflux Disease (GERD) ( 1.1 ) Maintenance of Healing of Erosive Esophagitis ( 1.2 ) Pathological Hypersecretory Conditions Including Zollinger-Ellison (ZE) Syndrome ( 1.3 ) 1.1 Short-Term Treatment of Erosive Esophagitis Associated With Gastroesophageal Reflux Disease (GERD) Pantoprazole is indicated in adults and pediatric patients five years of age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis (EE). For those adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of Pantoprazole may be considered. Safety of treatment beyond 8 weeks in pediatric patients has not been established. 1.2 Maintenance of Healing of Erosive Esophagitis Pantoprazole is indicated for maintenance of healing of EE and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with GERD. Controlled studies did not extend beyond 12 months. 1.3 Pathological Hypersecretory Conditions Including Zollinger-Ellison (ZE) Syndrome Pantoprazole is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison (ZE) Syndrome."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Gastric Malignancy: In adults, symptomatic response does not preclude presence of gastric malignancy. Consider additional follow-up and diagnostic testing. ( 5.1 ) Acute Interstitial Nephritis: Observed in patients taking PPIs. ( 5.2 ) Clostridium difficile- Associated Diarrhea: PPI therapy may be associated with increased risk of Clostridium difficile -associated diarrhea. ( 5.3 ) Bone Fracture: Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. ( 5.4 ) Cutaneous and Systemic Lupus Erythematosus: Mostly cutaneous; new onset or exacerbation of existing disease; discontinue Pantoprazole and refer to specialist for evaluation. ( 5.5 ) Cyanocobalamin (Vitamin B-12) Deficiency: Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin. ( 5.6 ) Hypomagnesemia: Reported rarely with prolonged treatment with PPIs. ( 5.7 ) Fundic Gland Polyps: Risk increases with long-term use, especially beyond one year. Use the shortest duration of therapy. ( 5.9 ) 5.1 Presence of Gastric Malignancy In adults, symptomatic response to therapy with Pantoprazole does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy. 5.2 Acute Interstitial Nephritis Acute interstitial nephritis has been observed in patients taking PPIs including Pantoprazole. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue Pantoprazole if acute interstitial nephritis develops [see Contraindications ( 4 )]. 5.3 Clostridium difficile- Associated Diarrhea Published observational studies suggest that PPI therapy like Pantoprazole may be associated with an increased risk of Clostridium difficile associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions ( 6.2 )]. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. 5.4 Bone Fracture Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration ( 2 ), Adverse Reactions ( 6.2 )]. 5.5 Cutaneous and Systemic Lupus Erythematosus Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including pantoprazole sodium. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematous cases were CLE. The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement. Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported. Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving Pantoprazole, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g. ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations. 5.6 Cyanocobalamin (Vitamin B-12) Deficiency Generally, daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (Vitamin B-12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed. 5.7 Hypomagnesemia Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions ( 6.2 )]. 5.8 Tumorigenicity Due to the chronic nature of GERD, there may be a potential for prolonged administration of Pantoprazole. In long-term rodent studies, pantoprazole was carcinogenic and caused rare types of gastrointestinal tumors. The relevance of these findings to tumor development in humans is unknown [see Nonclinical Toxicology ( 13.1 )]. 5.9 Fundic Gland Polyps PPI use is associated with an increased risk of fundic gland polyps that increases with long\xad term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated. 5.10 Interference with Investigations for Neuroendocrine Tumors Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop Pantoprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may very [see Clinical Pharmacology ( 12.2 )]. 5.11 Interference with Urine Screen for THC There have been reports of false-positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including Pantoprazole [see Drug Interactions ( 7 )]. 5.12 Concomitant Use of Pantoprazole with Methotrexate Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions ( 7 )]."}', 'overdosage': '{"10 OVERDOSAGE Experience in patients taking very high doses of Pantoprazole (greater than 240 mg) is limited. Spontaneous post-marketing reports of overdose are generally within the known safety profile of Pantoprazole. Pantoprazole is not removed by hemodialysis. In case of overdosage, treatment should be symptomatic and supportive. Single oral doses of pantoprazole at 709 mg/kg, 798 mg/kg, and 887 mg/kg were lethal to mice, rats, and dogs, respectively. The symptoms of acute toxicity were hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor. If overexposure to Pantoprazole occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage."}', 'active_flag': 'Y', 'generic_name': '{"PANTOPRAZOLE SODIUM"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Gastric Malignancy Advise patients to return to their healthcare provider if they have a suboptimal response or an early symptomatic relapse [see Warnings and Precautions ( 5.1 )]. Acute Interstitial Nephritis Advise patients to call their healthcare provider immediately if they experience signs and/or symptoms associated with acute interstitial nephritis [see Warnings and Precautions ( 5.2 )]. Clostridium difficile -Associated Diarrhea Advise patients to immediately call their healthcare provider if they experience diarrhea that does not improve [see Warnings and Precautions ( 5.3 )]. Bone Fracture Advise patients to report any fractures, especially of the hip, wrist or spine, to their healthcare provider [see Warnings and Precautions ( 5.4 )]. Cutaneous and Systemic Lupus Erythematosus Advise patients to immediately call their healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus [see Warnings and Precautions ( 5.5 )]. Cyanocobalamin (Vitamin B-12) Deficiency Advise patients to report any clinical symptoms that may be associated with cyancobalamin deficiency to their healthcare provider if they have been receiving Pantoprazole for longer than 3 years [see Warnings and Precautions ( 5.6 )]. Hypomagnesemia Advise patients to report any clinical symptoms that may be associated with hypomagnesemia to their healthcare provider, if they have been receiving Pantoprazole for at least 3 months [see Warnings and Precautions ( 5.7 )]. Drug Interactions Instruct patients to inform their healthcare provider of any other medications they are currently taking, including rilpivirine-containing products [see Contraindications ( 4 )] digoxin [see Warnings and Precautions ( 5.7 )] and high dose methotrexate [see Warnings and Precautions ( 5.12 )] . Pregnancy Inform female patients of reproductive potential that Pantoprazole may cause fetal harm and to inform their prescriber of a known or suspected pregnancy [see Use in Specific Populations ( 8.1 )]. Administration Do not split, crush, or chew Pantoprazole Sodium Delayed-Release Tablets. Swallow Pantoprazole Sodium Delayed-Release Tablets whole, with or without food in the stomach. Concomitant administration of antacids does not affect the absorption of Pantoprazole Sodium Delayed-Release Tablets. Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and take the next dose at the regular scheduled time. Do not take 2 doses at the same time. This product’s label may have been updated. For current full prescribing information, call 1-844-834-0530. Distributed by: Lannett Company, Inc. Philadelphia, PA 19154 CIA72949R Rev. 06/2018"}', 'pregnancy': '{"8.1 Pregnancy Teratogenic Effects Pregnancy Category C Reproduction studies have been performed in rats at oral pantoprazole doses up to 450 mg/kg/day (about 88 times the recommended human dose based on body surface area) and in rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose based on body surface area) with administration of pantoprazole sodium during organogenesis in pregnant animals. The studies have revealed no evidence of impaired fertility or harm to the fetus due to pantoprazole. A pre- and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. Oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day on a body surface area basis) were administered to pregnant females from gestation day (GD) 6 through lactation day (LD) 21. On postnatal day (PND 4) through PND 21, the pups were administered oral doses at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (AUC) in humans at a dose of 40 mg). There were no drug-related findings in maternal animals. During the preweaning dosing phase (PND 4 to 21) of the pups, there were increased mortality and/or moribundity and decreased body weight and body weight gain at 5 mg/kg/day (approximately equal exposures (AUC) in humans receiving the 40 mg dose) and higher doses. On PND 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (AUC) in humans at the 40 mg dose) and higher doses. The femur findings included lower total area, bone mineral content and density, periosteal and endosteal circumference, and cross-sectional moment of inertia. There were no microscopic changes in the distal femur, proximal tibia, or stifle joints. Changes in bone parameters were partially reversible following a recovery period, with findings on PND 70 limited to lower femur metaphysis cortical/subcortical bone mineral density in female pups at 5 mg/kg/day (approximately equal exposures (AUC) in humans at the 40 mg dose) and higher doses. There are no adequate and well-controlled studies in pregnant women. Advise pregnant women of the potential risk of fetal harm. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness of Pantoprazole for short-term treatment (up to eight weeks) of EE associated with GERD have been established in pediatric patients 1 year through 16 years of age. Effectiveness for EE has not been demonstrated in patients less than 1 year of age. In addition, for patients less than 5 years of age, there is no appropriate dosage strength in an age-appropriate formulation available. Therefore, Pantoprazole is indicated for the short-term treatment of EE associated with GERD for patients 5 years and older. The safety and effectiveness of Pantoprazole for pediatric uses other than EE have not been established. 1 year through 16 years of age Use of Pantoprazole in pediatric patients 1 year through 16 years of age for short-term treatment (up to eight weeks) of EE associated with GERD is supported by: a) extrapolation of results from adequate and well-controlled studies that supported the approval of Pantoprazole for treatment of EE associated with GERD in adults, and b) safety, effectiveness, and pharmacokinetic studies performed in pediatric patients [see Clinical Studies ( 14.1 ), Clinical Pharmacology ( 12.3 )]. Safety of Pantoprazole in the treatment of EE associated with GERD in pediatric patients 1 through 16 years of age was evaluated in three multicenter, randomized, double-blind, parallel-treatment studies, involving 249 pediatric patients, including 8 with EE (4 patients ages 1 year to 5 years and 4 patients 5 years to 11 years). The children ages 1 year to 5 years with endoscopically diagnosed EE (defined as an endoscopic Hetzel-Dent score ≥ 2) were treated once daily for 8 weeks with one of two dose levels of Pantoprazole (approximating 0.6 mg/kg or 1.2 mg/kg). All 4 of these patients with EE were healed (Hetzel-Dent score of 0 or 1) at 8 weeks. Because EE is uncommon in the pediatric population, predominantly pediatric patients with endoscopically-proven or symptomatic GERD were also included in these studies. Patients were treated with a range of doses of Pantoprazole once daily for 8 weeks. For safety findings see Adverse Reactions ( 6.1 ) . Because these pediatric trials had no placebo, active comparator, or evidence of a dose response, the trials were inconclusive regarding the clinical benefit of Pantoprazole for symptomatic GERD in the pediatric population. The effectiveness of Pantoprazole for treating symptomatic GERD in pediatric patients has not been established. Although the data from the clinical trials support use of Pantoprazole for the short-term treatment of EE associated with GERD in pediatric patients 1 year through 5 years, there is no commercially available dosage formulation appropriate for patients less than 5 years of age [see Dosage and Administration ( 2 )]. In a population pharmacokinetic analysis, clearance values in the children 1 to 5 years old with endoscopically proven GERD had a median value of 2.4 L/h. Following a 1.2 mg/kg equivalent dose (15 mg for ≤ 12.5 kg and 20 mg for > 12.5 to < 25 kg), the plasma concentrations of pantoprazole were highly variable and the median time to peak plasma concentration was 3 to 6 hours. The estimated AUC for patients 1 to 5 years old was 37% higher than for adults receiving a single 40 mg tablet, with a geometric mean AUC value of 6.8 mcg•hr/mL. Neonates to less than one year of age Pantoprazole was not found to be effective in a multicenter, randomized, double-blind, placebo-controlled, treatment-withdrawal study of 129 pediatric patients 1 through 11 months of age. Patients were enrolled if they had symptomatic GERD based on medical history and had not responded to non-pharmacologic interventions for GERD for two weeks. Patients received Pantoprazole daily for four weeks in an open-label phase, then patients were randomized in equal proportion to receive Pantoprazole treatment or placebo for the subsequent four weeks in a double-blind manner. Efficacy was assessed by observing the time from randomization to study discontinuation due to symptom worsening during the four-week treatment-withdrawal phase. There was no statistically significant difference between Pantoprazole and placebo in the rate of discontinuation. In this trial, the adverse reactions that were reported more commonly (difference of ≥ 4%) in the treated population compared to the placebo population were elevated CK, otitis media, rhinitis, and laryngitis. In a population pharmacokinetic analysis, the systemic exposure was higher in patients less than 1 year of age with GERD compared to adults who received a single 40 mg dose (geometric mean AUC was 103% higher in preterm infants and neonates receiving single dose of 2.5 mg of Pantoprazole, and 23% higher in infants 1 through 11 months of age receiving a single dose of approximately 1.2 mg/kg). In these patients, the apparent clearance (CL/F) increased with age (median clearance: 0.6 L/hr, range: 0.03 to 3.2 L/hr). These doses resulted in pharmacodynamic effects on gastric but not esophageal pH. Following once daily dosing of 2.5 mg of Pantoprazole in preterm infants and neonates, there was an increase in the mean gastric pH (from 4.3 at baseline to 5.2 at steady-state) and in the mean % time that gastric pH was > 4 (from 60% at baseline to 80% at steady-state). Following once daily dosing of approximately 1.2 mg/kg of Pantoprazole in infants 1 through 11 months of age, there was an increase in the mean gastric pH (from 3.1 at baseline to 4.2 at steady-state) and in the mean % time that gastric pH was > 4 (from 32% at baseline to 60% at steady-state). However, no significant changes were observed in mean intraesophageal pH or % time that esophageal pH was < 4 in either age group. Because Pantoprazole was not shown to be effective in the randomized, placebo-controlled study in this age group, the use of Pantoprazole for treatment of symptomatic GERD in infants less than 1 year of age is not indicated. Animal Toxicity Data In a pre- and post-natal development study in rats, the pups were administered oral doses of pantoprazole at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (AUC) in children aged 6 to 11 years at a dose of 40 mg) on postnatal day (PND 4) through PND 21, in addition to lactational exposure through milk. On PND 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (AUC) in children aged 6 to 11 years at the 40 mg dose) and higher doses. Changes in bone parameters were partially reversible following a recovery period. In neonatal/juvenile animals (rats and dogs) toxicities were similar to those observed in adult animals, including gastric alterations, decreases in red cell mass, increases in lipids, enzyme induction and hepatocellular hypertrophy. An increased incidence of eosinophilic chief cells in adult and neonatal/juvenile rats, and atrophy of chief cells in adult rats and in neonatal/juvenile dogs, was observed in the fundic mucosa of stomachs in repeated-dose studies. Full to partial recovery of these effects were noted in animals of both age groups following a recovery period."}', 'geriatric_use': '{"8.5 Geriatric Use In short-term US clinical trials, EE healing rates in the 107 elderly patients (≥ 65 years old) treated with Pantoprazole were similar to those found in patients under the age of 65. The incidence rates of adverse reactions and laboratory abnormalities in patients aged 65 years and older were similar to those associated with patients younger than 65 years of age."}'}

{"DARIFENACIN HYDROBROMIDE"}

{'contraindications': '{"4 CONTRAINDICATIONS Darifenacin is contraindicated in patients with, or at risk for, the following conditions: urinary retention gastric retention, or uncontrolled narrow-angle glaucoma. Darifenacin is contraindicated in patients with, or at risk for, the following conditions ( 4 ): urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The most frequently reported adverse reactions (>3 percent) for darifenacin are: constipation, dry mouth, headache, dyspepsia, nausea, urinary tract infection, accidental injury, and flu symptoms. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Polygen Pharmaceuticals Inc. at 1-888-291-7337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of darifenacin was evaluated in controlled clinical trials in a total of 8,830 patients, 6,001 of whom were treated with darifenacin. Of this total, 1,069 patients participated in three, 12-week, randomized, placebo-controlled, fixed-dose efficacy and safety studies (Studies 1, 2 and 3). Of this total, 337 and 334 patients received darifenacin 7.5 mg daily and 15 mg daily, respectively. In all long-term trials combined, 1,216 and 672 patients received treatment with darifenacin for at least 24 and 52 weeks, respectively. In Studies 1, 2 and 3 combined, the serious adverse reactions to darifenacin were urinary retention and constipation. In Studies 1, 2 and 3 combined, dry mouth leading to study discontinuation occurred in 0 percent, 0.9 percent, and 0 percent of patients treated with darifenacin 7.5 mg daily, darifenacin 15 mg daily and placebo, respectively. Constipation leading to study discontinuation occurred in 0.6 percent, 1.2 percent, and 0.3 percent of patients treated with darifenacin 7.5 mg daily, darifenacin 15 mg daily and placebo, respectively. Table 1 lists the rates of identified adverse reactions, derived from all reported adverse events in 2 percent or more of patients treated with 7.5 mg or 15 mg darifenacin, and greater than placebo in Studies 1, 2 and 3. In these studies, the most frequently reported adverse reactions were dry mouth and constipation. The majority of the adverse reactions were mild or moderate in severity and most occurred during the first two weeks of treatment. Table 1: Incidence of Identified Adverse Reactions, Derived from All Adverse Events Reported in ≥2 Percent of Patients Treated with Darifenacin Extended-Release Tablets and More Frequent with Darifenacin than with Placebo in Studies 1, 2, and 3 Body System Adverse Reaction Percentage of Subjects Darifenacin 7.5 mg N = 337 Darifenacin 15 mg N = 334 Placebo N = 388 Digestive Dry Mouth 20.2 35.3 8.2 Constipation 14.8 21.3 6.2 Dyspepsia 2.7 8.4 2.6 Abdominal Pain 2.4 3.9 0.5 Nausea 2.7 1.5 1.5 Diarrhea 2.1 0.9 1.8 Urogenital Urinary Tract Infection 4.7 4.5 2.6 Nervous Dizziness 0.9 2.1 1.3 Body as whole Asthenia 1.5 2.7 1.3 Eye Dry Eyes 1.5 2.1 0.5 Other adverse reactions reported by 1 percent to 2 percent of darifenacin-treated patients include: abnormal vision, accidental injury, back pain, dry skin, flu syndrome, hypertension, vomiting, peripheral edema, weight gain, arthralgia, bronchitis, pharyngitis, rhinitis, sinusitis, rash, pruritus, urinary tract disorder and vaginitis. Study 4 was a randomized, 12-week, placebo-controlled, dose-titration regimen study in which darifenacin was administered in accordance with dosing recommendations [see Dosage and Administration (2) ] . All patients initially received placebo or darifenacin 7.5 mg daily, and after two weeks, patients and physicians were allowed to adjust upward to darifenacin 15 mg if needed. In this study, the most commonly reported adverse reactions were also constipation and dry mouth. Table 2 lists the identified adverse reactions, derived from all adverse events reported in >3 percent of patients treated with darifenacin and greater than placebo. Table 2: Number (Percent) of Adverse Reactions, Derived from All Adverse Events Reported in >3 Percent of Patients Treated with Darifenacin Extended-Release Tablets, and More Frequent with Darifenacin than Placebo, in Study 4 Adverse Reaction Darifenacin 7.5 mg/15 mg N = 268 Placebo N = 127 Constipation 56 (20.9 percent) 10 (7.9 percent) Dry Mouth 50 (18.7 percent) 11 (8.7 percent) Headache 18 (6.7 percent) 7 (5.5 percent) Dyspepsia 12 (4.5 percent) 2 (1.6 percent) Nausea 11 (4.1 percent) 2 (1.6 percent) Urinary Tract Infection 10 (3.7 percent) 4 (3.1 percent) Accidental Injury 8 (3.0 percent) 3 (2.4 percent) Flu Syndrome 8 (3.0 percent) 3 (2.4 percent) 6.2 Post Marketing Experience The following adverse reactions have been reported during post approval use of darifenacin extended-release tablets (darifenacin). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate frequency or establish a causal relationship to drug exposure. Dermatologic: erythema multiforme, interstitial granuloma annulare General: hypersensitivity reactions, including angioedema with airway obstruction and anaphylactic reaction Central Nervous: confusion, hallucinations and somnolence Cardiovascular: palpitations and syncope"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Caution should be taken when darifenacin is used concomitantly with medications that are predominantly metabolized by CYP2D6 and which have a narrow therapeutic window, such as flecainide, thioridazine and tricyclic antidepressants. ( 7.2 ) The concomitant use of darifenacin with other anticholinergic agents may increase the frequency and/or severity of dry mouth, constipation, blurred vision and other anticholinergic pharmacological effects. Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to effects of gastrointestinal motility. ( 7.3 ) 7.1 CYP3A4 Inhibitors The systemic exposure of darifenacin from darifenacin extended-release tablets is increased in the presence of CYP3A4 inhibitors. The daily dose of darifenacin should not exceed 7.5 mg when co-administered with potent CYP3A4 inhibitors (for example, ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin and nefazadone). No dosing adjustments are recommended in the presence of moderate CYP3A4 inhibitors (for example, erythromycin, fluconazole, diltiazem and verapamil) [see Dosage and Administration (2) and Clinical Pharmacology (12.3) ] . 7.2 CYP2D6 Inhibitors No dosing adjustments are recommended in the presence of CYP2D6 inhibitors (for example, paroxetine, fluoxetine, quinidine and duloxetine) [see Clinical Pharmacology (12.3) ] . 7.3 CYP2D6 Substrates Caution should be taken when darifenacin is used concomitantly with medications that are predominantly metabolized by CYP2D6 and which have a narrow therapeutic window (for example, flecainide, thioridazine and tricyclic antidepressants) [see Clinical Pharmacology (12.3) ] . 7.4 CYP3A4 Substrates Darifenacin (30 mg daily) did not have a significant impact on midazolam (7.5 mg) pharmacokinetics [see Clinical Pharmacology (12.3) ] . 7.5 Combination oral contraceptives Darifenacin (10 mg three times daily) had no effect on the pharmacokinetics of the combination oral contraceptives containing levonorgestrel and ethinyl estradiol [see Clinical Pharmacology (12.3) ] . 7.6 Warfarin Darifenacin had no significant effect on prothrombin time when a single dose of warfarin 30 mg was co-administered with darifenacin (30 mg daily) at steady-state. Standard therapeutic prothrombin time monitoring for warfarin should be continued. 7.7 Digoxin Darifenacin (30 mg daily) did not have a clinically relevant effect on the pharmacokinetics of digoxin (0.25 mg) at steady-state. Routine therapeutic drug monitoring for digoxin should be continued [see Clinical Pharmacology (12.3) ] . 7.8 Other Anticholinergic Agents The concomitant use of darifenacin with other anticholinergic agents may increase the frequency and/or severity of dry mouth, constipation, blurred vision and other anticholinergic pharmacological effects. Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to effects on gastrointestinal motility."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Darifenacin extended-release tablets are muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency. Darifenacin is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency. ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Darifenacin should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention. ( 5.1 ) Darifenacin should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention. ( 5.2 ) Darifenacin should be used with caution in patients being treated for narrow- angle glaucoma and only where the potential benefits outweigh the risks. ( 5.3 ) Central Nervous System Effects: Somnolence has been reported with darifenacin. Advise patients not to drive or operate heavy machinery until they know how darifenacin affects them. ( 5.5 ) 5.1 Risk of Urinary Retention Darifenacin should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention. 5.2 Decreased Gastrointestinal Motility Darifenacin should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention. Darifenacin, like other anticholinergic drugs, may decrease gastrointestinal motility and should be used with caution in patients with conditions such as severe constipation, ulcerative colitis, and myasthenia gravis. 5.3 Controlled Narrow-Angle Glaucoma Darifenacin should be used with caution in patients being treated for narrow-angle glaucoma and only where the potential benefits outweigh the risks. 5.4 Angioedema Angioedema of the face, lips, tongue, and/or larynx have been reported with darifenacin. In some cases angioedema occurred after the first dose. Angioedema associated with upper airway swelling may be life threatening. If involvement of the tongue, hypopharynx, or larynx occurs, darifenacin should be promptly discontinued and appropriate therapy and/or measures necessary to ensure a patent airway should be promptly provided. 5.5 Central Nervous System Effects Darifenacin is associated with anticholinergic central nervous system (CNS) effects [see Adverse Reactions (6.2) ]. A variety of CNS anticholinergic effects have been reported, including headache, confusion, hallucinations and somnolence. Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing the dose. Advise patients not to drive or operate heavy machinery until they know how darifenacin affects them. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered. 5.6 Patients with Hepatic Impairment The daily dose of darifenacin should not exceed 7.5 mg for patients with moderate hepatic impairment (Child-Pugh B). Darifenacin has not been studied in patients with severe hepatic impairment (Child-Pugh C) and therefore is not recommended for use in this patient population [see Dosage and Administration (2) Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] ."}', 'overdosage': '{"10 OVERDOSAGE Overdosage with antimuscarinic agents, including darifenacin, can result in severe antimuscarinic effects. Treatment should be symptomatic and supportive. In the event of overdosage, ECG monitoring is recommended. Darifenacin has been administered in clinical trials at doses up to 75 mg (five times the maximum therapeutic dose) and signs of overdose were limited to abnormal vision."}', 'active_flag': 'Y', 'generic_name': '{"DARIFENACIN HYDROBROMIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION “See FDA-approved patient labeling (Patient Information)” Patients should be informed that anticholinergic agents, such as darifenacin, may produce clinically significant adverse effects related to anticholinergic pharmacological activity including constipation, urinary retention and blurred vision. Heat prostration (due to decreased sweating) can occur when anticholinergics such as darifenacin are used in a hot environment. Because anticholinergics, such as darifenacin, may produce dizziness or blurred vision, patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until the drug’s effects have been determined. Patients should read the patient information leaflet before starting therapy with darifenacin. Patients should be informed that darifenacin may produce clinically significant angioedema that may result in airway obstruction. Patients should be advised to promptly discontinue darifenacin therapy and seek immediate medical attention if they experience edema of the tongue or laryngopharynx, or difficulty breathing. Darifenacin extended-release tablets should be taken once daily with water. They may be taken with or without food, and should be swallowed whole and not chewed, divided or crushed."}', 'pregnancy': '{"8.1 Pregnancy Pregnancy Category C There are no studies of darifenacin in pregnant women. Darifenacin was not teratogenic in rats and rabbits at plasma exposures of free drug (via AUC) up to 59 times and 28 times, respectively (doses up to 50 and 30 mg/kg/day, respectively) the maximum recommended human dose [MRHD] of 15 mg. At approximately 59 times the MRHD in rats, there was a delay in the ossification of the sacral and caudal vertebrae which was not observed at approximately 13 times the AUC. Dystocia was observed in dams at approximately 17 times the AUC (10 mg/kg/day). Slight developmental delays were observed in pups at this dose. At five times the AUC (3 mg/kg/day), there were no effects on dams or pups. In rabbits, an exposure approximately 28 times (30 mg/kg/day) the MRHD of darifenacin was shown to increase post-implantation loss, with a no effect level at nine times (10 mg/kg/day) the AUC at the MRHD. Dilated ureter and/or kidney pelvis was also observed in offspring at this dose along with urinary bladder dilation consistent with the pharmacological action of darifenacin, with one case observed at nine times (10 mg/kg/day). No effect was observed at approximately 2.8 times (3 mg/kg/day) the AUC at the MRHD. Because animal reproduction studies are not always predictive of human response, darifenacin should be used during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness of darifenacin in pediatric patients have not been established."}', 'geriatric_use': '{"8.5 Geriatric Use In the fixed-dose, placebo-controlled, clinical studies, 30 percent of patients treated with darifenacin were over 65 years of age. No overall differences in safety or efficacy were observed between patients over 65 years (n = 207) and younger patients <65 years (n = 464). No dose adjustment is recommended for elderly patients [see Clinical Pharmacology (12.3) and Clinical Studies (14) ] ."}'}

{"FLUPHENAZINE HYDROCHLORIDE"}

{'contraindications': '{"CONTRAINDICATIONS Phenothiazines are contraindicated in patients with suspected or established subcortical brain damage, in patients receiving large doses of hypnotics, and in comatose or severely depressed states. The presence of blood dyscrasia or liver damage precludes the use of fluphenazine hydrochloride. Fluphenazine hydrochloride tablets are contraindicated in patients who have shown hypersensitivity to fluphenazine; cross-sensitivity to phenothiazine derivatives may occur."}', 'adverse_reactions': '{"ADVERSE REACTIONS Central Nervous System The side effects most frequently reported with phenothiazine compounds are extrapyramidal symptoms including pseudoparkinsonism, dystonia, dyskinesia, akathisia, oculogyric crises, opisthotonos, and hyperreflexia. Most often these extrapyramidal symptoms are reversible; however, they may be persistent (see below). With any given phenothiazine derivative, the incidence and severity of such reactions depend more on individual patient sensitivity than on other factors, but dosage level and patient age are also determinants. Extrapyramidal reactions may be alarming, and the patient should be forewarned and reassured. These reactions can usually be controlled by administration of antiparkinsonian drugs such as benztropine mesylate or intravenous caffeine and sodium benzoate injection, and by subsequent reduction in dosage. Extrapyramidal Symptoms Dystonia Class Effect Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups. Tardive Dyskinesia See WARNINGS . The syndrome is characterized by involuntary choreoathetoid movements which variously involve the tongue, face, mouth, lips, or jaw (e.g., protrusion of the tongue, puffing of cheeks, puckering of the mouth, chewing movements), trunk and extremities. The severity of the syndrome and the degree of impairment produced vary widely. The syndrome may become clinically recognizable either during treatment, upon dosage reduction, or upon withdrawal of treatment. Early detection of tardive dyskinesia is important. To increase the likelihood of detecting the syndrome at the earliest possible time, the dosage of neuroleptic drug should be reduced periodically (if clinically possible) and the patient observed for signs of the disorder. This maneuver is critical, since neuroleptic drugs may mask the signs of the syndrome. Other CNS Effects Occurrences of neuroleptic malignant syndrome (NMS) have been reported in patients on neuroleptic therapy (see WARNINGS: Neuroleptic Malignant Syndrome ); leukocytosis, elevated CPK, liver function abnormalities, and acute renal failure may also occur with NMS. Drowsiness or lethargy, if they occur, may necessitate a reduction in dosage; the induction of a catatonic-like state has been known to occur with dosages of fluphenazine far in excess of the recommended amounts. As with other phenothiazine compounds, reactivation or aggravation of psychotic processes may be encountered. Phenothiazine derivatives have been known to cause, in some patients, restlessness, excitement, or bizarre dreams. Autonomic Nervous System Hypertension and fluctuations in blood pressure have been reported with fluphenazine hydrochloride. Hypotension has rarely presented a problem with fluphenazine. However, patients with pheochromocytoma, cerebral vascular or renal insufficiency, or a severe cardiac reserve deficiency such as mitral insufficiency appear to be particularly prone to hypotensive reactions with phenothiazine compounds, and should therefore be observed closely when the drug is administered. If severe hypotension should occur, supportive measures including the use of intravenous vasopressor drugs should be instituted immediately. Norepinephrine bitartrate injection is the most suitable drug for this purpose; epinephrine should not be used since phenothiazine derivatives have been found to reverse its action, resulting in a further lowering of blood pressure. Autonomic reactions including nausea and loss of appetite, salivation, polyuria, perspiration, dry mouth, headache, and constipation may occur. Autonomic effects can usually be controlled by reducing or temporarily discontinuing dosage. In some patients, phenothiazine derivatives have caused blurred vision, glaucoma, bladder paralysis, fecal impaction, paralytic ileus, tachycardia, or nasal congestion. Metabolic and Endocrine Weight change, peripheral edema, abnormal lactation, gynecomastia, menstrual irregularities, false results on pregnancy tests, impotency in men and increased libido in women have all been known to occur in some patients on phenothiazine therapy. Allergic Reactions Skin disorders such as itching, erythema, urticaria, seborrhea, photosensitivity, eczema and even exfoliative dermatitis have been reported with phenothiazine derivatives. The possibility of anaphylactoid reactions occurring in some patients should be borne in mind. Hematologic Routine blood counts are advisable during therapy since blood dyscrasias including leukopenia, agranulocytosis, thrombocytopenic or nonthrombocytopenic purpura, eosinophilia, and pancytopenia have been observed with phenothiazine derivatives. Furthermore, if any soreness of the mouth, gums, or throat, or any symptoms of upper respiratory infection occur and confirmatory leukocyte count indicates cellular depression, therapy should be discontinued and other appropriate measures instituted immediately. Hepatic Liver damage as manifested by cholestatic jaundice may be encountered, particularly during the first months of therapy; treatment should be discontinued if this occurs. An increase in cephalin flocculation, sometimes accompanied by alterations in other liver function tests, has been reported in patients receiving fluphenazine hydrochloride who have had no clinical evidence of liver damage. Others Sudden, unexpected and unexplained deaths have been reported in hospitalized psychotic patients receiving phenothiazines. Previous brain damage or seizures may be predisposing factors; high doses should be avoided in known seizure patients. Several patients have shown sudden flare-ups of psychotic behavior patterns shortly before death. Autopsy findings have usually revealed acute fulminating pneumonia or pneumonitis, aspiration of gastric contents, or intramyocardial lesions. Although this is not a general feature of fluphenazine, potentiation of central nervous system depressants (opiates, analgesics, antihistamines, barbiturates, alcohol) may occur. The following adverse reactions have also occurred with phenothiazine derivatives: systemic lupus erythematosus-like syndrome, hypotension severe enough to cause fatal cardiac arrest, altered electrocardiographic and electroencephalographic tracings, altered cerebrospinal fluid proteins, cerebral edema, asthma, laryngeal edema, and angioneurotic edema; with long-term use–skin pigmentation, and lenticular and corneal opacities. To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE Fluphenazine hydrochloride tablets are indicated in the management of manifestations of psychotic disorders. Fluphenazine hydrochloride has not been shown effective in the management of behavioral complications in patients with mental retardation."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"FLUPHENAZINE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Fluphenazine hydrochloride is not approved for the treatment of patients with dementia-related psychosis (see BOXED WARNING ). Tardive Dyskinesia Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with neuroleptic (antipsychotic) drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of neuroleptic treatment, which patients are likely to develop the syndrome. Whether neuroleptic drug products differ in their potential to cause tardive dyskinesia is unknown. Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of neuroleptic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if neuroleptic treatment is withdrawn. Neuroleptic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying disease process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. Given these considerations, neuroleptics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic neuroleptic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to neuroleptic drugs, and, 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically. If signs and symptoms of tardive dyskinesia appear in a patient on neuroleptics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome. (For further information about the description of tardive dyskinesia and its clinical detection, please refer to the sections on PRECAUTIONS: Information for Patients and ADVERSE REACTIONS: Tardive Dyskinesia ). Neuroleptic Malignant Syndrome (NMS) A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias). The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology. The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS. If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported. The use of this drug may impair the mental and physical abilities required for driving a car or operating heavy machinery. Potentiation of the effects of alcohol may occur with the use of this drug. Since there is no adequate experience in children who have received this drug, safety and efficacy in children have not been established. Falls Fluphenazine hydrochloride tablets may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy. Usage in Pregnancy The safety for the use of this drug during pregnancy has not been established; therefore, the possible hazards should be weighed against the potential benefits when administering this drug to pregnant patients. Pregnancy Nonteratogenic Effects Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Fluphenazine hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus."}', 'precautions': '{"PRECAUTIONS General Because of the possibility of cross-sensitivity, fluphenazine hydrochloride should be used cautiously in patients who have developed cholestatic jaundice, dermatoses or other allergic reactions to phenothiazine derivatives. Psychotic patients on large doses of a phenothiazine drug who are undergoing surgery should be watched carefully for possible hypotensive phenomena. Moreover, it should be remembered that reduced amounts of anesthetics or central nervous system depressants may be necessary. The effects of atropine may be potentiated in some patients receiving fluphenazine because of added anticholinergic effects. Fluphenazine hydrochloride should be used cautiously in patients exposed to extreme heat or phosphorus insecticides; in patients with a history of convulsive disorders, since grand mal convulsions have been known to occur; and in patients with special medical disorders, such as mitral insufficiency or other cardiovascular diseases and pheochromocytoma. The possibility of liver damage, pigmentary retinopathy, lenticular and corneal deposits, and development of irreversible dyskinesia should be remembered when patients are on prolonged therapy. Neuroleptic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro , a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of neuroleptic drugs. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time. Information for Patients Given the likelihood that some patients exposed chronically to neuroleptics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk. The decision to inform patients and/or their guardians must obviously take into account the clinical circumstances and the competency of the patient to understand the information provided. Abrupt Withdrawal In general, phenothiazines do not produce psychic dependence; however, gastritis, nausea and vomiting, dizziness, and tremulousness have been reported following abrupt cessation of high dose therapy. Reports suggest that these symptoms can be reduced if concomitant antiparkinsonian agents are continued for several weeks after the phenothiazine is withdrawn. Facilities should be available for periodic checking of hepatic function, renal function and the blood picture. Renal function of patients on long-term therapy should be monitored; if BUN (blood urea nitrogen) becomes abnormal, treatment should be discontinued. As with any phenothiazine, the physician should be alert to the possible development of “silent pneumonias” in patients under treatment with fluphenazine hydrochloride. Leukopenia, Neutropenia and Agranulocytosis In clinical trial and post-marketing experience, events of leukopenia/neutropenia and agranulocytosis have been reported temporally related to antipsychotic agents. Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia. Patients with a preexisting low WBC or a history of drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue fluphenazine hydrochloride tablets at the first sign of a decline in WBC in the absence of other causative factors. Patients with neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms occur. Patients with severe neutropenia (absolute neutrophil count < 1000/mm 3 ) should discontinue fluphenazine hydrochloride tablets and have their WBC followed until recovery."}', 'information_for_patients': '{"Information for Patients Given the likelihood that some patients exposed chronically to neuroleptics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk. The decision to inform patients and/or their guardians must obviously take into account the clinical circumstances and the competency of the patient to understand the information provided."}', 'pregnancy': '{"Pregnancy Nonteratogenic Effects Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Fluphenazine hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus."}', 'pediatric_use': None, 'geriatric_use': None}

{"SENNOSIDES A AND B"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses For relief of occasional constipation and irregularity. This product produces a bowel movement in 6 to 12 hours."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{SENNOSIDES}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings Do not use laxative products for more than one week unless directed by a doctor Ask a doctor before use if you have stomach pains, nausea, vomiting, notice a sudden change in bowel habits that continues over a period of 2 weeks. Stop use and ask a doctor if rectal bleeding or failure to have a bowel movement occur after use of a laxative. These could be signs of a serious condition. If Pregnant or breast-feeding ask a health professional before use."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"ENALAPRIL MALEATE"}

{'contraindications': '{"CONTRAINDICATIONS Enalapril maleate is contraindicated in patients who are hypersensitive to this product and in patients with a history of angioedema related to previous treatment with an angiotensin-converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema. Do not coadminister aliskiren with enalapril maleate in patients with diabetes (see PRECAUTIONS, Drug Interactions ). Enalapril maleate is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer enalapril maleate within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor (see WARNINGS, Head and Neck Angioedema )."}', 'adverse_reactions': '{"ADVERSE REACTIONS Enalapril maleate has been evaluated for safety in more than 10,000 patients, including over 1000 patients treated for one year or more. Enalapril maleate has been found to be generally well tolerated in controlled clinical trials involving 2987 patients. For the most part, adverse experiences were mild and transient in nature. In clinical trials, discontinuation of therapy due to clinical adverse experiences was required in 3.3 percent of patients with hypertension and in 5.7 percent of patients with heart failure. The frequency of adverse experiences was not related to total daily dosage within the usual dosage ranges. In patients with hypertension the overall percentage of patients treated with enalapril maleate reporting adverse experiences was comparable to placebo. Hypertension Adverse experiences occurring in greater than one percent of patients with hypertension treated with enalapril maleate in controlled clinical trials are shown below. In patients treated with enalapril maleate, the maximum duration of therapy was three years; in placebo-treated patients the maximum duration of therapy was 12 weeks. Enalapril Maleate (n = 2314) Incidence (discontinuation) Placebo (n = 230) Incidence Body As A Whole Fatigue 3.0 (<0.1) 2.6 Orthostatic Effects 1.2 (<0.1) 0.0 Asthenia 1.1 (0.1) 0.9 Digestive Diarrhea 1.4 (<0.1) 1.7 Nausea 1.4 (0.2) 1.7 Nervous/Psychiatric Headache 5.2 (0.3) 9.1 Dizziness 4.3 (0.4) 4.3 Respiratory Cough 1.3 (0.1) 0.9 Skin Rash 1.4 (0.4) 0.4 Heart Failure Adverse experiences occurring in greater than one percent of patients with heart failure treated with enalapril maleate are shown below. The incidences represent the experiences from both controlled and uncontrolled clinical trials (maximum duration of therapy was approximately one year). In the placebo-treated patients, the incidences reported are from the controlled trials (maximum duration of therapy is 12 weeks). The percentage of patients with severe heart failure (NYHA Class IV) was 29 percent and 43 percent for patients treated with enalapril maleate and placebo, respectively. Enalapril Maleate (n = 673) Incidence (discontinuation) Placebo (n = 339) Incidence Body As A Whole Orthostatic Effects 2.2 (0.1) 0.3 Syncope 2.2 (0.1) 0.9 Chest Pain 2.1 (0.0) 2.1 Fatigue 1.8 (0.0) 1.8 Abdominal Pain 1.6 (0.4) 2.1 Asthenia 1.6 (0.1) 0.3 Cardiovascular Hypotension 6.7 (1.9) 0.6 Orthostatic Hypotension 1.6 (0.1) 0.3 Angina Pectoris 1.5 (0.1) 1.8 Myocardial Infarction 1.2 (0.3) 1.8 Digestive Diarrhea 2.1 (0.1) 1.2 Nausea 1.3 (0.1) 0.6 Vomiting 1.3 (0.0) 0.9 Nervous/Psychiatric Dizziness 7.9 (0.6) 0.6 Headache 1.8 (0.1) 0.9 Vertigo 1.6 (0.1) 1.2 Respiratory Cough 2.2 (0.0) 0.6 Bronchitis 1.3 (0.0) 0.9 Dyspnea 1.3 (0.1) 0.4 Pneumonia 1.0 (0.0) 2.4 Skin Rash 1.3 (0.0) 2.4 Urogenital Urinary Tract Infection 1.3 (0.0) 2.4 Other serious clinical adverse experiences occurring since the drug was marketed or adverse experiences occurring in 0.5 to 1.0 percent of patients with hypertension or heart failure in clinical trials are listed below and, within each category, are in order of decreasing severity. Body As A Whole: Anaphylactoid reactions (see WARNINGS, Anaphylactoid and Possibly Related Reactions ). Cardiovascular: Cardiac arrest; myocardial infarction or cerebrovascular accident, possibly secondary to excessive hypotension in high risk patients (see WARNINGS, Hypotension ); pulmonary embolism and infarction; pulmonary edema; rhythm disturbances including atrial tachycardia and bradycardia; atrial fibrillation; palpitation, Raynaud\'s phenomenon. Digestive: Ileus, pancreatitis, hepatic failure, hepatitis (hepatocellular [proven on rechallenge] or cholestatic jaundice) (see WARNINGS, Hepatic Failure ), melena, anorexia, dyspepsia, constipation, glossitis, stomatitis, dry mouth. Hematologic: Rare cases of neutropenia, thrombocytopenia and bone marrow depression. Musculoskeletal: Muscle cramps. Nervous/Psychiatric: Depression, confusion, ataxia, somnolence, insomnia, nervousness, peripheral neuropathy (e.g., paresthesia, dysesthesia), dream abnormality. Respiratory: Bronchospasm, rhinorrhea, sore throat and hoarseness, asthma, upper respiratory infection, pulmonary infiltrates, eosinophilic pneumonitis. Skin: Exfoliative dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, pemphigus, herpes zoster, erythema multiforme, urticaria, pruritus, alopecia, flushing, diaphoresis, photosensitivity. Special Senses: Blurred vision, taste alteration, anosmia, tinnitus, conjunctivitis, dry eyes, tearing. Urogenital: Renal failure, oliguria, renal dysfunction (see PRECAUTIONS and DOSAGE AND ADMINISTRATION ), flank pain, gynecomastia, impotence. Miscellaneous: A symptom complex has been reported which may include some or all of the following: a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia/myositis, fever, serositis, vasculitis, leukocytosis, eosinophilia, photosensitivity, rash and other dermatologic manifestations. Angioedema: Angioedema has been reported in patients receiving enalapril maleate, with an incidence higher in black than in non-black patients. Angioedema associated with laryngeal edema may be fatal. If angioedema of the face, extremities, lips, tongue, glottis and/or larynx occurs, treatment with enalapril maleate should be discontinued and appropriate therapy instituted immediately (see WARNINGS, Head and Neck Angioedema ). Hypotension: In the hypertensive patients, hypotension occurred in 0.9 percent and syncope occurred in 0.5 percent of patients following the initial dose or during extended therapy. Hypotension or syncope was a cause for discontinuation of therapy in 0.1 percent of hypertensive patients. In heart failure patients, hypotension occurred in 6.7 percent and syncope occurred in 2.2 percent of patients. Hypotension or syncope was a cause for discontinuation of therapy in 1.9 percent of patients with heart failure (see WARNINGS, Hypotension ). Cough: See PRECAUTIONS, Cough . Pediatric Patients The adverse experience profile for pediatric patients appears to be similar to that seen in adult patients. Clinical Laboratory Test Findings Serum Electrolytes Hyperkalemia (see PRECAUTIONS, Hyperkalemia ), hyponatremia. Creatinine, Blood Urea Nitrogen In controlled clinical trials minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 0.2 percent of patients with essential hypertension treated with enalapril maleate alone. Increases are more likely to occur in patients receiving concomitant diuretics or in patients with renal artery stenosis (see PRECAUTIONS, Impaired Renal Function ). In patients with heart failure who were also receiving diuretics with or without digitalis, increases in blood urea nitrogen or serum creatinine, usually reversible upon discontinuation of enalapril maleate and/or other concomitant diuretic therapy, were observed in about 11 percent of patients. Increases in blood urea nitrogen or creatinine were a cause for discontinuation in 1.2 percent of patients. Hematology Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.3 g percent and 1.0 vol percent, respectively) occur frequently in either hypertension or congestive heart failure patients treated with enalapril maleate but are rarely of clinical importance unless another cause of anemia coexists. In clinical trials, less than 0.1 percent of patients discontinued therapy due to anemia. Hemolytic anemia, including cases of hemolysis in patients with G6PD deficiency, has been reported; a causal relationship to enalapril cannot be excluded. Liver Function Tests Elevations of liver enzymes and/or serum bilirubin have occurred (see WARNINGS, Hepatic Failure ). To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc., at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch."}', 'drug_interactions': '{"Drug Interactions Neprilysin Inhibitors Patients taking concomitant neprilysin inhibitors may be at increased risk for angioedema (see WARNINGS ). Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function, and electrolytes in patients on enalapril maleate and other agents that affect the RAS. Do not coadminister aliskiren with enalapril maleate in patients with diabetes. Avoid use of aliskiren with enalapril maleate in patients with renal impairment (GFR <60 mL/min). Hypotension — Patients on Diuretic Therapy Patients on diuretics and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with enalapril. The possibility of hypotensive effects with enalapril can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with enalapril. If it is necessary to continue the diuretic, provide close medical supervision after the initial dose for at least two hours and until blood pressure has stabilized for at least an additional hour (See WARNINGS, Hypotension and DOSAGE AND ADMINISTRATION ). Agents Causing Renin Release The antihypertensive effect of enalapril maleate is augmented by antihypertensive agents that cause renin release (e.g., diuretics). Nonsteroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including enalapril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving enalapril and NSAID therapy. In a clinical pharmacology study, indomethacin or sulindac was administered to hypertensive patients receiving enalapril maleate. In this study there was no evidence of a blunting of the antihypertensive action of enalapril maleate. However, reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors. Other Cardiovascular Agents Enalapril maleate has been used concomitantly with beta adrenergic-blocking agents, methyldopa, nitrates, calcium-blocking agents, hydralazine, prazosin and digoxin without evidence of clinically significant adverse interactions. Agents Increasing Serum Potassium Enalapril maleate attenuates potassium loss caused by thiazide-type diuretics. Potassium-sparing diuretics (e.g., spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalemia, they should be used with caution and with frequent monitoring of serum potassium. Potassium-sparing agents should generally not be used in patients with heart failure receiving enalapril maleate. Lithium Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs which cause elimination of sodium, including ACE inhibitors. A few cases of lithium toxicity have been reported in patients receiving concomitant enalapril maleate and lithium and were reversible upon discontinuation of both drugs. It is recommended that serum lithium levels be monitored frequently if enalapril is administered concomitantly with lithium. Gold Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including enalapril maleate. mTOR (Mammalian Target of Rapamycin) Inhibitors Patients receiving coadministration of ACE inhibitor and mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema (see WARNINGS, Head and Neck Angioedema )."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Hypertension Enalapril maleate is indicated for the treatment of hypertension. Enalapril maleate is effective alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. The blood pressure lowering effects of enalapril maleate and thiazides are approximately additive. Heart Failure Enalapril maleate is indicated for the treatment of symptomatic congestive heart failure, usually in combination with diuretics and digitalis. In these patients enalapril maleate improves symptoms, increases survival, and decreases the frequency of hospitalization (see CLINICAL PHARMACOLOGY, Heart Failure, Mortality Trials for details and limitations of survival trials). Asymptomatic Left Ventricular Dysfunction In clinically stable asymptomatic patients with left ventricular dysfunction (ejection fraction ≤35 percent), enalapril maleate decreases the rate of development of overt heart failure and decreases the incidence of hospitalization for heart failure (see CLINICAL PHARMACOLOGY, Heart Failure, Mortality Trials for details and limitations of survival trials). In using enalapril maleate consideration should be given to the fact that another angiotensin-converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen vascular disease, and that available data are insufficient to show that enalapril maleate does not have a similar risk (see WARNINGS, Neutropenia/Agranulocytosis ). In considering use of enalapril maleate, it should be noted that in controlled clinical trials ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks. In addition, it should be noted that black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to non-blacks (see WARNINGS, Head and Neck Angioedema )."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Limited data are available in regard to overdosage in humans. Single oral doses of enalapril above 1,000 mg/kg and ≥1,775 mg/kg were associated with lethality in mice and rats, respectively. The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution. Enalaprilat may be removed from general circulation by hemodialysis and has been removed from neonatal circulation by peritoneal dialysis (see WARNINGS, Anaphylactoid Reactions during Membrane Exposure )."}', 'active_flag': 'Y', 'generic_name': '{"ENALAPRIL MALEATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Anaphylactoid and Possibly Related Reactions Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including enalapril maleate) may be subject to a variety of adverse reactions, some of them serious. Head and Neck Angioedema Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with angiotensin-converting enzyme inhibitors, including enalapril maleate. This may occur at any time during treatment. In such cases enalapril maleate should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms has occurred. In instances where swelling has been confined to the face and lips the condition has generally resolved without treatment, although antihistamines have been useful in relieving symptoms. Angioedema associated with laryngeal edema may be fatal. Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, appropriate therapy, e.g., subcutaneous epinephrine solution 1:1000 (0.3 mL to 0.5 mL) and/or measures necessary to ensure a patent airway, should be promptly provided (see ADVERSE REACTIONS ). Patients receiving coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema (see PRECAUTIONS ). Intestinal Angioedema Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see also INDICATIONS AND USAGE and CONTRAINDICATIONS ). Anaphylactoid Reactions During Desensitization Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge. Anaphylactoid Reactions During Membrane Exposure Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption. Hypotension Excessive hypotension is rare in uncomplicated hypertensive patients treated with enalapril maleate alone. Patients with heart failure given enalapril maleate commonly have some reduction in blood pressure, especially with the first dose, but discontinuation of therapy for continuing symptomatic hypotension usually is not necessary when dosing instructions are followed; caution should be observed when initiating therapy (see DOSAGE AND ADMINISTRATION ). Patients at risk for excessive hypotension, sometimes associated with oliguria and/or progressive azotemia, and rarely with acute renal failure and/or death, include those with the following conditions or characteristics: heart failure, hyponatremia, high-dose diuretic therapy, recent intensive diuresis or increase in diuretic dose, renal dialysis, or severe volume and/or salt depletion of any etiology. It may be advisable to eliminate the diuretic (except in patients with heart failure), reduce the diuretic dose or increase salt intake cautiously before initiating therapy with enalapril maleate in patients at risk for excessive hypotension who are able to tolerate such adjustments (see PRECAUTIONS, Drug Interactions and ADVERSE REACTIONS ). In patients at risk for excessive hypotension, therapy should be started under very close medical supervision and such patients should be followed closely for the first two weeks of treatment and whenever the dose of enalapril and/or diuretic is increased. Similar considerations may apply to patients with ischemic heart or cerebrovascular disease, in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident. If excessive hypotension occurs, the patient should be placed in the supine position and, if necessary, receive an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses of enalapril maleate, which usually can be given without difficulty once the blood pressure has stabilized. If symptomatic hypotension develops, a dose reduction or discontinuation of enalapril maleate or concomitant diuretic may be necessary. Neutropenia/Agranulocytosis Another angiotensin-converting enzyme inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression, rarely in uncomplicated patients but more frequently in patients with renal impairment, especially if they also have a collagen vascular disease. Available data from clinical trials of enalapril are insufficient to show that enalapril does not cause agranulocytosis at similar rates. Marketing experience has revealed cases of neutropenia or agranulocytosis in which a causal relationship to enalapril cannot be excluded. Periodic monitoring of white blood cell counts in patients with collagen vascular disease and renal disease should be considered. Hepatic Failure Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis, and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up. Fetal Toxicity Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue enalapril maleate as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue enalapril maleate, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to enalapril for hypotension, oliguria, and hyperkalemia (see PRECAUTIONS, Pediatric Use ). No teratogenic effects of enalapril were seen in studies of pregnant rats and rabbits. On a body surface area basis, the doses used were 57 times and 12 times, respectively, the maximum recommended human daily dose (MRHDD)."}', 'precautions': '{"PRECAUTIONS General Aortic Stenosis/Hypertrophic Cardiomyopathy As with all vasodilators, enalapril should be given with caution to patients with obstruction in the outflow tract of the left ventricle. Impaired Renal Function As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin-converting enzyme inhibitors, including enalapril maleate, may be associated with oliguria and/or progressive azotemia and rarely with acute renal failure and/or death (see PRECAUTIONS, Drug Interactions ). In clinical studies in hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine were observed in 20 percent of patients. These increases were almost always reversible upon discontinuation of enalapril and/or diuretic therapy. In such patients renal function should be monitored during the first few weeks of therapy. Some patients with hypertension or heart failure with no apparent pre-existing renal vascular disease have developed increases in blood urea and serum creatinine, usually minor and transient, especially when enalapril maleate has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or enalapril maleate may be required. Evaluation of patients with hypertension or heart failure should always include assessment of renal function (see DOSAGE AND ADMINISTRATION ). Hyperkalemia Elevated serum potassium (greater than 5.7 mEq/L) was observed in approximately one percent of hypertensive patients in clinical trials. In most cases these were isolated values which resolved despite continued therapy. Hyperkalemia was a cause of discontinuation of therapy in 0.28 percent of hypertensive patients. In clinical trials in heart failure, hyperkalemia was observed in 3.8 percent of patients but was not a cause for discontinuation. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes, which should be used cautiously, if at all, with enalapril maleate (see Drug Interactions ). Cough Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough. Surgery/Anesthesia In patients undergoing major surgery or during anesthesia with agents that produce hypotension, enalapril may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion. Information for Patients Angioedema Angioedema, including laryngeal edema, may occur at any time during treatment with angiotensin-converting enzyme inhibitors, including enalapril. Patients should be so advised and told to report immediately any signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing) and to take no more drug until they have consulted with the prescribing physician. Hypotension Patients should be cautioned to report lightheadedness, especially during the first few days of therapy. If actual syncope occurs, the patients should be told to discontinue the drug until they have consulted with the prescribing physician. All patients should be cautioned that excessive perspiration and dehydration may lead to an excessive fall in blood pressure because of reduction in fluid volume. Other causes of volume depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; patients should be advised to consult with the physician. Hyperkalemia Patients should be told not to use salt substitutes containing potassium without consulting their physician. Neutropenia Patients should be told to report promptly any indication of infection (e.g., sore throat, fever) which may be a sign of neutropenia. Pregnancy Female patients of childbearing age should be told about the consequences of exposure to enalapril maleate during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible. NOTE: As with many other drugs, certain advice to patients being treated with enalapril is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects. Drug Interactions Neprilysin Inhibitors Patients taking concomitant neprilysin inhibitors may be at increased risk for angioedema (see WARNINGS ). Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function, and electrolytes in patients on enalapril maleate and other agents that affect the RAS. Do not coadminister aliskiren with enalapril maleate in patients with diabetes. Avoid use of aliskiren with enalapril maleate in patients with renal impairment (GFR <60 mL/min). Hypotension — Patients on Diuretic Therapy Patients on diuretics and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with enalapril. The possibility of hypotensive effects with enalapril can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with enalapril. If it is necessary to continue the diuretic, provide close medical supervision after the initial dose for at least two hours and until blood pressure has stabilized for at least an additional hour (See WARNINGS, Hypotension and DOSAGE AND ADMINISTRATION ). Agents Causing Renin Release The antihypertensive effect of enalapril maleate is augmented by antihypertensive agents that cause renin release (e.g., diuretics). Nonsteroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including enalapril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving enalapril and NSAID therapy. In a clinical pharmacology study, indomethacin or sulindac was administered to hypertensive patients receiving enalapril maleate. In this study there was no evidence of a blunting of the antihypertensive action of enalapril maleate. However, reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors. Other Cardiovascular Agents Enalapril maleate has been used concomitantly with beta adrenergic-blocking agents, methyldopa, nitrates, calcium-blocking agents, hydralazine, prazosin and digoxin without evidence of clinically significant adverse interactions. Agents Increasing Serum Potassium Enalapril maleate attenuates potassium loss caused by thiazide-type diuretics. Potassium-sparing diuretics (e.g., spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalemia, they should be used with caution and with frequent monitoring of serum potassium. Potassium-sparing agents should generally not be used in patients with heart failure receiving enalapril maleate. Lithium Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs which cause elimination of sodium, including ACE inhibitors. A few cases of lithium toxicity have been reported in patients receiving concomitant enalapril maleate and lithium and were reversible upon discontinuation of both drugs. It is recommended that serum lithium levels be monitored frequently if enalapril is administered concomitantly with lithium. Gold Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including enalapril maleate. mTOR (Mammalian Target of Rapamycin) Inhibitors Patients receiving coadministration of ACE inhibitor and mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema (see WARNINGS, Head and Neck Angioedema ). Carcinogenesis, Mutagenesis, Impairment of Fertility There was no evidence of a tumorigenic effect when enalapril was administered for 106 weeks to male and female rats at doses up to 90 mg/kg/day or for 94 weeks to male and female mice at doses up to 90 and 180 mg/kg/day, respectively. These doses are 26 times (in rats and female mice) and 13 times (in male mice) the maximum recommended human daily dose (MRHDD) when compared on a body surface area basis. Neither enalapril maleate nor the active diacid was mutagenic in the Ames microbial mutagen test with or without metabolic activation. Enalapril was also negative in the following genotoxicity studies: rec-assay, reverse mutation assay with E. coli, sister chromatid exchange with cultured mammalian cells, and the micronucleus test with mice, as well as in an in vivo cytogenic study using mouse bone marrow. There were no adverse effects on reproductive performance of male and female rats treated with up to 90 mg/kg/day of enalapril (26 times the MRHDD when compared on a body surface area basis). Pregnancy Nursing Mothers Enalapril and enalaprilat have been detected in human breast milk. Because of the potential for serious adverse reactions in nursing infants from enalapril, a decision should be made whether to discontinue nursing or to discontinue enalapril maleate, taking into account the importance of the drug to the mother. Pediatric Use Neonates with a History of In Utero Exposure to Enalapril Maleate If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Enalapril, which crosses the placenta, has been removed from neonatal circulation by peritoneal dialysis with some clinical benefit, and theoretically may be removed by exchange transfusion, although there is no experience with the latter procedure. Antihypertensive effects of enalapril maleate have been established in hypertensive pediatric patients age 1 month to 16 years. Use of enalapril maleate in these age groups is supported by evidence from adequate and well-controlled studies of enalapril maleate in pediatric and adult patients as well as by published literature in pediatric patients (see CLINICAL PHARMACOLOGY, Clinical Pharmacology in Pediatric Patients and DOSAGE AND ADMINISTRATION ). Enalapril maleate is not recommended in neonates and in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m 2 , as no data are available."}', 'information_for_patients': '{"Information for Patients Angioedema Angioedema, including laryngeal edema, may occur at any time during treatment with angiotensin-converting enzyme inhibitors, including enalapril. Patients should be so advised and told to report immediately any signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing) and to take no more drug until they have consulted with the prescribing physician. Hypotension Patients should be cautioned to report lightheadedness, especially during the first few days of therapy. If actual syncope occurs, the patients should be told to discontinue the drug until they have consulted with the prescribing physician. All patients should be cautioned that excessive perspiration and dehydration may lead to an excessive fall in blood pressure because of reduction in fluid volume. Other causes of volume depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; patients should be advised to consult with the physician. Hyperkalemia Patients should be told not to use salt substitutes containing potassium without consulting their physician. Neutropenia Patients should be told to report promptly any indication of infection (e.g., sore throat, fever) which may be a sign of neutropenia. Pregnancy Female patients of childbearing age should be told about the consequences of exposure to enalapril maleate during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible. NOTE: As with many other drugs, certain advice to patients being treated with enalapril is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects."}', 'pregnancy': '{"Pregnancy Nursing Mothers Enalapril and enalaprilat have been detected in human breast milk. Because of the potential for serious adverse reactions in nursing infants from enalapril, a decision should be made whether to discontinue nursing or to discontinue enalapril maleate, taking into account the importance of the drug to the mother."}', 'pediatric_use': '{"Pediatric Use Neonates with a History of In Utero Exposure to Enalapril Maleate If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Enalapril, which crosses the placenta, has been removed from neonatal circulation by peritoneal dialysis with some clinical benefit, and theoretically may be removed by exchange transfusion, although there is no experience with the latter procedure. Antihypertensive effects of enalapril maleate have been established in hypertensive pediatric patients age 1 month to 16 years. Use of enalapril maleate in these age groups is supported by evidence from adequate and well-controlled studies of enalapril maleate in pediatric and adult patients as well as by published literature in pediatric patients (see CLINICAL PHARMACOLOGY, Clinical Pharmacology in Pediatric Patients and DOSAGE AND ADMINISTRATION ). Enalapril maleate is not recommended in neonates and in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m 2 , as no data are available."}', 'geriatric_use': None}

{PREDNISONE}

{'contraindications': '{"CONTRAINDICATIONS Systemic fungal infections and known hypersensitivity to components."}', 'adverse_reactions': '{"ADVERSE REACTIONS Fluid and Electrolyte Disturbances Sodium retention Fluid retention Congestive heart failure in susceptible patients Potassium loss Hypokalemic alkalosis Hypertension Musculoskeletal Muscle weakness Steroid myopathy Loss of muscle mass Osteoporosis Vertebral compression fractures Aseptic necrosis of femoral and humeral heads Pathologic fracture of long bones Gastrointestinal Peptic ulcer with possible perforation and hemorrhage Pancreatitis Abdominal distention Ulcerative esophagitis Dermatologic Impaired wound healing Thin fragile skin Petechiae and ecchymoses Facial erythema Increased sweating May suppress reactions to skin tests Metabolic Negative nitrogen balance due to protein catabolism Neurological Increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment Convulsions Vertigo Headache Endocrine Menstrual irregularities Development of Cushingoid state Secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery or illness Suppression of growth in children Decreased carbohydrate tolerance Manifestations of latent diabetes mellitus Increased requirements for insulin or oral hypoglycemic agents in diabetics Ophthalmic Posterior subcapsular cataracts Increased intraocular pressure Glaucoma Exophthalmos Additional Reactions Urticaria and other allergic, anaphylactic or hypersensitivity reactions"}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE Prednisone tablets are indicated in the following conditions: 1. Endocrine Disorders Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the first choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance) Congenital adrenal hyperplasia Hypercalcemia associated with cancer Nonsuppurative thyroiditis 2. Rheumatic Disorders As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: Psoriatic arthritis Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy) Ankylosing spondylitis Acute and subacute bursitis Acute nonspecific tenosynovitis Acute gouty arthritis Post-traumatic osteoarthritis Synovitis of osteoarthritis Epicondylitis 3. Collagen Diseases During an exacerbation or as maintenance therapy in selected cases of: Systemic lupus erythematosus Systemic dermatomyositis (polymyositis) Acute rheumatic carditis 4. Dermatologic Diseases Pemphigus Bullous dermatitis herpetiformis Severe erythema multiforme (Stevens-Johnson syndrome) Exfoliative dermatitis Mycosis fungoides Severe psoriasis Severe seborrheic dermatitis 5. Allergic States Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment: Seasonal or perennial allergic rhinitis Bronchial asthma Contact dermatitis Atopic dermatitis Serum sickness Drug hypersensitivity reactions 6. Ophthalmic Diseases Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as: Allergic corneal marginal ulcers Herpes zoster ophthalmicus Anterior segment inflammation Diffuse posterior uveitis and choroiditis Sympathetic ophthalmia Allergic conjunctivitis Keratitis Chorioretinitis Optic neuritis Iritis and iridocyclitis 7. Respiratory Diseases Symptomatic sarcoidosis Loeffler\'s syndrome not manageable by other means Berylliosis Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy Aspiration pneumonitis 8. Hematologic Disorders Idiopathic thrombocytopenic purpura in adults Secondary thrombocytopenia in adults Acquired (autoimmune) hemolytic anemia Erythroblastopenia (RBC anemia) Congenital (erythroid) hypoplastic anemia 9. Neoplastic Diseases For palliative management of: Leukemias and lymphomas in adults Acute leukemia of childhood 10. Edematous States To induce a diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus 11. Gastrointestinal Diseases To tide the patient over a critical period of the disease in: Ulcerative colitis Regional enteritis 12. Nervous System Acute exacerbations of multiple sclerosis 13. Miscellaneous Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy Trichinosis with neurologic or myocardial involvement"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{PREDNISONE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated. Corticosteroids may mask some signs of infection, and new infections may appear during their use. There may be decreased resistance and inability to localize infection when corticosteroids are used. Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses. Usage in pregnancy: Since adequate human reproduction studies have not been done with corticosteroids, the use of these drugs in pregnancy, nursing mothers or women of childbearing potential requires that the possible benefits of the drug be weighed against the potential hazards to the mother and embryo or fetus. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy, should be carefully observed for signs of hypoadrenalism. Average and large doses of hydrocortisone or cortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion. While on corticosteroid therapy patients should not be vaccinated against smallpox. Other immunization procedures should not be undertaken in patients who are on corticosteroids, especially on high dose, because of possible hazards of neurological complications and a lack of antibody response. The use of prednisone tablets in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate anti-tuberculous regimen. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis. Children who are on immunosuppressant drugs are more susceptible to infections than healthy children. Chickenpox and measles, for example, can have a more serious or even fatal course in children on immunosuppressant corticosteroids. In such children, or in adults who have not had these diseases, particular care should be taken to avoid exposure. If exposed, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobin (IVIG), as appropriate, may be indicated. If chickenpox develops, treatment with antiviral agents may be considered."}', 'precautions': '{"PRECAUTIONS General Precautions Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently. There is an enhanced effect of corticosteroids on patients with hypothyroidism and in those with cirrhosis. Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation. The lowest possible dose of corticosteroid should be used to control the condition under treatment, and when reduction in dosage is possible, the reduction should be gradual. Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. Steroids should be used with caution in nonspecific ulcerative colitis, if there is a probability of impending perforation, abscess or other pyogenic infection; diverticulitis; fresh intestinal anastomoses; active or latent peptic ulcer; renal insufficiency; hypertension; osteoporosis; and myasthenia gravis. Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed. Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not show that corticosteroids affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect. (See DOSAGE AND ADMINISTRATION.) Since complications of treatment with glucocorticoids are dependent on the size of the dose and the duration of treatment, a risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used. Convulsions have been reported with concurrent use of methylprednisolone and cyclosporin. Since concurrent use of these agents results in a mutual inhibition of metabolism, it is possible that adverse events associated with the individual use of either drug may be more apt to occur. Information for the Patient Patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles and, if exposed, to obtain medical advice."}', 'information_for_patients': '{"Information for the Patient Patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles and, if exposed, to obtain medical advice."}', 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"TERAZOSIN HYDROCHLORIDE"}

{'contraindications': '{"CONTRAINDICATIONS Terazosin capsules are contraindicated in patients known to be hypersensitive to terazosin hydrochloride."}', 'adverse_reactions': '{"ADVERSE REACTIONS Benign Prostatic Hyperplasia The incidence of treatment-emergent adverse events has been ascertained from clinical trials conducted worldwide. All adverse events reported during these trials were recorded as adverse reactions. The incidence rates presented below are based on combined data from six placebo-controlled trials involving once-a-day administration of terazosin at doses ranging from 1 to 20 mg. Table 1 summarizes those adverse events reported for patients in these trials when the incidence rate in the terazosin group was at least 1%, and was greater than that for the placebo group, or where the reaction is of clinical interest. Asthenia, postural hypotension, dizziness, somnolence, nasal congestion/rhinitis, and impotence were the only events that were significantly (p ≤ 0.05) more common in patients receiving terazosin than in patients receiving placebo. The incidence of urinary tract infection was significantly lower in the patients receiving terazosin than in patients receiving placebo. An analysis of the incidence rate of hypotensive adverse events (see PRECAUTIONS ) adjusted for the length of drug treatment has shown that the risk of the events is greatest during the initial seven days of treatment, but continues at all time intervals. TABLE 1. Adverse Reactions During Placebo-Controlled Trials Benign Prostatic Hyperplasia Body System Terazosin (N = 636) Placebo (N = 360) BODY AS A WHOLE Includes weakness, tiredness, lassitude, and fatigue. Asthenia Flu Syndrome Headache 7.4% p ≤ 0.05 comparison between groups. 2.4% 4.9% 3.3% 1.7% 5.8% CARDIOVASCULAR SYSTEM Hypotension Palpitations Postural Hypotension Syncope 0.6% 0.9% 3.9% 0.6% 0.6% 1.1% 0.8% 0.0% DIGESTIVE SYSTEM Nausea 1.7% 1.1% METABOLIC AND NUTRITIONAL DISORDERS Peripheral Edema Weight Gain 0.9% 0.5% 0.3% 0.0% NERVOUS SYSTEM Dizziness Somnolence Vertigo 9.1% 3.6% 1.4% 4.2% 1.9% 0.3% RESPIRATORY SYSTEM Dyspnea Nasal Congestion/Rhinitis 1.7% 1.9% 0.8% 0.0% SPECIAL SENSES Blurred Vision/Amblyopia 1.3% 0.6% UROGENITAL SYSTEM Impotence Urinary Tract Infection 1.6% 1.3% 0.6% 3.9% Additional adverse events have been reported, but these are, in general, not distinguishable from symptoms that might have occurred in the absence of exposure to terazosin. The safety profile of patients treated in the long-term open-label study was similar to that observed in the controlled studies. The adverse events were usually transient and mild or moderate in intensity, but sometimes were serious enough to interrupt treatment. In the placebo-controlled clinical trials, the rates of premature termination due to adverse events were not statistically different between the placebo and terazosin groups. The adverse events that were bothersome, as judged by their being reported as reasons for discontinuation of therapy by at least 0.5% of the terazosin group and being reported more often than in the placebo group, are shown in Table 2. TABLE 2. Discontinuation During Placebo-Controlled Trials Benign Prostatic Hyperplasia Body System Terazosin (N = 636) Placebo (N = 360) BODY AS A WHOLE Fever Headache 0.5% 1.1% 0.0% 0.8% CARDIOVASCULAR SYSTEM Postural Hypotension Syncope 0.5% 0.5% 0.0% 0.0% DIGESTIVE SYSTEM Nausea 0.5% 0.3% NERVOUS SYSTEM Dizziness Vertigo 2.0% 0.5% 1.1% 0.0% RESPIRATORY SYSTEM Dyspnea 0.5% 0.3% SPECIAL SENSES Blurred Vision/Amblyopia 0.6% 0.0% UROGENITAL SYSTEM Urinary Tract Infection 0.5% 0.3% Hypertension The prevalence of adverse reactions has been ascertained from clinical trials conducted primarily in the United States. All adverse experiences (events) reported during these trials were recorded as adverse reactions. The prevalence rates presented below are based on combined data from fourteen placebo-controlled trials involving once-a-day administration of terazosin, as monotherapy or in combination with other antihypertensive agents, at doses ranging from 1 to 40 mg. Table 3 summarizes those adverse experiences reported for patients in these trials where the prevalence rate in the terazosin group was at least 5%, where the prevalence rate for the terazosin group was at least 2% and was greater than the prevalence rate for the placebo group, or where the reaction is of particular interest. Asthenia, blurred vision, dizziness, nasal congestion, nausea, peripheral edema, palpitations and somnolence were the only symptoms that were significantly (p < 0.05) more common in patients receiving terazosin than in patients receiving placebo. Similar adverse reaction rates were observed in placebo-controlled monotherapy trials. TABLE 3. Adverse Reactions During Placebo-Controlled Trials Hypertension Body System Terazosin (N = 859) Placebo (N = 506) BODY AS A WHOLE Includes weakness, tiredness, lassitude, and fatigue. Asthenia Back Pain Headache 11.3% Statistically significant at p=0.05 level. 2.4% 16.2% 4.3% 1.2% 15.8% CARDIOVASCULAR SYSTEM Palpitations Postural Hypotension Tachycardia 4.3% 1.3% 1.9% 1.2% 0.4% 1.2% DIGESTIVE SYSTEM Nausea 4.4% 1.4% METABOLIC AND NUTRITIONAL DISORDERS Edema Peripheral Edema Weight Gain 0.9% 5.5% 0.5% 0.6% 2.4% 0.2% MUSCULOSKELETAL SYSTEM Pain – Extremities 3.5% 3.0% NERVOUS SYSTEM Depression Dizziness Libido Decreased Nervousness Paresthesia Somnolence 0.3% 19.3% 0.6% 2.3% 2.9% 5.4% 0.2% 7.5% 0.2% 1.8% 1.4% 2.6% RESPIRATORY SYSTEM Dyspnea Nasal Congestion Sinusitis 3.1% 5.9% 2.6% 2.4% 3.4% 1.4% SPECIAL SENSES Blurred Vision 1.6% 0.0% UROGENITAL SYSTEM Impotence 1.2% 1.4% Additional adverse reactions have been reported, but these are, in general, not distinguishable from symptoms that might have occurred in the absence of exposure to terazosin. The following additional adverse reactions were reported by at least 1% of 1987 patients who received terazosin in controlled or open, short- or long-term clinical trials or have been reported during marketing experience: Body as a Whole : Chest pain, facial edema, fever, abdominal pain, neck pain, shoulder pain. Cardiovascular System : Arrhythmia, vasodilation. Digestive System : Constipation, diarrhea, dry mouth, dyspepsia, flatulence, vomiting. Metabolic/Nutritional Disorders Gout. Musculoskeletal System : Arthralgia, arthritis, joint disorder, myalgia. Nervous System : Anxiety, insomnia. Respiratory System : Bronchitis, cold symptoms, epistaxis, flu symptoms, increased cough, pharyngitis, rhinitis. Skin and Appendages : Pruritus, rash, sweating. Special Senses : Abnormal vision, conjunctivitis, tinnitus. Urogenital System : Urinary frequency, urinary incontinence primarily reported in postmenopausal women, urinary tract infection. The adverse reactions were usually mild or moderate in intensity but sometimes were serious enough to interrupt treatment. The adverse reactions that were most bothersome, as judged by their being reported as reasons for discontinuation of therapy by at least 0.5% of the terazosin group and being reported more often than in the placebo group, are shown in Table 4. TABLE 4. Discontinuations During Placebo-Controlled Trials Hypertension Body System Terazosin (N = 859) Placebo (N = 506) BODY AS A WHOLE Asthenia Headache 1.6% 1.3% 0.0% 1.0% CARDIOVASCULAR SYSTEM Palpitations Postural Hypotension Syncope Tachycardia 1.4% 0.5% 0.5% 0.6% 0.2% 0.0% 0.2% 0.0% DIGESTIVE SYSTEM Nausea 0.8% 0.0% METABOLIC AND NUTRITIONAL DISORDERS Peripheral Edema 0.6% 0.0% NERVOUS SYSTEM Dizziness Paresthesia Somnolence 3.1% 0.8% 0.6% 0.4% 0.2% 0.2% RESPIRATORY SYSTEM Dyspnea Nasal Congestion 0.9% 0.6% 0.6% 0.0% SPECIAL SENSES Blurred Vision 0.6% 0.0% Post-marketing Experience Post-marketing experience indicates that in rare instances patients may develop allergic reactions, including anaphylaxis, following administration of terazosin hydrochloride. There have been reports of priapism and thrombocytopenia during post-marketing surveillance. Atrial fibrillation has been reported. During cataract surgery, a variant of small pupil syndrome known as Intraoperative Floppy Iris Syndrome (IFIS) has been reported in association with alpha-1 blocker therapy (see PRECAUTIONS )."}', 'drug_interactions': '{"Drug Interactions In controlled trials, terazosin have been added to diuretics, and several beta-adrenergic blockers; no unexpected interactions were observed. Terazosin has also been used in patients on a variety of concomitant therapies; while these were not formal interaction studies, no interactions were observed. Terazosin has been used concomitantly in at least 50 patients on the following drugs or drug classes: • analgesic/anti-inflammatory (e.g., acetaminophen, aspirin, codeine, ibuprofen, indomethacin); • antibiotics (e.g., erythromycin, trimethoprim and sulfamethoxazole); • anticholinergic/sympathomimetics (e.g., phenylephrine hydrochloride, phenylpropanolamine hydrochloride, pseudoephedrine hydrochloride); • antigout (e.g., allopurinol); • antihistamines (e.g., chlorpheniramine); • cardiovascular agents (e.g., atenolol, hydrochlorothiazide, methyclothiazide, propranolol); • corticosteroids; • gastrointestinal agents (e.g., antacids); • hypoglycemics; • sedatives and tranquilizers (e.g., diazepam)."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Terazosin capsules are indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH). There is a rapid response, with approximately 70% of patients experiencing an increase in urinary flow and improvement in symptoms of BPH when treated with terazosin capsules. The long-term effects of terazosin capsules on the incidence of surgery, acute urinary obstruction or other complications of BPH are yet to be determined. Terazosin capsules are also indicated for the treatment of hypertension. Terazosin capsules can be used alone or in combination with other antihypertensive agents such as diuretics or beta-adrenergic blocking agents."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Should overdosage of terazosin capsules lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. If this measure is inadequate, shock should first be treated with volume expanders. If necessary, vasopressors should then be used and renal function should be monitored and supported as needed. Laboratory data indicate that terazosin is 90-94% protein bound; therefore, dialysis may not be of benefit."}', 'active_flag': 'Y', 'generic_name': '{"TERAZOSIN HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Syncope and “First-dose” Effect Terazosin capsules, like other alpha-adrenergic blocking agents, can cause marked lowering of blood pressure, especially postural hypotension, and syncope in association with the first dose or first few days of therapy. A similar effect can be anticipated if therapy is interrupted for several days and then restarted. Syncope has also been reported with other alpha-adrenergic blocking agents in association with rapid dosage increases or the introduction of another antihypertensive drug. Syncope is believed to be due to an excessive postural hypotensive effect, although occasionally the syncopal episode has been preceded by a bout of severe supraventricular tachycardia with heart rates of 120 to 160 beats per minute. Additionally, the possibility of the contribution of hemodilution to the symptoms of postural hypotension should be considered. To decrease the likelihood of syncope or excessive hypotension, treatment should always be initiated with a 1 mg dose of terazosin capsules, given at bedtime. The 2 mg, 5 mg and 10 mg capsules are not indicated as initial therapy. Dosage should then be increased slowly, according to recommendations in the Dosage and Administration section and additional antihypertensive agents should be added with caution. The patient should be cautioned to avoid situations, such as driving or hazardous tasks, where injury could result should syncope occur during initiation of therapy. In early investigational studies, where increasing single doses up to 7.5 mg were given at 3 day intervals, tolerance to the first dose phenomenon did not necessarily develop and the “first-dose” effect could be observed at all doses. Syncopal episodes occurred in 3 of the 14 subjects given terazosin at doses of 2.5, 5 and 7.5 mg, which are higher than the recommended initial dose; in addition, severe orthostatic hypotension (blood pressure falling to 50/0 mmHg) was seen in two others and dizziness, tachycardia, and lightheadedness occurred in most subjects. These adverse effects all occurred within 90 minutes of dosing. In three placebo-controlled BPH studies 1, 2, and 3 (see CLINICAL PHARMACOLOGY ), the incidence of postural hypotension in the terazosin treated patients was 5.1%, 5.2%, and 3.7% respectively. In multiple dose clinical trials involving nearly 2000 hypertensive patients treated with terazosin capsules, syncope was reported in about 1% of patients. Syncope was not necessarily associated only with the first dose. If syncope occurs, the patient should be placed in a recumbent position and treated supportively as necessary. There is evidence that the orthostatic effect of terazosin is greater, even in chronic use, shortly after dosing. The risk of the events is greatest during the initial seven days of treatment, but continues at all time intervals. Priapism Rarely, (probably less than once in every several thousand patients), terazosin and other α 1 -antagonists have been associated with priapism (painful penile erection, sustained for hours and unrelieved by sexual intercourse or masturbation). Two or three dozen cases have been reported. Because this condition can lead to permanent impotence if not promptly treated, patients must be advised about the seriousness of the condition (see PRECAUTIONS: Information for Patients )."}', 'precautions': '{"PRECAUTIONS General Prostatic Cancer Carcinoma of the prostate and BPH cause many of the same symptoms. These two diseases frequently co-exist. Therefore, patients thought to have BPH should be examined prior to starting terazosin capsule therapy to rule out the presence of carcinoma of the prostate. Intraoperative Floppy Iris Syndrome (IFIS) Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients on/or previously treated with alpha-1 blockers. This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions. The patient’s ophthalmologist should be prepared for possible modifications to their surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances. There does not appear to be a benefit of stopping alpha-1 blocker therapy prior to cataract surgery. Orthostatic Hypotension While syncope is the most severe orthostatic effect of terazosin (see WARNINGS ), other symptoms of lowered blood pressure, such as dizziness, lightheadedness and palpitations, were more common and occurred in some 28% of patients in clinical trials of hypertension. In BPH clinical trials, 21% of the patients experienced one or more of the following: dizziness, hypotension, postural hypotension, syncope, and vertigo. Patients with occupations in which such events represent potential problems should be treated with particular caution. Information for Patients (see Patient Package Insert) Patients should be made aware of the possibility of syncopal and orthostatic symptoms, especially at the initiation of therapy, and to avoid driving or hazardous tasks for 12 hours after the first dose, after a dosage increase, and after interruption of therapy when treatment is resumed. They should be cautioned to avoid situations where injury could result should syncope occur during initiation of terazosin therapy. They should also be advised of the need to sit or lie down when symptoms of lowered blood pressure occur, although these symptoms are not always orthostatic, and to be careful when rising from a sitting or lying position. If dizziness, lightheadedness, or palpitations are bothersome they should be reported to the physician, so that dose adjustment can be considered. Patients should also be told that drowsiness or somnolence can occur with terazosin, requiring caution in people who must drive or operate heavy machinery. Patients should be advised about the possibility of priapism as a result of treatment with terazosin capsules and other similar medications. Patients should know that this reaction to terazosin capsules is extremely rare, but that if it is not brought to immediate medical attention, it can lead to permanent erectile dysfunction (impotence). Laboratory Tests Small but statistically significant decreases in hematocrit, hemoglobin, white blood cells, total protein and albumin were observed in controlled clinical trials. These laboratory findings suggested the possibility of hemodilution. Treatment with terazosin capsules for up to 24 months had no significant effect on prostate specific antigen (PSA) levels. Drug Interactions In controlled trials, terazosin have been added to diuretics, and several beta-adrenergic blockers; no unexpected interactions were observed. Terazosin has also been used in patients on a variety of concomitant therapies; while these were not formal interaction studies, no interactions were observed. Terazosin has been used concomitantly in at least 50 patients on the following drugs or drug classes: • analgesic/anti-inflammatory (e.g., acetaminophen, aspirin, codeine, ibuprofen, indomethacin); • antibiotics (e.g., erythromycin, trimethoprim and sulfamethoxazole); • anticholinergic/sympathomimetics (e.g., phenylephrine hydrochloride, phenylpropanolamine hydrochloride, pseudoephedrine hydrochloride); • antigout (e.g., allopurinol); • antihistamines (e.g., chlorpheniramine); • cardiovascular agents (e.g., atenolol, hydrochlorothiazide, methyclothiazide, propranolol); • corticosteroids; • gastrointestinal agents (e.g., antacids); • hypoglycemics; • sedatives and tranquilizers (e.g., diazepam). Use With Other Drugs In a study (n=24) where terazosin and verapamil were administered concomitantly, terazosin’s mean AUC 0-24 increased 11% after the first verapamil dose and after 3 weeks of verapamil treatment it increased by 24% with associated increases in C max (25%) and C min (32%) means. Terazosin mean T max decreased from 1.3 hours to 0.8 hours after 3 weeks of verapamil treatment. Statistically significant differences were not found in the verapamil level with and without terazosin. In a study (n=6) where terazosin and captopril were administered concomitantly, plasma disposition of captopril was not influenced by concomitant administration of terazosin and terazosin maximum plasma concentrations increased linearly with dose at steady-state after administration of terazosin plus captopril (see DOSAGE AND ADMINISTRATION ). Carcinogenesis, Mutagenesis, Impairment of Fertility : Terazosin was devoid of mutagenic potential when evaluated in vivo and in vitro (the Ames test, in vivo cytogenetics, the dominant lethal test in mice, in vivo Chinese hamster chromosome aberration test and V79 forward mutation assay). Terazosin administered in the feed to rats at doses of 8, 40, and 250 mg/kg/day (70, 350, and 2100 mg/M 2 /day), for two years, was associated with a statistically significant increase in benign adrenal medullary tumors of male rats exposed to the 250 mg/kg dose. This dose is 175 times the maximum recommended human dose of 20 mg (12 mg/M 2 ). Female rats were unaffected. Terazosin was not oncogenic in mice when administered in feed for 2 years at a maximum tolerated dose of 32 mg/kg/day (110 mg/M 2 ; 9 times the maximum recommended human dose). The absence of mutagenicity in a battery of tests, of tumorigenicity of any cell type in the mouse carcinogenicity assay, of increased total tumor incidence in either species, and of proliferative adrenal lesions in female rats, suggests a male rat species-specific event. Numerous other diverse pharmaceutical and chemical compounds have also been associated with benign adrenal medullary tumors in male rats without supporting evidence for carcinogenicity in man. The effect of terazosin on fertility was assessed in a standard fertility/reproductive performance study in which male and female rats were administered oral doses of 8, 30 and 120 mg/kg/day. Four of 20 male rats given 30 mg/kg (240 mg/M 2 ; 20 times the maximum recommended human dose) and five of 19 male rats given 120 mg/kg (960 mg/M 2 ; 80 times the maximum recommended human dose) failed to sire a litter. Testicular weights and morphology were unaffected by treatment. Vaginal smears at 30 and 120 mg/kg/day, however, appeared to contain less sperm than smears from control matings and good correlation was reported between sperm count and subsequent pregnancy. Oral administration of terazosin for one or two years elicited a statistically significant increase in the incidence of testicular atrophy in rats exposed to 40 and 250 mg/kg/day (29 and 175 times the maximum recommended human dose), but not in rats exposed to 8 mg/kg/day (> 6 times the maximum recommended human dose). Testicular atrophy was also observed in dogs dosed with 300 mg/kg/day (> 500 times the maximum recommended human dose) for three months but not after one year when dosed with 20 mg/kg/day (38 times the maximum recommended human dose). This lesion has also been seen with Minipress®, another (marketed) selective-alpha-1 blocking agent. Pregnancy Teratogenic Effects : Pregnancy Category C Terazosin capsules were not teratogenic in either rats or rabbits when administered at oral doses up to 280 and 60 times, respectively, the maximum recommended human dose. Fetal resorptions occurred in rats dosed with 480 mg/kg/day, approximately 280 times the maximum recommended human dose. Increased fetal resorptions, decreased fetal weight and an increased number of supernumerary ribs were observed in offspring of rabbits dosed with 60 times the maximum recommended human dose. These findings (in both species) were most likely secondary to maternal toxicity. There are no adequate and well-controlled studies in pregnant women and the safety of terazosin in pregnancy has not been established. Terazosin capsules are not recommended during pregnancy unless the potential benefit justifies the potential risk to the mother and fetus. Nonteratogenic Effects : In a peri- and post-natal development study in rats, significantly more pups died in the group dosed with 120 mg/kg/day (> 75 times the maximum recommended human dose) than in the control group during the three-week postpartum period. Nursing Mothers : It is not known whether terazosin is excreted in breast milk. Because many drugs are excreted in breast milk, caution should be exercised when terazosin capsules are administered to a nursing woman. Pediatric Use : Safety and effectiveness in pediatric patients have not been determined."}', 'information_for_patients': '{"Information for Patients (see Patient Package Insert) Patients should be made aware of the possibility of syncopal and orthostatic symptoms, especially at the initiation of therapy, and to avoid driving or hazardous tasks for 12 hours after the first dose, after a dosage increase, and after interruption of therapy when treatment is resumed. They should be cautioned to avoid situations where injury could result should syncope occur during initiation of terazosin therapy. They should also be advised of the need to sit or lie down when symptoms of lowered blood pressure occur, although these symptoms are not always orthostatic, and to be careful when rising from a sitting or lying position. If dizziness, lightheadedness, or palpitations are bothersome they should be reported to the physician, so that dose adjustment can be considered. Patients should also be told that drowsiness or somnolence can occur with terazosin, requiring caution in people who must drive or operate heavy machinery. Patients should be advised about the possibility of priapism as a result of treatment with terazosin capsules and other similar medications. Patients should know that this reaction to terazosin capsules is extremely rare, but that if it is not brought to immediate medical attention, it can lead to permanent erectile dysfunction (impotence)."}', 'pregnancy': '{"Pregnancy Teratogenic Effects : Pregnancy Category C Terazosin capsules were not teratogenic in either rats or rabbits when administered at oral doses up to 280 and 60 times, respectively, the maximum recommended human dose. Fetal resorptions occurred in rats dosed with 480 mg/kg/day, approximately 280 times the maximum recommended human dose. Increased fetal resorptions, decreased fetal weight and an increased number of supernumerary ribs were observed in offspring of rabbits dosed with 60 times the maximum recommended human dose. These findings (in both species) were most likely secondary to maternal toxicity. There are no adequate and well-controlled studies in pregnant women and the safety of terazosin in pregnancy has not been established. Terazosin capsules are not recommended during pregnancy unless the potential benefit justifies the potential risk to the mother and fetus. Nonteratogenic Effects : In a peri- and post-natal development study in rats, significantly more pups died in the group dosed with 120 mg/kg/day (> 75 times the maximum recommended human dose) than in the control group during the three-week postpartum period."}', 'pediatric_use': '{"Pediatric Use : Safety and effectiveness in pediatric patients have not been determined."}', 'geriatric_use': None}

{"CITALOPRAM HYDROBROMIDE"}

{'contraindications': '{"4 CONTRAINDICATIONS Citalopram tablets are contraindicated in patients: • taking, or within 14 days of stopping, MAOIs (including MAOIs such as linezolid or intravenous methylene blue) because of an increased risk of serotonin syndrome [see Warnings and Precautions ( 5.3 ), Drug Interactions ( 7 )] . • taking pimozide because of risk of QT prolongation [see Drug Interactions ( 7 )] . • with known hypersensitivity to citalopram or any of the inactive ingredients in citalopram tablets. Reactions have included angioedema and anaphylaxis [see Adverse Reactions ( 6.2 )] . • Concomitant use of monoamine oxidase inhibitors (MAOIs) or use within 14 days of discontinuing a MAOI ( 4 ) . • Concomiant use of pimozide ( 4 ) . • Known hypersensitivity to citalopram or any of the inactive ingredients of citalopram tablets ( 4 ) ."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: • Hypersensitivity reactions [see Contraindications ( 4 )] • Suicidal thoughts and behaviors in adolescents and young adults [see Warnings and Precautions ( 5.1 )] • QT-prolongation and torsade de pointes [see Warnings and Precautions ( 5.2 )] • Serotonin syndrome [see Warnings and Precautions ( 5.3 )] • Increased risk of bleeding [see Warnings and Precautions ( 5.4 )] • Activation of mania or hypomania [see Warnings and Precautions ( 5.5 )] • Discontinuation syndrome [see Warnings and Precautions ( 5.6 )] • Seizures [see Warnings and Precautions ( 5.7 )] • Angle-closure glaucoma [see Warnings and Precautions ( 5.8 )] • Hyponatremia [see Warnings and Precautions ( 5.9 )] • Sexual Dysfunction [see Warnings and Precautions ( 5.10 )] Most common adverse reaction (incidence ≥ 5% and twice placebo) is ejaculation disorder (primarily ejaculation delay) ( 6.1 ) . To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc . at 1-800-912-9561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Table 5 presents clinically important drug interactions with citalopram. Table 5: Clinically Important Drug Interactions with Citalopram Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact Concomitant use of SSRIs, including citalopram, and MAOIs increases the risk of serotonin syndrome. Intervention Citalopram is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration ( 2.5 ), Contraindications ( 4 ), Warnings and Precautions ( 5.3 )] . Pimozide Clinical Impact: Concomitant use of citalopram with pimozide increases plasma concentrations of pimozide, a drug with a narrow therapeutic index, and may increase the risk of QT prolongation and/or ventricular arrhythmias compared to use of citalopram alone [see Clinical Pharmacology ( 12.2 )]. Intervention: Citalopram is contraindicated in patients taking pimozide [see Contraindications ( 4 ), Warnings and Precautions ( 5.2 )]. Drugs that Prolong the QTc Interval Clinical Impact: Concomitant use of citalopram with drugs that prolong QT can cause additional QT prolongation compared to the use of citalopram alone [see Clinical Pharmacology ( 12.2 )]. Intervention: Avoid concomitant use of citalopram with drugs that prolong the QT interval (citalopram is contraindicated in patients taking pimozide) [see Contraindications ( 4 ), Warnings and Precautions ( 5.2 )]. CYP2C19 Inhibitors Clinical Impact: Concomitant use of citalopram with CYP2C19 inhibitors increases the risk of QT prolongation and/or ventricular arrhythmias compared to the use of citalopram alone [see Clinical Pharmacology ( 12.2 )]. Intervention: The maximum recommended dosage of citalopram is 20 mg daily when used concomitantly with a CYP2C19 inhibitor [see Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.2 )]. Serotonergic Drugs Clinical Impact: Concomitant use of citalopram and other serotonergic drugs increases the risk of serotonin syndrome. Intervention: Monitor patients for signs and symptoms of serotonin syndrome, particularly during citalopram initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of citalopram and/or concomitant serotonergic drugs [see Warning and Precautions ( 5.3 )]. Drugs That Interfere With Hemostasis (antiplatelet agents and anticoagulants) Clinical Impact: Concomitant use of citalopram and an antiplatelet or anticoagulant may potentiate the risk of bleeding. Intervention: Inform patients of the increased risk of bleeding associated with the concomitant use of citalopram and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [see Warning and Precautions ( 5.4 )]. CYP2C19 Inhibitors : Citalopram tablets 20 mg daily is the maximum recommended dosage for patients taking concomitant CYP2C19 inhibitors ( 5.2 , 7 ) ."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Citalopram tablets are indicated for the treatment of major depressive disorder (MDD) in adults [see Clinical Studies ( 14 )] . Citalopram is a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of major depressive disorder (MDD) in adults ( 1 ) ."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • QT-Prolongation and Torsade de Pointes: Dose-dependent QTc prolongation, Torsade de pointes, ventricular tachycardia, and sudden death have occurred. Avoid use of citalopram tablets in patients with congenital long QT syndrome, bradycardia, hypokalemia or hypomagnesemia, recent acute myocardial infarction, or uncompensated heart failure and patients taking other drugs that prolong the QTc interval. Monitor electrolytes in patients at high risk for hypokalemia or hypomagnesemia. Discontinue citalopram tablets in patients with persistent QTc measurements > 500 ms ( 5.2 , 7 ) . • Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents (e.g., SSRI, SNRI, triptans), but also when taken alone. If occurs, discontinue citalopram tablets and initiate supportive measures ( 5.3 ) . • Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti- inflammatory drugs, other antiplatelet drugs, warfarin and other anticoagulants may increase this risk ( 5.4 ) . • Activation of Mania/Hypomania: Screen patients for bipolar disorder ( 5.5 ) . • Seizures: Use with caution in patients with seizure disorder ( 5.7 ) . • Angle-Closure Glaucoma: Avoid use of citalopram tablets in patients with untreated anatomically narrow angles ( 5.8 ) . • Hyponatremia: Can occur in association with syndrome of inappropriate antidiuretic hormone secretion ( 5.9 ) . • Sexual Dysfunction: Citalopram tablets may cause symptoms of sexual dysfunction. ( 5.10 ) ."}', 'overdosage': '{"10 OVERDOSAGE The following have been reported with citalopram tablet overdosage: • Seizures, which may be delayed, and altered mental status including coma. • Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation, wide complex tachyarrhythmias, and torsade de pointes. Hypertension most commonly seen, but rarely can see hypotension alone or with co‐ingestants including alcohol. • Serotonin syndrome (patients with a multiple drug overdosage with other proserotonergic drugs may have a higher risk). Prolonged cardiac monitoring is recommended in citalopram overdosage ingestions due to the arrhythmia risk. Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a citalopram overdose. Consider contacting a Poison Center (1‐800‐221‐2222) or a medical toxicologist for additional overdosage management recommendations."}', 'active_flag': 'Y', 'generic_name': '{"CITALOPRAM HYDROBROMIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Suicidal Thoughts and Behaviors Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and when the dosage is adjusted up or down, and instruct them to report such symptoms to the healthcare provider [see Boxed Warning, Warnings and Precautions ( 5.1 )] . QT Prolongation and Torsade de Pointes Advise patients to consult their health care provider immediately if they feel faint, lose consciousness, or have heart palpitations. Instruct patients to inform their health care provider that they are taking citalopram before taking any new medications [see Warnings and Precautions ( 5.2 ), Drug Interactions ( 7 )] . Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of citalopram with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid). Instruct patients to contact their health care provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome [see Warnings and Precautions ( 5.3 ), Drug Interactions ( 7 )] . Increased Risk of Bleeding Inform patients about the concomitant use of citalopram with aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other anticoagulants because the combined use has been associated with an increased risk of bleeding. Advise patients to inform their health care providers if they are taking or planning to take any prescription or over-the counter medications that increase the risk of bleeding [see Warnings and Precautions ( 5.4 )] . Activation of Mania or Hypomania Advise patients and their caregivers to observe for signs of activation of mania/hypomania and instruct them to report such symptoms to the healthcare provider [see Warnings and Precautions ( 5.5 )] . Discontinuation Syndrome Advise patients not to abruptly discontinue citalopram and to discuss any tapering regimen with their healthcare provider. Inform patients that adverse reactions can occur when citalopram is discontinued [See Warnings and Precautions ( 5.6 )] . Sexual Dysfunction Advise patients that use of citalopram may cause symptoms of sexual dysfunction in both male and female patients. Inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider [see Warnings and Precautions ( 5.10 )] . Pregnancy • Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with citalopram [see Use in Specific Populations ( 8.1 )] . • Advise patients that citalopram use late in pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN) [see Use in Specific Populations ( 8.1 )] . • Advise women that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to citalopram during pregnancy [see Use in Specific Populations ( 8.1 )] . Lactation Advise breastfeeding women to monitor infants for excess sedation, restlessness, agitation, poor feeding and poor weight gain and to seek medical care if they notice these signs [see Use in Specific Populations ( 8.2 )] . Manufactured by: TORRENT PHARMACEUTICALS LTD., INDIA. Manufactured for: TORRENT PHARMA INC., Basking Ridge, NJ 07920 Repackaged by: PROFICIENT RX LP Thousand Oaks, CA 91320 8088041 Revised July 2022 image description"}', 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"DEXTROMETHORPHAN HYDROBROMIDE",GUAIFENESIN}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses • helps loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus and make coughs more productive • temporarily relieves: • cough due to minor throat and bronchial irritation as may occur with the common cold or inhaled irritants • the intensity of coughing • the impulse to cough to help you get to sleep"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"DEXTROMETHORPHAN HYDROBROMIDE, GUAIFENESIN"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if • cough lasts more than 7 days, comes back, or occurs with fever, rash, or persistent headache. These could be signs of a serious illness."}', 'do_not_use': '{"Do not use • for children under 12 years of age • if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric or emotional conditions, or Parkinson’s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product."}', 'when_using': '{"When using this product • do not use more than directed"}', 'warnings': '{"Warnings Do not use • for children under 12 years of age • if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric or emotional conditions, or Parkinson’s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product. Ask a doctor before use if you have • persistent or chronic cough such as occurs with smoking, asthma, chronic bronchitis, or emphysema • cough accompanied by too much phlegm (mucus) When using this product • do not use more than directed Stop use and ask a doctor if • cough lasts more than 7 days, comes back, or occurs with fever, rash, or persistent headache. These could be signs of a serious illness. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away. (1-800-222-1222)"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{EUCALYPTOL,MENTHOL,"METHYL SALICYLATE",THYMOL}

{'contraindications': None, 'adverse_reactions': '{"Adverse Reactions Section DISTRIBUTED BY: Wal-Mart Stores, Inc., Bentonville, AR 72716 *This product is not manufactured or distributed by Johnson & Johnson Healthcare Products, owner of the registered mark FreshBurst Listerine. how2recycle.info Discard Seal, Empty & Replace Cap Plastic Bottle"}', 'drug_interactions': None, 'indications_and_usage': '{"Use helps control plaque that leads to gingivitis"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"EUCALYPTOL, MENTHOL, METHYL SALICYLATE, THYMOL"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a dentist if gingivitis, bleeding, or rednss persists for more than 2 weeks"}', 'do_not_use': '{"Do not use if you have painful or swollen gums, pus from the gum line, loose teeth or incresed spacing between the teeth. See your dentist immediately. These may be signs of periodontitis, a serious form of gum disease."}', 'when_using': None, 'warnings': '{"Warnings For this product"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"BENZOYL PEROXIDE","CLINDAMYCIN PHOSPHATE"}

{'contraindications': '{"CONTRAINDICATIONS BenzaClin Topical Gel is contraindicated in those individuals who have shown hypersensitivity to any of its components or to lincomycin. It is also contraindicated in those having a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis."}', 'adverse_reactions': '{"ADVERSE REACTIONS During clinical trials, the most frequently reported adverse event in the BenzaClin treatment group was dry skin (12%). The table below lists local adverse events reported by at least 1% of patients in the BenzaClin and vehicle groups. Local Adverse Events - all causalities in >/= 1% of patients BenzaClin n = 420 Vehicle n = 168 Application site reaction 13 (3%) 1 (<1%) Dry skin 50 (12%) 10 (6%) Pruritus 8 (2%) 1 (<1%) Peeling 9 (2%) - Erythema 6 (1%) 1 (<1%) Sunburn 5 (1%) - The actual incidence of dry skin might have been greater were it not for the use of a moisturizer in these studies. Anaphylaxis, as well as allergic reactions leading to hospitalization, have been reported during postmarketing use of clindamycin/benzoyl peroxide products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. To report SUSPECTED ADVERSE REACTIONS, contact Valeant Pharmaceuticals North America LLC, at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch ."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE BenzaClin Topical Gel is indicated for the topical treatment of acne vulgaris."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"CLINDAMYCIN PHOSPHATE AND BENZOYL PEROXIDE"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS ORALLY AND PARENTERALLY ADMINISTERED CLINDAMYCIN HAS BEEN ASSOCIATED WITH SEVERE COLITIS WHICH MAY RESULT IN PATIENT DEATH. USE OF THE TOPICAL FORMULATION OF CLINDAMYCIN RESULTS IN ABSORPTION OF THE ANTIBIOTIC FROM THE SKIN SURFACE. DIARRHEA, BLOODY DIARRHEA, AND COLITIS (INCLUDING PSEUDOMEMBRANOUS COLITIS) HAVE BEEN REPORTED WITH THE USE OF TOPICAL AND SYSTEMIC CLINDAMYCIN. STUDIES INDICATE A TOXIN(S) PRODUCED BY CLOSTRIDIA IS ONE PRIMARY CAUSE OF ANTIBIOTIC-ASSOCIATED COLITIS. THE COLITIS IS USUALLY CHARACTERIZED BY SEVERE PERSISTENT DIARRHEA AND SEVERE ABDOMINAL CRAMPS AND MAY BE ASSOCIATED WITH THE PASSAGE OF BLOOD AND MUCUS. ENDOSCOPIC EXAMINATION MAY REVEAL PSEUDOMEMBRANOUS COLITIS. STOOL CULTURE FOR Clostridium Difficile AND STOOL ASSAY FOR C. difficile TOXIN MAY BE HELPFUL DIAGNOSTICALLY. WHEN SIGNIFICANT DIARRHEA OCCURS, THE DRUG SHOULD BE DISCONTINUED. LARGE BOWEL ENDOSCOPY SHOULD BE CONSIDERED TO ESTABLISH A DEFINITIVE DIAGNOSIS IN CASES OF SEVERE DIARRHEA. ANTIPERISTALTIC AGENTS SUCH AS OPIATES AND DIPHENOXYLATE WITH ATROPINE MAY PROLONG AND/OR WORSEN THE CONDITION. DIARRHEA, COLITIS, AND PSEUDOMEMBRANOUS COLITIS HAVE BEEN OBSERVED TO BEGIN UP TO SEVERAL WEEKS FOLLOWING CESSATION OF ORAL AND PARENTERAL THERAPY WITH CLINDAMYCIN. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation and treatment with an antibacterial drug clinically effective against C. difficile colitis."}', 'precautions': '{"PRECAUTIONS General: For dermatological use only; not for ophthalmic use. Concomitant topical acne therapy should be used with caution because a possible cumulative irritancy effect may occur, especially with the use of peeling, desquamating, or abrasive agents. The use of antibiotic agents may be associated with the overgrowth of nonsusceptible organisms including fungi. If this occurs, discontinue use of this medication and take appropriate measures. Avoid contact with eyes and mucous membranes. Clindamycin and erythromycin containing products should not be used in combination. In vitro studies have shown antagonism between these two antimicrobials. The clinical significance of this in vitro antagonism is not known. Information for Patients: Patients using BenzaClin Topical Gel should receive the following information and instructions: 1. BenzaClin Topical Gel is to be used as directed by the physician. It is for external use only. Avoid contact with eyes, and inside the nose, mouth, and all mucous membranes, as this product may be irritating. 2. This medication should not be used for any disorder other than that for which it was prescribed. 3. Patients should not use any other topical acne preparation unless otherwise directed by physician. 4. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using BenzaClin Topical Gel. To minimize exposure to sunlight, a wide-brimmed hat or other protective clothing should be worn, and a sunscreen with SPF 15 rating or higher should be used. 5. Patients who develop allergic symptoms such as severe swelling or shortness of breath should discontinue BenzaClin Topical Gel and contact their physician immediately. In addition, patients should report any signs of local adverse reactions to their physician. 6. BenzaClin Topical Gel may bleach hair or colored fabric. 7. BenzaClin Topical Gel can be stored at room temperature up to 25°C (77°F) for 3 months. Do not freeze. Discard any unused product after 3 months. 8. Before applying BenzaClin Topical Gel to affected areas, wash the skin gently, then rinse with warm water and pat dry. Carcinogenesis, Mutagenesis, Impairment of Fertility: Benzoyl peroxide has been shown to be a tumor promoter and progression agent in a number of animal studies. The clinical significance of this is unknown. Benzoyl peroxide in acetone at doses of 5 and 10 mg administered twice per week induced skin tumors in transgenic Tg.AC mice in a study using 20 weeks of topical treatment. In a 52-week dermal photocarcinogenicity study in hairless mice, the median time to onset of skin tumor formation was decreased and the number of tumors per mouse increased following chronic concurrent topical administration of BenzaClin Topical Gel with exposure to ultraviolet radiation (40 weeks of treatment followed by 12 weeks of observation). In a 2-year dermal carcinogenicity study in rats, treatment with BenzaClin Topical Gel at doses of 100, 500 and 2000 mg/kg/day caused a dose-dependent increase in the incidence of keratoacanthoma at the treated skin site of male rats. The incidence of keratoacanthoma at the treated site of males treated with 2000 mg/kg/day (8 times the highest recommended adult human dose of 2.5 g BenzaClin Topical Gel, based on mg/m2) was statistically significantly higher than that in the sham and vehicle controls. Genotoxicity studies were not conducted with BenzaClin Topical Gel. Clindamycin phosphate was not genotoxic in Salmonella typhimurium or in a rat micronucleus test. Clindamycin phosphate sulfoxide, an oxidative degradation product of clindamycin phosphate and benzoyl peroxide, was not clastogenic in a mouse micronucleus test. Benzoyl peroxide has been found to cause DNA strand breaks in a variety of mammalian cell types, to be mutagenic in S. typhimurium tests by some but not all investigators, and to cause sister chromatid exchanges in Chinese hamster ovary cells. Studies have not been performed with BenzaClin Topical Gel or benzoyl peroxide to evaluate the effect on fertility. Fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 120 times the amount of clindamycin in the highest recommended adult human dose of 2.5 g BenzaClin Topical Gel, based on mg/m 2 ) revealed no effects on fertility or mating ability. Pregnancy: Teratogenic Effects: Animal reproductive/developmental toxicity studies have not been conducted with BenzaClin Topical Gel or benzoyl peroxide. Developmental toxicity studies performed in rats and mice using oral doses of clindamycin up to 600 mg/kg/day (240 and 120 times amount of clindamycin in the highest recommended adult human dose based on mg/m 2 , respectively) or subcutaneous doses of clindamycin up to 250 mg/kg/day (100 and 50 times the amount of clindamycin in the highest recommended adult human dose based on mg/m 2 , respectively) revealed no evidence of teratogenicity. There are no well-controlled trials in pregnant women treated with BenzaClin Topical Gel. It also is not known whether BenzaClin Topical Gel can cause fetal harm when administered to a pregnant woman. Nursing Women: It is not known whether BenzaClin Topical Gel is excreted in human milk after topical application. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use: Safety and effectiveness of this product in pediatric patients below the age of 12 have not been established."}', 'information_for_patients': '{"Information for Patients: Patients using BenzaClin Topical Gel should receive the following information and instructions: 1. BenzaClin Topical Gel is to be used as directed by the physician. It is for external use only. Avoid contact with eyes, and inside the nose, mouth, and all mucous membranes, as this product may be irritating. 2. This medication should not be used for any disorder other than that for which it was prescribed. 3. Patients should not use any other topical acne preparation unless otherwise directed by physician. 4. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using BenzaClin Topical Gel. To minimize exposure to sunlight, a wide-brimmed hat or other protective clothing should be worn, and a sunscreen with SPF 15 rating or higher should be used. 5. Patients who develop allergic symptoms such as severe swelling or shortness of breath should discontinue BenzaClin Topical Gel and contact their physician immediately. In addition, patients should report any signs of local adverse reactions to their physician. 6. BenzaClin Topical Gel may bleach hair or colored fabric. 7. BenzaClin Topical Gel can be stored at room temperature up to 25°C (77°F) for 3 months. Do not freeze. Discard any unused product after 3 months. 8. Before applying BenzaClin Topical Gel to affected areas, wash the skin gently, then rinse with warm water and pat dry."}', 'pregnancy': '{"Pregnancy: Teratogenic Effects: Animal reproductive/developmental toxicity studies have not been conducted with BenzaClin Topical Gel or benzoyl peroxide. Developmental toxicity studies performed in rats and mice using oral doses of clindamycin up to 600 mg/kg/day (240 and 120 times amount of clindamycin in the highest recommended adult human dose based on mg/m 2 , respectively) or subcutaneous doses of clindamycin up to 250 mg/kg/day (100 and 50 times the amount of clindamycin in the highest recommended adult human dose based on mg/m 2 , respectively) revealed no evidence of teratogenicity. There are no well-controlled trials in pregnant women treated with BenzaClin Topical Gel. It also is not known whether BenzaClin Topical Gel can cause fetal harm when administered to a pregnant woman."}', 'pediatric_use': '{"Pediatric Use: Safety and effectiveness of this product in pediatric patients below the age of 12 have not been established."}', 'geriatric_use': None}

{ACETAMINOPHEN,"DEXTROMETHORPHAN HYDROBROMIDE","PHENYLEPHRINE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses temporarily relieves common cold/flu symptoms: nasal congestion cough due to minor throat & bronchial irritation sore throat headache minor aches & pains fever"}', 'warnings_and_cautions': None, 'overdosage': '{"Overdose warning Taking more than directed can cause serious health problems. In case of overdose, get medical help or contact a Poison Control Center right away. Quick medical attention is critical for adults & for children even if you do not notice any signs or symptoms."}', 'active_flag': 'Y', 'generic_name': '{"ACETAMINOPHEN, DEXTROMETHORPHAN HYDROBROMIDE, PHENYLEPHRINE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if you get nervous, dizzy or sleepless symptoms get worse or last more than 5 days (children) or 7 days (adults) fever gets worse or lasts more than 3 days redness or swelling is present new symptoms occur cough comes back, or occurs with rash or headache that lasts. These could be signs of a serious condition."}', 'do_not_use': '{"Do not use with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist. if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson\'s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product."}', 'when_using': '{"When using this product, do not use more than directed."}', 'warnings': '{"Warnings Liver warning This product contains acetaminophen. Severe liver damage may occur if you take more than 10 softgels in 24 hours, which is the maximum daily amount for this product with other drugs containing acetaminophen 3 or more alcoholic drinks every day while using this product Sore throat warning If sore throat is severe, persists for more than 2 days, is accompanied or followed by fever, headache, rash, nausea, or vomiting, consult a doctor promptly. Allergy alert: Acetaminophen may cause severe skin reactions. Symptoms may include: skin reddening blisters rash If a skin reaction occurs, stop use and seek medical help right away. Do not use with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist. if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson\'s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product. Ask a doctor before use if you have liver disease heart disease thyroid disease diabetes high blood pressure trouble urinating due to an enlarged prostate gland cough that occurs with excessive phlegm (mucus) persistent or chronic cough as occurs with smoking, asthma, or emphysema Ask a doctor or pharmacist before use if you are taking the blood thinning drug warfarin. When using this product, do not use more than directed. Stop use and ask a doctor if you get nervous, dizzy or sleepless symptoms get worse or last more than 5 days (children) or 7 days (adults) fever gets worse or lasts more than 3 days redness or swelling is present new symptoms occur cough comes back, or occurs with rash or headache that lasts. These could be signs of a serious condition. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. Overdose warning Taking more than directed can cause serious health problems. In case of overdose, get medical help or contact a Poison Control Center right away. Quick medical attention is critical for adults & for children even if you do not notice any signs or symptoms."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{PREDNISONE}

{'contraindications': '{"CONTRAINDICATIONS Prednisone tablets are contraindicated in systemic fungal infections and known hypersensitivity to components."}', 'adverse_reactions': '{"ADVERSE REACTIONS (listed alphabetically, under each subsection) The following adverse reactions have been reported with prednisone or other corticosteroids: Allergic Reactions anaphylactoid or hypersensitivity reactions, anaphylaxis, angioedema. Cardiovascular System bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, ECG changes caused by potassium deficiency, edema, fat embolism, hypertension or aggravation of hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction (see WARNINGS: Cardio-Renal ), necrotizing angiitis, pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis. Dermatologic acne, acneiform eruptions, allergic dermatitis, alopecia, angioedema, angioneurotic edema, atrophy and thinning of skin, dry scaly skin, ecchymoses and petechiae (bruising), erythema, facial edema, hirsutism, impaired wound healing, increased sweating, Karposi’s sarcoma (see PRECAUTIONS: General Precautions ), lupus erythematosus-like lesions, perineal irritation, purpura, rash, striae, subcutaneous fat atrophy, suppression of reactions to skin tests, striae, telangiectasis, thin fragile skin, thinning scalp hair, urticaria. Endocrine Adrenal insufficiency-greatest potential caused by high potency glucocorticoids with long duration of action (associated symptoms include; arthralgias, buffalo hump, dizziness, life-threatening hypotension, nausea, severe tiredness or weakness), amenorrhea, postmenopausal bleeding or other menstrual irregularities, decreased carbohydrate and glucose tolerance, development of cushingoid state, diabetes mellitus (new onset or manifestations of latent), glycosuria, hyperglycemia, hypertrichosis, hyperthyroidism (see WARNINGS: Endocrine ), hypothyroidism, increased requirements for insulin or oral hypoglycemic agents in diabetics, lipids abnormal, moon face, negative nitrogen balance caused by protein catabolism, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery or illness) (see WARNINGS: Endocrine ), suppression of growth in pediatric patients. Fluid and Electrolyte Disturbances congestive heart failure in susceptible patients, fluid retention, hypokalemia, hypokalemic alkalosis, metabolic alkalosis, hypotension or shock-like reaction, potassium loss, sodium retention with resulting edema. Gastrointestinal abdominal distention, abdominal pain, anorexia which may result in weight loss, constipation, diarrhea, elevation in serum liver enzyme levels (usually reversible upon discontinuation), gastric irritation, hepatomegaly, increased appetite and weight gain, nausea, oropharyngeal candidiasis, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease), ulcerative esophagitis, vomiting. Hematologic anemia, neutropenia (including febrile neutropenia). Metabolic negative nitrogen balance due to protein catabolism. Musculoskeletal arthralgias, aseptic necrosis of femoral and humeral heads, increase risk of fracture, loss of muscle mass, muscle weakness, myalgias, osteopenia, osteoporosis (see PRECAUTIONS: Musculoskeletal ), pathologic fracture of long bones, steroid myopathy, tendon rupture (particularly of the Achilles tendon), vertebral compression fractures. Neurological/Psychiatric amnesia, anxiety, benign intracranial hypertension, convulsions, delirium, dementia (characterized by deficits in memory retention, attention, concentration, mental speed and efficiency, and occupational performance), depression, dizziness, EEG abnormalities, emotional instability and irritability, euphoria, hallucinations, headache, impaired cognition, incidence of severe psychiatric symptoms, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, increased motor activity, insomnia, ischemic neuropathy, long-term memory loss, mania, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychiatric disorders including steroid psychoses or aggravation of pre-existing psychiatric conditions, restlessness, schizophrenia, verbal memory loss, vertigo, withdrawn behavior. Ophthalmic blurred vision, cataracts (including posterior subcapsular cataracts), central serous chorioretinopathy, establishment of secondary bacterial, fungal and viral infections, exophthalmos, glaucoma, increased intraocular pressure (see PRECAUTIONS: Ophthalmic ), optic nerve damage, papilledema. Other abnormal fat deposits, aggravation/masking of infections, decreased resistance to infection (see WARNINGS: Infection ), hiccups, immunosuppression, increased or decreased motility and number of spermatozoa, malaise, insomnia, moon face, pyrexia."}', 'drug_interactions': '{"Drug Interactions Amphotericin B Injection and Potassium-Depleting Agents When corticosteroids are administered concomitantly with potassium-depleting agents (e.g., amphotericin B, diuretics ), patients should be observed closely for development of hypokalemia. In addition, there have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure. Antibiotics Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance (see PRECAUTIONS: Drug Interactions: Hepatic Enzyme Inducers, Inhibitors and Substrates ). Anticholinesterases Concomitant use of anticholinesterase agents (e.g., neostigmine, pyridostigmine ) and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy. If concomitant therapy must occur, it should take place under close supervision and the need for respiratory support should be anticipated. Anticoagulants, Oral Co-administration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect. Antidiabetics Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required. Antitubercular drugs Serum concentrations of isoniazid may be decreased. Bupropion Since systemic steroids, as well as bupropion, can lower the seizure threshold, concurrent administration should be undertaken only with extreme caution; low initial dosing and small gradual increases should be employed. Cholestyramine Cholestyramine may increase the clearance of corticosteroids. Cyclosporine Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use. Digitalis Glycosides Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia. Estrogens, Including Oral Contraceptives Estrogens may decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effect. Fluoroquinolones Post-marketing surveillance reports indicate that the risk of tendon rupture may be increased in patients receiving concomitant fluoroquinolones (e.g., ciprofloxacin, levofloxacin ) and corticosteroids, especially in the elderly. Tendon rupture can occur during or after treatment with quinolones. Hepatic Enzyme Inducers, Inhibitors and Substrates Drugs which induce cytochrome P450 3A4 (CYP 3A4) enzyme activity (e.g., barbiturates, phenytoin, carbamazepine, rifampin ) may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased. Drugs which inhibit CYP 3A4 (e.g., ketoconazole, itraconazole, ritonavir, indinavir, macrolide antibiotics such as erythromycin ) have the potential to result in increased plasma concentrations of corticosteroids. Glucocorticoids are moderate inducers of CYP 3A4. Co-administration with other drugs that are metabolized by CYP 3A4 (e.g., indinavir, erythromycin ) may increase their clearance, resulting in decreased plasma concentration. Ketoconazole Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects. In addition, ketoconazole alone can inhibit adrenal corticosteroid synthesis and may cause adrenal insufficiency during corticosteroid withdrawal. Nonsteroidal Anti-Inflammatory Agents (NSAIDS) Concomitant use of aspirin (or other nonsteroidal anti-inflammatory agents ) and corticosteroids increases the risk of gastrointestinal side effects. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids; this could lead to decreased salicylate serum levels or increase the risk of salicylate toxicity when corticosteroid is withdrawn. Phenytoin In post-marketing experience, there have been reports of both increases and decreases in phenytoin levels with dexamethasone co-administration, leading to alterations in seizure control. Phenytoin has been demonstrated to increase the hepatic metabolism of corticosteroids, resulting in a decreased therapeutic effect of the corticosteroid. Quetiapine Increased doses of quetiapine may be required to maintain control of symptoms of schizophrenia in patients receiving a glucocorticoid, a hepatic enzyme inducer. Skin Tests Corticosteroids may suppress reactions to skin tests. Thalidomide Co-administration with thalidomide should be employed cautiously, as toxic epidermal necrolysis has been reported with concomitant use. Vaccines Patients on corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. Routine administration of vaccines or toxoids should be deferred until corticosteroid therapy is discontinued if possible (see WARNINGS: Infection: Vaccination ).","Amphotericin B Injection and Potassium-Depleting Agents When corticosteroids are administered concomitantly with potassium-depleting agents (e.g., amphotericin B, diuretics ), patients should be observed closely for development of hypokalemia. In addition, there have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure.","Antibiotics Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance (see PRECAUTIONS: Drug Interactions: Hepatic Enzyme Inducers, Inhibitors and Substrates ).","Anticholinesterases Concomitant use of anticholinesterase agents (e.g., neostigmine, pyridostigmine ) and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy. If concomitant therapy must occur, it should take place under close supervision and the need for respiratory support should be anticipated.","Anticoagulants, Oral Co-administration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect.","Antidiabetics Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required.","Antitubercular drugs Serum concentrations of isoniazid may be decreased.","Bupropion Since systemic steroids, as well as bupropion, can lower the seizure threshold, concurrent administration should be undertaken only with extreme caution; low initial dosing and small gradual increases should be employed.","Cholestyramine Cholestyramine may increase the clearance of corticosteroids.","Cyclosporine Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use.","Digitalis Glycosides Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia.","Estrogens, Including Oral Contraceptives Estrogens may decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effect.","Fluoroquinolones Post-marketing surveillance reports indicate that the risk of tendon rupture may be increased in patients receiving concomitant fluoroquinolones (e.g., ciprofloxacin, levofloxacin ) and corticosteroids, especially in the elderly. Tendon rupture can occur during or after treatment with quinolones.","Hepatic Enzyme Inducers, Inhibitors and Substrates Drugs which induce cytochrome P450 3A4 (CYP 3A4) enzyme activity (e.g., barbiturates, phenytoin, carbamazepine, rifampin ) may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased. Drugs which inhibit CYP 3A4 (e.g., ketoconazole, itraconazole, ritonavir, indinavir, macrolide antibiotics such as erythromycin ) have the potential to result in increased plasma concentrations of corticosteroids. Glucocorticoids are moderate inducers of CYP 3A4. Co-administration with other drugs that are metabolized by CYP 3A4 (e.g., indinavir, erythromycin ) may increase their clearance, resulting in decreased plasma concentration.","Ketoconazole Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects. In addition, ketoconazole alone can inhibit adrenal corticosteroid synthesis and may cause adrenal insufficiency during corticosteroid withdrawal.","Nonsteroidal Anti-Inflammatory Agents (NSAIDS) Concomitant use of aspirin (or other nonsteroidal anti-inflammatory agents ) and corticosteroids increases the risk of gastrointestinal side effects. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids; this could lead to decreased salicylate serum levels or increase the risk of salicylate toxicity when corticosteroid is withdrawn.","Phenytoin In post-marketing experience, there have been reports of both increases and decreases in phenytoin levels with dexamethasone co-administration, leading to alterations in seizure control. Phenytoin has been demonstrated to increase the hepatic metabolism of corticosteroids, resulting in a decreased therapeutic effect of the corticosteroid.","Quetiapine Increased doses of quetiapine may be required to maintain control of symptoms of schizophrenia in patients receiving a glucocorticoid, a hepatic enzyme inducer.","Skin Tests Corticosteroids may suppress reactions to skin tests.","Thalidomide Co-administration with thalidomide should be employed cautiously, as toxic epidermal necrolysis has been reported with concomitant use.","Vaccines Patients on corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. Routine administration of vaccines or toxoids should be deferred until corticosteroid therapy is discontinued if possible (see WARNINGS: Infection: Vaccination )."}', 'indications_and_usage': '{"INDICATIONS AND USAGE PredniSONE Tablets are indicated in the following conditions: Endocrine Disorders Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the first choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance) Congenital adrenal hyperplasia Nonsuppurative thyroiditis Hypercalcemia associated with cancer Rheumatic Disorders As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: Psoriatic arthritis Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy) Ankylosing spondylitis Acute and subacute bursitis Acute nonspecific tenosynovitis Acute gouty arthritis Post-traumatic osteoarthritis Synovitis of osteoarthritis Epicondylitis Collagen Diseases During an exacerbation or as maintenance therapy in selected cases of: Systemic lupus erythematosus Systemic dermatomyositis (polymyositis) Acute rheumatic carditis Dermatologic Diseases Pemphigus Bullous dermatitis herpetiformis Severe erythema multiforme (Stevens-Johnson syndrome) Exfoliative dermatitis Mycosis fungoides Severe psoriasis Severe seborrheic dermatitis Allergic States Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment: Seasonal or perennial allergic rhinitis Bronchial asthma Contact dermatitis Atopic dermatitis Serum sickness Drug hypersensitivity reactions Ophthalmic Diseases Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as: Allergic corneal marginal ulcers Herpes zoster ophthalmicus Anterior segment inflammation Diffuse posterior uveitis and choroiditis Sympathetic ophthalmia Allergic conjunctivitis Keratitis Chorioretinitis Optic neuritis Iritis and iridocyclitis Respiratory Diseases Symptomatic sarcoidosis Loeffler\'s syndrome not manageable by other means Berylliosis Aspiration pneumonitis Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy Hematologic Disorders Idiopathic thrombocytopenic purpura in adults Secondary thrombocytopenia in adults Acquired (autoimmune) hemolytic anemia Erythroblastopenia (RBC anemia) Congenital (erythroid) hypoplastic anemia Neoplastic Diseases For palliative management of: Leukemias and lymphomas in adults Acute leukemia of childhood Edematous States To induce a diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus Gastrointestinal Diseases To tide the patient over a critical period of the disease in: Ulcerative colitis Regional enteritis Miscellaneous Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy Trichinosis with neurologic or myocardial involvement"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{PREDNISONE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS General Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroid therapy (see ADVERSE REACTIONS: Allergic Reactions ). Increased dosage of rapidly acting corticosteroids is indicated in patients on corticosteroid therapy subjected to any unusual stress before, during and after the stressful situation. Cardio-Renal Average and large doses of hydrocortisone or cortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion. Literature reports suggest an apparent association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with corticosteroids should be used with great caution in these patients. Endocrine Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression with the potential for corticosteroid insufficiency after withdrawal of treatment. Adrenocortical insufficiency may result from too rapid withdrawal of corticosteroids and may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for up to 12 months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. If the patient is receiving steroids already, dosage may have to be increased. Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in dosage. Infection General Patients who are on corticosteroids are more susceptible to infections than are healthy individuals. There may be decreased resistance and inability to localize infection when corticosteroids are used. Infection with any pathogen (viral, bacterial, fungal, protozoan or helminthic) in any location of the body may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect cellular immunity, humoral immunity, or neutrophil function. 1 These infections may be mild, but may be severe and at times fatal. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. 2 Corticosteroids may also mask some signs of current infection. Fungal Infections Corticosteroids may exacerbate systemic fungal infections and therefore should not be used in the presence of such infections unless they are needed to control life-threatening drug reactions. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure (see PRECAUTIONS: Drug Interactions: Amphotericin B Injection and Potassium-Depleting Agents ). Special Pathogens Latent disease may be activated or there may be an exacerbation of intercurrent infections due to pathogens, including those caused by Amoeba, Candida, Cryptococcus, Mycobacterium, Nocardia, Pneumocystis, Toxoplasma . It is recommended that latent amebiasis or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics or any patient with unexplained diarrhea. Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. Corticosteroids should not be used in cerebral malaria. Tuberculosis The use of prednisone in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for management of the disease in conjunction with an appropriate antituberculous regimen. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis. Vaccination Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered. However, the response to such vaccines may be diminished and cannot be predicted. Indicated immunization procedures may be undertaken in patients receiving nonimmunosuppressive doses of corticosteroids as replacement therapy (e.g., for Addison’s disease). Viral Infections Chickenpox and measles can have a more serious or even fatal course in pediatric and adult patients on corticosteroids. In pediatric and adult patients who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered. Ophthalmic Use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to bacteria, fungi or viruses. The use of oral corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes. Corticosteroids should not be used in active ocular herpes simplex because of possible corneal perforation.","General Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroid therapy (see ADVERSE REACTIONS: Allergic Reactions ). Increased dosage of rapidly acting corticosteroids is indicated in patients on corticosteroid therapy subjected to any unusual stress before, during and after the stressful situation.","Cardio-Renal Average and large doses of hydrocortisone or cortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion. Literature reports suggest an apparent association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with corticosteroids should be used with great caution in these patients.","Endocrine Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression with the potential for corticosteroid insufficiency after withdrawal of treatment. Adrenocortical insufficiency may result from too rapid withdrawal of corticosteroids and may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for up to 12 months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. If the patient is receiving steroids already, dosage may have to be increased. Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in dosage.","Infection General Patients who are on corticosteroids are more susceptible to infections than are healthy individuals. There may be decreased resistance and inability to localize infection when corticosteroids are used. Infection with any pathogen (viral, bacterial, fungal, protozoan or helminthic) in any location of the body may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect cellular immunity, humoral immunity, or neutrophil function. 1 These infections may be mild, but may be severe and at times fatal. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. 2 Corticosteroids may also mask some signs of current infection. Fungal Infections Corticosteroids may exacerbate systemic fungal infections and therefore should not be used in the presence of such infections unless they are needed to control life-threatening drug reactions. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure (see PRECAUTIONS: Drug Interactions: Amphotericin B Injection and Potassium-Depleting Agents ). Special Pathogens Latent disease may be activated or there may be an exacerbation of intercurrent infections due to pathogens, including those caused by Amoeba, Candida, Cryptococcus, Mycobacterium, Nocardia, Pneumocystis, Toxoplasma . It is recommended that latent amebiasis or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics or any patient with unexplained diarrhea. Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. Corticosteroids should not be used in cerebral malaria. Tuberculosis The use of prednisone in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for management of the disease in conjunction with an appropriate antituberculous regimen. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis. Vaccination Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered. However, the response to such vaccines may be diminished and cannot be predicted. Indicated immunization procedures may be undertaken in patients receiving nonimmunosuppressive doses of corticosteroids as replacement therapy (e.g., for Addison’s disease). Viral Infections Chickenpox and measles can have a more serious or even fatal course in pediatric and adult patients on corticosteroids. In pediatric and adult patients who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered. Ophthalmic Use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to bacteria, fungi or viruses. The use of oral corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes. Corticosteroids should not be used in active ocular herpes simplex because of possible corneal perforation.","General Patients who are on corticosteroids are more susceptible to infections than are healthy individuals. There may be decreased resistance and inability to localize infection when corticosteroids are used. Infection with any pathogen (viral, bacterial, fungal, protozoan or helminthic) in any location of the body may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect cellular immunity, humoral immunity, or neutrophil function. 1 These infections may be mild, but may be severe and at times fatal. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. 2 Corticosteroids may also mask some signs of current infection.","Fungal Infections Corticosteroids may exacerbate systemic fungal infections and therefore should not be used in the presence of such infections unless they are needed to control life-threatening drug reactions. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure (see PRECAUTIONS: Drug Interactions: Amphotericin B Injection and Potassium-Depleting Agents ).","Special Pathogens Latent disease may be activated or there may be an exacerbation of intercurrent infections due to pathogens, including those caused by Amoeba, Candida, Cryptococcus, Mycobacterium, Nocardia, Pneumocystis, Toxoplasma . It is recommended that latent amebiasis or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics or any patient with unexplained diarrhea. Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. Corticosteroids should not be used in cerebral malaria.","Tuberculosis The use of prednisone in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for management of the disease in conjunction with an appropriate antituberculous regimen. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis.","Vaccination Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered. However, the response to such vaccines may be diminished and cannot be predicted. Indicated immunization procedures may be undertaken in patients receiving nonimmunosuppressive doses of corticosteroids as replacement therapy (e.g., for Addison’s disease).","Viral Infections Chickenpox and measles can have a more serious or even fatal course in pediatric and adult patients on corticosteroids. In pediatric and adult patients who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered.","Ophthalmic Use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to bacteria, fungi or viruses. The use of oral corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes. Corticosteroids should not be used in active ocular herpes simplex because of possible corneal perforation."}', 'precautions': '{"PRECAUTIONS General Precautions The lowest possible dose of corticosteroids should be used to control the condition under treatment. When reduction in dosage is possible, the reduction should be gradual. Since complications of treatment with glucocorticoids are dependent on the size of the dose and the duration of treatment, a risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used. Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement. Cardio-Renal As sodium retention with resultant edema and potassium loss may occur in patients receiving corticosteroids, these agents should be used with caution in patients with congestive heart failure, hypertension, or renal insufficiency. Endocrine Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for up to 12 months after discontinuation of therapy following large doses for prolonged periods; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently. There is an enhanced effect of corticosteroids on patients with hypothyroidism. Gastrointestinal Steroids should be used with caution in active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and nonspecific ulcerative colitis, since they may increase the risk of a perforation. Signs of peritoneal irritation following gastrointestinal perforation in patients receiving corticosteroids may be minimal or absent. There is an enhanced effect due to decreased metabolism of corticosteroids in patients with cirrhosis. Musculoskeletal Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (i.e., decreasing absorption and increasing excretion) and inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone secondary to an increase in protein catabolism, and reduced sex hormone production, may lead to inhibition of bone growth in pediatric patients and the development of osteoporosis at any age. Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed. Special consideration should be given to patients at increased risk of osteoporosis (e.g., postmenopausal women) before initiating corticosteroid therapy. Inclusion of therapy for osteoporosis prevention or treatment should be considered. To minimize the risk of glucocortoicoid-induced bone loss, the smallest possible effective dosage and duration should be used. Lifestyle modification to reduce the risk of osteoporosis (e.g., cigarette smoking cessation, limitation of alcohol consumption, participation in weight-bearing exercise for 30-60 minutes daily) should be encouraged. Calcium and vitamin D supplementation, bisphosphonate (e.g., alendronate, risedronate), and a weight-bearing exercise program that maintains muscle mass are suitable first-line therapies aimed at reducing the risk of adverse bone effects. Current recommendations suggest that all interventions be initiated in any patient in whom glucocorticoid therapy with at least the equivalent of 5 mg of prednisone for at least 3 months is anticipated; in addition, sex hormone replacement therapy (combined estrogen and progestin in women; testosterone in men) should be offered to such patients who are hypogonadal or in whom replacement is otherwise clinically indicated and biphosphonate therapy should be initiated (if not already) if bone mineral density (BMD) of the lumbar spine and/or hip is below normal. Neuro-Psychiatric Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not show that they affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect. (See DOSAGE AND ADMINISTRATION: Multiple Sclerosis .) An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatinine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years. Psychiatric derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids. Ophthalmic Intraocular pressure may become elevated in some individuals. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored. Information for Patients Patients should be warned not to discontinue the use of corticosteroids abruptly or without medical supervision. As prolonged use may cause adrenal insufficiency and make patients dependent on corticosteroids, they should advise any medical attendants that they are taking corticosteroids and they should seek medical advice at once should they develop an acute illness including fever or other signs of infection. Following prolonged therapy, withdrawal of corticosteroids may result in symptoms of the corticosteroid withdrawal syndrome including, myalgia, arthralgia, and malaise. Persons who are on corticosteroids should be warned to avoid exposure to chickenpox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay. Drug Interactions Amphotericin B Injection and Potassium-Depleting Agents When corticosteroids are administered concomitantly with potassium-depleting agents (e.g., amphotericin B, diuretics ), patients should be observed closely for development of hypokalemia. In addition, there have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure. Antibiotics Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance (see PRECAUTIONS: Drug Interactions: Hepatic Enzyme Inducers, Inhibitors and Substrates ). Anticholinesterases Concomitant use of anticholinesterase agents (e.g., neostigmine, pyridostigmine ) and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy. If concomitant therapy must occur, it should take place under close supervision and the need for respiratory support should be anticipated. Anticoagulants, Oral Co-administration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect. Antidiabetics Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required. Antitubercular drugs Serum concentrations of isoniazid may be decreased. Bupropion Since systemic steroids, as well as bupropion, can lower the seizure threshold, concurrent administration should be undertaken only with extreme caution; low initial dosing and small gradual increases should be employed. Cholestyramine Cholestyramine may increase the clearance of corticosteroids. Cyclosporine Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use. Digitalis Glycosides Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia. Estrogens, Including Oral Contraceptives Estrogens may decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effect. Fluoroquinolones Post-marketing surveillance reports indicate that the risk of tendon rupture may be increased in patients receiving concomitant fluoroquinolones (e.g., ciprofloxacin, levofloxacin ) and corticosteroids, especially in the elderly. Tendon rupture can occur during or after treatment with quinolones. Hepatic Enzyme Inducers, Inhibitors and Substrates Drugs which induce cytochrome P450 3A4 (CYP 3A4) enzyme activity (e.g., barbiturates, phenytoin, carbamazepine, rifampin ) may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased. Drugs which inhibit CYP 3A4 (e.g., ketoconazole, itraconazole, ritonavir, indinavir, macrolide antibiotics such as erythromycin ) have the potential to result in increased plasma concentrations of corticosteroids. Glucocorticoids are moderate inducers of CYP 3A4. Co-administration with other drugs that are metabolized by CYP 3A4 (e.g., indinavir, erythromycin ) may increase their clearance, resulting in decreased plasma concentration. Ketoconazole Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects. In addition, ketoconazole alone can inhibit adrenal corticosteroid synthesis and may cause adrenal insufficiency during corticosteroid withdrawal. Nonsteroidal Anti-Inflammatory Agents (NSAIDS) Concomitant use of aspirin (or other nonsteroidal anti-inflammatory agents ) and corticosteroids increases the risk of gastrointestinal side effects. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids; this could lead to decreased salicylate serum levels or increase the risk of salicylate toxicity when corticosteroid is withdrawn. Phenytoin In post-marketing experience, there have been reports of both increases and decreases in phenytoin levels with dexamethasone co-administration, leading to alterations in seizure control. Phenytoin has been demonstrated to increase the hepatic metabolism of corticosteroids, resulting in a decreased therapeutic effect of the corticosteroid. Quetiapine Increased doses of quetiapine may be required to maintain control of symptoms of schizophrenia in patients receiving a glucocorticoid, a hepatic enzyme inducer. Skin Tests Corticosteroids may suppress reactions to skin tests. Thalidomide Co-administration with thalidomide should be employed cautiously, as toxic epidermal necrolysis has been reported with concomitant use. Vaccines Patients on corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. Routine administration of vaccines or toxoids should be deferred until corticosteroid therapy is discontinued if possible (see WARNINGS: Infection: Vaccination ). Carcinogenesis, Mutagenesis, Impairment of Fertility No adequate studies have been conducted in animals to determine whether corticosteroids have a potential for carcinogenesis or mutagenesis. Steroids may increase or decrease motility and number of spermatozoa in some patients. Pregnancy Teratogenic Effects Pregnancy Category C Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose. Animal studies in which corticosteroids have been given to pregnant mice, rats, and rabbits have yielded an increased incidence of cleft palate in the offspring. There are no adequate and well-controlled studies in pregnant women. Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism. Nursing Mothers Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Because of the potential for serious adverse reactions in nursing infants from corticosteroids, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use The efficacy and safety of corticosteroids in the pediatric population are based on the well-established course of effect of corticosteroids, which is similar in pediatric and adult populations. Published studies provide evidence of efficacy and safety in pediatric patients for the treatment of nephrotic syndrome (patients >2 years of age), and aggressive lymphomas and leukemias (patients >1 month of age). Other indications for pediatric use of corticosteroids, e.g., severe asthma and wheezing, are based on adequate and well-controlled trials conducted in adults, on the premises that the course of the diseases and their pathophysiology are considered to be substantially similar in both populations. The adverse effects of corticosteroids in pediatric patients are similar to those in adults (see ADVERSE REACTIONS ). Like adults, pediatric patients should be carefully observed with frequent measurements of blood pressure, weight, height, intraocular pressure, and clinical evaluation for the presence of infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis. Pediatric patients who are treated with corticosteroids by any route, including systemically administered corticosteroids, may experience a decrease in their growth velocity. This negative impact of corticosteroids on growth has been observed at low systemic doses and in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression (i.e., cosyntropin stimulation and basal cortisol plasma levels). Growth velocity may therefore be a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The linear growth of pediatric patients treated with corticosteroids should be monitored, and the potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of treatment alternatives. In order to minimize the potential growth effects of corticosteroids, pediatric patients should be titrated to the lowest effective dose. Geriatric Use Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. In particular, the increased risk of diabetes mellitus, fluid retention and hypertension in elderly patients treated with corticosteroids should be considered.","Cardio-Renal As sodium retention with resultant edema and potassium loss may occur in patients receiving corticosteroids, these agents should be used with caution in patients with congestive heart failure, hypertension, or renal insufficiency.","Endocrine Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for up to 12 months after discontinuation of therapy following large doses for prolonged periods; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently. There is an enhanced effect of corticosteroids on patients with hypothyroidism.","Gastrointestinal Steroids should be used with caution in active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and nonspecific ulcerative colitis, since they may increase the risk of a perforation. Signs of peritoneal irritation following gastrointestinal perforation in patients receiving corticosteroids may be minimal or absent. There is an enhanced effect due to decreased metabolism of corticosteroids in patients with cirrhosis.","Musculoskeletal Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (i.e., decreasing absorption and increasing excretion) and inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone secondary to an increase in protein catabolism, and reduced sex hormone production, may lead to inhibition of bone growth in pediatric patients and the development of osteoporosis at any age. Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed. Special consideration should be given to patients at increased risk of osteoporosis (e.g., postmenopausal women) before initiating corticosteroid therapy. Inclusion of therapy for osteoporosis prevention or treatment should be considered. To minimize the risk of glucocortoicoid-induced bone loss, the smallest possible effective dosage and duration should be used. Lifestyle modification to reduce the risk of osteoporosis (e.g., cigarette smoking cessation, limitation of alcohol consumption, participation in weight-bearing exercise for 30-60 minutes daily) should be encouraged. Calcium and vitamin D supplementation, bisphosphonate (e.g., alendronate, risedronate), and a weight-bearing exercise program that maintains muscle mass are suitable first-line therapies aimed at reducing the risk of adverse bone effects. Current recommendations suggest that all interventions be initiated in any patient in whom glucocorticoid therapy with at least the equivalent of 5 mg of prednisone for at least 3 months is anticipated; in addition, sex hormone replacement therapy (combined estrogen and progestin in women; testosterone in men) should be offered to such patients who are hypogonadal or in whom replacement is otherwise clinically indicated and biphosphonate therapy should be initiated (if not already) if bone mineral density (BMD) of the lumbar spine and/or hip is below normal.","Neuro-Psychiatric Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not show that they affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect. (See DOSAGE AND ADMINISTRATION: Multiple Sclerosis .) An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatinine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years. Psychiatric derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.","Ophthalmic Intraocular pressure may become elevated in some individuals. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored."}', 'information_for_patients': '{"Information for Patients Patients should be warned not to discontinue the use of corticosteroids abruptly or without medical supervision. As prolonged use may cause adrenal insufficiency and make patients dependent on corticosteroids, they should advise any medical attendants that they are taking corticosteroids and they should seek medical advice at once should they develop an acute illness including fever or other signs of infection. Following prolonged therapy, withdrawal of corticosteroids may result in symptoms of the corticosteroid withdrawal syndrome including, myalgia, arthralgia, and malaise. Persons who are on corticosteroids should be warned to avoid exposure to chickenpox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay."}', 'pregnancy': '{"Pregnancy Teratogenic Effects Pregnancy Category C Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose. Animal studies in which corticosteroids have been given to pregnant mice, rats, and rabbits have yielded an increased incidence of cleft palate in the offspring. There are no adequate and well-controlled studies in pregnant women. Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism."}', 'pediatric_use': '{"Pediatric Use The efficacy and safety of corticosteroids in the pediatric population are based on the well-established course of effect of corticosteroids, which is similar in pediatric and adult populations. Published studies provide evidence of efficacy and safety in pediatric patients for the treatment of nephrotic syndrome (patients >2 years of age), and aggressive lymphomas and leukemias (patients >1 month of age). Other indications for pediatric use of corticosteroids, e.g., severe asthma and wheezing, are based on adequate and well-controlled trials conducted in adults, on the premises that the course of the diseases and their pathophysiology are considered to be substantially similar in both populations. The adverse effects of corticosteroids in pediatric patients are similar to those in adults (see ADVERSE REACTIONS ). Like adults, pediatric patients should be carefully observed with frequent measurements of blood pressure, weight, height, intraocular pressure, and clinical evaluation for the presence of infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis. Pediatric patients who are treated with corticosteroids by any route, including systemically administered corticosteroids, may experience a decrease in their growth velocity. This negative impact of corticosteroids on growth has been observed at low systemic doses and in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression (i.e., cosyntropin stimulation and basal cortisol plasma levels). Growth velocity may therefore be a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The linear growth of pediatric patients treated with corticosteroids should be monitored, and the potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of treatment alternatives. In order to minimize the potential growth effects of corticosteroids, pediatric patients should be titrated to the lowest effective dose."}', 'geriatric_use': '{"Geriatric Use Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. In particular, the increased risk of diabetes mellitus, fluid retention and hypertension in elderly patients treated with corticosteroids should be considered."}'}

{POMALIDOMIDE}

{'contraindications': '{"4 CONTRAINDICATIONS • Pregnancy ( 4.1 ) • Hypersensitivity ( 4.2 ) 4.1 Pregnancy POMALYST is contraindicated in females who are pregnant. POMALYST can cause fetal harm when administered to a pregnant female [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ]. Pomalidomide is a thalidomide analogue and is teratogenic in both rats and rabbits when administered during the period of organogenesis. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus. 4.2 Hypersensitivity POMALYST is contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, anaphylaxis) to pomalidomide or any of the excipients [see Warnings and Precautions (5.7) , Description (11) ] ."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following clinically significant adverse reactions are described in detail in other labeling sections: • Embryo-Fetal Toxicity [see Warnings and Precautions (5.1 , 5.2) ] • Venous and Arterial Thromboembolism [see Warnings and Precautions (5.3) ] • Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone [see Warnings and Precautions (5.4) ] • Hematologic Toxicity [see Warnings and Precautions (5.5)] • Hepatotoxicity [see Warnings and Precautions (5.6) ] • Severe Cutaneous Reactions [see Warnings and Precautions (5.7) ] • Dizziness and Confusional State [see Warnings and Precautions (5.8) ] • Neuropathy [see Warnings and Precautions (5.9) ] • Risk of Second Primary Malignancies [see Warnings and Precautions (5.10) ] • Tumor Lysis Syndrome [see Warnings and Precautions (5.11) ] • Hypersensitivity [see Warnings and Precautions (5.12) ] • MM: Most common adverse reactions (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, and pyrexia ( 6.1 ). • KS: Most common adverse reactions including laboratory abnormalities (≥30%) are decreased absolute neutrophil count or white blood cells, elevated creatinine or glucose, rash, constipation, fatigue, decreased hemoglobin, platelets, phosphate, albumin, or calcium, increased ALT, nausea, and diarrhea ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Bristol Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Multiple Myeloma (MM) In Trial 1, data were evaluated from 219 patients (safety population) who received treatment with POMALYST + Low-dose Dex (112 patients) or POMALYST alone (107 patients). Median number of treatment cycles was 5. Sixty-seven percent of patients in the study had a dose interruption of either drug due to adverse reactions. Forty-two percent of patients in the study had a dose reduction of either drug due to adverse reactions. The discontinuation rate due to adverse reactions was 11%. In Trial 2, data were evaluated from 450 patients (safety population) who received treatment with POMALYST + Low-dose Dex (300 patients) or High-dose Dexamethasone (High-dose Dex) (150 patients). The median number of treatment cycles for the POMALYST + Low-dose Dex arm was 5. In the POMALYST + Low-dose Dex arm, 67% of patients had a dose interruption of POMALYST, the median time to the first dose interruption of POMALYST was 4.1 weeks. Twenty-seven percent of patients had a dose reduction of POMALYST, the median time to the first dose reduction of POMALYST was 4.5 weeks. Eight percent of patients discontinued POMALYST due to adverse reactions. Tables 3 and 4 summarize the adverse reactions reported in Trials 1 and 2, respectively. Table 3: Adverse Reactions in Any POMALYST Treatment Arm in Trial 1* * Regardless of attribution of relatedness to POMALYST. a POMALYST alone arm includes all patients randomized to the POMALYST alone arm who took study drug; 61 of the 107 patients had dexamethasone added during the treatment period. b Serious adverse reactions were reported in at least 2 patients in any POMALYST treatment arm. Data cutoff: 01 March 2013 All Adverse Reactions ≥10% in Either Arm Grade 3 or 4 ≥5% in Either Arm Body System Adverse Reaction POMALYST a (N=107) POMALYST + Low-dose Dex (N=112) POMALYST (N=107) POMALYST + Low-dose Dex (N=112) Number (%) of patients with at least one adverse reaction 107 (100) 112 (100) 98 (92) 102 (91) Blood and lymphatic system disorders Neutropenia b 57 (53) 55 (49) 51 (48) 46 (41) Anemia b 41 (38) 47 (42) 25 (23) 24 (21) Thrombocytopenia b 28 (26) 26 (23) 24 (22) 21 (19) Leukopenia 14 (13) 22 (20) 7 (7) 11 (10) Febrile neutropenia b <10% <10% 6 (6) 3 (3) Lymphopenia 4 (4) 17 (15) 2 (2) 8 (7) General disorders and administration site conditions Fatigue and asthenia b 62 (58) 70 (63) 13 (12) 19 (17) Edema peripheral 27 (25) 19 (17) 0 (0.0) 0 (0.0) Pyrexia b 25 (23) 36 (32) <5% <5% Chills 11 (10) 14 (13) 0 (0.0) 0 (0.0) Gastrointestinal disorders Nausea b 39 (36) 27 (24) <5% <5% Constipation b 38 (36) 41 (37) <5% <5% Diarrhea 37 (35) 40 (36) <5% <5% Vomiting b 15 (14) 16 (14) <5% 0 (0.0) Musculoskeletal and connective tissue disorders Back pain b 37 (35) 36 (32) 15 (14) 11 (10) Musculoskeletal chest pain 25 (23) 22 (20) <5% 0 (0.0) Muscle spasms 23 (21) 22 (20) <5% <5% Arthralgia 18 (17) 17 (15) <5% <5% Muscular weakness 15 (14) 15 (13) 6 (6) 4 (4) Bone pain 13 (12) 8 (7) <5% <5% Musculoskeletal pain 13 (12) 19 (17) <5% <5% Pain in extremity 8 (7) 16 (14) 0 (0.0) <5% Infections and infestations Upper respiratory tract infection 40 (37) 32 (29) <5% <5% Pneumonia b 30 (28) 38 (34) 21 (20) 32 (29) Urinary tract infection b 11 (10) 19 (17) 2 (2) 10 (9) Sepsis b <10% <10% 6 (6) 5 (4) Metabolism and nutrition disorders Decreased appetite 25 (23) 21 (19) <5% 0 (0.0) Hypercalcemia b 23 (21) 13 (12) 11 (10) 1 (<1) Hypokalemia 13 (12) 13 (12) <5% <5% Hyperglycemia 12 (11) 17 (15) <5% <5% Hyponatremia 12 (11) 14 (13) <5% <5% Dehydration b <10% <10% 5 (4.7) 6 (5.4) Hypocalcemia 6 (6) 13 (12) 0 (0.0) <5% Respiratory, thoracic and mediastinal disorders Dyspnea b 38 (36) 50 (45) 8 (7) 14 (13) Cough 18 (17) 25 (22) 0 (0.0) 0 (0.0) Epistaxis 18 (17) 12 (11) <5% 0 (0.0) Productive cough 10 (9) 14 (13) 0 (0.0) 0 (0.0) Oropharyngeal pain 6 (6) 12 (11) 0 (0.0) 0 (0.0) Nervous system disorders Dizziness 24 (22) 20 (18) <5% <5% Peripheral neuropathy 23 (21) 20 (18) 0 (0.0) 0 (0.0) Headache 16 (15) 15 (13) 0 (0.0) <5% Tremor 11 (10) 15 (13) 0 (0.0) 0 (0.0) Skin and subcutaneous tissue disorders Rash 22 (21) 18 (16) 0 (0.0) <5% Pruritus 16 (15) 10 (9) 0 (0.0) 0 (0.0) Dry skin 10 (9) 12 (11) 0 (0.0) 0 (0.0) Hyperhidrosis 8 (7) 18 (16) 0 (0.0) 0 (0.0) Night sweats 5 (5) 14 (13) 0 (0.0) 0 (0.0) Investigations Blood creatinine increased b 20 (19) 11 (10) 6 (6) 3 (3) Weight decreased 16 (15) 10 (9) 0 (0.0) 0 (0.0) Weight increased 1 (<1) 12 (11) 0 (0.0) 0 (0.0) Psychiatric disorders Anxiety 14 (13) 8 (7) 0 (0.0) 0 (0.0) Confusional state b 13 (12) 15 (13) 6 (6) 3 (3) Insomnia 7 (7) 18 (16) 0 (0.0) 0 (0.0) Renal and urinary disorders Renal failure b 16 (15) 11 (10) 9 (8) 8 (7) Table 4: Adverse Reactions in Trial 2 a Percentage did not meet the criteria to be considered as an adverse reaction for POMALYST for that category of event (i.e., all adverse events or Grade 3 or 4 adverse events). b Serious adverse reactions were reported in at least 3 patients in the POM + Low-dose Dex arm, AND at least 1% higher than the High-dose-Dex arm percentage. Data cutoff: 01 March 2013 All Adverse Reactions (≥5% in POMALYST + Low-dose Dex arm, and at least 2% higher than the High-dose-Dex arm) Grade 3 or 4 (≥1% in POMALYST + Low-dose Dex arm, and at least 1% higher than the High-dose-Dex arm) Body System Adverse Reaction POMALYST + Low-dose Dex (N=300) High-dose Dex (N=150) POMALYST + Low-dose Dex (N=300) High-dose Dex (N=150) Number (%) of patients with at least one adverse reaction 297 (99) 149 (99) 259 (86) 127 (85) Blood and lymphatic system disorders Neutropenia b 154 (51) 31 (21) 145 (48) 24 (16) Thrombocytopenia 89 (30) a 44 (29) a 66 (22) a 39 (26) a Leukopenia 38 (13) 8 (5) 27 (9) 5 (3) Febrile neutropenia b 28 (9) 0 (0.0) 28 (9) 0 (0.0) General disorders and administration site conditions Fatigue and asthenia 140 (47) 64 (43) 26 (9) a 18 (12) a Pyrexia b 80 (27) 35 (23) 9 (3) a 7 (5) a Edema peripheral 52 (17) 17 (11) 4 (1) a 3 (2) a Pain 11 (4) a 3 (2) a 5 (2) 1 (<1) Infections and infestations Upper respiratory tract infection b 93 (31) 19 (13) 9 (3) 1 (<1) Pneumonia b 58 (19) 20 (13) 47 (16) 15 (10) Neutropenic sepsis b 3 (1) a 0 (0.0) a 3 (1) 0 (0.0) Gastrointestinal disorders Diarrhea 66 (22) 28 (19) 3 (1) a 2 (1) a Constipation 65 (22) 22 (15) 7 (2) 0 (0.0) Nausea 45 (15) 17 (11) 3 (1) a 2 (1) a Vomiting 23 (8) 6 (4) 3 (1) 0 (0.0) Musculoskeletal and connective tissue disorders Back pain b 59 (20) 24 (16) 15 (5) 6 (4) Bone pain b 54 (18) 21 (14) 22 (7) 7 (5) Muscle spasms 46 (15) 11 (7) 1 (<1) a 1 (<1) a Arthralgia 26 (9) 7 (5) 2 (<1) a 1 (<1) a Pain in extremity 20 (7) a 9 (6) a 6 (2) 0 (0.0) Respiratory, thoracic and mediastinal disorders Dyspnea b 76 (25) 25 (17) 17 (6) 7 (5) Cough 60 (20) 15 (10) 2 (<1) a 1 (<1) a Chronic obstructive pulmonary disease b 5 (2) a 0 (0.0) a 4 (1) 0 (0.0) Nervous system disorders Peripheral neuropathy 52 (17) 18 (12) 5 (2) a 2 (1) a Dizziness 37 (12) 14 (9) 4 (1) a 2 (1) a Headache 23 (8) 8 (5) 1 (<1) a 0 (0.0) a Tremor 17 (6) 2 (1) 2 (<1) a 0 (0.0) a Depressed level of consciousness 5 (2) a 0 (0.0) a 3 (1) 0 (0.0) Metabolism and nutrition disorders Decreased appetite 38 (13) 12 (8) 3 (1) a 2 (1) a Hypokalemia 28 (9) a 12 (8) a 12 (4) 4 (3) Hypocalcemia 12 (4) a 9 (6) a 5 (2) 1 (<1) Skin and subcutaneous tissue disorders Rash 23 (8) 2 (1) 3 (1) 0 (0.0) Pruritus 22 (7) 5 (3) 0 (0.0) a 0 (0.0) a Hyperhidrosis 15 (5) 1 (<1) 0 (0.0) a 0 (0.0) a Investigations Neutrophil count decreased 15 (5) 1 (<1) 14 (5) 1 (<1) Platelet count decreased 10 (3) a 3 (2) a 8 (3) 2 (1) White blood cell count decreased 8 (3) a 1 (<1) a 8 (3) 0 (0.0) Alanine aminotransferase increased 7 (2) a 2 (1) a 5 (2) 0 (0.0) Aspartate aminotransferase increased 4 (1) a 2 (1) a 3 (1) 0 (0.0) Lymphocyte count decreased 3 (1) a 1 (<1) a 3 (1) 0 (0.0) Renal and urinary disorders Renal failure 31 (10) a 18 (12) a 19 (6) 8 (5) Injury, poisoning and procedural complications Femur fracture b 5 (2) a 1 (<1) a 5 (2) 1 (<1) Reproductive system and breast disorders Pelvic pain 6 (2) a 3 (2) a 4 (1) 0 (0.0) Other Adverse Reactions Other adverse reactions of POMALYST in patients with MM, not described above, and considered important: Cardiac Disorders: Myocardial infarction, Atrial fibrillation, Angina pectoris, Cardiac failure congestive Ear and Labyrinth Disorders: Vertigo Gastrointestinal disorders: Abdominal pain General Disorders and Administration Site Conditions: General physical health deterioration, Non-cardiac chest pain, Multi-organ failure Hepatobiliary Disorders: Hyperbilirubinemia Infections and Infestations: Pneumocystis jiroveci pneumonia, Respiratory syncytial virus infection, Neutropenic sepsis, Bacteremia, Pneumonia respiratory syncytial viral, Cellulitis, Urosepsis, Septic shock, Clostridium difficile colitis, Pneumonia streptococcal, Lobar pneumonia, Viral infection, Lung infection Investigations: Alanine aminotransferase increased, Hemoglobin decreased Injury, poisoning and procedural complications: Fall, Compression fracture, Spinal compression fracture Metabolism and nutritional disorders: Hyperkalemia, Failure to thrive Nervous system disorders: Depressed level of consciousness, Syncope Psychiatric disorders: Mental status change Renal and urinary disorders: Urinary retention, Hyponatremia Reproductive system and breast disorders: Pelvic pain Respiratory, thoracic, and mediastinal disorders: Interstitial lung disease, Pulmonary embolism, Respiratory failure, Bronchospasm Vascular disorders: Hypotension Kaposi Sarcoma (KS) The safety of POMALYST in patients with KS was evaluated in Trial 12-C-0047 [see Clinical Studies (14.2) ] . Twenty-eight patients received POMALYST 5 mg taken orally once daily on Days 1 through 21 of repeated 28-day cycles. The study excluded patients with procoagulant disorders or a history of venous or arterial thromboembolism. Patients received DVT prophylaxis with daily low dose aspirin. Across all patients treated on Trial 12-C-0047, 75% were exposed to pomalidomide for 6 months or longer and 25% were exposed for greater than one year. Serious adverse reactions occurred in 18% (5/28) of patients who received POMALYST. The following serious adverse reactions each occurred in 1 patient: anemia, decreased neutrophil count, and hematuria. Permanent discontinuation due to an adverse reaction occurred in 11% (3/28) of patients who received POMALYST. Dosage interruptions due to an adverse reaction occurred in 14% (4/28) of patients who received POMALYST. The most frequent adverse reaction requiring dosage interruption was decreased neutrophil count, which occurred in 3 patients. The POMALYST dose was reduced due to an adverse reaction in 1 patient due to gout. Tables 5 and 6 summarize the adverse reactions and select laboratory abnormalities reported in Trial 12-C-0047. Table 5: Adverse Reactions (≥ 20%) in Patients Who Received POMALYST in Trial 12-C-0047 Adverse Reaction Grades 1-4 N=28 % Grade 3 or 4 N=28 % Rash, maculo-papular 71 3.6 Constipation 71 0 Fatigue 68 0 Nausea 36 0 Diarrhea 32 3.6 Cough 29 0 Dyspnea 29 0 Peripheral Edema 29 3.6 Upper respiratory tract infection 29 0 Muscle spasms 25 0 Hypothyroidism 21 0 Dry skin 21 0 Chills 21 0 Table 6: Frequency of Select Laboratory Abnormalities (≥ 10%) Worsening from Baseline in Patients Who Received POMALYST in Trial 12-C-0047 * Denominator is the number of patients for whom there is a baseline and at least one post baseline assessment for the laboratory parameter. Laboratory Abnormality Grades 1-4* % Grades 3-4* % Hematology Decreased Absolute Neutrophil Count 96 50 Decreased White Blood Cells 79 3.6 Decreased Hemoglobin 54 0 Decreased Platelets 54 0 Chemistry Elevated Creatinine 86 3.6 Elevated Glucose 57 7 Decreased Albumin 54 0 Decreased Phosphate 54 25 Decreased Calcium 50 0 Increased Alanine Aminotransferase (ALT) 32 0 Increased Aspartate Aminotransferase (AST) 25 0 Elevated Creatine Kinase 25 7 Decreased Magnesium 14 0 Elevated Alkaline Phosphate 14 3.6 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of POMALYST. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders: Pancytopenia Endocrine Disorders: Hypothyroidism, hyperthyroidism Gastrointestinal Disorders: Gastrointestinal hemorrhage Hepatobiliary Disorders: Hepatic failure (including fatal cases), elevated liver enzymes Immune system Disorders: Allergic reactions (e.g., angioedema, anaphylaxis, urticaria), solid organ transplant rejection Infections and Infestations: Hepatitis B virus reactivation, Herpes zoster, progressive multifocal leukoencephalopathy (PML) Neoplasms benign, malignant and unspecified (incl cysts and polyps): Tumor lysis syndrome, basal cell carcinoma, and squamous cell carcinoma of the skin Skin and Subcutaneous Tissue Disorders: Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS)"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Strong CYP1A2 Inhibitors: Avoid concomitant use of strong CYP1A2 inhibitors. If concomitant use of a strong CYP1A2 inhibitor is unavoidable, reduce POMALYST dose to 2 mg ( 2.6 , 7.1 , 12.3 ). 7.1 Drugs That Affect Pomalidomide Plasma Concentrations CYP1A2 inhibitors : In healthy subjects, co-administration of fluvoxamine, a strong CYP1A2 inhibitor, increased C max and AUC of pomalidomide by 24% and 125% respectively [see Clinical Pharmacology (12.3) ] . Increased pomalidomide exposure may increase the risk of exposure related toxicities. Avoid co-administration of strong CYP1A2 inhibitors (e.g. ciprofloxacin and fluvoxamine) . If co-administration is unavoidable, reduce the POMALYST dose [see Dosage and Administration (2.6) ] ."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE POMALYST is a thalidomide analogue indicated, for the treatment of adult patients: • in combination with dexamethasone, for patients with multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy ( 1.1 ). • with AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART) or in patients with KS who are HIV-negative. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s) ( 1.2 ). 1.1 Multiple Myeloma POMALYST, in combination with dexamethasone, is indicated for adult patients with multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy. 1.2 Kaposi Sarcoma POMALYST is indicated for the treatment of: • Adult patients with AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART). • Kaposi sarcoma (KS) in adult patients who are HIV-negative. This indication is approved under accelerated approval based on overall response rate [see Clinical Studies (14.2) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Increased Mortality: Observed in patients with MM when pembrolizumab was added to dexamethasone and a thalidomide analogue ( 5.4 ). • Hematologic Toxicity: Neutropenia was the most frequently reported Grade 3/4 adverse event. Monitor patients for hematologic toxicities, especially neutropenia ( 5.5 ). • Hepatotoxicity: Hepatic failure including fatalities; monitor liver function tests monthly ( 5.6 ). • Severe Cutaneous Reactions: Discontinue POMALYST for severe reactions ( 5.7 ). • Tumor Lysis Syndrome (TLS): Monitor patients at risk of TLS (i.e., those with high tumor burden) and take appropriate precautions ( 5.11 ). • Hypersensitivity: Monitor patients for potential hypersensitivity. Discontinue POMALYST for angioedema and anaphylaxis ( 5.12 ). 5.1 Embryo-Fetal Toxicity POMALYST is a thalidomide analogue and is contraindicated for use during pregnancy. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death [see Use in Specific Populations (8.1) ] . POMALYST is only available through the POMALYST REMS program [see Warnings and Precautions (5.2) ]. Females of Reproductive Potential Females of reproductive potential must avoid pregnancy for at least 4 weeks before beginning POMALYST therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy. Females must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control, beginning 4 weeks prior to initiating treatment with POMALYST, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of POMALYST therapy. Two negative pregnancy tests must be obtained prior to initiating therapy. The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing POMALYST therapy and then weekly during the first month, then monthly thereafter in females with regular menstrual cycles, or every 2 weeks in females with irregular menstrual cycles [see Use in Specific Populations (8.3) ]. Males Pomalidomide is present in the semen of patients receiving the drug. Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful vasectomy. Male patients taking POMALYST must not donate sperm [see Use in Specific Populations (8.3) ] . Blood Donation Patients must not donate blood during treatment with POMALYST and for 4 weeks following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST. 5.2 POMALYST REMS Program Because of the embryo-fetal risk [see Warnings and Precautions (5.1) ], POMALYST is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), the \\" POMALYST REMS\\" program. Required components of the POMALYST REMS program include the following: • Prescribers must be certified with the POMALYST REMS program by enrolling and complying with the REMS requirements. • Patients must sign a Patient-Physician Agreement Form and comply with the REMS requirements. In particular, female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements [see Use in Specific Populations (8.3) ] and males must comply with contraception requirements [see Use in Specific Populations (8.3) ]. • Pharmacies must be certified with the POMALYST REMS program, must only dispense to patients who are authorized to receive POMALYST and comply with REMS requirements. Further information about the POMALYST REMS program is available at www.pomalystrems.com or by telephone at 1-888-423-5436. 5.3 Venous and Arterial Thromboembolism Venous thromboembolic events (deep venous thrombosis and pulmonary embolism) and arterial thromboembolic events (myocardial infarction and stroke) have been observed in patients treated with POMALYST. In Trial 2, where anticoagulant therapies were mandated, thromboembolic events occurred in 8.0% of patients treated with POMALYST and low dose-dexamethasone (Low-dose Dex), and 3.3% of patients treated with high-dose dexamethasone. Venous thromboembolic events (VTE) occurred in 4.7% of patients treated with POMALYST and Low-dose Dex, and 1.3% of patients treated with high-dose dexamethasone. Arterial thromboembolic events include terms for arterial thromboembolic events, ischemic cerebrovascular conditions, and ischemic heart disease. Arterial thromboembolic events occurred in 3.0% of patients treated with POMALYST and Low-dose Dex, and 1.3% of patients treated with high-dose dexamethasone. Patients with known risk factors, including prior thrombosis, may be at greater risk, and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient\'s underlying risk factors. 5.4 Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone In two randomized clinical trials in patients with MM, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone, a use for which no PD-1 or PD-L1 blocking antibody is indicated, resulted in increased mortality. Treatment of patients with MM with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials. 5.5 Hematologic Toxicity Multiple Myeloma In trials 1 and 2 in patients who received POMALYST + Low-dose Dex, neutropenia was the most frequently reported Grade 3 or 4 adverse reaction, followed by anemia and thrombocytopenia. Neutropenia of any grade was reported in 51% of patients in both trials. The rate of Grade 3 or 4 neutropenia was 46%. The rate of febrile neutropenia was 8%. Monitor patients for hematologic toxicities, especially neutropenia. Monitor complete blood counts weekly for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification [see Dosage and Administration (2.4) ] . Kaposi Sarcoma In Trial 12-C-0047, hematologic toxicities were the most common (all grades and Grade 3 or 4) adverse reactions [see Adverse Reactions (6.1) ] . Fifty percent of patients had Grade 3 or 4 neutropenia. Monitor patients for hematologic toxicities, especially decreased neutrophils. Monitor complete blood counts every 2 weeks for the first 12 weeks and monthly thereafter. Withhold, reduce the dose, or permanently discontinue POMALYST based on the severity of the reaction [see Dosage and Administration (2.4) ] . 5.6 Hepatotoxicity Hepatic failure, including fatal cases, has occurred in patients treated with POMALYST. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with POMALYST. Monitor liver function tests monthly. Stop POMALYST upon elevation of liver enzymes and evaluate. After return to baseline values, treatment at a lower dose may be considered. 5.7 Severe Cutaneous Reactions Severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. These reactions can be fatal. Consider POMALYST interruption or discontinuation for Grade 2 or 3 skin rash. Permanently discontinue POMALYST for Grade 4 rash, exfoliative or bullous rash, or for other severe cutaneous reactions such as SJS, TEN or DRESS [see Dosage and Administration (2.5) ] . 5.8 Dizziness and Confusional State In trials 1 and 2 in patients who received POMALYST + Low-dose Dex, 14% of patients experienced dizziness and 7% of patients experienced a confusional state; 1% of patients experienced Grade 3 or 4 dizziness, and 3% of patients experienced Grade 3 or 4 confusional state. Instruct patients to avoid situations where dizziness or confusional state may be a problem and not to take other medications that may cause dizziness or confusional state without adequate medical advice. 5.9 Neuropathy In trials 1 and 2 in patients who received POMALYST + Low-dose Dex, 18% of patients experienced neuropathy, with approximately 12% of the patients experiencing peripheral neuropathy. Two percent of patients experienced Grade 3 neuropathy in trial 2. There were no cases of Grade 4 neuropathy adverse reactions reported in either trial. 5.10 Risk of Second Primary Malignancies Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of MM. 5.11 Tumor Lysis Syndrome Tumor lysis syndrome (TLS) may occur in patients treated with POMALYST. Patients at risk for TLS are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken. 5.12 Hypersensitivity Hypersensitivity, including angioedema, anaphylaxis, and anaphylactic reactions to POMALYST have been reported. Permanently discontinue POMALYST for angioedema or anaphylaxis [see Dosage and Administration (2.5) ] ."}', 'overdosage': '{"10 OVERDOSAGE Hemodialysis can remove pomalidomide from circulation."}', 'active_flag': 'Y', 'generic_name': '{POMALIDOMIDE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Embryo-Fetal Toxicity Advise patients that POMALYST is contraindicated in pregnancy [see Contraindications (4) ] . POMALYST is a thalidomide analogue and may cause serious birth defects or death to a developing baby [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] . • Advise females of reproductive potential that they must avoid pregnancy while taking POMALYST and for at least 4 weeks after completing therapy. • Initiate POMALYST treatment in females of reproductive potential only following a negative pregnancy test. • Advise females of reproductive potential of the importance of monthly pregnancy tests and the need to use 2 different forms of contraception, including at least 1 highly effective form, simultaneously during POMALYST therapy, during dose interruptions, and for 4 weeks after she has completely finished taking POMALYST. Highly effective forms of contraception other than tubal ligation include IUD and hormonal (birth control pills, injections, patch, or implants) and a partner\'s vasectomy. Additional effective contraceptive methods include latex or synthetic condom, diaphragm, and cervical cap. • Instruct patient to immediately stop taking POMALYST and contact her healthcare provider if she becomes pregnant while taking this drug, if she misses her menstrual period or experiences unusual menstrual bleeding, if she stops taking birth control, or if she thinks FOR ANY REASON that she may be pregnant. • Advise patient that if her healthcare provider is not available, she should call the REMS Call Center at 1-888-423-5436 [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3) ]. • Advise males to always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful vasectomy. • Advise male patients taking POMALYST that they must not donate sperm [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3) ] . • All patients must be instructed to not donate blood while taking POMALYST and for 4 weeks following discontinuation of POMALYST [see Warnings and Precautions (5.1) ] . POMALYST REMS Program Because of the risk of embryo-fetal toxicity, POMALYST is only available through a restricted program called POMALYST REMS [see Warnings and Precautions (5.2) ] . • Patients must sign a Patient-Physician Agreement Form and comply with the requirements to receive POMALYST. In particular, females of reproductive potential must comply with the pregnancy testing, contraception requirements, and participate in monthly telephone surveys. Males must comply with the contraception requirements [see Use in Specific Populations (8.3) ] . • POMALYST is available only from pharmacies that are certified in POMALYST REMS program. Provide patients with the telephone number and website for information on how to obtain the product. Pregnancy Exposure Registry Inform females that there is a Pregnancy Exposure Registry that monitors pregnancy outcomes in females exposed to POMALYST during pregnancy and that they can contact the Pregnancy Exposure Registry by calling 1-888-423-5436 [see Use in Specific Populations (8.1) ] . Venous and Arterial Thromboembolism Inform patients of the risk of developing DVT, PE, MI, and stroke and to report immediately any signs and symptoms suggestive of these events for evaluation [see Warnings and Precautions (5.3) ] . Hematologic Toxicities Inform patients on the risks of developing neutropenia, thrombocytopenia, and anemia and the need to report signs and symptoms associated with these events to their healthcare provider for further evaluation [see Warnings and Precautions (5.5) ] . Hepatotoxicity Inform patients on the risks of developing hepatotoxicity, including hepatic failure and death, and to report signs and symptoms associated with these events to their healthcare provider for evaluation [see Warnings and Precautions (5.6) ] . Severe Cutaneous Reactions Inform patients of the potential risk for severe skin reactions such as SJS, TEN and DRESS and to report any signs and symptoms associated with these reactions to their healthcare provider for evaluation [see Warnings and Precautions (5.7) ] . Dizziness and Confusional State Inform patients of the potential risk of dizziness and confusional state with the drug, to avoid situations where dizziness or confusional state may be a problem, and not to take other medications that may cause dizziness or confusional state without adequate medical advice [see Warnings and Precautions (5.8) ] . Neuropathy Inform patients of the risk of neuropathy and to report the signs and symptoms associated with these events to their healthcare provider for further evaluation [see Warnings and Precautions (5.9) ] . Second Primary Malignancies Inform the patient that the potential risk of developing acute myelogenous leukemia during treatment with POMALYST is unknown [see Warnings and Precautions (5.10) ] . Tumor Lysis Syndrome Inform patients of the potential risk of tumor lysis syndrome and to report any signs and symptoms associated with this event to their healthcare provider for evaluation [see Warnings and Precautions (5.11) ] . Hypersensitivity Inform patients of the potential for severe hypersensitivity reactions such as angioedema and anaphylaxis to POMALYST. Instruct patients to contact their healthcare provider right away for any signs and symptoms of these reactions. Advise patients to seek emergency medical attention for signs or symptoms of severe hypersensitivity reactions [see Warnings and Precautions (5.12) ] . Smoking Tobacco Advise patients that smoking tobacco may reduce the efficacy of POMALYST [see Use in Specific Populations (8.8) and Clinical Pharmacology (12.3) ] . Dosing Instructions Inform patients on how to take POMALYST [see Dosage and Administration (2.2 , 2.3 , 2.9) ] • POMALYST should be taken once daily at about the same time each day. • Patients on hemodialysis should take POMALYST following hemodialysis, on hemodialysis days. • POMALYST may be taken with or without food. • The capsules should not be opened, broken, or chewed. POMALYST should be swallowed whole with water. • Instruct patients that if they miss a dose of POMALYST, they may still take it up to 12 hours after the time they would normally take it. If more than 12 hours have elapsed, they should be instructed to skip the dose for that day. The next day, they should take POMALYST at the usual time. Warn patients not to take 2 doses to make up for the one that they missed."}', 'pregnancy': '{"8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to POMALYST during pregnancy as well as female partners of male patients who are exposed to POMALYST. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-FDA-1088 and also to the REMS Call Center at 1-888-423-5436. Risk Summary Based on the mechanism of action [see Clinical Pharmacology (12.1) ] and findings from animal studies, POMALYST can cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy [see Contraindications (4) , and Warnings and Precautions (5.1) ] . POMALYST is a thalidomide analogue. Thalidomide is a human teratogen, inducing a high frequency of severe and life-threatening birth defects such as amelia (absence of limbs), phocomelia (short limbs), hypoplasticity of the bones, absence of bones, external ear abnormalities (including anotia, micropinna, small or absent external auditory canals), facial palsy, eye abnormalities (anophthalmos, microphthalmos), and congenital heart defects. Alimentary tract, urinary tract, and genital malformations have also been documented, and mortality at or shortly after birth has been reported in about 40% of infants. Pomalidomide was teratogenic in both rats and rabbits when administered during the period of organogenesis. Pomalidomide crossed the placenta after administration to pregnant rabbits (see Data ) . If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus. If pregnancy does occur during treatment, immediately discontinue the drug. Under these conditions, refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-FDA-1088 and also to the REMS Call Center at 1-888-423-5436. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. The estimated background risk in the U.S. general population of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies. Data Animal Data Pomalidomide was teratogenic in both rats and rabbits in the embryo-fetal developmental studies when administered during the period of organogenesis. In rats, pomalidomide was administered orally to pregnant animals at doses of 25 to 1000 mg/kg/day. Malformations or absence of urinary bladder, absence of thyroid gland, and fusion and misalignment of lumbar and thoracic vertebral elements (vertebral, central, and/or neural arches) were observed at all dose levels. There was no maternal toxicity observed in this study. The lowest dose in rats resulted in an exposure (AUC) approximately 85-fold of the human exposure at the recommended dose of 4 mg/day. Other embryo-fetal toxicities included increased resorptions leading to decreased number of viable fetuses. In rabbits, pomalidomide was administered orally to pregnant animals at doses of 10 to 250 mg/kg/day. Increased cardiac malformations such as interventricular septal defect were seen at all doses with significant increases at 250 mg/kg/day. Additional malformations observed at 250 mg/kg/day included anomalies in limbs (flexed and/or rotated fore- and/or hindlimbs, unattached or absent digit) and associated skeletal malformations (not ossified metacarpal, misaligned phalanx and metacarpal, absent digit, not ossified phalanx, and short not ossified or bent tibia), moderate dilation of the lateral ventricle in the brain, abnormal placement of the right subclavian artery, absent intermediate lobe in the lungs, low-set kidney, altered liver morphology, incompletely or not ossified pelvis, an increased average for supernumerary thoracic ribs, and a reduced average for ossified tarsals. No maternal toxicity was observed at the low dose (10 mg/kg/day) that resulted in cardiac anomalies in fetuses; this dose resulted in an exposure (AUC) approximately equal to that reported in humans at the recommended dose of 4 mg/day. Additional embryo-fetal toxicity included increased resorption. Following daily oral administration of pomalidomide from Gestation Day 7 through Gestation Day 20 in pregnant rabbits, fetal plasma pomalidomide concentrations were approximately 50% of the maternal C max at all dosages (5 to 250 mg/kg/day), indicating that pomalidomide crossed the placenta."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness of POMALYST have not been established in pediatric patients. The safety and effectiveness were assessed but not established in two open-label studies: a dose escalation study in 25 pediatric patients aged 5 to <17 with recurrent, progressive or refractory CNS tumors [NCT02415153] and a parallel-group study conducted in 47 pediatric patients aged 4 to <17 years with recurrent or progressive high-grade glioma, medulloblastoma, ependymoma, or diffuse intrinsic pontine glioma (DIPG) [NCT03257631]. No new safety signals were observed in pediatric patients across these studies. At the same dose by body surface area, pomalidomide exposure in 55 pediatric patients aged 4 to < 17 years old was within the range observed in adult patients with MM but higher than the exposure observed in adult patients with KS [see Clinical Pharmacology (12.3) ] ."}', 'geriatric_use': '{"8.5 Geriatric Use Multiple Myeloma Of the total number of patients in clinical studies of POMALYST, 44% were aged older than 65 years, while 10% were aged older than 75 years. No overall differences in effectiveness were observed between these patients and younger patients. In these studies, patients older than 65 years were more likely than patients less than or equal to 65 years of age to experience pneumonia. Kaposi Sarcoma Of the 28 patients who received POMALYST, 11% were 65 years or older, and 3.6% were 75 years of age or older. The clinical study did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients."}'}

{"TESTOSTERONE CYPIONATE"}

{'contraindications': '{"CONTRAINDICATIONS 1. Known hypersensitivity to the drug 2. Males with carcinoma of the breast 3. Males with known or suspected carcinoma of the prostate gland 4. Women who are pregnant (see PRECAUTIONS, Pregnancy) 5. Patients with serious cardiac, hepatic or renal disease (see WARNINGS)"}', 'adverse_reactions': '{"ADVERSE REACTIONS The following adverse reactions in the male have occurred with some androgens: Endocrine and urogenital : Gynecomastia and excessive frequency and duration of penile erections. Oligospermia may occur at high dosages. Skin and appendages: Hirsutism, male pattern of baldness, seborrhea, and acne. Cardiovascular Disorders: myocardial infarction, stroke Fluid and electrolyte disturbances: Retention of sodium, chloride, water, potassium, calcium, and inorganic phosphates. Gastrointestinal: Nausea, cholestatic jaundice, alterations in liver function tests, rarely hepatocellular neoplasms and peliosis hepatis (see WARNINGS). Hematologic: Suppression of clotting factors II, V, VII, and X, bleeding in patients on concomitant anticoagulant therapy, and polycythemia. Nervous system: Increased or decreased libido, headache, anxiety, depression, and generalized paresthesia. Allergic: Hypersensitivity, including skin manifestations and anaphylactoid reactions. Vascular Disorders: Venous thromboembolism. Special senses: Rare cases of central serous chorioretinopathy (CSCR). Miscellaneous: Inflammation and pain at the site of intramuscular injection. To report SUSPECTED ADVERSE REACTIONS, contact Perrigo at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch ."}', 'drug_interactions': '{"Drug interactions: Androgens may increase sensitivity to oral anticoagulants. Dosage of the anticoagulant may require reduction in order to maintain satisfactory therapeutic hypoprothrombinemia. Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, insulin requirements."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Testosterone cypionate injection is indicated for replacement therapy in the male in conditions associated with symptoms of deficiency or absence of endogenous testosterone. 1. Primary hypogonadism (congenital or acquired)-testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy. 2. Hypogonadotropic hypogonadism (congenital or acquired)-gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation. Safety and efficacy of testosterone cypionate in men with \\"age-related hypogonadism\\" (also referred to as \\"late-onset hypogonadism\\") have not been established."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE There have been no reports of acute overdosage with the androgens."}', 'active_flag': 'Y', 'generic_name': '{"TESTOSTERONE CYPIONATE"}', 'route': '{INTRAMUSCULAR}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Hypercalcemia may occur in immobilized patients. If this occurs, the drug should be discontinued. Prolonged use of high doses of androgens (principally the 17-α alkyl-androgens) has been associated with development of hepatic adenomas, hepatocellular carcinoma, and peliosis hepatis – all potentially life-threatening complications. Geriatric patients treated with androgens may be at an increased risk of developing prostatic hypertrophy and prostatic carcinoma although conclusive evidence to support this concept is lacking. There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as testosterone cypionate. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with testosterone cypionate and initiate appropriate workup and management. Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use testosterone cypionate. Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [see Drug Abuse and Dependence]. If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events. Edema, with or without congestive heart failure, may be a serious complication in patients with preexisting cardiac, renal or hepatic disease. Gynecomastia may develop and occasionally persists in patients being treated for hypogonadism. The preservative benzyl alcohol has been associated with serious adverse events, including the \\"gasping syndrome\\", and death in pediatric patients. Although normal therapeutic doses of this product ordinarily deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the \\"gasping syndrome\\", the minimum amount of benzyl alcohol at which toxicity may occur is not known. The risk of benzyl alcohol toxicity depends on the quantity administered and the liver and kidneys’ capacity to detoxify the chemical. Premature and low-birth weight infants may be more likely to develop toxicity. Androgen therapy should be used cautiously in healthy males with delayed puberty. The effect on bone maturation should be monitored by assessing bone age of the wrist and hand every 6 months. In children, androgen treatment may accelerate bone maturation without producing compensatory gain in linear growth. This adverse effect may result in compromised adult stature. The younger the child the greater the risk of compromising final mature height. This drug has not been shown to be safe and effective for the enhancement of athletic performance. Because of the potential risk of serious adverse health effects, this drug should not be used for such purpose."}', 'precautions': '{"PRECAUTIONS General: Patients with benign prostatic hypertrophy may develop acute urethral obstruction. Priapism or excessive sexual stimulation may develop. Oligospermia may occur after prolonged administration or excessive dosage. If any of these effects appear, the androgen should be stopped and if restarted, a lower dosage should be utilized. Testosterone cypionate should not be used interchangeably with testosterone propionate because of differences in duration of action. Testosterone cypionate is not for intravenous use. Information for patients: Patients should be instructed to report any of the following: nausea, vomiting, changes in skin color, ankle swelling, too frequent or persistent erections of the penis. Laboratory tests: Hemoglobin and hematocrit levels (to detect polycythemia) should be checked periodically in patients receiving long-term androgen administration. Serum cholesterol may increase during androgen therapy. Drug interactions: Androgens may increase sensitivity to oral anticoagulants. Dosage of the anticoagulant may require reduction in order to maintain satisfactory therapeutic hypoprothrombinemia. Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, insulin requirements. Drug/Laboratory test interferences: Androgens may decrease levels of thyroxine-binding globulin, resulting in decreased total T 4 serum levels and increased resin uptake of T 3 and T 4 . Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction. Carcinogenesis: Animal data. Testosterone has been tested by subcutaneous injection and implantation in mice and rats. The implant induced cervical-uterine tumors in mice, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically-induced carcinomas of the liver in rats. Human data. There are rare reports of hepatocellular carcinoma in patients receiving long-term therapy with androgens in high doses. Withdrawal of the drugs did not lead to regression of the tumors in all cases. Geriatric patients treated with androgens may be at an increased risk of developing prostatic hypertrophy and prostatic carcinoma although conclusive evidence to support this concept is lacking. Pregnancy: Teratogenic Effects. The use of testosterone in women who are pregnant is contraindicated. Testosterone is teratogenic and may cause fetal harm. Testosterone is known to cause virilization of the female fetus when administrated to pregnant women. Benzyl alcohol can cross the placenta. See WARNINGS. Nursing mothers: Testosterone cypionate is not recommended for use in nursing mothers. Pediatric use: Safety and effectiveness in pediatric patients below the age of 12 years have not been established."}', 'information_for_patients': '{"Information for patients: Patients should be instructed to report any of the following: nausea, vomiting, changes in skin color, ankle swelling, too frequent or persistent erections of the penis."}', 'pregnancy': '{"Pregnancy: Teratogenic Effects. The use of testosterone in women who are pregnant is contraindicated. Testosterone is teratogenic and may cause fetal harm. Testosterone is known to cause virilization of the female fetus when administrated to pregnant women. Benzyl alcohol can cross the placenta. See WARNINGS."}', 'pediatric_use': '{"Pediatric use: Safety and effectiveness in pediatric patients below the age of 12 years have not been established."}', 'geriatric_use': None}

{CHLOROXYLENOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses For handwashing to decrease bacteria on the skin."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{CHLOROXYLENOL}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': '{"Do not use In eyes"}', 'when_using': '{"When using this product If in eyes, rinse promptly and thoroughly with water Discontinue use if irritation and redness develop"}', 'warnings': '{"Warnings For external use only Do not use In eyes When using this product If in eyes, rinse promptly and thoroughly with water Discontinue use if irritation and redness develop Stop use and ask a doctor if Skin irritation or redness occurs for more than 72 hours Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{ADAPALENE}

{'contraindications': '{"4 CONTRAINDICATIONS Adapalene gel is contraindicated in patients who have known hypersensitivity to adapalene or any excipient of adapalene gel [see WARNINGS AND PRECAUTIONS (5.1)]. Contraindicated in patients who have known hypersensitivity to adapalene or any excipient of adapalene gel. ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The most frequently reported (≥1%) adverse reactions were erythema, scaling, dryness, and/or burning/stinging. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals, Inc. at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In the multi-center, controlled clinical trial, signs and symptoms of local cutaneous irritation were monitored in 258 acne subjects who used adapalene gel once daily for 12 weeks. Of the subjects who experienced cutaneous irritation (erythema, scaling, dryness, and/or burning/stinging), the majority of cases were mild to moderate in severity, occurred early in treatment and decreased thereafter. The incidence of local cutaneous irritation with adapalene gel from the controlled clinical trial is provided in the following table: Table 1: Physician assessed local cutaneous irritation with Adapalene Gel * Total number of subjects with local cutaneous data for at least one post-Baseline evaluation. Incidence of Local Cutaneous Irritation with Adapalene Gel (N = 253*) Maximum Severity Scores Higher Than Mild Moderate Severe Erythema 66 (26.1%) 33 (13.0%) 1 (0.4%) Scaling 110 (43.5%) 47 (18.6%) 3 (1.2%) Dryness 113 (44.7%) 43 (17.0%) 2 (0.8%) Burning/Stinging 72 (28.5%) 36 (14.2%) 9 (3.6%) Table 2: Patient reported local cutaneous adverse reactions with Adapalene Gel *Selected adverse reactions defined by investigator as Possibly, Probably or Definitely Related Adapalene Gel Vehicle Gel N=258 N=134 Related* Adverse Reactions 57 (22.1%) 6 (4.5%) Dry Skin 36 (14%) 2 (1.5%) Skin Discomfort 15 (5.8%) 0 (0.0%) Desquamation 4 (1.6%) 0 (0.0%) The following adverse reactions occurred in less than 1% of subjects: acne flare, contact dermatitis, eyelid edema, conjunctivitis, erythema, pruritus, skin discoloration, rash, and eczema. In a one-year, open-label safety trial of 551 subjects with acne who received adapalene gel, the pattern of adverse reactions was similar to the 12-week controlled study. 6.2 Post-Marketing Experience The following adverse reactions have been identified during post approval use of adapalene: Immune system disorders: angioedema, face edema, lip swelling Skin disorders: application site pain Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure."}', 'drug_interactions': None, 'indications_and_usage': '{"1 INDICATIONS AND USAGE Adapalene gel, 0.3% is indicated for the topical treatment of acne vulgaris in patients 12 years of age and older. Adapalene gel, 0.3%, is a retinoid, indicated for the topical treatment of acne vulgaris in patients 12 years of age and older. ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Allergic/ Hypersensitivity Reactions: Allergy/hypersensitivity reactions include anaphylaxis angioedema, face edema, eyelid edema, lip swelling, and pruritis. Discontinue adapalene gel in the event of an allergic/hypersensitivity reaction. ( 5.1 ) Ultraviolet Light and Environmental Exposure: Avoid exposure to sunlight and sunlamps. Wear sunscreen when sun exposure cannot be avoided ( 5.2 ). Local Cutaneous Reactions: Erythema, scaling, dryness, and stinging/burning were reported with use of adapalene gel. Concomitant use of other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect and products with high concentrations of alcohol, astringents, spices, or lime) should be approached with caution. ( 5.3 ). 5.1 Allergic/ Hypersensitivity Reactions Adverse reactions including anaphylaxis angioedema, face edema, eyelid edema, lip swelling, and pruritus that sometimes required medical treatment have been reported during postmarketing use of adapalene. Advise a patient to stop using adapalene gel and seek medical attention if experiencing allergic or anaphylactoid/anaphylactic reactions during treatment. 5.2 Ultraviolet Light and Environmental Exposure Exposure to sunlight, including sunlamps, should be minimized during use of adapalene gel. Patients who normally experience high levels of sun exposure, and those with inherent sensitivity to sun, should be warned to exercise caution. Use of sunscreen products and protective clothing over treated areas is recommended when exposure cannot be avoided. Weather extremes, such as wind or cold, also may be irritating to patients under treatment with adapalene gel. 5.3 Local Cutaneous Reactions Cutaneous signs and symptoms such as erythema, scaling, dryness, and stinging/burning were reported with use of adapalene gel. These were most likely to occur during the first four weeks of treatment, were mostly mild to moderate in intensity, and usually lessened with continued use of the medication. Depending upon the severity of these side effects, patients should be instructed to either use a moisturizer, reduce the frequency of application of adapalene gel or discontinue use. Avoid application to cuts, abrasions, eczematous or sunburned skin. As with other retinoids, use of \\"waxing\\" as a depilatory method should be avoided on skin treated with adapalene. As adapalene gel has the potential to induce local irritation in some patients, concomitant use of other potentially irritating topical products (medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect and products with high concentrations of alcohol, astringents, spices, or lime) should be approached with caution."}', 'overdosage': '{"10 OVERDOSAGE Chronic ingestion of the drug may lead to the same side effects as those associated with excessive oral intake of vitamin A."}', 'active_flag': 'Y', 'generic_name': '{ADAPALENE}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information) Information for Patients Patients using adapalene gel should receive the following information and instructions: Apply a thin film of adapalene gel to the entire face and any other affected areas of the skin once daily in the evening. Apply a thin film of adapalene gel to the entire face and any other affected areas of the skin once daily in the evening, after washing gently with a non- medicated soap. Avoid contact with the eyes, lips, angles of the nose, and mucous membranes Moisturizers may be used if necessary; however, products containing alpha hydroxy or glycolic acids should be avoided. This medication should not be applied to cuts, abrasions, eczematous, or sunburned skin. Wax depilation should not be performed on treated skin due to the potential for skin erosions. Minimize exposure to sunlight including sunlamps. Recommend the use of sunscreen products and protective apparel (e.g., hat) when exposure cannot be avoided. Contact the doctor if skin rash, pruritus, hives, chest pain, edema, and shortness of breath occurs, as these may be signs of allergy or hypersensitivity. This product is for external use only. Lactation: Use adapalene gel on the smallest area of skin and for the shortest duration possible while breastfeeding. Avoid application of adapalene gel to areas with increased risk for potential ingestion by or ocular exposure to the breastfeeding child. [ See Use in Specific Populations, Lactation (8.2)] Manufactured for: Alembic Pharmaceuticals, Inc. Bedminster, NJ 07921, USA Manufactured by: Alembic Pharmaceuticals Limited (Derma Division), Karakhadi, Vadodara 391450, India. Mfg. License No.: G/25/2216 Revised: 06/2024"}', 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{LANSOPRAZOLE}

{'contraindications': '{"4 CONTRAINDICATIONS PREVACID and PREVACID SoluTab are contraindicated in patients with known hypersensitivity to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions (5.2) , Adverse Reactions (6) ] . Proton Pump Inhibitors (PPIs), including PREVACID and PREVACID SoluTab, are contraindicated with rilpivirine-containing products [see Drug Interactions (7) ] . For information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with PREVACID or PREVACID SoluTab, refer to the Contraindications section of their prescribing information. Contraindicated in patients with known hypersensitivity to any component of the PREVACID or PREVACID SoluTab formulations. ( 4 ) Patients receiving rilpivirine-containing products. ( 4 , 7 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in labeling: Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.2) ] Clostridium difficile -Associated Diarrhea [see Warnings and Precautions (5.3) ] Bone Fracture [see Warnings and Precautions (5.4) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5) ] Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.6) ] Cyanocobalamin (Vitamin B12) Deficiency [see Warnings and Precautions (5.7) ] Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions (5.8) ] Fundic Gland Polyps [see Warnings and Precautions (5.12) ] Most commonly reported adverse reactions (≥1%): diarrhea, abdominal pain, nausea and constipation. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals America, Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Worldwide, over 10,000 patients have been treated with PREVACID in Phase 2 or Phase 3 clinical trials involving various dosages and durations of treatment. In general, PREVACID treatment has been well-tolerated in both short-term and long-term trials. The following adverse reactions were reported by the treating physician to have a possible or probable relationship to drug in 1% or more of PREVACID-treated patients and occurred at a greater rate in PREVACID-treated patients than placebo-treated patients in Table 1 . Table 1. Incidence of Possibly or Probably Treatment-Related Adverse Reactions in Short-Term, Placebo-Controlled PREVACID Studies Body System/Adverse Reaction PREVACID (N=2768) % Placebo (N=1023) % Body as a Whole Abdominal Pain 2.1 1.2 Digestive System Constipation 1.0 0.4 Diarrhea 3.8 2.3 Nausea 1.3 1.2 Headache was also seen at greater than 1% incidence but was more common on placebo. The incidence of diarrhea was similar between patients who received placebo and patients who received 15 and 30 mg of PREVACID, but higher in the patients who received 60 mg of PREVACID (2.9, 1.4, 4.2, and 7.4%, respectively). The most commonly reported possibly or probably treatment-related adverse event during maintenance therapy was diarrhea. In the risk reduction study of PREVACID for NSAID-associated gastric ulcers, the incidence of diarrhea for patients treated with PREVACID, misoprostol, and placebo was 5, 22, and 3%, respectively. Another study for the same indication, where patients took either a COX-2 inhibitor or lansoprazole and naproxen, demonstrated that the safety profile was similar to the prior study. Additional reactions from this study not previously observed in other clinical trials with PREVACID included contusion, duodenitis, epigastric discomfort, esophageal disorder, fatigue, hunger, hiatal hernia, hoarseness, impaired gastric emptying, metaplasia, and renal impairment. Additional adverse experiences occurring in less than 1% of patients or subjects who received PREVACID in domestic trials are shown below: Body as a Whole – abdomen enlarged, allergic reaction, asthenia, back pain, candidiasis, carcinoma, chest pain (not otherwise specified), chills, edema, fever, flu syndrome, halitosis, infection (not otherwise specified), malaise, neck pain, neck rigidity, pain, pelvic pain Cardiovascular System – angina, arrhythmia, bradycardia, cerebrovascular accident/cerebral infarction, hypertension/hypotension, migraine, myocardial infarction, palpitations, shock (circulatory failure), syncope, tachycardia, vasodilation Digestive System – abnormal stools, anorexia, bezoar, cardiospasm, cholelithiasis, colitis, dry mouth, dyspepsia, dysphagia, enteritis, eructation, esophageal stenosis, esophageal ulcer, esophagitis, fecal discoloration, flatulence, gastric nodules/fundic gland polyps, gastritis, gastroenteritis, gastrointestinal anomaly, gastrointestinal disorder, gastrointestinal hemorrhage, glossitis, gum hemorrhage, hematemesis, increased appetite, increased salivation, melena, mouth ulceration, nausea and vomiting, nausea and vomiting and diarrhea, gastrointestinal moniliasis, rectal disorder, rectal hemorrhage, stomatitis, tenesmus, thirst, tongue disorder, ulcerative colitis, ulcerative stomatitis Endocrine System – diabetes mellitus, goiter, hypothyroidism Hemic and Lymphatic System – anemia, hemolysis, lymphadenopathy Metabolism and Nutritional Disorders – avitaminosis, gout, dehydration, hyperglycemia/hypoglycemia, peripheral edema, weight gain/loss Musculoskeletal System – arthralgia, arthritis, bone disorder, joint disorder, leg cramps, musculoskeletal pain, myalgia, myasthenia, ptosis, synovitis Nervous System – abnormal dreams, agitation, amnesia, anxiety, apathy, confusion, convulsion, dementia, depersonalization, depression, diplopia, dizziness, emotional lability, hallucinations, hemiplegia, hostility aggravated, hyperkinesia, hypertonia, hypesthesia, insomnia, libido decreased/increased, nervousness, neurosis, paresthesia, sleep disorder, somnolence, thinking abnormality, tremor, vertigo Respiratory System – asthma, bronchitis, cough increased, dyspnea, epistaxis, hemoptysis, hiccup, laryngeal neoplasia, lung fibrosis, pharyngitis, pleural disorder, pneumonia, respiratory disorder, upper respiratory inflammation/infection, rhinitis, sinusitis, stridor Skin and Appendages – acne, alopecia, contact dermatitis, dry skin, fixed eruption, hair disorder, maculopapular rash, nail disorder, pruritus, rash, skin carcinoma, skin disorder, sweating, urticaria Special Senses – abnormal vision, amblyopia, blepharitis, blurred vision, cataract, conjunctivitis, deafness, dry eyes, ear/eye disorder, eye pain, glaucoma, otitis media, parosmia, photophobia, retinal degeneration/disorder, taste loss, taste perversion, tinnitus, visual field defect Urogenital System – abnormal menses, breast enlargement, breast pain, breast tenderness, dysmenorrhea, dysuria, gynecomastia, impotence, kidney calculus, kidney pain, leukorrhea, menorrhagia, menstrual disorder, penis disorder, polyuria, testis disorder, urethral pain, urinary frequency, urinary retention, urinary tract infection, urinary urgency, urination impaired, vaginitis 6.2 Postmarketing Experience Additional adverse experiences have been reported since PREVACID and PREVACID SoluTab have been marketed. The majority of these cases are foreign-sourced and a relationship to PREVACID or PREVACID SoluTab has not been established. Because these reactions were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events are listed below by COSTART body system. Body as a Whole – anaphylactic/anaphylactoid reactions, systemic lupus erythematosus; Digestive System – hepatotoxicity, pancreatitis, vomiting; Hemic and Lymphatic System – agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, and thrombotic thrombocytopenic purpura; Infections and Infestations – Clostridium difficile -associated diarrhea; Metabolism and Nutritional Disorders – hypomagnesemia, hypocalcemia, hypokalemia, hyponatremia; Musculoskeletal System – bone fracture, myositis; Skin and Appendages – severe dermatologic reactions including erythema multiforme, SJS/TEN (some fatal), DRESS, AGEP, cutaneous lupus erythematosus; Special Senses – speech disorder; Urogenital System – interstitial nephritis, urinary retention. 6.3 Combination Therapy with Amoxicillin and Clarithromycin In clinical trials using combination therapy with PREVACID plus amoxicillin and clarithromycin, and PREVACID plus amoxicillin, no adverse reactions peculiar to these drug combinations were observed. Adverse reactions that have occurred have been limited to those that had been previously reported with PREVACID, amoxicillin, or clarithromycin. Triple Therapy: PREVACID/amoxicillin/clarithromycin The most frequently reported adverse reactions for patients who received triple therapy for 14 days were diarrhea (7%), headache (6%), and taste perversion (5%). There were no statistically significant differences in the frequency of reported adverse reactions between the 10 and 14 day triple therapy regimens. No treatment-emergent adverse reactions were observed at significantly higher rates with triple therapy than with any dual therapy regimen. Dual Therapy: PREVACID/amoxicillin The most frequently reported adverse reactions for patients who received PREVACID three times daily plus amoxicillin three times daily dual therapy were diarrhea (8%) and headache (7%). No treatment-emergent adverse reactions were observed at significantly higher rates with PREVACID three times daily plus amoxicillin three times daily dual therapy than with PREVACID alone. For information about adverse reactions with antibacterial agents (amoxicillin and clarithromycin) indicated in combination with PREVACID or PREVACID SoluTab, refer to the Adverse Reactions section of their prescribing information. 6.4 Laboratory Values The following changes in laboratory parameters in patients who received PREVACID were reported as adverse reactions: Abnormal liver function tests, increased SGOT (AST), increased SGPT (ALT), increased creatinine, increased alkaline phosphatase, increased globulins, increased GGTP, increased/decreased/abnormal WBC, abnormal AG ratio, abnormal RBC, bilirubinemia, blood potassium increased, blood urea increased, crystal urine present, eosinophilia, hemoglobin decreased, hyperlipemia, increased/decreased electrolytes, increased/decreased cholesterol, increased glucocorticoids, increased LDH, increased/decreased/abnormal platelets, increased gastrin levels and positive fecal occult blood. Urine abnormalities such as albuminuria, glycosuria, and hematuria were also reported. Additional isolated laboratory abnormalities were reported. In the placebo-controlled studies, when SGOT (AST) and SGPT (ALT) were evaluated, 0.4% (4/978) and 0.4% (11/2677) patients, who received placebo and PREVACID, respectively, had enzyme elevations greater than three times the upper limit of normal range at the final treatment visit. None of these patients who received PREVACID reported jaundice at any time during the study. In clinical trials using combination therapy with PREVACID plus amoxicillin and clarithromycin, and PREVACID plus amoxicillin, no increased laboratory abnormalities particular to these drug combinations were observed. For information about laboratory value changes with antibacterial agents (amoxicillin and clarithromycin) indicated in combination with PREVACID or PREVACID SoluTab, refer to the Adverse Reactions section of their prescribing information."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Tables 2 and 3 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with PREVACID or PREVACID SoluTab and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. Table 2. Clinically Relevant Interactions Affecting Drugs Coadministered with PREVACID or PREVACID SoluTab and Interactions with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with lansoprazole may reduce antiviral effect and promote the development of drug resistance. Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with lansoprazole may increase toxicity of the antiretroviral drugs. There are other antiretroviral drugs which do not result in clinically relevant interactions with lansoprazole. Intervention: Rilpivirine-containing products : Concomitant use with PREVACID or PREVACID SoluTab is contraindicated [see Contraindications (4) ] . See prescribing information. Atazanavir : See prescribing information for atazanavir for dosing information. Nelfinavir : Avoid concomitant use with PREVACID or PREVACID SoluTab. See prescribing information for nelfinavir. Saquinavir : See the prescribing information for saquinavir and monitor for potential saquinavir toxicities. Other antiretrovirals : See prescribing information. Warfarin Clinical Impact: Increased INR and prothrombin time in patients receiving PPIs and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Intervention: Monitor INR and prothrombin time. Dose adjustment of warfarin may be needed to maintain target INR range. See prescribing information for warfarin. Methotrexate Clinical Impact: Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [see Warnings and Precautions (5.10) ] . Intervention: A temporary withdrawal of PREVACID or PREVACID SoluTab may be considered in some patients receiving high-dose methotrexate. Digoxin Clinical Impact: Potential for increased exposure of digoxin. Intervention: Monitor digoxin concentrations. Dose adjustment of digoxin may be needed to maintain therapeutic drug concentrations. See prescribing information for digoxin. Theophylline Clinical Impact: Increased clearance of theophylline [see Clinical Pharmacology (12.3) ] . Intervention: Individual patients may require additional titration of their theophylline dosage when PREVACID or PREVACID SoluTab is started or stopped to ensure clinically effective blood concentrations. Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Impact: Lansoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity. Intervention: Mycophenolate mofetil (MMF): Coadministration of PPIs in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PREVACID and MMF. Use PREVACID and PREVACID SoluTab with caution in transplant patients receiving MMF. See the prescribing information for other drugs dependent on gastric pH for absorption. Combination Therapy with Clarithromycin and Amoxicillin Clinical Impact: Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated. Amoxicillin also has drug interactions. Intervention: See Contraindications and Warnings and Precautions in prescribing information for clarithromycin. See Drug Interactions in prescribing information for amoxicillin. Tacrolimus Clinical Impact: Potentially increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19. Intervention: Monitor tacrolimus whole blood trough concentrations. Dose adjustment of tacrolimus may be needed to maintain therapeutic drug concentrations. See prescribing information for tacrolimus. Interactions with Investigations of Neuroendocrine Tumors Clinical Impact: CgA levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors [see Warnings and Precautions (5.9) , Clinical Pharmacology (12.2) ] . Intervention: Temporarily stop PREVACID or PREVACID SoluTab treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary. Interaction with Secretin Stimulation Test Clinical Impact: Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma. Intervention: Temporarily stop PREVACID or PREVACID SoluTab treatment at least 28 days before assessing to allow gastrin levels to return to baseline [see Clinical Pharmacology (12.2) ] . False Positive Urine Tests for THC Clinical Impact: There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs. Intervention: An alternative confirmatory method should be considered to verify positive results. Table 3. Clinically Relevant Interactions Affecting PREVACID or PREVACID SoluTab When Coadministered with Other Drugs CYP2C19 OR CYP3A4 Inducers Clinical Impact: Decreased exposure of lansoprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ] . Intervention: St John\'s Wort, rifampin : Avoid concomitant use with PREVACID or PREVACID SoluTab. Ritonavir-containing products : See prescribing information. CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of lansoprazole is expected when used concomitantly with strong inhibitors [see Clinical Pharmacology (12.3) ] . Intervention: Voriconazole : See prescribing information. Sucralfate Clinical Impact: Decreased and delayed absorption of lansoprazole [see Clinical Pharmacology (12.3) ] . Intervention: Take PREVACID or PREVACID SoluTab at least 30 minutes prior to sucralfate [see Dosage and Administration (2.4) ] . See full prescribing information for a list of clinically important drug interactions. ( 7 )"}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE PREVACID and PREVACID SoluTab are proton pump inhibitors (PPIs) indicated for the: Treatment of active duodenal ulcer in adults. ( 1.1 ) Eradication of H. pylori to reduce the risk of duodenal ulcer recurrence in adults. ( 1.2 ) Maintenance of healed duodenal ulcers in adults. ( 1.3 ) Treatment of active benign gastric ulcer in adults. ( 1.4 ) Healing of nonsteroidal anti-inflammatory drugs (NSAID)-associated gastric ulcer in adults. ( 1.5 ) Risk reduction of NSAID-associated gastric ulcer in adults. ( 1.6 ) Treatment of symptomatic gastroesophageal reflux disease (GERD) in adults and pediatric patients 1 year of age and older. ( 1.7 ) Treatment of erosive esophagitis (EE) in adults and pediatric patients 1 year of age and older. ( 1.8 ) Maintenance of healing of EE in adults. ( 1.9 ) Pathological hypersecretory conditions, including Zollinger-Ellison syndrome (ZES) in adults. ( 1.10 ) 1.1 Treatment of Active Duodenal Ulcer PREVACID and PREVACID SoluTab are indicated in adults for short-term treatment (for four weeks) for healing and symptom relief of active duodenal ulcer [see Clinical Studies (14.1) ] . 1.2 Eradication of H. pylori to Reduce the Risk of Duodenal Ulcer Recurrence Triple Therapy: PREVACID or PREVACID SoluTab/amoxicillin/clarithromycin PREVACID or PREVACID SoluTab in combination with amoxicillin plus clarithromycin as triple therapy is indicated in adults for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or one year history of a duodenal ulcer) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see Clinical Studies (14.2) ] . Please refer to the full prescribing information for amoxicillin and clarithromycin. Dual Therapy: PREVACID or PREVACID SoluTab/amoxicillin PREVACID or PREVACID SoluTab in combination with amoxicillin as dual therapy is indicated in adults for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or one year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected (see the clarithromycin prescribing information, Microbiology section). Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see Clinical Studies (14.2) ] . Please refer to the full prescribing information for amoxicillin. 1.3 Maintenance of Healed Duodenal Ulcers PREVACID and PREVACID SoluTab are indicated in adults to maintain healing of duodenal ulcers. Controlled studies do not extend beyond 12 months [see Clinical Studies (14.3) ] . 1.4 Treatment of Active Benign Gastric Ulcer PREVACID and PREVACID SoluTab are indicated in adults for short-term treatment (up to eight weeks) for healing and symptom relief of active benign gastric ulcer [see Clinical Studies (14.4) ] . 1.5 Healing of NSAID-Associated Gastric Ulcer PREVACID and PREVACID SoluTab are indicated in adults for the treatment of NSAID-associated gastric ulcer in patients who continue NSAID use. Controlled studies did not extend beyond eight weeks [see Clinical Studies (14.5) ] . 1.6 Risk Reduction of NSAID-Associated Gastric Ulcer PREVACID and PREVACID SoluTab are indicated in adults for reducing the risk of NSAID-associated gastric ulcers in patients with a history of a documented gastric ulcer who require the use of an NSAID. Controlled studies did not extend beyond 12 weeks [see Clinical Studies (14.6) ] . 1.7 Treatment of Symptomatic Gastroesophageal Reflux Disease (GERD) PREVACID and PREVACID SoluTab are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for the treatment of heartburn and other symptoms associated with GERD [see Clinical Studies (14.7) ] . 1.8 Treatment of Erosive Esophagitis (EE) PREVACID and PREVACID SoluTab are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for healing and symptom relief of all grades of EE. For adults who do not heal with PREVACID or PREVACID SoluTab for eight weeks (5 to 10%), it may be helpful to give an additional eight weeks of treatment. If there is a recurrence of erosive esophagitis an additional eight week course of PREVACID or PREVACID SoluTab may be considered [see Clinical Studies (14.8) ] . 1.9 Maintenance of Healing of EE PREVACID and PREVACID SoluTab are indicated in adults to maintain healing of EE. Controlled studies did not extend beyond 12 months [see Clinical Studies (14.9) ] . 1.10 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome (ZES) PREVACID and PREVACID SoluTab are indicated in adults for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome [see Clinical Studies (14.10) ] ."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Gastric Malignancy : In adults, symptomatic response with PREVACID or PREVACID SoluTab does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing. ( 5.1 ) Acute Tubulointerstitial Nephritis : Discontinue treatment and evaluate patients. ( 5.2 ) Clostridium difficile -Associated Diarrhea : PPI therapy may be associated with increased risk of Clostridium difficile -associated diarrhea. ( 5.3 ) Bone Fracture : Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. ( 5.4 ) Severe Cutaneous Adverse Reactions: Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. ( 5.5 ) Cutaneous and Systemic Lupus Erythematosus : Mostly cutaneous; new onset or exacerbation of existing disease; discontinue PREVACID and PREVACID SoluTab and refer to specialist for evaluation. ( 5.6 ) Cyanocobalamin (Vitamin B12) Deficiency : Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin. ( 5.7 ) Hypomagnesemia and Mineral Metabolism : Hypomagnesemia has been reported rarely with prolonged treatment with PPIs. ( 5.8 ) Interactions with Investigations for Neuroendocrine Tumors : Increases in intragastric pH may result in hypergastrinemia and enterochromaffin-like cell hyperplasia and increased chromogranin A levels which may interfere with diagnostic investigations for neuroendocrine tumors. ( 5.9 , 7 ) Interaction with Methotrexate : Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. With high-dose methotrexate administration, consider a temporary withdrawal of PREVACID. ( 5.10 , 7 ) Patients with Phenylketonuria : Each 15 mg PREVACID SoluTab contains 2.5 mg and each 30 mg PREVACID SoluTab contains 5.1 mg of phenylalanine. ( 5.11 ) Fundic Gland Polyps : Risk increases with long-term use, especially beyond 1 year. Use the shortest duration of therapy. ( 5.12 ) Risk of Heart Valve Thickening in Pediatric Patients Less than One Year of Age : PREVACID is not recommended in pediatric patients less than 1 year of age. ( 5.13 , 8.4 ) 5.1 Presence of Gastric Malignancy In adults, symptomatic response to therapy with PREVACID or PREVACID SoluTab does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy. 5.2 Acute Tubulointerstitial Nephritis Acute tubulointerstial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue PREVACID or PREVACID SoluTab and evaluate patients with suspected acute TIN [see Contraindications (4) ] . 5.3 Clostridium difficile -Associated Diarrhea Published observational studies suggest that PPI therapy like PREVACID and PREVACID SoluTab may be associated with an increased risk of Clostridium difficile -associated diarrhea (CDAD), especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.2) ] . Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. CDAD has been reported with use of nearly all antibacterial agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with PREVACID or PREVACID SoluTab, refer to Warnings and Precautions section of their prescribing information. 5.4 Bone Fracture Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2) , Adverse Reactions (6.2) ] . 5.5 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs [see Adverse Reactions (6.2) ]. Discontinue PREVACID or PREVACID SoluTab at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. 5.6 Cutaneous and Systemic Lupus Erythematosus Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including lansoprazole. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases were CLE. The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement. Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI-associated SLE is usually milder than nondrug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported. Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving PREVACID or PREVACID SoluTab, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in four to 12 weeks. Serological testing (e.g., ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations. 5.7 Cyanocobalamin (Vitamin B12) Deficiency Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than three years) may lead to malabsorption of cyanocobalamin (Vitamin B12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed in patients treated with PREVACID or PREVACID SoluTab. 5.8 Hypomagnesemia and Mineral Metabolism Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2) ] . Consider monitoring magnesium and calcium levels prior to initiation of PREVACID or PREVACID SoluTab and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium, as necessary. If hypocalcemia is refractory to treatment, consider discontinuing the PPI. 5.9 Interactions with Investigations for Neuroendocrine Tumors Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop lansoprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary [see Drug Interactions (7) , Clinical Pharmacology (12.2) ] . 5.10 Interaction with Methotrexate Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions (7) , Clinical Pharmacology (12.3) ] . 5.11 Patients with Phenylketonuria Phenylalanine can be harmful to patients with phenylketonuria (PKU). PREVACID SoluTab contains phenylalanine, a component of aspartame. Each 15 mg tablet contains 2.5 mg and each 30 mg tablet contains 5.1 mg of phenylalanine. Before prescribing PREVACID SoluTab to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including PREVACID SoluTab. 5.12 Fundic Gland Polyps PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated. 5.13 Risk of Heart Valve Thickening in Pediatric Patients Less Than One Year of Age PREVACID and PREVACID SoluTab are not approved in pediatric patients less than one year of age. Nonclinical studies in juvenile rats with lansoprazole have demonstrated an adverse effect of heart valve thickening. The risk of heart valve injury does not appear to be relevant to patients one year of age and older [see Use in Specific Populations (8.4) ]."}', 'overdosage': '{"10 OVERDOSAGE Lansoprazole is not removed from the circulation by hemodialysis. In one reported overdose, a patient consumed 600 mg of PREVACID with no adverse reaction. Oral lansoprazole doses up to 5000 mg/kg in rats [approximately 1300 times the 30 mg human dose based on body surface area (BSA)] and in mice (about 675.7 times the 30 mg human dose based on BSA) did not produce deaths or any clinical signs. In the event of over-exposure, treatment should be symptomatic and supportive. If over-exposure occurs, call your poison control center at 1-800-222-1222 for current information on the management of poisoning or over-exposure."}', 'active_flag': 'Y', 'generic_name': '{LANSOPRAZOLE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Advise patients to: Acute Tubulointerstitial Nephritis To call their healthcare provider if they experience signs and/or symptoms associated with acute tubulointerstitial nephritis [see Warnings and Precautions (5.2) ] . Clostridium difficile -Associated Diarrhea To immediately call their healthcare provider if they experience diarrhea that does not improve [see Warnings and Precautions (5.3) ] . Bone Fracture To report any fractures, especially of the hip, wrist or spine, to their healthcare provider [see Warnings and Precautions (5.4) ] . Severe Cutaneous Adverse Reactions To discontinue PREVACID or PREVACID SoluTab and immediately call their healthcare provider for further evaluation [see Warnings and Precautions (5.5) ]. Cutaneous and Systemic Lupus Erythematosus To immediately call their healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus [see Warnings and Precautions (5.6) ] . Cyanocobalamin (Vitamin B12) Deficiency To report any clinical symptoms that may be associated with cyanocobalamin deficiency to their healthcare provider, if they have been receiving PREVACID or PREVACID SoluTab for longer than three years [see Warnings and Precautions (5.7) ] . Hypomagnesemia and Mineral Metabolism To report any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia, and/or hypokalemia to their healthcare provider, if they have been receiving PREVACID or PREVACID SoluTab for at least three months [see Warnings and Precautions (5.8) ] . Drug Interactions Advise patients to report to their healthcare provider if they are taking rilpivirine-containing products [see Contraindications (4) ] or high-dose methotrexate [see Warnings and Precautions (5.10) ] . Pregnancy Advise a pregnant woman of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1) ]. Administration Missed doses: If a dose is missed, administer as soon as possible. However, if the next scheduled dose is due, do not take the missed dose, and take the next dose on time. Do not take two doses at one time to make up for a missed dose. PREVACID or PREVACID SoluTab should be taken before eating. Do not crush or chew PREVACID capsule or PREVACID SoluTab. Take PREVACID or PREVACID SoluTab at least 30 minutes prior to sucralfate. Phenylketonurics: Contains Phenylalanine 2.5 mg per 15 mg PREVACID SoluTab Tablet and 5.1 mg per 30 mg PREVACID SoluTab Tablet. PREVACID Capsules Swallow whole; do not chew. For patients who have difficulty swallowing capsules: PREVACID capsules can be opened and sprinkled on applesauce, ENSURE pudding, cottage cheese, yogurt or strained pears PREVACID capsules may also be emptied into a small volume of either apple juice, orange juice or tomato juice Alternatively, PREVACID capsules can be administered with apple juice via nasogastric tube See the Instructions for Use for a description of all preparation and administration instructions PREVACID SoluTab Do not break or cut. Place the tablet on the tongue; allow it to disintegrate, with or without water, until the particles can be swallowed. Do not chew the particles. The tablet typically disintegrates in less than one minute. Alternatively, for children or other patients who have difficulty swallowing tablets, PREVACID SoluTab can be administered with water via oral syringe or NG tube, as described in the Instructions for Use."}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Available data from published observational studies overall do not indicate an association of adverse pregnancy outcomes with lansoprazole treatment (see Data ) . In animal reproduction studies, oral administration of lansoprazole to rats during organogenesis through lactation at 6.4 times the maximum recommended human dose produced reductions in the offspring in femur weight, femur length, crown-rump length and growth plate thickness (males only) on postnatal Day 21 (see Data ) . These effects were associated with reduction in body weight gain. Advise pregnant women of the potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. If PREVACID or PREVACID SoluTab is administered with clarithromycin, the pregnancy information for clarithromycin also applies to the combination regimen. Refer to the prescribing information for clarithromycin for more information on use in pregnancy. Data Human Data Available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and lansoprazole use. Methodological limitations of these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. In a prospective study by the European Network of Teratology Information Services, outcomes from a group of 62 pregnant women administered median daily doses of 30 mg of lansoprazole were compared to a control group of 868 pregnant women who did not take any PPIs. There was no difference in the rate of major malformations between women exposed to PPIs and the control group, corresponding to a Relative Risk (RR)=1.04, [95% Confidence Interval (CI) 0.25-4.21]. In a population-based retrospective cohort study covering all live births in Denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to lansoprazole in 794 live births. A meta-analysis that compared 1,530 pregnant women exposed to PPIs in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to PPIs (for major malformations Odds Ratio (OR)=1.12, [95% CI 0.86-1.45] and for spontaneous abortions OR=1.29, [95% CI 0.84-1.97]). Animal Data No adverse effects on embryo-fetal development occurred in studies performed in pregnant rats at oral lansoprazole doses up to 150 mg/kg/day (40 times the recommended human dose [30 mg/day] based on body surface area) administered during organogenesis and pregnant rabbits at oral lansoprazole doses up to 30 mg/kg/day (16 times the recommended human dose based on body surface area) administered during organogenesis. A pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with lansoprazole at oral doses of 10 to 100 mg/kg/day (0.7 to 6.4 times the maximum recommended human lansoprazole dose of 30 mg based on AUC [area under the plasma concentration-time curve]) administered during organogenesis through lactation. Maternal effects observed at 100 mg/kg/day (6.4 times the maximum recommended human lansoprazole dose of 30 mg based on AUC) included increased gestation period, decreased body weight gain during gestation, and decreased food consumption. The number of stillbirths was increased at this dose, which may have been secondary to maternal toxicity. Body weight of pups was reduced at 100 mg/kg/day starting on postnatal Day 11. Femur weight, femur length, and crown-rump length were reduced at 100 mg/kg/day on postnatal Day 21. Femur weight was still decreased in the 100 mg/kg/day group at age 17 to 18 weeks. Growth plate thickness was decreased in the 100 mg/kg/day males on postnatal Day 21, and was increased in the 30 and 100 mg/kg/day males at age 17 to 18 weeks. The effects on bone parameters were associated with reduction in body weight gain."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness of PREVACID and PREVACID SoluTab have been established in pediatric patients one year to 17 years of age for short-term treatment of symptomatic GERD and erosive esophagitis. In clinical studies of symptomatic GERD and erosive esophagitis, PREVACID was not administered beyond 12 weeks in patients one year to 11 years of age. It is not known if PREVACID and PREVACID SoluTab are safe and effective if used longer than the recommended duration. Do not exceed the recommended dose and duration of use in pediatric patients (see Juvenile Animal Toxicity Data ) . PREVACID was not effective in pediatric patients with symptomatic GERD one month to less than one year of age in a multicenter, double-blind, placebo - controlled study. Therefore, safety and effectiveness have not been established in patients less than one year of age. Nonclinical studies in juvenile rats have demonstrated an adverse effect of heart valve thickening and bone changes at lansoprazole doses higher than the maximum recommended equivalent human dose. Neonate to less than one year of age The pharmacokinetics of lansoprazole were studied in pediatric patients with GERD aged less than 28 days and one to 11 months. Compared to healthy adults receiving 30 mg, neonates had higher exposure (mean weight-based normalized AUC values 2.04 and 1.88 fold higher at doses of 0.5 and 1 mg/kg/day, respectively). Infants aged ≤10 weeks had clearance and exposure values that were similar to neonates. Infants aged greater than 10 weeks who received 1 mg/kg/day had mean AUC values that were similar to adults who received a 30 mg dose. Lansoprazole was not found to be effective in a US and Polish four week, multicenter, double-blind, placebo-controlled, parallel-group study of 162 patients between one month and less than 12 months of age with symptomatic GERD based on a medical history of crying/fussing/irritability associated with feedings who had not responded to conservative GERD management (i.e., nonpharmacologic intervention) for seven to 14 days. Patients received lansoprazole as a suspension daily (0.2 to 0.3 mg/kg/day in infants ≤10 weeks of age or 1.0 to 1.5 mg/kg/day in infants greater than 10 weeks or placebo) for up to four weeks of double-blind treatment. The primary efficacy endpoint was assessed by greater than 50% reduction from baseline in either the percent of feedings with a crying/fussing/irritability episode or the duration (minutes) of a crying/fussing/irritability episode within one hour after feeding. There was no difference in the percentage of responders between the lansoprazole pediatric suspension group and placebo group (54% in both groups). There were no adverse events reported in pediatric clinical studies (one month to less than 12 months of age) that were not previously observed in adults. Based on the results of the Phase 3 efficacy study, lansoprazole was not shown to be effective. Therefore, these results do not support the use of lansoprazole in treating symptomatic GERD in infants. One year to 11 years of age In an uncontrolled, open-label, US multicenter study, 66 pediatric patients (one year to 11 years of age) with GERD were assigned, based on body weight, to receive an initial dose of either PREVACID 15 mg daily if ≤30 kg or PREVACID 30 mg daily if greater than 30 kg administered for eight to 12 weeks. The PREVACID dose was increased (up to 30 mg twice daily) in 24 of 66 pediatric patients after two or more weeks of treatment if they remained symptomatic. At baseline, 85% of patients had mild to moderate overall GERD symptoms (assessed by investigator interview), 58% had non-erosive GERD and 42% had erosive esophagitis (assessed by endoscopy). After eight to 12 weeks of PREVACID treatment, the intent-to-treat analysis demonstrated an approximate 50% reduction in frequency and severity of GERD symptoms. Twenty -one of 27 erosive esophagitis patients were healed at eight weeks and 100% of patients were healed at 12 weeks by endoscopy (Table 4) . Table 4. GERD Symptom Improvement and Erosive Esophagitis Healing Rates in Pediatric Patients Age 1 Year to 11 Years of Age GERD Final Visit At Week 8 or Week 12 % (n/N) Symptomatic GERD Improvement in Overall GERD Symptoms Symptoms assessed by patients diary kept by caregiver. 76% (47/62 No data were available for four pediatric patients. ) Erosive Esophagitis Improvement in Overall GERD Symptoms 81% (22/27) Healing Rate 100% (27/27) In a study of 66 pediatric patients in the age group one year to 11 years old after treatment with PREVACID given orally in doses of 15 mg daily to 30 mg twice daily, increases in serum gastrin levels were similar to those observed in adult studies. Median fasting serum gastrin levels increased 89% from 51 pg/mL at baseline to 97 pg/mL [interquartile range (25 th to 75 th percentile) of 71 to 130 pg/mL] at the final visit. The pediatric safety of PREVACID capsules has been assessed in 66 pediatric patients aged one to 11 years of age. Of the 66 patients with GERD, 85% (56/66) took PREVACID for eight weeks and 15% (10/66) took it for 12 weeks. The most frequently reported (two or more patients) treatment-related adverse reactions in patients one to 11 years of age (N=66) were constipation (5%) and headache (3%). Twelve years to 17 years of age In an uncontrolled, open-label, US multicenter study, 87 adolescent patients (12 years to 17 years of age) with symptomatic GERD were treated with PREVACID for eight to 12 weeks. Baseline upper endoscopies classified these patients into two groups: 64 (74%) non-erosive GERD and 23 (26%) erosive esophagitis (EE). The non-erosive GERD patients received PREVACID 15 mg daily for eight weeks and the EE patients received PREVACID 30 mg daily for eight to 12 weeks. At baseline, 89% of these patients had mild to moderate overall GERD symptoms (assessed by investigator interviews). During eight weeks of PREVACID treatment, adolescent patients experienced a 63% reduction in frequency and a 69% reduction in severity of GERD symptoms based on diary results. Twenty -one of 22 (95.5%) adolescent erosive esophagitis patients were healed after eight weeks of PREVACID treatment. One patient remained unhealed after 12 weeks of treatment (Table 5) . Table 5. GERD Symptom Improvement and Erosive Esophagitis Healing Rates in Pediatric Patients Age 12 Years to 17 Years of Age GERD Final Visit % (n/N) Symptomatic GERD (All Patients) Improvement in Overall GERD Symptoms Symptoms assessed by patient diary (parents/caregivers as necessary). 73.2% (60/82) No data available for five patients. Non-erosive GERD Improvement in Overall GERD Symptoms 71.2% (42/59) Erosive Esophagitis Improvement in Overall GERD Symptoms 78.3% (18/23) Healing Rate Data from one healed patient was excluded from this analysis due to timing of final endoscopy. 95.5% (21/22) In these 87 adolescent patients, increases in serum gastrin levels were similar to those observed in adult studies, median fasting serum gastrin levels increased 42% from 45 pg/mL at baseline to 64 pg/mL [interquartile range (25 th to 75 th percentile) of 44 to 88 pg/mL] at the final visit. (Normal serum gastrin levels are 25 to 111 pg/mL.) The safety of PREVACID capsules has been assessed in these 87 adolescent patients. Of the 87 adolescent patients with GERD, 6% (5/87) took PREVACID for less than six weeks, 93% (81/87) for six to 10 weeks, and 1% (1/87) for greater than 10 weeks. The most frequently reported (at least 3%) treatment-related adverse reactions in these patients were headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%). Treatment-related dizziness, reported in this prescribing information as occurring in less than 1% of adult patients, was reported in this study by three adolescent patients with non-erosive GERD, who had dizziness concurrently with other reactions (such as migraine, dyspnea, and vomiting). Juvenile Animal Toxicity Data Heart Valve Thickening In two oral toxicity studies, thickening of the mitral heart valve occurred in juvenile rats treated with lansoprazole. Heart valve thickening was observed primarily with oral dosing initiated on postnatal Day 7 (age equivalent to neonatal humans) and postnatal Day 14 (human age equivalent of approximately one year) at doses of 250 mg/kg/day and higher (at postnatal Day 7 and postnatal Day 14, respectively 6.2 times and 4.2 times the daily pediatric dose of 15 mg in pediatric patients age one to 11 years weighing 30 kg or less, based on AUC). The treatment durations associated with heart valve thickening ranged from 5 days to 8 weeks. The findings reversed or trended towards reversibility after a 4-week drug-free recovery period. The incidence of heart valve thickening after initiation of dosing on postnatal Day 21 (human age equivalent of approximately two years) was limited to a single rat (1/24) in groups given 500 mg/kg/day for 4 or 8 weeks (approximately 5.2 times the daily pediatric dose of 15 mg in pediatric patients age one to 11 years weighing 30 kg or less, based on AUC). Based on exposure margins, the risk of heart valve injury does not appear to be relevant to patients one year of age and older. Bone Changes In an eight-week oral toxicity study in juvenile rats with dosing initiated on postnatal Day 7, doses equal to or greater than 100 mg/kg/day (2.5 times the daily pediatric dose of 15 mg in children age one to 11 years weighing 30 kg or less, based on AUC) produced delayed growth, with impairment of weight gain observed as early as postnatal Day 10 (age equivalent to neonatal humans). At the end of treatment, the signs of impaired growth at 100 mg/kg/day and higher included reductions in body weight (14 to 44% compared to controls), absolute weight of multiple organs, femur weight, femur length, and crown-rump length. Femoral growth plate thickness was reduced only in males and only at the 500 mg/kg/day dose. The effects related to delayed growth persisted through the end of the four -week recovery period. Longer term data were not collected."}', 'geriatric_use': '{"8.5 Geriatric Use Of the total number of patients (n=21,486) in clinical studies of PREVACID, 16% of patients were aged 65 years and over, while 4% were 75 years and over. No overall differences in safety or effectiveness were observed between these patients and younger patients and other reported clinical experience has not identified significant differences in responses between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3) ] ."}'}

{"FLUOXETINE HYDROCHLORIDE"}

{'contraindications': '{"4 CONTRAINDICATIONS When using fluoxetine capsules and olanzapine in combination, also refer to the Contraindications section of the package insert for Symbyax. Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with fluoxetine capsules or within 5 weeks of stopping treatment with fluoxetine capsules. Do not use fluoxetine capsules within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start fluoxetine capsules in a patient who is being treated with linezolid or intravenous methylene blue (4.1) Pimozide: Do not use. Risk of QT prolongation and drug interaction (4.2 , 5.11 , 7.7 , 7.8) Thioridazine: Do not use. Risk of QT interval prolongation and elevated thioridazine plasma levels. Do not use thioridazine within 5 weeks of discontinuing fluoxetine (4.2 , 5.11 , 7.7 , 7.8) When using fluoxetine capsules and olanzapine in combination, also refer to the Contraindications section of the package insert for Symbyax (4) 4.1 Monoamine Oxidase Inhibitors (MAOIs) The use of MAOIs intended to treat psychiatric disorders with fluoxetine capsules or within 5 weeks of stopping treatment with fluoxetine capsules is contraindicated because of an increased risk of serotonin syndrome. The use of fluoxetine capsules within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.9) and Warnings and Precautions (5.2) ]. Starting fluoxetine capsules in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration (2.10) and Warnings and Precautions (5.2) ]. 4.2 Other Contraindications The use of fluoxetine capsules is contraindicated with the following: Pimozide [see Warnings and Precautions (5.11) and Drug Interactions (7.7 , 7.8) ] Thioridazine [see Warnings and Precautions (5.11) and Drug Interactions (7.7 , 7.8) ] Pimozide and thioridazine prolong the QT interval. Fluoxetine capsules can increase the levels of pimozide and thioridazine through inhibition of CYP2D6. Fluoxetine capsules can also prolong the QT interval."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults [see Boxed Warning and Warnings and Precautions (5.1) ] Serotonin Syndrome [see Warnings and Precautions (5.2) ] Allergic Reactions and Rash [see Warnings and Precautions (5.3) ] Screening Patients for Bipolar Disorder and Monitoring for Mania/Hypomania [see Warnings and Precautions (5.4) ] Seizures [see Warnings and Precautions (5.5) ] Altered Appetite and Weight [see Warnings and Precautions (5.6) ] Increased Risk of Bleeding [see Warnings and Precautions (5.7) ] Angle-Closure Glaucoma [see Warnings and Precautions (5.8) ] Hyponatremia [see Warnings and Precautions (5.9) ] Anxiety and Insomnia [see Warnings and Precautions (5.10) ] QT Prolongation [see Warnings and Precautions (5.11) ] Potential for Cognitive and Motor Impairment [see Warnings and Precautions (5.13) ] Discontinuation Adverse Reactions [see Warnings and Precautions (5.15) ] Sexual Dysfunction [see Warnings and Precautions (5.17) ] When using fluoxetine and olanzapine in combination, also refer to the Adverse Reactions section of the package insert for Symbyax. Most common adverse reactions (≥5% and at least twice that for placebo) associated with: Major Depressive Disorder, Obsessive Compulsive Disorder, Bulimia, and Panic Disorder: abnormal dreams, abnormal ejaculation, anorexia, anxiety, asthenia, diarrhea, dry mouth, dyspepsia, flu syndrome, impotence, insomnia, libido decreased, nausea, nervousness, pharyngitis, rash, sinusitis, somnolence, sweating, tremor, vasodilatation, and yawn (6.1) Fluoxetine and olanzapine in combination - Also refer to the Adverse Reactions section of the package insert for Symbyax (6) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect or predict the rates observed in practice. Multiple doses of fluoxetine have been administered to 10,782 patients with various diagnoses in U.S. clinical trials. In addition, there have been 425 patients administered fluoxetine in panic clinical trials. The stated frequencies represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. A reaction was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Incidence in Major Depressive Disorder, OCD, bulimia, and Panic Disorder placebo-controlled clinical trials (excluding data from extensions of trials) — Table 3 enumerates the most common treatment-emergent adverse reactions associated with the use of fluoxetine (incidence of at least 5% for fluoxetine and at least twice that for placebo within at least 1 of the indications) for the treatment of Major Depressive Disorder, OCD, and bulimia in U.S. controlled clinical trials and Panic Disorder in U.S. plus non-U.S. controlled trials. Table 5 enumerates treatment-emergent adverse reactions that occurred in 2% or more patients treated with fluoxetine and with incidence greater than placebo who participated in U.S. Major Depressive Disorder, OCD, and bulimia controlled clinical trials and U.S. plus non-U.S. Panic Disorder controlled clinical trials. Table 4 provides combined data for the pool of studies that are provided separately by indication in Table 3. Table 3: Most Common Treatment-Emergent Adverse Reactions: Incidence in Major Depressive Disorder, OCD, Bulimia, and Panic Disorder Placebo-Controlled Clinical Trials 1,2 Percentage of Patients Reporting Event Major Depressive Disorder OCD Bulimia Panic Disorder 1 Incidence less than 1%. 2 Includes U.S. data for Major Depressive Disorder, OCD, Bulimia, and Panic Disorder clinical trials, plus non-U.S. data for Panic Disorder clinical trials. 3 Denominator used was for males only (N=690 fluoxetine Major Depressive Disorder; N=410 placebo Major Depressive Disorder; N=116 fluoxetine OCD; N=43 placebo OCD; N=14 fluoxetine bulimia; N=1 placebo bulimia; N=162 fluoxetine panic; N=121 placebo panic). Body System/ Adverse Reaction Fluoxetine (N=1728) Placebo (N=975) Fluoxetine (N=266) Placebo (N=89) Fluoxetine (N=450) Placebo (N=267) Fluoxetine (N=425) Placebo (N=342) Body as a Whole Asthenia 9 5 15 11 21 9 7 7 Flu syndrome 3 4 10 7 8 3 5 5 Cardiovascular System Vasodilatation 3 2 5 -- 2 1 1 -- Digestive System Nausea 21 9 26 13 29 11 12 7 Diarrhea 12 8 18 13 8 6 9 4 Anorexia 11 2 17 10 8 4 4 1 Dry mouth 10 7 12 3 9 6 4 4 Dyspepsia 7 5 10 4 10 6 6 2 Nervous System Insomnia 16 9 28 22 33 13 10 7 Anxiety 12 7 14 7 15 9 6 2 Nervousness 14 9 14 15 11 5 8 6 Somnolence 13 6 17 7 13 5 5 2 Tremor 10 3 9 1 13 1 3 1 Libido decreased 3 -- 11 2 5 1 1 2 Abnormal dreams 1 1 5 2 5 3 1 1 Respiratory System Pharyngitis 3 3 11 9 10 5 3 3 Sinusitis 1 4 5 2 6 4 2 3 Yawn -- -- 7 -- 11 -- 1 -- Skin and Appendages Sweating 8 3 7 -- 8 3 2 2 Rash 4 3 6 3 4 4 2 2 Urogenital System Impotence 3 2 -- -- -- 7 -- 1 -- Abnormal ejaculation 3 -- -- 7 -- 7 -- 2 1 Table 4: Treatment-Emergent Adverse Reactions: Incidence in Major Depressive Disorder, OCD, Bulimia, and Panic Disorder Placebo-Controlled Clinical Trials 1,2 Percentage of Patients Reporting Event Major Depressive Disorder, OCD, Bulimia, and Panic Disorder Combined 1 Incidence less than 1%. 2 Includes U.S. data for Major Depressive Disorder, OCD, Bulimia, and Panic Disorder clinical trials, plus non-U.S. data for Panic Disorder clinical trials. Body System/Adverse Reaction Fluoxetine (N=2869) Placebo (N=1673) Body as a Whole Headache 21 19 Asthenia 11 6 Flu syndrome 5 4 Fever 2 1 Cardiovascular System Vasodilatation 2 1 Digestive System Nausea 22 9 Diarrhea 11 7 Anorexia 10 3 Dry mouth 9 6 Dyspepsia 8 4 Constipation 5 4 Flatulence 3 2 Vomiting 3 2 Metabolic and Nutritional Disorders Weight loss 2 1 Nervous System Insomnia 19 10 Nervousness 13 8 Anxiety 12 6 Somnolence 12 5 Dizziness 9 6 Tremor 9 2 Libido decreased 4 1 Thinking abnormal 2 1 Respiratory System Yawn 3 -- Skin and Appendages Sweating 7 3 Rash 4 3 Pruritus 3 2 Special Senses Abnormal vision 2 1 Associated with discontinuation in Major Depressive Disorder, OCD, bulimia, and Panic Disorder placebo-controlled clinical trials (excluding data from extensions of trials) — Table 5 lists the adverse reactions associated with discontinuation of fluoxetine treatment (incidence at least twice that for placebo and at least 1% for fluoxetine in clinical trials collecting only a primary reaction associated with discontinuation) in Major Depressive Disorder, OCD, bulimia, and Panic Disorder clinical trials, plus non-U.S. Panic Disorder clinical trials. Table 5: Most Common Adverse Reactions Associated with Discontinuation in Major Depressive Disorder, OCD, Bulimia, and Panic Disorder Placebo-Controlled Clinical Trials 1 1 Includes U.S. Major Depressive Disorder, OCD, Bulimia, and Panic Disorder clinical trials, plus non-U.S. Panic Disorder clinical trials. Major Depressive Disorder, OCD, Bulimia, and Panic Disorder Combined (N=1533) Major Depressive Disorder (N=392) OCD (N=266) Bulimia (N=450) Panic Disorder (N=425) Anxiety (1%) -- Anxiety (2%) -- Anxiety (2%) -- -- -- Insomnia (2%) -- -- Nervousness (1%) -- -- Nervousness (1%) -- -- Rash (1%) -- -- Other adverse reactions in pediatric patients (children and adolescents) — Treatment-emergent adverse reactions were collected in 322 pediatric patients (180 fluoxetine-treated, 142 placebo-treated). The overall profile of adverse reactions was generally similar to that seen in adult studies, as shown in Tables 4 and 5. However, the following adverse reactions (excluding those which appear in the body or footnotes of Tables 4 and 5 and those for which the COSTART terms were uninformative or misleading) were reported at an incidence of at least 2% for fluoxetine and greater than placebo: thirst, hyperkinesia, agitation, personality disorder, epistaxis, urinary frequency, and menorrhagia. The most common adverse reaction (incidence at least 1% for fluoxetine and greater than placebo) associated with discontinuation in 3 pediatric placebo-controlled trials (N=418 randomized; 228 fluoxetine-treated; 190 placebo-treated) was mania/hypomania (1.8% for fluoxetine-treated, 0% for placebo-treated). In these clinical trials, only a primary reaction associated with discontinuation was collected. Male and female sexual dysfunction with SSRIs — Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that SSRIs can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and healthcare providers may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance, cited in product labeling, are likely to underestimate their actual incidence. In patients enrolled in U.S. Major Depressive Disorder, OCD, and bulimia placebo-controlled clinical trials, decreased libido was the only sexual side effect reported by at least 2% of patients taking fluoxetine (4% fluoxetine, <1% placebo). There have been spontaneous reports in women taking fluoxetine of orgasmic dysfunction, including anorgasmia. There are no adequate and well-controlled studies examining sexual dysfunction with fluoxetine treatment. Symptoms of sexual dysfunction occasionally persist after discontinuation of fluoxetine treatment. Priapism has been reported with all SSRIs. While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, healthcare providers should routinely inquire about such possible side effects. Other Reactions Following is a list of treatment-emergent adverse reactions reported by patients treated with fluoxetine in clinical trials. This listing is not intended to include reactions (1) already listed in previous tables or elsewhere in labeling, (2) for which a drug cause was remote, (3) which were so general as to be uninformative, (4) which were not considered to have significant clinical implications, or (5) which occurred at a rate equal to or less than placebo. Reactions are classified by body system using the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients. Body as a Whole — Frequent: chills; Infrequent: suicide attempt; Rare: acute abdominal syndrome, photosensitivity reaction. Cardiovascular System — Frequent: palpitation; Infrequent: arrhythmia, hypotension 1 . Digestive System — Infrequent: dysphagia, gastritis, gastroenteritis, melena, stomach ulcer; Rare: bloody diarrhea, duodenal ulcer, esophageal ulcer, gastrointestinal hemorrhage, hematemesis, hepatitis, peptic ulcer, stomach ulcer hemorrhage. Hemic and Lymphatic System — Infrequent: ecchymosis; Rare: petechia, purpura. Investigations — Frequent: QT interval prolongation (QT c F ≥450 msec) 3 . Nervous System — Frequent: emotional lability; Infrequent: akathisia, ataxia, balance disorder 1 , bruxism 1 , buccoglossal syndrome, depersonalization, euphoria, hypertonia, libido increased, myoclonus, paranoid reaction; Rare: delusions. Respiratory System — Rare: larynx edema. Skin and Appendages — Infrequent: alopecia; Rare: purpuric rash. Special Senses — Frequent: taste perversion; Infrequent: mydriasis. Urogenital System — Frequent: micturition disorder; Infrequent: dysuria, gynecological bleeding 2 . 1 MedDRA dictionary term from integrated database of placebo controlled trials of 15870 patients, of which 9673 patients received fluoxetine. 2 Group term that includes individual MedDRA terms: cervix hemorrhage uterine, dysfunctional uterine bleeding, genital hemorrhage, menometrorrhagia, menorrhagia, metrorrhagia, polymenorrhea, postmenopausal hemorrhage, uterine hemorrhage, vaginal hemorrhage. Adjusted for gender. 3 QT prolongation data are based on routine ECG measurements in clinical trials. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of fluoxetine . Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or evaluate a causal relationship to drug exposure. Voluntary reports of adverse reactions temporally associated with fluoxetine that have been received since market introduction and that may have no causal relationship with the drug include the following: anosmia, aplastic anemia, atrial fibrillation 1 , cataract, cerebrovascular accident 1 , cholestatic jaundice, drug reaction with eosinophilia and systemic symptoms (DRESS), dyskinesia (including, for example, a case of buccal-lingual-masticatory syndrome with involuntary tongue protrusion reported to develop in a 77-year-old female after 5 weeks of fluoxetine therapy and which completely resolved over the next few months following drug discontinuation), eosinophilic pneumonia 1 , epidermal necrolysis, erythema multiforme, erythema nodosum, exfoliative dermatitis, galactorrhea, gynecomastia, heart arrest 1 , hepatic failure/necrosis, hyperprolactinemia, hypoglycemia, hyposmia, immune-related hemolytic anemia, kidney failure, memory impairment, movement disorders developing in patients with risk factors including drugs associated with such reactions and worsening of pre-existing movement disorders, optic neuritis, pancreatitis 1 , pancytopenia, pulmonary embolism, pulmonary hypertension, QT prolongation, Stevens-Johnson syndrome, thrombocytopenia 1 , thrombocytopenic purpura, ventricular tachycardia (including Torsades de Pointes–type arrhythmias), vaginal bleeding, and violent behaviors 1 . 1 These terms represent serious adverse events, but do not meet the definition for adverse drug reactions. They are included here because of their seriousness."}', 'drug_interactions': '{"7 DRUG INTERACTIONS As with all drugs, the potential for interaction by a variety of mechanisms (e.g., pharmacodynamic, pharmacokinetic drug inhibition or enhancement, etc.) is a possibility. Monoamine Oxidase Inhibitors (MAOIs): (2.9 , 2.10 , 4.1 , 5.2 ) Drugs Metabolized by CYP2D6: Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway (7.7) Tricyclic Antidepressants (TCAs): Monitor TCA levels during coadministration with fluoxetine or when fluoxetine has been recently discontinued (5.2 , 7.7) CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs (7.2) Benzodiazepines: Diazepam - increased t½, alprazolam – further psychomotor performance decrement due to increased levels (7.7) Antipsychotics: Potential for elevation of haloperidol and clozapine levels (7.7) Anticonvulsants: Potential for elevated phenytoin and carbamazepine levels and clinical anticonvulsant toxicity (7.7) Serotonergic Drugs: (2.9 , 2.10 , 4.1 , 5.2) Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, Warfarin): May potentiate the risk of bleeding (7.4) Drugs Tightly Bound to Plasma Proteins: May cause a shift in plasma concentrations (7.6 , 7.7) Olanzapine: When used in combination with fluoxetine, also refer to the Drug Interactions section of the package insert for Symbyax (7.7) Drugs that Prolong the QT Interval: Do not use fluoxetine with thioridazine or pimozide. Use with caution in combination with other drugs that prolong the QT interval ( 4.2 , 5.11 , 7.7 , 7.8 ) 7.1 Monoamine Oxidase Inhibitors (MAOI) [See Dosage and Administration (2.9, 2.10 ), Contraindications (4.1) , and Warnings and Precautions (5.2) ]. 7.2 CNS Acting Drugs Caution is advised if the concomitant administration of fluoxetine and such drugs is required. In evaluating individual cases, consideration should be given to using lower initial doses of the concomitantly administered drugs, using conservative titration schedules, and monitoring of clinical status [see Clinical Pharmacology (12.3) ] . 7.3 Other Serotonergic Drugs The concomitant use of serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John\'s Wort) with fluoxetine increases the risk of serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of fluoxetine and/or concomitant serotonergic drugs [see Warnings and Precautions (5.2) ]. 7.4 Drugs that Interfere with Hemostasis (e.g., NSAIDS, Aspirin, Warfarin) Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SNRIs or SSRIs are coadministered with warfarin. Patients receiving warfarin therapy should be carefully monitored when fluoxetine is initiated or discontinued [see Warnings and Precautions (5.7) ] . 7.5 Electroconvulsive Therapy (ECT) There are no clinical studies establishing the benefit of the combined use of ECT and fluoxetine. There have been rare reports of prolonged seizures in patients on fluoxetine receiving ECT treatment. 7.6 Potential for Other Drugs to affect Fluoxetine Drugs Tightly Bound to Plasma Proteins — Because fluoxetine is tightly bound to plasma proteins, adverse effects may result from displacement of protein-bound fluoxetine by other tightly-bound drugs [see Clinical Pharmacology (12.3) ] . 7.7 Potential for Fluoxetine to affect Other Drugs Pimozide — Concomitant use in patients taking pimozide is contraindicated. Pimozide can prolong the QT interval. Fluoxetine can increase the level of pimozide through inhibition of CYP2D6. Fluoxetine can also prolong the QT interval. Clinical studies of pimozide with other antidepressants demonstrate an increase in drug interaction or QT prolongation. While a specific study with pimozide and fluoxetine has not been conducted, the potential for drug interactions or QT prolongation warrants restricting the concurrent use of pimozide and fluoxetine [see Contraindications (4.2) , Warnings and Precautions (5.11) , and Drug Interactions (7.8) ] . Thioridazine — Thioridazine should not be administered with fluoxetine or within a minimum of 5 weeks after fluoxetine has been discontinued, because of the risk of QT Prolongation [see Contraindications (4.2) , Warnings and Precautions (5.11) , and Drug Interactions (7.8) ] . In a study of 19 healthy male subjects, which included 6 slow and 13 rapid hydroxylators of debrisoquin, a single 25 mg oral dose of thioridazine produced a 2.4-fold higher C max and a 4.5-fold higher AUC for thioridazine in the slow hydroxylators compared with the rapid hydroxylators. The rate of debrisoquin hydroxylation is felt to depend on the level of CYP2D6 isozyme activity. Thus, this study suggests that drugs which inhibit CYP2D6, such as certain SSRIs, including fluoxetine, will produce elevated plasma levels of thioridazine. Thioridazine administration produces a dose-related prolongation of the QT interval, which is associated with serious ventricular arrhythmias, such as Torsades de Pointes-type arrhythmias, and sudden death. This risk is expected to increase with fluoxetine-induced inhibition of thioridazine metabolism. Drugs Metabolized by CYP2D6 — Fluoxetine inhibits the activity of CYP2D6, and may make individuals with normal CYP2D6 metabolic activity resemble a poor metabolizer. Coadministration of fluoxetine with other drugs that are metabolized by CYP2D6, including certain antidepressants (e.g., TCAs), antipsychotics (e.g., phenothiazines and most atypicals), and antiarrhythmics (e.g., propafenone, flecainide, and others) should be approached with caution. Therapy with medications that are predominantly metabolized by the CYP2D6 system and that have a relatively narrow therapeutic index (see list below) should be initiated at the low end of the dose range if a patient is receiving fluoxetine concurrently or has taken it in the previous 5 weeks. Thus, his/her dosing requirements resemble those of poor metabolizers. If fluoxetine is added to the treatment regimen of a patient already receiving a drug metabolized by CYP2D6, the need for decreased dose of the original medication should be considered. Drugs with a narrow therapeutic index represent the greatest concern (e.g., flecainide, propafenone, vinblastine, and TCAs). Due to the risk of serious ventricular arrhythmias and sudden death potentially associated with elevated plasma levels of thioridazine, thioridazine should not be administered with fluoxetine or within a minimum of 5 weeks after fluoxetine has been discontinued [see Contraindications (4.2 )] . Tricyclic Antidepressants (TCAs) — In 2 studies, previously stable plasma levels of imipramine and desipramine have increased greater than 2- to 10-fold when fluoxetine has been administered in combination. This influence may persist for 3 weeks or longer after fluoxetine is discontinued. Thus, the dose of TCAs may need to be reduced and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is coadministered or has been recently discontinued [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ] . Benzodiazepines — The half-life of concurrently administered diazepam may be prolonged in some patients [see Clinical Pharmacology (12.3) ] . Coadministration of alprazolam and fluoxetine has resulted in increased alprazolam plasma concentrations and in further psychomotor performance decrement due to increased alprazolam levels. Antipsychotics — Some clinical data suggests a possible pharmacodynamic and/or pharmacokinetic interaction between SSRIs and antipsychotics. Elevation of blood levels of haloperidol and clozapine has been observed in patients receiving concomitant fluoxetine. Anticonvulsants — Patients on stable doses of phenytoin and carbamazepine have developed elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity following initiation of concomitant fluoxetine treatment. Lithium — There have been reports of both increased and decreased lithium levels when lithium was used concomitantly with fluoxetine. Cases of lithium toxicity and increased serotonergic effects have been reported. Lithium levels should be monitored when these drugs are administered concomitantly [see Warnings and Precautions (5.2) ] . Drugs Tightly Bound to Plasma Proteins — Because fluoxetine is tightly bound to plasma proteins, the administration of fluoxetine to a patient taking another drug that is tightly bound to protein (e.g., Coumadin, digitoxin) may cause a shift in plasma concentrations potentially resulting in an adverse effect [see Clinical Pharmacology (12.3) ] . Drugs Metabolized by CYP3A4 — In an in vivo interaction study involving coadministration of fluoxetine with single doses of terfenadine (a CYP3A4 substrate), no increase in plasma terfenadine concentrations occurred with concomitant fluoxetine. Additionally, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than fluoxetine or norfluoxetine as an inhibitor of the metabolism of several substrates for this enzyme, including astemizole, cisapride, and midazolam. These data indicate that fluoxetine’s extent of inhibition of CYP3A4 activity is not likely to be of clinical significance. Olanzapine — Fluoxetine (60 mg single dose or 60 mg daily dose for 8 days) causes a small (mean 16%) increase in the maximum concentration of olanzapine and a small (mean 16%) decrease in olanzapine clearance. The magnitude of the impact of this factor is small in comparison to the overall variability between individuals, and therefore dose modification is not routinely recommended. When using fluoxetine and olanzapine and in combination, also refer to the Drug Interactions section of the package insert for Symbyax. 7.8 Drugs that Prolong the QT Interval Do not use fluoxetine in combination with thioridazine or pimozide. Use fluoxetine with caution in combination with other drugs that cause QT prolongation. These include: specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus). Fluoxetine is primarily metabolized by CYP2D6. Concomitant treatment with CYP2D6 inhibitors can increase the concentration of fluoxetine. Concomitant use of other highly protein-bound drugs can increase the concentration of fluoxetine [see Contraindications (4.2) , Warnings and Precautions (5.11) , Drug Interactions (7.7) , and Clinical Pharmacology (12.3) ]."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Fluoxetine capsules are indicated for the treatment of: Acute and maintenance treatment of Major Depressive Disorder [see Clinical Studies (14.1) ] . Acute and maintenance treatment of obsessions and compulsions in patients with Obsessive Compulsive Disorder (OCD) [see Clinical Studies (14.2) ] . Acute and maintenance treatment of binge-eating and vomiting behaviors in patients with moderate to severe Bulimia Nervosa [see Clinical Studies (14.3) ] . Acute treatment of Panic Disorder, with or without agoraphobia [see Clinical Studies (14.4) ] . Fluoxetine capsules and Olanzapine in Combination are indicated for the treatment of: Acute treatment of depressive episodes associated with Bipolar I Disorder. Treatment resistant depression (Major Depressive Disorder in patients, who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode). Fluoxetine capsules monotherapy is not indicated for the treatment of depressive episodes associated with Bipolar I Disorder or the treatment of treatment resistant depression. When using fluoxetine capsules and olanzapine in combination, also refer to the Clinical Studies section of the package insert for Symbyax ® . Fluoxetine capsules are a selective serotonin reuptake inhibitor indicated for: Acute and maintenance treatment of Major Depressive Disorder (MDD) ( 1 ) Acute and maintenance treatment of Obsessive Compulsive Disorder (OCD) ( 1 ) Acute and maintenance treatment of Bulimia Nervosa ( 1 ) Acute treatment of Panic Disorder, with or without agoraphobia ( 1 ) Fluoxetine capsules and olanzapine in combination for treatment of: Acute Depressive Episodes Associated with Bipolar I Disorder ( 1 ) Treatment Resistant Depression ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS When using fluoxetine and olanzapine in combination, also refer to the Warnings and Precautions section of the package insert for Symbyax. Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults: Monitor for clinical worsening and suicidal thinking and behavior (5.1) Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including fluoxetine , both when taken alone, but especially when co-administered with other serotonergic agents. If such symptoms occur, discontinue fluoxetine and serotonergic agents and initiate supportive treatment. If concomitant use of fluoxetine with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases (5.2) Allergic Reactions and Rash: Discontinue upon appearance of rash or allergic phenomena (5.3) Activation of Mania/Hypomania: Screen for Bipolar Disorder and monitor for mania/hypomania (5.4) Seizures: Use cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold (5.5) Altered Appetite and Weight: Significant weight loss has occurred (5.6) Increased Risk of Bleeding: May increase the risk of bleeding. Use with NSAIDs, aspirin, warfarin, or other drugs that affect coagulation may potentiate the risk of gastrointestinal or other bleeding (5.7) Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants (5.8) Hyponatremia: Has been reported with fluoxetine in association with syndrome of inappropriate antidiuretic hormone (SIADH). Consider discontinuing if symptomatic hyponatremia occurs (5.9) Anxiety and Insomnia: May occur (5.10) QT Prolongation: QT prolongation and ventricular arrhythmia including Torsades de Pointes have been reported with fluoxetine use. Use with caution in conditions that predispose to arrhythmias or increased fluoxetine exposure. Use cautiously in patients with risk factors for QT prolongation (4.2 , 5.11 ) Potential for Cognitive and Motor Impairment: Has potential to impair judgment, thinking, and motor skills. Use caution when operating machinery ( 5.13 ) Long Half-Life: Changes in dose will not be fully reflected in plasma for several weeks ( 5.14 ) Fluoxetine and Olanzapine in Combination: When using fluoxetine and olanzapine in combination, also refer to the Warnings and Precautions section of the package insert for Symbyax ( 5.16 ) Sexual Dysfunction: Fluoxetine may cause symptoms of sexual dysfunction ( 5.17 ) 5.1 Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults Patients with Major Depressive Disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with Major Depressive Disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, Obsessive Compulsive Disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug versus placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 2. Table 2: Suicidality per 1000 Patients Treated Age Range Drug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated Increases Compared to Placebo <18 14 additional cases 18 to 24 5 additional cases Decreases Compared to Placebo 25 to 64 1 fewer case ≥65 6 fewer cases No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for Major Depressive Disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms [see Warnings and Precautions (5.15) ] . Families and caregivers of patients being treated with antidepressants for Major Depressive Disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for fluoxetine should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose. It should be noted that fluoxetine is approved in the pediatric population for Major Depressive Disorder and Obsessive Compulsive Disorder; and fluoxetine in combination with olanzapine for the acute treatment of depressive episodes associated with Bipolar I Disorder. 5.2 Serotonin Syndrome Selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, meperidine, methadone, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications (4) , Drug Interactions (7.1) ] . Serotonin syndrome can also occur when these drugs are used alone. Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of fluoxetine with MAOIs is contraindicated. In addition, do not initiate fluoxetine in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking fluoxetine, discontinue fluoxetine before initiating treatment with the MAOI [see Contraindications (4) and Drug Interactions (7.1) ] . Monitor all patients taking fluoxetine for the emergence of serotonin syndrome. Discontinue treatment with fluoxetine and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of fluoxetine with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.3 Allergic Reactions and Rash In U.S. fluoxetine clinical trials, 7% of 10,782 patients developed various types of rashes and/or urticaria. Among the cases of rash and/or urticaria reported in premarketing clinical trials, almost a third were withdrawn from treatment because of the rash and/or systemic signs or symptoms associated with the rash. Clinical findings reported in association with rash include fever, leukocytosis, arthralgias, edema, carpal tunnel syndrome, respiratory distress, lymphadenopathy, proteinuria, and mild transaminase elevation. Most patients improved promptly with discontinuation of fluoxetine and/or adjunctive treatment with antihistamines or steroids, and all patients experiencing these reactions were reported to recover completely. In premarketing clinical trials, 2 patients are known to have developed a serious cutaneous systemic illness. In neither patient was there an unequivocal diagnosis, but one was considered to have a leukocytoclastic vasculitis, and the other, a severe desquamating syndrome that was considered variously to be a vasculitis or erythema multiforme. Other patients have had systemic syndromes suggestive of serum sickness. Since the introduction of fluoxetine, systemic reactions, possibly related to vasculitis and including lupus-like syndrome, have developed in patients with rash. Although these reactions are rare, they may be serious, involving the lung, kidney, or liver. Death has been reported to occur in association with these systemic reactions. Anaphylactoid reactions, including bronchospasm, angioedema, laryngospasm, and urticaria alone and in combination, have been reported. Pulmonary reactions, including inflammatory processes of varying histopathology and/or fibrosis, have been reported rarely. These reactions have occurred with dyspnea as the only preceding symptom. Whether these systemic reactions and rash have a common underlying cause or are due to different etiologies or pathogenic processes is not known. Furthermore, a specific underlying immunologic basis for these reactions has not been identified. Upon the appearance of rash or of other possibly allergic phenomena for which an alternative etiology cannot be identified, fluoxetine should be discontinued. 5.4 Screening Patients for Bipolar Disorder and Monitoring for Mania/Hypomania A major depressive episode may be the initial presentation of Bipolar Disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for Bipolar Disorder. Whether any of the symptoms described for clinical worsening and suicide risk represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for Bipolar Disorder; such screening should include a detailed psychiatric history, including a family history of suicide, Bipolar Disorder, and depression. It should be noted that fluoxetine and olanzapine in combination is approved for the acute treatment of depressive episodes associated with Bipolar I Disorder [see Warnings and Precautions section of the package insert for Symbyax] . Fluoxetine monotherapy is not indicated for the treatment of depressive episodes associated with Bipolar I Disorder. In U.S. placebo-controlled clinical trials for Major Depressive Disorder, mania/hypomania was reported in 0.1% of patients treated with fluoxetine and 0.1% of patients treated with placebo. Activation of mania/hypomania has also been reported in a small proportion of patients with Major Affective Disorder treated with other marketed drugs effective in the treatment of Major Depressive Disorder [see Use in Specific Populations (8.4) ] . In U.S. placebo-controlled clinical trials for OCD, mania/hypomania was reported in 0.8% of patients treated with fluoxetine and no patients treated with placebo. No patients reported mania/hypomania in U.S. placebo-controlled clinical trials for bulimia. In U.S. fluoxetine clinical trials, 0.7% of 10,782 patients reported mania/hypomania [see Use in Specific Populations (8.4) ] . 5.5 Seizures In U.S. placebo-controlled clinical trials for Major Depressive Disorder, convulsions (or reactions described as possibly having been seizures) were reported in 0.1% of patients treated with fluoxetine and 0.2% of patients treated with placebo. No patients reported convulsions in U.S. placebo-controlled clinical trials for either OCD or bulimia. In U.S. fluoxetine clinical trials, 0.2% of 10,782 patients reported convulsions. The percentage appears to be similar to that associated with other marketed drugs effective in the treatment of Major Depressive Disorder. Fluoxetine should be introduced with care in patients with a history of seizures. 5.6 Altered Appetite and Weight Significant weight loss, especially in underweight depressed or bulimic patients, may be an undesirable result of treatment with fluoxetine. In U.S. placebo-controlled clinical trials for Major Depressive Disorder, 11% of patients treated with fluoxetine and 2% of patients treated with placebo reported anorexia (decreased appetite). Weight loss was reported in 1.4% of patients treated with fluoxetine and in 0.5% of patients treated with placebo. However, only rarely have patients discontinued treatment with fluoxetine because of anorexia or weight loss [see Use in Specific Populations (8.4) ] . In U.S. placebo-controlled clinical trials for OCD, 17% of patients treated with fluoxetine and 10% of patients treated with placebo reported anorexia (decreased appetite). One patient discontinued treatment with fluoxetine because of anorexia [see Use in Specific Populations (8.4) ] . In U.S. placebo-controlled clinical trials for Bulimia Nervosa, 8% of patients treated with fluoxetine 60 mg and 4% of patients treated with placebo reported anorexia (decreased appetite). Patients treated with fluoxetine 60 mg on average lost 0.45 kg compared with a gain of 0.16 kg by patients treated with placebo in the 16-week double-blind trial. Weight change should be monitored during therapy. 5.7 Increased Risk of Bleeding SNRIs and SSRIs, including fluoxetine, may increase the risk of bleeding reactions. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anti-coagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Based on data from the published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Use in Specific Populations (8.1) ]. Bleeding reactions related to SNRIs and SSRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages. Patients should be cautioned about the increased risk of bleeding associated with the concomitant use of fluoxetine and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation [see Drug Interactions (7.4) ] . 5.8 Angle-Closure Glaucoma Angle-Closure Glaucoma – The pupillary dilation that occurs following use of many antidepressant drugs including fluoxetine may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. 5.9 Hyponatremia Hyponatremia has been reported during treatment with SNRIs and SSRIs, including fluoxetine. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Cases with serum sodium lower than 110 mmol/L have been reported and appeared to be reversible when fluoxetine was discontinued. Elderly patients may be at greater risk of developing hyponatremia with SNRIs and SSRIs. Also, patients taking diuretics or who are otherwise volume depleted may be at greater risk [see Use in Specific Populations (8.5) ] . Discontinuation of fluoxetine should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. More severe and/or acute cases have been associated with hallucination, syncope, seizure, coma, respiratory arrest, and death. 5.10 Anxiety and Insomnia In U.S. placebo-controlled clinical trials for Major Depressive Disorder, 12% to 16% of patients treated with fluoxetine and 7% to 9% of patients treated with placebo reported anxiety, nervousness, or insomnia. In U.S. placebo-controlled clinical trials for OCD, insomnia was reported in 28% of patients treated with fluoxetine and in 22% of patients treated with placebo. Anxiety was reported in 14% of patients treated with fluoxetine and in 7% of patients treated with placebo. In U.S. placebo-controlled clinical trials for Bulimia Nervosa, insomnia was reported in 33% of patients treated with fluoxetine 60 mg, and 13% of patients treated with placebo. Anxiety and nervousness were reported, respectively, in 15% and 11% of patients treated with fluoxetine 60 mg and in 9% and 5% of patients treated with placebo. Among the most common adverse reactions associated with discontinuation (incidence at least twice that for placebo and at least 1% for fluoxetine in clinical trials collecting only a primary reaction associated with discontinuation) in U.S. placebo-controlled fluoxetine clinical trials were anxiety (2% in OCD), insomnia (1% in combined indications and 2% in bulimia), and nervousness (1% in Major Depressive Disorder) [see Table 5] . 5.11 QT Prolongation Post-marketing cases of QT interval prolongation and ventricular arrhythmia including Torsades de Pointes have been reported in patients treated with fluoxetine. Fluoxetine should be used with caution in patients with congenital long QT syndrome; a previous history of QT prolongation; a family history of long QT syndrome or sudden cardiac death; and other conditions that predispose to QT prolongation and ventricular arrhythmia. Such conditions include concomitant use of drugs that prolong the QT interval; hypokalemia or hypomagnesemia; recent myocardial infarction, uncompensated heart failure, bradyarrhythmias, and other significant arrhythmias; and conditions that predispose to increased fluoxetine exposure (overdose, hepatic impairment, use of CYP2D6 inhibitors, CYP2D6 poor metabolizer status, or use of other highly protein-bound drugs). Fluoxetine is primarily metabolized by CYP2D6 [see Contraindications (4.2) , Adverse Reactions (6.2) , Drug Interactions (7.7 , 7.8) , Overdosage (10) , and Clinical Pharmacology (12.3) ]. Pimozide and thioridazine are contraindicated for use with fluoxetine. Avoid the concomitant use of drugs known to prolong the QT interval. These include specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol,); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus) [see Drug Interactions (7.7, 7.8) and Clinical Pharmacology (12.3) ]. Consider ECG assessment and periodic ECG monitoring if initiating treatment with fluoxetine in patients with risk factors for QT prolongation and ventricular arrhythmia. Consider discontinuing fluoxetine and obtaining a cardiac evaluation if patients develop signs or symptoms consistent with ventricular arrhythmia. 5.12 Use in Patients with Concomitant Illness Clinical experience with fluoxetine in patients with concomitant systemic illness is limited. Caution is advisable in using fluoxetine in patients with diseases or conditions that could affect metabolism or hemodynamic responses. Cardiovascular — Fluoxetine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were systematically excluded from clinical studies during the product’s premarket testing. However, the electrocardiograms of 312 patients who received fluoxetine in double-blind trials were retrospectively evaluated; no conduction abnormalities that resulted in heart block were observed. The mean heart rate was reduced by approximately 3 beats/min. Glycemic Control — In patients with diabetes, fluoxetine may alter glycemic control. Hypoglycemia has occurred during therapy with fluoxetine, and hyperglycemia has developed following discontinuation of the drug. As is true with many other types of medication when taken concurrently by patients with diabetes, insulin and/or oral hypoglycemic, dosage may need to be adjusted when therapy with fluoxetine is instituted or discontinued. 5.13 Potential for Cognitive and Motor Impairment As with any CNS-active drug, fluoxetine has the potential to impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that the drug treatment does not affect them adversely. 5.14 Long Elimination Half-Life Because of the long elimination half-lives of the parent drug and its major active metabolite, changes in dose will not be fully reflected in plasma for several weeks, affecting both strategies for titration to final dose and withdrawal from treatment. This is of potential consequence when drug discontinuation is required or when drugs are prescribed that might interact with fluoxetine and norfluoxetine following the discontinuation of fluoxetine [see Clinical Pharmacology (12.3) ] . 5.15 Discontinuation Adverse Reactions During marketing of fluoxetine, SNRIs, and SSRIs, there have been spontaneous reports of adverse reactions occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania. While these reactions are generally self-limiting, there have been reports of serious discontinuation symptoms. Patients should be monitored for these symptoms when discontinuing treatment with fluoxetine. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the healthcare provider may continue decreasing the dose but at a more gradual rate. Plasma fluoxetine and norfluoxetine concentration decrease gradually at the conclusion of therapy which may minimize the risk of discontinuation symptoms with this drug. 5.16 Fluoxetine and Olanzapine in Combination When using fluoxetine and olanzapine in combination, also refer to the Warnings and Precautions section of the package insert for Symbyax. 5.17 Sexual Dysfunction Use of SSRIs, including fluoxetine, may cause symptoms of sexual dysfunction [see Adverse Reactions (6.1)]. In male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, SSRI use may result in decreased libido and delayed or absent orgasm. It is important for prescribers to inquire about sexual function prior to initiation of fluoxetine and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported. When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder. Discuss potential management strategies to support patients in making informed decisions about treatment."}', 'overdosage': '{"10 OVERDOSAGE The following have been reported with fluoxetine overdosage: Seizures, which may be delayed, and altered mental status including coma. Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation, wide complex tachyarrhythmias, torsade de pointes, and cardiac arrest. Hypertension most commonly seen, but rarely can see hypotension alone or with co-ingestants including alcohol. Serotonin syndrome (patients with a multiple drug overdosage with other pro-serotonergic drugs may have a higher risk). Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a fluoxetine overdose. Consider contacting a Poison Center (1-800-221-2222) or a medical toxicologist for additional overdosage management recommendations."}', 'active_flag': 'Y', 'generic_name': '{"FLUOXETINE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking fluoxetine as monotherapy or in combination with olanzapine. When using fluoxetine and olanzapine in combination, also refer to the Patient Counseling Information section of the package insert for Symbyax. General Information Healthcare providers should instruct their patients to read the Medication Guide before starting therapy with fluoxetine and to reread it each time the prescription is renewed. Healthcare providers should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with fluoxetine and should counsel them in its appropriate use. Healthcare providers should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. Patients should be advised of the following issues and asked to alert their healthcare provider if these occur while taking fluoxetine. When using fluoxetine and olanzapine in combination, also refer to the Medication Guide for Symbyax. Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient’s prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication [see Box Warning and Warnings a nd Precautions (5.1) ]. Serotonin Syndrome Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of fluoxetine and other serotonergic agents including triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort [see Contraindications (4.1) , Warnings and Precautions (5.2) , and Drug Interactions (7.3) ] . Patients should be advised of the signs and symptoms associated with serotonin syndrome that may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular changes (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be cautioned to seek medical care immediately if they experience these symptoms. Allergic Reactions and Rash Patients should be advised to notify their healthcare provider if they develop a rash or hives [see Warnings and Precautions (5.3) ]. Patients should also be advised of the signs and symptoms associated with a severe allergic reaction, including swelling of the face, eyes, or mouth, or have trouble breathing. Patients should be cautioned to seek medical care immediately if they experience these symptoms. Increased Risk of Bleeding Patients should be cautioned about the concomitant use of fluoxetine and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation since combined use of psychotropic drugs that interfere with serotonin reuptake and these agents have been associated with an increased risk of bleeding [see Warnings and Precautions (5.7) and Drug Interactions (7.4) ]. Patients should be advised to call their healthcare provider if they experience any increased or unusual bruising or bleeding while taking fluoxetine. Angle-Closure Glaucoma Patients should be advised that taking fluoxetine can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle-closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible [see Warnings and Precautions (5.8) ]. Hyponatremia Patients should be advised that hyponatremia has been reported as a result of treatment with SNRIs and SSRIs, including fluoxetine. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. More severe and/or acute cases have been associated with hallucination, syncope, seizure, coma, respiratory arrest, and death [see Warnings and Precautions (5.9) ]. QT Prolongation Patients should be advised that QT interval prolongation and ventricular arrhythmia including Torsades de Pointes have been reported in patients treated with fluoxetine. Signs and symptoms of ventricular arrhythmia include fast, slow, or irregular heart rate, dyspnea, syncope, or dizziness, which may indicate serious cardiac arrhythmia [see Warnings and Precautions (5.11) ] . Potential for Cognitive and Motor Impairment Fluoxetine may impair judgment, thinking, or motor skills. Patients should be advised to avoid driving a car or operating hazardous machinery until they are reasonably certain that their performance is not affected [see Warnings and Precautions (5.13) ]. Use of Concomitant Medications Patients should be advised to inform their healthcare provider if they are taking, or plan to take, any prescription medication, including Symbyax, Sarafem, or over-the-counter drugs, including herbal supplements or alcohol. Patients should also be advised to inform their healthcare providers if they plan to discontinue any medications they are taking while on fluoxetine. Discontinuation of Treatment Patients should be advised to take fluoxetine exactly as prescribed, and to continue taking fluoxetine as prescribed even after their symptoms improve. Patients should be advised that they should not alter their dosing regimen, or stop taking fluoxetine without consulting their healthcare provider [see Warnings and Precautions (5.15) ] . Patients should be advised to consult with their healthcare provider if their symptoms do not improve with fluoxetine. Sexual Dysfunction Advise patients that use of fluoxetine may cause symptoms of sexual dysfunction in both male and female patients. Inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider [see Warnings and Precautions (5.17) ]. Use in Specific Populations Pregnancy — Advise pregnant women to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with fluoxetine. Advise patients that fluoxetine use later in pregnancy may lead to increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN) [see Use in Specific Populations (8.1) ] . Advise women that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to fluoxetine during pregnancy [see Use in Specific Populations (8.1) ] . Lactation —Advise breastfeeding women using fluoxetine to monitor infants for agitation, irritability, poor feeding and poor weight gain and to seek medical care if they notice these signs [see Use in Specific Populations (8.2) ] . Pediatric Use of Fluoxetine — Fluoxetine is approved for use in pediatric patients with MDD and OCD [see Box Warning and Warnings and Precautions (5.1)] . Limited evidence is available concerning the longer-term effects of fluoxetine on the development and maturation of children and adolescent patients. Height and weight should be monitored periodically in pediatric patients receiving fluoxetine [see Warnings and Precautions (5.6) and Use in Specific Populations (8.4) ] . Pediatric Use of fluoxetine and olanzapine in combination – Safety and efficacy of fluoxetine and olanzapine in combination in patients 10 to 17 years of age have been established for the acute treatment of depressive episodes associated with Bipolar I Disorder [see Warnings and Precautions (5.16) and Use in Specific Populations (8.4) ]. Symbyax ® and Sarafem ® are registered trademarks of Eli Lilly. Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad–500 032, India Revised: 09/2023 Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides"}', 'pregnancy': '{"8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research\xadprograms/pregnancyregistry/antidepressants/. Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.7) and Clinical Considerations]. Available data from published epidemiologic studies and postmarketing reports over several decades have not established an increased risk of major birth defects or miscarriage. Some studies have reported an increased incidence of cardiovascular malformations; however, these studies results do not establish a causal relationship (see Data) . There are risks associated with untreated depression in pregnancy and risks of persistent pulmonary hypertension of the newborn (PPHN) (see Data) and poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, during pregnancy (see Clinical Considerations). In rats and rabbits treated with fluoxetine during the period of organogenesis, there was no evidence of developmental effects at doses up to 1.6 and 3.9 times, respectively, the maximum recommended human dose (MRHD) of 60 mg/day given to adolescents on a mg/m 2 basis. However, in other reproductive studies in rats, an increase in stillborn pups, a decrease in pup weight, and an increase in pup deaths early after birth occurred at doses that are 1.5 times (during gestation) and 0.97 time (during gestation and lactation) the MRHD given to adolescents on a mg/m 2 basis. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Maternal Adverse Reactions Use of fluoxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.7) ]. Fetal/Neonatal adverse reactions Neonates exposed to fluoxetine and other SSRI or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability, and constant crying. These findings are consistent with either a direct toxic effect of SSRIs and SNRIs or possibly a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions (5.2) ] . Data Human Data — It has been shown that SSRIs (including fluoxetine) can cross the placenta. Published epidemiological studies of pregnant women exposed to fluoxetine have not established an increased risk of major birth defects, miscarriage, and other adverse developmental outcomes. Several publications reported an increased incidence of cardiovascular malformations in children with in utero exposure to fluoxetine. However, these studies results do not establish a causal relationship. Methodologic limitations of these observational studies include possible exposure and outcome misclassification, lack of adequate controls, adjustment for confounders and confirmatory studies. However, these studies cannot definitely establish or exclude any drug-associated risk during pregnancy. Exposure to SSRIs, particularly later in pregnancy, may have an increased risk for PPHN. PPHN occurs in 1 to 2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal Data — In embryofetal development studies in rats and rabbits, there was no evidence of malformations or developmental variations following administration of fluoxetine at doses up to 12.5 and 15 mg/kg/day, respectively (1.6 and 3.9 times, respectively, the MRHD of 60 mg given to adolescents on a mg/m 2 basis) throughout organogenesis. However, in rat reproduction studies, an increase in stillborn pups, a decrease in pup weight, and an increase in pup deaths during the first 7 days postpartum occurred following maternal exposure to 12 mg/kg/day (1.5 times the MRHD given to adolescents on a mg/m 2 basis) during gestation or 7.5 mg/kg/day (0.97 time the MRHD given to adolescents on a mg/m 2 basis) during gestation and lactation. There was no evidence of developmental neurotoxicity in the surviving offspring of rats treated with 12 mg/kg/day during gestation. The no-effect dose for rat pup mortality was 5 mg/kg/day (0.65 time the MRHD given to adolescents on a mg/m 2 basis)."}', 'pediatric_use': '{"8.4 Pediatric Use Use of fluoxetine in children - The efficacy of fluoxetine for the treatment of Major Depressive Disorder was demonstrated in two 8- to 9-week placebo-controlled clinical trials with 315 pediatric outpatients ages 8 to ≤18 [see Clinical Studies (14.1) ] . The efficacy of fluoxetine for the treatment of OCD was demonstrated in one 13-week placebo-controlled clinical trial with 103 pediatric outpatients ages 7 to <18 [see Clinical Studies (14.2) ] . The safety and effectiveness in pediatric patients <8 years of age in Major Depressive Disorder and <7 years of age in OCD have not been established. Fluoxetine pharmacokinetics were evaluated in 21 pediatric patients (ages 6 to ≤18) with Major Depressive Disorder or OCD [see Clinical Pharmacology (12.3) ] . The acute adverse reaction profiles observed in the 3 studies (N=418 randomized; 228 fluoxetine-treated, 190 placebo-treated) were generally similar to that observed in adult studies with fluoxetine. The longer-term adverse reaction profile observed in the 19-week Major Depressive Disorder study (N=219 randomized; 109 fluoxetine-treated, 110 placebo-treated) was also similar to that observed in adult trials with fluoxetine [see Adverse Reactions (6.1) ] . Manic reaction, including mania and hypomania, was reported in 6 (1 mania, 5 hypomania) out of 228 (2.6%) fluoxetine-treated patients and in 0 out of 190 (0%) placebo-treated patients. Mania/hypomania led to the discontinuation of 4 (1.8%) fluoxetine-treated patients from the acute phases of the 3 studies combined. Consequently, regular monitoring for the occurrence of mania/hypomania is recommended. As with other SSRIs, decreased weight gain has been observed in association with the use of fluoxetine in children and adolescent patients. After 19 weeks of treatment in a clinical trial, pediatric subjects treated with fluoxetine gained an average of 1.1 cm less in height and 1.1 kg less in weight than subjects treated with placebo. In addition, fluoxetine treatment was associated with a decrease in alkaline phosphatase levels. The safety of fluoxetine treatment for pediatric patients has not been systematically assessed for chronic treatment longer than several months in duration. In particular, there are no studies that directly evaluate the longer-term effects of fluoxetine on the growth, development and maturation of children and adolescent patients. Therefore, height and weight should be monitored periodically in pediatric patients receiving fluoxetine [see Warnings and Precautions (5.6) ] . Fluoxetine is approved for use in pediatric patients with MDD and OCD [see Box Warning and Warnings and Precautions (5.1) ] . Anyone considering the use of fluoxetine in a child or adolescent must balance the potential risks with the clinical need. Animal Data - Significant toxicity on muscle tissue, neurobehavior, reproductive organs, and bone development has been observed following exposure of juvenile rats to fluoxetine from weaning through maturity. Oral administration of fluoxetine to rats from weaning postnatal day 21 through adulthood day 90 at 3, 10, or 30 mg/kg/day was associated with testicular degeneration and necrosis, epididymal vacuolation and hypospermia (at 30 mg/kg/day corresponding to plasma exposures [AUC] approximately 5 to 10 times the average AUC in pediatric patients at the MRHD of 20 mg/day), increased serum levels of creatine kinase (at AUC as low as 1 to 2 times the average AUC in pediatric patients at the MRHD of 20 mg/day), skeletal muscle degeneration and necrosis, decreased femur length/growth and body weight gain (at AUC 5 to 10 times the average AUC in pediatric patients at the MRHD of 20 mg/day). The high dose of 30 mg/kg/day exceeded a maximum tolerated dose. When animals were evaluated after a drug-free period (up to 11 weeks after cessation of dosing), fluoxetine was associated with neurobehavioral abnormalities (decreased reactivity at AUC as low as approximately 0.1 to 0.2 times the average AUC in pediatric patients at the MRHD and learning deficit at the high dose), and reproductive functional impairment (decreased mating at all doses and impaired fertility at the high dose). In addition, the testicular and epididymal microscopic lesions and decreased sperm concentrations found in high dose group were also observed, indicating that the drug effects on reproductive organs are irreversible. The reversibility of fluoxetine-induced muscle damage was not assessed. These fluoxetine toxicities in juvenile rats have not been observed in adult animals. Plasma exposures (AUC) to fluoxetine in juvenile rats receiving 3, 10, or 30 mg/kg/day doses in this study are approximately 0.1 to 0.2, 1 to 2, and 5 to 10 times, respectively, the average exposure in pediatric patients receiving the MRHD of 20 mg/day. Rat exposures to the major metabolite, norfluoxetine, are approximately 0.3 to 0.8, 1 to 8, and 3 to 20 times, respectively, the pediatric exposure at the MRHD. A specific effect on bone development was reported in juvenile mice administered fluoxetine by the intraperitoneal route to 4 week old mice for 4 weeks at doses 0.5 and 2 times the oral MRHD of 20 mg/day on mg/m 2 basis. There was a decrease in bone mineralization and density at both doses, but the overall growth (body weight gain or femur length) was not affected. Use of fluoxetine in combination with olanzapine in children and adolescents: Safety and efficacy of fluoxetine and olanzapine in combination in patients 10 to 17 years of age have been established for the acute treatment of depressive episodes associated with Bipolar I Disorder. Safety and effectiveness of fluoxetine and olanzapine in combination in patients less than 10 years of age have not been established."}', 'geriatric_use': '{"8.5 Geriatric Use U.S. fluoxetine clinical trials included 687 patients ≥65 years of age and 93 patients ≥75 years of age. The efficacy in geriatric patients has been established [see Clinical Studies (14.1) ] . For pharmacokinetic information in geriatric patients, [see Clinical Pharmacology (12.4) ] . No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. SNRIs and SSRIs, including fluoxetine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see Warnings and Precautions (5.9) ] . Clinical studies of olanzapine and fluoxetine in combination did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger patients."}'}

{TERIFLUNOMIDE}

{'contraindications': '{"4 CONTRAINDICATIONS Severe hepatic impairment ( 4 , 5.1 ) Pregnancy ( 4 , 5.2 , 8.1 ) Hypersensitivity ( 4 , 5.5 ) Current leflunomide treatment ( 4 ) Teriflunomide tablets are contraindicated in/with: Patients with severe hepatic impairment [see Warnings and Precautions (5.1 ) ]. Pregnant women and females of reproductive potential not using effective contraception. Teriflunomide tablet may cause fetal harm [see Warnings and Precautions (5.2 , 5.3 ) and Use in Specific Populations (8.1) ]. Patients with a history of a hypersensitivity reaction to teriflunomide, leflunomide, or to any of the inactive ingredients in teriflunomide tablet. Reactions have included anaphylaxis, angioedema, and serious skin reactions [see Warnings and Precautions (5.5) ]. Coadministration with leflunomide [see Clinical Pharmacology (12.3) ]."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the prescribing information: Hepatotoxicity [ see Contraindications (4) and Warnings and Precautions (5.1) ] Bone Marrow Effects/Immunosuppression Potential/Infections [ see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [ see Contraindications (4) and Warnings and Precautions (5.5)] Serious Skin Reactions [ see Warnings and Precautions (5.6) ] Drug Reaction with Eosinophilia and Systemic Symptoms [ see Warnings and Precautions (5.7) ] Peripheral Neuropathy [ see Warnings and Precautions (5.8) ] Increased Blood Pressure [ see Warnings and Precautions (5.9) ] Respiratory Effects [ see Warnings and Precautions (5.10) ] Pancreatitis in Pediatric Patients [ see Warnings and Precautions (5.11) ] Most common adverse reactions (≥10% and ≥2% greater than placebo): headache, diarrhea, nausea, alopecia, increase in ALT. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Biocon Pharma Inc., at 1-866-924-6266 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A total of 2047 patients receiving teriflunomide (7 mg or 14 mg once daily) constituted the safety population in the pooled analysis of placebo controlled studies in patients with relapsing forms of multiple sclerosis; of these, 71% were female. The average age was 37 years. Table 1 lists adverse reactions in placebo-controlled trials with rates that were at least 2% for teriflunomide patients and also at least 2% above the rate in placebo patients. The most common were headache, an increase in ALT, diarrhea, alopecia, and nausea. The adverse reaction most commonly associated with discontinuation was an increase in ALT (3.3%, 2.6%, and 2.3% of all patients in the teriflunomide 7 mg, teriflunomide 14 mg, and placebo treatment arms, respectively). Table 1: Adverse Reactions in Pooled Placebo-Controlled Studies in Patients with Relapsing Forms of Multiple Sclerosis Adverse Reaction Teriflunomide 7 mg (N=1045) Teriflunomide 14 mg (N=1002) Placebo (N=997) Headache 18% 16% 15% Increase in Alanine aminotransferase 13% 15% 9% Diarrhea 13% 14% 8% Alopecia 10% 13% 5% Nausea 8% 11% 7% Paresthesia 8% 9% 7% Arthralgia 8% 6% 5% Neutropenia 4% 6% 2% Hypertension 3% 4% 2% Cardiovascular Deaths Four cardiovascular deaths, including three sudden deaths, and one myocardial infarction in a patient with a history of hyperlipidemia and hypertension were reported among approximately 2600 patients exposed to teriflunomide in the premarketing database. These cardiovascular deaths occurred during uncontrolled extension studies, one to nine years after initiation of treatment. A relationship between teriflunomide and cardiovascular death has not been established. Acute Renal Failure In placebo-controlled studies, creatinine values increased more than 100% over baseline in 8/1045 (0.8%) patients in the 7 mg teriflunomide group and 6/1002 (0.6%) patients in the 14 mg teriflunomide group versus 4/997 (0.4%) patients in the placebo group. These elevations were transient. Some elevations were accompanied by hyperkalemia. Teriflunomide may cause acute uric acid nephropathy with transient acute renal failure because teriflunomide increases renal uric acid clearance. Hypophosphatemia In clinical trials, 18% of teriflunomide-treated patients had hypophosphatemia with serum phosphorus levels of at least 0.6 mmol/L, compared to 7% of placebo-treated patients; 4% of teriflunomide-treated patients had hypophosphatemia with serum phosphorus levels at least 0.3 mmol/L but less than 0.6 mmol/L, compared to 0.8% of placebo-treated patients. No patient in any treatment group had a serum phosphorus below 0.3 mmol/L. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of teriflunomide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders : Thrombocytopenia [ see Warnings and Precautions (5.4) ] Gastrointestinal Disorders: Pancreatitis, colitis Hepatobiliary Disorders : Drug-induced liver injury (DILI) [ see Warnings and Precautions (5.1) ] Immune System Disorders: Hypersensitivity reactions, some of which were severe, such as anaphylaxis and angioedema [ see Warnings and Precautions (5.5) ] Respiratory, Thoracic, and Mediastinal Disorders: Interstitial lung disease [ see Warnings and Precautions (5.10) ] Skin and Subcutaneous Tissue Disorders : Severe skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome [ see Warnings and Precautions (5.6) ]; drug reaction with eosinophilia and systemic symptoms (DRESS) [ see Warnings and Precautions (5.7) ]; psoriasis or worsening of psoriasis (including pustular psoriasis and nail psoriasis); nail disorders"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Drugs metabolized by CYP2C8 and OAT3 transporters: Monitor patients because teriflunomide may increase exposure of these drugs. ( 7 ) Teriflunomide may increase exposure of ethinylestradiol and levonorgestrel. Choose an appropriate oral contraceptive. ( 7 ) Drugs metabolized by CYP1A2: Monitor patients because teriflunomide may decrease exposure of these drugs. ( 7 ) Warfarin: Monitor INR as teriflunomide may decrease INR. ( 7 ) Drugs metabolized by BCRP and OATP1B1/B3 transporters: Monitor patients because teriflunomide may increase exposure of these drugs. ( 7 ) Rosuvastatin: The dose of rosuvastatin should not exceed 10 mg once daily in patients taking teriflunomide. ( 7 ) Effect of Teriflunomide on CYP2C8 Substrates Teriflunomide is an inhibitor of CYP2C8 in vivo . In patients taking teriflunomide, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide, rosiglitazone) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP2C8 as required [see Clinical Pharmacology (12.3) ] . Effect of Teriflunomide on Warfarin Coadministration of teriflunomide with warfarin requires close monitoring of the international normalized ratio (INR) because teriflunomide may decrease peak INR by approximately 25%. Effect of Teriflunomide on Oral Contraceptives Teriflunomide may increase the systemic exposures of ethinylestradiol and levonorgestrel. Consideration should be given to the type or dose of contraceptives used in combination with teriflunomide [see Clinical Pharmacology (12.3) ] . Effect of Teriflunomide on CYP1A2 Substrates Teriflunomide may be a weak inducer of CYP1A2 in vivo . In patients taking teriflunomide, exposure of drugs metabolized by CYP1A2 (e.g., alosetron, duloxetine, theophylline, tizanidine) may be reduced. Monitor these patients and adjust the dose of the concomitant drug(s) metabolized by CYP1A2 as required [see Clinical Pharmacology (12.3) ] . Effect of Teriflunomide on Organic Anion Transporter 3 (OAT3) Substrates Teriflunomide inhibits the activity of OAT3 in vivo . In patients taking teriflunomide, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. Monitor these patients and adjust the dose of the concomitant drug(s) which are OAT3 substrates as required [see Clinical Pharmacology (12.3) ] . Effect of Teriflunomide on BCRP and Organic Anion Transporting Polypeptide B1 and B3 (OATP1B1/1B3) Substrates Teriflunomide inhibits the activity of BCRP and OATP1B1/1B3 in vivo . For a patient taking teriflunomide, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking teriflunomide [see Clinical Pharmacology (12.3) ] ."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Teriflunomide tablet is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Teriflunomide is a pyrimidine synthesis inhibitor indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Elimination of teriflunomide can be accelerated by administration of cholestyramine or activated charcoal for 11 days. ( 5.3 ) Teriflunomide may decrease WBC. A recent CBC should be available before starting teriflunomide. Monitor for signs and symptoms of infection. Consider suspending treatment with teriflunomide in case of serious infection. Do not start teriflunomide in patients with active infections. ( 5.4 ) Stop teriflunomide if patient has anaphylaxis, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms; initiate rapid elimination. ( 5.3 , 5.5 , 5.6 , 5.7 ) If patient develops symptoms consistent with peripheral neuropathy, evaluate patient and consider discontinuing teriflunomide. ( 5.8 ) Teriflunomide may increase blood pressure. Measure blood pressure at treatment initiation and monitor blood pressure during treatment. ( 5.9 ) 5.1 Hepatotoxicity Clinically significant and potentially life-threatening liver injury, including acute liver failure requiring transplant, has been reported in patients treated with teriflunomide in the postmarketing setting. Patients with pre-existing liver disease and patients taking other hepatotoxic drugs may be at increased risk for developing liver injury when taking teriflunomide. Clinically significant liver injury can occur at any time during treatment with teriflunomide. Patients with pre-existing acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) greater than two times the upper limit of normal (ULN) before initiating treatment, should not normally be treated with teriflunomide. Teriflunomide is contraindicated in patients with severe hepatic impairment [see Contraindications (4) ] . In placebo-controlled trials in adult patients, ALT greater than three times the ULN occurred in 61/1045 (5.8%) and 62/1002 (6.2%) of patients receiving teriflunomide 7 mg and 14 mg, respectively, and 38/997 (3.8%) of patients receiving placebo, during the treatment period. These elevations occurred mostly within the first year of treatment. Half of the cases returned to normal without drug discontinuation. In clinical trials, if ALT elevation was greater than three times the ULN on two consecutive tests, teriflunomide was discontinued and patients underwent an accelerated elimination procedure [see Warnings and Precautions (5.3) ] . Of the patients who underwent discontinuation and accelerated elimination in controlled trials, half returned to normal or near normal values within 2 months. One patient in the controlled trials in adult patients developed ALT 32 times the ULN and jaundice 5 months after initiation of teriflunomide 14 mg treatment. The patient was hospitalized for 5 weeks and recovered after plasmapheresis and cholestyramine accelerated elimination procedure. Teriflunomide-induced liver injury in this patient could not be ruled out. Obtain serum transaminase and bilirubin levels within 6 months before initiation of teriflunomide therapy. Monitor ALT levels at least monthly for six months after starting teriflunomide. Consider additional monitoring when teriflunomide is given with other potentially hepatotoxic drugs. Consider discontinuing teriflunomide if serum transaminase increase (greater than three times the ULN) is confirmed. Monitor serum transaminase and bilirubin on teriflunomide therapy, particularly in patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine. If liver injury is suspected to be teriflunomide-induced, discontinue teriflunomide and start an accelerated elimination procedure [see Warnings and Precautions (5.3) ] and monitor liver tests weekly until normalized. If teriflunomide-induced liver injury is unlikely because some other probable cause has been found, resumption of teriflunomide therapy may be considered. 5.2 Embryofetal Toxicity Teriflunomide may cause fetal harm when administered to a pregnant woman. Teratogenicity and embryofetal lethality occurred in animal reproduction studies in multiple animal species at plasma teriflunomide exposures similar to or lower than that in humans at the maximum recommended human dose (MRHD) of 14 mg/day [see Use in Specific Populations (8.1) ]. Teriflunomide is contraindicated for use in pregnant women and in females of reproductive potential not using effective contraception [ see Contraindications (4) ]. Exclude pregnancy before starting treatment with teriflunomide in females of reproductive potential [ see Dosage and Administration (2) ]. Advise females of reproductive potential to use effective contraception during teriflunomide treatment and during an accelerated drug elimination procedure after teriflunomide treatment [ see Use in Specific Populations (8.3) ]. If a woman becomes pregnant while taking teriflunomide, stop treatment with teriflunomide, apprise the patient of the potential risk to a fetus, and perform an accelerated drug elimination procedure to achieve a plasma teriflunomide concentration of less than 0.02 mg/L [ see Warnings and Precautions (5.3) ]. Upon discontinuing teriflunomide, it is recommended that all females of reproductive potential undergo an accelerated drug elimination procedure. Women receiving teriflunomide treatment who wish to become pregnant must discontinue teriflunomide and undergo an accelerated drug elimination procedure, which includes verification that plasma concentrations of teriflunomide are less than 0.02 mg/L (0.02 mcg/mL). Men wishing to father a child should also discontinue use of teriflunomide and either undergo an accelerated elimination procedure or wait until verification that the plasma teriflunomide concentration is less than 0.02 mg/L (0.02 mcg/mL) [ see Use in Specific Populations (8.3) ]. Based on animal data, human plasma concentrations of teriflunomide of less than 0.02 mg/L (0.02 mcg/mL) are expected to have minimal embryofetal risk [ see Contraindications (4) , Warnings and Precautions (5.3) , and Use in Specific Populations (8.1) ]. 5.3 Procedure for Accelerated Elimination of Teriflunomide Teriflunomide is eliminated slowly from the plasma [see Clinical Pharmacology (12.3) ]. Without an accelerated elimination procedure, it takes on average 8 months to reach plasma concentrations less than 0.02 mg/L, although because of individual variations in drug clearance it may take as long as 2 years. An accelerated elimination procedure could be used at any time after discontinuation of teriflunomide. Elimination can be accelerated by either of the following procedures: Administration of cholestyramine 8 g every 8 hours for 11 days. If cholestyramine 8 g three times a day is not well tolerated, cholestyramine 4 g three times a day can be used. Administration of 50 g oral activated charcoal powder every 12 hours for 11 days. If either elimination procedure is poorly tolerated, treatment days do not need to be consecutive unless there is a need to lower teriflunomide plasma concentration rapidly. At the end of 11 days, both regimens successfully accelerated teriflunomide elimination, leading to more than 98% decrease in teriflunomide plasma concentrations. Use of the accelerated elimination procedure may potentially result in return of disease activity if the patient had been responding to teriflunomide treatment. 5.4 Bone Marrow Effects/Immunosuppression Potential/Infections Bone Marrow Effects A mean decrease compared to baseline in white blood cell (WBC) count of approximately 15% (mainly neutrophils and lymphocytes) and in platelet count of approximately 10% was observed in placebo-controlled trials in adult patients with 7 mg and 14 mg of teriflunomide. The decrease in mean WBC count occurred during the first 6 weeks and WBC count remained low during treatment. In placebo-controlled studies in adult patients, neutrophil count < 1.5x10 9 /L was observed in 12% and 16% of patients receiving teriflunomide 7 mg and 14 mg, respectively, compared with 7% of patients receiving placebo; lymphocyte count <0.8x10 9 /L was observed in 10% and 12% of patients receiving teriflunomide 7 mg and 14 mg, respectively, compared with 6% of patients receiving placebo. No cases of serious pancytopenia were reported in premarketing clinical trials of teriflunomide but rare cases of pancytopenia and agranulocytosis have been reported in the postmarketing setting with leflunomide. A similar risk would be expected for teriflunomide [see Clinical Pharmacology (12.3) ] . Cases of thrombocytopenia with teriflunomide, including rare cases with platelet counts less than 50,000/mm 3 , have been reported in post-marketing setting. Obtain a complete blood cell count (CBC) within 6 months before the initiation of treatment with teriflunomide. Further monitoring should be based on signs and symptoms suggestive of bone marrow suppression. Risk of Infection / Tuberculosis Screening Patients with active acute or chronic infections should not start treatment until the infection(s) is resolved. If a patient develops a serious infection consider suspending treatment with teriflunomide and using an accelerated elimination procedure. Reassess the benefits and risks prior to resumption of therapy. Instruct patients receiving teriflunomide to report symptoms of infections to a physician. Teriflunomide is not recommended for patients with severe immunodeficiency, bone marrow disease, or severe, uncontrolled infections. Medications like teriflunomide that have immunosuppression potential may cause patients to be more susceptible to infections, including opportunistic infections. In placebo-controlled studies of teriflunomide in adult patients, no overall increase in the risk of serious infections was observed with teriflunomide 7 mg (2.2%) or 14 mg (2.7%) compared to placebo (2.2%). However, one fatal case of klebsiella pneumonia sepsis occurred in a patient taking teriflunomide 14 mg for 1.7 years. Fatal infections have been reported in the postmarketing setting in patients receiving leflunomide, especially Pneumocystis jirovecii pneumonia and aspergillosis. Most of the reports were confounded by concomitant immunosuppressant therapy and/or comorbid illness which, in addition to rheumatoid disease, may predispose patients to infection. In clinical studies with teriflunomide, cytomegalovirus hepatitis reactivation has been observed. In clinical studies with teriflunomide in adult patients, cases of tuberculosis have been observed. Prior to initiating teriflunomide, screen patients for latent tuberculosis infection with a tuberculin skin test or with a blood test for mycobacterium tuberculosis infection. Teriflunomide has not been studied in patients with a positive tuberculosis screen, and the safety of teriflunomide in individuals with latent tuberculosis infection is unknown. For patients testing positive in tuberculosis screening, treat by standard medical practice prior to therapy with teriflunomide. Vaccination No clinical data are available on the efficacy and safety of live vaccinations in patients taking teriflunomide. Vaccination with live vaccines is not recommended. The long half-life of teriflunomide should be considered when contemplating administration of a live vaccine after stopping teriflunomide. Malignancy The risk of malignancy, particularly lymphoproliferative disorders, is increased with the use of some immunosuppressive medications. There is a potential for immunosuppression with teriflunomide. No apparent increase in the incidence of malignancies and lymphoproliferative disorders was reported in the teriflunomide clinical trials, but larger and longer-term studies would be needed to determine whether there is an increased risk of malignancy or lymphoproliferative disorders with teriflunomide. 5.5 Hypersensitivity Reactions Teriflunomide can cause anaphylaxis and severe allergic reactions [ see Contraindications (4) ]. Signs and symptoms have included dyspnea, urticaria, and angioedema including lips, eyes, throat, and tongue. Inform patients of the signs and symptoms of anaphylaxis and angioedema. 5.6 Serious Skin Reactions Cases of serious skin reactions, sometimes fatal, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) [ see Warnings and Precautions (5.7) ], have been reported with teriflunomide. Fatal outcomes were reported in one case of TEN and one case of DRESS . Inform patients of the signs and symptoms that may signal a serious skin reaction. Instruct patients to discontinue teriflunomide and seek immediate medical care should these signs and symptoms occur. Unless the reaction is clearly not drug related, discontinue teriflunomide and begin an accelerated elimination procedure immediately [ see Warnings and Precautions (5.3) ]. In such cases, patients should not be re-exposed to teriflunomide [ see Contraindications (4) ]. 5.7 Drug Reaction with Eosinophilia and Systemic Symptoms Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity, has occurred with teriflunomide. One fatal case of DRESS that occurred in close temporal association (34 days) with the initiation of teriflunomide treatment has been reported in the postmarketing setting. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Discontinue teriflunomide, unless an alternative etiology for the signs or symptoms is established, and begin an accelerated elimination procedure immediately [ see Warnings and Precautions (5.3) ]. In such cases, patients should not be re-exposed to teriflunomide [ see Contraindications (4) ]. 5.8 Peripheral Neuropathy In placebo-controlled studies in adult patients, peripheral neuropathy, including both polyneuropathy and mononeuropathy (e.g., carpal tunnel syndrome), occurred more frequently in patients taking teriflunomide than in patients taking placebo. The incidence of peripheral neuropathy confirmed by nerve conduction studies was 1.4% (13 patients) and 1.9% (17 patients) of patients receiving 7 mg and 14 mg of teriflunomide, respectively, compared with 0.4% receiving placebo (4 patients). Treatment was discontinued in 0.7% (8 patients) with confirmed peripheral neuropathy (3 patients receiving teriflunomide 7 mg and 5 patients receiving teriflunomide 14 mg). Five of them recovered following treatment discontinuation. Not all cases of peripheral neuropathy resolved with continued treatment. Peripheral neuropathy also occurred in patients receiving leflunomide. Age older than 60 years, concomitant neurotoxic medications, and diabetes may increase the risk for peripheral neuropathy. If a patient taking teriflunomide develops symptoms consistent with peripheral neuropathy, such as bilateral numbness or tingling of hands or feet, consider discontinuing teriflunomide therapy and performing an accelerated elimination procedure [ see Warnings and Precautions (5.3) ]. 5.9 Increased Blood Pressure In placebo-controlled studies in adult patients, the mean change from baseline to the end of study in systolic blood pressure was +2.3 mmHg and +2.7 mmHg for teriflunomide 7 mg and 14 mg, respectively, and -0.6 mmHg for placebo. The change from baseline in diastolic blood pressure was +1.4 mmHg and +1.9 mmHg for teriflunomide 7 mg and 14 mg, respectively, and -0.3 mmHg for placebo. Hypertension was an adverse reaction in 3.1% and 4.3% of patients treated with 7 mg or 14 mg of teriflunomide compared with 1.8% for placebo. Check blood pressure before start of teriflunomide treatment and periodically thereafter. Elevated blood pressure should be appropriately managed during treatment with teriflunomide. 5.10 Respiratory Effects Interstitial lung disease, including acute interstitial pneumonitis, has been reported with teriflunomide in the postmarketing setting. Interstitial lung disease and worsening of pre-existing interstitial lung disease have been reported during treatment with leflunomide. Interstitial lung disease may be fatal and may occur acutely at any time during therapy with a variable clinical presentation. New onset or worsening pulmonary symptoms, such as cough and dyspnea, with or without associated fever, may be a reason for discontinuation of therapy and for further investigation as appropriate. If discontinuation of the drug is necessary, consider initiation of an accelerated elimination procedure [see Warnings and Precautions (5.3) ]. 5.11 Pancreatitis in Pediatric Patients Teriflunomide is not approved for use in pediatric patients. In the pediatric clinical trial, cases of pancreatitis were observed in 1.8% (2/109) of patients receiving teriflunomide; one of these cases was serious [ see Use in Specific Populations (8.4) ]. If pancreatitis is suspected, discontinue teriflunomide and start an accelerated elimination procedure [ see Warnings and Precautions (5.3) ]. 5.12 Concomitant Use with Immunosuppressive or Immunomodulating Therapies Coadministration with antineoplastic or immunosuppressive therapies used for treatment of multiple sclerosis has not been evaluated. Safety studies in which teriflunomide was concomitantly administered with other immune modulating therapies for up to one year (interferon beta, glatiramer acetate) did not reveal any specific safety concerns. The long term safety of these combinations in the treatment of multiple sclerosis has not been established. In any situation in which the decision is made to switch from teriflunomide to another agent with a known potential for hematologic suppression, it would be prudent to monitor for hematologic toxicity, because there will be overlap of systemic exposure to both compounds. Use of an accelerated elimination procedure may decrease this risk, but may also potentially result in return of disease activity if the patient had been responding to teriflunomide treatment [ see Warnings and Precautions (5.3) ].","5.12 Concomitant Use with Immunosuppressive or Immunomodulating Therapies Coadministration with antineoplastic or immunosuppressive therapies used for treatment of multiple sclerosis has not been evaluated. Safety studies in which teriflunomide was concomitantly administered with other immune modulating therapies for up to one year (interferon beta, glatiramer acetate) did not reveal any specific safety concerns. The long term safety of these combinations in the treatment of multiple sclerosis has not been established. In any situation in which the decision is made to switch from teriflunomide to another agent with a known potential for hematologic suppression, it would be prudent to monitor for hematologic toxicity, because there will be overlap of systemic exposure to both compounds. Use of an accelerated elimination procedure may decrease this risk, but may also potentially result in return of disease activity if the patient had been responding to teriflunomide treatment [ see Warnings and Precautions (5.3) ]."}', 'overdosage': '{"10 OVERDOSAGE There is no experience regarding teriflunomide overdose or intoxication in humans. Teriflunomide 70 mg daily up to 14 days was well tolerated by healthy subjects. In the event of clinically significant overdose or toxicity, cholestyramine or activated charcoal is recommended to accelerate elimination [see Warnings and Precautions (5.3) ] ."}', 'active_flag': 'Y', 'generic_name': '{TERIFLUNOMIDE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). A Medication Guide is required for distribution with teriflunomide tablets. Hepatotoxicity Inform patients that teriflunomide may cause liver injury, which can be life-threatening, and that their liver enzymes will be checked before starting teriflunomide and at least monthly for 6 months after starting teriflunomide [ see Dosage and Administration (2) and Warnings and Precautions (5.1) ]. Advise patients that they should contact their physician if they have any unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine. Embryofetal Toxicity Advise females of reproductive potential of the potential for fetal harm if teriflunomide is taken during pregnancy to notify their healthcare provider immediately if a pregnancy occurs or is suspected to use effective contraception during treatment with teriflunomide and until the teriflunomide plasma concentration is verified to be less than 0.02 mg/L [ see Warnings and Precautions (5.2 , 5.3 ), Use in Specific Populations (8.1 , 8.3 ), Clinical Pharmacology (12.3) ] Instruct men taking teriflunomide and not wishing to father a child to use effective contraception to minimize any possible risk to the fetus; their female partners should also use effective contraception. Advise men wishing to father a child to discontinue use of teriflunomide and undergo an accelerated elimination procedure. Availability of an Accelerated Elimination Procedure Advise patients that teriflunomide may stay in the blood for up to 2 years after the last dose and that an accelerated elimination procedure may be used if needed [ see Warnings and Precautions (5.3) ]. Risk of Infections Inform patients that they may develop a lowering of their white blood cell counts and that their blood counts will be checked before starting teriflunomide. Inform patients that they may be more likely to get infections when taking teriflunomide and that they should contact their physician if they develop symptoms of infection, particularly in case of fever [ see Warnings and Precautions (5.4) ]. Advise patients that the use of some vaccines should be avoided during treatment with teriflunomide and for at least 6 months after discontinuation. Hypersensitivity Reactions Advise patients to discontinue teriflunomide and seek immediate medical attention if any signs or symptoms of a hypersensitivity reaction occur [ see Contraindications (4) and Warnings and Precautions (5.5) ]. Signs and symptoms can include dyspnea, urticaria, angioedema involving the lips, eyes, throat, or tongue, or skin rash. Serious Skin Reactions Advise patients to discontinue teriflunomide and seek immediate medical attention if any signs of a serious skin reaction, such as SJS or TEN, occur [ see Warnings and Precautions (5.6) ]. Signs and symptoms can include rash, mouth sores, blisters, or peeling skin. DRESS/Multi-organ Hypersensitivity Instruct patients and caregivers that a fever or rash associated with signs of other organ system involvement (e.g., lymphadenopathy, hepatic dysfunction) may be drug-related and should be reported to their healthcare provider immediately. Teriflunomide should be discontinued immediately if a serious hypersensitivity reaction is suspected [ see Warnings and Precautions (5.7) ]. Peripheral Neuropathy Inform patients that they may develop peripheral neuropathy. Advise patients that they should contact their physician if they develop symptoms of peripheral neuropathy, such as numbness or tingling of hands or feet [ see Warnings and Precautions (5.8) ]. Increased Blood Pressure Inform patients that teriflunomide may increase blood pressure [ see Warnings and Precautions (5.9) ]. Lactation Advise females not to breastfeed during treatment with teriflunomide [ see Use in Specific Populations (8.2) ]. Manufactured by: Biocon Pharma Limited Bengaluru, India - 560099 Manufactured for: Biocon Pharma Inc., Iselin, New Jersey, 08830-3009 United States of America Revised: 01/2023"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Teriflunomide is contraindicated for use in pregnant women and females of reproductive potential not using effective contraception because of the potential for fetal harm based on animal data.[ see Contraindications (4) and Warnings and Precautions (5.2) ]. In animal reproduction studies in rat and rabbit, oral administration of teriflunomide during organogenesis caused teratogenicity and embryolethality at plasma exposures (AUC) lower than that at the maximum recommended human dose (MRHD) of 14 mg/day [see Data ] . Available human data from pregnancy registries, clinical trials, pharmacovigilance cases, and published literature are too limited to draw any conclusions, but they do not clearly indicate increased birth defects or miscarriage associated with inadvertent teriflunomide exposure in the early first trimester when followed by an accelerated elimination procedure [see Clinical Considerations and Data] . There are no human data pertaining to exposures later in the first trimester or beyond. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage in the indicated population is unknown. Clinical Considerations Fetal/Neonatal adverse reactions Lowering the plasma concentration of teriflunomide by instituting an accelerated drug elimination procedure as soon as pregnancy is detected may decrease the risk to the fetus from teriflunomide. The accelerated drug elimination procedure includes verification that the plasma teriflunomide concentration is less than 0.02 mg/L [ see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3) ]. Data Human data Available human data are limited. Prospectively reported data (from clinical trials and postmarketing reports) from >150 pregnancies in patients treated with teriflunomide and >300 pregnancies in patients treated with leflunomide have not demonstrated an increased rate of congenital malformations or miscarriage following teriflunomide exposure in the early first trimester when followed by an accelerated elimination procedure. Specific patterns of major congenital malformations in humans have not been observed. Limitations of these data include an inadequate number of reported pregnancies from which to draw conclusions, the short duration of drug exposure in reported pregnancies, which precludes a full evaluation of the fetal risks, incomplete reporting, and the inability to control for confounders (such as underlying maternal disease and use of concomitant medications). Animal data When teriflunomide (oral doses of 1, 3, or 10 mg/kg/day) was administered to pregnant rats throughout the period of organogenesis, high incidences of fetal malformation (primarily craniofacial, and axial and appendicular skeletal defects) and fetal death were observed at doses not associated with maternal toxicity. Adverse effects on fetal development were observed following dosing at various stages throughout organogenesis. Maternal plasma exposure at the no-effect level (1.0 mg/kg/day) for fetal developmental toxicity in rats was less than that in humans at the maximum recommended human dose (MRHD, 14 mg/day). Administration of teriflunomide (oral doses of 1, 3.5, or 12 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in high incidences of fetal malformation (primarily craniofacial, and axial and appendicular skeletal defects) and fetal death at doses associated with minimal maternal toxicity. Maternal plasma exposure at the no-effect dose (1.0 mg/kg/day) for fetal developmental toxicity in rabbits was less than that in humans at the MRHD. In studies in which teriflunomide (oral doses of 0.05, 0.1, 0.3, 0.6, or 1.0 mg/kg/day) was administered to rats during gestation and lactation, decreased growth, eye and skin abnormalities, and high incidences of malformation (limb defects) and postnatal death were observed in the offspring at doses not associated with maternal toxicity. Maternal plasma exposure at the no-effect dose for prenatal and postnatal developmental toxicity in rats (0.10 mg/kg/day) was less than that in humans at the MRHD. In animal reproduction studies of leflunomide, embryolethality and teratogenic effects were observed in pregnant rat and rabbit at or below clinically relevant plasma teriflunomide exposures (AUC). In published reproduction studies in pregnant mice, leflunomide was embryolethal and increased the incidence of malformations (craniofacial, axial skeletal, heart and great vessel). Supplementation with exogenous uridine reduced the teratogenic effects in pregnant mice, suggesting that the mode of action (inhibition of mitochondrial enzyme dihydroorotate dehydrogenase) is the same for therapeutic efficacy and developmental toxicity. At recommended doses in humans, teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide."}', 'pediatric_use': '{"8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. Effectiveness of teriflunomide for the treatment of relapsing form of multiple sclerosis in pediatric patients (10 to 17 years of age) was not established in an adequate and well-controlled clinical study in 166 patients (109 patients received once daily doses of teriflunomide and 57 patients received placebo) for up to 96 weeks. Pancreatitis has been reported in adults in the postmarketing setting, but appears to occur at higher frequency in the pediatric population. In this pediatric study, cases of pancreatitis were reported in 1.8% (2/109) of patients who received teriflunomide compared to no patients in the placebo group. All patients in the pediatric trial recovered or were recovering after treatment discontinuation and accelerated elimination procedure [ see Warnings and Precautions (5.11) ]. Additionally, elevated or abnormal blood creatine phosphokinase was reported in 6.4% of pediatric patients who received teriflunomide compared to no patients in the placebo group. Juvenile Animal Toxicity Data Oral administration of teriflunomide (0, 0.3, 3, or 6 mg/kg/day) to young rats on postnatal days 21 to 70 resulted in suppression of immune function (T-cell dependent antibody response) at the mid and high doses, and adverse effects on male reproductive organs (reduced sperm count) and altered neurobehavioral function (increased locomotor activity) at the high dose. At the no-effect dose (0.3 mg/kg/day) for developmental toxicity in juvenile rats, plasma exposures were less than those in pediatric patients at the doses of teriflunomide tested in the clinical study."}', 'geriatric_use': '{"8.5 Geriatric Use Clinical studies of teriflunomide did not include patients over 65 years old."}'}

{ACETAMINOPHEN,ASPIRIN,CAFFEINE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses temporarily relieves minor aches and pains due to: headache a cold arthritis muscular aches toothache premenstrual and menstrual cramps"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"ACETAMINOPHEN, ASPIRIN, CAFFEINE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask doctor if an allergic reaction occurs. Seek medical help right away. any new symptoms appear you experience any of the following signs of stomach bleeding feel faint vomit blood have bloody or black stools have stomach pain that does not get better ringing in the ears or loss of hearing occurs pain gets worse or lasts for more than 10 days fever gets worse or lasts for more than 3 days painful area is red or swollen These could be signs of a serious condition."}', 'do_not_use': '{"Do not use if you have ever had an allergic reaction to acetaminophen, aspirin or any other pain reliever/fever reducer with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist."}', 'when_using': None, 'warnings': '{"Warnings Reye\'s syndrome: Children and teenagers who have or are recovering from chicken pox or flu-like symptoms should not use this product. When using this product, if changes in behavior with nausea and vomiting occur, consult a doctor because these symptoms could be an early sign of Reye’s syndrome, a rare but serious illness Allergy alert : Acetaminophen may cause severe skin reactions. Symptoms may include: skin reddening blisters rash If a skin reaction occurs, stop use and seek medical help right away. Allergy alert : Aspirin may cause a severe allergic reaction, which may include: hives facial swelling shock asthma (wheezing) Liver warning : This product contains acetaminophen. Severe liver damage may occur if you take: more than 4,000 mg of acetaminophen in 24 hours with other drugs containing acetaminophen 3 or more alcoholic drinks every day while using this product Stomach bleeding warning : This product contains an NSAID, which may cause severe stomach bleeding. The chance is higher if you: are age 60 or older have had stomach ulcers or bleeding problems take a blood thinning (anticoagulant) or steroid drug take other drugs containing prescription or nonprescription NSAIDs (aspirin, ibuprofen, naproxen, or others) have 3 or more alcoholic drinks every day while using this product take more or for a longer time than directed Caffeine warning : The recommended dose of this product contains about as much caffeine as a cup of coffee. Limit the use of caffeine-containing medications, foods, or beverages while taking this product because too much caffeine may cause nervousness, irritability, sleeplessness, and, occasionally, rapid heartbeat. Do not use if you have ever had an allergic reaction to acetaminophen, aspirin or any other pain reliever/fever reducer with any other drug containing acetaminophen (prescription or nonprescription). If you are not sure whether a drug contains acetaminophen, ask a doctor or pharmacist. Ask a doctor before use if you have liver disease stomach bleeding warning applies to you you have a history of stomach problems, such as heartburn you have high blood pressure, heart disease, liver cirrhosis, or kidney disease you have asthma you are taking a diuretic Ask a doctor or pharmacist before use if you are taking a prescription drug for diabetes, gout, or arthritis taking any other drug or are under a doctor’s care for any serious condition Stop use and ask doctor if an allergic reaction occurs. Seek medical help right away. any new symptoms appear you experience any of the following signs of stomach bleeding feel faint vomit blood have bloody or black stools have stomach pain that does not get better ringing in the ears or loss of hearing occurs pain gets worse or lasts for more than 10 days fever gets worse or lasts for more than 3 days painful area is red or swollen These could be signs of a serious condition. If pregnant or breast-feeding, ask a health professional before use. It is especially important not to use aspirin during the last 3 months of pregnancy unless definitely directed to do so by a doctor because it may cause problems in the unborn child or complications during delivery. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center (1-800-222-1222) right away. Quick medical attention is critical for adults as well as for children even if you do not notice any signs or symptoms."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"OSELTAMIVIR PHOSPHATE"}

{'contraindications': '{"4 CONTRAINDICATIONS Oseltamivir phosphate capsules are contraindicated in patients with known serious hypersensitivity to oseltamivir or any component of the product. Severe allergic reactions have included anaphylaxis and serious skin reactions including toxic epidermal necrolysis, Stevens-Johnson Syndrome, and erythema multiforme [see Warnings and Precautions ( 5.1 )] . Patients with known serious hypersensitivity to oseltamivir or any of the components of oseltamivir phosphate capsules ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are discussed below and elsewhere in the labeling: • Serious skin and hypersensitivity reactions [ see Warnings and Precautions ( 5.1 ) ] • Neuropsychiatric events [ see Warnings and Precautions ( 5.2 ) ] Most common adverse reactions (>1% and more common than with placebo): • Treatment studies – Nausea, vomiting, headache. ( 6.1 ) • Prophylaxis studies – Nausea, vomiting, headache, pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Macleods Pharma USA, Inc. at 1-888-943-3210 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions from Treatment and Prophylaxis Trials in Adult and Adolescent Subjects (13 years of age and older) The overall safety profile of oseltamivir phosphate is based on data from 2,646 adult and adolescent subjects that received the recommended dosage of 75 mg orally twice daily for 5 days for treatment of influenza and 1,943 adult and adolescent subjects that received the recommended dosage of 75 mg orally once daily for up to 6 weeks for prophylaxis of influenza in clinical trials. The most common adverse reactions in the pooled treatment and pooled prophylaxis trials in adults and adolescents are displayed in Table 5. The majority of these adverse reactions were reported on a single occasion, occurred on either the first or second treatment day and resolved spontaneously within 1-2 days. This summary includes otherwise healthy adults/adolescents and subjects “at risk” (subjects at higher risk of developing complications associated with influenza, e.g., elderly patients and patients with chronic cardiac or respiratory disease). In general, the safety profile in the subjects “at risk” was qualitatively similar to that in otherwise healthy adults/adolescents. Table 5 Adverse Reactions Occurring in ≥1% of Adults and Adolescents (13 years of age and older) in Treatment and Prophylaxis Trials* System Organ Class Adverse Reaction Treatment Trials Prophylaxis Trials Oseltamivir phosphate 75 mg twice daily (n = 2646) Placebo (n = 1977) Oseltamivir phosphate 75 mg once daily (n = 1943) Placebo (n = 1586) Gastrointestinal Disorders Nausea 10% 6% 8% 4% Vomiting 8% 3% 2% 1% Nervous System Disorders Headache General Disorders Pain 2% <1% 1% <1% 17% 4% 16% 3% * Adverse reactions that occurred in ≥1% of oseltamivir phosphate-treated adults and adolescents and ≥1% greater in oseltamivir phosphate-treated subjects compared to placebo-treated subjects in either the treatment or prophylaxis trials. Adverse Reactions from Treatment and Prophylaxis Trials in Pediatric Subjects (1 year to 12 years of age) A total of 1,481 pediatric subjects (including otherwise healthy pediatric subjects aged 1 year to 12 years and asthmatic pediatric subjects aged 6 to 12 years) participated in clinical trials of oseltamivir phosphate for the treatment of influenza. A total of 859 pediatric subjects received treatment with oseltamivir phosphate for oral suspension either at a 2 mg per kg twice daily for 5 days or weight-band dosing. Vomiting was the only adverse reaction reported at a frequency of >1% in subjects receiving oseltamivir phosphate (16%) compared to placebo (8%). Amongst the 148 pediatric subjects aged 1 year to 12 years who received oseltamivir phosphate at doses of 30 to 60 mg once daily for 10 days in a post-exposure prophylaxis study in household contacts (n = 99), and in a separate 6– week seasonal influenza prophylaxis safety study (n = 49), vomiting was the most frequent adverse reaction (8% on oseltamivir phosphate versus 2% in the no prophylaxis group). Adverse Reactions from Treatment Trials in Pediatric Subjects (2 weeks to less than 1 year of age ) Assessment of adverse reactions in pediatric subjects 2 weeks to less than 1 year of age was based on two open-label studies that included safety data on 135 influenza-infected subjects 2 weeks to less than 1 year of age (including premature infants at least 36 weeks post conceptional age) exposed to oseltamivir phosphate at doses ranging from 2 to 3.5 mg per kg of the formulation for oral suspension twice daily orally for 5 days. The safety profile of oseltamivir phosphate was similar across the age range studied, with vomiting (9%), diarrhea (7%) and diaper rash (7%) being the most frequently reported adverse reactions, and was generally comparable to that observed in older pediatric and adult subjects. Adverse Reactions from the Prophylaxis Trial in Immunocompromised Subjects In a 12-week seasonal prophylaxis study in 475 immunocompromised subjects, including 18 pediatric subjects 1 year to 12 years of age, the safety profile in the 238 subjects receiving oseltamivir phosphate 75 mg once daily was consistent with that previously observed in other oseltamivir phosphate prophylaxis clinical trials [ see Clinical Studies ( 14.2 ) ]. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of oseltamivir phosphate. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to oseltamivir phosphate exposure. General disorders and administration site conditions: Swelling of the face or tongue, allergy, anaphylactic/anaphylactoid reactions, hypothermia Skin and subcutaneous tissue disorders: Rash, dermatitis, urticaria, eczema, toxic epidermal necrolysis, Stevens-Johnson Syndrome, erythema multiforme [see Warnings and Precautions ( 5.1 )] Gastrointestinal Disorders: Gastrointestinal bleeding, hemorrhagic colitis Cardiac Disorders: Arrhythmia Hepatobiliary Disorders: Hepatitis, abnormal liver function tests Nervous System Disorders: Seizure Metabolism and Nutrition Disorders: Aggravation of diabetes Psychiatric Disorders: Abnormal behavior, delirium, including symptoms such as hallucinations, agitation, anxiety, altered level of consciousness, confusion, nightmares, delusions [see Warnings and Precautions ( 5.2 )]"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Live attenuated influenza vaccine (LAIV), intranasal: Avoid administration of LAIV within 2 weeks before or 48 hours after oseltamivir phosphate capsules use, unless medically indicated. ( 7 ) 7.1 Influenza Vaccines Live Attenuated Influenza Vaccine The concurrent use of oseltamivir phosphate capsules with live attenuated influenza vaccine (LAIV) intranasal has not been evaluated. However, because of the potential for oseltamivir phosphate capsules to inhibit replication of live vaccine virus and possibly reduce the efficacy of LAIV, avoid administration of LAIV within 2 weeks before or 48 hours after oseltamivir phosphate capsules administration, unless medically indicated. Inactivated Influenza Vaccine Inactivated influenza vaccine can be administered at any time relative to use of oseltamivir phosphate capsules. 7.2 Drugs Without Clinically Significant Drug Interaction with Oseltamivir Phosphate Capsules No dose adjustments are needed for either oseltamivir or the concomitant drug when coadministering oseltamivir with amoxicillin, acetaminophen, aspirin, cimetidine, antacids (magnesium and aluminum hydroxides and calcium carbonates), rimantadine, amantadine, or warfarin [see Clinical Pharmacology ( 12.3 )] ."}', 'indications_and_usage': '{"1 INDICATIONS & USAGE Oseltamivir phosphate capsules USP, is an influenza neuraminidase inhibitor (NAI) indicated for: • Treatment of acute, uncomplicated influenza A and B in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours. ( 1.1 ) • Prophylaxis of influenza A and B in patients 1 year and older. ( 1.2 ) Limitations of Use: • Not a substitute for annual influenza vaccination. ( 1.3 ) • Consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use. ( 1.3 ) • Not recommended for patients with end-stage renal disease not undergoing dialysis. ( 1.3 ) 1.1 Treatment of Influenza Oseltamivir phosphate capsule is indicated for the treatment of acute, uncomplicated illness due to influenza A and B infection in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours. 1.2 Prophylaxis of Influenza Oseltamivir phosphate capsule is indicated for the prophylaxis of influenza A and B in patients 1 year and older. 1.3 Limitations of Use • Oseltamivir phosphate capsule is not a substitute for early influenza vaccination on an annual basis as recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices. • Influenza viruses change over time. Emergence of resistance substitutions could decrease drug effectiveness. Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use Oseltamivir phosphate capsules [ see Microbiology ( 12.4 ) ]. • Oseltamivir phosphate capsule is not recommended for patients with end-stage renal disease not undergoing dialysis [ see Dosage and Administration ( 2.4 ) and Use in Specific Populations ( 8.6 ) ]."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Serious skin/hypersensitivity reactions such as Stevens-Johnson Syndrome, toxic epidermal necrolysis and erythema multiforme: Discontinue oseltamivir phosphate capsules and initiate appropriate treatment if allergic-like reactions occur or are suspected. ( 5.1 ) • Neuropsychiatric events: Patients with influenza, including those receiving oseltamivir phosphate capsules, particularly pediatric patients, may be at an increased risk of confusion or abnormal behavior early in their illness. Monitor for signs of abnormal behavior. ( 5.2 ) 5.1 Serious Skin/Hypersensitivity Reactions Cases of anaphylaxis and serious skin reactions including toxic epidermal necrolysis, Stevens-Johnson Syndrome, and erythema multiforme have been reported in postmarketing experience with oseltamivir phosphate capsules. Stop oseltamivir phosphate capsules and institute appropriate treatment if an allergic-like reaction occurs or is suspected. The use of oseltamivir phosphate capsules is contraindicated in patients with known serious hypersensitivity to oseltamivir phosphate [see Contraindications ( 4 ) and Adverse Reactions ( 6.2 )] . 5.2 Neuropsychiatric Events There have been postmarketing reports of delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, in patients with influenza who were receiving oseltamivir phosphate [ see Adverse Reactions ( 6.2 ) ]. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made but they appear to be uncommon based on oseltamivir phosphate usage data. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of oseltamivir phosphate to these events has not been established. Influenza can be associated with a variety of neurologic and behavioral symptoms that can include events such as hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease. Closely monitor oseltamivir phosphate capsules-treated patients with influenza for signs of abnormal behavior. If neuropsychiatric symptoms occur, evaluate the risks and benefits of continuing oseltamivir phosphate capsules for each patient. 5.3 Risk of Bacterial Infections There is no evidence for efficacy of oseltamivir phosphate capsules in any illness caused by pathogens other than influenza viruses. Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications during the course of influenza. Oseltamivir phosphate capsules has not been shown to prevent such complications. Prescribers should be alert to the potential for secondary bacterial infections and treat them as appropriate."}', 'overdosage': '{"10 OVERDOSAGE Reports of overdoses with oseltamivir phosphate have been received from clinical trials and during postmarketing experience. In the majority of cases reporting overdose, no adverse reactions were reported. Adverse reactions reported following overdose were similar in nature to those observed with therapeutic doses of oseltamivir phosphate [see Adverse Reactions ( 6 )] ."}', 'active_flag': 'Y', 'generic_name': '{"OSELTAMAVIR PHOSPHATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Serious Skin/Hypersensitivity Reactions Advise patients and/or caregivers of the risk of severe allergic reactions (including anaphylaxis) or serious skin reactions. Instruct patients and/or caregiver to stop oseltamivir phosphate capsules and seek immediate medical attention if an allergic-like reaction occurs or is suspected [ see Warnings and Precautions ( 5.1 )] . Neuropsychiatric Events Advise patients and/or caregivers of the risk of neuropsychiatric events in oseltamivir phosphate capsules-treated patients with influenza and instruct patients to contact their physician if they experience signs of abnormal behavior while receiving oseltamivir phosphate capsules [see Warnings and Precautions ( 5.2 )] . Important Dosing Information Instruct patients to begin treatment with oseltamivir phosphate capsules as soon as possible from the first appearance of flu symptoms, within 48 hours of onset of symptoms. Similarly, instruct patients to start taking oseltamivir phosphate capsules for prevention as soon as possible after exposure [ see Dosage and Administration ( 2 )] . Instruct patients to take any missed doses as soon as they remember, except if it is near the next scheduled dose (within 2 hours), and then continue to take oseltamivir phosphate capsules at the usual times. Influenza Vaccines Instruct patients that oseltamivir phosphate capsules are not a substitute for receiving an annual flu vaccination. Patients should continue receiving an annual flu vaccination according to guidelines on immunization practices. Because of the potential for oseltamivir phosphate capsules to inhibit replication of live attenuated influenza vaccine (LAIV) and possibly reduce efficacy of LAIV, avoid administration of LAIV within 2 weeks or 48 hours after oseltamivir phosphate capsules administration, unless medically necessary [see Drug Interactions ( 7.1 )]. Manufactured for: Macleods Pharma USA, Inc. Plainsboro, NJ 08536 Manufactured by: Macleods Pharmaceuticals Ltd. Baddi, Himachal Pradesh, INDIA Revised October 2017 Relabeled By: Proficient Rx LP Thousand Oaks, CA 91320 . ."}', 'pregnancy': '{"8.1 Pregnancy Pregnancy Category C Risk Summary There are no adequate and well-controlled studies with oseltamivir phosphate in pregnant women. Available published epidemiological data suggest that oseltamivir phosphate, taken in any trimester, is not associated with an increased risk of birth defects. However, these studies individually are limited by small sample sizes, use of different comparison groups, and some lacked information on dose, which preclude a definitive assessment of the risk. In animal studies, there was a dose-dependent increase in the incidence rates of a variety of minor skeletal abnormalities and variants in offspring of rats and rabbits exposed at maternally toxic doses 100 and 50 times human exposures, respectively. Oseltamivir phosphate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus [see Clinical Pharmacology ( 12.3 )] . Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women are at higher risk of severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes including maternal death, still births, birth defects, preterm delivery, low birth weight and small for gestational age. Data Human Data Published prospective and retrospective observational studies of approximately 1,500 women exposed to oseltamivir phosphate during pregnancy, including approximately 400 women exposed in the first trimester, suggest that the observed rate of congenital malformations was not increased above the rate in the general comparison population, regardless of when therapy was administered during the gestational period. However, individually, none of these studies had adequate sample sizes and some lacked information on dose, which preclude a definitive assessment of the risk. Animal Data Studies for effects on embryo-fetal development were conducted in rats (50, 250, and 1500 mg/kg/day) and rabbits (50, 150, and 500 mg/kg/day) by the oral route. Relative exposures at these doses were, respectively, 2, 13, and 100 times human exposure in the rat and 4, 8, and 50 times human exposure in the rabbit, based on AUC. Pharmacokinetic studies indicated that there was fetal exposure in both species. In the rat study, minimal maternal toxicity was reported in the 1500 mg/kg/day group. In the rabbit study, slight and marked maternal toxicities were observed, respectively, in the 150 and 500 mg/kg/day groups. At the maternally toxic doses, statistically significant increases in the incidence rates of a variety of minor skeletal abnormalities and variants were observed in the exposed offspring. However, the individual incidence rate of each skeletal abnormality or variant remained within the background rates of occurrence in the species studied."}', 'pediatric_use': '{"8.4 Pediatric Use Treatment of Influenza The safety and efficacy of oseltamivir phosphate for the treatment of influenza in pediatric patients 2 weeks old to 17 years of age has been established [see Dosage and Administration ( 2.2 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14.1 )] and is based on: · 13 to 17 years of age: Safety and efficacy in adolescent patients 13 to 17 years of age was supported by adequate and well-controlled trials in adults and adolescents and younger pediatric patients and safety data in adolescents treated with oseltamivir phosphate in a study of treatment and prophylaxis. · 1 year to 12 years of age: Safety and efficacy in pediatric patients 1 year to 12 years of age was supported by results of one double-blind, placebo-controlled trial in 452 pediatric patients with influenza in whom oseltamivir phosphate 2 mg per kg twice daily or placebo was administered within 48 hours of symptom onset [see Clinical Studies ( 14.1 )]. Additional safety information was provided in a double-blind, placebo-controlled trial in pediatric patients 6 to 12 years of age with known asthma. Efficacy could not be established in pediatric patients with asthma. · 2 weeks to less than 1 year of age: Safety and efficacy in pediatric patients 2 weeks to less than 1 year of age is supported by adequate and well-controlled trials in adults and older pediatric patients and two open-label trials of oseltamivir phosphate (2 to 3.5 mg per kg twice daily for 5 days) in 136 pediatric subjects 2 weeks to less than 1 year of age. In these two trials, the oseltamivir plasma concentrations in these subjects were similar to or higher than the oseltamivir plasma concentrations observed in older pediatric subjects and adults [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.1 )] . The safety and efficacy of oseltamivir phosphate for treatment of influenza in pediatric patients less than 2 weeks of age have not been established. Prophylaxis of Influenza The safety and efficacy of oseltamivir phosphate for the prophylaxis of influenza in pediatric patients 1 year to 17 years old has been established [see Dosage and Administration ( 2.3 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14.2 )] and is based on: · 13 to 17 years of age: Prophylaxis in adolescent patients 13 to 17 years of age is supported by one randomized, placebo-controlled post-exposure household prophylaxis trial of oseltamivir phosphate 75 mg taken orally once daily for 7 days in household contacts including 207 adolescents [see Clinical Studies ( 14.2 )]. · 1 year to 12 years of age: Oseltamivir phosphate for prophylaxis in pediatric patients 1 year to 12 years of age is supported by one randomized, open-label, post-exposure household prophylaxis trial including pediatric subjects 1 year to 12 years of age who received 30 to 60 mg of oseltamivir phosphate for oral suspension (supplied as powder) taken orally once daily for 10 days [see Clinical Studies ( 14.2 )]. Additional safety information was provided in a 6-week seasonal prophylaxis (community outbreak) safety study in 49 patients 1 year to 12 years of age. The safety and efficacy of oseltamivir phosphate for prophylaxis of influenza have not been established for pediatric patients less than 1 year of age."}', 'geriatric_use': '{"8.5 Geriatric Use Treatment of Influenza Of the 4,765 adults in clinical trials of oseltamivir phosphate for the treatment of influenza, 948 (20%) were 65 years and older, while 329 (7%) were 75 years and older. In three double-blind, placebo-controlled trials in the treatment of influenza in patients at least 65 years old, that enrolled 741 subjects (374 received placebo and 362 received oseltamivir phosphate), no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects [see Clinical Studies ( 14.1 )] . Prophylaxis of Influenza Of the 4,603 adults in clinical trials of oseltamivir phosphate for the prophylaxis of influenza, 1,046 (23%) were 65 years and older, while 719 (16%) were 75 years and older. In a randomized, placebo-controlled trial in elderly residents of nursing homes who took oseltamivir phosphate for up to 42 days for the prophylaxis of influenza (oseltamivir phosphate n=276, placebo n=272), no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects [see Clinical Studies ( 14.2 )] ."}'}

{"BENZETHONIUM CHLORIDE",LIDOCAINE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"\u200bUses to help control superficial bleeding, help prevent infection and temporarily relieve pain in minor cuts scrapes burns"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"BENZETHONIUM CHLORIDE"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if redness, swelling, irritation or infection occurs condition gets worse or lasts for more than 7 days"}', 'do_not_use': '{"Do not use in the eyes or on other mucous membranes over large areas of the body on deep or puncture wounds on animal bites on serious burns"}', 'when_using': None, 'warnings': '{"\u200bWarnings For external use only. Caution: FLAMMABLE, Keep away from fire or flame. Contents under pressure. Do not use in the eyes or on other mucous membranes over large areas of the body on deep or puncture wounds on animal bites on serious burns Stop use and ask a doctor if redness, swelling, irritation or infection occurs condition gets worse or lasts for more than 7 days Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{GEMFIBROZIL}

{'contraindications': '{"CONTRAINDICATIONS Hepatic or severe renal dysfunction, including primary biliary cirrhosis. Preexisting gallbladder disease (see WARNINGS ). Hypersensitivity to gemfibrozil. Combination therapy of gemfibrozil with simvastatin (see WARNINGS and PRECAUTIONS ). Combination therapy of gemfibrozil with repaglinide (see PRECAUTIONS ). Combination therapy of gemfibrozil with dasabuvir (see PRECAUTIONS )."}', 'adverse_reactions': '{"ADVERSE REACTIONS In the double-blind controlled phase of the primary prevention component of the Helsinki Heart Study, 2,046 patients received gemfibrozil for up to five years. In that study, the following adverse reactions were statistically more frequent in subjects in the gemfibrozil group: Gemfibrozil (N = 2,046) Placebo (N = 2,035) Frequency in percent of subjects Gastrointestinal reactions 34.2 23.8 Dyspepsia 19.6 11.9 Abdominal pain 9.8 5.6 Acute appendicitis 1.2 0.6 (histologically confirmed in most cases where data were available) Atrial fibrillation 0.7 0.1 Adverse events reported by more than 1% of subjects, but without a significant difference between groups: Diarrhea 7.2 6.5 Fatigue 3.8 3.5 Nausea/Vomiting 2.5 2.1 Eczema 1.9 1.2 Rash 1.7 1.3 Vertigo 1.5 1.3 Constipation 1.4 1.3 Headache 1.2 1.1 Gallbladder surgery was performed in 0.9% of gemfibrozil and 0.5% of placebo subjects in the primary prevention component, a 64% excess, which is not statistically different from the excess of gallbladder surgery observed in the clofibrate group compared to the placebo group of the WHO study. Gallbladder surgery was also performed more frequently in the gemfibrozil group compared to the placebo group (1.9% versus 0.3%, p=0.07) in the secondary prevention component. A statistically significant increase in appendectomy in the gemfibrozil group was seen also in the secondary prevention component (6 on gemfibrozil vs 0 on placebo, p=0.014). Nervous system and special senses adverse reactions were more common in the gemfibrozil group. These included hypesthesia, paresthesias, and taste perversion. Other adverse reactions that were more common among gemfibrozil treatment group subjects but where a causal relationship was not established include cataracts, peripheral vascular disease, and intracerebral hemorrhage. From other studies it seems probable that gemfibrozil is causally related to the occurrence of MUSCULOSKELETAL SYMPTOMS (see WARNINGS ), and to ABNORMAL LIVER FUNCTION TESTS and HEMATOLOGIC CHANGES (see PRECAUTIONS ). Reports of viral and bacterial infections (common cold, cough, urinary tract infections) were more common in gemfibrozil treated patients in other controlled clinical trials of 805 patients. Additional adverse reactions that have been reported for gemfibrozil are listed below by system. These are categorized according to whether a causal relationship to treatment with gemfibrozil is probable or not established: CAUSAL RELATIONSHIP PROBABLE CAUSAL RELATIONSHIP NOT ESTABLISHED General: Weight loss Cardiac: extrasystoles Gastrointestinal: cholestatic jaundice pancreatitis hepatoma colitis Central Nervous System: dizziness Somnolence Paresthesia peripheral neuritis decreased libido depression headache confusion convulsions syncope Eye: blurred vision retinal edema Genitourinary: impotence decreased male fertility renal dysfunction Musculoskeletal: myopathy myasthenia myalgia painful extremities arthralgia synovitis rhabdomyolysis (see WARNINGS and Drug Interactions under PRECUATIONS ) Clinical Laboratory: increased creatine phosphokinase increased bilirubin increased liver transaminases (AST, ALT) increased alkaline phosphatase positive antinuclear antibody Hematopoietic: anemia leukopenia bone marrow hypoplasia eosinophilia thrombocytopenia Immunologic: angioedema laryngeal edema urticaria anaphylaxis Lupus-like syndrome vasculitis Integumentary: exfoliative dermatitis rash dermatitis pruritis alopecia photosensitivity Additional adverse reactions that have been reported include cholecystitis and cholelithiasis ( see WARNINGS )."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE Gemfibrozil Tablets, USP are indicated as adjunctive therapy to diet for: 1. Treatment of adult patients with very high elevations of serum triglyceride levels (Types IV and V hyperlipidemia) who present a risk of pancreatitis and who do not respond adequately to a determined dietary effort to control them. Patients who present such risk typically have serum triglycerides over 2,000 mg/dL and have elevations of VLDL-cholesterol as well as fasting chylomicrons (Type V hyperlipidemia). Subjects who consistently have total serum or plasma triglycerides below 1,000 mg/dL are unlikely to present a risk of pancreatitis. Gemfibrozil therapy may be considered for those subjects with triglyceride elevations between 1,000 and 2,000 mg/dL who have a history of pancreatitis or of recurrent abdominal pain typical of pancreatitis. It is recognized that some Type IV patients with triglycerides under 1,000 mg/dL may, through dietary or alcoholic indiscretion, convert to a Type V pattern with massive triglyceride elevations accompanying fasting chylomicronemia, but the influence of gemfibrozil therapy on the risk of pancreatitis in such situations has not been adequately studied. Drug therapy is not indicated for patients with Type I hyperlipoproteinemia, who have elevations of chylomicrons and plasma triglycerides, but who have normal levels of very low density lipoprotein (VLDL). Inspection of plasma refrigerated for 14 hours is helpful in distinguishing Types I, IV, and V hyperlipoproteinemia. 2. Reducing the risk of developing coronary heart disease only in Type IIb patients without history of or symptoms of existing coronary heart disease who have had an inadequate response to weight loss, dietary therapy, exercise, and other pharmacologic agents (such as bile acid sequestrants and nicotinic acid, known to reduce LDL- and raise HDL-cholesterol) and who have the following triad of lipid abnormalities: low HDL-cholesterol levels in addition to elevated LDL-cholesterol and elevated triglycerides (see WARNINGS , PRECAUTIONS , and CLINICAL PHARMACOLOGY ). The National Cholesterol Education Program has defined a serum HDL-cholesterol value that is consistently below 35 mg/dL as constituting an independent risk factor for coronary heart disease. Patients with significantly elevated triglycerides should be closely observed when treated with gemfibrozil. In some patients with high triglyceride levels, treatment with gemfibrozil is associated with a significant increase in LDL-cholesterol. BECAUSE OF POTENTIAL TOXICITY SUCH AS MALIGNANCY, GALLBLADDER DISEASE, ABDOMINAL PAIN LEADING TO APPENDECTOMY AND OTHER ABDOMINAL SURGERIES, AN INCREASED INCIDENCE IN NON-CORONARY MORTALITY, AND THE 44% RELATIVE INCREASE DURING THE TRIAL PERIOD IN AGE-ADJUSTED ALL-CAUSE MORTALITY SEEN WITH THE CHEMICALLY AND PHARMACOLOGICALLY RELATED DRUG, CLOFIBRATE, THE POTENTIAL BENEFIT OF GEMFIBROZIL IN TREATING TYPE IIA PATIENTS WITH ELEVATIONS OF LDL-CHOLESTEROL ONLY IS NOT LIKELY TO OUTWEIGH THE RISKS. GEMFIBROZIL IS ALSO NOT INDICATED FOR THE TREATMENT OF PATIENTS WITH LOW HDL-CHOLESTEROL AS THEIR ONLY LIPID ABNORMALITY. In a subgroup analysis of patients in the Helsinki Heart Study with above-median HDL-cholesterol values at baseline (greater than 46.4 mg/dL), the incidence of serious coronary events was similar for gemfibrozil and placebo subgroups (see Table I). The initial treatment for dyslipidemia is dietary therapy specific for the type of lipoprotein abnormality. Excess body weight and excess alcohol intake may be important factors in hypertriglyceridemia and should be managed prior to any drug therapy. Physical exercise can be an important ancillary measure, and has been associated with rises in HDL-cholesterol. Diseases contributory to hyperlipidemia such as hypothyroidism or diabetes mellitus should be looked for and adequately treated. Estrogen therapy is sometimes associated with massive rises in plasma triglycerides, especially in subjects with familial hypertriglyceridemia. In such cases, discontinuation of estrogen therapy may obviate the need for specific drug therapy of hypertriglyceridemia. The use of drugs should be considered only when reasonable attempts have been made to obtain satisfactory results with nondrug methods. If the decision is made to use drugs, the patient should be instructed that this does not reduce the importance of adhering to diet."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE There have been reported cases of overdosage with gemfibrozil. In one case, a 7-year-old child recovered after ingesting up to 9 grams of gemfibrozil. Symptoms reported with overdosage were abdominal cramps, abnormal liver function tests, diarrhea, increased CPK, joint and muscle pain, nausea and vomiting. Symptomatic supportive measures should be taken, should an overdose occur."}', 'active_flag': 'Y', 'generic_name': '{GEMFIBROZIL}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS 1. Because of chemical, pharmacological, and clinical similarities between gemfibrozil and clofibrate, the adverse findings with clofibrate in two large clinical studies may also apply to gemfibrozil. In the first of those studies, the Coronary Drug Project, 1,000 subjects with previous myocardial infarction were treated for five years with clofibrate. There was no difference in mortality between the clofibrate-treated subjects and 3,000 placebo-treated subjects, but twice as many clofibrate-treated subjects developed cholelithiasis and cholecystitis requiring surgery. In the other study, conducted by the World Health Organization (WHO), 5,000 subjects without known coronary heart disease were treated with clofibrate for five years and followed one year beyond. There was a statistically significant (44%) higher age-adjusted total mortality in the clofibrate-treated group than in a comparable placebo-treated control group during the trial period. The excess mortality was due to a 33% increase in non-cardiovascular causes, including malignancy, post-cholecystectomy complications, and pancreatitis. The higher risk of clofibrate-treated subjects for gallbladder disease was confirmed. Because of the more limited size of the Helsinki Heart Study, the observed difference in mortality from any cause between the gemfibrozil and placebo groups is not statistically significantly different from the 29% excess mortality reported in the clofibrate group in the separate WHO study at the nine year follow-up (see CLINICAL PHARMACOLOGY ). Noncoronary heart disease related mortality showed an excess in the group originally randomized to gemfibrozil primarily due to cancer deaths observed during the open-label extension. During the five year primary prevention component of the Helsinki Heart Study, mortality from any cause was 44 (2.2%) in the gemfibrozil group and 43 (2.1%) in the placebo group; including the 3.5 year follow-up period since the trial was completed, cumulative mortality from any cause was 101 (4.9%) in the gemfibrozil group and 83 (4.1%) in the group originally randomized to placebo (hazard ratio 1:20 in favor of placebo). Because of the more limited size of the Helsinki Heart Study, the observed difference in mortality from any cause between the gemfibrozil and placebo groups at Year-5 or at year-8.5 is not statistically significantly different from the 29% excess mortality reported in the clofibrate group in the separate WHO study at the nine year follow-up. Noncoronary heart disease related mortality showed an excess in the group originally randomized to gemfibrozil at the 8.5 year follow-up (65 gemfibrozil versus 45 placebo noncoronary deaths). The incidence of cancer (excluding basal cell carcinoma) discovered during the trial and in the 3.5 years after the trial was completed was 51 (2.5%) in both originally randomized groups. In addition, there were 16 basal cell carcinomas in the group originally randomized to gemfibrozil and 9 in the group originally randomized to placebo (p=0.22). There were 30 (1.5%) deaths attributed to cancer in the group originally randomized to gemfibrozil and 18 (0.9%) in the group originally randomized to placebo (p=0.11). Adverse outcomes, including coronary events, were higher in gemfibrozil patients in a corresponding study in men with a history of known or suspected coronary heart disease in the secondary prevention component of the Helsinki Heart Study (see CLINICAL PHARMACOLOGY ). A comparative carcinogenicity study was also done in rats comparing three drugs in this class: fenofibrate (10 and 60 mg/kg; 0.3 and 1.6 times the human dose, respectively), clofibrate (400 mg/kg; 1.6 times the human dose), and gemfibrozil (250 mg/kg; 1.7 times the human dose). Pancreatic acinar adenomas were increased in males and females on fenofibrate; hepatocellular carcinoma and pancreatic acinar adenomas were increased in males and hepatic neoplastic nodules in females treated with clofibrate; hepatic neoplastic nodules were increased in males and females treated with clofibrate; hepatic neoplastic nodules were increased in males and females treated with gemfibrozil while testicular interstitial cell (Leydig cell) tumors were increased in males on all three drugs. 2. A gallstone prevalence substudy of 450 Helsinki Heart Study participants showed a trend toward a greater prevalence of gallstones during the study within the gemfibrozil treatment group (7.5% versus 4.9% for the placebo group, a 55% excess for the gemfibrozil group). A trend toward a greater incidence of gallbladder surgery was observed for the gemfibrozil group (17 versus 11 subjects, a 54% excess). This result did not differ statistically from the increased incidence of cholecystectomy observed in the WHO study in the group treated with clofibrate. Both clofibrate and gemfibrozil may increase cholesterol excretion into the bile, leading to cholelithiasis. If cholelithiasis is suspected, gallbladder studies are indicated. Gemfibrozil therapy should be discontinued if gallstones are found. Cases of cholelithiasis have been reported with gemfibrozil therapy. 3. Since a reduction of mortality from coronary heart disease has not been demonstrated and because liver and interstitial cell testicular tumors were increased in rats, gemfibrozil should be administered only to those patients described in the INDICATIONS AND USAGE section. If a significant serum lipid response is not obtained, gemfibrozil should be discontinued. 4. Concomitant Anticoagulants-Caution should be exercised when warfarin is given in conjunction with gemfibrozil. The dosage of the warfarin should be reduced to maintain the prothrombin time at the desired level to prevent bleeding complications. Frequent prothrombin determinations are advisable until it has been definitely determined that the prothrombin level has stabilized. 5. The concomitant administration of gemfibrozil with simvastatin is contraindicated (see CONTRAINDICATIONS and PRECAUTIONS). Concomitant therapy with gemfibrozil and an HMG-CoA reductase inhibitor is associated with an increased risk of skeletal muscle toxicity manifested as rhabdomyolysis, markedly elevated creatine kinase (CPK) levels, and myoglobinuria, leading in a high proportion of cases to acute renal failure and death. IN PATIENTS WHO HAVE HAD AN UNSATISFACTORY LIPID RESPONSE TO EITHER DRUG ALONE, THE BENEFIT OF COMBINED THERAPY WITH GEMFIBROZIL AND an HMG-CoA REDUCTASE INHIBITOR DOES NOT OUTWEIGH THE RISKS OF SEVERE MYOPATHY, RHABDOMYOLYSIS, AND ACUTE RENAL FAILURE (see PRECAUTIONS , Drug Interactions ). The use of fibrates alone, including gemfibrozil, may occasionally be associated with myositis. Patients receiving gemfibrozil and complaining of muscle pain, tenderness, or weakness should have prompt medical evaluation for myositis, including serum creatine-kinase level determination. If myositis is suspected or diagnosed, gemfibrozil therapy should be withdrawn. 6. Cataracts-Subcapsular bilateral cataracts occurred in 10%, and unilateral in 6.3%, of male rats treated with gemfibrozil at 10 times the human dose. 7. CYP2C8 substrates -Gemfibrozil, a strong inhibitor of CYP2C8, may increase exposure of CYP2C8 substrates when administered concomitantly (see PRECAUTIONS , Drug Interactions ). 8. OATP1B1 substrates – Gemfibrozil is an inhibitor of organic anion-transporter polyprotein (OATP) 1B1 and may increase exposure of drugs that are substrates of OATP1B1 (e.g., atrasentan, atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, SN38 [active metabolite of irinotecan], rosuvastatin, pitavastatin, pravastatin, rifampin, valsartan, olmesartan). Therefore, dosing reductions of drugs that are substrates of OATP1B1 may be required when gemfibrozil is used concomitantly (see PRECAUTIONS , Drug Interactions ). Combination therapy of gemfibrozil with simvastatin or with repaglinide, which are OATP1B1 substrates, is contraindicated (see CONTRAINDICATIONS)."}', 'precautions': '{"PRECAUTIONS 1. Initial Therapy- Laboratory studies should be done to ascertain that the lipid levels are consistently abnormal. Before instituting gemfibrozil therapy, every attempt should be made to control serum lipids with appropriate diet, exercise, weight loss in obese patients, and control of any medical problems such as diabetes mellitus and hypothyroidism that are contributing to the lipid abnormalities. 2. Continued Therapy- Periodic determination of serum lipids should be obtained, and the drug withdrawn if lipid response is inadequate after three months of therapy. 3. Drug Interactions (A) HMG-CoA Reductase Inhibitors: The concomitant administration of gemfibrozil with simvastatin is contraindicated (see CONTRAINDICATIONS and WARNINGS ). The risk of myopathy and rhabdomyolysis is increased with combined gemfibrozil and HMG-CoA reductase inhibitor therapy. Myopathy or rhabdomyolysis with or without acute renal failure have been reported as early as three weeks after initiation of combined therapy or after several months (see WARNINGS ). There is no assurance that periodic monitoring of creatine kinase will prevent the occurrence of severe myopathy and kidney damage. (B) Anticoagulants: CAUTION SHOULD BE EXERCISED WHEN WARFARIN IS GIVEN IN CONJUNCTION WITH GEMFIBROZIL. THE DOSAGE OF THE WARFARIN SHOULD BE REDUCED TO MAINTAIN THE PROTHROMBIN TIME AT THE DESIRED LEVEL TO PREVENT BLEEDING COMPLICATIONS. FREQUENT PROTHROMBIN DETERMINATIONS ARE ADVISABLE UNTIL IT HAS BEEN DEFINITELY DETERMINED THAT THE PROTHROMBIN LEVEL HAS STABILIZED. (C) CYP2C8 Substrates: Gemfibrozil is a strong inhibitor of CYP2C8 and may increase exposure of drugs mainly metabolized by CYP2C8 (e.g., dabrafenib, enzalutamide, loperamide, montelukast, paclitaxel, pioglitazone, rosiglitazone). Therefore, dosing reduction of drugs that are mainly metabolized by CYP2C8 enzyme may be required when gemfibrozil is used concomitantly (see WARNINGS ). Repaglinide: In healthy volunteers, co-administration with gemfibrozil (600 mg twice daily for 3 days) resulted in an 8.1-fold (range 5.5-to 15.0-fold) higher repaglinide AUC and a 28.6-fold (range 18.5-to 80.1-fold) higher repaglinide plasma concentration 7 hours after the dose. In the same study, gemfibrozil (600 mg twice daily for 3 days) + itraconazole (200 mg in the morning and 100 mg in the evening at Day 1, then 100 mg twice daily at Day 2 to 3) resulted in a 19.4-(range 12.9-to 24.7-fold) higher repaglinide AUC and a 70.4-fold (range 42.9-to 119.2-fold) higher repaglinide plasma concentration 7 hours after the dose. In addition, gemfibrozil alone or gemfibrozil + itraconazole prolonged the hypoglycemic effects of repaglinide. Co-administration of gemfibrozil and repaglinide increases the risk of severe hypoglycemia and is contraindicated (see CONTRAINDICATIONS ). Dasabuvir: Co-administration of gemfibrozil with dasabuvir increased dasabuvir AUC and Cmax (ratios: 11.3 and 2.01, respectively) due to CYP2C8 inhibition. Increased dasabuvir exposure may increase the risk of QT prolongation, therefore, coadministration of gemfibrozil with dasabuvir is contraindicated (see CONTRAINDICATIONS ). Enzalutamide: In healthy volunteers given a single 160 mg dose of enzalutamide after gemfibrozil 600 mg twice daily, the AUC of enzalutamide plus active metabolite (N-desmethyl enzalutamide) was increased by 2.2 fold and corresponding C max was decreased by 16%. Increased enzalutamide exposure may increase the risk of seizures. If co-administration is considered necessary, the dose of enzalutamide should be reduced (see WARNINGS ). (D) OATP1B1 substrates: Gemfibrozil is an inhibitor of OATP1B1 transporter and may increase exposure of drugs that are substrates of OATP1B1 (e.g., atrasentan, atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, SN-38 [active metabolite of irinotecan], rosuvastatin, pitavastatin, pravastatin, rifampin, valsartan, olmesartan). Therefore, dosing reductions of drugs that are substrates of OATP1B1 may be required when gemfibrozil is used concomitantly (see WARNINGS ). Combination therapy of gemfibrozil with simvastatin or with repaglinide, which are OATP1B1 substrates, is contraindicated (see CONTRAINDICATIONS ). (E) In vitro studies of CYP enzymes, UGTA enzymes and OATP1B1 transporter: In vitro studies have shown that gemfibrozil is an inhibitor of CYP1A2, CYP2C8, CYP2C9, CYP2C19, OATP1B1, and UDP-glucuronosyltransferase (UGT) 1A1 and 1A3 (see WARNINGS ). (F) Bile Acid-Binding Resins: Gemfibrozil AUC was reduced by 30% when gemfibrozil was given (600 mg) simultaneously with resin-granule drugs such as colestipol (5 g). Administration of the drugs two hours or more apart is recommended because gemfibrozil exposure was not significantly affected when it was administered two hours apart from colestipol. (G) Colchicine: Myopathy, including rhabdomyolysis, has been reported with chronic administration of colchicine at therapeutic doses. Concomitant use of gemfibrozil may potentiate the development of myopathy. Patients with renal dysfunction and elderly patients are at increased risk. Caution should be exercised when prescribing gemfibrozil with colchicine, especially in elderly patients or patients with renal dysfunction. 4. Carcinogenesis, Mutagenesis, Impairment of Fertility - Long-term studies have been conducted in rats at 0.2 and 1.3 times the human exposure (based on AUC). The incidence of benign liver nodules and liver carcinomas was significantly increased in high dose male rats. The incidence of liver carcinomas increased also in low dose males, but this increase was not statistically significant (p=0.1). Male rats had a dose-related and statistically significant increase of benign Leydig cell tumors. The higher dose female rats had a significant increase in the combined incidence of benign and malignant liver neoplasms. Long-term studies have been conducted in mice at 0.1 and 0.7 times the human exposure (based on AUC). There were no statistically significant differences from controls in the incidence of liver tumors, but the doses tested were lower than those shown to be carcinogenic with other fibrates. Electron microscopy studies have demonstrated a florid hepatic peroxisome proliferation following gemfibrozil administration to the male rat. An adequate study to test for peroxisome proliferation has not been done in humans but changes in peroxisome morphology have been observed. Peroxisome proliferation has been shown to occur in humans with either of two other drugs of the fibrate class when liver biopsies were compared before and after treatment in the same individual. Administration of approximately 2 times the human dose (based on surface area) to male rats for 10 weeks resulted in a dose-related decrease of fertility. Subsequent studies demonstrated that this effect was reversed after a drug-free period of about eight weeks, and it was not transmitted to the offspring. 5. Pregnancy Category C- Gemfibrozil has been shown to produce adverse effects in rats and rabbits at doses between 0.5 and 3 times the human dose (based on surface area). There are no adequate and well-controlled studies in pregnant women. Gemfibrozil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Administration of gemfibrozil to female rats at 2 times the human dose (based on surface area) before and throughout gestation caused a dose-related decrease in conception rate, an increase in stillborns, and a slight reduction in pup weight during lactation. There were also dose-related increased skeletal variations. Anophthalmia occurred, but rarely. Administration of 0.6 and 2 times the human dose (based on surface area) of gemfibrozil to female rats from gestation day 15 through weaning caused dose-related decreases in birth weight and suppressions of pup growth during lactation. Administration of 1 and 3 times the human dose (based on surface area) of gemfibrozil to female rabbits during organogenesis caused a dose-related decrease in litter size and, at the high dose, an increased incidence of parietal bone variations. 6. Nursing Mothers- It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for gemfibrozil in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. 7. Hematologic Changes- Mild hemoglobin, hematocrit and white blood cell decreases have been observed in occasional patients following initiation of gemfibrozil therapy. However, these levels stabilize during longterm administration. Rarely, severe anemia, leukopenia, thrombocytopenia, and bone marrow hypoplasia have been reported. Therefore, periodic blood counts are recommended during the first 12 months of gemfibrozil administration. 8. Liver Function– Abnormal liver function tests have been observed occasionally during gemfibrozil administration, including elevations of AST, ALT, LDH, bilirubin, and alkaline phosphatase. These are usually reversible when gemfibrozil is discontinued. Therefore, periodic liver function studies are recommended and gemfibrozil therapy should be terminated if abnormalities persist. 9. Kidney Function- There have been reports of worsening renal insufficiency upon the addition of gemfibrozil therapy in individuals with baseline plasma creatinine >2.0 mg/dL. In such patients, the use of alternative therapy should be considered against the risks and benefits of a lower dose of gemfibrozil. 10. Pediatric Use- Safety and efficacy in pediatric patients have not been established."}', 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{ENTACAPONE}

{'contraindications': '{"CONTRAINDICATIONS Entacapone tablets are contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients."}', 'adverse_reactions': '{"ADVERSE REACTIONS Because clinical studies are conducted under widely varying conditions, the incidence of adverse reactions (number of unique patients experiencing an adverse reaction associated with treatment per total number of patients treated) observed in the clinical studies of a drug cannot be directly compared to the incidence of adverse reactions in the clinical studies of another drug and may not reflect the incidence of adverse reactions observed in practice. A total of 1,450 patients with Parkinson’s disease were treated with entacapone in premarketing clinical studies. Included were patients with fluctuating symptoms, as well as those with stable responses to levodopa therapy. All patients received concomitant treatment with levodopa preparations, however, and were similar in other clinical aspects. The most commonly observed adverse reactions (incidence at least 3% greater than placebo) in double-blind, placebo-controlled studies (N=1,003) associated with the use of entacapone were: dyskinesia, urine discoloration, diarrhea, nausea, hyperkinesia, abdominal pain, vomiting, and dry mouth. Approximately 14% of the 603 patients given entacapone in the double-blind, placebo-controlled studies discontinued treatment due to adverse reactions, compared to 9% of the 400 patients who received placebo. The most frequent causes of discontinuation in decreasing order were: psychiatric disorders (2% vs. 1%), diarrhea (2% vs. 0%), dyskinesia and hyperkinesia (2% vs. 1%), nausea (2% vs. 1%), and abdominal pain (1% vs. 0%). Adverse Event Incidence in Controlled Clinical Studies Table 4 lists treatment-emergent adverse events that occurred in at least 1% of patients treated with entacapone participating in the double-blind, placebo-controlled studies and that were numerically more common in the entacapone group, compared to placebo. In these studies, either entacapone or placebo was added to levodopa and carbidopa (or levodopa and benserazide). Table 4: Summary of Patients with Adverse Events after Start of Trial Drug Administration At least 1% in Entacapone Group and Greater Than Placebo SYSTEM ORGAN CLASS Preferred term Entacapone (n = 603) % of patients Placebo (n = 400) % of patients SKIN AND APPENDAGES DISORDERS Sweating increased 2 1 MUSCULOSKELETAL SYSTEM DISORDERS Back pain 2 1 CENTRAL AND PERIPHERAL NERVOUS SYSTEM DISORDERS Dyskinesia Hyperkinesia Hypokinesia Dizziness 25 10 9 8 15 5 8 6 SPECIAL SENSES, OTHER DISORDERS Taste perversion 1 0 PSYCHIATRIC DISORDERS Anxiety Somnolence Agitation 2 2 1 1 0 0 GASTROINTESTINAL SYSTEM DISORDERS Nausea Diarrhea Abdominal pain Constipation Vomiting Mouth dry Dyspepsia Flatulence Gastritis Gastrointestinal disorders 14 10 8 6 4 3 2 2 1 1 8 4 4 4 1 0 1 0 0 0 RESPIRATORY SYSTEM DISORDERS Dyspnea 3 1 PLATELET, BLEEDING AND CLOTTING DISORDERS Purpura 2 1 URINARY SYSTEM DISORDERS Urine discoloration 10 0 BODY AS A WHOLE - GENERAL DISORDERS Back pain Fatigue Asthenia 4 6 2 2 4 1 RESISTANCE MECHANISM DISORDERS Infection bacterial 1 0 Effects of Gender and Age on Adverse Reactions No differences were noted in the rate of adverse events attributable to entacapone by age or gender. Postmarketing Reports The following spontaneous reports of adverse events temporally associated with entacapone have been identified since market introduction and are not listed in Table 4. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish causal relationship to entacapone exposure. Hepatitis with mainly cholestatic features has been reported."}', 'drug_interactions': '{"Drug Interactions In vitro studies of human CYP enzymes showed that entacapone inhibited the CYP enzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A only at very high concentrations (IC50 from 200 microM to over 1,000 microM; an oral 200 mg dose achieves a highest level of approximately 5 microM in people); these enzymes would therefore not be expected to be inhibited in clinical use. In an interaction study in healthy volunteers, entacapone did not significantly change the plasma levels of S-warfarin while the AUC for R-warfarin increased on average by 18% [Cl90 11% to 26%], and the INR values increased on average by 13% [Cl90 6% to 19%]. Nevertheless, cases of significantly increased INR in patients concomitantly using warfarin have been reported during the postapproval use of entacapone. Therefore, monitoring of INR is recommended when entacapone treatment is initiated or when the dose is increased for patients receiving warfarin. Protein Binding Entacapone is highly protein bound (98%). In vitro studies have shown no binding displacement between entacapone and other highly bound drugs, such as warfarin, salicylic acid, phenylbutazone, and diazepam. Drugs Metabolized by Catechol- O-Methyltransferase (COMT) See WARNINGS . Hormone Levels Levodopa is known to depress prolactin secretion and increase growth hormone levels. Treatment with entacapone coadministered with levodopa and dopa decarboxylase inhibitor does not change these effects. Effect of Entacapone on the Metabolism of Other Drugs See WARNINGS regarding concomitant use of entacapone and non-selective MAO inhibitors. No interaction was noted with the MAO-B inhibitor selegiline in two multiple-dose interaction studies when entacapone was coadministered with a levodopa and dopa decarboxylase inhibitor (n=29). More than 600 patients with Parkinson’s disease in clinical studies have used selegiline in combination with entacapone and levodopa and dopa decarboxylase inhibitor. As most entacapone excretion is via the bile, caution should be exercised when drugs known to interfere with biliary excretion, glucuronidation, and intestinal beta-glucuronidase are given concurrently with entacapone. These include probenecid, cholestyramine, and some antibiotics (e.g., erythromycin, rifampicin, ampicillin, and chloramphenicol). No interaction with the tricyclic antidepressant imipramine was shown in a single-dose study with entacapone without coadministered levodopa and dopa-decarboxylase inhibitor."}', 'indications_and_usage': '{"INDICATIONS Entacapone tablets, USP are indicated as an adjunct to levodopa and carbidopa to treat end-of-dose “wearing-off” in patients with Parkinson’s disease (see CLINICAL PHARMACOLOGY, Clinical Studies ). Entacapone tablets, USP effectiveness has not been systematically evaluated in patients with Parkinson’s disease who do not experience end-of-dose “wearing-off”."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE The postmarketing data include several cases of overdose. The highest reported dose of entacapone was at least 40,000 mg. The acute symptoms and signs commonly seen in these cases included somnolence and decreased activity, states related to depressed level of consciousness (e.g., coma, confusion and disorientation) and discolorations of skin, tongue, and urine, as well as restlessness, agitation, and aggression. COMT inhibition by entacapone treatment is dose-dependent. A massive overdose of entacapone may theoretically produce a 100% inhibition of the COMT enzyme in humans, thereby preventing the metabolism of endogenous and exogenous catechols. The highest daily dose given to humans was 2,400 mg, administered in one study as 400 mg six times daily with levodopa and carbidopa for 14 days in 15 Parkinson’s disease patients, and in another study as 800 mg three times daily for 7 days in 8 healthy volunteers. At this daily dose, the peak plasma concentrations of entacapone averaged 2 mcg per mL (at 45 minutes, compared to 1 mcg per mL and 1.2 mcg per mL with 200 mg entacapone at 45 minutes). Abdominal pain and loose stools were the most commonly observed adverse events during this study. Daily doses as high as 2,000 mg entacapone have been administered as 200 mg 10 times daily with levodopa and carbidopa or levodopa and benserazide for at least 1 year in 10 patients, for at least 2 years in 8 patients and for at least 3 years in 7 patients. Overall, however, clinical experience with daily doses above 1,600 mg is limited. The range of lethal plasma concentrations of entacapone based on animal data was 80 mcg per mL to 130 mcg per mL in mice. Respiratory difficulties, ataxia, hypoactivity, and convulsions were observed in mice after high oral (gavage) doses. Management of Overdose Management of entacapone overdose is symptomatic; there is no known antidote to entacapone. Hospitalization is advised, and general supportive care is indicated. There is no experience with hemodialysis or hemoperfusion, but these procedures are unlikely to be of benefit, because entacapone is highly bound to plasma proteins. An immediate gastric lavage and repeated doses of charcoal over time may hasten the elimination of entacapone by decreasing its absorption and reabsorption from the gastrointestinal (GI) tract. The adequacy of the respiratory and circulatory systems should be carefully monitored and appropriate supportive measures employed. The possibility of drug interactions, especially with catechol-structured drugs, should be borne in mind."}', 'active_flag': 'Y', 'generic_name': '{ENTACAPONE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Monoamine oxidase (MAO) and COMT are the two major enzyme systems involved in the metabolism of catecholamines. It is theoretically possible, therefore, that the combination of entacapone and a non-selective MAO inhibitor (e.g., phenelzine and tranylcypromine) would result in inhibition of the majority of the pathways responsible for normal catecholamine metabolism. For this reason, patients should ordinarily not be treated concomitantly with entacapone and a non-selective MAO inhibitor. Entacapone can be taken concomitantly with a selective MAO-B inhibitor (e.g., selegiline). Drugs Metabolized By Catechol-O-Methyltransferase (COMT) When a single 400 mg dose of entacapone was given with intravenous isoprenaline (isoproterenol) and epinephrine without coadministered levodopa and dopa decarboxylase inhibitor, the overall mean maximal changes in heart rate during infusion were about 50% and 80% higher than with placebo, for isoprenaline and epinephrine, respectively. Therefore, drugs known to be metabolized by COMT, such as isoproterenol, epinephrine, norepinephrine, dopamine, dobutamine, alpha-methyldopa, apomorphine, isoetherine, and bitolterol should be administered with caution in patients receiving entacapone regardless of the route of administration (including inhalation), as their interaction may result in increased heart rates, possible arrhythmias, and excessive changes in blood pressure. Ventricular tachycardia was noted in one 32-year-old healthy male volunteer in an interaction study after epinephrine infusion and oral entacapone administration. Treatment with propranolol was required. A causal relationship to entacapone administration appears probable but cannot be attributed with certainty. Falling Asleep During Activities of Daily Living and Somnolence Patients with Parkinson’s disease treated with entacapone, which increases plasma levodopa levels, or with levodopa have reported suddenly falling asleep without prior warning of sleepiness while engaged in activities of daily living (including the operation of motor vehicles). Some of these episodes resulted in accidents. Although many of these patients reported somnolence while on entacapone, some did not perceive warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some of these events have been reported as late as one year after initiation of treatment. The risk of somnolence was increased (entacapone 2% and placebo 0%) in controlled studies. It has been reported that falling asleep while engaged in activities of daily living always occurs in a setting of pre\xad-existing somnolence, although patients may not give such a history. For this reason, prescribers should reassess patients for drowsiness or sleepiness especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Patients should be advised to exercise caution while driving, operating machines, or working at heights during treatment with entacapone. Patients who have already experienced somnolence and/or an episode of sudden sleep onset should not participate in these activities during treatment with entacapone. Before initiating treatment with entacapone, advise patients of the potential to develop drowsiness and specifically ask about factors that may increase this risk such as concomitant use of sedating medications and the presence of sleep disorders. If a patient develops daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), entacapone should ordinarily be discontinued (see DOSAGE AND ADMINISTRATION for guidance on discontinuing entacapone). If the decision is made to continue entacapone, patients should be advised not to drive and to avoid other potentially dangerous activities. There is insufficient information to establish whether dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living."}', 'precautions': '{"PRECAUTIONS Hypotension, Orthostatic Hypotension, and Syncope Dopaminergic therapy in Parkinson’s disease patients has been associated with orthostatic hypotension. Entacapone enhances levodopa bioavailability and, therefore, might be expected to increase the occurrence of orthostatic hypotension. In controlled studies, approximately 1.2% and 0.8% of 200 mg entacapone and placebo patients, respectively, reported at least one episode of syncope. Reports of syncope were generally more frequent in patients in both treatment groups who had an episode of documented hypotension. Hallucinations and Psychotic-Like Behavior Dopaminergic therapy in patients with Parkinson’s disease has been associated with hallucinations. In clinical studies, hallucinations led to drug discontinuation and premature withdrawal in 0.8% and 0% of patients treated with 200 mg entacapone and placebo, respectively. Hallucinations led to hospitalization in 1% and 0.3% of patients in the 200 mg entacapone and placebo groups, respectively. Agitation occurred in 1% of patients treated with entacapone and 0% treated with placebo. Postmarketing reports indicate that patients may experience new or worsening mental status and behavioral changes, which may be severe, including psychotic-like behavior during entacapone treatment or after starting or increasing the dose of entacapone. Other drugs prescribed to improve the symptoms of Parkinson’s disease can have similar effects on thinking and behavior. Abnormal thinking and behavior can cause paranoid ideation, delusions, hallucinations, confusion, disorientation, aggressive behavior, agitation, and delirium. Psychotic-like behaviors were also observed during the clinical development of entacapone. Patients with a major psychotic disorder should ordinarily not be treated with entacapone because of the risk of exacerbating psychosis. In addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson\'s disease and may decrease the effectiveness of entacapone (see PRECAUTIONS ). Impulse Control and Compulsive Behaviors Postmarketing reports suggest that patients treated with anti-Parkinson medications can experience intense urges to gamble, increased sexual urges, intense urges to spend money uncontrollably, and other intense urges. Patients may be unable to control these urges while taking one or more of the medications that are used for the treatment of Parkinson’s disease and that increase central dopaminergic tone, including entacapone taken with levodopa and carbidopa. In some cases, although not all, these urges were reported to have stopped when the dose of anti-Parkinson medications was reduced or discontinued. Because patients may not recognize these behaviors as abnormal it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with entacapone. Physicians should consider dose reduction or stopping entacapone if a patient develops such urges while taking entacapone. Diarrhea and Colitis In clinical studies, diarrhea developed in 60 of 603 (10%) and 16 of 400 (4%) of patients treated with 200 mg entacapone and placebo, respectively. In patients treated with entacapone, diarrhea was generally mild to moderate in severity (8.6%) but was regarded as severe in 1.3%. Diarrhea resulted in withdrawal in 10 of 603 (1.7%) patients, 7 (1.2%) with mild and moderate diarrhea and 3 (0.5%) with severe diarrhea. Diarrhea generally resolved after discontinuation of entacapone. Two patients with diarrhea were hospitalized. Typically, diarrhea presents within 4 weeks to 12 weeks after entacapone is started, but it may appear as early as the first week and as late as many months after the initiation of treatment. Diarrhea may be associated with weight loss, dehydration, and hypokalemia. Postmarketing experience has shown that diarrhea may be a sign of drug-induced microscopic colitis, primarily lymphocytic colitis. In these cases diarrhea has usually been moderate to severe, watery, and non-bloody, at times associated with dehydration, abdominal pain, weight loss, and hypokalemia. In the majority of cases, diarrhea and other colitis-related symptoms resolved or significantly improved when entacapone treatment was stopped. In some patients with biopsy confirmed colitis, diarrhea had resolved or significantly improved after discontinuation of entacapone but recurred after retreatment with entacapone. If prolonged diarrhea is suspected to be related to entacapone, the drug should be discontinued and appropriate medical therapy considered. If the cause of prolonged diarrhea remains unclear or continues after stopping entacapone, then further diagnostic investigations including colonoscopy and biopsies should be considered. Dyskinesia Entacapone may potentiate the dopaminergic side effects of levodopa and may cause or exacerbate preexisting dyskinesia. Although decreasing the dose of levodopa may ameliorate this side effect, many patients in controlled studies continued to experience frequent dyskinesia despite a reduction in their dose of levodopa. The incidence of dyskinesia was 25% for treatment with entacapone and 15% for placebo. The incidence of study withdrawal for dyskinesia was 1.5% for 200 mg entacapone and 0.8% for placebo. Other Events Reported With Dopaminergic Therapy The events listed below are events associated with the use of drugs that increase dopaminergic activity. Rhabdomyolysis Cases of severe rhabdomyolysis have been reported following the approval of entacapone. Although the reactions typically occurred while patients were treated with entacapone, the complicated nature of these cases makes it difficult to determine what role, if any, entacapone played in their pathogenesis. Severe prolonged motor activity including dyskinesia may account for rhabdomyolysis. Signs and symptoms include fever, alteration of consciousness, myalgia, increased values of creatine phosphokinase (CPK) and myoglobin. Hyperpyrexia and Confusion Cases of a symptom complex resembling neuroleptic malignant syndrome (NMS) characterized by elevated temperature, muscular rigidity, altered consciousness, and elevated CPK have been reported in association with the rapid dose reduction or withdrawal of other dopaminergic drugs. In most of these cases, symptoms began after abrupt discontinuation of treatment with entacapone or reduction of its dose, or after the initiation of treatment with entacapone. The complicated nature of these cases makes it difficult to determine what role, if any, entacapone may have played in their pathogenesis. No cases have been reported following the abrupt withdrawal or dose reduction of entacapone treatment during clinical studies. Prescribers should exercise caution when discontinuing entacapone treatment. When considered necessary, withdrawal should proceed slowly. If the decision is made to discontinue treatment with entacapone, recommendations include monitoring the patient closely and adjusting other dopaminergic treatments as needed. This syndrome should be considered in the differential diagnosis for any patient who develops a high fever or severe rigidity. Tapering entacapone has not been systematically evaluated. Fibrotic Complications Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, and pleural thickening have been reported in some patients treated with ergot derived dopaminergic agents. These complications may resolve when the drug is discontinued, but complete resolution does not always occur. Although these adverse events are believed to be related to the ergoline structure of these compounds, whether other, nonergot derived drugs (e.g., entacapone) that increase dopaminergic activity can cause them is unknown. It should be noted that the expected incidence of fibrotic complications is so low that even if entacapone caused these complications at rates similar to those attributable to other dopaminergic therapies, it is unlikely that it would have been detected in a cohort of the size exposed to entacapone. Four cases of pulmonary fibrosis were reported during clinical development of entacapone; three of these patients were also treated with pergolide and one with bromocriptine. The duration of treatment with entacapone ranged from 7 months to 17 months. Melanoma Epidemiological studies have shown that patients with Parkinson’s disease have a higher risk (2-to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson’s disease or other factors, such as drugs used to treat Parkinson’s disease, is unclear. For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using entacapone for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists). Renal Toxicity In a 1-year toxicity study, entacapone (plasma exposure 20 times that in humans receiving the maximum recommended daily dose of 1,600 mg) caused an increased incidence of nephrotoxicity in male rats that was characterized by regenerative tubules, thickening of basement membranes, infiltration of mononuclear cells, and tubular protein casts. These effects were not associated with changes in clinical chemistry parameters, and there is no established method for monitoring for the possible occurrence of these lesions in humans. Although this toxicity could represent a species-specific effect, there is not yet evidence that this is so. Hepatic Impairment Patients with hepatic impairment should be treated with caution. The AUC and C max of entacapone approximately doubled in patients with documented liver disease compared to controls (see CLINICAL PHARMACOLOGY, Pharmacokinetics of Entacapone and DOSAGE AND ADMINISTRATION ). Information for Patients Instruct patients to take entacapone only as prescribed. Inform patients that hallucinations and/or other psychotic-like behavior can occur. Advise patients that they may develop postural (orthostatic) hypotension with or without symptoms such as dizziness, nausea, syncope, and sweating. Hypotension may occur more frequently during initial therapy. Accordingly, patients should be cautioned against rising rapidly after sitting or lying down, especially if they have been doing so for prolonged periods, and especially at the initiation of treatment with entacapone. Advise patients that they should neither drive a car nor operate other complex machinery until they have gained sufficient experience on entacapone to gauge whether or not it affects their mental and/or motor performance adversely. Warn patients about the possibility of sudden onset of sleep during daily activities, in some cases without awareness or warning signs, when they are taking dopaminergic agents, including entacapone. Because of the possible additive sedative effects, caution should be used when patients are taking other CNS depressants in combination with entacapone. Inform patients that nausea may occur, especially at the initiation of treatment with entacapone. Inform patients that diarrhea may occur with entacapone and it may have a delayed onset. Sometimes prolonged diarrhea may be caused by colitis (inflammation of the large intestine). Patients with diarrhea should drink fluids to maintain adequate hydration and monitor for weight loss. If diarrhea associated with entacapone is prolonged, discontinuing the drug is expected to lead to resolution, if diarrhea continues after stopping entacapone, further diagnostic investigations may be needed. Advise patients about the possibility of an increase in dyskinesia. Tell patients that treatment with entacapone may cause a change in the color of their urine (a brownish orange discoloration) that is not clinically relevant. In controlled studies, 10% of patients treated with entacapone reported urine discoloration compared to 0% of placebo patients. Although entacapone has not been shown to be teratogenic in animals, it is always given in conjunction with levodopa and carbidopa, which is known to cause visceral and skeletal malformations in rabbits. Accordingly, patients should be advised to notify their physicians if they become pregnant or intend to become pregnant during therapy (see PRECAUTIONS, Pregnancy ). Entacapone is excreted into maternal milk in rats. Because of the possibility that entacapone may be excreted into human maternal milk, advise patients to notify their physicians if they intend to breastfeed or are breastfeeding an infant. Tell patients and family members to notify their healthcare practitioner if they notice that the patient develops unusual urges or behaviors. Laboratory Tests Entacapone is a chelator of iron. The impact of entacapone on the body’s iron stores is unknown; however, a tendency towards decreasing serum iron concentrations was noted in clinical studies. In a controlled clinical study serum ferritin levels (as marker of iron deficiency and subclinical anemia) were not changed with entacapone compared to placebo after one year of treatment and there was no difference in rates of anemia or decreased hemoglobin levels. Special Populations Patients with hepatic impairment should be treated with caution (see INDICATIONS , DOSAGE AND ADMINISTRATION ). Drug Interactions In vitro studies of human CYP enzymes showed that entacapone inhibited the CYP enzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A only at very high concentrations (IC50 from 200 microM to over 1,000 microM; an oral 200 mg dose achieves a highest level of approximately 5 microM in people); these enzymes would therefore not be expected to be inhibited in clinical use. In an interaction study in healthy volunteers, entacapone did not significantly change the plasma levels of S-warfarin while the AUC for R-warfarin increased on average by 18% [Cl90 11% to 26%], and the INR values increased on average by 13% [Cl90 6% to 19%]. Nevertheless, cases of significantly increased INR in patients concomitantly using warfarin have been reported during the postapproval use of entacapone. Therefore, monitoring of INR is recommended when entacapone treatment is initiated or when the dose is increased for patients receiving warfarin. Protein Binding Entacapone is highly protein bound (98%). In vitro studies have shown no binding displacement between entacapone and other highly bound drugs, such as warfarin, salicylic acid, phenylbutazone, and diazepam. Drugs Metabolized by Catechol- O-Methyltransferase (COMT) See WARNINGS . Hormone Levels Levodopa is known to depress prolactin secretion and increase growth hormone levels. Treatment with entacapone coadministered with levodopa and dopa decarboxylase inhibitor does not change these effects. Effect of Entacapone on the Metabolism of Other Drugs See WARNINGS regarding concomitant use of entacapone and non-selective MAO inhibitors. No interaction was noted with the MAO-B inhibitor selegiline in two multiple-dose interaction studies when entacapone was coadministered with a levodopa and dopa decarboxylase inhibitor (n=29). More than 600 patients with Parkinson’s disease in clinical studies have used selegiline in combination with entacapone and levodopa and dopa decarboxylase inhibitor. As most entacapone excretion is via the bile, caution should be exercised when drugs known to interfere with biliary excretion, glucuronidation, and intestinal beta-glucuronidase are given concurrently with entacapone. These include probenecid, cholestyramine, and some antibiotics (e.g., erythromycin, rifampicin, ampicillin, and chloramphenicol). No interaction with the tricyclic antidepressant imipramine was shown in a single-dose study with entacapone without coadministered levodopa and dopa-decarboxylase inhibitor. Carcinogenesis Two-year carcinogenicity studies of entacapone were conducted in mice and rats. In mice, no increase in tumors was observed at oral doses of 100, 200 and 400 mg/kg/day. At the highest dose tested, plasma exposures (AUC) were 4 times higher than that in humans at the maximum recommended daily dose (MRDD) of 1,600 mg. In rats administered oral doses of 20, 90, or 400 mg/kg/day, an increased incidence of renal tubular adenomas and carcinomas was observed in males at the highest dose tested. Plasma AUCs at the higher dose not associated with increased renal tumors (90 mg/kg/day) were approximately 5 times that in humans at the MRDD of entacapone. The carcinogenic potential of entacapone administered in combination with levodopa and carbidopa has not been evaluated. Mutagenesis Entacapone was mutagenic and clastogenic in the in vitro mouse lymphoma tk assay in the presence and absence of metabolic activation, and was clastogenic in cultured human lymphocytes in the presence of metabolic activation. Entacapone, either alone or in combination with levodopa and carbidopa, was not clastogenic in the in vivo mouse micronucleus test or mutagenic in the bacterial reverse mutation assay (Ames test). Impairment of Fertility Entacapone did not impair fertility or general reproductive performance in rats treated with up to 700 mg/kg/day (plasma AUCs 28 times those in humans receiving the MRDD of 1,600 mg). Delayed mating, but no fertility impairment, was evident in female rats treated with 700 mg/kg/day of entacapone. Pregnancy In embryofetal development studies, entacapone was administered to pregnant animals throughout organogenesis at doses of up to 1,000 mg/kg/day in rats and 300 mg/kg/day in rabbits. Increased incidences of fetal variations were evident in litters from rats treated with the highest dose, in the absence of overt signs of maternal toxicity. The maternal plasma drug exposure (AUC) associated with this dose was approximately 34 times the estimated plasma exposure in humans receiving the maximum recommended daily dose (MRDD) of 1,600 mg. Increased frequencies of abortions, late and total resorptions, and decreased fetal weights were observed in the litters of rabbits treated with maternally toxic doses of 100 mg/kg/day (plasma AUCs 0.4 times those in humans receiving the MRDD) or greater. There was no evidence of teratogenicity in these studies. However, when entacapone was administered to female rats prior to mating and during early gestation, an increased incidence of fetal eye anomalies (macrophthalmia, microphthalmia, anophthalmia) was observed in the litters of dams treated with doses of 160 mg/kg/day (plasma AUCs 7 times those in humans receiving the MRDD) or greater, in the absence of maternal toxicity. Administration of up to 700 mg/kg/day (plasma AUCs 28 times those in humans receiving the MRDD) to female rats during the latter part of gestation and throughout lactation produced no evidence of developmental impairment in the offspring. Entacapone is always given concomitantly with levodopa and carbidopa, which is known to cause visceral and skeletal malformations in rabbits. The teratogenic potential of entacapone in combination with levodopa and carbidopa was not assessed in animals. There is no experience from clinical studies regarding the use of entacapone in pregnant women. Therefore, entacapone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Women In animal studies, entacapone was excreted into maternal rat milk. It is not known whether entacapone is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when entacapone is administered to a nursing woman. Pediatric Use Safety and effectiveness in pediatric patients have not been established."}', 'information_for_patients': '{"Information for Patients Instruct patients to take entacapone only as prescribed. Inform patients that hallucinations and/or other psychotic-like behavior can occur. Advise patients that they may develop postural (orthostatic) hypotension with or without symptoms such as dizziness, nausea, syncope, and sweating. Hypotension may occur more frequently during initial therapy. Accordingly, patients should be cautioned against rising rapidly after sitting or lying down, especially if they have been doing so for prolonged periods, and especially at the initiation of treatment with entacapone. Advise patients that they should neither drive a car nor operate other complex machinery until they have gained sufficient experience on entacapone to gauge whether or not it affects their mental and/or motor performance adversely. Warn patients about the possibility of sudden onset of sleep during daily activities, in some cases without awareness or warning signs, when they are taking dopaminergic agents, including entacapone. Because of the possible additive sedative effects, caution should be used when patients are taking other CNS depressants in combination with entacapone. Inform patients that nausea may occur, especially at the initiation of treatment with entacapone. Inform patients that diarrhea may occur with entacapone and it may have a delayed onset. Sometimes prolonged diarrhea may be caused by colitis (inflammation of the large intestine). Patients with diarrhea should drink fluids to maintain adequate hydration and monitor for weight loss. If diarrhea associated with entacapone is prolonged, discontinuing the drug is expected to lead to resolution, if diarrhea continues after stopping entacapone, further diagnostic investigations may be needed. Advise patients about the possibility of an increase in dyskinesia. Tell patients that treatment with entacapone may cause a change in the color of their urine (a brownish orange discoloration) that is not clinically relevant. In controlled studies, 10% of patients treated with entacapone reported urine discoloration compared to 0% of placebo patients. Although entacapone has not been shown to be teratogenic in animals, it is always given in conjunction with levodopa and carbidopa, which is known to cause visceral and skeletal malformations in rabbits. Accordingly, patients should be advised to notify their physicians if they become pregnant or intend to become pregnant during therapy (see PRECAUTIONS, Pregnancy ). Entacapone is excreted into maternal milk in rats. Because of the possibility that entacapone may be excreted into human maternal milk, advise patients to notify their physicians if they intend to breastfeed or are breastfeeding an infant. Tell patients and family members to notify their healthcare practitioner if they notice that the patient develops unusual urges or behaviors."}', 'pregnancy': '{"Pregnancy In embryofetal development studies, entacapone was administered to pregnant animals throughout organogenesis at doses of up to 1,000 mg/kg/day in rats and 300 mg/kg/day in rabbits. Increased incidences of fetal variations were evident in litters from rats treated with the highest dose, in the absence of overt signs of maternal toxicity. The maternal plasma drug exposure (AUC) associated with this dose was approximately 34 times the estimated plasma exposure in humans receiving the maximum recommended daily dose (MRDD) of 1,600 mg. Increased frequencies of abortions, late and total resorptions, and decreased fetal weights were observed in the litters of rabbits treated with maternally toxic doses of 100 mg/kg/day (plasma AUCs 0.4 times those in humans receiving the MRDD) or greater. There was no evidence of teratogenicity in these studies. However, when entacapone was administered to female rats prior to mating and during early gestation, an increased incidence of fetal eye anomalies (macrophthalmia, microphthalmia, anophthalmia) was observed in the litters of dams treated with doses of 160 mg/kg/day (plasma AUCs 7 times those in humans receiving the MRDD) or greater, in the absence of maternal toxicity. Administration of up to 700 mg/kg/day (plasma AUCs 28 times those in humans receiving the MRDD) to female rats during the latter part of gestation and throughout lactation produced no evidence of developmental impairment in the offspring. Entacapone is always given concomitantly with levodopa and carbidopa, which is known to cause visceral and skeletal malformations in rabbits. The teratogenic potential of entacapone in combination with levodopa and carbidopa was not assessed in animals. There is no experience from clinical studies regarding the use of entacapone in pregnant women. Therefore, entacapone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus."}', 'pediatric_use': '{"Pediatric Use Safety and effectiveness in pediatric patients have not been established."}', 'geriatric_use': None}

{NITROFURANTOIN}

{'contraindications': '{"CONTRAINDICATIONS Anuria, oliguria, or significant impairment of renal function (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine) are contraindications. Treatment of this type of patient carries an increased risk of toxicity because of impaired excretion of the drug. Because of the possibility of hemolytic anemia due to immature erythrocyte enzyme systems (glutathione instability), the drug is contraindicated in pregnant patients at term (38 to 42 weeks’ gestation), during labor and delivery, or when the onset of labor is imminent. For the same reason, the drug is contraindicated in neonates under one month of age. Nitrofurantoin macrocrystals are contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin. Nitrofurantoin macrocrystals are also contraindicated in those patients with known hypersensitivity to nitrofurantoin."}', 'adverse_reactions': '{"ADVERSE REACTIONS Respiratory CHRONIC, SUBACUTE, OR ACUTE PULMONARY HYPERSENSITIVITY REACTIONS MAY OCCUR. CHRONIC PULMONARY REACTIONS OCCUR GENERALLY IN PATIENTS WHO HAVE RECEIVED CONTINUOUS TREATMENT FOR SIX MONTHS OR LONGER. MALAISE, DYSPNEA ON EXERTION, COUGH, AND ALTERED PULMONARY FUNCTION ARE COMMON MANIFESTATIONS WHICH CAN OCCUR INSIDIOUSLY. RADIOLOGIC AND HISTOLOGIC FINDINGS OF DIFFUSE INTERSTITIAL PNEUMONITIS OR FIBROSIS, OR BOTH, ARE ALSO COMMON MANIFESTATIONS OF THE CHRONIC PULMONARY REACTION. FEVER IS RARELY PROMINENT. THE SEVERITY OF CHRONIC PULMONARY REACTIONS AND THEIR DEGREE OF RESOLUTION APPEAR TO BE RELATED TO THE DURATION OF THERAPY AFTER THE FIRST CLINICAL SIGNS APPEAR. PULMONARY FUNCTION MAY BE IMPAIRED PERMANENTLY, EVEN AFTER CESSATION OF THERAPY. THE RISK IS GREATER WHEN CHRONIC PULMONARY REACTIONS ARE NOT RECOGNIZED EARLY. In subacute pulmonary reactions, fever and eosinophilia occur less often than in the acute form. Upon cessation of therapy, recovery may require several months. If the symptoms are not recognized as being drug-related and nitrofurantoin therapy is not stopped, the symptoms may become more severe. Acute pulmonary reactions are commonly manifested by fever, chills, cough, chest pain, dyspnea, pulmonary infiltration with consolidation or pleural effusion on x-ray, and eosinophilia. Acute reactions usually occur within the first week of treatment and are reversible with cessation of therapy. Resolution often is dramatic (see WARNINGS ). Changes in EKG (e.g., non-specific ST/T wave changes, bundle branch block) have been reported in association with pulmonary reactions. Cyanosis has been reported rarely. Hepatic Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely (see WARNINGS ). Neurologic Peripheral neuropathy, which may become severe or irreversible, has occurred. Fatalities have been reported. Conditions such as renal impairment (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating diseases may increase the possibility of peripheral neuropathy (see WARNINGS ). Asthenia, vertigo, nystagmus, dizziness, headache, and drowsiness also have been reported with the use of nitrofurantoin. Benign intracranial hypertension (pseudotumor cerebri), confusion, depression, optic neuritis, and psychotic reactions have been reported rarely. Bulging fontanels, as a sign of benign intracranial hypertension in infants, have been reported rarely. Dermatologic Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson syndrome) have been reported rarely. Transient alopecia also has been reported. Allergic A lupus-like syndrome associated with pulmonary reactions to nitrofurantoin has been reported. Also, angioedema; maculopapular, erythematous, or eczematous eruptions; pruritus; urticaria; anaphylaxis; arthralgia; myalgia; drug fever; chills; and vasculitis (sometimes associated with pulmonary reactions) have been reported. Hypersensitivity reactions represent the most frequent spontaneously-reported adverse events in worldwide postmarketing experience with nitrofurantoin formulations. Gastrointestinal Nausea, emesis, and anorexia occur most often. Abdominal pain and diarrhea are less common gastrointestinal reactions. These dose-related reactions can be minimized by reduction of dosage. Sialadenitis and pancreatitis have been reported. There have been sporadic reports of pseudomembranous colitis with the use of nitrofurantoin. The onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment (see WARNINGS ). Hematologic Cyanosis secondary to methemoglobinemia has been reported rarely. Miscellaneous As with other antimicrobial agents, superinfections caused by resistant organisms, e.g., Pseudomonas species or Candida species, can occur. Laboratory Adverse Events The following laboratory adverse events have been reported with the use of nitrofurantoin: increased AST (SGOT), increased ALT (SGPT), decreased hemoglobin, increased serum phosphorus, eosinophilia, glucose-6-phosphate dehydrogenase deficiency anemia (see WARNINGS ), agranulocytosis, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia, megaloblastic anemia. In most cases, these hematologic abnormalities resolved following cessation of therapy. Aplastic anemia has been reported rarely."}', 'drug_interactions': '{"Drug Interactions Antacids containing magnesium trisilicate, when administered concomitantly with nitrofurantoin, reduce both the rate and extent of absorption. The mechanism for this interaction probably is adsorption of nitrofurantoin onto the surface of magnesium trisilicate. Uricosuric drugs, such as probenecid and sulfinpyrazone, can inhibit renal tubular secretion of nitrofurantoin. The resulting increase in nitrofurantoin serum levels may increase toxicity, and the decreased urinary levels could lessen its efficacy as a urinary tract antibacterial."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Nitrofurantoin Capsules USP (Macrocrystals) are specifically indicated for the treatment of urinary tract infections when due to susceptible strains of Escherichia coli , enterococci, Staphylococcus aureus , and certain susceptible strains of Klebsiella and Enterobacter species. Nitrofurantoin is not indicated for the treatment of pyelonephritis or perinephric abscesses. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Nitrofurantoin Capsules USP (Macrocrystals) and other antibacterial drugs, Nitrofurantoin Capsules USP (Macrocrystals) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Nitrofurantoins lack the broader tissue distribution of other therapeutic agents approved for urinary tract infections. Consequently, many patients who are treated with Nitrofurantoin Capsules USP (Macrocrystals) are predisposed to persistence or reappearance of bacteriuria. Urine specimens for culture and susceptibility testing should be obtained before and after completion of therapy. If persistence or reappearance of bacteriuria occurs after treatment with Nitrofurantoin Capsules USP (Macrocrystals), other therapeutic agents with broader tissue distribution should be selected. In considering the use of Nitrofurantoin Capsules USP (Macrocrystals), lower eradication rates should be balanced against the increased potential for systemic toxicity and for the development of antimicrobial resistance when agents with broader tissue distribution are utilized."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Occasional incidents of acute overdosage of nitrofurantoin macrocrystals have not resulted in any specific symptoms other than vomiting. Induction of emesis is recommended. There is no specific antidote, but a high fluid intake should be maintained to promote urinary excretion of the drug. It is dialyzable."}', 'active_flag': 'Y', 'generic_name': '{"NITROFURANTOIN MACROCRYSTALS"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Pulmonary Reactions ACUTE, SUBACUTE, OR CHRONIC PULMONARY REACTIONS HAVE BEEN OBSERVED IN PATIENTS TREATED WITH NITROFURANTOIN. IF THESE REACTIONS OCCUR, NITROFURANTOIN MACROCRYSTALS SHOULD BE DISCONTINUED AND APPROPRIATE MEASURES TAKEN. REPORTS HAVE CITED PULMONARY REACTIONS AS A CONTRIBUTING CAUSE OF DEATH. CHRONIC PULMONARY REACTIONS (DIFFUSE INTERSTITIAL PNEUMONITIS OR PULMONARY FIBROSIS, OR BOTH) CAN DEVELOP INSIDIOUSLY. THESE REACTIONS OCCUR RARELY AND GENERALLY IN PATIENTS RECEIVING THERAPY FOR SIX MONTHS OR LONGER. CLOSE MONITORING OF THE PULMONARY CONDITION OF PATIENTS RECEIVING LONG-TERM THERAPY IS WARRANTED AND REQUIRES THAT THE BENEFITS OF THERAPY BE WEIGHED AGAINST POTENTIAL RISKS (SEE ADVERSE REACTIONS, Respiratory ). Hepatotoxicity Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely. Fatalities have been reported. The onset of chronic active hepatitis may be insidious, and patients should be monitored periodically for changes in biochemical tests that would indicate liver injury. If hepatitis occurs, the drug should be withdrawn immediately and appropriate measures should be taken. Neuropathy Peripheral neuropathy, which may become severe or irreversible, has occurred. Fatalities have been reported. Conditions such as renal impairment (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating disease may enhance the occurrence of peripheral neuropathy. Patients receiving long-term therapy should be monitored periodically for changes in renal function. Optic neuritis has been reported rarely in postmarketing experience with nitrofurantoin formulations. Hemolytic Anemia Cases of hemolytic anemia of the primaquine-sensitivity type have been induced by nitrofurantoin. Hemolysis appears to be linked to a glucose-6-phosphate dehydrogenase deficiency in the red blood cells of the affected patients. This deficiency is found in 10 percent of Blacks and a small percentage of ethnic groups of Mediterranean and Near-Eastern origin. Hemolysis is an indication for discontinuing nitrofurantoin macrocrystals; hemolysis ceases when the drug is withdrawn. Clostridium difficile -Associated Diarrhea Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including nitrofurantoin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated."}', 'precautions': '{"PRECAUTIONS Information for Patients Patients should be advised to take nitrofurantoin macrocrystals with food to further enhance tolerance and improve drug absorption. Patients should be instructed to complete the full course of therapy; however, they should be advised to contact their physician if any unusual symptoms occur during therapy. Many patients who cannot tolerate microcrystalline nitrofurantoin are able to take nitrofurantoin macrocrystals without nausea. Patients should be advised not to use antacid preparations containing magnesium trisilicate while taking nitrofurantoin macrocrystals. Patients should be counseled that antibacterial drugs including nitrofurantoin macrocrystals should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When nitrofurantoin macrocrystals are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by nitrofurantoin macrocrystals or other antibacterial drugs in the future. Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible. General Prescribing nitrofurantoin macrocrystals in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Drug Interactions Antacids containing magnesium trisilicate, when administered concomitantly with nitrofurantoin, reduce both the rate and extent of absorption. The mechanism for this interaction probably is adsorption of nitrofurantoin onto the surface of magnesium trisilicate. Uricosuric drugs, such as probenecid and sulfinpyrazone, can inhibit renal tubular secretion of nitrofurantoin. The resulting increase in nitrofurantoin serum levels may increase toxicity, and the decreased urinary levels could lessen its efficacy as a urinary tract antibacterial. Drug/Laboratory Test Interactions As a result of the presence of nitrofurantoin, a false-positive reaction for glucose in the urine may occur. This has been observed with Benedict\'s and Fehling\'s solutions but not with the glucose enzymatic test. Carcinogenesis, Mutagenesis, Impairment of Fertility Nitrofurantoin was not carcinogenic when fed to female Holtzman rats for 44.5 weeks or to female Sprague-Dawley rats for 75 weeks. Two chronic rodent bioassays utilizing male and female Sprague-Dawley rats and two chronic bioassays in Swiss mice and in BDF 1 mice revealed no evidence of carcinogenicity. Nitrofurantoin presented evidence of carcinogenic activity in female B6C3F 1 mice as shown by increased incidences of tubular adenomas, benign mixed tumors, and granulosa cell tumors of the ovary. In male F344/N rats, there were increased incidences of uncommon kidney tubular cell neoplasms, osteosarcomas of the bone, and neoplasms of the subcutaneous tissue. In one study involving subcutaneous administration of 75 mg/kg nitrofurantoin to pregnant female mice, lung papillary adenomas of unknown significance were observed in the F1 generation. Nitrofurantoin has been shown to induce point mutations in certain strains of Salmonella typhimurium and forward mutations in L5178Y mouse lymphoma cells. Nitrofurantoin induced increased numbers of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells but not in human cells in culture. Results of the sex-linked recessive lethal assay in Drosophila were negative after administration of nitrofurantoin by feeding or by injection. Nitrofurantoin did not induce heritable mutation in the rodent models examined. The significance of the carcinogenicity and mutagenicity findings relative to the therapeutic use of nitrofurantoin in humans is unknown. The administration of high doses of nitrofurantoin to rats causes temporary spermatogenic arrest; this is reversible on discontinuing the drug. Doses of 10 mg/kg/day or greater in healthy human males may, in certain unpredictable instances, produce a slight to moderate spermatogenic arrest with a decrease in sperm count. Pregnancy Teratogenic Effects Pregnancy Category B Several reproduction studies have been performed in rabbits and rats at doses up to six times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to nitrofurantoin. In a single published study conducted in mice at 68 times the human dose (based on mg/kg administered to the dam), growth retardation and a low incidence of minor and common malformations were observed. However, at 25 times the human dose, fetal malformations were not observed; the relevance of these findings to humans is uncertain. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Non-Teratogenic Effects Nitrofurantoin has been shown in one published transplacental carcinogenicity study to induce lung papillary adenomas in the F1 generation mice at doses 19 times the human dose on a mg/kg basis. The relationship of this finding to potential human carcinogenesis is presently unknown. Because of the uncertainty regarding the human implications of these animal data, this drug should be used during pregnancy only if clearly needed. Labor and Delivery See CONTRAINDICATIONS . Nursing Mothers Nitrofurantoin has been detected in human breast milk in trace amounts. Because of the potential for serious adverse reactions from nitrofurantoin in nursing infants under one month of age, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother (see CONTRAINDICATIONS ). Pediatric Use Nitrofurantoin macrocrystals are contraindicated in infants below the age of one month (see CONTRAINDICATIONS ). Geriatric Use Clinical studies of nitrofurantoin macrocrystals did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Spontaneous reports suggest a higher proportion of pulmonary reactions, including fatalities, in elderly patients; these differences appear to be related to the higher proportion of elderly patients receiving long-term nitrofurantoin therapy. As in younger patients, chronic pulmonary reactions generally are observed in patients receiving therapy for six months or longer (see WARNINGS ). Spontaneous reports also suggest an increased proportion of severe hepatic reactions, including fatalities, in elderly patients (see WARNINGS ). In general, the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy should be considered when prescribing nitrofurantoin macrocrystals. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Anuria, oliguria, or significant impairment of renal function (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine) are contraindications (see CONTRAINDICATIONS ). Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function."}', 'information_for_patients': '{"Information for Patients Patients should be advised to take nitrofurantoin macrocrystals with food to further enhance tolerance and improve drug absorption. Patients should be instructed to complete the full course of therapy; however, they should be advised to contact their physician if any unusual symptoms occur during therapy. Many patients who cannot tolerate microcrystalline nitrofurantoin are able to take nitrofurantoin macrocrystals without nausea. Patients should be advised not to use antacid preparations containing magnesium trisilicate while taking nitrofurantoin macrocrystals. Patients should be counseled that antibacterial drugs including nitrofurantoin macrocrystals should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When nitrofurantoin macrocrystals are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by nitrofurantoin macrocrystals or other antibacterial drugs in the future. Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible."}', 'pregnancy': '{"Pregnancy Teratogenic Effects Pregnancy Category B Several reproduction studies have been performed in rabbits and rats at doses up to six times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to nitrofurantoin. In a single published study conducted in mice at 68 times the human dose (based on mg/kg administered to the dam), growth retardation and a low incidence of minor and common malformations were observed. However, at 25 times the human dose, fetal malformations were not observed; the relevance of these findings to humans is uncertain. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Non-Teratogenic Effects Nitrofurantoin has been shown in one published transplacental carcinogenicity study to induce lung papillary adenomas in the F1 generation mice at doses 19 times the human dose on a mg/kg basis. The relationship of this finding to potential human carcinogenesis is presently unknown. Because of the uncertainty regarding the human implications of these animal data, this drug should be used during pregnancy only if clearly needed."}', 'pediatric_use': '{"Pediatric Use Nitrofurantoin macrocrystals are contraindicated in infants below the age of one month (see CONTRAINDICATIONS )."}', 'geriatric_use': '{"Geriatric Use Clinical studies of nitrofurantoin macrocrystals did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Spontaneous reports suggest a higher proportion of pulmonary reactions, including fatalities, in elderly patients; these differences appear to be related to the higher proportion of elderly patients receiving long-term nitrofurantoin therapy. As in younger patients, chronic pulmonary reactions generally are observed in patients receiving therapy for six months or longer (see WARNINGS ). Spontaneous reports also suggest an increased proportion of severe hepatic reactions, including fatalities, in elderly patients (see WARNINGS ). In general, the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy should be considered when prescribing nitrofurantoin macrocrystals. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Anuria, oliguria, or significant impairment of renal function (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine) are contraindications (see CONTRAINDICATIONS ). Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function."}'}

{"ISOPROPYL ALCOHOL"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses first aid to help prevent the risk of infection in minor cuts scrapes burns"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"ISOPROPYL ALCOHOL"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings For external use only. If taken internally serioun gastric disturbances will result. Flammable, keep away from fire or flame, heat, spark, electrical."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"FEXOFENADINE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses temporarily relieves these symptoms due to hay fever or other upper respiratory allergies: • runny nose • itchy, watery eyes • sneezing • itching of the nose or throat"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"FEXOFENADINE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if an allergic reaction to this product occurs. Seek medical help right away."}', 'do_not_use': '{"Do not use if you have ever had an allergic reaction to this product or any of its ingredients."}', 'when_using': '{"When using this product • do not take more than directed • do not take at the same time as aluminum or magnesium antacids • do not take with fruit juices (see Directions)"}', 'warnings': '{"Warnings Do not use if you have ever had an allergic reaction to this product or any of its ingredients. Ask a doctor before use if you have kidney disease. Your doctor should determine if you need a different dose. When using this product • do not take more than directed • do not take at the same time as aluminum or magnesium antacids • do not take with fruit juices (see Directions) Stop use and ask a doctor if an allergic reaction to this product occurs. Seek medical help right away. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away (1-800-222-1222)."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{LORATADINE,"PSEUDOEPHEDRINE SULFATE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses • temporarily relieves these symptoms due to hay fever or other upper respiratory allergies: • sneezing • itchy, watery eyes • runny nose • itching of the nose or throat • temporarily relieves nasal congestion due to the common cold, hay fever or other upper respiratory allergies • reduces swelling of nasal passages • temporarily relieves sinus congestion and pressure • temporarily restores freer breathing through the nose"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"LORATADINE, PSEUDOEPHEDRINE SULFATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if • an allergic reaction to this product occurs. Seek medical help right away. • symptoms do not improve within 7 days or are accompanied by a fever • nervousness, dizziness or sleeplessness occurs"}', 'do_not_use': '{"Do not use • if you have ever had an allergic reaction to this product or any of its ingredients • if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson’s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product."}', 'when_using': '{"When using this product do not take more than directed. Taking more than directed may cause drowsiness."}', 'warnings': '{Warnings}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"ATROPINE SULFATE"}

{'contraindications': '{"4 CONTRAINDICATIONS None. None. (4)"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following adverse reactions have been identified during post-approval use of atropine sulfate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Most of the side effects of atropine are directly related to its antimuscarinic action. Dryness of the mouth, blurred vision, photophobia and tachycardia commonly occur. Anhidrosis can produce heat intolerance. Constipation and difficulty in micturition may occur in elderly patients. Occasional hypersensitivity reactions have been observed, especially skin rashes which in some instances progressed to exfoliation. Most adverse reactions are directly related to atropine’s antimuscarinic action. Dryness of the mouth, blurred vision, photophobia and tachycardia commonly occur with chronic administration of therapeutic doses. (6) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Mexiletine: Decreases rate of mexiletine absorption. (7.1) 7.1 Mexiletine Atropine sulfate injection decreased the rate of mexiletine absorption without altering the relative oral bioavailability; this delay in mexiletine absorption was reversed by the combination of atropine and intravenous metoclopramide during pretreatment for anesthesia."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Atropine sulfate injection is indicated for temporary blockade of severe or life-threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus or muscarinic mushroom poisoning and to treat bradyasystolic cardiac arrest. Atropine is a muscarinic antagonist indicated for temporary blockade of severe or life-threatening muscarinic effects. (1)"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Tachycardia. (5.1) Glaucoma. (5.2) Pyloric obstruction. (5.3) Worsening urinary retention. (5.4) Viscid bronchial plugs. (5.5) 5.1 Tachycardia When the recurrent use of atropine is essential in patients with coronary artery disease, the total dose should be restricted to 2 mg to 3 mg (maximum 0.03 mg/kg to 0.04 mg/kg) to avoid the detrimental effects of atropine-induced tachycardia on myocardial oxygen demand. 5.2 Acute Glaucoma Atropine may precipitate acute glaucoma. 5.3 Pyloric Obstruction Atropine may convert partial organic pyloric stenosis into complete obstruction. 5.4 Complete Urinary Retention Atropine may lead to complete urinary retention in patients with prostatic hypertrophy. 5.5 Viscid Plugs Atropine may cause inspissation of bronchial secretions and formation of viscid plugs in patients with chronic lung disease."}', 'overdosage': '{"10 OVERDOSAGE Excessive dosing may cause palpitation, dilated pupils, difficulty in swallowing, hot dry skin, thirst, dizziness, restlessness, tremor, fatigue and ataxia. Toxic doses lead to restlessness and excitement, hallucinations, delirium and coma. Depression and circulatory collapse occur only with severe intoxication. In such cases, blood pressure declines and death due to respiratory failure may ensue following paralysis and coma. The fatal adult dose of atropine is not known. In pediatric populations, 10 mg or less may be fatal. In the event of toxic overdosage, a short acting barbiturate or diazepam may be given as needed to control marked excitement and convulsions. Large doses for sedation should be avoided because central depressant action may coincide with the depression occurring late in atropine poisoning. Central stimulants are not recommended. Physostigmine, given as an atropine antidote by slow intravenous injection of 1 mg to 4 mg (0.5 mg to 1 mg in pediatric populations), rapidly abolishes delirium and coma caused by large doses of atropine. Since physostigmine is rapidly destroyed, the patient may again lapse into coma after one to two hours, and repeated doses may be required. Artificial respiration with oxygen may be necessary. Ice bags and alcohol sponges help to reduce fever, especially in pediatric populations. Atropine is not removed by dialysis."}', 'active_flag': 'Y', 'generic_name': '{"ATROPINE SULFATE"}', 'route': '{INTRAVENOUS}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': None, 'pregnancy': '{"8.1 Pregnancy Animal reproduction studies have not been conducted with atropine. It also is not known whether atropine can cause fetal harm when given to a pregnant woman or can affect reproduction capacity."}', 'pediatric_use': '{"8.4 Pediatric Use Recommendations for use in pediatric patients are not based on clinical trials."}', 'geriatric_use': '{"8.5 Geriatric Use An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy."}'}

{DIAZEPAM}

{'contraindications': '{"CONTRAINDICATIONS Diazepam is contraindicated in patients with a known hypersensitivity to this drug; acute narrow angle glaucoma; and open angle glaucoma unless patients are receiving appropriate therapy."}', 'adverse_reactions': '{"ADVERSE REACTIONS Side effects most commonly reported were drowsiness, fatigue, and ataxia; venous thrombosis and phlebitis at the site of injection. Other adverse reactions less frequently reported include: CNS: Confusion, depression [including respiratory depression (see WARNINGS; Pediatric Use )], dysarthria, headache, hypoactivity, slurred speech, syncope, tremor, vertigo. G.I.: Constipation, nausea. G.U.: Incontinence, changes in libido, urinary retention. Cardiovascular: Bradycardia, cardiovascular collapse, hypotension. EENT: Blurred vision, diplopia, nystagmus. Skin: Urticaria, skin rash. Other: Hiccups, changes in salivation, neutropenia, jaundice. Paradoxical reactions such as acute hyperexcited states, anxiety, hallucinations, increased muscle spasticity, insomnia, rage, sleep disturbances and stimulation have been reported; should these occur, use of the drug should be discontinued. Minor changes in EEG patterns, usually low-voltage fast activity, have been observed in patients during and after diazepam therapy and are of no known significance. In peroral endoscopic procedures, coughing, depressed respiration, dyspnea, hyperventilation, laryngospasm, and pain in throat or chest have been reported. Because of isolated reports of neutropenia and jaundice, periodic blood counts and liver function tests are advisable during long-term therapy."}', 'drug_interactions': '{"Drug Interactions The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites and opioids interact primarily at mµ receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and monitor patients closely for respiratory depression and sedation. If diazepam is to be combined with other psychotropic agents or anticonvulsant drugs, careful consideration should be given to the pharmacology of the agents to be employed, particularly with known compounds which may potentiate the action of diazepam, such as phenothiazines, narcotics, barbiturates, MAO inhibitors, and other antidepressants. In highly anxious patients with evidence of accompanying depression, particularly those who may have suicidal tendencies, protective measures may be necessary. Diazepam injection has produced hypotension or muscular weakness in some patients particularly when used with narcotics, barbiturates, or alcohol. The clearance of diazepam and certain other benzodiazepines can be delayed in association with cimetidine administration. The clinical significance of this is unclear. Pregnancy: Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as Diazepam injection, during pregnancy. Healthcare providers are encouraged to recommend that pregnant patient taking diazepam injection enroll in the North American NAAED Pregnancy Registry by calling 1-888- 233-2334 or online at http://www.aedpregnancyregistry.org/. Risk Summary Neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal (see WARNINGS: Neonatal Sedation and Withdrawal Syndrome, and PRECAUTIONS: Clinical Considerations ). Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects (see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in neonates. Monitor neonates exposed to diazepam injection during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems Monitor neonates exposed to diazepam injection during pregnancy for signs of withdrawal. Manage these neonates accordingly (see WARNINGS: Neonatal Sedation and Withdrawal Syndrome ). Data Human Data Published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol, tobacco and other medications, have not confirmed these findings. Animal Data Diazepam has been shown to produce increased incidences of fetal malformations in mice and hamsters when given orally at single doses of 100 mg/kg or greater (approximately 20 times the maximum recommended adult dose [0.4 mg/kg/day] or greater on a mg/m2 basis). Cleft palate and exencephaly are the most common and consistently reported malformations produced in these species by administration of high, maternally-toxic doses of diazepam during organogenesis. In published animal studies, administration of benzodiazepines or other drugs that enhance GABAergic inhibition to neonatal rats has been reported to result in widespread apoptotic neurodegeneration in the developing brain at plasma concentrations relevant for seizure control in humans. The window of vulnerability to these changes in rats (postnatal days 0-14) includes a period of brain development that takes place during the third trimester of pregnancy in humans. Nursing Mothers: Risk Summary Diazepam is present in breastmilk. There are reports of sedation, poor feeding and poor weight gain in infants exposed to benzodiazepines through breast milk. There are no data on the effects of diazepam on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother\'s clinical need for diazepam injection and any potential adverse effects on the breastfed infant from diazepam injection or from the underlying maternal condition. Clinical Considerations Infants exposed to diazepam injection through breast milk should be monitored for sedation, poor feeding and poor weight gain."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Diazepam is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. In acute alcohol withdrawal, diazepam may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis. As an adjunct prior to endoscopic procedures if apprehension, anxiety or acute stress reactions are present, and to diminish the patient\'s recall of the procedures (see WARNINGS ). Diazepam is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma); spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia); athetosis; stiff-man syndrome; and tetanus. Diazepam injection is a useful adjunct in status epilepticus. Diazepam is a useful premedication (the intramuscular route is preferred) for relief of anxiety and tension in patients who are to undergo surgical procedures. Intravenously, prior to cardioversion for the relief of anxiety and tension and to diminish the patient\'s recall of the procedure."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory depression and coma. Overdosage of benzodiazepines in combination with other CNS depressants (including alcohol and opioids) may be fatal (see Warnings: Abuse, Misuse, and Addiction ). Markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raise the concern that additional drugs and/or alcohol are involved in the overdosage. In managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway maintenance. Flumazenil, a specific benzodiazepine receptor antagonist indicated for the complete or partial reversal of the sedative effects of benzodiazepines in the management of benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures, particularly in the context of mixed overdosage with drugs that increase seizure risk (e.g., tricyclic and tetracyclic antidepressants) and in patients with long-term benzodiazepine use and physical dependency. The risk of withdrawal seizures with flumazenil use may be increased in patients with epilepsy. Flumazenil is contraindicated in patients who have received a benzodiazepine for control of a potentially life-threatening condition (e.g., status epilepticus). If the decision is made to use flumazenil, it should be used as an adjunct to, not as a substitute for, supportive management of benzodiazepine overdosage. See the flumazenil injection Prescribing Information. Consider contacting a poison center (1-800-222-1222), poisoncontrol.org, or a medical toxicologist for additional overdosage management recommendations."}', 'active_flag': 'Y', 'generic_name': '{DIAZEPAM}', 'route': '{INTRAMUSCULAR,INTRAVENOUS}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Risks from Concomitant Use with Opioids Concomitant use of benzodiazepines, including diazepam, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of benzodiazepines and opioids in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe diazepam concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. Advise both patients and caregivers about the risks of respiratory depression and sedation when diazepam is used with opioids (see PRECAUTIONS; Drug Interactions ). Abuse, Misuse, and Addiction The use of benzodiazepines, including diazepam, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death (see DRUG ABUSE AND DEPENDENCE: Abuse ). Before prescribing diazepam and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction. Use of diazepam, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of diazepam along with monitoring for signs and symptoms of abuse, misuse, and addiction. Do not exceed the recommended dosing frequency; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. If a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate. Dependence and Withdrawal Reactions After Use of Diazepam More Frequently Than Recommended For patients using diazepam more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue diazepam (a patient-specific plan should be used to taper the dose). Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use. Acute Withdrawal Reactions The continued use of benzodiazepines may lead to clinically significant physical dependence. Although diazepam is indicated only for intermittent use (see INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION ), if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction of diazepam, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) (see DRUG ABUSE AND DEPENDENCE, Dependence ). Protracted Withdrawal Syndrome In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see DRUG ABUSE AND DEPENDENCE: Dependence ). When used intravenously, the following procedures should be undertaken to reduce the possibility of venous thrombosis, phlebitis, local irritation, swelling, and, rarely, vascular impairment; the solution should be injected slowly, taking at least one minute for each 5 mg (1 mL) given except for treatment of status epilepticus in children (see DOSAGE AND ADMINISTRATION); do not use small veins, such as those on the dorsum of the hand or wrist; extreme care should be taken to avoid intra-arterial administration or extravasation. Do not mix or dilute diazepam injection with other solutions or drugs in syringe or infusion container. If it is not feasible to administer diazepam directly intravenous, it may be injected slowly through the infusion tubing as close as possible to the vein insertion. Extreme care must be used in administering diazepam injection, particularly by the intravenous route, to the elderly, to very ill patients, and to those with limited pulmonary reserve because of the possibility that apnea and/or cardiac arrest may occur. Concomitant use of barbiturates, alcohol or other central nervous system depressants increases depression with increased risk of apnea. Resuscitative equipment including that necessary to support respiration should be readily available. When diazepam is used with a narcotic analgesic, the dosage of the narcotic should be reduced by at least one-third and administered in small increments. In some cases the use of a narcotic may not be necessary. Diazepam injection should not be administered to patients in shock, coma, or in acute alcoholic intoxication with depression of vital signs. As is true of most CNS-acting drugs, patients receiving diazepam should be cautioned against engaging in hazardous occupations requiring complete mental alertness, such as operating machinery or driving a motor vehicle. Tonic status epilepticus has been precipitated in patients treated with intravenous diazepam for petit mal status or petit mal variant status. Neonatal Sedation and Withdrawal Syndrome Use of diazepam injection late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate (see PRECAUTIONS: Pregnancy ). Monitor neonates exposed to diazepam injection during pregnancy or labor for signs of sedation and monitor neonates exposed to diazepam injection during pregnancy for signs of withdrawal; manage these neonates accordingly. Pediatric Use: Efficacy and safety of parenteral diazepam has not been established in the neonate (30 days or less of age). Prolonged central nervous system depression has been observed in neonates, apparently due to inability to biotransform diazepam into inactive metabolites. In pediatric use for the treatment of status epilepticus, in order to obtain maximal clinical effect with the minimum amount of drug and thus to reduce the risk of hazardous side effects, such as apnea or prolonged periods of somnolence, it is recommended that the drug be given as a slow intravenous push over 1 minute (see DOSAGE AND ADMINISTRATION ). The safety and tolerability of the recommended dosage regimen is supported by a randomized, double-blind study that included 162 pediatric patients ages 3 months to 17 years who received intravenous diazepam for the treatment of status epilepticus. In this study, 16% of pediatric patients who received diazepam experienced severe or life-threatening respiratory depression. Benzyl alcohol has been reported to be associated with a fatal gasping syndrome in premature infants."}', 'precautions': '{"PRECAUTIONS General: Although seizures may be brought under control promptly, a significant proportion of patients experience a return to seizure activity, presumably due to the short-lived effect of diazepam after intravenous administration. The physician should be prepared to readminister the drug. However, diazepam is not recommended for maintenance, and once seizures are brought under control, consideration should be given to the administration of agents useful in longer term control of seizures. The usual precautions in treating patients with impaired hepatic function should be observed. Metabolites of diazepam are excreted by the kidney; to avoid their excess accumulation, caution should be exercised in the administration to patients with compromised kidney function. Since an increase in cough reflex and laryngospasm may occur with peroral endoscopic procedures, the use of a topical anesthetic agent, and the availability of necessary countermeasures are recommended. Propylene glycol toxicity has been reported in patients treated with diazepam injection at doses significantly greater than recommended. In these cases, diazepam was being used to treat alcohol withdrawal symptoms at doses greater than 900 mg/day. Propylene glycol toxicity is associated with an anion gap metabolic acidosis, serum hyperosmolality, and increased lactate. Propylene glycol toxicity can cause acute tubular necrosis (which can progress to multi-organ failure), mental status changes, hypotension, seizures, and cardiac arrhythmias. Patients at high risk for propylene glycol toxicity include those with renal dysfunction, hepatic dysfunction, impaired alcohol dehydrogenase enzymes, or other comorbidities (such as a history of alcoholism). Until additional information is available, diazepam injection is not recommended for obstetrical use. Lower doses (usually 2 mg to 5 mg) should be used for elderly and debilitated patients. Risks from Concomitant Use with Opioids Advise both patients and caregivers about the risks of potentially fatal respiratory depression and sedation when diazepam is used with opioids and not to use such drugs concomitantly unless supervised by a health care provider. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined (see WARNINGS: Risks from Concomitant Use with Opioids and PRECAUTIONS: Drug Interactions ). Abuse, Misuse, and Addiction Inform patients that the use of diazepam more frequently than recommended, even at recommended dosages, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose and death, especially when used in combination with other medications (e.g., opioid analgesics), alcohol, and/or illicit substances. Inform patients about the signs and symptoms of benzodiazepine abuse, misuse, and addiction; to seek medical help if they develop these signs and/or symptoms; and on the proper disposal of unused drug (see WARNINGS and DRUG ABUSE AND DEPENDENCE ). Withdrawal Reactions Inform patients that use of diazepam more frequently than recommended may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction of diazepam may precipitate acute withdrawal reactions, which can be life-threatening. Inform patients that in some cases, patients taking benzodiazepines have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see WARNINGS and DRUG ABUSE AND DEPENDENCE ). Pregnancy Advise pregnant females that use of diazepam injection late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in newborns (see WARNINGS: Neonatal Sedation and Withdrawal Syndrome and PRECAUTIONS: Pregnancy ). Instruct patients to inform their healthcare provider if they are pregnant. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to diazepam injection during pregnancy (see Precautions, Pregnancy ). Nursing Advise patients that breastfeeding is not recommended during treatment with diazepam injection (see PRECAUTIONS: Nursing Mothers ). Drug Interactions The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites and opioids interact primarily at mµ receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and monitor patients closely for respiratory depression and sedation. If diazepam is to be combined with other psychotropic agents or anticonvulsant drugs, careful consideration should be given to the pharmacology of the agents to be employed, particularly with known compounds which may potentiate the action of diazepam, such as phenothiazines, narcotics, barbiturates, MAO inhibitors, and other antidepressants. In highly anxious patients with evidence of accompanying depression, particularly those who may have suicidal tendencies, protective measures may be necessary. Diazepam injection has produced hypotension or muscular weakness in some patients particularly when used with narcotics, barbiturates, or alcohol. The clearance of diazepam and certain other benzodiazepines can be delayed in association with cimetidine administration. The clinical significance of this is unclear. Pregnancy: Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as Diazepam injection, during pregnancy. Healthcare providers are encouraged to recommend that pregnant patient taking diazepam injection enroll in the North American NAAED Pregnancy Registry by calling 1-888- 233-2334 or online at http://www.aedpregnancyregistry.org/. Risk Summary Neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal (see WARNINGS: Neonatal Sedation and Withdrawal Syndrome, and PRECAUTIONS: Clinical Considerations ). Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects (see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in neonates. Monitor neonates exposed to diazepam injection during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems Monitor neonates exposed to diazepam injection during pregnancy for signs of withdrawal. Manage these neonates accordingly (see WARNINGS: Neonatal Sedation and Withdrawal Syndrome ). Data Human Data Published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol, tobacco and other medications, have not confirmed these findings. Animal Data Diazepam has been shown to produce increased incidences of fetal malformations in mice and hamsters when given orally at single doses of 100 mg/kg or greater (approximately 20 times the maximum recommended adult dose [0.4 mg/kg/day] or greater on a mg/m2 basis). Cleft palate and exencephaly are the most common and consistently reported malformations produced in these species by administration of high, maternally-toxic doses of diazepam during organogenesis. In published animal studies, administration of benzodiazepines or other drugs that enhance GABAergic inhibition to neonatal rats has been reported to result in widespread apoptotic neurodegeneration in the developing brain at plasma concentrations relevant for seizure control in humans. The window of vulnerability to these changes in rats (postnatal days 0-14) includes a period of brain development that takes place during the third trimester of pregnancy in humans. Nursing Mothers: Risk Summary Diazepam is present in breastmilk. There are reports of sedation, poor feeding and poor weight gain in infants exposed to benzodiazepines through breast milk. There are no data on the effects of diazepam on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother\'s clinical need for diazepam injection and any potential adverse effects on the breastfed infant from diazepam injection or from the underlying maternal condition. Clinical Considerations Infants exposed to diazepam injection through breast milk should be monitored for sedation, poor feeding and poor weight gain."}', 'information_for_patients': None, 'pregnancy': '{"Pregnancy Advise pregnant females that use of diazepam injection late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in newborns (see WARNINGS: Neonatal Sedation and Withdrawal Syndrome and PRECAUTIONS: Pregnancy ). Instruct patients to inform their healthcare provider if they are pregnant. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to diazepam injection during pregnancy (see Precautions, Pregnancy )."}', 'pediatric_use': '{"Pediatric Use: Efficacy and safety of parenteral diazepam has not been established in the neonate (30 days or less of age). Prolonged central nervous system depression has been observed in neonates, apparently due to inability to biotransform diazepam into inactive metabolites. In pediatric use for the treatment of status epilepticus, in order to obtain maximal clinical effect with the minimum amount of drug and thus to reduce the risk of hazardous side effects, such as apnea or prolonged periods of somnolence, it is recommended that the drug be given as a slow intravenous push over 1 minute (see DOSAGE AND ADMINISTRATION ). The safety and tolerability of the recommended dosage regimen is supported by a randomized, double-blind study that included 162 pediatric patients ages 3 months to 17 years who received intravenous diazepam for the treatment of status epilepticus. In this study, 16% of pediatric patients who received diazepam experienced severe or life-threatening respiratory depression. Benzyl alcohol has been reported to be associated with a fatal gasping syndrome in premature infants."}', 'geriatric_use': None}

{ALCOHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses For handwashing to decrease bacteria on the skin"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{ALCOHOL}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': '{"Do not use In eyes On deep cuts or puncture wounds"}', 'when_using': '{"When using this product If in eyes, rinse promptly and thoroughly with water Discontinue use if irritation and redness develop"}', 'warnings': '{"Warnings For external use only FLAMMABLE, keep away from fire or flame, heat, sparks and sources of static discharge Do not use In eyes On deep cuts or puncture wounds When using this product If in eyes, rinse promptly and thoroughly with water Discontinue use if irritation and redness develop Stop use and ask a doctor if eye or skin irritation or redness occurs for more than 72 hours Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"SERTRALINE HYDROCHLORIDE"}

{'contraindications': '{"4 CONTRAINDICATIONS Sertraline hydrochloride tablets are contraindicated in patients: Taking, or within 14 days of stopping, MAOIs, (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [See Warnings and Precautions (5.2) , Drug Interactions (7.1) ] . Taking pimozide [See Drug Interactions (7.1) ] . With known hypersensitivity to sertraline (e.g., anaphylaxis, angioedema) [See Adverse Reactions (6.1 , 6.2 )]. Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping MAOIs ( 4 , 7.1 ) Concomitant use of pimozide ( 4, 7.1 ) Known hypersensitivity to sertraline or excipients ( 4 , 5.4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following adverse reactions are described in more detail in other sections of the prescribing information: Hypersensitivity reactions to sertraline [See Contraindications (4) ] QTc prolongation and ventricular arrhythmias when taken with pimozide [See Contraindications (4) , Clinical Pharmacology (12.2) ] Suicidal thoughts and behaviors [See Warnings and Precautions (5.1) ] Serotonin syndrome [See Contraindications (4) , Warnings and Precautions (5.2) , Drug Interactions (7.1) ] Increased risk of bleeding [See Warnings and Precautions (5.3) ] Activation of mania/hypomania [See Warnings and Precautions (5.4) ] Discontinuation syndrome [See Warnings and Precautions (5.5) ] Seizures [See Warnings and Precautions (5.6) ] Angle-closure glaucoma [See Warnings and Precautions (5.7) ] Hyponatremia [See Warnings and Precautions (5.8) ] Sexual Dysfunction [See Warnings and Precautions (5.11) ] Most common adverse reactions (≥5% and twice placebo) in pooled placebo-controlled MDD, OCD, PD, PTSD, SAD and PMDD clinical trials were nausea, diarrhea/loose stool, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx LLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below are from randomized, double-blind, placebo-controlled trials of sertraline hydrochloride (mostly 50 mg to 200 mg per day) in 3066 adults diagnosed with MDD, OCD, PD, PTSD, SAD, and PMDD. These 3066 patients exposed to sertraline hydrochloride for 8 to12 weeks represent 568 patient-years of exposure. The mean age was 40 years; 57% were females and 43% were males. The most common adverse reactions (≥5% and twice placebo) in all pooled placebo-controlled clinical trials of all sertraline hydrochloride-treated patients with MDD, OCD, PD, PTSD, SAD and PMDD were nausea, diarrhea/loose stool, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido (see Table 3). The following are the most common adverse reactions in trials of sertraline hydrochloride (≥5% and twice placebo) by indication that were not mentioned previously. MDD: somnolence; OCD: insomnia, agitation; PD: constipation, agitation; PTSD: fatigue; PMDD: somnolence, dry mouth, dizziness, fatigue, and abdominal pain; SAD: insomnia, dizziness, fatigue, dry mouth, malaise. Table 3: Common Adverse Reactions in Pooled Placebo-Controlled Trials in Adults with MDD, OCD, PD, PTSD, SAD, and PMDD* (1) Denominator used was for male patients only (n=1316 sertraline hydrochloride; n=973 placebo). * Adverse reactions that occurred greater than 2% in sertraline hydrochloride-treated patients and at least 2% greater in sertraline hydrochloride-treated patients than placebo-treated patients. Sertraline Hydrochloride (N=3066) Placebo (N=2293) Cardiac disorders Palpitations 4% 2% Eye disorders Visual impairment 4% 2% Gastrointestinal disorders Nausea 26% 12% Diarrhea/Loose stools 20% 10% Dry mouth 14% 9% Dyspepsia 8% 4% Constipation 6% 4% Vomiting 4% 1% General disorders and administration site conditions Fatigue 12% 8% Metabolism and nutrition disorders Decreased appetite 7% 2% Nervous system disorders Dizziness 12% 8% Somnolence 11% 6% Tremor 9% 2% Psychiatric Disorders Insomnia 20% 13% Agitation 8% 5% Libido decreased 6% 2% Reproductive system and breast disorders Ejaculation failure (1) 8% 1% Erectile dysfunction (1) 4% 1% Ejaculation disorder (1) 3% 0% Male sexual dysfunction (1) 2% 0% Skin and subcutaneous tissue disorders Hyperhidrosis 7% 3% Adverse Reactions Leading to Discontinuation in Placebo-Controlled Clinical Trials In all placebo-controlled studies in patients with MDD, OCD, PD, PTSD, SAD and PMDD, 368 (12%) of the 3066 patients who received sertraline hydrochloride discontinued treatment due to an adverse reaction, compared with 93 (4%) of the 2293 placebo-treated patients. In placebo-controlled studies, the following were the common adverse reactions leading to discontinuation in sertraline hydrochloride-treated patients: MDD, OCD, PD, PTSD, SAD and PMDD: nausea (3%), diarrhea (2%), agitation (2%), and insomnia (2%). MDD (>2% and twice placebo): decreased appetite, dizziness, fatigue, headache, somnolence, tremor, and vomiting. OCD: somnolence. PD: nervousness and somnolence. Male and Female Sexual Dysfunction Although changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of SSRI treatment. However, reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance and satisfaction are difficult to obtain, in part because patients and healthcare providers may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in labeling may underestimate their actual incidence. Table 4 below displays the incidence of sexual adverse reactions reported by at least 2% of sertraline hydrochloride-treated patients and twice placebo from pooled placebo-controlled trials. For men and all indications, the most common adverse reactions (>2% and twice placebo) included: ejaculation failure, decreased libido, erectile dysfunction, ejaculation disorder, and male sexual dysfunction. For women, the most common adverse reaction (≥2% and twice placebo) was decreased libido. Table 4: Most Common Sexual Adverse Reactions (≥2% and twice placebo) in Men or Women from Sertraline Hydrochloride Pooled Controlled Trials in Adults with MDD, OCD, PD, PTSD, SAD, and PMDD Sertraline Hydrochloride Placebo Men only (N=1316) (N=973) Ejaculation failure 8% 1% Libido decreased 7% 2% Erectile dysfunction 4% 1% Ejaculation disorder 3% 0% Male sexual dysfunction 2% 0% Women only (N=1750) (N=1320) Libido decreased 4% 2% Adverse Reactions in Pediatric Patients In 281 pediatric patients treated with sertraline hydrochloride in placebo-controlled studies, the overall profile of adverse reactions was generally similar to that seen in adult studies. Adverse reactions that do not appear in Table 3 (most common adverse reactions in adults) yet were reported in at least 2% of pediatric patients and at a rate of at least twice the placebo rate include fever, hyperkinesia, urinary incontinence, aggression, epistaxis, purpura, arthralgia, decreased weight, muscle twitching, and anxiety. Other Adverse Reactions Observed During the Premarketing Evaluation of Sertraline Hydrochloride Other infrequent adverse reactions, not described elsewhere in the prescribing information, occurring at an incidence of < 2% in patients treated with sertraline hydrochloride were: Cardiac disorders – tachycardia Ear and labyrinth disorders – tinnitus Endocrine disorders - hypothyroidism Eye disorders - mydriasis, blurred vision Gastrointestinal disorders - hematochezia, melena, rectal hemorrhage General disorders and administration site conditions - edema, gait disturbance, irritability, pyrexia Hepatobiliary disorders - elevated liver enzymes Immune system disorders - anaphylaxis Metabolism and nutrition disorders - diabetes mellitus, hypercholesterolemia, hypoglycemia, increased appetite Musculoskeletal and connective tissue disorders – arthralgia, muscle spasms, tightness, or twitching Nervous system disorders - ataxia, coma, convulsion, decreased alertness, hypoesthesia, lethargy, psychomotor hyperactivity, syncope Psychiatric disorders - aggression, bruxism, confusional state, euphoric mood, hallucination Renal and urinary disorders - hematuria Reproductive system and breast disorders - galactorrhea, priapism, vaginal hemorrhage Respiratory, thoracic and mediastinal disorders - bronchospasm, epistaxis, yawning Skin and subcutaneous tissue disorders - alopecia; cold sweat; dermatitis; dermatitis bullous; pruritus; purpura; erythematous, follicular, or maculopapular rash; urticaria Vascular disorders - hemorrhage, hypertension, vasodilation 6.2 Post-marketing Experience The following adverse reactions have been identified during postapproval use of sertraline hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Bleeding or clotting disorders - increased coagulation times (altered platelet function) Cardiac disorders – AV block, bradycardia, atrial arrhythmias, QTc-interval prolongation, ventricular tachycardia (including Torsade de Pointes) [See Clinical Pharmacology (12.2) ] Endocrine disorders - gynecomastia, hyperprolactinemia, menstrual irregularities, SIADH Eye disorders - blindness, optic neuritis, cataract Hepatobiliary disorders – severe liver events (including hepatitis, jaundice, liver failure with some fatal outcomes), pancreatitis Hemic and lymphatic disorders – agranulocytosis, aplastic anemia and pancytopenia, leukopenia, thrombocytopenia, lupus-like syndrome, serum sickness Immune system disorders - angioedema Metabolism and nutrition disorders – hyponatremia, hyperglycemia Musculoskeletal and connective tissue disorders - rhabdomyolysis, trismus Nervous system disorders - serotonin syndrome, extrapyramidal symptoms (including akathisia and dystonia), oculogyric crisis Psychiatric disorders – psychosis, enuresis, paroniria Renal and urinary disorders - acute renal failure Respiratory, thoracic and mediastinal disorders - pulmonary hypertension, eosinophilic pneumonia, anosmia, hyposmia Skin and subcutaneous tissue disorders - photosensitivity skin reaction and other severe cutaneous reactions, which potentially can be fatal, such as Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) Vascular disorders - cerebrovascular spasm (including reversible cerebral vasoconstriction syndrome and Call-Fleming syndrome), vasculitis"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Protein-bound drugs: Monitor for adverse reactions and reduce dosage of sertraline hydrochloride or other protein-bound drugs (e.g., warfarin) as warranted. ( 7.1 , 12.3 ) CYP2D6 substrates: Reduce dosage of drugs metabolized by CYP2D6. ( 7.1 , 12.3 ) 7.1 Clinically Significant Drug Interactions Table 5 includes clinically significant drug interactions with sertraline hydrochloride [See Clinical Pharmacology (12.3)] . Table 5. Clinically-Significant Drug Interactions with Sertraline Hydrochloride Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: The concomitant use of SSRIs including sertraline hydrochloride and MAOIs increases the risk of serotonin syndrome. Intervention: Sertraline hydrochloride is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [See Dosage and Administration (2.5) , Contraindications (4) , Warnings and Precautions (5.2) ]. Examples: selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Pimozide Clinical Impact: Increased plasma concentrations of pimozide, a drug with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. Intervention: Concomitant use of pimozide and sertraline hydrochloride is contraindicated [See Contraindications (4) ]. Other Serotonergic Drugs Clinical Impact: The concomitant use of serotonergic drugs with sertraline hydrochloride increases the risk of serotonin syndrome. Intervention: Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of sertraline hydrochloride and/or concomitant serotonergic drugs [See Warnings and Precautions (5.2) ]. Examples: Other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort. Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants) Clinical Impact: The concurrent use of an antiplatelet agent or anticoagulant with sertraline hydrochloride may potentiate the risk of bleeding. Intervention: Inform patients of the increased risk of bleeding associated with the concomitant use of sertraline hydrochloride and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [See Warnings and Precautions (5.3) ]. Examples: aspirin, clopidogrel, heparin, warfarin Drugs Highly Bound to Plasma Protein Clinical Impact: Sertraline hydrochloride is highly bound to plasma protein. The concomitant use of sertraline hydrochloride with another drug that is highly bound to plasma protein may increase free concentrations of sertraline hydrochloride or other tightly-bound drugs in plasma [See Clinical Pharmacology (12.3) ] . Intervention: Monitor for adverse reactions and reduce dosage of sertraline hydrochloride or other protein-bound drugs as warranted. Examples: warfarin Drugs Metabolized by CYP2D6 Clinical Impact: Sertraline hydrochloride is a CYP2D6 inhibitor [See Clinical Pharmacology (12.3)] . The concomitant use of sertraline hydrochloride with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. Intervention: Decrease the dosage of a CYP2D6 substrate if needed with concomitant sertraline hydrochloride use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if sertraline hydrochloride is discontinued. Examples: propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, thioridazine, tolterodine, venlafaxine Phenytoin Clinical Impact: Phenytoin is a narrow therapeutic index drug. Sertraline hydrochloride may increase phenytoin concentrations. Intervention: Monitor phenytoin levels when initiating or titrating sertraline hydrochloride. Reduce phenytoin dosage if needed. Examples: phenytoin, fosphenytoin Drugs that Prolong the QTc Interval Clinical Impact: The risk of QTc prolongation and/or ventricular arrhythmias (e.g., TdP) is increased with concomitant use of other drugs which prolong the QTc interval [See Warnings and Precautions (5.10) , Clinical Pharmacology (12.2) ] . Intervention: Pimozide is contraindicated for use with sertraline. Avoid the concomitant use of drugs known to prolong the QTc interval. Examples: Specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus). 7.2 Drugs Having No Clinically Important Interactions with Sertraline Hydrochloride Based on pharmacokinetic studies, no dosage adjustment of sertraline hydrochloride is necessary when used in combination with cimetidine. Additionally, no dosage adjustment is required for diazepam, lithium, atenolol, tolbutamide, digoxin, and drugs metabolized by CYP3A4, when sertraline hydrochloride is administered concomitantly [See Clinical Pharmacology (12.3) ] . 7.3 False-Positive Screening Tests for Benzodiazepines False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking sertraline hydrochloride. This finding is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of sertraline hydrochloride. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish sertraline from benzodiazepines."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Sertraline hydrochloride tablets are indicated for the treatment of the following [See Clinical Studies (14) ] : Major depressive disorder (MDD) Obsessive-compulsive disorder (OCD) Panic disorder (PD) Posttraumatic stress disorder (PTSD) Social anxiety disorder (SAD) Premenstrual dysphoric disorder (PMDD) Sertraline hydrochloride tablets are a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of ( 1 ): Major depressive disorder (MDD) Obsessive-compulsive disorder (OCD) Panic disorder (PD) Posttraumatic stress disorder (PTSD) Social anxiety disorder (SAD) Premenstrual dysphoric disorder (PMDD)"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone. If it occurs, discontinue sertraline hydrochloride and serotonergic agents and initiate supportive treatment. ( 5.2 ) Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk. ( 5.3 ) Activation of Mania/Hypomania: Screen patients for bipolar disorder. ( 5.4 ) Seizures: Use with caution in patients with seizure disorders. ( 5.6 ) Angle Closure Glaucoma: Avoid use of antidepressants, including sertraline hydrochloride, in patients with untreated anatomically narrow angles. ( 5.7 ) QTc Prolongation: Sertraline hydrochloride should be used with caution in patients with risk factors for QTc prolongation. ( 5.10 ) Sexual Dysfunction: sertraline hydrochloride may cause symptoms of sexual dysfunction. ( 5.11 ) 5.1 Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and over 4,400 pediatric patients, the incidence of suicidal thoughts and behaviors in pediatric and young adult patients was greater in antidepressant-treated patients than in placebo-treated patients. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 2. No suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the number was not sufficient to reach any conclusion about antidepressant drug effect on suicide. Table 2: Risk Differences of the Number of Cases of Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range (years) Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1000 Patients Treated Increases Compared to Placebo <18 14 additional patients 18 to 24 5 additional patients Decreases Compared to Placebo 25 to 64 1 fewer patient ≥65 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in pediatric and young adult patients extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression. Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing sertraline hydrochloride, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome Serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs), including sertraline hydrochloride, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [See Contraindications (4) , Drug Interactions (7.1) ]. Serotonin syndrome can also occur when these drugs are used alone. Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of sertraline hydrochloride with MAOIs is contraindicated. In addition, do not initiate sertraline hydrochloride in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking sertraline hydrochloride tablets, discontinue sertraline hydrochloride tablets before initiating treatment with the MAOI [See Contraindications (4) , Drug Interactions (7.1) ]. Monitor all patients taking sertraline hydrochloride for the emergence of serotonin syndrome. Discontinue treatment with sertraline hydrochloride and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of sertraline hydrochloride with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.3 Increased Risk of Bleeding Drugs that interfere with serotonin reuptake inhibition, including sertraline hydrochloride, increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Based on data from the published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Use in Specific Populations (8.1) ] . Bleeding events related to drugs that interfere with serotonin reuptake have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages. Inform patients of the increased risk of bleeding associated with the concomitant use of sertraline hydrochloride and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio. 5.4 Activation of Mania or Hypomania In patients with bipolar disorder, treating a depressive episode with sertraline hydrochloride or another antidepressant may precipitate a mixed/manic episode. In controlled clinical trials, patients with bipolar disorder were generally excluded; however, symptoms of mania or hypomania were reported in 0.4% of patients treated with sertraline hydrochloride. Prior to initiating treatment with sertraline hydrochloride, screen patients for any personal or family history of bipolar disorder, mania, or hypomania. 5.5 Discontinuation Syndrome Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible [See Dosage and Administration (2.6) ]. 5.6 Seizures Sertraline hydrochloride has not been systematically evaluated in patients with seizure disorders. Patients with a history of seizures were excluded from clinical studies. Sertraline hydrochloride should be prescribed with caution in patients with a seizure disorder. 5.7 Angle-Closure Glaucoma The pupillary dilation that occurs following use of many antidepressant drugs including sertraline hydrochloride may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of antidepressants, including sertraline hydrochloride, in patients with untreated anatomically narrow angles. 5.8 Hyponatremia Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including sertraline hydrochloride. Cases with serum sodium lower than 110 mmol/L have been reported. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In patients with symptomatic hyponatremia, discontinue sertraline hydrochloride and institute appropriate medical intervention. Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with SSRIs and SNRIs [See Use in Specific Populations (8.5) ] . 5.9 False-Positive Effects on Screening Tests for Benzodiazepines False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking sertraline hydrochloride. This finding is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of sertraline hydrochloride. Confirmatory tests, such as gas chromatography/mass spectrometry, will help distinguish sertraline hydrochloride from benzodiazepines [See Drug Interactions (7.3) ] . 5.10 QTc Prolongation During post-marketing use of sertraline, cases of QTc prolongation and Torsade de Pointes (TdP) have been reported. Most reports were confounded by other risk factors. In a randomized, double-blind, placebo- and positive-controlled three-period crossover thorough QTc study in 54 healthy adult subjects, there was a positive relationship between the length of the rate-adjusted QTc interval and serum sertraline concentration. Therefore, sertraline hydrochloride should be used with caution in patients with risk factors for QTc prolongation [See Drug Interactions (7.1) , Clinical Pharmacology (12.2) ]. 5.11 Sexual Dysfunction Use of SSRIs, including sertraline hydrochloride, may cause symptoms of sexual dysfunction [see Adverse Reactions (6.1) ] . In male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, SSRI use may result in decreased libido and delayed or absent orgasm. It is important for prescribers to inquire about sexual function prior to initiation of sertraline hydrochloride and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported. When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder. Discuss potential management strategies to support patients in making informed decisions about treatment."}', 'overdosage': '{"10 OVERDOSAGE The following have been reported with sertraline tablet overdosage: Seizures, which may be delayed, and altered mental status including coma. Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation. Hypertension most commonly seen, but rarely can see hypotension alone or with co-ingestants including alcohol. Serotonin syndrome (patients with a multiple drug overdosage with other proserotonergic drugs may have a higher risk). Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a sertraline overdose. Consider contacting a Poison Center (1-800-221-2222) or a medical toxicologist for additional overdosage management recommendations."}', 'active_flag': 'Y', 'generic_name': '{"SERTRALINE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Suicidal Thoughts and Behaviors Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and when the dosage is adjusted up or down, and instruct them to report such symptoms to the healthcare provider [See Boxed Warning and Warnings and Precautions (5.1) ] . Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of sertraline hydrochloride with other serotonergic drugs including triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid). Patients should contact their health care provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome [See Warnings and Precautions (5.2) , Drug Interactions (7.1) ] . Increased Risk of Bleeding Inform patients about the concomitant use of sertraline hydrochloride with aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other anticoagulants because the combined use has been associated with an increased risk of bleeding. Advise patients to inform their health care providers if they are taking or planning to take any prescription or over-the-\xadcounter medications that increase the risk of bleeding [See Warnings and Precautions (5.3) ]. Activation of Mania/Hypomania Advise patients and their caregivers to observe for signs of activation of mania/hypomania and instruct them to report such symptoms to the healthcare provider [See Warnings and Precautions (5.4) ] . Discontinuation Syndrome Advise patients not to abruptly discontinue sertraline hydrochloride and to discuss any tapering regimen with their healthcare provider. Adverse reactions can occur when sertraline hydrochloride is discontinued [See Warnings and Precautions (5.5) ]. Sexual Dysfunction Advise patients that use of sertraline hydrochloride may cause symptoms of sexual dysfunction in both male and female patients. Inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider [see Warnings and Precautions (5.11) ]. Allergic Reactions Advise patients to notify their healthcare provider if they develop an allergic reaction such as rash, hives, swelling, or difficulty breathing [See Adverse Reactions (6.2) ] . Pregnancy Inform pregnant women that sertraline hydrochloride may cause withdrawal symptoms in the newborn or persistent pulmonary hypertension of the newborn (PPHN) [See Use in Specific Populations (8.1) ] . Advise women that there is a pregnancy exposure registry that monitors pregnancy outcomes of women exposed to sertraline hydrochloride during pregnancy. Medication Guides available at www.northstarrxllc.com/products or call 1-800-206-7821. Manufactured for: Northstar Rx LLC Memphis, TN 38141. Manufactured by: APL Healthcare Limited Unit-IV (MP SEZ), Tirupati (Dt)-524421 Andhra Pradesh, India. M.L.No.: 04/NLR/AP/2016/F/CC Revised: 10/2023 Medication Guides available at www.northstarrxllc.com/products or call 1-800-206-7821."}', 'pregnancy': '{"8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers should encourage patients to enroll by calling the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants. Risk Summary Based on data from published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.3) and Clinical Considerations] . Overall, available published epidemiologic studies of pregnant women exposed to sertraline in the first trimester suggest no difference in major birth defect risk compared to the background rate for major birth defects in comparator populations. Some studies have reported increases for specific major birth defects; however, these study results are inconclusive [See Data] . There are clinical considerations regarding neonates exposed to SSRIs and SNRIs, including sertraline hydrochloride, during the third trimester of pregnancy [See Clinical Considerations]. Although no teratogenicity was observed in animal reproduction studies, delayed fetal ossification was observed when sertraline was administered during the period of organogenesis at doses less than the maximum recommended human dose (MRHD) in rats and doses 3.1 times the MRHD in rabbits on a mg/m 2 basis in adolescents. When sertraline was administered to female rats during the last third of gestation, there was an increase in the number of stillborn pups and pup deaths during the first four days after birth at the MRHD [See Data] . The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Advise a pregnant woman of possible risks to the fetus when prescribing sertraline hydrochloride. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk A prospective longitudinal study followed 201 pregnant women with a history of major depression who were euthymic taking antidepressants at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. Consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Maternal Adverse Reactions Use of sertraline hydrochloride in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.3) ]. Fetal/Neonatal adverse reactions Exposure to SSRIs and SNRIs, including sertraline hydrochloride in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN). When treating a pregnant woman with sertraline hydrochloride during the third trimester, carefully consider both the potential risks and benefits of treatment. Monitor neonates who were exposed to sertraline hydrochloride in the third trimester of pregnancy for PPHN and drug discontinuation syndrome [See Data]. Data Human Data Third Trimester Exposure Neonates exposed to sertraline hydrochloride and other SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. These findings are based on post-marketing reports. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. In some cases, the clinical picture was consistent with serotonin syndrome [See Warnings and Precautions (5.2) ] . Exposure during late pregnancy to SSRIs may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. In a retrospective case-control study of 377 women whose infants were born with PPHN and 836 women whose infants were born healthy, the risk for developing PPHN was approximately six-fold higher for infants exposed to SSRIs after the 20 th week of gestation compared to infants who had not been exposed to antidepressants during pregnancy. A study of 831,324 infants born in Sweden in 1997 to 2005 found a PPHN risk ratio of 2.4 (95% CI 1.2 to 4.3) associated with patient-reported maternal use of SSRIs “in early pregnancy” and a PPHN risk ratio of 3.6 (95% CI 1.2 to 8.3) associated with a combination of patient-reported maternal use of SSRIs “in early pregnancy” and an antenatal SSRI prescription “in later pregnancy”. First Trimester Exposure The weight of evidence from epidemiologic studies of pregnant women exposed to sertraline in the first trimester suggest no difference in major birth defect risk compared to the background rate for major birth defects in pregnant women who were not exposed to sertraline. A meta-analysis of studies suggest no increase in the risk of total malformations (summary odds ratio=1.01, 95% CI=0.88 to 1.17) or cardiac malformations (summary odds ratio=0.93, 95% CI=0.70 to 1.23) among offspring of women with first trimester exposure to sertraline. An increased risk of congenital cardiac defects, specifically septal defects, the most common type of congenital heart defect, was observed in some published epidemiologic studies with first trimester sertraline exposure; however, most of these studies were limited by the use of comparison populations that did not allow for the control of confounders such as the underlying depression and associated conditions and behaviors, which may be factors associated with increased risk of these malformations. Animal Data Reproduction studies have been performed in rats and rabbits at doses up to 80 mg/kg/day and 40 mg/kg/day, respectively. These doses correspond to approximately 3.1 times the maximum recommended human dose (MRHD) of 200 mg/day on a mg/m 2 basis in adolescents. There was no evidence of teratogenicity at any dose level. When pregnant rats and rabbits were given sertraline during the period of organogenesis, delayed ossification was observed in fetuses at doses of 10 mg/kg (0.4 times the MRHD on a mg/m 2 basis) in rats and 40 mg/kg (3.1 times the MRHD on a mg/m 2 basis) in rabbits. When female rats received sertraline during the last third of gestation and throughout lactation, there was an increase in stillborn pups and pup deaths during the first 4 days after birth. Pup body weights were also decreased during the first four days after birth. These effects occurred at a dose of 20 mg/kg (0.8 times the MRHD on a mg/m 2 basis). The no effect dose for rat pup mortality was 10 mg/kg (0.4 times the MRHD on a mg/m 2 basis). The decrease in pup survival was shown to be due to in utero exposure to sertraline. The clinical significance of these effects is unknown."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and efficacy of sertraline hydrochloride have been established in the treatment of OCD in pediatric patients aged 6 to 17 [See Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , Clinical Studies (14.2) ] . Safety and effectiveness in pediatric patients in patients with OCD below the age of 6 have not been established. Safety and effectiveness have not been established in pediatric patients for indications other than OCD. Two placebo-controlled trials were conducted in pediatric patients with MDD, but the data were not sufficient to support an indication for use in pediatric patients. Monitoring Pediatric Patients Treated with Sertraline Hydrochloride Monitor all patients being treated with antidepressants for clinical worsening, suicidal thoughts, and unusual changes in behavior, especially during the initial few months of treatment, or at times of dose increases or decreases [See Boxed Warning, Warnings and Precautions (5.1) ] . Decreased appetite and weight loss have been observed with the use of SSRIs. Monitor weight and growth in pediatric patients treated with an SSRI such as sertraline hydrochloride. Weight Loss in Studies in Pediatric Patients with MDD In a pooled analysis of two 10-week, double-blind, placebo-controlled, flexible dose (50 to 200 mg) outpatient trials for MDD (n=373), there was a difference in weight change between sertraline hydrochloride and placebo of roughly 1 kg, for both children (ages 6 to 11) and adolescents (ages 12 to 17), in both age groups representing a slight weight loss for the sertraline hydrochloride group compared to a slight gain for the placebo group. For children, about 7% of the sertraline hydrochloride-treated patients had a weight loss greater than 7% of body weight compared to 0% of the placebo-treated patients; for adolescents, about 2% of sertraline hydrochloride-treated patients had a weight loss > 7% of body weight compared to about 1% of placebo-treated patients. A subset of patients who completed the randomized controlled trials in patients with MDD (sertraline hydrochloride n=99, placebo n=122) were continued into a 24-week, flexible-dose, open-label, extension study. Those subjects who completed 34 weeks of sertraline hydrochloride treatment (10 weeks in a placebo-controlled trial + 24 weeks open-label, n=68) had weight gain that was similar to that expected using data from age-adjusted peers. However, there are no studies that directly evaluate the long-term effects of sertraline hydrochloride on the growth, development, and maturation in pediatric patients. Juvenile Animal Data A study conducted in juvenile rats at clinically relevant doses showed delay in sexual maturation, but there was no effect on fertility in either males or females. In this study in which juvenile rats were treated with oral doses of sertraline at 0, 10, 40 or 80 mg/kg/day from postnatal day 21 to 56, a delay in sexual maturation was observed in males treated with 80 mg/kg/day and females treated with doses ≥10 mg/kg/day. There was no effect on male and female reproductive endpoints or neurobehavioral development up to the highest dose tested (80 mg/kg/day), except a decrease in auditory startle response in females at 40 and 80 mg/kg/day at the end of treatment but not at the end of the drug-free period. The highest dose of 80 mg/kg/day produced plasma levels (AUC) of sertraline 5 times those seen in pediatric patients (6 to 17 years of age) receiving the maximum recommended dose of sertraline (200 mg/day)."}', 'geriatric_use': '{"8.5 Geriatric Use Of the total number of patients in clinical studies of sertraline hydrochloride in patients with MDD, OCD, PD, PTSD, SAD and PMDD, 797 (17%) were ≥ 65 years old, while 197 (4%) were ≥ 75 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. In 354 geriatric subjects treated with sertraline hydrochloride in MDD placebo-controlled trials, the overall profile of adverse reactions was generally similar to that shown in Table 3 [See Adverse Reactions (6.1) ], except for tinnitus, arthralgia with an incidence of at least 2% and at a rate greater than placebo in geriatric patients. SNRIs and SSRIs, including sertraline hydrochloride, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [See Warnings and Precautions (5.8) ]."}'}

{ALBENDAZOLE}

{'contraindications': '{"4 CONTRAINDICATIONS Albendazole is contraindicated in patients with known hypersensitivity to the benzimidazole class of compounds or any components of albendazole. Patients with known hypersensitivity to the benzimidazole class of compounds or any components of albendazole. ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS Adverse reactions 1% or greater in hydatid disease: abnormal liver function tests, abdominal pain, nausea/vomiting, reversible alopecia, headache, dizziness/vertigo, fever. ( 6.1 ) Adverse reactions 1% or greater in neurocysticercosis: headache, nausea/vomiting, raised intracranial pressure, meningeal signs. ( 6.1) To report SUSPECTED ADVERSE REACTIONS, contact Novadoz Pharmaceuticals LLC at 1-855-668-2369 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction profile of albendazole differs between hydatid disease and neurocysticercosis. Adverse reactions occurring with a frequency of 1% or greater in either disease are described in Table 2 below. These symptoms were usually mild and resolved without treatment. Treatment discontinuations were predominantly due to leukopenia (0.7%) or hepatic abnormalities (3.8% in hydatid disease). The following incidence reflects adverse reactions that were reported to be at least possibly or probably related to albendazole. Table 2:Adverse Reaction Incidence 1% or Greater in Hydatid Disease and Neurocysticercosis Adverse Reaction Hydatid Disease Neurocysticercosis Gastrointestinal Abdominal Pain 6 0 Nausea 4 6 Vomiting 4 6 General disorders and administration site conditions Fever 1 0 Investigations Elevated Hepatic Enzymes 16 less than 1 Nervous system disorders Dizziness 1 less than 1 Headache 1 11 Meningeal Signs 0 1 Raised Intracranial Pressure 0 2 Vertigo 1 less than 1 Skin and subcutaneous tissue disorders Reversible Alopecia 2 less than 1 The following adverse events were observed at an incidence of less than 1%: Blood and Lymphatic System Disorders: There have been reports of leukopenia, granulocytopenia, pancytopenia, agranulocytosis, or thrombocytopenia [ see Warnings and Precautions (5.1)]. Immune System Disorders: Hypersensitivity reactions, including rash and urticaria. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of albendazole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders: Aplastic anemia, bone marrow suppression, neutropenia. Eye Disorders: Vision blurred. Gastrointestinal Disorders: Diarrhea. General System Disorders : Asthenia. Hepatobiliary Disorders: Elevations of hepatic enzymes, hepatitis, acute liver failure. Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis. Nervous System Disorders: Somnolence, convulsion. Renal and Urinary Disorders: Acute renal failure. Skin and Subcutaneous Tissue Disorders: Erythema multiforme, Stevens-Johnson syndrome."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Dexamethasone: Steady-state trough concentrations of albendazole sulfoxide were about 56% higher when dexamethasone was coadministered with each dose of albendazole. ( 7.1 ) Praziquantel: In the fed state increased mean maximum plasma concentration and area under the curve of albendazole sulfoxide by about 50% in healthy subjects. ( 7.2 ) Cimetidine: Increased albendazole sulfoxide concentrations in bile and cystic fluid by about 2-fold in hydatid cyst patients. ( 7.3 ) Theophylline: Albendazole induces cytochrome P450 1A in human hepatoma cells; therefore, it is recommended that plasma concentrations of theophylline be monitored during and after treatment. ( 5.5 , 7.4 ) 7.1 Dexamethasone Steady-state trough concentrations of albendazole sulfoxide were about 56% higher when 8 mg dexamethasone was co-administered with each dose of albendazole (15 mg/kg/day) in 8 neurocysticercosis patients. 7.2 Praziquantel In the fed state, praziquantel (40 mg/kg) increased mean maximum plasma concentration and area under the curve of albendazole sulfoxide by about 50% in healthy subjects (n = 10) compared with a separate group of subjects (n = 6) given albendazole alone. Mean T max and mean plasma elimination half-life of albendazole sulfoxide were unchanged. The pharmacokinetics of praziquantel were unchanged following co-administration with albendazole (400 mg). 7.3 Cimetidine Albendazole sulfoxide concentrations in bile and cystic fluid were increased (about 2-fold) in hydatid cyst patients treated with cimetidine (10 mg/kg/day) (n = 7) compared with albendazole (20 mg/kg/day) alone (n = 12). Albendazole sulfoxide plasma concentrations were unchanged 4 hours after dosing. 7.4 Theophylline Following a single dose of albendazole (400 mg), the pharmacokinetics of theophylline (aminophylline 5.8 mg/kg infused over 20 minutes) were unchanged. Albendazole induces cytochrome P450 1A in human hepatoma cells; therefore, it is recommended that plasma concentrations of theophylline be monitored during and after treatment."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Albendazole tablet is an anthelmintic drug indicated for: Treatment of parenchymal neurocysticercosis due to active lesions caused by larval forms of the pork tapeworm, Taenia solium . ( 1.1 ) Treatment of cystic hydatid disease of the liver, lung, and peritoneum, caused by the larval form of the dog tapeworm, Echinococcus granulosus . ( 1.2 ) 1.1 Neurocysticercosis Albendazole tablets are indicated for the treatment of parenchymal neurocysticercosis due to active lesions caused by larval forms of the pork tapeworm, Taenia solium . 1.2 Hydatid Disease Albendazole tablets are indicated for the treatment of cystic hydatid disease of the liver, lung, and peritoneum, caused by the larval form of the dog tapeworm, Echinococcus granulosus ."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Bone Marrow Suppression: Fatalities have been reported due to bone marrow suppression; monitor blood counts in all patients at the beginning of each 28-day cycle of therapy, and every 2 weeks while on therapy. Discontinue albendazole if clinically significant changes in blood counts occur. ( 5.1 , 5.4 ) Embryo-Fetal Toxicity: May cause fetal harm. Pregnancy testing is recommended for females of reproductive potential prior to therapy. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception. ( 2.3 , 5.2 , 8.1 , 8.3 ) Risk of Neurologic Symptoms: Neurocysticercosis patients may experience cerebral hypertensive episodes, seizures or focal neurologic deficits after initiation of therapy; begin appropriate steroid and anticonvulsant therapy. ( 5.3 ) Risk of Retinal Damage in Retinal Cysticercosis: Cases of retinal involvement have been reported; examine the patient for the presence of retinal lesions before initiating therapy for neurocysticercosis. ( 5.4 ) Hepatic Effects. Elevations of liver enzymes may occur. Monitor liver enzymes before the start of each treatment cycle and at least every 2 weeks while on albendazole therapy and discontinue if clinically significant elevations occur. ( 5.5 ) 5.1 Bone Marrow Suppression Fatalities associated with the use of albendazole have been reported due to granulocytopenia or pancytopenia. Albendazole may cause bone marrow suppression, aplastic anemia, and agranulocytosis. Monitor blood counts at the beginning of each 28-day cycle of therapy, and every 2 weeks while on therapy with albendazole in all patients. Patients with liver disease and patients with hepatic echinococcosis are at increased risk for bone marrow suppression and warrant more frequent monitoring of blood counts. Discontinue albendazole if clinically significant decreases in blood cell counts occur. 5.2 Embryo-Fetal Toxicity Based on findings from animal reproduction studies, albendazole may cause fetal harm when administered to a pregnant woman. Embryotoxicity and skeletal malformations were reported in rats and rabbits when treated during the period of organogenesis (at oral doses approximately 0.1 to 0.6 times the recommended human dose normalized for total body surface area). Advise pregnant women of the potential risk to a fetus. Pregnancy testing is recommended for females of reproductive potential prior to initiating albendazole [ see Dosage and Administration (2.3) ]. Advise females of reproductive potential to use an effective method of contraception during treatment with albendazole and for 3 days after the final dose [ see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.3) ]. 5.3 Risk of Neurologic Symptoms in Neurocysticercosis Patients being treated for neurocysticercosis should receive steroid and anticonvulsant therapy to prevent neurological symptoms (e.g. seizures, increased intracranial pressure and focal signs) as a result of an inflammatory reaction caused by death of the parasite within the brain. 5.4 Risk of Retinal Damage in Patients with Retinal Neurocysticercosis Cysticercosis may involve the retina. Before initiating therapy for neurocysticercosis, examine the patient for the presence of retinal lesions. If such lesions are visualized, weigh the need for anticysticeral therapy against the possibility of retinal damage resulting from inflammatory damage caused by albendazole-induced death of the parasite. 5.5 Hepatic Effects In clinical trials, treatment with albendazole has been associated with mild to moderate elevations of hepatic enzymes in approximately 16% of patients. These elevations have generally returned to normal upon discontinuation of therapy. There have also been case reports of acute liver failure of uncertain causality and hepatitis [ see Adverse Reactions (6)]. Monitor liver enzymes (transaminases) before the start of each treatment cycle and at least every 2 weeks during treatment. If hepatic enzymes exceed twice the upper limit of normal, consideration should be given to discontinuing albendazole therapy based on individual patient circumstances. Restarting albendazole treatment in patients whose hepatic enzymes have normalized off treatment is an individual decision that should take into account the risk/benefit of further albendazole usage. Perform laboratory tests frequently if albendazole treatment is restarted. Patients with elevated liver enzyme test results are at increased risk for hepatotoxicity and bone marrow suppression [ see Warnings and Precautions (5.1)]. Discontinue therapy if liver enzymes are significantly increased or if clinically significant decreases in blood cell counts occur. 5.6 Unmasking of Neurocysticercosis in Hydatid Patients Undiagnosed neurocysticercosis may be uncovered in patients treated with albendazole for other conditions. Patients with epidemiologic factors who are at risk for neurocysticercosis should be evaluated prior to initiation of therapy."}', 'overdosage': '{"10 OVERDOSAGE In case of overdosage, symptomatic therapy and general supportive measures are recommended."}', 'active_flag': 'Y', 'generic_name': '{ALBENDAZOLE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Patients should be advised that: Some people, particularly children, may experience difficulties swallowing the albendazole tablets whole. Take albendazole tablets with food. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females to inform their prescriber of a known or suspected pregnancy [ see Warnings and Precautions (5.2), Use in Specific Populations (8.1) ]. Advise females of reproductive potential to use effective contraception during treatment with albendazole tablets and for 3 days after the final dose [ see Use in Specific Populations (8.3 )]. During albendazole tablets therapy, monitor blood counts and liver enzymes every 2 weeks because of the possibility of harm to the liver or bone marrow [ see Warnings and Precautions (5.5) ]. Manufactured by: MSN Laboratories Private Limited Telangana – 509 228, INDIA Distributed by: Novadoz Pharmaceuticals LLC Piscataway, NJ 08854-3714 Issued on: 02/2020"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Based on findings from animal reproduction studies, albendazole may cause fetal harm when administered to a pregnant woman. However, available human data from a small number of published case series and reports on the use of multiple-dose albendazole in the 1st trimester of pregnancy, and several published studies on single-dose albendazole use later in pregnancy, have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproductive studies, oral administration of albendazole during the period of organogenesis caused embryotoxicity and skeletal malformations in pregnant rats (at doses of 0.10 times and 0.32 times the maximum recommended human dose based on body surface area in mg/m 2 ) and pregnant rabbits (at doses of 0.60 times the maximum recommended human dose based on body surface area in mg/m 2 ). Albendazole was also associated with maternal toxicity in rabbits (at doses of 0.60 times the recommended human dose based on body surface area in mg/m 2 ) ( see Data ). Advise a pregnant woman of the potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Albendazole has been shown to be teratogenic (to cause embryotoxicity and skeletal malformations) in pregnant rats and rabbits. The teratogenic response in the rat was shown at oral doses of 10 and 30 mg/kg/day (0.10 times and 0.32 times the maximum recommended human dose based on body surface area in mg/m 2 , respectively) during organogenesis (gestation days 6 to 15) and in pregnant rabbits at oral doses of 30 mg/kg/day (0.60 times the maximum recommended human dose based on body surface area in mg/m 2 ) administered during organogenesis (gestation days 7 to 19). In the rabbit study, maternal toxicity (33% mortality) was noted at 30 mg/kg/day. In mice, no teratogenic effects were observed at oral doses up to 30 mg/kg/day (0.16 times the recommended human dose based on body surface area in mg/m 2 ), administered during gestation days 6 to 15."}', 'pediatric_use': '{"8.4 Pediatric Use Hydatid disease is uncommon in infants and young children. In neurocysticercosis, the efficacy of albendazole in children appears to be similar to that in adults."}', 'geriatric_use': '{"8.5 Geriatric Use In patients aged 65 and older with either hydatid disease or neurocysticercosis, there was insufficient data to determine whether the safety and effectiveness of albendazole is different from that of younger patients."}'}

{"HYDROCORTISONE ACETATE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses For temporarily relief of itching associated with minor skin irritations, inflammation, and rashes due to: ■ eczema ■ psoriasis ■ poison ivy, oak, sumac ■ insect bites ■ detergents ■ jewelry ■ cosmetics ■ soaps ■ seborrheic dermatitis Other uses of this product should only be under the advice and supervision of a doctor"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"1% HYDROCORTISONE"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if condition worsens, symptoms persist for more than 7 days or clear up and occur again within a few days, and do not begin use of any other hydrocortisone product unless you have asked a doctor"}', 'do_not_use': '{"Do not use for the treatment of diaper rash. Consult a doctor. for external genital itching if you have a vaginal discharge, consult a doctor."}', 'when_using': '{"When using this product Avoid contact with the eyes Do not begin the use of any other hydrocortisone products unless you have consulted a doctor. For genital, feminine and anal itching do not exceed the recommended daily dose unless directed by a doctor, in case of bleeding , stop use and consult a doctor Do not put this product into the rectum by using fingers or any mechanical device or applicator."}', 'warnings': '{"Warnings For external use only"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{BISACODYL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses for relief of occasional constipation and irregularity this product generally produces bowel movement in 6 to 12 hours"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{BISACODYL}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if you have rectal bleeding or fail to have a bowel movement after use of a laxative. These could be signs of a serious condition. you need to use a laxative for more than 1 week"}', 'do_not_use': '{"Do not use if you cannot swallow without chewing."}', 'when_using': '{"When using this product do not chew or crush tablet(s) do not use within 1 hour after taking an antacid or milk it may cause stomach discomfort, faintness, and cramps"}', 'warnings': '{"Warnings Do not use if you cannot swallow without chewing. Ask a doctor before use if you have stomach pain, nausea or vomiting a sudden change in bowel habits that lasts more than 2 weeks When using this product do not chew or crush tablet(s) do not use within 1 hour after taking an antacid or milk it may cause stomach discomfort, faintness, and cramps Stop use and ask a doctor if you have rectal bleeding or fail to have a bowel movement after use of a laxative. These could be signs of a serious condition. you need to use a laxative for more than 1 week If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{TACROLIMUS}

{'contraindications': '{"4 CONTRAINDICATIONS Tacrolimus capsules are contraindicated in patients with a hypersensitivity to tacrolimus. Tacrolimus injection is contraindicated in patients with a hypersensitivity to HCO-60 (polyoxyl 60 hydrogenated castor oil). Hypersensitivity symptoms reported include dyspnea, rash, pruritus, and acute respiratory distress syndrome [see Adverse Reactions (6) ]. Hypersensitivity to tacrolimus or HCO-60 (polyoxyl 60 hydrogenated castor oil). ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling: Lymphoma and Other Malignancies [see Warnings and Precautions (5.1) ] Serious Infections [see Warnings and Precautions ( 5.2 )] New Onset Diabetes After Transplant [see Warnings and Precautions ( 5.4 ) ] Nephrotoxicity [see Warnings and Precautions ( 5.5 )] Neurotoxicity [see Warnings and Precautions ( 5.6 )] Hyperkalemia [see Warnings and Precautions ( 5.7 )] Hypertension [see Warnings and Precautions ( 5.8 )] Anaphylactic Reactions with Tacrolimus Injection [see Warnings and Precautions ( 5.9 )] Myocardial Hypertrophy [see Warnings and Precautions ( 5.13 )] Pure Red Cell Aplasia [see Warnings and Precautions ( 5.15 )] Thrombotic Microangiopathy, Including Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura [see Warnings and Precautions ( 5.16) ] The most common adverse reactions (≥ 15%) were abnormal renal function, hypertension, diabetes mellitus, fever, CMV infection, tremor, hyperglycemia, leukopenia, infection, anemia, bronchitis, pericardial effusion, urinary tract infection, constipation, diarrhea, headache, abdominal pain, insomnia, paresthesia, peripheral edema, nausea, hyperkalemia, hypomagnesemia, and hyperlipemia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy’s Laboratories Inc., at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In addition, the clinical trials were not designed to establish comparative differences across study arms with regards to the adverse reactions discussed below. Kidney Transplantation The incidence of adverse reactions was determined in three randomized kidney transplant trials. One of the trials used azathioprine (AZA) and corticosteroids and two of the trials used mycophenolate mofetil (MMF) and corticosteroids concomitantly for maintenance immunosuppression. Tacrolimus-based immunosuppression in conjunction with azathioprine and corticosteroids following kidney transplantation was assessed in a trial where 205 patients received tacrolimus-based immunosuppression and 207 patients received cyclosporine-based immunosuppression. The trial population had a mean age of 43 years (mean±SD was 43±13 years on tacrolimus and 44±12 years on cyclosporine arm), the distribution was 61% male, and the composition was White (58%), African-American (25%), Hispanic (12%), and Other (5%). The 12 month post-transplant information from this trial is presented below. The most common adverse reactions (≥ 30%) observed in tacrolimus-treated kidney transplant patients are: infection, tremor, hypertension, abnormal renal function, constipation, diarrhea, headache, abdominal pain, insomnia, nausea, hypomagnesemia, urinary tract infection, hypophosphatemia, peripheral edema, asthenia, pain, hyperlipidemia, hyperkalemia, and anemia. Based on reported adverse reaction terms related to decreased renal function, nephrotoxicity was reported in approximately 52% of kidney transplantation patients. Adverse reactions that occurred in ≥ 15% of kidney transplant patients treated with tacrolimus in conjunction with azathioprine are presented below: Table 4. Kidney Transplantation: Adverse Reactions Occurring in ≥ 15% of Patients Treated with Tacrolimus in Conjunction with Azathioprine (AZA) Tacrolimus/AZA (N=205) Cyclosporine/AZA (N=207) Nervous System Tremor Headache Insomnia Paresthesia Dizziness 54% 44% 32% 23% 19% 34% 38% 30% 16% 16% Gastrointestinal Diarrhea Nausea Constipation Vomiting Dyspepsia 44% 38% 35% 29% 28% 41% 36% 43% 23% 20% Cardiovascular Hypertension Chest Pain 50% 19% 52% 13% Urogenital Creatinine Increased Urinary Tract Infection 45% 34% 42% 35% Metabolic and Nutritional Hypophosphatemia Hypomagnesemia Hyperlipemia Hyperkalemia Diabetes Mellitus Hypokalemia Hyperglycemia Edema 49% 34% 31% 31% 24% 22% 22% 18% 53% 17% 38% 32% 9% 25% 16% 19% Hemic and Lymphatic Anemia Leukopenia 30% 15% 24% 17% Miscellaneous Infection 45% 49% Peripheral Edema Asthenia Abdominal Pain Pain Fever Back Pain 36% 34% 33% 32% 29% 24% 48% 30% 31% 30% 29% 20% Respiratory System Dyspnea Cough Increased 22% 18% 18% 15% Musculoskeletal Arthralgia 25% 24% Skin Rash Pruritus 17% 15% 12% 7% Two trials were conducted for tacrolimus-based immunosuppression in conjunction with MMF and corticosteroids. In the non-US trial (Study 1), the incidence of adverse reactions was based on 1195 kidney transplant patients that received tacrolimus (Group C, n=403), or one of two cyclosporine (CsA) regimens (Group A, n=384 and Group B, n=408) in combination with MMF and corticosteroids; all patients, except those in one of the two cyclosporine groups, also received induction with daclizumab. The trial population had a mean age of 46 years (range 17 to 76); the distribution was 65% male, and the composition was 93% Caucasian. The 12 month post-transplant information from this trial is presented below. Adverse reactions that occurred in ≥ 10% of kidney transplant patients treated with tacrolimus in conjunction with MMF in Study 1 [Note: This trial was conducted entirely outside of the United States. Such trials often report a lower incidence of adverse reactions in comparison to U.S. trials] are presented below: Table 5. Kidney Transplantation: Adverse Reactions Occurring in ≥ 10% of Patients Treated with Tacrolimus in Conjunction with MMF (Study 1) Tacrolimus Cyclosporine Cyclosporine (Group C) (Group A) (Group B) (N=403) (N=384) (N=408) Diarrhea 25% 16% 13% Urinary Tract Infection 24% 28% 24% Anemia 17% 19% 17% Hypertension 13% 14% 12% Leukopenia 13% 10% 10% Edema Peripheral 11% 12% 13% Hyperlipidemia 10% 15% 13% Key: Group A = CsA/MMF/CS, B = CsA/MMF/CS/Daclizumab, C = Tac/MMF/CS/Daclizumab CsA = Cyclosporine, CS = Corticosteroids, Tac = Tacrolimus, MMF = mycophenolate mofetil In the U.S. trial (Study 2) with tacrolimus-based immunosuppression in conjunction with MMF and corticosteroids, 424 kidney transplant patients received tacrolimus (n=212) or cyclosporine (n=212) in combination with MMF 1 gram twice daily, basiliximab induction, and corticosteroids. The trial population had a mean age of 48 years (range 17 to 77); the distribution was 63% male, and the composition was White (74%), African-American (20%), Asian (3%), and Other (3%). The 12-month post-transplant information from this trial is presented below. Adverse reactions that occurred in ≥15% of kidney transplant patients treated with tacrolimus in conjunction with MMF in Study 2 are presented below: Table 6. Kidney Transplantation: Adverse Reactions Occurring in ≥ 15% of Patients Treated with Tacrolimus in Conjunction with MMF (Study 2) Tacrolimus/MMF Cyclosporine/MMF (N=212) (N=212) Gastrointestinal Disorders Diarrhea 44% 26% Nausea 39% 47% Constipation 36% 41% Vomiting 26% 25% Dyspepsia 18% 15% Injury, Poisoning, and Procedural Complications Post-Procedural Pain 29% 27% Incision Site Complication 28% 23% Graft Dysfunction 24% 18% Metabolism and Nutrition Disorders Hypomagnesemia 28% 22% Hypophosphatemia 28% 21% Hyperkalemia 26% 19% Hyperglycemia 21% 15% Hyperlipidemia 18% 25% Hypokalemia 16% 18% Nervous System Disorders Tremor 34% 20% Headache 24% 25% Blood and Lymphatic System Disorders Anemia 30% 28% Leukopenia 16% 12% Miscellaneous Edema Peripheral 35% 46% Hypertension 32% 35% Insomnia 30% 21% Urinary Tract Infection 26% 22% Blood Creatinine Increased 23% 23% Less frequently observed adverse reactions in kidney transplantation patients are described under the subsection \\"Less Frequently Reported Adverse Reactions (> 3% and < 15%) in Liver, Kidney, and Heart Transplant Studies.” Liver Transplantation There were two randomized comparative liver transplant trials. In the U.S. trial, 263 adult and pediatric patients received tacrolimus and steroids and 266 patients received cyclosporine-based immunosuppressive regimen (CsA/AZA). The trial population had a mean age of 44 years (range 0.4 to 70); the distribution was 52% male, and the composition was White (78%), African-American (5%), Asian (2%), Hispanic (13%), and Other (2%). In the European trial, 270 patients received tacrolimus and steroids and 275 patients received CsA/AZA. The trial population had a mean age of 46 years (range 15 to 68); the distribution was 59% male, and the composition was White (95.4%), Black (1%), Asian (2%), and Other (2%). The proportion of patients reporting more than one adverse event was > 99% in both the tacrolimus group and the CsA/AZA group. Precautions must be taken when comparing the incidence of adverse reactions in the U.S. trial to that in the European trial. The 12 month post-transplant information from the U.S. trial and from the European trial is presented below. The two trials also included different patient populations and patients were treated with immunosuppressive regimens of differing intensities. Adverse reactions reported in ≥15% in tacrolimus patients (combined trial results) are presented below for the two controlled trials in liver transplantation. The most common adverse reactions (≥ 38%) observed in tacrolimus-treated liver transplant patients are: tremor, headache, diarrhea, hypertension, nausea, abnormal renal function, abdominal pain, insomnia, paresthesia, anemia, pain, fever, asthenia, hyperkalemia, hypomagnesemia, and hyperglycemia. These all occur with oral and IV administration of tacrolimus and some may respond to a reduction in dosing (e.g., tremor, headache, paresthesia, hypertension). Diarrhea was sometimes associated with other gastrointestinal complaints such as nausea and vomiting. Based on reported adverse reaction terms related to decreased renal function, nephrotoxicity was reported in approximately 40% and 36% of liver transplantation patients receiving tacrolimus in the U.S. and European randomized trials. Table 7. Liver Transplantation: Adverse Reactions Occurring in ≥ 15% of Patients Treated with Tacrolimus U.S. TRIAL EUROPEAN TRIAL T acrolimus (N=250 ) Cyclosporine/AZA (N=250) Tacrolimus (N=264) Cyclosporine/AZA (N=265) Nervous System Headache 64% 60% 37% 26% Insomnia 64% 68% 32% 23% Tremor 56% 46% 48% 32% Paresthesia 40% 30% 17% 17% Gastrointestinal Diarrhea 72% 47% 37% 27% Nausea 46% 37% 32% 27% LFT Abnormal 36% 30% 6% 5% Anorexia 34% 24% 7% 5% Vomiting 27% 15% 14% 11% Constipation 24% 27% 23% 21% Cardiovascular Hypertension 47% 56% 38% 43% Urogenital Kidney Function Abnormal 40% 27% 36% 23% Creatinine Increased 39% 25% 24% 19% BUN Increased 30% 22% 12% 9% Oliguria 18% 15% 19% 12% Urinary Tract Infection 16% 18% 21% 19% Metabolic and Nutritional Hypomagnesemia 48% 45% 16% 9% Hyperglycemia 47% 38% 33% 22% Hyperkalemia 45% 26% 13% 9% Hypokalemia 29% 34% 13% 16% Hemic and Lymphatic Anemia 47% 38% 5% 1% Leukocytosis 32% 26% 8% 8% Thrombocytopenia 24% 20% 14% 19% Miscellaneous Pain 63% 57% 24% 22% Abdominal Pain 59% 54% 29% 22% Asthenia 52% 48% 11% 7% Fever 48% 56% 19% 22% Back Pain 30% 29% 17% 17% Ascites 27% 22% 7% 8% Peripheral Edema 26% 26% 12% 14% Respiratory System Pleural Effusion 30% 32% 36% 35% Dyspnea 29% 23% 5% 4% Atelectasis 28% 30% 5% 4% Skin and Appendages Pruritus 36% 20% 15% 7% Rash 24% 19% 10% 4% Less frequently observed adverse reactions in liver transplantation patients are described under the subsection “Less Frequently Reported Adverse Reactions (> 3% and < 15%) in Liver, Kidney, and Heart Transplant Studies.” Heart Transplantation The incidence of adverse reactions was determined based on two trials in primary orthotopic heart transplantation. In a trial conducted in Europe, 314 patients received a regimen of antibody induction, corticosteroids, and azathioprine (AZA) in combination with tacrolimus (n=157) or cyclosporine (n=157) for 18 months. The trial population had a mean age of 51 years (range 18 to 65); the distribution was 82% male, and the composition was White (96%), Black (3%), and Other (1%). The most common adverse reactions (≥ 15%) observed in tacrolimus-treated heart transplant patients are: abnormal renal function, hypertension, diabetes mellitus, CMV infection, tremor, hyperglycemia, leukopenia, infection, anemia, bronchitis, pericardial effusion, urinary tract infection, and hyperlipemia. Based on reported adverse reaction terms related to decreased renal function, nephrotoxicity was reported in approximately 59% of heart transplantation patients in the European trial. Adverse reactions in heart transplant patients in the European trial are presented below: Table 9. Heart Transplantation: Adverse Reactions Occurring in ≥15% of Patients Treated with Tacrolimus in Conjunction with Azathioprine (AZA) Tacrolimus/AZA (N=157) Cyclosporine/AZA (N=157) Cardiovascular System Hypertension 62% 69% Pericardial Effusion 15% 14% Body as a Whole CMV Infection 32% 30% Infection 24% 21% Metabolic and Nutritional Disorders Diabetes Mellitus 26% 16% Hyperglycemia 23% 17% Hyperlipemia 18% 27% Hemic and Lymphatic System Anemia 50% 36% Leukopenia 48% 39% Urogenital System Kidney Function Abnormal 56% 57% Urinary Tract Infection 16% 12% Respiratory System Bronchitis 17% 18% Nervous System Tremor 15% 6% In the European trial, the cyclosporine trough concentrations were above the pre-defined target range (i.e., 100 to 200 ng/mL) at Day 122 and beyond in 32% to 68% of the patients in the cyclosporine treatment arm, whereas the tacrolimus trough concentrations were within the pre-defined target range (i.e., 5 to 15 ng/mL) in 74% to 86% of the patients in the tacrolimus treatment arm. In a U.S. trial, the incidence of adverse reactions was based on 331 heart transplant patients that received corticosteroids and tacrolimus in combination with sirolimus (n=109), tacrolimus in combination with MMF (n=107) or cyclosporine modified in combination with MMF (n=115) for 1 year. The trial population had a mean age of 53 years (range 18 to 75); the distribution was 78% male, and the composition was White (83%), African-American (13%) and Other (4%). Only selected targeted treatment-emergent adverse reactions were collected in the U.S. heart transplantation trial. Those reactions that were reported at a rate of 15% or greater in patients treated with tacrolimus and MMF include the following: any target adverse reactions (99%), hypertension (89%), hyperglycemia requiring antihyperglycemic therapy (70%), hypertriglyceridemia (65%), anemia (hemoglobin <10 g/dL) (65%), fasting blood glucose >140 mg/dL (on two separate occasions) (61%), hypercholesterolemia (57%), hyperlipidemia (34%), WBCs <3,000 cells/mcL (34%), serious bacterial infections (30%), magnesium <1.2 mEq/L (24%), platelet count <75,000 cells/mcL (19%), and other opportunistic infections (15%). Other targeted treatment-emergent adverse reactions in tacrolimus-treated patients occurred at a rate of less than 15%, and include the following: Cushingoid features, impaired wound healing, hyperkalemia, Candida infection, and CMV infection/syndrome. Other less frequently observed adverse reactions in heart transplantation patients are described under the subsection “Less Frequently Reported Adverse Reactions (> 3% and < 15%) in Liver, Kidney and Heart Transplant Studies.” New Onset Diabetes After Transplant Kidney Transplantation New Onset Diabetes After Transplant (NODAT) is defined as a composite of fasting plasma glucose ≥126 mg/dL, HbA 1C ≥ 6%, insulin use ≥ 30 days, or oral hypoglycemic use. In a trial in kidney transplant patients (Study 2), NODAT was observed in 75% in the tacrolimus-treated and 61% in the NEORAL-treated patients without pre-transplant history of diabetes mellitus (Table 10) [see Clinical Studies (14.1) ]. Table 10. Incidence of New Onset Diabetes After Transplant at 1 year in Kidney Transplant Recipients in a Phase 3 Trial (Study 2) Parameter Treatment Group Tacrolimus/MMF (N = 212) NEORAL/MMF (N = 212) NODAT 112/150 (75%) 93/152 (61%) Fasting Plasma Glucose ≥ 126 mg/dL 96/150 (64%) 80/152 (53%) HbA 1C ≥ 6% 59/150 (39%) 28/152 (18%) Insulin Use ≥ 30 days 9/150 (6%) 4/152 (3%) Oral Hypoglycemic Use 15/150 (10%) 5/152 (3%) In early trials of tacrolimus, Post-Transplant Diabetes Mellitus (PTDM) was evaluated with a more limited criterion of “use of insulin for 30 or more consecutive days with < 5 day gap” in patients without a prior history of insulin-dependent diabetes mellitus or non-insulin dependent diabetes mellitus. Data are presented in Tables 11 to 14. PTDM was reported in 20% of Tacrolimus/Azathioprine (AZA)-treated kidney transplant patients without pre-transplant history of diabetes mellitus in a Phase 3 trial (Table 11). The median time to onset of PTDM was 68 days. Insulin dependence was reversible in 15% of these PTDM patients at one year and in 50% at 2 years post-transplant. African-American and Hispanic kidney transplant patients were at an increased risk of development of PTDM (Table 12). Table 11. Incidence of Post-Transplant Diabetes Mellitus and Insulin Use at 2 Years in Kidney Transplant Recipients in a Phase 3 Trial using Azathioprine (AZA) Status of PTDM * Tacrolimus/AZA CsA/AZA Patients without pre-transplant history of diabetes mellitus 151 151 New onset PTDM * , 1 st Year 30/151 (20%) 6/151 (4%) Still insulin-dependent at one year in those without prior history of diabetes 25/151 (17%) 5/151 (3%) New onset PTDM * post 1 year 1 0 Patients with PTDM * at 2 years 16/151 (11%) 5/151 (3%) * Use of insulin for 30 or more consecutive days, with < 5-day gap, without a prior history of insulin-dependent diabetes mellitus or non-insulin dependent diabetes mellitus. Table 12. Development of Post-Transplant Diabetes Mellitus by Race or Ethnicity and by Treatment Group During First Year Post Kidney Transplantation in a Phase 3 Trial Patient Race Patients Who Developed PTDM * Tacrolimus Cyclosporine African-American 15/41 (37%) 3 (8%) Hispanic 5/17 (29%) 1 (6%) Caucasian 10/82 (12%) 1 (1%) Other 0/11 (0%) 1 (10%) Total 30/151 (20%) 6 (4%) * Use of insulin for 30 or more consecutive days, with < 5-day gap, without a prior history of insulin-dependent diabetes mellitus or non-insulin dependent diabetes mellitus. Liver Transplantation Insulin-dependent PTDM was reported in 18% and 11% of tacrolimus-treated liver transplant patients and was reversible in 45% and 31% of these patients at 1 year post-transplant, in the U.S. and European randomized trials, respectively, (Table 13). Hyperglycemia was associated with the use of tacrolimus in 47% and 33% of liver transplant recipients in the U.S. and European randomized trials, respectively, and may require treatment [see Adverse Reactions (6.1) ]. Table 13. Incidence of Post-Transplant Diabetes Mellitus and Insulin Use at 1 Year in Liver Transplant Recipients Status of PTDM * U.S. Trial European Trial Tacrolimus Cyclosporine Tacrolimus Cyclosporine Patients at risk † 239 236 239 249 New Onset PTDM * 42 (18%) 30 (13%) 26 (11%) 12 (5%) Patients still on insulin at 1 year 23 (10%) 19 (8%) 18 (8%) 6 (2%) * Use of insulin for 30 or more consecutive days, with < 5-day gap, without a prior history of insulin-dependent diabetes mellitus or non-insulin dependent diabetes mellitus. † Patients without pre-transplant history of diabetes mellitus. Heart Transplantation Insulin-dependent PTDM was reported in 13% and 22% of tacrolimus-treated heart transplant patients receiving mycophenolate mofetil (MMF) or azathioprine (AZA) and was reversible in 30% and 17% of these patients at one year post-transplant, in the U.S. and European randomized trials, respectively (Table 14). Hyperglycemia, defined as two fasting plasma glucose levels ≥126 mg/dL, was reported with the use of tacrolimus plus MMF or AZA in 32% and 35% of heart transplant recipients in the U.S. and European randomized trials, respectively, and may require treatment [see Adverse Reactions ( 6.1 ) ]. Table 14. Incidence of Post-Transplant Diabetes Mellitus and Insulin Use at 1 Year in Heart Transplant Recipients Status of PTDM * U.S. Trial European Trial Tacrolimus/ MMF Cyclosporine/MMF Tacrolimus/ AZA Cyclosporine/ AZA Patients at risk † 75 83 132 138 New Onset PTDM * 10 (13%) 6 (7%) 29 (22%) 5 (4%) Patients still on insulin at 1 year ‡ 7 (9%) 1 (1%) 24 (18%) 4 (3%) * Use of insulin for 30 or more consecutive days without a prior history of insulin-dependent diabetes mellitus or non-insulin dependent diabetes mellitus. † Patients without pre-transplant history of diabetes mellitus. ‡ 7 to 12 months for the U.S. trial. Less Frequently Reported Adverse Reactions (>3% and <15%) in Liver, Kidney, and Heart Transplant Studies The following adverse reactions were reported in either liver, kidney, and/or heart transplant recipients who were treated with tacrolimus in clinical trials. Nervous System : Abnormal dreams, agitation, amnesia, anxiety, confusion, convulsion, crying, depression, elevated mood, emotional lability, encephalopathy, hemorrhagic stroke, hallucinations, hypertonia, incoordination, monoparesis, myoclonus, nerve compression, nervousness, neuralgia, neuropathy, paralysis flaccid, psychomotor skills impaired, psychosis, quadriparesis, somnolence, thinking abnormal, vertigo, writing impaired Special Senses: Abnormal vision, amblyopia, ear pain, otitis media, tinnitus Gastrointestinal: Cholangitis, cholestatic jaundice, duodenitis, dysphagia, esophagitis, flatulence, gastritis, gastroesophagitis, gastrointestinal hemorrhage, GGT increase, GI disorder, GI perforation, hepatitis, hepatitis granulomatous, ileus, increased appetite, jaundice, liver damage, esophagitis ulcerative, oral moniliasis, pancreatic pseudocyst, stomatitis Cardiovascular: Abnormal ECG, angina pectoris, arrhythmia, atrial fibrillation, atrial flutter, bradycardia, cardiac fibrillation, cardiopulmonary failure, congestive heart failure, deep thrombophlebitis, echocardiogram abnormal, electrocardiogram QRS complex abnormal, electrocardiogram ST segment abnormal, heart failure, heart rate decreased, hemorrhage, hypotension, phlebitis, postural hypotension, syncope, tachycardia, thrombosis, vasodilatation Urogenital: Acute kidney failure, albuminuria, BK nephropathy, bladder spasm, cystitis, dysuria, hematuria, hydronephrosis, kidney failure, kidney tubular necrosis, nocturia, pyuria, toxic nephropathy, urge incontinence, urinary frequency, urinary incontinence, urinary retention, vaginitis Metabolic/Nutritional: Acidosis, alkaline phosphatase increased, alkalosis, ALT (SGPT) increased, AST (SGOT) increased, bicarbonate decreased, bilirubinemia, dehydration, GGT increased, gout, healing abnormal, hypercalcemia, hypercholesterolemia, hyperphosphatemia, hyperuricemia, hypervolemia, hypocalcemia, hypoglycemia, hyponatremia, hypoproteinemia, lactic dehydrogenase increased, weight gain Endocrine: Cushing’s syndrome Hemic/Lymphatic: Coagulation disorder, ecchymosis, hematocrit increased, hypochromic anemia, leukocytosis, polycythemia, prothrombin decreased, serum iron decreased Miscellaneous: Abdomen enlarged, abscess, accidental injury, allergic reaction, cellulitis, chills, fall, flu syndrome, generalized edema, hernia, mobility decreased, peritonitis, photosensitivity reaction, sepsis, temperature intolerance, ulcer Musculoskeletal: Arthralgia, cramps, generalized spasm, leg cramps, myalgia, myasthenia, osteoporosis Respiratory: Asthma, emphysema, hiccups, lung function decreased, pharyngitis, pneumonia, pneumothorax, pulmonary edema, rhinitis, sinusitis, voice alteration Skin: Acne, alopecia, exfoliative dermatitis, fungal dermatitis, herpes simplex, herpes zoster, hirsutism, neoplasm skin benign, skin discoloration, skin ulcer, sweating Additional pediatric use information is approved for Astellas Pharma US, Inc.’s Prograf (tacrolimus) products. However, due to Astellas Pharma US, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information 6.2 Postmarketing Experience The following adverse reactions have been reported from worldwide marketing experience with tacrolimus. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of the reporting, or (3) strength of causal connection to the drug. Other reactions include: Cardiovascular: Atrial fibrillation, atrial flutter, cardiac arrhythmia, cardiac arrest, electrocardiogram T wave abnormal, flushing, myocardial infarction, myocardial ischemia, pericardial effusion, QT prolongation, Torsades de pointes , venous thrombosis deep limb, ventricular extrasystoles, ventricular fibrillation, myocardial hypertrophy Gastrointestinal: Bile duct stenosis, colitis, enterocolitis, gastroenteritis, gastrooesophageal reflux disease, hepatic cytolysis, hepatic necrosis, hepatotoxicity, impaired gastric emptying, liver fatty, mouth ulceration, pancreatitis hemorrhagic, pancreatitis necrotizing, stomach ulcer, veno-occlusive liver disease Hemic/Lymphatic: Agranulocytosis, disseminated intravascular coagulation, hemolytic anemia, neutropenia, febrile neutropenia, pancytopenia, thrombocytopenic purpura, thrombotic thrombocytopenic purpura, pure red cell aplasia thrombotic microangiopathy Infections: Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal; -polyoma virus-associated nephropathy (PVAN) including graft loss Metabolic/Nutritional: Glycosuria, increased amylase including pancreatitis, weight decreased Miscellaneous: Feeling hot and cold, feeling jittery, hot flushes, multi-organ failure, primary graft dysfunction Musculoskeletal and Connective Tissue Disorders: Pain in extremity including Calcineurin-Inhibitor Induced Pain Syndrome (CIPS) Nervous System: Carpal tunnel syndrome, cerebral infarction, hemiparesis, leukoencephalopathy, mental disorder, mutism, posterior reversible encephalopathy syndrome (PRES), progressive multifocal leukoencephalopathy (PML), quadriplegia, speech disorder, syncope Respiratory: Acute respiratory distress syndrome, interstitial lung disease, lung infiltration, respiratory distress, respiratory failure Skin: Stevens-Johnson syndrome, toxic epidermal necrolysis Special Senses: Blindness, optic neuropathy, blindness cortical, hearing loss including deafness, photophobia Urogenital: Acute renal failure, cystitis hemorrhagic, hemolytic-uremic syndrome"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Mycophenolic Acid Products: Can increase MPA exposure after crossover from cyclosporine to tacrolimus; monitor for MPA-related adverse reactions and adjust MMF or MPA dose as needed. ( 7.1 ) Nelfinavir and Grapefruit Juice: Increased tacrolimus concentrations via CYP3A inhibition; avoid concomitant use. ( 7.2 ) CYP3A Inhibitors: Increased tacrolimus concentrations; monitor concentrations and adjust tacrolimus dose as needed. ( 5.11 , 7.2 ) CYP3A4 Inducers: Decreased tacrolimus concentrations; monitor concentrations and adjust tacrolimus dose as needed. ( 5.11 , 7.2 ) Therapeutic drug monitoring and dose reduction for tacrolimus should be considered when tacrolimus is co-administered with cannabidiol. ( 5.17 , 7.3 ) 7.1 Mycophenolic Acid When tacrolimus is prescribed with a given dose of a mycophenolic acid (MPA) product, exposure to MPA is higher with tacrolimus co-administration than with cyclosporine co-administration with MPA, because cyclosporine interrupts the enterohepatic recirculation of MPA while tacrolimus does not. Monitor for MPA-associated adverse reactions and reduce the dose of concomitantly administered mycophenolic acid products as needed. 7.2 Effects of Other Drugs on Tacrolimus Table 15 displays the effects of other drugs on tacrolimus Table 15: Effects of Other Drugs/Substances on Tacrolimus * Drug/Substance Class or Name Drug Interaction Effect Recommendations Grapefruit or grapefruit juice † May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions ( 5.6 , 5.11 , 5.12 )] . Avoid grapefruit or grapefruit juice. Strong CYP3A Inducers ‡ : Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s Wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions ( 5.11 )]. Increase tacrolimus dose and monitor tacrolimus whole blood trough concentrations [see Dosage and Administration ( 2.2 , 2.6 ) and Clinical Pharmacology ( 12.3 )]. Strong CYP3A Inhibitors ‡ : Protease inhibitors (e.g., nelfinavir, telaprevir, boceprevir, ritonavir), azole antifungals (e.g., voriconazole, posaconazole, itraconazole, ketoconazole), antibiotics (e.g., clarithromycin, troleandomycin, chloramphenicol), nefazodone, letermovir, Schisandra sphenanthera extracts May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) A rapid, sharp rise in tacrolimus levels may occur early, despite an immediate reduction of tacrolimus dose [see Warnings and Precautions ( 5.6 , 5.11, 5.12 )] . Reduce tacrolimus dose (for voriconazole and posaconazole, give one-third of the original dose) and adjust dose based on tacrolimus whole blood trough concentrations [see Dosage and Administration ( 2.2 , 2.6 ) and Clinical Pharmacology ( 12.3 )]. Early and frequent monitoring of tacrolimus whole blood trough levels should start within 1 to 3 days and continue monitoring as necessary [see Warnings and Precautions ( 5.11 )]. Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., erythromycin, fluconazole), calcium channel blockers (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions ( 5.6 , 5.11 , 5.12 )]. Monitor tacrolimus whole blood trough concentrations and reduce tacrolimus dose if needed [see Dosage and Administration ( 2.2 , 2.6 ) and Clinical Pharmacology ( 12.3 )]. Other drugs, such as: Magnesium and aluminum hydroxide antacids Metoclopramide May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions ( 5.6 , 5.11 , 5.12 )]. Monitor tacrolimus whole blood trough concentrations and reduce tacrolimus dose if needed [see Dosage and Administration ( 2.2 , 2.6 ) and Clinical Pharmacology ( 12.3 ) ]. Mild or Moderate CYP3A Inducers Methylprednisolone, prednisone May decrease tacrolimus whole blood trough concentrations. Monitor tacrolimus whole blood trough concentrations and adjust tacrolimus dose if needed [see Dosage and Administration ( 2.2 , 2.6 )]. Caspofungin May decrease tacrolimus whole blood trough concentrations. Monitor tacrolimus whole blood trough concentrations and adjust tacrolimus capsules dose if needed [see Dosage and Administration ( 2.2 , 2.6 )]. * Tacrolimus dosage adjustment recommendation based on observed effect of coadministered drug on tacrolimus exposures [see Clinical Pharmacology ( 12.3 )], literature reports of altered tacrolimus exposures, or the other drug’s known CYP3A inhibitor/inducer status. † High dose or double strength grapefruit juice is a strong CYP3A inhibitor; low dose or single strength grapefruit juice is a moderate CYP3A inhibitor. ‡ Strong CYP3A inhibitor/inducer, based on reported effect on exposures to tacrolimus along with supporting in vitro CYP3A inhibitor/inducer data, or based on drug-drug interaction studies with midazolam (sensitive CYP3A probe substrate). Direct Acting Antiviral (DAA) Therapy The pharmacokinetics of tacrolimus may be impacted by changes in liver function during DAA therapy, related to clearance of HCV virus. Close monitoring and potential dose adjustment of tacrolimus is warranted to ensure continued efficacy and safety [see Dosage and Administration ( 2.2 , 2.6 )]. 7.3 Cannabidiol The blood levels of tacrolimus may increase upon concomitant use with cannabidiol. When cannabidiol and tacrolimus are co-administered, closely monitor for an increase in tacrolimus blood levels and for adverse reactions suggestive of tacrolimus toxicity. A dose reduction of tacrolimus should be considered as needed when ta crolimus is co-administered with cannabidiol [see Dosage and Administration ( 2.2 , 2.6 )and Warnings and Precautions ( 5.17 )]."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Tacrolimus capsule is a calcineurin-inhibitor immunosuppressant indicated for the prophylaxis of organ rejection in adult patients receiving allogeneic liver, kidney, or heart transplants, and pediatric patients receiving allogeneic liver transplants in combination with other immunosuppressants. ( 1.1 ) 1.1 Prophylaxis of Organ Rejection in Kidney, Liver or Heart Transplant Tacrolimus capsules are indicated for the prophylaxis of organ rejection, in adult patients receiving allogeneic kidney transplant [see Clinical Studies ( 14.1 )] , liver transplant [see Clinical Studies ( 14.2 )] , heart transplant [ see Clinical Studies ( 14.3 )] , and pediatric patients receiving allogeneic liver transplants [see Clinical Studies ( 14.2) ] in combination with other immunosuppressants. Additional pediatric use information is approved for Astellas Pharma US, Inc.’s Prograf (tacrolimus) products. However, due to Astellas Pharma US, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Not Interchangeable with Extended-Release Tacrolimus Products-Medication Errors: Instruct patients or caregivers to recognize the appearance of tacrolimus capsules. ( 5.3 ) New Onset Diabetes After Transplant: Monitor blood glucose. ( 5.4 ) Nephrotoxicity (acute and/or chronic): Reduce the dose; use caution with other nephrotoxic drugs. ( 5.5 ) Neurotoxicity: Including risk of Posterior Reversible Encephalopathy Syndrome (PRES); monitor for neurologic abnormalities; reduce or discontinue tacrolimus capsules. ( 5.6 ) Hyperkalemia: Monitor serum potassium levels. Consider carefully before using with other agents also associated with hyperkalemia. ( 5.7 ) Hypertension: May require antihypertensive therapy. Monitor relevant drug-drug interactions. ( 5.8 ) Anaphylactic Reactions with IV formulation: Observe patients receiving tacrolimus injection for signs and symptoms of anaphylaxis. ( 5.9 ) Not recommended for use with sirolimus: Not recommended in liver and heart transplant due to increased risk of serious adverse reactions. ( 5.10 ) Myocardial Hypertrophy: Consider dose reduction/discontinuation. ( 5.13 ) Immunizations: Avoid live vaccines. ( 5.14 ) Pure Red Cell Aplasia: Consider discontinuation of tacrolimus. ( 5.15 ) Thrombotic Microangiopathy, Including Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura: May occur, especially in patients with infections and certain concomitant medications. ( 5.16 ) 5.1 Lymphoma and Other Malignancies Patients receiving immunosuppressants, including tacrolimus, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. As usual for patients with increased risk for skin cancer, examine patients for skin changes; exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen with a high protection factor. Post-transplant lymphoproliferative disorder (PTLD) has been reported in immunosuppressed organ transplant recipients. The majority of PTLD events appear related to Epstein-Barr Virus (EBV) infection. The risk of PTLD appears greatest in those individuals who are EBV seronegative, a population which includes many young children. Monitor EBV serology during treatment. 5.2 Serious Infections Patients receiving immunosuppressants, including tacrolimus, are at increased risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections. These infections may lead to serious, including fatal, outcomes. Serious viral infections reported include: • Polyomavirus-associated nephropathy (PVAN), mostly due to BK virus infection • JC virus-associated progressive multifocal leukoencephalopathy (PML) • Cytomegalovirus infections: CMV seronegative transplant patients who receive an organ from a CMV seropositive donor disease are at higher risk of developing CMV viremia and CMV disease. Monitor for the development of infection and adjust the immunosuppressive regimen to balance the risk of rejection with the risk of infection [see Adverse Reactions ( 6.1 , 6.2) ]. 5.3 Not Interchangeable with Extended-Release Tacrolimus Products-Medication Errors Medication errors, including substitution and dispensing errors, between tacrolimus immediate-release products and tacrolimus extended-release products were reported outside the U.S. This led to serious adverse reactions, including graft rejection, or other adverse reactions due to under-or overexposure to tacrolimus. Tacrolimus is not interchangeable or substitutable for tacrolimus extended-release products. Changes between tacrolimus immediate-release and extended-release dosage forms must occur under physician supervision. Instruct patients and caregivers to recognize the appearance of tacrolimus dosage forms [see Dosage Forms and Strengths ( 3 ) ] and to confirm with the healthcare provider if a different product is dispensed. 5.4 New Onset Diabetes After Transplant Tacrolimus was shown to cause new onset diabetes mellitus in clinical trials of kidney, liver or heart transplantation. New onset diabetes after transplantation may be reversible in some patients. African-American and Hispanic kidney transplant patients are at an increased risk. Blood glucose concentrations should be monitored closely in patients using tacrolimus [see Adverse Reactions (6.1) ]. 5.5 Nephrotoxicity due to Tacrolimus capsules and Drug Interactions Tacrolimus, like other calcineurin inhibitors, can cause acute or chronic nephrotoxicity. in transplant patients due to its vasoconstrictive effect on renal vasculature, toxic tubulopathy and tubular-interstitial effects. Nephrotoxicity was reported in clinical trials [see Adverse Reactions ( 6.1) ]. Acute renal impairment associated with tacrolimus toxicity can result in high serum creatinine, hyperkalemia, decreased secretion of urea and hyperuricemia, and is usually reversible. In patients with elevated serum creatinine and tacrolimus whole blood trough concentrations greater than the recommended range, consider dosage reduction or temporary interruption of tacrolimus administration. The risk for nephrotoxicity may increase when tacrolimus is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors) . When tacrolimus is used concurrently with other known nephrotoxic drugs, monitor renal function and tacrolimus blood concentrations, and adjust doses of both tacrolimus and/or concomitant medications during concurrent use [see Drug Interactions ( 7.2 )]. 5.6 Neurotoxicity Tacrolimus may cause a spectrum of neurotoxicities. The most severe neurotoxicities include posterior reversible encephalopathy syndrome (PRES), delirium, seizure and coma; others include tremors, paresthesias, headache, mental status changes, and changes in motor and sensory functions [see Adverse Reactions (6.1 , 6.2 )] . As symptoms may be associated with tacrolimus whole blood trough concentrations at or above the recommended range, monitor for neurologic symptoms and consider dosage reduction or discontinuation of tacrolimus if neurotoxicity occurs. 5.7 Hyperkalemia Hyperkalemia has been reported with tacrolimus use. Serum potassium levels should be monitored. Careful consideration should be given prior to use of other agents also associated with hyperkalemia (e.g., potassium-sparing diuretics, ACE inhibitors, angiotensin receptor blockers) during tacrolimus therapy [see Adverse Reactions (6.1) ] . Monitor serum potassium levels periodically during treatment. 5.8 Hypertension Hypertension is a common adverse effect of tacrolimus therapy and may require antihypertensive therapy [see Adverse Reactions (6.1) ] . The control of blood pressure can be accomplished with any of the common antihypertensive agents, though careful consideration should be given prior to use of antihypertensive agents associated with hyperkalemia (e.g., potassium-sparing diuretics, ACE inhibitors, angiotensin receptor blockers) [see Warnings and Precautions ( 5.7 )] . Calcium-channel blocking agents may increase tacrolimus blood concentrations and therefore require dosage reduction of tacrolimus [see Drug Interactions (7.2 )] . 5.9 Anaphylactic Reactions with Tacrolimus Injection Anaphylactic reactions have occurred with injectables containing castor oil derivatives, including tacrolimus, in a small percentage of patients (0.6%). The exact cause of these reactions is not known. Tacrolimus injection should be reserved for patients who are unable to take tacrolimus orally. Monitor patients for anaphylaxis when using the intravenous route of administration [see Dosage and Administratio n ( 2.1 )]. 5.10 Not Recommended for Use with Sirolimus Tacrolimus capsules are not recommended for use with sirolimus: The use of sirolimus with tacrolimus in studies of de novo liver transplant patients was associated with an excess mortality, graft loss, and hepatic artery thrombosis (HAT) and is not recommended. The use of sirolimus (2 mg per day) with tacrolimus in heart transplant patients in a U.S. trial was associated with increased risk of renal function impairment, wound healing complications, and insulin-dependent post-transplant diabetes mellitus, and is not recommended [see Clinical Studies ( 14.3 )]. The use of sirolimus with tacrolimus capsules may increase the risk of thrombotic microangiopathy [see Warnings and Precautions ( 5.16 )]. 5.11 Interactions with CYP3A4 Inhibitors and Inducers When co-administering tacrolimus with strong CYP3A4 inhibitors (e.g., telaprevir, boceprevir, ritonavir, ketoconazole, itraconazole, voriconazole, clarithromycin) and strong inducers (e.g., rifampin, rifabutin), adjustments in the dosing regimen of tacrolimus and subsequent frequent monitoring of tacrolimus whole blood trough concentrations and tacrolimus-associated adverse reactions are recommended A rapid, sharp rise in tacrolimus levels has been reported after co-administration with a strong CYP3A4 inhibitor, clarithromycin, despite an initial reduction of tacrolimus dose. Early and frequent monitoring of tacrolimus whole blood trough levels is recommended [see Drug Interactions (7.2) ]. 5.12 QT Prolongation Tacrolimus may prolong the QT/QTc interval and may cause Torsades de pointes . Avoid tacrolimus in patients with congenital long QT syndrome. In patients with congestive heart failure, bradyarrhythmias, those taking certain antiarrhythmic medications or other medicinal products that lead to QT prolongation, and those with electrolyte disturbances such as hypokalemia, hypocalcemia, or hypomagnesemia, consider obtaining electrocardiograms and monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment. When co-administering tacrolimus with other substrates and/or inhibitors of CYP3A4 that also have the potential to prolong the QT interval, a reduction in tacrolimus dose, frequent monitoring of tacrolimus whole blood concentrations, and monitoring for QT prolongation is recommended. Use of tacrolimus with amiodarone has been reported to result in increased tacrolimus whole blood concentrations with or without concurrent QT prolongation [see Drug Interactions ( 7.2 ) ]. 5.13 Myocardial Hypertrophy Myocardial hypertrophy has been reported in infants, children, and adults, particularly those with high tacrolimus trough concentrations, and is generally manifested by echocardiographically demonstrated concentric increases in left ventricular posterior wall and interventricular septum thickness. This condition appears reversible in most cases following dose reduction or discontinuance of therapy. In patients who develop renal failure or clinical manifestations of ventricular dysfunction while receiving tacrolimus therapy, echocardiographic evaluation should be considered. If myocardial hypertrophy is diagnosed, dosage reduction or discontinuation of tacrolimus should be considered [see Adverse Reactions (6.2) ]. 5.14 Immunizations Whenever possible, administer the complete complement of vaccines before transplantation and treatment with tacrolimus. The use of live vaccines should be avoided during treatment with tacrolimus; examples include (not limited to) the following: intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines. Inactivated vaccines noted to be safe for administration after transplantation may not be sufficiently immunogenic during treatment with tacrolimus. 5.15 Pure Red Cell Aplasia Cases of pure red cell aplasia (PRCA) have been reported in patients treated with tacrolimus. A mechanism for tacrolimus-induced PRCA has not been elucidated. All patients reported risk factors for PRCA such as parvovirus B19 infection, underlying disease, or concomitant medications associated with PRCA. If PRCA is diagnosed, discontinuation of tacrolimus should be considered [see Adverse Reactions (6.2) ]. 5.16 Thrombotic Microangiopathy (Including Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura) Cases of thrombotic microangiopathy (TMA), including hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP), have been reported in patients treated with tacrolimus capsules. TMA may have a multifactorial etiology. Risk factors for TMA that can occur in transplant patients include, for example, severe infections, graft-versus-host disease (GVHD), Human Leukocyte Antigen (HLA) mismatch, the use of calcineurin inhibitors and mammalian target of rapamycin (mTOR) inhibitors. These risk factors may, either alone or combined, contribute to the risk of TMA. In patients with signs and symptoms of TMA, consider tacrolimus as a risk factor. Concurrent use of tacrolimus and mTOR inhibitors may contribute to the risk of TMA. 5.17 Cannabidiol Drug Interactions When cannabidiol and tacrolimus are co-administered, closely monitor for an increase in tacrolimus blood levels and for adverse reactions suggestive of tacrolimus toxicity. A dose reduction of tacrolimus should be considered as needed when tacrolimus is co-administered with cannabidiol [see Dosage and Administration ( 2.2 , 2.6 ) and Drug Interactions (7.3) ] ."}', 'overdosage': '{"10 OVERDOSAGE Limited overdosage experience is available. Acute overdosages of up to 30 times the intended dose have been reported. Almost all cases have been asymptomatic and all patients recovered with no sequelae. Acute overdosage was sometimes followed by adverse reactions consistent with those reported with the use of tacrolimus [see Adverse Reactions ( 6.1 , 6.2 )] including tremors, abnormal renal function, hypertension, and peripheral edema; in one case of acute overdosage, transient urticaria and lethargy were observed. Based on the poor aqueous solubility and extensive erythrocyte and plasma protein binding, it is anticipated that tacrolimus is not dialyzable to any significant extent; there is no experience with charcoal hemoperfusion. The oral use of activated charcoal has been reported in treating acute overdoses, but experience has not been sufficient to warrant recommending its use. General supportive measures and treatment of specific symptoms should be followed in all cases of overdosage."}', 'active_flag': 'Y', 'generic_name': '{TACROLIMUS}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). 17.1 Administration Advise the patient or caregiver to: Inspect their tacrolimus medicine when they receive a new prescription and before taking it. If the appearance of the capsule is not the same as usual, or if dosage instructions have changed, advise patients to contact their healthcare provider as soon as possible to make sure that they have the right medicine. Other tacrolimus products cannot be substituted for tacrolimus capsules. Take tacrolimus at the same 12 hour intervals every day to achieve consistent blood concentrations. Take tacrolimus consistently either with or without food because the presence and composition of food decreases the bioavailability of tacrolimus. Not to eat grapefruit or drink grapefruit juice in combination with tacrolimus [see Drug Interactions (7.2) ]. 17.2 Development of Lymphoma and Other Malignancies Inform patients they are at increased risk of developing lymphomas and other malignancies, particularly of the skin, due to immunosuppression. Advise patients to limit exposure to sunlight and ultraviolet (UV) light by wearing protective clothing and using a broad spectrum sunscreen with a high protection factor [see Warnings and Precautions ( 5.1 )]. 17.3 Increased Risk of Infection Inform patients they are at increased risk of developing a variety of infections, including opportunistic infections, due to immunosuppression and to contact their physician if they develop any symptoms of infection such as fever, sweats or chills, cough or flu-like symptoms, muscle aches, or warm, red, painful areas on the skin [see Warnings and Precautions (5.2 )]. 17.4 New Onset Diabetes After Transplant Inform patients that tacrolimus can cause diabetes mellitus and should be advised to contact their physician if they develop frequent urination, increased thirst or hunger [see Warnings and Precautions ( 5.4 )]. 17.5 Nephrotoxicity Inform patients that tacrolimus can have toxic effects on the kidney that should be monitored. Advise patients to attend all visits and complete all blood tests ordered by their medical team [see Warnings and Precautions ( 5.5 )]. 17.6 Neurotoxicity Inform patients that they are at risk of developing adverse neurologic reactions including seizure, altered mental status, and tremor. Advise patients to contact their physician should they develop vision changes, delirium, or tremors [see Warnings and Precautions ( 5.6 )]. 17.7 Hyperkalemia Inform patients that tacrolimus can cause hyperkalemia. Monitoring of potassium levels may be necessary, especially with concomitant use of other drugs known to cause hyperkalemia [see Warnings and Precautions ( 5.7 )]. 17.8 Hypertension Inform patients that tacrolimus can cause high blood pressure which may require treatment with antihypertensive therapy. Advise patients to monitor their blood pressure [see Warnings and Precautions ( 5.8 )]. 17.9 Thrombotic Microangiopathy Inform patients that tacrolimus capsules can cause blood clotting problems. The risk of this occurring increases when patients take tacrolimus capsules and sirolimus or everolimus concomitantly, or when patients develop certain infections. Advise them to seek medical attention promptly if they develop fever, petequiae or bruises, fatigue, confusion, jaundice, oliguria. [see Warnings and Precautions ( 5.16 )]. 17.10 Drug Interactions Instruct patients to tell their healthcare providers when they start or stop taking any medicines, including prescription medicines and nonprescription medicines, natural or herbal remedies, nutritional supplements, and vitamins. Advise patients to avoid grapefruit and grapefruit juice [see Drug Interactions ( 7 )]. 17.11 Pregnancy, Lactation and Infertility Inform women of childbearing potential that tacrolimus can harm the fetus. Instruct male and female patients to discuss with their healthcare provider family planning options including appropriate contraception. Also, discuss with pregnant patients the risks and benefits of breastfeeding their infant [see Use in Specific Populations ( 8.1 , 8.2 , 8.3 )]. Encourage female transplant patients who become pregnant and male patients who have fathered a pregnancy, exposed to immunosuppressants including tacrolimus, to enroll in the voluntary Transplantation Pregnancy Registry International. To enroll or register, patients can call the toll free number 1-877-955-6877 or https://www.transplantpregnancyregistry.org/ [see Use in Specific Populations ( 8.1 )]. Based on animal studies, tacrolimus may affect fertility in males and females [see Nonclinical Toxicology ( 13.1 )]. 17.12 Myocardial Hypertrophy Inform patients to report symptoms of tiredness, swelling, and/or shortness of breath (heart failure). 17.13 Immunizations Inform patients that tacrolimus can interfere with the usual response to immunizations and that they should avoid live vaccines [see Warnings and Precautions ( 5.14 )]. All other trademarks and registered trademarks are the property of their respective owners . Rx Only Manufactured by Dr. Reddy’s Laboratories Limited Bachupally – 500 090 INDIA Revised: 11/2023"}', 'pregnancy': '{"8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy registry that monitors pregnancy outcomes in women exposed to tacrolimus during pregnancy. The Transplantation Pregnancy Registry International (TPRI) is a voluntary pregnancy exposure registry that monitors outcomes of pregnancy in female transplant recipients and those fathered by male transplant recipients exposed to immunosuppressants including tacrolimus. Healthcare providers are encouraged to advise their patients to register by contacting the Transplantation Pregnancy Registry International at 1-877-955-6877 or https://www.transplantpregnancyregistry.org/. Risk Summary Tacrolimus can cause fetal harm when administered to a pregnant woman. Data from postmarketing surveillance and TPRI suggest that infants exposed to tacrolimus in utero are at a risk of prematurity, birth defects/congenital anomalies, low birth weight, and fetal distress [see Human Data] . Advise pregnant women of the potential risk to the fetus. Administration of oral tacrolimus to pregnant rabbits and rats throughout the period of organogenesis was associated with maternal toxicity/lethality, and an increased incidence of abortion, malformation and embryofetal death at clinically relevant doses (0.5 to 6.9 times the recommended clinical dose range [0.2 to 0.075 mg/kg/day], on a mg/m 2 basis). Administration of oral tacrolimus to pregnant rats after organogenesis and throughout lactation produced maternal toxicity, effects on parturition, reduced pup viability and reduced pup weight at clinically relevant doses (0.8 to 6.9 times the recommended clinical dose range, on a mg/m 2 basis). Administration of oral tacrolimus to rats prior to mating, and throughout gestation and lactation produced maternal toxicity/lethality, marked effects on parturition, embryofetal loss, malformations, and reduced pup viability at clinically relevant doses (0.8 to 6.9 times the recommended clinical dose range, on a mg/m 2 basis). Interventricular septal defects, hydronephrosis, craniofacial malformations and skeletal effects were observed in offspring that died [see Animal Data] . The background risk of major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo-Fetal Risk Risks during pregnancy are increased in organ transplant recipients. The risk of premature delivery following transplantation is increased. Pre-existing hypertension and diabetes confer additional risk to the pregnancy of an organ transplant recipient. Pre-gestational and gestational diabetes are associated with birth defects/congenital anomalies, hypertension, low birth weight and fetal death. Cholestasis of pregnancy (COP) was reported in 7% of liver or liver-kidney (LK) transplant recipients, compared with approximately 1% of pregnancies in the general population. However, COP symptoms resolved postpartum and no long-term effects on the offspring were reported. Maternal Adverse Reactions Tacrolimus may increase hyperglycemia in pregnant women with diabetes (including gestational diabetes). Monitor maternal blood glucose levels regularly [see Warnings and Precautions (5.4) ]. Tacrolimus may exacerbate hypertension in pregnant women and increase pre-eclampsia. Monitor and control blood pressure [see Warnings and Precautions ( 5.7 , 5.8 )]. Fetal/Neonatal Adverse Reactions Renal dysfunction, transient neonatal hyperkalemia and low birth weight have been reported at the time of delivery in infants of mothers taking tacrolimus. Labor or Delivery There is an increased risk for premature delivery (< 37 weeks) following transplantation and maternal exposure to tacrolimus. Data Human Data There are no adequate and well controlled studies on the effects of tacrolimus in human pregnancy. Safety data from the TPRI and postmarketing surveillance suggest infants exposed to tacrolimus in utero have an increased risk for miscarriage, pre-term delivery (< 37 weeks), low birth weight (< 2500 g), birth defects/congenital anomalies and fetal distress. TPRI reported 450 and 241 total pregnancies in kidney and liver transplant recipients exposed to tacrolimus, respectively. The TPRI pregnancy outcomes are summarized in Table 16. In the table below, the number of recipients exposed to tacrolimus concomitantly with mycophenolic acid (MPA) products during the preconception and first trimester periods is high (27% and 29% for renal and liver transplant recipients, respectively). Because MPA products may also cause birth defects, the birth defect rate may be confounded and this should be taken into consideration when reviewing the data, particularly for birth defects. Birth defects observed include cardiac malformations, craniofacial malformations, renal/urogenital disorders, skeletal abnormalities, neurological abnormalities and multiple malformations. Table 16. TPRI Reported Pregnancy Outcomes in Transplant Recipients with Exposure to Tacrolimus Kidney Liver Pregnancy Outcomes* 462 253 Miscarriage 24.5% 25% Live births 331 180 Pre-term delivery (< 37 weeks) 49% 42% Low birth weight (< 2500 g) 42% 30% Birth defects 8%† 5% * Includes multiple births and terminations. † Birth defect rate confounded by concomitant MPA products exposure in over half of offspring with birth defects. Additional information reported by TPRI in pregnant transplant patients receiving tacrolimus included diabetes during pregnancy in 9% of kidney recipients and 13% of liver recipients and hypertension during pregnancy in 53% of kidney recipients and 16.2% of liver recipients. Animal Data Administration of oral tacrolimus to pregnant rabbits throughout organogenesis produced maternal toxicity and abortion at 0.32 mg/kg (0.5 to 1.4 times the recommended clinical dose range [0.2 to 0.075 mg/kg/day], on a mg/m 2 basis). At 1 mg/kg (1.6 to 4.3 times the recommended clinical dose range), embryofetal lethality and fetal malformations (ventricular hypoplasia, interventricular septal defect, bulbous aortic arch, stenosis of ductus arteriosus, omphalocele, gallbladder agenesis, skeletal anomalies) were observed. Administration of 3.2 mg/kg oral tacrolimus (2.6 to 6.9 times the recommended clinical dose range) to pregnant rats throughout organogenesis produced maternal toxicity/lethality, embryofetal lethality and decreased fetal body weight in the offspring of C-sectioned dams; and decreased pup viability and interventricular septal defect in offspring of dams that delivered. In a peri-/postnatal development study, oral administration of tacrolimus to pregnant rats during late gestation (after organogenesis) and throughout lactation produced maternal toxicity, effects on parturition, and reduced pup viability at 3.2 mg/kg (2.6 to 6.9 times the recommended clinical dose range); among these pups that died early, an increased incidence of kidney hydronephrosis was observed. Reduced pup weight was observed at 1 mg/kg (0.8 to 2.2 times the recommended clinical dose range). Administration of oral tacrolimus to rats prior to mating, and throughout gestation and lactation, produced maternal toxicity/lethality, embryofetal loss and reduced pup viability at 3.2 mg/kg (2.6 to 6.9 times the recommended clinical dose range). Interventricular septal defects, hydronephrosis, craniofacial malformations and skeletal effects were observed in offspring that died. Effects on parturition (incomplete delivery of nonviable pups) were observed at 1 mg/kg (0.8 to 2.2 times the recommended clinical dose range) [see Nonclinical Toxicology ( 13.1 )]."}', 'pediatric_use': '{"8.4 Pediatric Use Safety and effectiveness have been established in pediatric liver transplant patients. Liver Transplantation Safety and efficacy in pediatric de novo liver transplant patients less than 16 years of age are based on evidence from active controlled studies that included 56 pediatric patients, 31 of which received tacrolimus. Additionally, 122 pediatric patients were studied in an uncontrolled trial of tacrolimus in living related donor liver transplantation. Pediatric patients generally required higher doses of tacrolimus to maintain blood trough concentrations of tacrolimus similar to adult patients [see Dosage and Administration (2.3) , Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3) and Clinical Studies ( 14.2 )]. Additional pediatric use information is approved for Astellas Pharma US, Inc.’s Prograf (tacrolimus) products. However, due to Astellas Pharma US, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information."}', 'geriatric_use': '{"8.5 Geriatric Use Clinical trials of tacrolimus did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy."}'}

{"PENICILLIN G POTASSIUM"}

{'contraindications': '{"CONTRAINDICATIONS A history of a hypersensitivity (anaphylactic) reaction to any penicillin is a contraindication."}', 'adverse_reactions': '{"ADVERSE REACTIONS Body as a whole The Jarisch-Herxheimer reaction is a systemic reaction that may occur after the initiation of penicillin therapy in patients with syphilis or other spirochetal infections ( i.e. , Lyme disease and Relapsing fever). The reaction begins one or two hours after initiation of therapy and disappears within 12 to 24 hours. It is characterized by fever, chills, myalgias, headache, exacerbation of cutaneous lesions, tachycardia, hyperventilation, vasodilation with flushing and mild hypotension. The pathogenesis of the Herxheimer reaction may be due to the release from the spirochetes of heat-stable pyrogen. Hypersensitivity reactions The reported incidence of allergic reactions to all penicillins ranges from 0.7 to 10 percent in different studies (see Warnings ). Sensitization is usually the result of previous treatment with a penicillin, but some individuals have had immediate reactions when first treated. In such cases, it is postulated that prior exposure to penicillin may have occurred via trace amounts present in milk or vaccines. Two types of allergic reactions to penicillin are noted clinically – immediate and delayed. Immediate reactions usually occur within 20 minutes of administration and range in severity from urticaria and pruritus to angioneurotic edema, laryngospasm, bronchospasm, hypotension, vascular collapse and death (see Warnings ). Such immediate anaphylactic reactions are very rare and usually occur after parenteral therapy, but a few cases of anaphylaxis have been reported following oral therapy. Another type of immediate reaction, an accelerated reaction, may occur between 20 minutes and 48 hours after administration and may include urticaria, pruritus, fever and, occasionally, laryngeal edema. Delayed reactions to penicillin therapy usually occur within 1–2 weeks after initiation of therapy. Manifestations include serum sickness-like symptoms, i.e ., fever, malaise, urticaria, myalgia, arthralgia, abdominal pain and various skin rashes, ranging from maculopapular eruptions to exfoliative dermatitis. Contact dermatitis has been observed in individuals who prepare penicillin solutions. Gastrointestinal system Pseudomembranous colitis has been reported with the onset occurring during or after penicillin G treatment. Nausea, vomiting, stomatitis, black or hairy tongue, and other symptoms of gastrointestinal irritation may occur, especially during oral therapy. Hematologic system Reactions include neutropenia, which resolves after penicillin therapy is discontinued; Coombs-positive hemolytic anemia, an uncommon reaction, occurs in patients treated with intravenous penicillin G in doses greater than 10 million units/day and who have previously received large doses of the drug; and with large doses of penicillin, a bleeding diathesis can occur secondary to platelet dysfunction. Metabolic Penicillin G Potassium for Injection, USP (1 million units contains 1.68 mEq of potassium ion) may cause serious and even fatal electrolyte disturbances, i.e ., hyperkalemia, when given intravenously in large doses. Nervous system Neurotoxic reactions including hyperreflexia, myoclonic twitches, seizures and coma have been reported following the administration of massive intravenous doses, and are more likely in patients with impaired renal function. Urogenital system Renal tubular damage and interstitial nephritis have been associated with large intravenous doses of penicillin G. Manifestations of this reaction may include fever, rash, eosinophilia, proteinuria, eosinophiluria, hematuria and a rise in serum urea nitrogen. Discontinuation of penicillin G results in resolution in the majority of patients. Local reactions Phlebitis and thrombophlebitis may occur, and pain at the injection site has been reported with intravenous administration. To report SUSPECTED ADVERSE EVENTS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or http://www.fda.gov/ for voluntary reporting of adverse reactions."}', 'drug_interactions': '{"Drug Interactions Bacteriostatic antibacterials ( i.e ., chloramphenicol, erythromycins, sulfonamides or tetracyclines) may antagonize the bactericidal effect of penicillin, and concurrent use of these drugs should be avoided. This has been documented in vitro ; however, the clinical significance of this interaction is not well-documented. Penicillin blood levels may be prolonged by concurrent administration of probenecid which blocks the renal tubular secretion of penicillins. Other drugs may compete with penicillin G for renal tubular secretion and thus prolong the serum half-life of penicillin. These drugs include: aspirin, phenylbutazone, sulfonamides, indomethacin, thiazide diuretics, furosemide and ethacrynic acid."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Therapy Penicillin G Potassium for Injection, USP is indicated in the treatment of serious infections caused by susceptible strains of the designated microorganisms in the conditions listed below. Appropriate culture and susceptibility tests should be done before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to penicillin G. Therapy with Penicillin G Potassium for Injection, USP may be initiated before results of such tests are known when there is reason to believe the infection may involve any of the organisms listed below; however, once these results become available, appropriate therapy should be continued. CLINICAL INDICATION INFECTING ORGANISM Septicemia, empyema, pneumonia, pericarditis, endocarditis, meningitis Streptococcus pyogenes (group A β-hemolytic streptococcus), other β-hemolytic streptococci including groups C, H, G, L and M, Streptococcus pneumoniae and Staphylococcus species (non-penicillinase producing strains) Anthrax Bacillus anthracis Actinomycosis (cervico-facial disease and thoracic and abdominal disease) Actinomyces israelii Botulism (adjunctive therapy to antitoxin), gas gangrene, and tetanus (adjunctive therapy to human tetanus immune globulin) Clostridium species Diphtheria (adjunctive therapy to antitoxin and prevention of the carrier state) Corynebacterium diphtheriae Erysipelothrix endocarditis Erysipelothrix rhusiopathiae Fusospirochetosis (severe infections of the oropharynx [Vincent\'s], lower respiratory tract and genital area) Fusobacterium species and spirochetes Listeria infections including meningitis and endocarditis Listeria monocytogenes Pasteurella infections including bacteremia and meningitis Pasteurella multocida Haverhill fever Streptobacillus moniliformis Rat bite fever Spirillum minus or Streptobacillus moniliformis Disseminated gonococcal infections Neisseria gonorrhoeae (Penicillin-susceptible) Syphilis (congenital and neurosyphilis) Treponema pallidum Meningococcal meningitis and/or septicemia Neisseria meningitidis Gram-negative bacillary infections (bacteremias) Penicillin G is not the drug of choice in the treatment of Gram-negative bacillary infections. Gram-negative bacillary organisms ( i.e . Enterobacteriaceae) To reduce the development of drug-resistant bacteria and maintain effectiveness of Penicillin G Potassium and other antibacterial drugs, Penicillin G Potassium should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Dose related toxicity may arise with the use of massive doses of intravenous penicillins (40 to 100 million units per day), particularly in patients with severe renal impairment (see Precautions ). The manifestations may include agitation, confusion, asterixis, hallucinations, stupor, coma, multifocal myoclonus, seizures and encephalopathy. Hyperkalemia is also possible (see Adverse Reactions-Metabolic ). In case of overdosage, discontinue penicillin, treat symptomatically, and institute supportive measures as required. If necessary, hemodialysis may be used to reduce blood levels of Penicillin G, although the degree of effectiveness of this procedure is questionable."}', 'active_flag': 'Y', 'generic_name': '{"PENICILLIN G POTASSIUM"}', 'route': '{INTRAMUSCULAR,INTRAPLEURAL,INTRATHECAL,INTRAVENOUS}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Anaphylaxis Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before initiating therapy with penicillin G, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, penicillin G should be discontinued and appropriate therapy instituted. Severe cutaneous adverse reactions Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in patients taking beta-lactam antibiotics. When SCAR is suspected, Penicillin G Potassium for Injection, USP should be discontinued immediately and an alternative treatment should be considered. Clostridioides difficile associated diarrhea Clostridioides difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Penicillin G Potassium for Injection, USP, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated."}', 'precautions': '{"PRECAUTIONS General Penicillin should be used with caution in individuals with histories of significant allergies and/or asthma (see Warnings ). Whenever allergic reactions occur, penicillin should be withdrawn unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to penicillin therapy. Penicillin G Potassium for Injection, USP by the intravenous route in high doses (above 10 million units) should be administered slowly because of the potential adverse effects of electrolyte imbalance from the potassium content of the penicillin. Penicillin G Potassium for Injection, USP contains 1.68 mEq potassium and 0.3 mEq of sodium per million units. The use of antibiotics may promote overgrowth of nonsusceptible organisms, including fungi. Indwelling intravenous catheters encourage superinfections. Should superinfection occur, appropriate measures should be taken. When indicated, incision and drainage or other surgical procedures should be performed in conjunction with antibiotic therapy. Prescribing Penicillin G Potassium for Injection, USP in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Intramuscular and Intravenous Therapy Care should be taken to avoid intravenous or accidental intraarterial administration, or injection into or near major peripheral nerves or blood vessels, since such injections may produce neurovascular damage. Particular care should be taken with IV administration because of the possibility of thrombophlebitis. Information for Patients Patients should be counseled that antibacterial drugs including Penicillin G Potassium for Injection, USP should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Penicillin G Potassium for Injection, USP is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Penicillin G Potassium for Injection, USP or other antibacterial drugs in the future. Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible. Laboratory Tests Periodic assessment of organ system function, including frequent evaluation of electrolyte balance, hepatic, renal and hematopoietic systems, and cardiac and vascular status should be performed during prolonged therapy with high doses of intravenous penicillin G (see Adverse Reactions ). If any impairment of function is suspected or known to exist, a reduction in the total dosage should be considered (see Dosage and Administration ). In suspected staphylococcal infections, proper laboratory studies, including susceptibility tests should be performed. All infections due to Group A beta-hemolytic streptococci should be treated for at least 10 days. Patients being treated for gonococcal infection should have a serologic test for syphilis before receiving penicillin. All cases of penicillin treated syphilis should receive adequate follow-up including clinical and serological examinations. The recommended follow-up varies with the stage of syphilis being treated. Drug Interactions Bacteriostatic antibacterials ( i.e ., chloramphenicol, erythromycins, sulfonamides or tetracyclines) may antagonize the bactericidal effect of penicillin, and concurrent use of these drugs should be avoided. This has been documented in vitro ; however, the clinical significance of this interaction is not well-documented. Penicillin blood levels may be prolonged by concurrent administration of probenecid which blocks the renal tubular secretion of penicillins. Other drugs may compete with penicillin G for renal tubular secretion and thus prolong the serum half-life of penicillin. These drugs include: aspirin, phenylbutazone, sulfonamides, indomethacin, thiazide diuretics, furosemide and ethacrynic acid. Drug/Laboratory Test Interactions After treatment with penicillin G, a false-positive reaction for glucose in the urine may occur with Benedict\'s solution, Fehling\'s solution or Clinitest ® tablet, but not with the enzyme-based tests, such as Clinistix ® and Tes-Tape ® . Penicillin G has been associated with pseudoproteinuria by certain test methods. Carcinogenesis, Mutagenesis, Impairment of Fertility No long term animal studies have been conducted with this drug. Pregnancy Teratogenic Effects Reproduction studies performed in the mouse, rat, and rabbit have revealed no evidence of impaired fertility or harm to the fetus due to penicillin G. Human experience with the penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. There are, however, no adequate and well controlled studies in pregnant women showing conclusively that harmful effects of these drugs on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing Mothers Penicillins are excreted in human milk. Caution should be exercised when penicillins are administered to a nursing woman. Pediatric Use Incompletely developed renal function in newborns may delay elimination of penicillin; therefore, appropriate reductions in the dosage and frequency of administration should be made in these patients. All newborns treated with penicillins should be monitored closely for clinical and laboratory evidence of toxic or adverse effects (see Precautions ). Pediatric doses are generally determined on a weight basis and should be calculated for each patient individually. Recommended guidelines for pediatric dosages are presented in Dosage and Administration . Geriatric Use Clinical studies of penicillin G injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Penicillin G Potassium for Injection, USP contains 6.8 mg (0.3 mEq) of sodium per million units. At the usual recommended doses of 10 to 20 million units per day patients would receive between 68 and 136 mg/day (3 and 6 mEq) of sodium per day. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure."}', 'information_for_patients': '{"Information for Patients Patients should be counseled that antibacterial drugs including Penicillin G Potassium for Injection, USP should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Penicillin G Potassium for Injection, USP is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Penicillin G Potassium for Injection, USP or other antibacterial drugs in the future. Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible."}', 'pregnancy': '{"Pregnancy Teratogenic Effects Reproduction studies performed in the mouse, rat, and rabbit have revealed no evidence of impaired fertility or harm to the fetus due to penicillin G. Human experience with the penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. There are, however, no adequate and well controlled studies in pregnant women showing conclusively that harmful effects of these drugs on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed."}', 'pediatric_use': '{"Pediatric Use Incompletely developed renal function in newborns may delay elimination of penicillin; therefore, appropriate reductions in the dosage and frequency of administration should be made in these patients. All newborns treated with penicillins should be monitored closely for clinical and laboratory evidence of toxic or adverse effects (see Precautions ). Pediatric doses are generally determined on a weight basis and should be calculated for each patient individually. Recommended guidelines for pediatric dosages are presented in Dosage and Administration ."}', 'geriatric_use': '{"Geriatric Use Clinical studies of penicillin G injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Penicillin G Potassium for Injection, USP contains 6.8 mg (0.3 mEq) of sodium per million units. At the usual recommended doses of 10 to 20 million units per day patients would receive between 68 and 136 mg/day (3 and 6 mEq) of sodium per day. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure."}'}

{"METOPROLOL SUCCINATE"}

{'contraindications': '{"4 CONTRAINDICATIONS Metoprolol succinate extended-release tablet is contraindicated in severe bradycardia, second or third degree heart block, cardiogenic shock, decompensated cardiac failure, sick sinus syndrome (unless a permanent pacemaker is in place), and in patients who are hypersensitive to any component of this product. • Known hypersensitivity to product components. (4) • Severe bradycardia. (4) • Heart block greater than first degree. (4) • Cardiogenic shock. (4) • Decompensated cardiac failure. (4) • Sick sinus syndrome without a pacemaker. (4)"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in labeling: • Worsening angina or myocardial infarction. [see Warnings and Precautions (5) ] • Worsening heart failure. [see Warnings and Precautions (5) ] • Worsening AV block. [see Contraindications (4) ] Most common adverse reactions: tiredness, dizziness, depression, shortness of breath, bradycardia, hypotension, diarrhea, pruritus, rash. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Aralez Pharmaceuticals US, Inc. at 1-833-694-8235 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates. Hypertension and Angina: Most adverse reactions have been mild and transient. The most common (>2%) adverse reactions are tiredness, dizziness, depression, diarrhea, shortness of breath, bradycardia, and rash. Heart Failure: In the MERIT-HF study comparing metoprolol succinate extended-release tablets in daily doses up to 200 mg (mean dose 159 mg once-daily; n=1990) to placebo (n=2001), 10.3% of metoprolol succinate extended-release tablet patients discontinued for adverse reactions vs. 12.2% of placebo patients. The table below lists adverse reactions in the MERIT-HF study that occurred at an incidence of ≥ 1% in the metoprolol succinate extended-release tablet group and greater than placebo by more than 0.5%, regardless of the assessment of causality. Adverse Reactions Occurring in the MERIT-HF Study at an Incidence ≥ 1 % in the Metoprolol Succinate Extended-Release Tablet Group and Greater Than Placebo by More Than 0.5 % Metoprolol Succinate Extended-release Tablets n=1990 % of patients Placebo n=2001 % of patients Dizziness/vertigo 1.8 1.0 Bradycardia 1.5 0.4 Accident and/or injury 1.4 0.8 Post-operative Adverse Events: In a randomized, double-blind, placebo-controlled trial of 8351 patients with or at risk for atherosclerotic disease undergoing non-vascular surgery and who were not taking beta–blocker therapy, metoprolol succinate extended-release 100 mg was started 2 to 4 hours prior to surgery then continued for 30 days at 200 mg per day. Metoprolol succinate extended-release use was associated with a higher incidence of bradycardia (6.6% vs. 2.4%; HR 2.74; 95% CI 2.19, 3.43), hypotension (15% vs. 9.7%; HR 1.55; 95% CI 1.37, 1.74), stroke (1.0% vs. 0.5%; HR 2.17; 95% CI 1.26, 3.74) and death (3.1% vs. 2.3%; HR 1.33; 95% CI 1.03, 1.74) compared to placebo. 6.2 Post-Marketing Experience The following adverse reactions have been identified during post-approval use of metoprolol succinate or immediate-release metoprolol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular: Cold extremities, arterial insufficiency (usually of the Raynaud type), palpitations, peripheral edema, syncope, chest pain and hypotension. Respiratory: Wheezing (bronchospasm), dyspnea. Central Nervous System: Confusion, short-term memory loss, headache, somnolence, nightmares, insomnia, anxiety/nervousness, hallucinations, paresthesia. Gastrointestinal: Nausea, dry mouth, constipation, flatulence, heartburn, hepatitis, vomiting. Hypersensitive Reactions: Pruritus. Miscellaneous: Musculoskeletal pain, arthralgia, blurred vision, decreased libido, male impotence, tinnitus, reversible alopecia, agranulocytosis, dry eyes, worsening of psoriasis, Peyronie’s disease, sweating, photosensitivity, taste disturbance. Potential Adverse Reactions: In addition, there are adverse reactions not listed above that have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to metoprolol succinate. Central Nervous System: Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, clouded sensorium, and decreased performance on neuropsychometrics. Hematologic: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura. Hypersensitive Reactions: Laryngospasm, respiratory distress. 6.3 Laboratory Test Findings Clinical laboratory findings may include elevated levels of serum transaminase, alkaline phosphatase, and lactate dehydrogenase."}', 'drug_interactions': '{"7 DRUG INTERACTIONS • Catecholamine-depleting drugs may have an additive effect when given with beta-blocking agents. (7.1) • CYP2D6 Inhibitors are likely to increase metoprolol concentration. (7.2) • Concomitant use of glycosides, clonidine, and diltiazem and verapamil with beta-blockers can increase the risk of bradycardia. (7.3) • Beta-blockers including metoprolol, may exacerbate the rebound hypertension that can follow the withdrawal of clonidine. (7.3) 7.1 Catecholamine Depleting Drugs Catecholamine depleting drugs (e.g. reserpine, monoamine oxidase (MAO) inhibitors) may have an additive effect when given with beta-blocking agents. Observe patients treated with metoprolol succinate extended-release tablets plus a catecholamine depletor for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension. 7.2 CYP2D6 Inhibitors Drugs that inhibit CYP2D6 such as quinidine, fluoxetine, paroxetine, and propafenone are likely to increase metoprolol concentration. In healthy subjects with CYP2D6 extensive metabolizer phenotype, coadministration of quinidine 100 mg and immediate-release metoprolol 200 mg tripled the concentration of S-metoprolol and doubled the metoprolol elimination half-life. In four patients with cardiovascular disease, coadministration of propafenone 150 mg t.i.d. with immediate-release metoprolol 50 mg t.i.d. resulted in two- to five-fold increases in the steady-state concentration of metoprolol. These increases in plasma concentration would decrease the cardioselectivity of metoprolol. 7.3 Digitalis, Clonidine, and Calcium Channel Blockers Digitalis glycosides, clonidine, diltiazem and verapamil slow atrioventricular conduction and decrease heart rate. Concomitant use with beta blockers can increase the risk of bradycardia. If clonidine and a beta blocker, such as metoprolol are coadministered, withdraw the beta-blocker several days before the gradual withdrawal of clonidine because beta-blockers may exacerbate the rebound hypertension that can follow the withdrawal of clonidine. If replacing clonidine by beta-blocker therapy, delay the introduction of beta-blockers for several days after clonidine administration has stopped [see Warnings and Precautions (5.11) ]."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Metoprolol Succinate is a beta 1 -selective adrenoceptor blocking agent. Metoprolol Succinate is indicated for the treatment of: • Hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. (1.1) • Angina Pectoris. (1.2) • Heart Failure - for the treatment of stable, symptomatic (NYHA Class II or III) heart failure of ischemic, hypertensive, or cardiomyopathic origin. (1.3) 1.1 Hypertension Metoprolol succinate is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure lowers the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including metoprolol. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than 1 drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g. on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Metoprolol succinate extended-release tablet may be administered with other antihypertensive agents. 1.2 Angina Pectoris Metoprolol succinate extended-release tablet is indicated in the long-term treatment of angina pectoris, to reduce angina attacks and to improve exercise tolerance. 1.3 Heart Failure Metoprolol succinate extended-release tablet is indicated for the treatment of stable, symptomatic (NYHA Class II or III) heart failure of ischemic, hypertensive, or cardiomyopathic origin. It was studied in patients already receiving ACE inhibitors, diuretics, and, in the majority of cases, digitalis. In this population, metoprolol succinate extended-release tablet decreased the rate of mortality plus hospitalization, largely through a reduction in cardiovascular mortality and hospitalizations for heart failure."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Heart Failure: Worsening cardiac failure may occur. (5.2) • Bronchospastic Disease: Avoid beta blockers. (5.3) • Pheochromocytoma: If required, first initiate therapy with an alpha blocker. (5.4) • Major Surgery: Avoid initiation of high-dose extended-release metoprolol in patients undergoing non-cardiac surgery because it has been associated with bradycardia, hypotension, stroke and death. Do not routinely withdraw chronic beta blocker therapy prior to surgery. ( 5.5 , 6.1 ) • Diabetes and Hypoglycemia: May mask tachycardia occurring with hypoglycemia. (5.6) • Patients with Hepatic Impairment: (5.7) • Thyrotoxicosis: Abrupt withdrawal in patients with thyrotoxicosis might precipitate a thyroid storm. (5.8) • Anaphylactic Reactions: Patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction. (5.9) • Peripheral Vascular Disease: Can aggravate symptoms of arterial insufficiency. (5.10) • Calcium Channel Blockers: Because of significant inotropic and chronotropic effects in patients treated with beta-blockers and calcium channel blockers of the verapamil and diltiazem type, caution should be exercised in patients treated with these agents concomitantly. (5.11) 5.1 Ischemic Heart Disease Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, myocardial infarction have occurred. When discontinuing chronically administered metoprolol succinate extended-release tablets, particularly in patients with ischemic heart disease, gradually reduce the dosage over a period of 1 - 2 weeks and monitor the patient. If angina markedly worsens or acute coronary ischemia develops, promptly reinstate metoprolol succinate extended-release, and take measures appropriate for the management of unstable angina. Warn patients not to interrupt therapy without their physician’s advice. Because coronary artery disease is common and may be unrecognized, avoid abruptly discontinuing metoprolol succinate in patients treated only for hypertension. 5.2 Heart Failure Worsening cardiac failure may occur during up-titration of metoprolol succinate extended-release tablets. If such symptoms occur, increase diuretics and restore clinical stability before advancing the dose of metoprolol succinate extended-release tablets [see Dosage and Administration (2) ]. It may be necessary to lower the dose of metoprolol succinate extended-release tablet or temporarily discontinue it. Such episodes do not preclude subsequent successful titration of metoprolol succinate extended-release tablets. 5.3 Bronchospastic Disease PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD, IN GENERAL, NOT RECEIVE BETA-BLOCKERS. Because of its relative beta 1 cardio-selectivity, however, metoprolol succinate extended-release tablet may be used in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Because beta 1 -selectivity is not absolute, use the lowest possible dose of metoprolol succinate extended-release tablets. Bronchodilators, including beta 2 -agonists, should be readily available or administered concomitantly [see Dosage and Administration (2) ]. 5.4 Pheochromocytoma If metoprolol succinate extended-release is used in the setting of pheochromocytoma, it should be given in combination with an alpha blocker, and only after the alpha blocker has been initiated. Administration of beta-blockers alone in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure due to the attenuation of beta-mediated vasodilatation in skeletal muscle. 5.5 Major Surgery Avoid initiation of a high-dose regimen of extended-release metoprolol in patients undergoing non-cardiac surgery, since such use in patients with cardiovascular risk factors has been associated with bradycardia, hypotension, stroke and death. Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery, however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures. 5.6 Diabetes and Hypoglycemia Beta-blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected. 5.7 Hepatic Impairment Consider initiating metoprolol succinate extended-release therapy at doses lower than those recommended for a given indication; gradually increase dosage to optimize therapy, while monitoring closely for adverse events. 5.8 Thyrotoxicosis Beta-adrenergic blockade may mask certain clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of beta-blockade may precipitate a thyroid storm. 5.9 Anaphylactic Reaction While taking beta-blockers, patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated challenge and may be unresponsive to the usual doses of epinephrine used to treat an allergic reaction. 5.10 Peripheral Vascular Disease Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. 5.11 Calcium Channel Blockers Because of significant inotropic and chronotropic effects in patients treated with beta-blockers and calcium channel blockers of the verapamil and diltiazem type, caution should be exercised in patients treated with these agents concomitantly."}', 'overdosage': '{"10 OVERDOSAGE Signs and Symptoms - Overdosage of metoprolol succinate extended-release tablets may lead to severe bradycardia, hypotension, and cardiogenic shock. Clinical presentation can also include: atrioventricular block, heart failure, bronchospasm, hypoxia, impairment of consciousness/coma, nausea and vomiting. Treatment - Consider treating the patient with intensive care. Patients with myocardial infarction or heart failure may be prone to significant hemodynamic instability. Seek consultation with a regional poison control center and a medical toxicologist as needed. Beta-blocker overdose may result in significant resistance to resuscitation with adrenergic agents, including beta-agonists. On the basis of the pharmacologic actions of metoprolol, employ the following measures. There is very limited experience with the use of hemodialysis to remove metoprolol, however metoprolol is not highly protein bound. Bradycardia: Evaluate the need for atropine, adrenergic-stimulating drugs or pacemaker to treat bradycardia and conduction disorders. Hypotension: Treat underlying bradycardia. Consider intravenous vasopressor infusion, such as dopamine or norepinephrine. Heart failure and shock: May be treated when appropriate with suitable volume expansion, injection of glucagon (if necessary, followed by an intravenous infusion of glucagon), intravenous administration of adrenergic drugs such as dobutamine, with α 1 receptor agonistic drugs added in presence of vasodilation. Bronchospasm: Can usually be reversed by bronchodilators."}', 'active_flag': 'Y', 'generic_name': '{"METOPROLOL SUCCINATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise patients to take metoprolol succinate extended–release tablets regularly and continuously, as directed, preferably with or immediately following meals. If a dose is missed, the patient should take only the next scheduled dose (without doubling it). Patients should not interrupt or discontinue metoprolol succinate extended-release tablets without consulting the physician. Advise patients (1) to avoid operating automobiles and machinery or engaging in other tasks requiring alertness until the patient’s response to therapy with metoprolol succinate extended-release tablets has been determined; (2) to contact the physician if any difficulty in breathing occurs; (3) to inform the physician or dentist before any type of surgery that he or she is taking metoprolol succinate extended-release tablets. Heart failure patients should be advised to consult their physician if they experience signs or symptoms of worsening heart failure such as weight gain or increasing shortness of breath. PLENDIL is a trademark of the AstraZeneca group of companies. © Aralez Pharmaceuticals US, Inc. 2019 Distributed by: Lannett Company, Inc. Philadelphia, PA 19136 Rev. 10/2019"}', 'pregnancy': '{"8.1 Pregnancy Pregnancy Category C Metoprolol tartrate has been shown to increase post-implantation loss and decrease neonatal survival in rats at doses up to 22 times, on a mg/m 2 basis, the daily dose of 200 mg in a 60-kg patient. Distribution studies in mice confirm exposure of the fetus when metoprolol tartrate is administered to the pregnant animal. These studies have revealed no evidence of impaired fertility or teratogenicity. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, use this drug during pregnancy only if clearly needed."}', 'pediatric_use': '{"8.4 Pediatric Use One hundred forty-four hypertensive pediatric patients aged 6 to 16 years were randomized to placebo or to one of three dose levels of metoprolol succinate extended-release tablets (0.2, 1.0 or 2.0 mg/kg once daily) and followed for 4 weeks. The study did not meet its primary endpoint (dose response for reduction in SBP). Some pre-specified secondary endpoints demonstrated effectiveness including: • Dose-response for reduction in DBP, • 1 mg/kg vs. placebo for change in SBP, and • 2 mg/kg vs. placebo for change in SBP and DBP. The mean placebo corrected reductions in SBP ranged from 3 to 6 mmHg, and DBP from 1 to 5 mmHg. Mean reduction in heart rate ranged from 5 to 7 bpm but considerably greater reductions were seen in some individuals [see Dosage and Administration (2.1) ] . No clinically relevant differences in the adverse event profile were observed for pediatric patients aged 6 to 16 years as compared with adult patients. Safety and effectiveness of metoprolol succinate extended-release tablets have not been established in patients < 6 years of age."}', 'geriatric_use': '{"8.5 Geriatric Use Clinical studies of metoprolol succinate extended-release tablets in hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience in hypertensive patients has not identified differences in responses between elderly and younger patients. Of the 1,990 patients with heart failure randomized to metoprolol succinate extended-release tablets in the MERIT-HF trial, 50% (990) were 65 years of age and older and 12% (238) were 75 years of age and older. There were no notable differences in efficacy or the rate of adverse reactions between older and younger patients. In general, use a low initial starting dose in elderly patients given their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy."}'}

{"FOLIC ACID"}

{'contraindications': '{"CONTRAINDICATIONS Folic acid, USP is contraindicated in patients who have shown previous intolerance to the drug."}', 'adverse_reactions': '{"ADVERSE REACTIONS Allergic sensitization has been reported following both oral and parenteral administration of folic acid. Folic acid is relatively nontoxic in man. Rare instances of allergic responses to folic acid preparations have been reported and have included erythema, skin rash, itching, general malaise, and respiratory difficulty due to bronchospasm. One patient experienced symptoms suggesting anaphylaxis following injection of the drug. Gastrointestinal side effects, including anorexia, nausea, abdominal distention, flatulence, and a bitter or bad taste, have been reported in patients receiving 15 mg folic acid daily for 1 month. Other side effects reported in patients receiving 15 mg daily include altered sleep patterns, difficulty in concentrating, irritability, overactivity, excitement, mental depression, confusion, and impaired judgment. Decreased vitamin B12 serum levels may occur in patients receiving prolonged folic acid therapy. In an uncontrolled study, orally administered folic acid was reported to increase the incidence of seizures in some epileptic patients receiving phenobarbital, primidone, or diphenylhydantoin. Another investigator reported decreased diphenylhydantoin serum levels in folate-deficient patients receiving diphenylhydantoin who were treated with 5 mg or 15 mg of folic acid daily."}', 'drug_interactions': '{"Drug Interactions There is evidence that the anticonvulsant action of phenytoin is antagonized by folic acid. A patient whose epilepsy is completely controlled by phenytoin may require increased doses to prevent convulsions if folic acid is given. Folate deficiency may result from increased loss of folate, as in renal dialysis and/or interference with metabolism (e.g., folic acid antagonists such as methotrexate); the administration of anticonvulsants, such as diphenylhydantoin, primidone, and barbiturates; alcohol consumption and, especially, alcoholic cirrhosis; and the administration of pyrimethamine and nitrofurantoin. False low serum and red cell folate levels may occur if the patient has been taking antibiotics, such as tetracycline, which suppress the growth of Lactobacillus casei."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Folic acid, USP is effective in the treatment of megaloblastic anemias due to a deficiency of folic acid, USP (as may be seen in tropical or nontropical sprue) and in anemias of nutritional origin, pregnancy, infancy, or childhood."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Except during pregnancy and lactation, folic acid should not be given in therapeutic doses greater than 0.4 mg daily until pernicious anemia has been ruled out. Patients with pernicious anemia receiving more than 0.4 mg of folic acid daily who are inadequately treated with vitamin B12 may show reversion of the hematologic parameters to normal, but neurologic manifestations due to vitamin B12 deficiency will progress. Doses of folic acid exceeding the Recommended Dietary Allowance (RDA) should not be included in multivitamin preparations; if therapeutic amounts are necessary, folic acid should be given separately."}', 'active_flag': 'Y', 'generic_name': '{"FOLIC ACID"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNING Administration of folic acid alone is improper therapy for pernicious anemia and other megaloblastic anemias in which vitamin B12 is deficient."}', 'precautions': '{"PRECAUTIONS General Folic acid in doses above 0.1 mg daily may obscure pernicious anemia in that hematologic remission can occur while neurologic manifestations remain progressive. There is a potential danger in administering folic acid to patients with undiagnosed anemia, since folic acid may obscure the diagnosis of pernicious anemia by alleviating the hematologic manifestations of the disease while allowing the neurologic complications to progress. This may result in severe nervous system damage before the correct diagnosis is made. Adequate doses of vitamin B12 may prevent, halt, or improve the neurologic changes caused by pernicious anemia. Drug Interactions There is evidence that the anticonvulsant action of phenytoin is antagonized by folic acid. A patient whose epilepsy is completely controlled by phenytoin may require increased doses to prevent convulsions if folic acid is given. Folate deficiency may result from increased loss of folate, as in renal dialysis and/or interference with metabolism (e.g., folic acid antagonists such as methotrexate); the administration of anticonvulsants, such as diphenylhydantoin, primidone, and barbiturates; alcohol consumption and, especially, alcoholic cirrhosis; and the administration of pyrimethamine and nitrofurantoin. False low serum and red cell folate levels may occur if the patient has been taking antibiotics, such as tetracycline, which suppress the growth of Lactobacillus casei. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals to evaluate carcinogenic potential and studies to evaluate the mutagenic potential or effect on fertility have not been conducted. Pregnancy Teratogenic Effects Pregnancy Category A Folic acid is usually indicated in the treatment of megaloblastic anemias of pregnancy. Folic acid requirements are markedly increased during pregnancy, and deficiency will result in fetal damage (see INDICATIONS AND USAGE ) . Studies in pregnant women have not shown that folic acid increases the risk of fetal abnormalities if administered during pregnancy. If the drug is used during pregnancy, the possibility of fetal harm appears remote. Because studies cannot rule out the possibility of harm, however, folic acid should be used during pregnancy only if clearly needed. Nursing Mothers Folic acid is excreted in the milk of lactating mothers. During lactation, folic acid requirements are markedly increased; however, amounts present in human milk are adequate to fulfill infant requirements, although supplementation may be needed in low-birth-weight infants, in those who are breast-fed by mothers with folic acid deficiency (50 mcg daily), or in those with infections or prolonged diarrhea."}', 'information_for_patients': None, 'pregnancy': '{"Pregnancy Teratogenic Effects Pregnancy Category A Folic acid is usually indicated in the treatment of megaloblastic anemias of pregnancy. Folic acid requirements are markedly increased during pregnancy, and deficiency will result in fetal damage (see INDICATIONS AND USAGE ) . Studies in pregnant women have not shown that folic acid increases the risk of fetal abnormalities if administered during pregnancy. If the drug is used during pregnancy, the possibility of fetal harm appears remote. Because studies cannot rule out the possibility of harm, however, folic acid should be used during pregnancy only if clearly needed."}', 'pediatric_use': None, 'geriatric_use': None}

{MINOXIDIL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use to regrow hair on the top of the scalp (vertex only, see pictures on side of carton)"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{MINOXIDIL}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if • chest pain, rapid heartbeat, faintness, or dizziness occurs • sudden, unexplained weight gain occurs • your hands or feet swell • scalp irritation or redness occurs • unwanted facial hair growth occurs • you do not see hair regrowth in 4 months"}', 'do_not_use': '{"Do not use if • you are a woman • your amount of hair loss is different than that shown on the side of this carton or your hair loss is on the front of the scalp. Minoxidil topical solution 5% is not intended for frontal baldness or receding hairline. • you have no family history of hair loss • your hair loss is sudden and/or patchy • you do not know the reason for your hair loss • you are under 18 years of age. Do not use on babies and children. • your scalp is red, inflamed, infected, irritated, or painful • you use other medicines on the scalp"}', 'when_using': '{"When using this product • do not apply on other parts of the body • avoid contact with the eyes. In case of accidental contact, rinse eyes with large amounts of cool tap water. • some people have experienced changes in hair color and/or texture • it takes time to regrow hair. Results may occur at 2 months with twice a day usage. For some men, you may need to use this product for at least 4 months before you see results. • the amount of hair regrowth is different for each person. This product will not work for all men."}', 'warnings': '{"Warnings For external use only. For use by men only. Flammable: Keep away from fire or flame Do not use if • you are a woman • your amount of hair loss is different than that shown on the side of this carton or your hair loss is on the front of the scalp. Minoxidil topical solution 5% is not intended for frontal baldness or receding hairline. • you have no family history of hair loss • your hair loss is sudden and/or patchy • you do not know the reason for your hair loss • you are under 18 years of age. Do not use on babies and children. • your scalp is red, inflamed, infected, irritated, or painful • you use other medicines on the scalp Ask a doctor before use if you have heart disease When using this product • do not apply on other parts of the body • avoid contact with the eyes. In case of accidental contact, rinse eyes with large amounts of cool tap water. • some people have experienced changes in hair color and/or texture • it takes time to regrow hair. Results may occur at 2 months with twice a day usage. For some men, you may need to use this product for at least 4 months before you see results. • the amount of hair regrowth is different for each person. This product will not work for all men. Stop use and ask a doctor if • chest pain, rapid heartbeat, faintness, or dizziness occurs • sudden, unexplained weight gain occurs • your hands or feet swell • scalp irritation or redness occurs • unwanted facial hair growth occurs • you do not see hair regrowth in 4 months May be harmful if used when pregnant or breast-feeding. Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away. (1-800-222-1222)"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{LORATADINE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses temporarily relieves these symptoms due to hay fever or other upper respiratory allergies: runny nose sneezing itchy, watery eyes itching of the nose or throat"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{LORATADINE}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if an allergic reaction to this product occurs. Seek medical help right away."}', 'do_not_use': '{"Do not use if you have ever had an allergic reaction to this product or any of its ingredients."}', 'when_using': '{"When using this product do not take more than directed. Taking more than directed may cause drowsiness."}', 'warnings': '{Warnings}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{PREDNISONE}

{'contraindications': '{"CONTRAINDICATIONS Prednisone tablets are contraindicated in systemic fungal infections and known hypersensitivity to components."}', 'adverse_reactions': '{"ADVERSE REACTIONS Fluid and Electrolyte Disturbances Sodium retention Fluid retention Congestive heart failure in susceptible patients Potassium loss Hypokalemic alkalosis Hypertension Musculoskeletal Muscle weakness Steroid myopathy Loss of muscle mass Osteoporosis Vertebral compression fractures Aseptic necrosis of femoral and humeral heads Pathologic fracture of long bones Gastrointestinal Peptic ulcer with possible perforation and hemorrhage Pancreatitis Abdominal distention Ulcerative esophagitis Dermatologic Impaired wound healing Thin fragile skin Petechiae and ecchymoses Facial erythema Increased sweating May suppress reactions to skin tests Metabolic Negative nitrogen balance due to protein catabolism Neurological Increased intracranial pressure with papilledema (pseudo-tumor cerebri) usually after treatment Convulsions Vertigo Headache Endocrine Menstrual irregularities Development of Cushingoid state Secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery or illness Suppression of growth in children Decreased carbohydrate tolerance Manifestations of latent diabetes mellitus Increased requirements for insulin or oral hypoglycemic agents in diabetics Ophthalmic Posterior subcapsular cataracts Increased intraocular pressure Glaucoma Exophthalmos Additional Reactions Urticaria and other allergic, anaphylactic or hypersensitivity reactions. To report SUSPECTED ADVERSE REACTIONS, contact Strides Pharma Inc. at 1-877-244-9825 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch"}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE Prednisone tablets USP are indicated in the following conditions: Endocrine Disorders Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the first choice: synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance); congenital adrenal hyperplasia; hypercalcemia associated with cancer; nonsuppurative thyroiditis. Rheumatic Disorders As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: psoriatic arthritis, rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy), ankylosing spondylitis, acute and subacute bursitis, acute nonspecific tenosynovitis, acute gouty arthritis, post-traumatic osteoarthritis, synovitis of osteoarthritis, epicondylitis. Collagen Diseases During an exacerbation or as maintenance therapy in selected cases of: systemic lupus erythematosus, systemic dermatomyositis (polymyositis), acute rheumatic carditis. Dermatologic Diseases Pemphigus; bullous dermatitis herpetiformis; severe erythema multiforme (Stevens-Johnson syndrome); exfoliative dermatitis; mycosis fungoides; severe psoriasis; severe seborrheic dermatitis. Allergic States Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment: seasonal or perennial allergic rhinitis; bronchial asthma; contact dermatitis; atopic dermatitis; serum sickness; drug hypersensitivity reactions. Ophthalmic Diseases Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as: allergic corneal marginal ulcers, herpes zoster ophthalmicus, anterior segment inflammation, diffuse posterior uveitis and choroiditis, sympathetic ophthalmia, allergic conjunctivitis, keratitis, chorioretinitis, optic neuritis, iritis and iridocyclitis. Respiratory Diseases Symptomatic sarcoidosis; Loeffler\'s syndrome not manageable by other means; berylliosis; fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy; aspiration pneumonitis. Hematologic Disorders Idiopathic thrombocytopenic purpura in adults; secondary thrombocytopenia in adults; acquired (autoimmune) hemolytic anemia; erythroblastopenia (RBC anemia); congenital (erythroid) hypoplastic anemia. Neoplastic Diseases For palliative management of: leukemias and lymphomas in adults, acute leukemia of childhood. Edematous States To induce a diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus. Gastrointestinal Diseases To tide the patient over a critical period of the disease in: ulcerative colitis, regional enteritis. Nervous System Acute exacerbations of multiple sclerosis. Miscellaneous Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy; trichinosis with neurologic or myocardial involvement."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{PREDNISONE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during and after the stressful situation is indicated. Immunosuppression and Increased Risk of Infection Corticosteroids, including prednisone tablets, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can: • Reduce resistance to new infections • Exacerbate existing infections • Increase the risk of disseminated infections • Increase the risk of reactivation or exacerbation of latent infections • Mask some signs of infection Corticosteroid-associated infections can be mild but can be severe and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages. Monitor for the development of infection and consider prednisone tablets withdrawal or dosage reduction as needed. Tuberculosis If prednisone tablets is used to treat a condition in patients with latent tuberculosis or tuberculin reactivity, reactivation of tuberculosis may occur. Closely monitor such patients for reactivation. During prolonged prednisone tablets therapy, patients with latent tuberculosis or tuberculin reactivity should receive chemoprophylaxis. Varicella Zoster and Measles Viral Infections Varicella and measles can have a serious or even fatal course in non-immune patients taking corticosteroids, including prednisone tablets. In corticosteroid-treated patients who have not had these diseases or are non-immune, particular care should be taken to avoid exposure to varicella and measles: • If a prednisone tablets-treated patient is exposed to varicella, prophylaxis with varicella zoster immune globulin may be indicated. If varicella develops, treatment with antiviral agents may be considered. • If a prednisone tablets-treated patient is exposed to measles, prophylaxis with immunoglobulin may be indicated. Hepatitis B Virus Reactivation Hepatitis B virus reactivation can occur in patients who are hepatitis B carriers treated with immunosuppressive dosages of corticosteroids, including prednisone tablets. Reactivation can also occur infrequently in corticosteroid-treated patients who appear to have resolved hepatitis B infection. Screen patients for hepatitis B infection before initiating immunosuppressive (e.g., prolonged) treatment with prednisone tablets. For patients who show evidence of hepatitis B infection, recommend consultation with physicians with expertise in managing hepatitis B regarding monitoring and consideration for hepatitis B antiviral therapy. Fungal Infections Corticosteroids, including prednisone tablets, may exacerbate systemic fungal infections; therefore, avoid prednisone tablets use in the presence of such infections unless prednisone tablets is needed to control drug reactions. For patients on chronic prednisone tablets therapy who develop systemic fungal infections, prednisone tablets withdrawal or dosage reduction is recommended. Amebiasis Corticosteroids, including prednisone tablets, may activate latent amebiasis. Therefore, it is recommended that latent amebiasis or active amebiasis be ruled out before initiating prednisone tablets in patients who have spent time in the tropics or patients with unexplained diarrhea. Strongyloides Infestation Corticosteroids, including prednisone tablets, should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. Cerebral Malaria Avoid corticosteroids, including prednisone tablets, in patients with cerebral malaria. Kaposi\'s Sarcoma Kaposi\'s sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement of Kaposi\'s sarcoma. Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses. Usage in pregnancy: Since adequate human reproduction studies have not been done with corticosteroids, the use of these drugs in pregnancy, nursing mothers or women of childbearing potential requires that the possible benefits of the drug be weighed against the potential hazards to the mother and embryo or fetus. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy, should be carefully observed for signs of hypoadrenalism. Average and large doses of hydrocortisone or cortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion. While on corticosteroid therapy patients should not be vaccinated against smallpox. Other immunization procedures should not be undertaken in patients who are on corticosteroids, especially on high dose, because of possible hazards of neurological complications and a lack of antibody response."}', 'precautions': '{"PRECAUTIONS General Precautions Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently. There is an enhanced effect of corticosteroids on patients with hypothyroidism and in those with cirrhosis. Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation. The lowest possible dose of corticosteroid should be used to control the condition under treatment, and when reduction in dosage is possible, the reduction should be gradual. Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations. Also existing emotional instability or psychotic tendencies may be aggravated by corticosteroids. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. Steroids should be used with caution in nonspecific ulcerative colitis, if there is a probability of impending perforation, abscess or other pyogenic infection: diverticulitis; fresh intestinal anastomoses; active or latent peptic ulcer; renal insufficiency; hypertension; osteoporosis: and myasthenia gravis. Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed. Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not show that corticosteroids affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect (See DOSAGE AND ADMINISTRATION). Since complications of treatment with glucocorticoids are dependent on the size of the dose and the duration of treatment, a risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used. Convulsions have been reported with concurrent use of methylprednisolone and cyclosporine. Since concurrent use of these agents results in a mutual inhibition of metabolism, it is possible that adverse events associated with the individual use of either drug may be more apt to occur. Information for the Patient Patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles and, if exposed, to obtain medical advice."}', 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{TAFENOQUINE}

{'contraindications': '{"4 CONTRAINDICATIONS ARAKODA is contraindicated in: • patients with G6PD deficiency or unknown G6PD status due to the risk of hemolytic anemia [see Warnings and Precautions ( 5.2 )] . • breastfeeding by a lactating woman when the infant is found to be G6PD deficient or if the G6PD status of the infant is unknown [see Warnings and Precautions ( 5.3 ), Use in Specific Populations ( 8.2 )] . • patients with a history of psychotic disorders or current psychotic symptoms (i.e., hallucinations, delusions, and/or grossly disorganized behavior) [see Warnings and Precautions ( 5.4 )] • patients with known hypersensitivity reactions to tafenoquine, other 8-aminoquinolines, or any component of ARAKODA [see Warnings and Precautions ( 5.5 )] . • G6PD deficiency or unknown G6PD status ( 4 ) • Breastfeeding by a lactating woman when the infant is found to be G6PD deficient or if G6PD status is unknown ( 4 , 8.2 ) • Patients with a history of psychotic disorders or current psychotic symptoms ( 4 , 5.4 ) • Known hypersensitivity reactions to tafenoquine, other 8-aminoquinolines, or any component of ARAKODA. ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following clinically significant adverse reactions observed with ARAKODA are discussed in detail in the Warnings and Precautions section: • Hemolytic Anemia [see Warnings and Precautions ( 5.2 )] • Methemoglobinemia [see Warnings and Precautions ( 5.3 )] • Psychiatric Effects [see Warnings and Precautions ( 5.4 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.5 )] The most common adverse reactions (incidence ≥1%) were: headache, dizziness, back pain, diarrhea, nausea, vomiting, increased alanine aminotransferase (ALT), motion sickness, insomnia, depression, abnormal dreams, anxiety. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact 60 Degrees Pharmaceuticals at 1-888-834-0225 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of tafenoquine was studied in clinical trials at various doses and regimens in 3,184 subjects. The recommended ARAKODA regimen was evaluated in 825 subjects in 5 controlled clinical trials (Trials 1, Trial 2, Trial 3, Trial 4 and Trial 5). The mean duration of exposure to ARAKODA in these five clinical trials was 21 weeks (range 10-29 weeks). Trial 1, 2 and 4 were conducted in healthy semi-immune volunteers in Ghana or Kenya and were placebo-controlled; a mefloquine arm was included in Trials 2 and 4 as a benchmark. Trial 3, an active comparator (mefloquine) controlled trial was conducted in healthy soldiers deployed in East Timor (Timor Leste). A placebo-controlled Trial 5 was conducted in healthy volunteers in the United States and United Kingdom. The mean age of the subjects included in the five trials was 29 years (range 17 to 69 years); 84% were male. Adverse Reactions Reported with ARAKODA in Trial 3 and Pooled Trials 1, 2, 4, and 5 Adverse reactions occurring in ≥1% of subjects in the ARAKODA group in the placebo-controlled pooled Trials 1, 2, 3, and 4 are presented in Table 3 . Table 3: Selected Adverse Reactions Occurring in ≥1% of Subjects Receiving ARAKODA in Pooled Trials 1, 2, 4, and 5 (Non-Deployed Subjects) Adverse Reaction ARAKODA 1 (n=333) % Placebo (n=295) % Mefloquine 2 (n=147) % 1 ARAKODA was administered as 200 mg daily for 3 days, then 200 mg weekly 2 Mefloquine was administered as 250 mg daily for 3 days, then 250 mg weekly 3 Includes headache, sinus headache, migraine and tension headache. 4 Includes dizziness and dizziness postural 5 Includes abnormal dreams, insomnia, nightmares, sleep disorder, and somnambulism. Nervous system Disorders 35 34 47 Headache 3 32 32 44 Dizziness 4 5 3 10 Musculoskeletal and connective tissue disorders 27 26 37 Back pain 14 9 11 Gastrointestinal disorders 31 33 46 Diarrhea 5 3 1 Nausea 5 2 2 Vomiting 2 2 1 Investigations 8 7 11 Alanine Aminotransferase (ALT) increased/abnormal 4 2 3 Psychiatric disorders 2 1 2 Any sleep symptom 5 1 1 0 Insomnia 1 1 0 Depression/depressed mood 1 0 0 Adverse reactions occurring in ≥1% of subjects in the ARAKODA group in the active-control Trial 3 conducted in military personnel deployed to malaria endemic areas are presented in Table 4 . Table 4: Selected Adverse Reactions Occurring in ≥1% of Subjects Receiving ARAKODA in Trial 3 (Deployed Subjects) Adverse Reaction ARAKODA 1 (n=492) % Mefloquine 2 (n=162) % 1 ARAKODA was administered as 200 mg daily for 3 days, then 200 mg weekly 2 Mefloquine was administered as 250 mg daily for 3 days, then 250 mg weekly 3 Includes headache, sinus headache, migraine and tension headache. 4 Includes dizziness and dizziness postural 5 Includes motion sickness, vertigo and vertigo positional. 6 Includes abnormal dreams, insomnia, nightmares, sleep disorder, and somnambulism. 7 Includes abnormal dreams, nightmares 8 Includes anxiety disorder, panic attack and stress. Nervous system Disorders 22 27 Headache 3 15 19 Dizziness 4 1 1 Ear and labyrinth Disorders 7 11 Motion sicknesss 5 5 6 Musculoskeletal and connective tissue disorders 29 30 Back pain 14 15 Gastrointestinal disorders 36 41 Diarrhea 18 20 Nausea 7 9 Vomiting 5 6 Psychiatric disorders 5 4 Any sleep symptom 6 4 4 Insomnia 2 1 Abnormal dreams 7 2 2 Anxiety 8 1 0 Clinically Significant Adverse Reactions in Trials 1 to 5 (Overall Safety Population) Clinically significant adverse reactions with ARAKODA (200 mg daily for 3 days, followed by 200 mg weekly) in Trials 1 to 5 (n= 825) are described below: Ocular Adverse Reactions Vortex keratopathy was reported in 21% to 93% of subjects receiving ARAKODA in the trials which included ophthalmic evaluations (Trials 3, 5, and Trial 6 (NCT # 01290601, an active-control trial in patients from Thailand with P. vivax malaria. The keratopathy did not result in any apparent functional visual changes and resolved within one year after drug cessation in all patients. Retinal abnormalities were noted in less than 1% of subjects receiving ARAKODA. A total of 7 serious ocular adverse reactions (SARs) were reported in ARAKODA-treated subjects in the trials which included ophthalmic evaluations: 5 reports of keratopathy and two reports of retinal disorders. Laboratory Abnormalities Methemoglobinemia: Asymptomatic methemoglobin elevations were observed in 13% of subjects receiving ARAKODA. Hemoglobin decrease: Hemoglobin decreases of ≥ 3 g/dL were observed in 2.3% of subjects receiving ARAKODA. Adverse Reactions Reported in < 1% of Subjects Receiving ARAKODA in Trials 1 to 5 The following selected adverse reactions were reported in subjects receiving ARAKODA in Trials 1 to 5 at a rate of less than 1%. Blood and lymphatic system disorders: hemolytic anemia, anemia, thrombocytopenia Ear and labyrinth disorders: hyperacusis, Meniere’s disease Eye disorders: night blindness, photophobia, blurred vision, visual acuity reduced, visual impairment, vitreous floaters Hepatobiliary disorders: hyperbilirubinemia, jaundice cholestatic Immune system disorders: hypersensitivity Investigations: blood bilirubin increased, blood creatinine increased, glomerular filtration rate decreased Nervous system disorders: amnesia, coordination abnormal, hyperesthesia, hypoesthesia, somnolence, syncope, tremor, visual field defect Psychiatric disorders: agitation, neurosis Skin and subcutaneous tissue disorders: urticaria."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Avoid co-administration with drugs that are substrates of organic cation transporter-2 (OCT2) or multidrug and toxin extrusion (MATE) transporters ( 7.1 ) 7.1 Effect of ARAKODA on Organic Cation Transporter-2 (OCT2) and Multidrug and Toxin Extrusion (MATE) Substrates The effect of coadministration of tafenoquine on the pharmacokinetics of OCT2 and MATE substrates in humans is unknown. However, in vitro observations suggest the potential for increased concentrations of these substrates [see Clinical Pharmacology ( 12.3 )] which may increase the risk of toxicity of these drugs. Avoid coadministration of ARAKODA with OCT2 and MATE substrates (e.g., dofetilide, metformin). If coadministration cannot be avoided, monitor for drug-related toxicities and consider dosage reduction if needed based on approved product labeling of the coadministered drug."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE ARAKODA is indicated for the prophylaxis of malaria in patients aged 18 years and older. ARAKODA is an antimalarial indicated for the prophylaxis of malaria in patients aged 18 years and older. ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Hemolytic Anemia : G6PD testing must be performed before prescribing ARAKODA due to the risk of hemolytic anemia. Monitor patients for signs or symptoms of hemolysis. ( 5.1 ) • G6PD Deficiency in Pregnancy or Lactation : ARAKODA may cause fetal harm when administered to a pregnant woman with a G6PD-deficient fetus. ARAKODA is not recommended during pregnancy. A G6PD-deficient infant may be at risk for hemolytic anemia from exposure to ARAKODA through breast milk. Check infant’s G6PD status before breastfeeding begins. ( 5.2 , 8.1 , 8.2 ) • Methemoglobinemia : Asymptomatic elevations in blood methemoglobin have been observed. Initiate appropriate therapy if signs or symptoms of methemoglobinemia occur. ( 5.3 ) • Psychiatric Effects : Serious psychotic adverse reactions have been observed in patients with a history of psychosis or schizophrenia, at doses different from the approved dose. If psychotic symptoms (hallucinations, delusions, or grossly disorganized thinking or behavior) occur, consider discontinuation of ARAKODA therapy and, evaluation by a mental health professional as soon as possible. ( 5.4 ) • Hypersensitivity Reactions : Serious hypersensitivity reactions have been observed with administration of ARAKODA. If hypersensitivity reactions occur, institute appropriate therapy. ( 5.5 ) • Delayed Adverse Reactions : Due to the long half-life of ARAKODA (approximately 17 days), psychiatric effects, hemolytic anemia, methemoglobinemia, and hypersensitivity reactions may be delayed in onset and/or duration. ( 5.6 , 12.3 ) 5.1 Hemolytic Anemia Due to the risk of hemolytic anemia in patients with G6PD deficiency, G6PD testing must be performed before prescribing ARAKODA [see Contraindications ( 4 )] . Due to the limitations with G6PD tests, physicians need to be aware of residual risk of hemolysis and adequate medical support and follow-up to manage hemolytic risk should be available. Treatment with ARAKODA is contraindicated in patients with G6PD deficiency or unknown G6PD status [see Contraindications ( 4 )] . In clinical trials, declines in hemoglobin levels were reported in some G6PD-normal patients [see Adverse Reactions ( 6.1 )] . Monitor patients for clinical signs or symptoms of hemolysis [see Warnings and Precautions ( 5.6 )] . Advise patients to discontinue ARAKODA and seek medical attention if signs of hemolysis occur. 5.2 G6PD Deficiency in Pregnancy and Lactation Potential Harm to the Fetus The use of ARAKODA during pregnancy may cause hemolytic anemia in a G6PD-deficient fetus. Even if a pregnant woman has normal levels of G6PD, the fetus could be G6PD deficient. Advise females of reproductive potential that treatment with ARAKODA during pregnancy is not recommended and to avoid pregnancy or use effective contraception during treatment and for 3 months after the last dose of ARAKODA. If a pregnancy is detected during ARAKODA use, discontinue ARAKODA as soon as possible and switch to an alternative prophylactic drug for malaria during pregnancy [see Use in Specific Populations ( 8.1 and 8.3 )] . Potential Harm to the Breastfeeding Infant A G6PD-deficient infant may be at risk for hemolytic anemia from exposure to ARAKODA through breast milk. Infant G6PD status should be checked before breastfeeding begins. ARAKODA is contraindicated in breastfeeding women when the infant is found to be G6PD deficient or the G6PD status of the infant is unknown [see Contraindications ( 4 )] . Advise the woman with a G6PD-deficient infant or if the G6PD status of the infant is unknown not to breastfeed during treatment with ARAKODA and for 3 months after the final dose [see Use in Specific Populations ( 8.2 )] . 5.3 Methemoglobinemia Asymptomatic elevations in methemoglobin have been observed in the clinical trials of ARAKODA [see Adverse Reactions ( 6.1 )] . Institute appropriate therapy if signs or symptoms of methemoglobinemia occur [see Warnings and Precautions ( 5.6 )] . Carefully monitor individuals with nicotinamide adenine dinucleotide (NADH)-dependent methemoglobin reductase deficiency. Advise patients to discontinue ARAKODA and seek medical attention if signs of methemoglobinemia occur. 5.4 Psychiatric Effects In patients receiving ARAKODA in clinical trials, psychiatric adverse reactions included sleep disturbances (2.5%), depression/depressed mood (0.3%), and anxiety (0.2%) [see Adverse Reactions ( 6.1 )] . ARAKODA was discontinued in a subject with an adverse reaction of suicide attempt (0.1%). Subjects with a history of psychiatric disorders were excluded from three of five ARAKODA trials in which mefloquine was included as a comparator. Psychosis was reported in three patients with a history of psychosis or schizophrenia who received tafenoquine doses (350 mg to 500 mg single dose, or 400 mg daily for 3 days) different from the approved ARAKODA regimen. Safety and effectiveness of ARAKODA have not been established at doses or regimens other than the approved regimen; use of ARAKODA at doses or regimens other than a 200-mg weekly dose is not approved by FDA. ARAKODA is contraindicated in patients with a history of psychotic disorders or current psychotic symptoms [see Contraindication ( 4 )] . If psychotic symptoms (hallucinations, delusions, or grossly disorganized thinking or behavior) occur, consider discontinuation of ARAKODA and prompt evaluation by a mental health professional as soon as possible. Other psychiatric symptoms, such as changes in mood, anxiety, insomnia, and nightmares, should be promptly evaluated by a medical professional if they are moderate and last more than three days or are severe [see Warnings and Precautions ( 5.6 )] . 5.5 Hypersensitivity Reactions Serious hypersensitivity reactions (e.g., angioedema and urticaria) have been observed with administration of tafenoquine. Hypersensitivity reactions have been reported in clinical trials of ARAKODA [see Adverse Reactions ( 6.1 )] . Discontinue prophylaxis with ARAKODA and institute appropriate therapy if hypersensitivity reactions occur [see Warnings and Precautions ( 5.6 )] . ARAKODA is contraindicated in patients who develop hypersensitivity to tafenoquine or any component of ARAKODA or other 8-aminoquinolines [see Contraindications ( 4 )] . 5.6 Delayed Adverse Reactions, Including Hemolytic Anemia, Methemoglobinemia, Psychiatric Effects, and Hypersensitivity Reactions Adverse reactions including hemolytic anemia, methemoglobinemia, psychiatric effects, and hypersensitivity reactions were reported with the use of ARAKODA or tafenoquine in clinical trials [see Warnings and Precautions ( 5.1 , 5.3 , 5.4 , 5.5 )] . Due to the long half-life of ARAKODA (approximately 17 days), psychiatric effects, hemolytic anemia, methemoglobinemia, and signs or symptoms of hypersensitivity reactions that may occur could be delayed in onset and/or duration. Advise patients to seek medical attention if signs of hypersensitivity occur [see Clinical Pharmacology ( 12.3 )] ."}', 'overdosage': '{"10 OVERDOSAGE There were no reported cases of ARAKODA overdose. Hemoglobin decline and methemoglobinemia may be encountered in an overdose with ARAKODA. Treatment of overdosage consists of institution of appropriate symptomatic and/or supportive therapy."}', 'active_flag': 'Y', 'generic_name': '{TAFENOQUINE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). G6PD Testing and Hemolytic Anemia Inform patients of the need for testing for G6PD deficiency before starting ARAKODA. Advise patients on the symptoms of hemolytic anemia and instruct them to seek medical advice promptly if such symptoms occur. Patients should contact their health care provider if they have darker lips or urine as these may be signs of hemolysis or methemoglobinemia [see Warnings and Precautions ( 5.1 )] . Important Administration Instructions • Advise patients to take ARAKODA with food. • Advise patients to swallow the tablet whole and not to break, crush or chew it. • Advise patients to complete the full course of ARAKODA including the loading dose, maintenance dose and terminal dose. Potential Harm to the Fetus Advise females of reproductive potential of the potential risk of ARAKODA to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.1 )] . Advise females of reproductive potential to avoid pregnancy or use effective contraception during treatment with ARAKODA and for 3 months after the final dose [see Use in Specific Populations ( 8.3 )] . Lactation Advise women with a G6PD-deficient infant, or if they do not know the G6PD status of their infant, not to breastfeed during treatment with ARAKODA and for 3 months after the final dose [see Contraindication ( 4 ), Warnings and Precautions ( 5.2 ), Use in Specific Populations ( 8.2 )] . Methemoglobinemia Inform patients that methemoglobinemia has occurred with ARAKODA. Advise patients on the symptoms of methemoglobinemia and instruct them to seek medical advice promptly if such symptoms occur [see Warnings and Precautions ( 5.3 )] . Psychiatric Symptoms Advise patients who experience hallucinations, delusions, or confused thinking while taking ARAKODA to seek medical attention as soon as possible. Other psychiatric symptoms, such as changes in mood, anxiety, insomnia, and nightmares, should be promptly evaluated by a medical professional if they last more than three days or severe [see Warnings and Precautions ( 5.4 )] . Hypersensitivity Reactions Inform patients that hypersensitivity reactions have occurred with ARAKODA. Advise patients on the symptoms of hypersensitivity reactions and instruct them to seek medical advice promptly if such symptoms occur [see Warnings and Precautions ( 5.5 )] . Manufactured For: 60 Degrees Pharmaceuticals LLC, 1025 Connecticut Avenue NW, Suite 1000, Washington DC 20036 1217a"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary The use of ARAKODA during pregnancy may cause hemolytic anemia in a fetus who is G6PD-deficient. Treatment with ARAKODA during pregnancy is not recommended. If a pregnancy is detected during ARAKODA use, discontinue ARAKODA as soon as possible and switch to an alternative prophylactic drug for malaria during pregnancy [see Warnings and Precautions ( 5.2 )] . Available data with use of ARAKODA in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal studies, there were increased abortions, with and without maternal toxicity when tafenoquine was given orally to pregnant rabbits at and above doses equivalent to about 0.4 times the clinical exposure based on body surface area comparisons. No fetotoxicity was observed at doses about 1.5 times the clinical exposure (based on body surface area comparisons) in a similar study in rats. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk: Malaria during pregnancy increases the risk for adverse pregnancy outcomes, including maternal anemia, prematurity, spontaneous abortion and stillbirth. Data Animal Data: Tafenoquine resulted in dose-related abortions when given orally to pregnant rabbits during organogenesis (Gestation Days 6 to 18), at doses of 7 mg/kg (about 0.4 times the clinical exposure based on body surface area comparisons) and above. Doses higher than 7 mg/kg were also associated with maternal toxicity (mortality and reduced body weight gain). In a similar study in rats, doses of 3, 10, or 30 mg/kg/day resulted in maternal toxicity (enlarged spleen, reduced body weight and reduced food intake) but no fetotoxicity at the high dose (about 1.5 times the clinical exposure based on body surface area comparisons). There was no evidence of malformations in either species. In a pre- and postnatal development study in rats, tafenoquine administered throughout pregnancy and lactation produced maternal toxicity and a reversible decrease in offspring body weight gain and decrease in motor activity at 18 mg/kg/day, which is equivalent to about 0.6 times the clinical dose based on body surface area comparisons."}', 'pediatric_use': '{"8.4 Pediatric Use Safety and effectiveness of ARAKODA in pediatric patients have not been established."}', 'geriatric_use': '{"8.5 Geriatric Use Clinical trials of ARAKODA did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients [see Clinical Pharmacology ( 12.3 )] ."}'}

{"VARDENAFIL HYDROCHLORIDE"}

{'contraindications': '{"4 CONTRAINDICATIONS Administration with nitrates and nitric oxide donors ( 2.4 , 4.1 ) Administration with guanylate cyclase (GC) stimulators, such as riociguat ( 2.4 , 4.2 ) 4.1 Nitrates Administration of vardenafil hydrochloride tablets with nitrates (either regularly and/or intermittently) and nitric oxide donors is contraindicated [see Clinical Pharmacology ( 12.2 )] . Consistent with the effects of PDE5 inhibition on the nitric oxide/cyclic guanosine monophosphate pathway, PDE5 inhibitors, including vardenafil hydrochloride tablets, may potentiate the hypotensive effects of nitrates. A suitable time interval following dosing of vardenafil hydrochloride tablets for the safe administration of nitrates or nitric oxide donors has not been determined. 4.2 Guanylate Cyclase (GC) Stimulators Do not use vardenafil hydrochloride tablets in patients who are using a GC stimulator, such as riociguat. PDE5 inhibitors, including vardenafil hydrochloride tablets may potentiate the hypotensive effects of GC stimulators."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions with the use of vardenafil are discussed elsewhere in the labeling: Cardiovascular Effects [see Contraindications ( 4.1 ) and Warnings and Precautions ( 5.1 )] Priapism [see Warnings and Precautions ( 5.3 )] Effects on Eye [see Warnings and Precautions ( 5.4 )] Sudden Hearing Loss [see Warnings and Precautions ( 5.5 )] QT Prolongation [see Warnings and Precautions ( 5.7 )] Most common adverse reactions reported (≥2% of patients) are headache, flushing, nasal congestion, dyspepsia, sinusitis, flu syndrome, dizziness, increased creatine kinase, nausea, back pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Vardenafil hydrochloride was administered to over 4,430 men (mean age 56, range 18 to 89 years; 81% White, 6% Black, 2% Asian, 2% Hispanic and 9% Other) during controlled and uncontrolled clinical trials worldwide. Over 2,200 patients were treated for 6 months or longer and 880 patients were treated for at least 1 year. In placebo-controlled clinical trials, the discontinuation rate due to adverse events was 3.4% for vardenafil hydrochloride compared to 1.1% for placebo. When vardenafil hydrochloride was taken as recommended in placebo-controlled clinical trials, the following adverse reactions were reported (see Table 1). Table 1: Adverse Reactions Reported by ≥2% of Patients Treated with Vardenafil Hydrochloride Tablets and More Frequent on Drug than Placebo in Fixed and Flexiblea Dose Randomized, Controlled Trials of 5 mg, 10 mg, or 20 mg Vardenafil Adverse Reaction Percentage of Patients Reporting Reactions Placebo Vardenafil hydrochloride N = 1,199 N = 2,203 Headache 4% 15% Flushing 1% 11% Rhinitis 3% 9% Dyspepsia 1% 4% Accidental Injury b 2% 3% Sinusitis 1% 3% Flu Syndrome 2% 3% Dizziness 1% 2% Increased Creatine Kinase 1% 2% Nausea 1% 2% a) Flexible dose studies started all patients at vardenafil 10 mg and allowed decrease in dose to 5 mg or increase in dose to 20 mg based on side effects and efficacy. b) All the events listed in the above table were deemed to be adverse drug reactions with the exception of accidental injury. Back pain was reported in 2.0% of patients treated with vardenafil hydrochloride and 1.7% of patients on placebo. Placebo-controlled trials suggested a dose effect in the incidence of some adverse reactions (headache, flushing, dyspepsia, nausea, and rhinitis) over the 5 mg, 10 mg, and 20 mg doses of vardenafil. All Vardenafil Studies: Vardenafil hydrochloride film-coated tablets and vardenafil orally disintegrating tablets have been administered to over 17,000 men (mean age 54.5, range 18 to 89 years; 70% White, 5% Black, 13% Asian, 4% Hispanic and 8% Other) during controlled and uncontrolled clinical trials worldwide. The number of patients treated for 6 months or longer was 3,357, and 1,350 patients were treated for at least 1 year. In the placebo-controlled clinical trials for vardenafil hydrochloride film-coated tablets and vardenafil orally disintegrating tablets, the discontinuation rate due to adverse events was 1.9% for vardenafil compared to 0.8% for placebo. The following section identifies additional, less frequent adverse reactions (< 2%) reported during the clinical development of vardenafil hydrochloride film-coated tablets and vardenafil orally disintegrating tablets. Excluded from this list are those adverse reactions that are infrequent and minor, those events that may be commonly observed in the absence of drug therapy, and those events that are not reasonably associated with the drug: Body as a whole: allergic edema and angioedema, feeling unwell, allergic reactions, chest pain Auditory: tinnitus, vertigo Cardiovascular: palpitation, tachycardia, angina pectoris, myocardial infarction, ventricular tachyarrhythmias, hypotension Digestive: nausea, gastrointestinal and abdominal pain, dry mouth, diarrhea, gastroesophageal reflux disease, gastritis, vomiting, increase in transaminases Musculoskeletal: increase in creatine phosphokinase (CPK), increased muscle tone and cramping, myalgia Nervous: paresthesia and dysesthesia, somnolence, sleep disorder, syncope, amnesia, seizure Respiratory: dyspnea, sinus congestion Skin and appendages: erythema, rash Ophthalmologic: visual disturbance, ocular hyperemia, visual color distortions, eye pain and eye discomfort, photophobia, increase in intraocular pressure, conjunctivitis Urogenital: increase in erection, priapism 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of vardenafil hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure. Ophthalmologic: Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely postmarketing in temporal association with the use of PDE5 inhibitors, including vardenafil. Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking [see Warnings and Precautions ( 5.4 ) and Patient Counseling Information ( 17 )] . Visual disturbances including vision loss (temporary or permanent), such as visual field defect, retinal vein occlusion, and reduced visual acuity, have also been reported rarely in postmarketing experience. It is not possible to determine whether these events are related directly to the use of vardenafil. Neurologic: Seizure, seizure recurrence and transient global amnesia have been reported postmarketing in temporal association with vardenafil. Otologic: Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including vardenafil. In some cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of vardenafil, to the patient’s underlying risk factors for hearing loss, a combination of these factors, or to other factors [see Patient Counseling Information ( 17 )] ."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Vardenafil hydrochloride can potentiate the hypotensive effects of nitrates, alpha-blockers, and antihypertensives. ( 7.1 ) 7.1 Potential for Pharmacodynamic Interactions with Vardenafil Hydrochloride Nitrates: Concomitant use of vardenafil hydrochloride and nitrates and nitric oxide donors is contraindicated. The blood pressure lowering effects of sublingual nitrates (0.4 mg) taken 1 and 4 hours after vardenafil and increases in heart rate when taken at 1, 4 and 8 hours after vardenafil were potentiated by a 20 mg dose of vardenafil in healthy middle-aged subjects. These effects were not observed when vardenafil 20 mg was taken 24 hours before the nitroglycerin (NTG). Potentiation of the hypotensive effects of nitrates for patients with ischemic heart disease has not been evaluated, and concomitant use of vardenafil hydrochloride and nitrates is contraindicated [see Contraindications ( 4.1 ) and Clinical Pharmacology ( 12.2 )] . Alpha-Blockers: Caution is advised when PDE5 inhibitors are coadministered with alpha-blockers. PDE5 inhibitors, including vardenafil hydrochloride and alpha-adrenergic blocking agents are both vasodilators with blood-pressure-lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated. Clinical pharmacology studies have been conducted with coadministration of vardenafil with alfuzosin, terazosin or tamsulosin [see Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.6 ), and Clinical Pharmacology ( 12.2 )] . Antihypertensives: Vardenafil hydrochloride may add to the blood pressure lowering effects of antihypertensive agents. In a clinical pharmacology study of patients with erectile dysfunction, single doses of vardenafil 20 mg caused a mean maximum decrease in supine blood pressure of 7 mmHg systolic and 8 mmHg diastolic (compared to placebo), accompanied by a mean maximum increase of heart rate of 4 beats per minute. The maximum decrease in blood pressure occurred between 1 and 4 hours after dosing. Following multiple dosing for 31 days, similar blood pressure responses were observed on Day 31 as on Day 1. Alcohol: Vardenafil (20 mg) did not potentiate the hypotensive effects of alcohol during the 4-hour observation period in healthy volunteers when administered with alcohol (0.5 g/kg body weight, approximately 40 mL of absolute alcohol in a 70 kg person). Alcohol and vardenafil plasma levels were not altered when dosed simultaneously. 7.2 Effect of Other Drugs on Vardenafil In vitro studies Studies in human liver microsomes showed that vardenafil is metabolized primarily by cytochrome P450 (CYP) isoforms 3A4/5, and to a lesser degree by CYP2C9. Therefore, inhibitors of these enzymes are expected to reduce vardenafil clearance [see Dosage and Administration ( 2.4 ) and Warnings and Precautions ( 5.2 )] . In vivo studies Strong CYP3A4 inhibitors Ketoconazole (200 mg once daily) produced a 10-fold increase in vardenafil AUC and a 4-fold increase in maximum concentration (C max ) when coadministered with vardenafil (5 mg) in healthy volunteers. A 5 mg vardenafil dose should not be exceeded in a 24-hour period when used in combination with 200 mg once daily ketoconazole. Since higher doses of ketoconazole (400 mg daily) may result in higher increases in C max and AUC, a single 2.5 mg dose of vardenafil should not be exceeded in a 24-hour period when used in combination with ketoconazole 400 mg daily [see Dosage and Administration ( 2.4 ) and Warnings and Precautions ( 5 )] . Indinavir (800 mg t.i.d.) coadministered with vardenafil 10 mg resulted in a 16-fold increase in vardenafil AUC, a 7-fold increase in vardenafil C max and a 2-fold increase in vardenafil half-life. It is recommended not to exceed a single 2.5 mg vardenafil dose in a 24-hour period when used in combination with indinavir [see Dosage and Administration ( 2.4 ) and Warnings and Precautions ( 5.2 )] . Ritonavir (600 mg b.i.d.) coadministered with vardenafil 5 mg resulted in a 49-fold increase in vardenafil AUC and a 13-fold increase in vardenafil C max . The interaction is a consequence of blocking hepatic metabolism of vardenafil by ritonavir, a HIV protease inhibitor and a highly strong CYP3A4 inhibitor, which also inhibits CYP2C9. Ritonavir significantly prolonged the half-life of vardenafil to 26 hours. Consequently, it is recommended not to exceed a single 2.5 mg vardenafil dose in a 72-hour period when used in combination with ritonavir [see Dosage and Administration ( 2.4 ) and Warnings and Precautions ( 5.2 )] . Cobicistat with vardenafil can result in increased plasma concentrations, therefore it is recommended that a single 2.5 mg dose of vardenafil should not be exceeded in a 72-hour period [See Dosage and Administration ( 2.4 ) and Warnings and Precautions ( 5 )]. Moderate CYP3A4 inhibitors Erythromycin (500 mg t.i.d.) produced a 4-fold increase in vardenafil AUC and a 3-fold increase in C max when coadministered with vardenafil 5 mg in healthy volunteers. It is recommended not to exceed a single 5 mg dose of vardenafil in a 24-hour period when used in combination with erythromycin [see Dosage and Administration ( 2.4 ) and Warnings and Precautions ( 5 )] . Although specific interactions have not been studied, other CYP3A4 inhibitors, including grapefruit juice would likely increase vardenafil exposure. Other Drug Interactions No pharmacokinetic interactions were observed between vardenafil and the following drugs: glyburide, warfarin, digoxin, an antacid based on magnesium-aluminum hydroxide, and ranitidine. In the warfarin study, vardenafil had no effect on the prothrombin time or other pharmacodynamic parameters. Cimetidine (400 mg b.i.d.) had no effect on vardenafil bioavailability (AUC) and maximum concentration (C max ) of vardenafil when coadministered with 20 mg vardenafil in healthy volunteers. 7.3 Effects of Vardenafil on Other Drugs In vitro studies Vardenafil and its metabolites had no effect on CYP1A2, 2A6, and 2E1 (Ki > 100 micromolar). Weak inhibitory effects toward other isoforms (CYP2C8, 2C9, 2C19, 2D6, 3A4) were found, but Ki values were in excess of plasma concentrations achieved following dosing. The most potent inhibitory activity was observed for vardenafil metabolite M1, which had a Ki of 1.4 micromolar toward CYP3A4, which is about 20 times higher than the M1 C max values after an 80 mg vardenafil dose. In vitro data suggest that vardenafil has the potential to inhibit P-glycoprotein (P-gp) at therapeutic doses. While concomitant use of vardenafil did not significantly increase plasma concentrations of digoxin, a P-gp substrate, the effect on plasma concentrations of P-gp substrates that are more sensitive than digoxin (e.g. dabigatran) is not known. In vivo studies Nifedipine: Vardenafil 20 mg, when coadministered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the AUC or C max of nifedipine, a drug that is metabolized via CYP3A4. Nifedipine did not alter the plasma levels of vardenafil when taken in combination. In these patients whose hypertension was controlled with nifedipine, vardenafil 20 mg produced mean additional supine systolic/diastolic blood pressure reductions of 6/5 mmHg compared to placebo. Ritonavir and Indinavir: Upon concomitant administration of 5 mg of vardenafil with 600 mg BID ritonavir, the C max and AUC of ritonavir were reduced by approximately 20%. Upon administration of 10 mg of vardenafil with 800 mg TID indinavir, the C max and AUC of indinavir were reduced by 40% and 30%, respectively. Aspirin: Vardenafil (10 mg and 20 mg) did not potentiate the increase in bleeding time caused by aspirin (two 81 mg tablets). Other interactions: Vardenafil hydrochloride had no effect on the pharmacodynamics of glyburide (glucose and insulin concentrations) and warfarin (prothrombin time or other pharmacodynamic parameters)."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Vardenafil hydrochloride tablets are indicated for the treatment of erectile dysfunction. Vardenafil hydrochloride tablets are a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction. ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS The evaluation of erectile dysfunction should include a medical assessment, a determination of potential underlying causes and the identification of appropriate treatment. Before prescribing vardenafil hydrochloride, it is important to note the following: Cardiovascular Effects : Patients should not use vardenafil hydrochloride if sex is inadvisable due to cardiovascular status. ( 5.1 ) Risk of Priapism : In the event that an erection lasts more than 4 hours, the patient should seek immediate medical assistance. ( 5.3 ) Effects on the Eye : Patients should stop use of vardenafil hydrochloride, and seek medical attention in the event of sudden loss of vision in one or both eyes, which could be a sign of nonarteritic anterior ischemic optic neuropathy (NAION). Vardenafil hydrochloride should be used with caution, and only when the anticipated benefits outweigh the risks, in patients with a history of NAION. Patients with a “crowded” optic disc may also be at an increased risk of NAION. ( 5.4 , 6.2 ) Sudden Hearing Loss : Patients should stop vardenafil hydrochloride and seek medical attention in the event of sudden decrease or loss in hearing. ( 5.5 , 6.2 ) Alpha-Blockers : Caution is advised when PDE5 inhibitors are coadministered with alpha-blockers. In some patients, concomitant use of these two drug classes can lower blood pressure significantly leading to symptomatic hypotension (for example, fainting). ( 2.4 , 5.6 ) QT Prolongation : Patients with congenital QT syndrome or taking class IA or III antiarrhythmics should avoid using vardenafil hydrochloride. ( 5.7 , 12.2 ) 5.1 Cardiovascular Effects General Physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. Therefore, treatment for erectile dysfunction, including vardenafil hydrochloride, should not be used in men for whom sexual activity is not recommended because of their underlying cardiovascular status. There are no controlled clinical data on the safety or efficacy of vardenafil in the following patients; and therefore its use is not recommended until further information is available: unstable angina; hypotension (resting systolic blood pressure of < 90 mmHg); uncontrolled hypertension (> 170/110 mmHg); recent history of stroke, life-threatening arrhythmia, or myocardial infarction (within the last 6 months); severe cardiac failure. Left Ventricular Outflow Obstruction Patients with left ventricular outflow obstruction, (for example, aortic stenosis and idiopathic hypertrophic subaortic stenosis) can be sensitive to the action of vasodilators including PDE5 inhibitors. Blood Pressure Effects Vardenafil hydrochloride has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers (mean maximum decrease of 7 mmHg systolic and 8 mmHg diastolic) [see Clinical Pharmacology ( 12.2 )] . While this normally would be expected to be of little consequence in most patients, prior to prescribing vardenafil hydrochloride, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects. 5.2 Potential for Drug Interactions with Strong or Moderate CYP3A4 Inhibitors Concomitant administration with strong CYP3A4 inhibitors (such as ritonavir, indinavir, cobicistat, ketoconazole) or moderate CYP3A4 inhibitors (such as erythromycin) increases plasma concentrations of vardenafil. Dosage adjustment is necessary when vardenafil hydrochloride is administered with certain CYP3A4 inhibitors [see Dosage and Administration ( 2.4 ), and Drug Interactions ( 7.2 )] . Long-term safety information is not available on the concomitant administration of vardenafil with HIV protease inhibitors. 5.3 Risk of Priapism There have been rare reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for this class of compounds, including vardenafil. In the event that an erection persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result. Vardenafil hydrochloride should be used with caution by patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie’s disease) or by patients who have conditions that may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia). 5.4 Effects on the Eye Physicians should advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including vardenafil hydrochloride, and seek medical attention in the event of sudden loss of vision in one or both eyes. Such an event may be a sign of nonarteritic anterior ischemic optic neuropathy (NAION), a rare condition and a cause of decreased vision, including permanent loss of vision, that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors. Based on published literature, the annual incidence of NAION is 2.5 to 11.8 cases per 100,000 in males aged ≥50. An observational case-crossover study evaluated the risk of NAION when PDE5 inhibitor use, as a class, occurred immediately before NAION onset (within 5 half-lives), compared to PDE5 inhibitor use in a prior time period. The results suggest an approximate 2-fold increase in the risk of NAION, with a risk estimate of 2.15 (95% CI 1.06, 4.34). A similar study reported a consistent result, with a risk estimate of 2.27 (95% CI 0.99, 5.20). Other risk factors for NAION, such as the presence of “crowded” optic disc, may have contributed to the occurrence of NAION in these studies. Neither the rare postmarketing reports, nor the association of PDE5 inhibitor use and NAION in the observational studies, substantiate a causal relationship between PDE5 inhibitor use and NAION [see Adverse Reactions ( 6.2 )] . Physicians should consider whether their patients with underlying NAION risk factors could be adversely affected by use of PDE5 inhibitors. Individuals who have already experienced NAION are at increased risk of NAION recurrence. Therefore, PDE5 inhibitors, including vardenafil hydrochloride, should be used with caution in these patients and only when the anticipated benefits outweigh the risks. Individuals with “crowded” optic disc are also considered at greater risk for NAION compared to the general population, however, evidence is insufficient to support screening of prospective users of PDE5 inhibitors, including vardenafil hydrochloride, for this uncommon condition. Vardenafil hydrochloride has not been evaluated in patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa, therefore its use is not recommended until further information is available in those patients. 5.5 Sudden Hearing Loss Physicians should advise patients to stop taking all PDE5 inhibitors, including vardenafil hydrochloride, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including vardenafil. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see Adverse Reactions ( 6.2 )] . 5.6 Alpha-Blockers Caution is advised when PDE5 inhibitors are coadministered with alpha-blockers. PDE5 inhibitors, including vardenafil hydrochloride, and alpha-adrenergic blocking agents are both vasodilators with blood-pressure lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated. In some patients, concomitant use of these two drug classes can lower blood pressure significantly leading to symptomatic hypotension (for example, fainting) [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.2 )] . Consideration should be given to the following: Patients should be stable on alpha-blocker therapy prior to initiating a PDE5 inhibitor. Patients who demonstrate hemodynamic instability on alpha-blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of PDE5 inhibitors. In those patients who are stable on alpha-blocker therapy, PDE5 inhibitors should be initiated at the lowest recommended starting dose [see Dosage and Administration ( 2.4 )] . In those patients already taking an optimized dose of PDE5 inhibitor, alpha-blocker therapy should be initiated at the lowest dose. Stepwise increase in alpha-blocker dose may be associated with further lowering of blood pressure in patients taking a PDE5 inhibitor. Safety of combined use of PDE5 inhibitors and alpha-blockers may be affected by other variables, including intravascular volume depletion and other anti-hypertensive drugs. 5.7 Congenital or Acquired QT Prolongation In a study of the effect of vardenafil hydrochloride on QT interval in 59 healthy males [see Clinical Pharmacology ( 12.2 )] , therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil and the active control moxifloxacin (400 mg) produced similar increases in QT c interval. A postmarketing study evaluating the effect of combining vardenafil hydrochloride with another drug of comparable QT effect showed an additive QT effect when compared with either drug alone [see Clinical Pharmacology ( 12.2 )] . These observations should be considered in clinical decisions when prescribing vardenafil hydrochloride to patients with known history of QT prolongation or patients who are taking medications known to prolong the QT interval. Patients taking Class 1A (for example, quinidine, procainamide) or Class III (for example, amiodarone, sotalol) antiarrhythmic medications or those with congenital QT prolongation, should avoid using vardenafil hydrochloride. 5.8 Hepatic Impairment Dosage adjustment is necessary in patients with moderate hepatic impairment (Child-Pugh B). Do not use vardenafil hydrochloride in patients with severe (Child-Pugh C) hepatic impairment [see Dosage and Administration ( 2.3 ), Clinical Pharmacology ( 12.3 ), and Use in Specific Populations ( 8.6 )] . 5.9 Renal Impairment Do not use vardenafil hydrochloride in patients on renal dialysis, as vardenafil has not been evaluated in this population [see Dosage and Administration ( 2.3 ) and Use in Specific Populations ( 8.7 )] . 5.10 Combination with Other Erectile Dysfunction Therapies The safety and efficacy of vardenafil hydrochloride used in combination with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended. 5.11 Effects on Bleeding In humans, vardenafil alone in doses up to 20 mg does not prolong the bleeding time. There is no clinical evidence of any additive prolongation of the bleeding time when vardenafil is administered with aspirin. Vardenafil hydrochloride has not been administered to patients with bleeding disorders or significant active peptic ulceration. Therefore vardenafil hydrochloride should be administered to these patients after careful benefit-risk assessment. 5.12 Sexually Transmitted Disease The use of vardenafil hydrochloride offers no protection against sexually transmitted diseases. Counseling of patients about protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), should be considered."}', 'overdosage': '{"10 OVERDOSAGE The maximum dose of vardenafil for which human data are available is a single 120 mg dose administered to healthy male volunteers. The majority of these subjects experienced reversible back pain/myalgia and/or “abnormal vision.” Single doses up to 80 mg vardenafil and multiple doses up to 40 mg vardenafil administered once daily over 4 weeks were tolerated without producing serious adverse side effects. When 40 mg of vardenafil was administered twice daily, cases of severe back pain were observed. No muscle or neurological toxicity was identified. In cases of overdose, standard supportive measures should be taken as required. Renal dialysis is not expected to accelerate clearance as vardenafil is highly bound to plasma proteins and not significantly eliminated in the urine."}', 'active_flag': 'Y', 'generic_name': '{"VARDENAFIL HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION “See FDA-approved patient labeling (Patient Information)” Nitrates Inform patients that vardenafil hydrochloride is contraindicated with regular and/or intermittent use of organic nitrates. Patients should be counseled that concomitant use of vardenafil hydrochloride with nitrates could cause blood pressure to suddenly drop to an unsafe level, resulting in dizziness, syncope, or even heart attack or stroke. Guanylate Cyclase (GC) Stimulators Inform patients that vardenafil hydrochloride is contraindicated in patients who use guanylate cyclase stimulators, such as riociguat. Cardiovascular Discuss with patients the potential cardiac risk of sexual activity for patients with preexisting cardiovascular risk factors. Concomitant Use with Drugs which Lower Blood Pressure Inform patients that in some patients concomitant use of PDE5 inhibitors, including vardenafil hydrochloride, with alpha-blockers can lower blood pressure significantly leading to symptomatic hypotension (for example, fainting). Patients prescribed vardenafil hydrochloride who are taking alpha-blockers should be started on the lowest recommended starting dose of vardenafil hydrochloride [see Dosage and Administration (2.4) and Drug Interactions (7)] . Patients should be advised of the possible occurrence of symptoms related to postural hypotension and appropriate countermeasures. Patients should be advised to contact the prescribing physician if other anti-hypertensive drugs or new medications that may interact with vardenafil hydrochloride are prescribed by another healthcare provider. Recommended Administration Discuss with patients the appropriate use of vardenafil hydrochloride tablets and their anticipated benefits. It should be explained that sexual stimulation is required for an erection to occur after taking vardenafil hydrochloride tablets. Vardenafil hydrochloride tablets should be taken approximately 60 minutes before sexual activity. Patients should be counseled regarding the dosing of vardenafil hydrochloride tablets especially regarding the maximum daily dose. Patients should be advised to contact their healthcare provider for dose modification if they are not satisfied with the quality of their sexual performance with vardenafil hydrochloride tablets or in the case of an unwanted effect. Priapism Inform patients that there have been rare reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for vardenafil hydrochloride and this class of compounds. In the event that an erection persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result. Drug Interactions Advise patients to contact the prescribing physician if new medications that may interact with vardenafil hydrochloride are prescribed by another healthcare provider. Sudden Loss of Vision Inform patients to stop use of all PDE5 inhibitors, including vardenafil hydrochloride tablets, and seek medical attention in the event of sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision, including permanent loss of vision, that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors. Physicians should also discuss with patients the increased risk of NAION in individuals who have already experienced NAION in one eye. Physicians should also discuss with patients the increased risk of NAION among the general population in patients with a “crowded” optic disc, although evidence is insufficient to support screening of prospective users of PDE5 inhibitor, including vardenafil hydrochloride tablets, for this uncommon condition [see Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.1 )] . Sudden Hearing Loss Advise patients to stop taking PDE5 inhibitors, including vardenafil hydrochloride tablets, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including vardenafil hydrochloride. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see Adverse Reactions ( 6 )] . Sexually Transmitted Disease Inform patients that vardenafil hydrochloride tablets offer no protection against sexually transmitted diseases. Counsel patients that protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), should be considered. Dose Adjustment Inform patients that the recommended starting dose of vardenafil is 10 mg. The dose may be increased to a maximum recommended dose of 20 mg or decreased to 5 mg based on efficacy and tolerability. The maximum recommended dosing frequency is one tablet per day. Dispense with Patient Package Insert available at: www.tevausa.com/PatientPI Manufactured In Israel By: Teva Pharmaceutical Ind. Ltd. Kfar Saba, 4410202, Israel Manufactured For: Teva Pharmaceuticals Parsippany, NJ 07054 Rev. C 12/2023"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Vardenafil hydrochloride is not indicated for use in females. There are no data with the use of vardenafil hydrochloride in pregnant women to inform any drug-associated risks. In animal reproduction studies conducted in pregnant rats and rabbits, no adverse developmental outcomes were observed with oral administration of vardenafil during organogenesis at exposures for unbound vardenafil and its major metabolite at approximately 100 and 29 times, respectively, the maximum recommended human dose (MRHD) of 20 mg based on AUC (see Data) . Data Animal Data No evidence of specific potential for teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits that received vardenafil at up to 18 mg/kg/day during organogenesis. This dose is approximately 100 fold (rat) and 29 fold (rabbit) greater than the AUC values for unbound vardenafil and its major metabolite in humans given the MRHD of 20 mg. In the rat pre- and postnatal development study, the NOAEL (no observed adverse effect level) for maternal toxicity was 8 mg/kg/day. Retarded physical development of pups in the absence of maternal effects was observed following maternal exposure to 1 and 8 mg/kg possibly due to vasodilatation and/or secretion of the drug into milk. The number of living pups born to rats exposed pre- and postnatally was reduced at 60 mg/kg/day. Based on the results of the pre- and postnatal study, the developmental NOAEL is less than 1 mg/kg/day. Based on plasma exposures in the rat developmental toxicity study, 1 mg/kg/day in the pregnant rat is estimated to produce total AUC values for unbound vardenafil and its major metabolite comparable to the human AUC at the MRHD of 20 mg."}', 'pediatric_use': '{"8.4 Pediatric Use Vardenafil hydrochloride is not indicated for use in pediatric patients. Safety and efficacy have not been established in this population."}', 'geriatric_use': '{"8.5 Geriatric Use Elderly males 65 years of age and older have higher vardenafil plasma concentrations than younger males (18 to 45 years), mean C max and AUC were 34% and 52% higher, respectively. Phase 3 clinical trials included more than 834 elderly patients, and no differences in safety or effectiveness of vardenafil 5, 10, or 20 mg were noted when these elderly patients were compared to younger patients. However, due to increased vardenafil concentrations in the elderly, a starting dose of 5 mg vardenafil should be considered in patients ≥65 years of age [see Clinical Pharmacology ( 12.3 )] ."}'}

{"BROMPHENIRAMINE MALEATE","DEXTROMETHORPHAN HYDROBROMIDE","PHENYLEPHRINE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses ▪ temporarily relieves: ▪ Nasal congestion ▪ runny nose ▪ cough ▪ sneezing ▪ itchy, watery eyes due to hay fever ▪ itching of the nose or throat ▪ temporarily restores freer breathing through the nose"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"BROMPHENIRAMINE MALEATE, DEXTROMETHORPHAN HBR, PHENYLEPHRINE HCL"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if • nervousness, dizziness, or sleeplessness occurs • symptoms do not get better within 7 days or are accompanied by fever, rash, or persistent headache. These could be signs of a serious condition."}', 'do_not_use': '{"Do not use ▪ to sedate a child or to make a child sleepy ▪ if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson\'s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product."}', 'when_using': '{"When using this product ▪ do not use more than directed ▪ may cause marked drowsiness ▪ avoid alcoholic beverages ▪ alcohol, sedatives, and tranquilizers may increase drowsiness ▪ be careful when driving a motor vehicle or operating machinery ▪ excitability may occur, especially in children"}', 'warnings': '{"Warnings Do not use ▪ to sedate a child or to make a child sleepy ▪ if you are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson\'s disease), or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product. Ask a doctor before use if you have ▪ heart disease ▪ high blood pressure ▪ thyroid disease ▪ diabetes ▪ trouble urinating due to an enlarged prostate gland ▪ glaucoma ▪ cough that occurs with too much phlegm (mucus) ▪ a breathing problem or persistent or chronic cough that lasts such as occurs with smoking, asthma, chronic bronchitis, or emphysema Ask a doctor or pharmacist before use if you are ▪ taking any other oral nasal decongestant or stimulant ▪ taking sedatives or tranquilizers When using this product ▪ do not use more than directed ▪ may cause marked drowsiness ▪ avoid alcoholic beverages ▪ alcohol, sedatives, and tranquilizers may increase drowsiness ▪ be careful when driving a motor vehicle or operating machinery ▪ excitability may occur, especially in children Stop use and ask a doctor if • nervousness, dizziness, or sleeplessness occurs • symptoms do not get better within 7 days or are accompanied by fever, rash, or persistent headache. These could be signs of a serious condition. If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away at 1-800-222-1222."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"BENZALKONIUM CHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses • For handwashing to decrease bacteria on the skin. • After changing diapers. • After assisting ill persons. • Before contact with a person under medical care or treatment. • Recommended for repeat use."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"BENZALKONIUM CHLORIDE"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings For external use only. Do not use in the eyes. When using this product do not get into eyes. If contact occurs, rinse thoroughly with water. Stop use and ask a doctor if irritation and redness develop. If condition persists for more than 72 hours consult a doctor. Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"SERTRALINE HYDROCHLORIDE"}

{'contraindications': '{"4 CONTRAINDICATIONS Sertraline hydrochloride tablets are contraindicated in patients: Taking, or within 14 days of stopping, MAOIs, (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [See Warnings and Precautions (5.2) , Drug Interactions (7.1) ] . Taking pimozide [See Drug Interactions (7.1) ] . With known hypersensitivity to sertraline (e.g., anaphylaxis, angioedema) [See Adverse Reactions (6.1 , 6.2) ]. Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping MAOIs ( 4 , 7.1 ) Concomitant use of pimozide ( 4 , 7.1 ) Known hypersensitivity to sertraline or excipients ( 4 , 5.4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following adverse reactions are described in more detail in other sections of the prescribing information: Hypersensitivity reactions to sertraline [See Contraindications (4) ] QTc prolongation and ventricular arrhythmias when taken with pimozide [See Contraindications (4) , Clinical Pharmacology (12.2) ] Suicidal thoughts and behaviors [See Warnings and Precautions (5.1) ] Serotonin syndrome [See Contraindications (4) , Warnings and Precautions (5.2) , Drug Interactions (7.1) ] Increased risk of bleeding [See Warnings and Precautions (5.3) ] Activation of mania/hypomania [See Warnings and Precautions (5.4) ] Discontinuation syndrome [See Warnings and Precautions (5.5) ] Seizures [See Warnings and Precautions (5.6) ] Angle-closure glaucoma [See Warnings and Precautions (5.7) ] Hyponatremia [See Warnings and Precautions (5.8) ] Sexual Dysfunction [See Warnings and Precautions (5.11) ] Most common adverse reactions (≥5% and twice placebo) in pooled placebo-controlled MDD, OCD, PD, PTSD, SAD and PMDD clinical trials were nausea, diarrhea/loose stool, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below are from randomized, double-blind, placebo-controlled trials of sertraline hydrochloride (mostly 50 mg to 200 mg per day) in 3066 adults diagnosed with MDD, OCD, PD, PTSD, SAD, and PMDD. These 3066 patients exposed to sertraline hydrochloride for 8 to12 weeks represent 568 patient-years of exposure. The mean age was 40 years; 57% were females and 43% were males. The most common adverse reactions (≥5% and twice placebo) in all pooled placebo-controlled clinical trials of all sertraline hydrochloride-treated patients with MDD, OCD, PD, PTSD, SAD and PMDD were nausea, diarrhea/loose stool, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido (see Table 3). The following are the most common adverse reactions in trials of sertraline hydrochloride (≥5% and twice placebo) by indication that were not mentioned previously. MDD: somnolence; OCD: insomnia, agitation; PD: constipation, agitation; PTSD: fatigue; PMDD: somnolence, dry mouth, dizziness, fatigue, and abdominal pain; SAD: insomnia, dizziness, fatigue, dry mouth, malaise. Table 3: Common Adverse Reactions in Pooled Placebo-Controlled Trials in Adults with MDD, OCD, PD, PTSD, SAD, and PMDD* (1) Denominator used was for male patients only (n=1316 sertraline hydrochloride; n=973 placebo). * Adverse reactions that occurred greater than 2% in sertraline hydrochloride-treated patients and at least 2% greater in sertraline hydrochloride-treated patients than placebo-treated patients. Sertraline Hydrochloride (N=3066) Placebo (N=2293) Cardiac disorders Palpitations 4% 2% Eye disorders Visual impairment 4% 2% Gastrointestinal disorders Nausea 26% 12% Diarrhea/Loose stools 20% 10% Dry mouth 14% 9% Dyspepsia 8% 4% Constipation 6% 4% Vomiting 4% 1% General disorders and administration site conditions Fatigue 12% 8% Metabolism and nutrition disorders Decreased appetite 7% 2% Nervous system disorders Dizziness 12% 8% Somnolence 11% 6% Tremor 9% 2% Psychiatric Disorders Insomnia 20% 13% Agitation 8% 5% Libido decreased 6% 2% Reproductive system and breast disorders Ejaculation failure (1) 8% 1% Erectile dysfunction (1) 4% 1% Ejaculation disorder (1) 3% 0% Male sexual dysfunction (1) 2% 0% Skin and subcutaneous tissue disorders Hyperhidrosis 7% 3% Adverse Reactions Leading to Discontinuation in Placebo-Controlled Clinical Trials In all placebo-controlled studies in patients with MDD, OCD, PD, PTSD, SAD and PMDD, 368 (12%) of the 3066 patients who received sertraline hydrochloride discontinued treatment due to an adverse reaction, compared with 93 (4%) of the 2293 placebo-treated patients. In placebo-controlled studies, the following were the common adverse reactions leading to discontinuation in sertraline hydrochloride-treated patients: MDD, OCD, PD, PTSD, SAD and PMDD: nausea (3%), diarrhea (2%), agitation (2%), and insomnia (2%). MDD (>2% and twice placebo): decreased appetite, dizziness, fatigue, headache, somnolence, tremor, and vomiting. OCD: somnolence. PD: nervousness and somnolence. Male and Female Sexual Dysfunction Although changes in sexual desire, sexual performance and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of SSRI treatment. However, reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance and satisfaction are difficult to obtain, in part because patients and healthcare providers may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in labeling may underestimate their actual incidence. Table 4 below displays the incidence of sexual adverse reactions reported by at least 2% of sertraline hydrochloride-treated patients and twice placebo from pooled placebo-controlled trials. For men and all indications, the most common adverse reactions (>2% and twice placebo) included: ejaculation failure, decreased libido, erectile dysfunction, ejaculation disorder, and male sexual dysfunction. For women, the most common adverse reaction (≥2% and twice placebo) was decreased libido. Table 4: Most Common Sexual Adverse Reactions (≥2% and twice placebo) in Men or Women from Sertraline Hydrochloride Pooled Controlled Trials in Adults with MDD, OCD, PD, PTSD, SAD, and PMDD Sertraline Hydrochloride Placebo Men only (N=1316) (N=973) Ejaculation failure 8% 1% Libido decreased 7% 2% Erectile dysfunction 4% 1% Ejaculation disorder 3% 0% Male sexual dysfunction 2% 0% Women only (N=1750) (N=1320) Libido decreased 4% 2% Adverse Reactions in Pediatric Patients In 281 pediatric patients treated with sertraline hydrochloride in placebo-controlled studies, the overall profile of adverse reactions was generally similar to that seen in adult studies. Adverse reactions that do not appear in Table 3 (most common adverse reactions in adults) yet were reported in at least 2% of pediatric patients and at a rate of at least twice the placebo rate include fever, hyperkinesia, urinary incontinence, aggression, epistaxis, purpura, arthralgia, decreased weight, muscle twitching, and anxiety. Other Adverse Reactions Observed During the Premarketing Evaluation of Sertraline Hydrochloride Other infrequent adverse reactions, not described elsewhere in the prescribing information, occurring at an incidence of < 2% in patients treated with sertraline hydrochloride were: Cardiac disorders - tachycardia Ear and labyrinth disorders - tinnitus Endocrine disorders - hypothyroidism Eye disorders - mydriasis, blurred vision Gastrointestinal disorders - hematochezia, melena, rectal hemorrhage General disorders and administration site conditions - edema, gait disturbance, irritability, pyrexia Hepatobiliary disorders - elevated liver enzymes Immune system disorders - anaphylaxis Metabolism and nutrition disorders - diabetes mellitus, hypercholesterolemia, hypoglycemia, increased appetite Musculoskeletal and connective tissue disorders - arthralgia, muscle spasms, tightness, or twitching Nervous system disorders - ataxia, coma, convulsion, decreased alertness, hypoesthesia, lethargy, psychomotor hyperactivity, syncope Psychiatric disorders - aggression, bruxism, confusional state, euphoric mood, hallucination Renal and urinary disorders - hematuria Reproductive system and breast disorders - galactorrhea, priapism, vaginal hemorrhage Respiratory, thoracic and mediastinal disorders - bronchospasm, epistaxis, yawning Skin and subcutaneous tissue disorders - alopecia; cold sweat; dermatitis; dermatitis bullous; pruritus; purpura; erythematous, follicular, or maculopapular rash; urticaria Vascular disorders - hemorrhage, hypertension, vasodilation 6.2 Post-marketing Experience The following adverse reactions have been identified during postapproval use of sertraline hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Bleeding or clotting disorders - increased coagulation times (altered platelet function) Cardiac disorders - AV block, bradycardia, atrial arrhythmias, QTc-interval prolongation, ventricular tachycardia (including Torsade de Pointes) [See Clinical Pharmacology (12.2) ] Endocrine disorders - gynecomastia, hyperprolactinemia, menstrual irregularities, SIADH Eye disorders - blindness, optic neuritis, cataract Hepatobiliary disorders - severe liver events (including hepatitis, jaundice, liver failure with some fatal outcomes), pancreatitis Hemic and lymphatic disorders - agranulocytosis, aplastic anemia and pancytopenia, leukopenia, thrombocytopenia, lupus-like syndrome, serum sickness Immune system disorders - angioedema Metabolism and nutrition disorders - hyponatremia, hyperglycemia Musculoskeletal and connective tissue disorders - rhabdomyolysis, trismus Nervous system disorders - serotonin syndrome, extrapyramidal symptoms (including akathisia and dystonia), oculogyric crisis Psychiatric disorders – psychosis, enuresis, paroniria Renal and urinary disorders - acute renal failure Respiratory, thoracic and mediastinal disorders - pulmonary hypertension, eosinophilic pneumonia, anosmia, hyposmia Skin and subcutaneous tissue disorders - photosensitivity skin reaction and other severe cutaneous reactions, which potentially can be fatal, such as Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) Vascular disorders - cerebrovascular spasm (including reversible cerebral vasoconstriction syndrome and Call-Fleming syndrome), vasculitis"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Protein-bound drugs: Monitor for adverse reactions and reduce dosage of sertraline hydrochloride or other protein-bound drugs (e.g., warfarin) as warranted. ( 7.1 , 12.3 ) CYP2D6 substrates: Reduce dosage of drugs metabolized by CYP2D6. ( 7.1 , 12.3 ) 7.1 Clinically Significant Drug Interactions Table 5 includes clinically significant drug interactions with sertraline hydrochloride [See Clinical Pharmacology (12.3) ] . Table 5. Clinically-Significant Drug Interactions with Sertraline Hydrochloride Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: The concomitant use of SSRIs including sertraline hydrochloride and MAOIs increases the risk of serotonin syndrome. Intervention: Sertraline hydrochloride is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [See Dosage and Administration (2.5) , Contraindications (4) , Warnings and Precautions (5.2) ]. Examples: selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Pimozide Clinical Impact: Increased plasma concentrations of pimozide, a drug with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. Intervention: Concomitant use of pimozide and sertraline hydrochloride is contraindicated [See Contraindications (4) ]. Other Serotonergic Drugs Clinical Impact: The concomitant use of serotonergic drugs with sertraline hydrochloride increases the risk of serotonin syndrome. Intervention: Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of sertraline hydrochloride and/or concomitant serotonergic drugs [See Warnings and Precautions (5.2) ]. Examples: Other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort. Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants) Clinical Impact: The concurrent use of an antiplatelet agent or anticoagulant with sertraline hydrochloride may potentiate the risk of bleeding. Intervention: Inform patients of the increased risk of bleeding associated with the concomitant use of sertraline hydrochloride and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [See Warnings and Precautions (5.3) ]. Examples: aspirin, clopidogrel, heparin, warfarin Drugs Highly Bound to Plasma Protein Clinical Impact: Sertraline hydrochloride is highly bound to plasma protein. The concomitant use of sertraline hydrochloride with another drug that is highly bound to plasma protein may increase free concentrations of sertraline hydrochloride or other tightly-bound drugs in plasma [See Clinical Pharmacology (12.3) ] . Intervention: Monitor for adverse reactions and reduce dosage of sertraline hydrochloride or other protein-bound drugs as warranted. Examples: warfarin Drugs Metabolized by CYP2D6 Clinical Impact: Sertraline hydrochloride is a CYP2D6 inhibitor [See Clinical Pharmacology (12.3) ] . The concomitant use of sertraline hydrochloride with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. Intervention: Decrease the dosage of a CYP2D6 substrate if needed with concomitant sertraline hydrochloride use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if sertraline hydrochloride is discontinued. Examples: propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, thioridazine, tolterodine, venlafaxine Phenytoin Clinical Impact: Phenytoin is a narrow therapeutic index drug. Sertraline hydrochloride may increase phenytoin concentrations. Intervention: Monitor phenytoin levels when initiating or titrating sertraline hydrochloride. Reduce phenytoin dosage if needed. Examples: phenytoin, fosphenytoin Drugs that Prolong the QTc Interval Clinical Impact: The risk of QTc prolongation and/or ventricular arrhythmias (e.g., TdP) is increased with concomitant use of other drugs which prolong the QTc interval [See Warnings and Precautions (5.10) , Clinical Pharmacology (12.2) ] . Intervention: Pimozide is contraindicated for use with sertraline. Avoid the concomitant use of drugs known to prolong the QTc interval. Examples: Specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus). 7.2 Drugs Having No Clinically Important Interactions with Sertraline Hydrochloride Based on pharmacokinetic studies, no dosage adjustment of sertraline hydrochloride is necessary when used in combination with cimetidine. Additionally, no dosage adjustment is required for diazepam, lithium, atenolol, tolbutamide, digoxin, and drugs metabolized by CYP3A4, when sertraline hydrochloride is administered concomitantly [See Clinical Pharmacology (12.3) ] . 7.3 False-Positive Screening Tests for Benzodiazepines False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking sertraline hydrochloride. This finding is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of sertraline hydrochloride. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish sertraline from benzodiazepines."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Sertraline hydrochloride tablets are indicated for the treatment of the following [See Clinical Studies (14) ] : Major depressive disorder (MDD) Obsessive-compulsive disorder (OCD) Panic disorder (PD) Posttraumatic stress disorder (PTSD) Social anxiety disorder (SAD) Premenstrual dysphoric disorder (PMDD) Sertraline hydrochloride tablets are a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of ( 1 ): Major depressive disorder (MDD) Obsessive-compulsive disorder (OCD) Panic disorder (PD) Posttraumatic stress disorder (PTSD) Social anxiety disorder (SAD) Premenstrual dysphoric disorder (PMDD)"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone. If it occurs, discontinue sertraline hydrochloride and serotonergic agents and initiate supportive treatment. ( 5.2 ) Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk. ( 5.3 ) Activation of Mania/Hypomania: Screen patients for bipolar disorder. ( 5.4 ) Seizures: Use with caution in patients with seizure disorders. ( 5.6 ) Angle Closure Glaucoma: Avoid use of antidepressants, including sertraline hydrochloride, in patients with untreated anatomically narrow angles. ( 5.7 ) QTc Prolongation: Sertraline hydrochloride should be used with caution in patients with risk factors for QTc prolongation. ( 5.10 ) Sexual Dysfunction: sertraline hydrochloride may cause symptoms of sexual dysfunction. ( 5.11 ) 5.1 Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and over 4,400 pediatric patients, the incidence of suicidal thoughts and behaviors in pediatric and young adult patients was greater in antidepressant-treated patients than in placebo-treated patients. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 2. No suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the number was not sufficient to reach any conclusion about antidepressant drug effect on suicide. Table 2: Risk Differences of the Number of Cases of Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range (years) Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1000 Patients Treated Increases Compared to Placebo <18 14 additional patients 18 to 24 5 additional patients Decreases Compared to Placebo 25 to 64 1 fewer patient ≥65 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in pediatric and young adult patients extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression. Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing sertraline hydrochloride, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome Serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs), including sertraline hydrochloride, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [See Contraindications (4) , Drug Interactions (7.1) ]. Serotonin syndrome can also occur when these drugs are used alone. Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of sertraline hydrochloride with MAOIs is contraindicated. In addition, do not initiate sertraline hydrochloride in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking sertraline hydrochloride tablets, discontinue sertraline hydrochloride tablets before initiating treatment with the MAOI [See Contraindications (4) , Drug Interactions (7.1) ]. Monitor all patients taking sertraline hydrochloride for the emergence of serotonin syndrome. Discontinue treatment with sertraline hydrochloride and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of sertraline hydrochloride with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.3 Increased Risk of Bleeding Drugs that interfere with serotonin reuptake inhibition, including sertraline hydrochloride, increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Based on data from the published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Use in Specific Populations (8.1)] . Bleeding events related to drugs that interfere with serotonin reuptake have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages. Inform patients of the increased risk of bleeding associated with the concomitant use of sertraline hydrochloride and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio. 5.4 Activation of Mania or Hypomania In patients with bipolar disorder, treating a depressive episode with sertraline hydrochloride or another antidepressant may precipitate a mixed/manic episode. In controlled clinical trials, patients with bipolar disorder were generally excluded; however, symptoms of mania or hypomania were reported in 0.4% of patients treated with sertraline hydrochloride. Prior to initiating treatment with sertraline hydrochloride, screen patients for any personal or family history of bipolar disorder, mania, or hypomania. 5.5 Discontinuation Syndrome Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible [See Dosage and Administration (2.6) ]. 5.6 Seizures Sertraline hydrochloride has not been systematically evaluated in patients with seizure disorders. Patients with a history of seizures were excluded from clinical studies. Sertraline hydrochloride should be prescribed with caution in patients with a seizure disorder. 5.7 Angle-Closure Glaucoma The pupillary dilation that occurs following use of many antidepressant drugs including sertraline hydrochloride may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of antidepressants, including sertraline hydrochloride, in patients with untreated anatomically narrow angles. 5.8 Hyponatremia Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including sertraline hydrochloride. Cases with serum sodium lower than 110 mmol/L have been reported. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In patients with symptomatic hyponatremia, discontinue sertraline hydrochloride and institute appropriate medical intervention. Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with SSRIs and SNRIs [See Use in Specific Populations (8.5) ] . 5.9 False-Positive Effects on Screening Tests for Benzodiazepines False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking sertraline hydrochloride. This finding is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of sertraline hydrochloride. Confirmatory tests, such as gas chromatography/mass spectrometry, will help distinguish sertraline hydrochloride from benzodiazepines [See Drug Interactions (7.3) ] . 5.10 QTc Prolongation During post-marketing use of sertraline, cases of QTc prolongation and Torsade de Pointes (TdP) have been reported. Most reports were confounded by other risk factors. In a randomized, double-blind, placebo- and positive-controlled three-period crossover thorough QTc study in 54 healthy adult subjects, there was a positive relationship between the length of the rate-adjusted QTc interval and serum sertraline concentration. Therefore, sertraline hydrochloride should be used with caution in patients with risk factors for QTc prolongation [See Drug Interactions (7.1) , Clinical Pharmacology (12.2) ]. 5.11 Sexual Dysfunction Use of SSRIs, including sertraline hydrochloride, may cause symptoms of sexual dysfunction [see Adverse Reactions (6.1) ] . In male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, SSRI use may result in decreased libido and delayed or absent orgasm. It is important for prescribers to inquire about sexual function prior to initiation of sertraline hydrochloride and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported. When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder. Discuss potential management strategies to support patients in making informed decisions about treatment."}', 'overdosage': '{"10 OVERDOSAGE The following have been reported with sertraline tablet overdosage: Seizures, which may be delayed, and altered mental status including coma. Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation. Hypertension most commonly seen, but rarely can see hypotension alone or with co-ingestants including alcohol. Serotonin syndrome (patients with a multiple drug overdosage with other proserotonergic drugs may have a higher risk). Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a sertraline overdose. Consider contacting a Poison Center (1-800-221-2222) or a medical toxicologist for additional overdosage management recommendations."}', 'active_flag': 'Y', 'generic_name': '{"SERTRALINE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Suicidal Thoughts and Behaviors Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and when the dosage is adjusted up or down, and instruct them to report such symptoms to the healthcare provider [See Boxed Warning and Warnings and Precautions (5.1) ] . Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of sertraline hydrochloride with other serotonergic drugs including triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid). Patients should contact their health care provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome [See Warnings and Precautions (5.2) , Drug Interactions (7.1) ] . Increased Risk of Bleeding Inform patients about the concomitant use of sertraline hydrochloride with aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other anticoagulants because the combined use has been associated with an increased risk of bleeding. Advise patients to inform their health care providers if they are taking or planning to take any prescription or over-the-\xadcounter medications that increase the risk of bleeding [See Warnings and Precautions (5.3) ]. Activation of Mania/Hypomania Advise patients and their caregivers to observe for signs of activation of mania/hypomania and instruct them to report such symptoms to the healthcare provider [See Warnings and Precautions (5.4) ] . Discontinuation Syndrome Advise patients not to abruptly discontinue sertraline hydrochloride and to discuss any tapering regimen with their healthcare provider. Adverse reactions can occur when sertraline hydrochloride is discontinued [See Warnings and Precautions (5.5) ]. Sexual Dysfunction Advise patients that use of sertraline hydrochloride may cause symptoms of sexual dysfunction in both male and female patients. Inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider [see Warnings and Precautions (5.11) ]. Allergic Reactions Advise patients to notify their healthcare provider if they develop an allergic reaction such as rash, hives, swelling, or difficulty breathing [See Adverse Reactions (6.2) ] . Pregnancy Inform pregnant women that sertraline hydrochloride may cause withdrawal symptoms in the newborn or persistent pulmonary hypertension of the newborn (PPHN) [See Use in Specific Populations (8.1) ] . Advise women that there is a pregnancy exposure registry that monitors pregnancy outcomes of women exposed to sertraline hydrochloride during pregnancy. Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Revised: 09/2023 Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides"}', 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{GABAPENTIN}

{'contraindications': '{"4 CONTRAINDICATIONS Gabapentin is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients. Known hypersensitivity to gabapentin or its ingredients ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.1) ] Anaphylaxis and Angioedema [see Warnings and Precautions (5.2) ] Somnolence/Sedation and Dizziness [see Warnings and Precautions (5.4) ] Withdrawal Precipitated Seizure, Status Epilepticus [see Warnings and Precautions (5.5) ] Suicidal Behavior and Ideation [see Warnings and Precautions (5.6) ] Respiratory Depression [see Warnings and Precautions (5.7) ] Neuropsychiatric Adverse Reactions (Pediatric Patients 3 to 12 Years of Age) [ see Warnings and Precautions (5.8) ] Sudden and Unexplained Death in Patients with Epilepsy [ see Warnings and Precautions (5.10) ] Most common adverse reactions (incidence ≥8% and at least twice that for placebo) were: Postherpetic neuralgia: Dizziness, somnolence, and peripheral edema ( 6.1 ) Epilepsy in patients >12 years of age: Somnolence, dizziness, ataxia, fatigue, and nystagmus ( 6.1 ) Epilepsy in patients 3 to 12 years of age: Viral infection, fever, nausea and/or vomiting, somnolence, and hostility ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ScieGen Pharmaceuticals, Inc. at 1-855-724-3436 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Postherpetic Neuralgia The most common adverse reactions associated with the use of gabapentin in adults, not seen at an equivalent frequency among placebo-treated patients, were dizziness, somnolence, and peripheral edema. In the 2 controlled trials in postherpetic neuralgia, 16% of the 336 patients who received gabapentin and 9% of the 227 patients who received placebo discontinued treatment because of an adverse reaction. The adverse reactions that most frequently led to withdrawal in gabapentin -treated patients were dizziness, somnolence, and nausea. Table 3 lists adverse reactions that occurred in at least 1% of gabapentin -treated patients with postherpetic neuralgia participating in placebo-controlled trials and that were numerically more frequent in the gabapentin group than in the placebo group. Table 3 Adverse Reactions in Pooled Placebo-Controlled Trials in Postherpetic Neuralgia Gabapentin N=336 % Placebo N=227 % Body as a Whole Asthenia 6 5 Infection 5 4 Accidental injury 3 1 Digestive System Diarrhea 6 3 Dry mouth 5 1 Constipation 4 2 Nausea 4 3 Vomiting 3 2 Metabolic and Nutritional Disorders Peripheral edema 8 2 Weight gain 2 0 Hyperglycemia 1 0 Nervous System Dizziness 28 8 Somnolence 21 5 Ataxia 3 0 Abnormal thinking 3 0 Abnormal gait 2 0 Incoordination 2 0 Respiratory System Pharyngitis 1 0 Special Senses Amblyopia a 3 1 Conjunctivitis 1 0 Diplopia 1 0 Otitis media 1 0 a Reported as blurred vision Other reactions in more than 1% of patients but equally or more frequent in the placebo group included pain, tremor, neuralgia, back pain, dyspepsia, dyspnea, and flu syndrome. There were no clinically important differences between men and women in the types and incidence of adverse reactions. Because there were few patients whose race was reported as other than white, there are insufficient data to support a statement regarding the distribution of adverse reactions by race. Epilepsy with Partial Onset Seizures (Adjunctive Therapy) The most common adverse reactions with gabapentin in combination with other antiepileptic drugs in patients >12 years of age, not seen at an equivalent frequency among placebo-treated patients, were somnolence, dizziness, ataxia, fatigue, and nystagmus. The most common adverse reactions with gabapentin in combination with other antiepileptic drugs in pediatric patients 3 to 12 years of age, not seen at an equal frequency among placebo-treated patients, were viral infection, fever, nausea and/or vomiting, somnolence, and hostility [see Warnings and Precautions (5.8) ] . Approximately 7% of the 2,074 patients >12 years of age and approximately 7% of the 449 pediatric patients 3 to 12 years of age who received gabapentin in premarketing clinical trials discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with withdrawal in patients >12 years of age were somnolence (1.2%), ataxia (0.8%), fatigue (0.6%), nausea and/or vomiting (0.6%), and dizziness (0.6%). The adverse reactions most commonly associated with withdrawal in pediatric patients were emotional lability (1.6%), hostility (1.3%), and hyperkinesia (1.1%). Table 4 lists adverse reactions that occurred in at least 1% of gabapentin-treated patients >12 years of age with epilepsy participating in placebo-controlled trials and were numerically more common in the gabapentin group. In these studies, either gabapentin or placebo was added to the patient’s current antiepileptic drug therapy. TABLE 4. Adverse Reactions in Pooled Placebo-Controlled Add-On Trials In Epilepsy Patients >12 years of age Gabapentin a N = 543 % Placebo a N = 378 % Body as a Whole Fatigue 11 5 Increased Weight 3 2 Back Pain 2 1 Peripheral Edema 2 1 Cardiovascular Vasodilatation 1 0 Digestive System Dyspepsia 2 1 Dry Mouth or Throat 2 1 Constipation 2 1 Dental Abnormalities 2 0 Nervous System Somnolence 19 9 Dizziness 17 7 Ataxia 13 6 Nystagmus 8 4 Tremor 7 3 Dysarthria 2 1 Amnesia 2 0 Depression 2 1 Abnormal Thinking 2 1 Abnormal Coordination 1 0 Respiratory System Pharyngitis 3 2 Coughing 2 1 Skin and Appendages Abrasion 1 0 Urogenital System Impotence 2 1 Special Senses Diplopia 6 2 Amblyopia b 4 1 a Plus background antiepileptic drug therapy b Amblyopia was often described as blurred vision. Among the adverse reactions occurring at an incidence of at least 10% in gabapentin-treated patients, somnolence and ataxia appeared to exhibit a positive dose-response relationship. The overall incidence of adverse reactions and the types of adverse reactions seen were similar among men and women treated with gabapentin. The incidence of adverse reactions increased slightly with increasing age in patients treated with either gabapentin or placebo. Because only 3% of patients (28/921) in placebo-controlled studies were identified as nonwhite (black or other), there are insufficient data to support a statement regarding the distribution of adverse reactions by race. Table 5 lists adverse reactions that occurred in at least 2% of gabapentin-treated patients, age 3 to 12 years of age with epilepsy participating in placebo-controlled trials, and which were numerically more common in the gabapentin group. TABLE 5. Adverse Reactions in a Placebo-Controlled Add-On Trial in Pediatric Epilepsy Patients Age 3 to 12 Years Gabapentin a N = 119 % Placebo a N = 128 % Body as a Whole Viral Infection 11 3 Fever 10 3 Increased Weight 3 1 Fatigue 3 2 Digestive System Nausea and/or Vomiting 8 7 Nervous System Somnolence 8 5 Hostility 8 2 Emotional Lability 4 2 Dizziness 3 2 Hyperkinesia 3 1 Respiratory System Bronchitis 3 1 Respiratory Infection 3 1 a Plus background antiepileptic drug therapy Other reactions in more than 2% of pediatric patients 3 to 12 years of age but equally or more frequent in the placebo group included: pharyngitis, upper respiratory infection, headache, rhinitis, convulsions, diarrhea, anorexia, coughing, and otitis media. 6.2 Postmarketing Experience The following adverse reactions have been identified during postmarketing use of gabapentin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hepatobiliary disorders: jaundice Investigations: elevated creatine kinase, elevated liver function tests Metabolism and nutrition disorders: hyponatremia Musculoskeletal and connective tissue disorder: rhabdomyolysis Nervous system disorders: movement disorder Psychiatric disorders: agitation Reproductive system and breast disorders: breast enlargement, changes in libido, ejaculation disorders and anorgasmia Skin and subcutaneous tissue disorders: angioedema [see Warnings and Precautions (5.2) ] , bullous pemphigoid, erythema multiforme, Stevens-Johnson syndrome. There are postmarketing reports of life-threatening or fatal respiratory depression in patients taking gabapentin with opioids or other CNS depressants, or in the setting of underlying respiratory impairment [see Warnings and Precautions (5.7) ] . Adverse reactions following the abrupt discontinuation of gabapentin have also been reported. The most frequently reported reactions were anxiety, insomnia, nausea, pain, and sweating."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Concentrations increased by morphine; may need dose adjustment ( 5.4 , 7.1 ) 7.1 Opioids Respiratory depression and sedation, sometimes resulting in death, have been reported following coadministration of gabapentin with opioids (e.g., morphine, hydrocodone, oxycodone, buprenorphine) [see Warnings and Precautions (5.7) ]. Hydrocodone Coadministration of gabapentin with hydrocodone decreases hydrocodone exposure [see Clinical Pharmacology (12.3) ]. The potential for alteration in hydrocodone exposure and effect should be considered when gabapentin is started or discontinued in a patient taking hydrocodone. Morphine When gabapentin is administered with morphine, patients should be observed for signs of CNS depression, such as somnolence, sedation and respiratory depression [see Clinical Pharmacology (12.3) ]. 7.2 Other Antiepileptic Drugs Gabapentin is not appreciably metabolized nor does it interfere with the metabolism of commonly coadministered antiepileptic drugs [see Clinical Pharmacology (12.3) ] . 7.3 Maalox ® (aluminum hydroxide, magnesium hydroxide) The mean bioavailability of gabapentin was reduced by about 20% with concomitant use of an antacid (Maalox ® ) containing magnesium and aluminum hydroxides. It is recommended that gabapentin be taken at least 2 hours following Maalox administration [see Clinical Pharmacology (12.3) ]. 7.4 Drug/Laboratory Test Interactions Because false positive readings were reported with the Ames N-Multistix SG ® dipstick test for urinary protein when gabapentin was added to other antiepileptic drugs, the more specific sulfosalicylic acid precipitation procedure is recommended to determine the presence of urine protein."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Gabapentin is indicated for: Management of postherpetic neuralgia in adults Adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization, in adults and pediatric patients 3 years and older with epilepsy Gabapentin is indicated for: Postherpetic neuralgia in adults ( 1 ) Adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization, in adults and pediatric patients 3 years and older with epilepsy ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Drug Reaction with Eosinophilia and Systemic Symptoms (Multiorgan hypersensitivity): Discontinue if alternative etiology is not established ( 5.1 ) Anaphylaxis and Angioedema: Discontinue and evaluate patient immediately ( 5.2 ) Driving Impairment; Somnolence/Sedation and Dizziness: Warn patients not to drive until they have gained sufficient experience to assess whether their ability to drive or operate heavy machinery will be impaired ( 5.3 , 5.4 ) Increased seizure frequency may occur in patients with seizure disorders if gabapentin is abruptly discontinued ( 5.5 ) Suicidal Behavior and Ideation: Monitor for suicidal thoughts/behavior ( 5.6 ) Respiratory Depression: May occur with Gabapentin when used with concomitant central nervous system (CNS) depressants, including opioids, or in the setting of underlying respiratory impairment. Monitor patients and adjust dosage as appropriate ( 5.7 ) Neuropsychiatric Adverse Reactions in Children 3 to 12 Years of Age: Monitor for such events ( 5.8 ) 5.1 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has occurred with gabapentin. Some of these reactions have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Gabapentin should be discontinued if an alternative etiology for the signs or symptoms cannot be established. 5.2 Anaphylaxis and Angioedema Gabapentin can cause anaphylaxis and angioedema after the first dose or at any time during treatment. Signs and symptoms in reported cases have included difficulty breathing, swelling of the lips, throat, and tongue, and hypotension requiring emergency treatment. Patients should be instructed to discontinue gabapentin and seek immediate medical care should they experience signs or symptoms of anaphylaxis or angioedema. 5.3 Effects on Driving and Operating Heavy Machinery Patients taking gabapentin should not drive until they have gained sufficient experience to assess whether gabapentin impairs their ability to drive. Driving performance studies conducted with a prodrug of gabapentin (gabapentin enacarbil tablet, extended-release) indicate that gabapentin may cause significant driving impairment. Prescribers and patients should be aware that patients’ ability to assess their own driving competence, as well as their ability to assess the degree of somnolence caused by gabapentin, can be imperfect. The duration of driving impairment after starting therapy with gabapentin is unknown. Whether the impairment is related to somnolence [see Warnings and Precautions (5.4 ) ] or other effects of gabapentin is unknown. Moreover, because gabapentin causes somnolence and dizziness [see Warnings and Precautions (5.4 )] , patients should be advised not to operate complex machinery until they have gained sufficient experience on gabapentin to assess whether gabapentin impairs their ability to perform such tasks. 5.4 Somnolence/Sedation and Dizziness During the controlled epilepsy trials in patients older than 12 years of age receiving doses of gabapentin up to 1,800 mg daily, somnolence, dizziness, and ataxia were reported at a greater rate in patients receiving gabapentin compared to placebo: i.e., 19% in drug versus 9% in placebo for somnolence, 17% in drug versus 7% in placebo for dizziness, and 13% in drug versus 6% in placebo for ataxia. In these trials somnolence, ataxia and fatigue were common adverse reactions leading to discontinuation of gabapentin in patients older than 12 years of age, with 1.2%, 0.8% and 0.6% discontinuing for these events, respectively. During the controlled trials in patients with post-herpetic neuralgia, somnolence, and dizziness were reported at a greater rate compared to placebo in patients receiving gabapentin, in dosages up to 3600 mg per day: i.e., 21% in gabapentin-treated patients versus 5% in placebo-treated patients for somnolence and 28% in Gabapentin-treated patients versus 8% in placebo-treated patients for dizziness. Dizziness and somnolence were among the most common adverse reactions leading to discontinuation of gabapentin. Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when gabapentin is used with other drugs with sedative properties because of potential synergy. In addition, patients who require concomitant treatment with morphine may experience increases in gabapentin concentrations and may require dose adjustment [see Drug Interactions (7.1) ]. 5.5 Withdrawal Precipitated Seizure, Status Epilepticus Antiepileptic drugs should not be abruptly discontinued because of the possibility of increasing seizure frequency. In the placebo-controlled epilepsy studies in patients >12 years of age, the incidence of status epilepticus in patients receiving gabapentin was 0.6% (3 of 543) versus 0.5% in patients receiving placebo (2 of 378). Among the 2,074 patients >12 years of age treated with gabapentin across all epilepsy studies (controlled and uncontrolled), 31 (1.5%) had status epilepticus. Of these, 14 patients had no prior history of status epilepticus either before treatment or while on other medications. Because adequate historical data are not available, it is impossible to say whether or not treatment with gabapentin is associated with a higher or lower rate of status epilepticus than would be expected to occur in a similar population not treated with gabapentin. 5.6 Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including gabapentin, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono-and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Table 2 shows absolute and relative risk by indication for all evaluated AEDs. Table 2. Risk by Indication for Antiepileptic Drugs in the Pooled Analysis Indication Placebo Patients with Events Per 1,000 Patients Drug Patients with Events Per 1,000 Patients Relative Risk:Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1,000 Patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing gabapentin or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers. 5.7 Respiratory Depression There is evidence from case reports, human studies, and animal studies associating gabapentin with serious, life-threatening, or fatal respiratory depression when coadministered with CNS depressants, including opioids, or in the setting of underlying respiratory impairment. When the decision is made to co-prescribe gabapentin with another CNS depressant, particularly an opioid, or to prescribe gabapentin to patients with underlying respiratory impairment, monitor patients for symptoms of respiratory depression and sedation, and consider initiating gabapentin at a low dose. The management of respiratory depression may include close observation, supportive measures, and reduction or withdrawal of CNS depressants (including gabapentin). 5.8 Neuropsychiatric Adverse Reactions (Pediatric Patients 3 to 12 Years of Age) Gabapentin use in pediatric patients with epilepsy 3 to 12 years of age is associated with the occurrence of CNS related adverse reactions. The most significant of these can be classified into the following categories: 1) emotional lability (primarily behavioral problems), 2) hostility, including aggressive behaviors, 3) thought disorder, including concentration problems and change in school performance, and 4) hyperkinesia (primarily restlessness and hyperactivity). Among the gabapentin-treated patients, most of the reactions were mild to moderate in intensity. In controlled clinical epilepsy trials in pediatric patients 3 to 12 years of age, the incidence of these adverse reactions was: emotional lability 6% (gabapentin-treated patients) versus 1.3% (placebo-treated patients); hostility 5.2% versus 1.3%; hyperkinesia 4.7% versus 2.9%; and thought disorder 1.7% versus 0%. One of these reactions, a report of hostility, was considered serious. Discontinuation of gabapentin treatment occurred in 1.3% of patients reporting emotional lability and hyperkinesia and 0.9% of gabapentin-treated patients reporting hostility and thought disorder. One placebo-treated patient (0.4%) withdrew due to emotional lability. 5.9 Tumorigenic Potential In an oral carcinogenicity study, gabapentin increased the incidence of pancreatic acinar cell tumors in rats [see Nonclinical Toxicology (13.1) ] . The clinical significance of this finding is unknown. Clinical experience during gabapentin’s premarketing development provides no direct means to assess its potential for inducing tumors in humans. In clinical studies in adjunctive therapy in epilepsy comprising 2,085 patient-years of exposure in patients >12 years of age, new tumors were reported in 10 patients (2 breast, 3 brain, 2 lung, 1 adrenal, 1 non-Hodgkin’s lymphoma, 1 endometrial carcinoma in situ ), and preexisting tumors worsened in 11 patients (9 brain, 1 breast, 1 prostate) during or up to 2 years following discontinuation of gabapentin. Without knowledge of the background incidence and recurrence in a similar population not treated with gabapentin, it is impossible to know whether the incidence seen in this cohort is or is not affected by treatment. 5.10 Sudden and Unexplained Death in Patients with Epilepsy During the course of premarketing development of gabapentin, 8 sudden and unexplained deaths were recorded among a cohort of 2,203 epilepsy patients treated (2,103 patient-years of exposure) with gabapentin. Some of these could represent seizure-related deaths in which the seizure was not observed, e.g., at night. This represents an incidence of 0.0038 deaths per patient-year. Although this rate exceeds that expected in a healthy population matched for age and sex, it is within the range of estimates for the incidence of sudden unexplained deaths in patients with epilepsy not receiving gabapentin (ranging from 0.0005 for the general population of epileptics to 0.003 for a clinical trial population similar to that in the gabapentin program, to 0.005 for patients with refractory epilepsy). Consequently, whether these figures are reassuring or raise further concern depends on comparability of the populations reported upon to the gabapentin cohort and the accuracy of the estimates provided."}', 'overdosage': '{"10 OVERDOSAGE Signs of acute toxicity in animals included ataxia, labored breathing, ptosis, sedation, hypoactivity, or excitation. Acute oral overdoses of gabapentin have been reported. Symptoms have included double vision, tremor, slurred speech, drowsiness, altered mental status, dizziness, lethargy, and diarrhea. Fatal respiratory depression has been reported with gabapentin overdose, alone and in combination with other CNS depressants. Gabapentin can be removed by hemodialysis. If overexposure occurs, call your poison control center at 1-800-222-1222."}', 'active_flag': 'Y', 'generic_name': '{GABAPENTIN}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Administration Information Inform patients that gabapentin is taken orally with or without food. Inform patients that, should they divide the scored 600 mg or 800 mg tablet in order to administer a half-tablet, they should take the unused half-tablet as the next dose. Advise patients to discard half-tablets not used within 28 days of dividing the scored tablet. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Prior to initiation of treatment with gabapentin, instruct patients that a rash or other signs or symptoms of hypersensitivity (such as fever or lymphadenopathy) may herald a serious medical event and that the patient should report any such occurrence to a physician immediately [see Warnings and Precautions (5.1) ] . Anaphylaxis and Angioedema Advise patients to discontinue gabapentin and seek medical care if they develop signs or symptoms of anaphylaxis or angioedema [see Warnings and Precautions (5.2) ] . Dizziness and Somnolence and Effects on Driving and Operating Heavy Machinery Advise patients that gabapentin may cause dizziness, somnolence, and other symptoms and signs of CNS depression. Other drugs with sedative properties may increase these symptoms. Accordingly, although patients’ ability to determine their level of impairment can be unreliable, advise them neither to drive a car nor to operate other complex machinery until they have gained sufficient experience on gabapentin to gauge whether or not it affects their mental and/or motor performance adversely. Inform patients that it is not known how long this effect lasts [see Warnings and Precautions (5.3) and Warnings and Precautions (5.4) ] . Suicidal Thinking and Behavior Counsel the patient, their caregivers, and families that AEDs, including gabapentin, may increase the risk of suicidal thoughts and behavior. Advise patients of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Instruct patients to report behaviors of concern immediately to healthcare providers [see Warnings and Precautions (5.6) ] . Respiratory Depression Inform patients about the risk of respiratory depression. Include information that the risk is greatest for those using concomitant CNS depressants (such as opioid analgesics) or those with underlying respiratory impairment. Teach patients how to recognize respiratory depression and advise them to seek medical attention immediately if it occurs [see Warnings and Precautions (5.7) ] . Use in Pregnancy Instruct patients to notify their physician if they become pregnant or intend to become pregnant during therapy, and to notify their physician if they are breast feeding or intend to breast feed during therapy [see Use in Specific Populations (8.1) and (8.2) ] . Encourage patients to enroll in the NAAED Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 [see Use in Specific Populations (8.1) ] . Manufactured by: ScieGen Pharmaceuticals, Inc. Hauppauge, NY 11788 USA Rx Only Rev: 1/2021"}', 'pregnancy': '{"8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as gabapentin, during pregnancy. Encourage women who are taking gabapentin during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. Risk Summary There are no adequate data on the developmental risks associated with the use of gabapentin in pregnant women. In nonclinical studies in mice, rats, and rabbits, gabapentin was developmentally toxic (increased fetal skeletal and visceral abnormalities, and increased embryofetal mortality) when administered to pregnant animals at doses similar to or lower than those used clinically [see Data] . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal data When pregnant mice received oral doses of gabapentin (500 mg/kg/day, 1,000 mg/kg/day, or 3,000 mg/kg/day) during the period of organogenesis, embryofetal toxicity (increased incidences of skeletal variations) was observed at the two highest doses. The no-effect dose for embryofetal developmental toxicity in mice (500 mg/kg/day) is less than the maximum recommended human dose (MRHD) of 3,600 mg/kg on a body surface area (mg/m 2 ) basis. In studies in which rats received oral doses of gabapentin (500 mg/kg/day to 2,000 mg/kg/day) during pregnancy, adverse effect on offspring development (increased incidences of hydroureter and/or hydronephrosis) were observed at all doses. The lowest dose tested is similar to the MRHD on a mg/m 2 basis. When pregnant rabbits were treated with gabapentin during the period of organogenesis, an increase in embryofetal mortality was observed at all doses tested (60 mg/kg, 300 mg/kg, or 1,500 mg/kg). The lowest dose tested is less than the MRHD on a mg/m 2 basis. In a published study, gabapentin (400 mg/kg/day) was administered by intraperitoneal injection to neonatal mice during the first postnatal week, a period of synaptogenesis in rodents (corresponding to the last trimester of pregnancy in humans). Gabapentin caused a marked decrease in neuronal synapse formation in brains of intact mice and abnormal neuronal synapse formation in a mouse model of synaptic repair. Gabapentin has been shown in vitro to interfere with activity of the α2δ subunit of voltage-activated calcium channels, a receptor involved in neuronal synaptogenesis. The clinical significance of these findings is unknown."}', 'pediatric_use': '{"8.4 Pediatric Use Safety and effectiveness of Gabapentin in the management of postherpetic neuralgia in pediatric patients have not been established. Safety and effectiveness as adjunctive therapy in the treatment of partial seizures in pediatric patients below the age of 3 years has not been established [see Clinical Studies (14.2) ] ."}', 'geriatric_use': '{"8.5 Geriatric Use The total number of patients treated with gabapentin in controlled clinical trials in patients with postherpetic neuralgia was 336, of which 102 (30%) were 65 to 74 years of age, and 168 (50%) were 75 years of age and older. There was a larger treatment effect in patients 75 years of age and older compared to younger patients who received the same dosage. Since gabapentin is almost exclusively eliminated by renal excretion, the larger treatment effect observed in patients ≥75 years may be a consequence of increased gabapentin exposure for a given dose that results from an age-related decrease in renal function. However, other factors cannot be excluded. The types and incidence of adverse reactions were similar across age groups except for peripheral edema and ataxia, which tended to increase in incidence with age. Clinical studies of gabapentin in epilepsy did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients [see Dosage and Administration (2.4) , Adverse Reactions (6) , and Clinical Pharmacology (12.3) ] ."}'}

{"METHYLPHENIDATE HYDROCHLORIDE"}

{'contraindications': '{"CONTRAINDICATIONS Marked anxiety, tension, and agitation are contraindications to methylphenidate hydrochloride, since the drug may aggravate these symptoms. Methylphenidate hydrochloride is contraindicated also in patients known to be hypersensitive to the drug, in patients with glaucoma, and in patients with motor tics or with a family history or diagnosis of Tourette’s syndrome. Methylphenidate hydrochloride is contraindicated during treatment with monoamine oxidase inhibitors, and also within a minimum of 14 days following discontinuation of a monoamine oxidase inhibitor (hypertensive crises may result)."}', 'adverse_reactions': '{"ADVERSE REACTIONS Nervousness and insomnia are the most common adverse reactions but are usually controlled by reducing dosage and omitting the drug in the afternoon or evening. Other reactions include hypersensitivity (including skin rash, urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme with histopathological findings of necrotizing vasculitis, and thrombocytopenic purpura); anorexia; nausea; dizziness; palpitations; headache; dyskinesia; drowsiness; blood pressure and pulse changes, both up and down; tachycardia; angina; cardiac arrhythmia; abdominal pain; weight loss during prolonged therapy; libido changes; and rhabdomyolysis. There have been rare reports of Tourette’s syndrome. Toxic psychosis has been reported. Although a definite causal relationship has not been established, the following have been reported in patients taking this drug: instances of abnormal liver function, ranging from transaminase elevation to severe hepatic injury; isolated cases of cerebral arteritis and/or occlusion; leukopenia and/or anemia; transient depressed mood; a few instances of scalp hair loss; serotonin syndrome in combination with serotonergic drugs. Very rare reports of neuroleptic malignant syndrome (NMS) have been received, and, in most of these, patients were concurrently receiving therapies associated with NMS. In a single report, a ten year old boy who had been taking methylphenidate for approximately 18 months experienced an NMS-like event within 45 minutes of ingesting his first dose of venlafaxine. It is uncertain whether this case represented a drug-drug interaction, a response to either drug alone, or some other cause. In children, loss of appetite, abdominal pain, weight loss during prolonged therapy, insomnia, and tachycardia may occur more frequently; however, any of the other adverse reactions listed above may also occur."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE Attention Deficit Disorders, Narcolepsy Attention Deficit Disorders (previously known as Minimal Brain Dysfunction in Children). Other terms being used to describe the behavioral syndrome below include: Hyperkinetic Child Syndrome, Minimal Brain Damage, Minimal Cerebral Dysfunction, Minor Cerebral Dysfunction. Methylphenidate hydrochloride is indicated as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. The diagnosis of this syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or may not be warranted. Special Diagnostic Considerations Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use not only of medical but of special psychological, educational, and social resources. Characteristics commonly reported include: chronic history of short attention span, distractibility, emotional lability, impulsivity, and moderate-to-severe hyperactivity; minor neurological signs and abnormal EEG. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the child and not solely on the presence of one or more of these characteristics. Drug treatment is not indicated for all children with this syndrome. Stimulants are not intended for use in the child who exhibits symptoms secondary to environmental factors and/or primary psychiatric disorders, including psychosis. Appropriate educational placement is essential and psychosocial intervention is generally necessary. When remedial measures alone are insufficient, the decision to prescribe stimulant medication will depend upon the physician’s assessment of the chronicity and severity of the child’s symptoms."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Signs and symptoms of acute overdosage, resulting principally from overstimulation of the central nervous system and from excessive sympathomimetic effects, may include the following: vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias, hypertension, mydriasis, dryness of mucous membranes, and rhabdomyolysis. Consult with a Certified Poison Control Center regarding treatment for up-to-date guidance and advice. Treatment consists of appropriate supportive measures. The patient must be protected against self-injury and against external stimuli that would aggravate overstimulation already present. Gastric contents may be evacuated by gastric lavage. In the presence of severe intoxication, use a carefully titrated dosage of a short-acting barbiturate before performing gastric lavage. Other measures to detoxify the gut include administration of activated charcoal and a cathartic. Intensive care must be provided to maintain adequate circulation and respiratory exchange; external cooling procedures may be required for hyperpyrexia. Efficacy of peritoneal dialysis or extracorporeal hemodialysis for methylphenidate overdosage has not been established."}', 'active_flag': 'Y', 'generic_name': '{"METHYLPHENIDATE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Serious Cardiovascular Events Sudden Death and Pre-Existing Structural Cardiac Abnormalities or Other Serious Heart Problems Children and Adolescents – Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug. Adults – Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs. Hypertension and Other Cardiovascular Conditions Stimulant medications cause a modest increase in average blood pressure (about 2 to 4 mmHg) and average heart rate (about 3 to 6 bpm), and individuals may have larger increases. While the mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia. Assessing Cardiovascular Status in Patients being Treated with Stimulant Medications Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation. Psychiatric Adverse Events Pre-Existing Psychosis – Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. Bipolar Illness – Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. Emergence of New Psychotic or Manic Symptoms – Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3,482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients. Aggression – Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for the appearance of or worsening of aggressive behavior or hostility. Seizures There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued. Priapism Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products in both pediatric and adult patients. Priapism was not reported with drug initiation but developed after some time on the drug, often subsequent to an increase in dose. Priapism has also appeared during a period of drug withdrawal (drug holidays or discontinuation): Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention. Peripheral Vasculopathy, Including Raynaud’s Phenomenon Stimulants, including methylphenidate hydrochloride, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in postmarketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. Long-Term Suppression of Growth Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. Published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted. Visual Disturbance Difficulties with accommodation and blurring of vision have been reported with stimulant treatment. USE IN CHILDREN LESS THAN SIX YEARS OF AGE Methylphenidate hydrochloride should not be used in children under six years, since safety and efficacy in this age group have not been established. DRUG ABUSE AND DEPENDENCE Methylphenidate hydrochloride should be given cautiously to emotionally unstable patients, such as those with a history of drug dependence or alcoholism, because such patients may increase dosage on their own initiative. Chronically abusive use can lead to marked tolerance and psychic dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful supervision is required during drug withdrawal, since severe depression as well as the effects of chronic overactivity can be unmasked. Long-term follow-up may be required because of the patient’s basic personality disturbances."}', 'precautions': '{"PRECAUTIONS General Patients with an element of agitation may react adversely; discontinue therapy if necessary. Periodic CBC, differential, and platelet counts are advised during prolonged therapy. Drug treatment is not indicated in all cases of this behavioral syndrome and should be considered only in light of the complete history and evaluation of the child. The decision to prescribe methylphenidate hydrochloride should depend on the physician’s assessment of the chronicity and severity of the child’s symptoms and their appropriateness for his/her age. Prescription should not depend solely on the presence of one or more of the behavioral characteristics. When these symptoms are associated with acute stress reactions, treatment with methylphenidate hydrochloride is usually not indicated. Long-term effects of methylphenidate hydrochloride in children have not been well established. Information for Patients Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with methylphenidate and should counsel them in its appropriate use. A patient Medication Guide is available for methylphenidate hydrochloride chewable tablets. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document. Physicians are advised to discuss the following issues with patients for whom they prescribe methylphenidate hydrochloride: Choking – Taking this product without adequate fluid may cause it to swell and block your throat or esophagus and may cause choking. Do not take this product if you have difficulty in swallowing. If you experience chest pain, vomiting, or difficulty in swallowing or breathing after taking this product, seek immediate medical attention. Directions – Take this product (child or adult dose) with at least 8 ounces (a full glass) of water or other fluid. Taking this product without enough liquid may cause choking. See choking warning. Priapism Advise patients, caregivers, and family members of the possibility of painful or prolonged penile erections (priapism). Instruct the patient to seek immediate medical attention in the event of priapism. Circulation Problems in Fingers and Toes [Peripheral Vasculopathy, Including Raynaud’s Phenomenon] Instruct patients beginning treatment with methylphenidate hydrochloride about the risk of peripheral vasculopathy, including Raynaud’s phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red. Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes. Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking methylphenidate hydrochloride. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. Phenylketonurics – Phenylalanine is a component of aspartame. Each 2.5 mg methylphenidate hydrochloride chewable tablet contains 0.35 mg of phenylalanine; each 5 mg methylphenidate hydrochloride chewable tablet contains 0.70 mg of phenylalanine and each 10 mg methylphenidate hydrochloride chewable tablet contains 1.40 mg of phenylalanine. Drug Interactions Monoamine Oxidase Inhibitors (MAOI) Concomitant use of MAOIs and CNS stimulants, including methylphenidate hydrochloride can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure ( see CONTRAINDICATIONS ). Concomitant use of methylphenidate hydrochloride with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated. Antihypertensive Drugs Methylphenidate hydrochloride may decrease the effectiveness of drugs used to treat hypertension. Monitor blood pressure and adjust the dosage of the antihypertensive drug as needed. Risperidone Combined use of methylphenidate with risperidone when there is a change, whether an increase or decrease, in dosage of either or both medications, may increase the risk of extrapyramidal symptoms (EPS). Monitor for signs of EPS. Methylphenidate hydrochloride may decrease the hypotensive effect of guanethidine. Use cautiously with pressor agents. Human pharmacologic studies have shown that methylphenidate hydrochloride may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (phenobarbital, diphenylhydantoin, primidone), phenylbutazone, and tricyclic drugs (imipramine, clomipramine, desipramine). Downward dosage adjustments of these drugs may be required when given concomitantly with methylphenidate hydrochloride. Carcinogenesis, Mutagenesis, Impairment of Fertility In a lifetime carcinogenicity study carried out in B6C3F1 mice, methylphenidate caused an increase in hepatocellular adenomas and, in males only, an increase in hepatoblastomas, at a daily dose of approximately 60 mg/kg/day. This dose is approximately 30 times and 2.5 times the maximum recommended human dose on a mg/kg and mg/m 2 basis, respectively. Hepatoblastoma is a relatively rare rodent malignant tumor type. There was no increase in total malignant hepatic tumors. The mouse strain used is sensitive to the development of hepatic tumors, and the significance of these results to humans is unknown. Methylphenidate did not cause any increase in tumors in a lifetime carcinogenicity study carried out in F344 rats; the highest dose used was approximately 45 mg/kg/day, which is approximately 22 times and 4 times the maximum recommended human dose on a mg/kg and mg/m 2 basis, respectively. Methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay or in the in vitro mouse lymphoma cell forward mutation assay. Sister chromatid exchanges and chromosome aberrations were increased, indicative of a weak clastogenic response, in an in vitro assay in cultured Chinese Hamster Ovary (CHO) cells. The genotoxic potential of methylphenidate has not been evaluated in an in vivo assay. Usage in Pregnancy Adequate animal reproduction studies to establish safe use of methylphenidate hydrochloride chewable tablet during pregnancy have not been conducted. However, in a recently conducted study, methylphenidate has been shown to have teratogenic effects in rabbits when given in doses of 200 mg/kg/day, which is approximately 167 times and 78 times the maximum recommended human dose on a mg/kg and a mg/m 2 basis, respectively. In rats, teratogenic effects were not seen when the drug was given in doses of 75 mg/kg/day, which is approximately 62.5 and 13.5 times the maximum recommended human dose on a mg/kg and a mg/m 2 basis, respectively. Therefore, until more information is available, methylphenidate should not be prescribed for women of childbearing age unless, in the opinion of the physician, the potential benefits outweigh the possible risks."}', 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"VARENICLINE TARTRATE"}

{'contraindications': '{"4 CONTRAINDICATIONS Varenicline tablets are contraindicated in patients with a known history of serious hypersensitivity reactions or skin reactions to varenicline. History of serious hypersensitivity or skin reactions to varenicline ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions were reported in postmarketing experience and are discussed in greater detail in other sections of the labeling: Neuropsychiatric Adverse Events including Suicidality [see Warnings and Precautions ( 5.1 )] Seizures [see Warnings and Precautions ( 5.2 )] Interaction with Alcohol [see Warnings and Precautions ( 5.3 )] Accidental Injury [see Warnings and Precautions ( 5.4 )] Cardiovascular Events [see Warnings and Precautions ( 5.5 )] Somnambulism [see Warnings and Precautions ( 5.6 )] Angioedema and Hypersensitivity Reactions [see Warnings and Precautions ( 5.7 )] Serious Skin Reactions [see Warnings and Precautions ( 5.8 )] In the placebo-controlled premarketing studies, the most common adverse events associated with varenicline tablets (>5% and twice the rate seen in placebo-treated patients) were nausea, abnormal (vivid, unusual, or strange) dreams, constipation, flatulence, and vomiting. The treatment discontinuation rate due to adverse events in patients dosed with 1 mg twice daily was 12% for varenicline tablets, compared to 10% for placebo in studies of three months’ treatment. In this group, the discontinuation rates that are higher than placebo for the most common adverse events in varenicline-treated patients were as follows: nausea (3% vs. 0.5% for placebo), insomnia (1.2% vs. 1.1% for placebo), and abnormal dreams (0.3% vs. 0.2% for placebo). Smoking cessation, with or without treatment, is associated with nicotine withdrawal symptoms and has also been associated with the exacerbation of underlying psychiatric illness. Most common adverse reactions (>5% and twice the rate seen in placebo-treated patients) were nausea, abnormal (e.g., vivid, unusual, or strange) dreams, constipation, flatulence, and vomiting. ( 6 .) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. During the premarketing development of varenicline tablets, over 4500 subjects were exposed to varenicline tablets, with over 450 treated for at least 24 weeks and approximately 100 for a year. Most study participants were treated for 12 weeks or less. The most common adverse event associated with varenicline tablets treatment is nausea, occurring in 30% of patients treated at the recommended dose, compared with 10% in patients taking a comparable placebo regimen [see Warnings and Precautions ( 5.9 )]. Table 1 shows the adverse events for varenicline tablets and placebo in the 12-week fixed dose premarketing studies with titration in the first week [Studies 2 (titrated arm only), 4, and 5]. Adverse events were categorized using the Medical Dictionary for Regulatory Activities (MedDRA, Version 7.1). MedDRA High Level Group Terms (HLGT) reported in ≥ 5% of patients in the varenicline tablet 1 mg twice daily dose group, and more commonly than in the placebo group, are listed, along with subordinate Preferred Terms (PT) reported in ≥ 1% of varenicline patients (and at least 0.5% more frequent than placebo). Closely related Preferred Terms such as ‘Insomnia’, ‘Initial insomnia’, ‘Middle insomnia’, ‘Early morning awakening’ were grouped, but individual patients reporting two or more grouped events are only counted once. Table 1. Common Treatment Emergent AEs (%) in the Fixed-Dose, Placebo-Controlled Studies (HLGTs > 5% of patients in the 1 mg BID Varenicline Tablet Group and More Commonly than Placebo and PT ≥ 1% in the 1 mg BID Varenicline Tablet Group, and 1 mg BID Varenicline Tablet at Least 0.5% More than Placebo) SYSTEM ORGAN CLASS High Level Group Term Preferred Term Varenicline Tablets 0.5 mg BID N=129 Varenicline Tablets 1 mg BID N=821 Placebo N=805 GASTROINTESTINAL (GI) GI Signs and Symptoms Nausea 16 30 10 Abdominal Pain * 5 7 5 Flatulence 9 6 3 Dyspepsia 5 5 3 Vomiting 1 5 2 GI Motility/Defecation Conditions Constipation 5 8 3 Gastroesophageal reflux disease 1 1 0 Salivary Gland Conditions Dry mouth 4 6 4 PSYCHIATRIC DISORDERS Sleep Disorder/Disturbances Insomnia ** 19 18 13 Abnormal dreams 9 13 5 Sleep disorder 2 5 3 Nightmare 2 1 0 NERVOUS SYSTEM Headaches Headache 19 15 13 Neurological Disorders NEC Dysgeusia 8 5 4 Somnolence 3 3 2 Lethargy 2 1 0 GENERAL DISORDERS General Disorders NEC Fatigue/Malaise/Asthenia 4 7 6 RESPIR/THORACIC/MEDIAST Respiratory Disorders NEC Rhinorrhea 0 1 0 Dyspnea 2 1 1 Upper Respiratory Tract Disorder 7 5 4 SKIN/SUBCUTANEOUS TISSUE Epidermal and Dermal Conditions Rash 1 3 2 Pruritis 0 1 1 METABOLISM and NUTRITION Appetite/General Nutrition. Disorders Increased appetite 4 3 2 Decreased appetite/Anorexia 1 2 1 *Includes PTs Abdominal (pain, pain upper, pain lower, discomfort, tenderness, distension) and Stomach discomfort ** Includes PTs Insomnia/Initial insomnia/Middle insomnia/Early morning awakening The overall pattern and frequency of adverse events during the longer-term premarketing trials was similar to those described in Table 1, though several of the most common events were reported by a greater proportion of patients with long-term use (e.g., nausea was reported in 40% of patients treated with varenicline tablets 1 mg twice daily in a one-year study, compared to 8% of placebo-treated patients). Following is a list of treatment-emergent adverse events reported by patients treated with varenicline tablets during all premarketing clinical trials and updated based on pooled data from 18 placebo-controlled pre- and postmarketing studies, including approximately 5,000 patients treated with varenicline. Adverse events were categorized using MedDRA, Version 16.0. The listing does not include those events already listed in the previous tables or elsewhere in labeling, those events for which a drug cause was remote, those events which were so general as to be uninformative, and those events reported only once which did not have a substantial probability of being acutely life-threatening. Blood and Lymphatic System Disorders. Infrequent: anemia, lymphadenopathy. Rare: leukocytosis, splenomegaly, thrombocytopenia. Cardiac Disorders. Infrequent: angina pectoris, myocardial infarction, palpitations, tachycardia. Rare: acute coronary syndrome, arrhythmia, atrial fibrillation, bradycardia, cardiac flutter, cor pulmonale, coronary artery disease, ventricular extrasystoles. Ear and Labyrinth Disorders. Infrequent: tinnitus, vertigo. Rare: deafness, Meniere’s disease. Endocrine Disorders. Infrequent: thyroid gland disorders. Eye Disorders. Infrequent: conjunctivitis, eye irritation, eye pain, vision blurred, visual impairment. Rare: blindness transient, cataract subcapsular, dry eye, night blindness, ocular vascular disorder, photophobia, vitreous floaters Gastrointestinal Disorders. Frequent: diarrhea, toothache. Infrequent: dysphagia, eructation, gastritis, gastrointestinal hemorrhage, mouth ulceration. Rare: enterocolitis, esophagitis, gastric ulcer, intestinal obstruction, pancreatitis acute. General Disorders and Administration Site Conditions. Frequent: chest pain. Infrequent: chest discomfort, chills, edema, influenza-like illness, pyrexia. Hepatobiliary Disorders Rare: gall bladder disorder. Investigations . Frequent: liver function test abnormal, weight increased. Infrequent: electrocardiogram abnormal. Rare: muscle enzyme increased, urine analysis abnormal. Metabolism and Nutrition Disorders. Infrequent: diabetes mellitus, hypoglycemia. Rare: hyperlipidemia, hypokalemia. Musculoskeletal and Connective Tissue Disorders. Frequent: arthralgia, back pain, myalgia. Infrequent: arthritis, muscle cramp, musculoskeletal pain. . Rare: myositis, osteoporosis. Nervous System Disorders. Frequent: disturbance in attention, dizziness, Infrequent: amnesia, convulsion, migraine, parosmia, syncope, tremor. Rare: balance disorder, cerebrovascular accident, dysarthria, mental impairment, multiple sclerosis, VII th nerve paralysis, nystagmus, psychomotor hyperactivity, psychomotor skills impaired, restless legs syndrome, sensory disturbance, transient ischemic attack, visual field defect. Psychiatric Disorders. Infrequent: dissociation, libido decreased, mood swings, thinking abnormal. Rare: bradyphrenia, disorientation, euphoric mood. Renal and Urinary Disorders. Infrequent: nocturia, pollakiuria, urine abnormality. Rare: nephrolithiasis, polyuria, renal failure acute, urethral syndrome, urinary retention. Reproductive System and Breast Disorders . Frequent: menstrual disorder. Infrequent: erectile dysfunction. Rare: sexual dysfunction. Respiratory, Thoracic and Mediastinal Disorders. Frequent: respiratory disorders. Infrequent: asthma, epistaxis, rhinitis allergic, upper respiratory tract inflammation. Rare: pleurisy, pulmonary embolism. Skin and Subcutaneous Tissue Disorders. Infrequent: acne, dry skin, eczema, erythema, hyperhidrosis, urticaria. Rare: photosensitivity reaction, psoriasis. Vascular Disorders. Infrequent: hot flush. Rare: thrombosis. Varenicline tablets has also been studied in postmarketing trials including (1) a trial conducted in patients with chronic obstructive pulmonary disease (COPD), (2) a trial conducted in generally healthy patients (similar to those in the premarketing studies) in which they were allowed to select a quit date between days 8 and 35 of treatment (“alternative quit date instruction trial”), (3) a trial conducted in patients who did not succeed in stopping smoking during prior varenicline tablet therapy, or who relapsed after treatment (“re-treatment trial”), (4) a trial conducted in patients with stable cardiovascular disease, (5) a trial conducted in patients with stable schizophrenia or schizoaffective disorder, (6) a trial conducted in patients with major depressive disorder, (7) a postmarketing neuropsychiatric safety outcome trial in patients without or with a history of psychiatric disorder, (8) a non-treatment extension of the postmarketing neuropsychiatric safety outcome trial that assessed CV safety, (9) a trial in patients who were not able or willing to quit abruptly and who were instructed to quit gradually (“gradual approach to quitting smoking trial”). Adverse events in the trial of patients with COPD (1), in the alternative quit date instruction trial (2), and in the gradual approach to quitting smoking trial (9) were similar to those observed in premarketing studies. In the re-treatment trial (3), the profile of common adverse events was similar to that previously reported, but, in addition, varenicline-treated patients also commonly reported diarrhea (6% vs. 4% in placebo-treated patients), depressed mood disorders and disturbances (6% vs. 1%), and other mood disorders and disturbances (5% vs. 2%). In the trial of patients with stable cardiovascular disease (4), more types and a greater number of cardiovascular events were reported compared to premarketing studies, as shown in Table 1 and in Table 2 below. Table 2. Cardiovascular Mortality and Nonfatal Cardiovascular Events (%) with a Frequency >1% in Either Treatment Group in the Trial of Patients with Stable Cardiovascular Disease Varenicline Tablets 1 mg BID N=353 Placebo N=350 Adverse Events ≥1% in either treatment group Up to 30 days after treatment Angina pectoris 3.7 2.0 Chest pain 2.5 2.3 Peripheral edema 2.0 1.1 Hypertension 1.4 2.6 Palpitations 0.6 1.1 Adjudicated Cardiovascular Mortality (up to 52 weeks) 0.3 0.6 Adjudicated Nonfatal Serious Cardiovascular Events ≥1% in either treatment group Up to 30 days after treatment Nonfatal MI 1.1 0.3 Hospitalization for angina pectoris 0.6 1.1 Beyond 30 days after treatment and up to 52 weeks Need for coronary revascularization* 2.0 0.6 Hospitalization for angina pectoris 1.7 1.1 New diagnosis of peripheral vascular disease (PVD) or admission for a PVD procedure 1.4 0.6 *some procedures were part of management of nonfatal MI and hospitalization for angina In the trial of patients with stable schizophrenia or schizoaffective disorder (5), 128 smokers on antipsychotic medication were randomized 2:1 to varenicline (1 mg twice daily) or placebo for 12 weeks with 12-week non-drug follow-up. The most common treatment emergent adverse events reported in this trial are shown in Table 3 below. Table 3. Common Treatment Emergent AEs (%) in the Trial of Patients with Stable Schizophrenia or Schizoaffective Disorder Varenicline Tablets 1 mg BID N=84 Placebo N=43 Adverse Events ≥10% in the varenicline group Nausea 24 14 Headache 11 19 Vomiting 11 9 Psychiatric Adverse Events ≥5% and at a higher rate than in the placebo group Insomnia 10 5 For the trial of patients with major depressive disorder (6), the most common treatment emergent adverse events reported are shown in Table 4 below. Additionally, in this trial, patients treated with varenicline were more likely than patients treated with placebo to report one of events related to hostility and aggression (3% vs. 1%). Table 4. Common Treatment Emergent AEs (%) in the Trial of Patients with Major Depressive Disorder Varenicline Tablets 1 mg BID N=256 Placebo N=269 Adverse Events ≥10% in either treatment group Nausea 27 10 Headache 17 11 Abnormal dreams 11 8 Insomnia 11 5 Irritability 11 8 Psychiatric Adverse Events ≥2% in any treatment group and not included above Depressed mood disorders and disturbances 11 9 Anxiety 7 9 Agitation 7 4 Tension 4 3 Hostility 2 0.4 Restlessness 2 2 In the trial of patients without or with a history of psychiatric disorder (7), the most common adverse events in subjects treated with varenicline were similar to those observed in premarketing studies. Most common treatment-emergent adverse events reported in this trial are shown in Table 5 below. Table 5. Treatment Emergent Common AEs (%) in the Trial of Patients without or with a History of Psychiatric Disorder Varenicline Tablets 1 mg BID Placebo Adverse Events ≥10% in the varenicline group Entire study population, N 1982 1979 Nausea 25 7 Headache 12 10 Psychiatric Adverse Events ≥2% in any treatment group Non-psychiatric cohort, N 975 982 Abnormal dreams 8 4 Agitation 3 3 Anxiety 5 6 Depressed mood 3 3 Insomnia 10 7 Irritability 3 4 Sleep disorder 3 2 Psychiatric cohort, N 1007 997 Abnormal dreams 12 5 Agitation 5 4 Anxiety 8 6 Depressed mood 5 5 Depression 5 5 Insomnia 9 7 Irritability 5 7 Nervousness 2 3 Sleep disorder 3 2 In the non-treatment extension of the postmarketing neuropsychiatric safety outcomes trial that assessed CV safety (8), the most common adverse events in subjects treated with varenicline and occurring up to 30 days after last dose of treatment were similar to those observed in premarketing studies. 6.2 Postmarketing Experience The following adverse events have been reported during post-approval use of varenicline tablets. Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. There have been reports of depression, mania, psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide in patients attempting to quit smoking while taking varenicline tablets [see Warnings and Precautions ( 5.1 )]. There have been postmarketing reports of new or worsening seizures in patients treated with varenicline tablets [see Warnings and Precautions ( 5.2 )]. There have been postmarketing reports of patients experiencing increased intoxicating effects of alcohol while taking varenicline tablets. Some reported neuropsychiatric events, including unusual and sometimes aggressive behavior [see Warnings and Precautions ( 5.1 ) and ( 5.3 )]. There have been reports of hypersensitivity reactions, including angioedema [see Warnings and Precautions ( 5.7 )]. There have also been reports of serious skin reactions, including Stevens-Johnson Syndrome and erythema multiforme, in patients taking varenicline tablets [see Warnings and Precautions ( 5.8 )]. There have been reports of myocardial infarction (MI) and cerebrovascular accident (CVA) including ischemic and hemorrhagic events in patients taking varenicline tablets. In the majority of the reported cases, patients had pre-existing cardiovascular disease and/or other risk factors. Although smoking is a risk factor for MI and CVA, based on temporal relationship between medication use and events, a contributory role of varenicline cannot be ruled out [see Warnings and Precautions ( 5.5 )]. There have been reports of hyperglycemia in patients following initiation of varenicline tablets. There have been reports of somnambulism, some resulting in harmful behavior to self, others, or property in patients treated with varenicline tablets [see Warnings and Precautions ( 5.6 )]."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Based on varenicline characteristics and clinical experience to date, varenicline tablets have no clinically meaningful pharmacokinetic drug interactions [see Clinical Pharmacology ( 12.3 )]. Other smoking cessation therapies: Safety and efficacy in combination with other smoking cessation therapies has not been established. Coadministration of varenicline and transdermal nicotine resulted in a high rate of discontinuation due to adverse events. ( 7.1 ) Effect of smoking cessation on Other Drugs: Pharmacokinetics or pharmacodynamics of certain drugs (e.g., theophylline, warfarin, insulin) may be altered, necessitating dose adjustment. ( 7.2 ) 7.1 Use with Other Drugs for Smoking Cessation Safety and efficacy of varenicline tablets in combination with other smoking cessation therapies have not been studied. Bupropion Varenicline (1 mg twice daily) did not alter the steady-state pharmacokinetics of bupropion (150 mg twice daily) in 46 smokers. The safety of the combination of bupropion and varenicline has not been established. Nicotine replacement therapy (NRT) Although co-administration of varenicline (1 mg twice daily) and transdermal nicotine (21 mg/day) for up to 12 days did not affect nicotine pharmacokinetics, the incidence of nausea, headache, vomiting, dizziness, dyspepsia, and fatigue was greater for the combination than for NRT alone. In this study, eight of twenty-two (36%) patients treated with the combination of varenicline and NRT prematurely discontinued treatment due to adverse events, compared to 1 of 17 (6%) of patients treated with NRT and placebo. 7.2 Effect of Smoking Cessation on Other Drugs Physiological changes resulting from smoking cessation, with or without treatment with varenicline tablets, may alter the pharmacokinetics or pharmacodynamics of certain drugs (e.g., theophylline, warfarin, insulin) for which dosage adjustment may be necessary."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Varenicline tablets are indicated for use as an aid to smoking cessation treatment. Varenicline tablets are a nicotinic receptor partial agonist indicated for use as an aid to smoking cessation treatment. ( 1 and 2.1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Neuropsychiatric Adverse Events: Postmarketing reports of serious or clinically significant neuropsychiatric adverse events have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Observe patients attempting to quit smoking with varenicline tablets for the occurrence of such symptoms and instruct them to discontinue varenicline tablets and contact a healthcare provider if they experience such adverse events. ( 5.1 ) Seizures : New or worsening seizures have been observed in patients taking varenicline tablets. Varenicline tablets should be used cautiously in patients with a history of seizures or other factors that can lower the seizure threshold. ( 5.2 ) Interaction with Alcohol: Increased effects of alcohol have been reported. Instruct patients to reduce the amount of alcohol they consume until they know whether varenicline tablets affects them. ( 5.3 ) Accidental injury: Accidental injuries (e.g., traffic accidents) have been reported. Instruct patients to use caution driving or operating machinery until they know how varenicline tablets may affect them. ( 5.4 ) Cardiovascular Events: Patients with underlying cardiovascular (CV) disease may be at increased risk of CV events; however, these concerns must be balanced with the health benefits of smoking cessation. Instruct patients to notify their healthcare providers of new or worsening CV symptoms and to seek immediate medical attention if they experience signs and symptoms of myocardial infarction (MI) or stroke. ( 5.5 and 6.1 ) Somnambulism: Cases of somnambulism have been reported in patients taking varenicline tablets. Some cases described harmful behavior to self, others, or property. Instruct patients to discontinue varenicline tablets and notify their healthcare provider if they experience somnambulism. ( 5.6 and 6.2 ) Angioedema and Hypersensitivity Reactions: Such reactions, including angioedema, infrequently life-threatening, have been reported. Instruct patients to discontinue varenicline tablets and immediately seek medical care if symptoms occur. ( 5.7 and 6.2 ) Serious Skin Reactions: Rare, potentially life-threatening skin reactions have been reported. Instruct patients to discontinue varenicline tablets and contact a healthcare provider immediately at first appearance of skin rash with mucosal lesions. ( 5.8 and 6.2 ) Nausea: Nausea is the most common adverse reaction (up to 30% incidence rate). Dose reduction may be helpful. ( 5.9 ) 5.1 Neuropsychiatric Adverse Events including Suicidality Serious neuropsychiatric adverse events have been reported in patients being treated with varenicline tablets [see Adverse Reactions ( 6.2 )]. These postmarketing reports have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Some patients who stopped smoking may have been experiencing symptoms of nicotine withdrawal, including depressed mood. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication. However, some of these adverse events occurred in patients taking varenicline tablets who continued to smoke. Neuropsychiatric adverse events occurred in patients without and with pre-existing psychiatric disease; some patients experienced worsening of their psychiatric illnesses. Some neuropsychiatric adverse events, including unusual and sometimes aggressive behavior directed to oneself or others, may have been worsened by concomitant use of alcohol [see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6.2 )]. Observe patients for the occurrence of neuropsychiatric adverse events. Advise patients and caregivers that the patient should stop taking varenicline tablets and contact a healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior. The healthcare provider should evaluate the severity of the symptoms and the extent to which the patient is benefiting from treatment, and consider options including dose reduction, continued treatment under closer monitoring, or discontinuing treatment. In many post marketing cases, resolution of symptoms after discontinuation of varenicline tablets was reported. However, the symptoms persisted in some cases; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve. The neuropsychiatric safety of varenicline tablets was evaluated in a randomized, double-blind, active and placebo-controlled study that included patients without a history of psychiatric disorder (non-psychiatric cohort, N=3912) and patients with a history of psychiatric disorder (psychiatric cohort, N=4003). In the non-psychiatric cohort, varenicline tablets were not associated with an increased incidence of clinically significant neuropsychiatric adverse events in a composite endpoint comprising anxiety, depression, feeling abnormal, hostility, agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, and irritability. In the psychiatric cohort, there were more events reported in each treatment group compared to the non-psychiatric cohort, and the incidence of events in the composite endpoint was higher for each of the active treatments compared to placebo: Risk Differences (RDs) (95%CI) vs. placebo were 2.7% (-0.05, 5.4) for varenicline tablets, 2.2% (-0.5, 4.9) for bupropion, and 0.4% (-2.2, 3.0) for transdermal nicotine. In the non-psychiatric cohort, neuropsychiatric adverse events of a serious nature were reported in 0.1% of varenicline-treated patients and 0.4% of placebo-treated patients. In the psychiatric cohort, neuropsychiatric events of a serious nature were reported in 0.6% of varenicline-treated patients, with 0.5% involving psychiatric hospitalization. In placebo-treated patients, serious neuropsychiatric events occurred in 0.6%, with 0.2% requiring psychiatric hospitalization [see Clinical Studies ( 14.10 )]. 5.2 Seizures During clinical trials and the postmarketing experience, there have been reports of seizures in patients treated with varenicline tablets. Some patients had no history of seizures, whereas others had a history of seizure disorder that was remote or well-controlled. In most cases, the seizure occurred within the first month of therapy. Weigh this potential risk against the potential benefits before prescribing varenicline tablets in patients with a history of seizures or other factors that can lower the seizure threshold. Advise patients to discontinue varenicline tablets and contact a healthcare provider immediately if they experience a seizure while on treatment [see Adverse Reactions ( 6.2 )] . 5.3 Interaction with Alcohol There have been postmarketing reports of patients experiencing increased intoxicating effects of alcohol while taking varenicline tablets. Some cases described unusual and sometimes aggressive behavior and were often accompanied by amnesia for the events. Advise patients to reduce the amount of alcohol they consume while taking varenicline tablets until they know whether varenicline tablets affect their tolerance for alcohol [see Adverse Reactions ( 6.2 )]. 5.4 Accidental Injury There have been postmarketing reports of traffic accidents, near-miss incidents in traffic, or other accidental injuries in patients taking varenicline tablets. In some cases, the patients reported somnolence, dizziness, loss of consciousness or difficulty concentrating that resulted in impairment, or concern about potential impairment, in driving or operating machinery. Advise patients to use caution driving or operating machinery or engaging in other potentially hazardous activities until they know how varenicline tablets may affect them. 5.5 Cardiovascular Events A comprehensive evaluation of cardiovascular (CV) risk with varenicline tablets suggests that patients with underlying CV disease may be at increased risk; however, these concerns must be balanced with the health benefits of smoking cessation. CV risk has been assessed for varenicline tablets in randomized controlled trials (RCT) and meta-analyses of RCTs. In a smoking cessation trial in patients with stable CV disease, CV events were infrequent overall; however, nonfatal myocardial infarction (MI) and nonfatal stroke occurred more frequently in patients treated with varenicline tablets compared to placebo. All-cause and CV mortality was lower in patients treated with varenicline tablets [see Clinical Studies ( 14.8 )]. This study was included in a meta-analysis of 15 varenicline tablets efficacy trials in various clinical populations that showed an increased hazard ratio for Major Adverse Cardiovascular Events (MACE) of 1.95; however, the finding was not statistically significant (95% CI: 0.79, 4.82). In the large postmarketing neuropsychiatric safety outcome trial, an analysis of adjudicated MACE events was conducted for patients while in the trial and during a 28-week non-treatment extension period. Few MACE events occurred during the trial; therefore, the findings did not contribute substantively to the understanding of CV risk with varenicline tablets. Instruct patients to notify their healthcare providers of new or worsening CV symptoms and to seek immediate medical attention if they experience signs and symptoms of MI or stroke [see Clinical Studies ( 14.10 )]. 5.6 Somnambulism Cases of somnambulism have been reported in patients taking varenicline tablets. Some cases described harmful behavior to self, others, or property. Instruct patients to discontinue varenicline tablets and notify their healthcare provider if they experience somnambulism [see Adverse Reactions ( 6.2 )]. 5.7 Angioedema and Hypersensitivity Reactions There have been postmarketing reports of hypersensitivity reactions including angioedema in patients treated with varenicline tablets [see Adverse Reactions ( 6.2 ), Patient Counseling Information ( 17 )]. Clinical signs included swelling of the face, mouth (tongue, lips, and gums), extremities, and neck (throat and larynx). There were infrequent reports of life-threatening angioedema requiring emergent medical attention due to respiratory compromise. Instruct patients to discontinue varenicline tablets and immediately seek medical care if they experience these symptoms. 5.8 Serious Skin Reactions There have been postmarketing reports of rare but serious skin reactions, including Stevens-Johnson Syndrome and erythema multiforme, in patients using varenicline tablets [see Adverse Reactions ( 6.2 )]. As these skin reactions can be life-threatening, instruct patients to stop taking varenicline tablets and contact a healthcare provider immediately at the first appearance of a skin rash with mucosal lesions or any other signs of hypersensitivity. 5.9 Nausea Nausea was the most common adverse reaction reported with varenicline tablets treatment. Nausea was generally described as mild or moderate and often transient; however, for some patients, it was persistent over several months. The incidence of nausea was dose-dependent. Initial dose-titration was beneficial in reducing the occurrence of nausea. For patients treated to the maximum recommended dose of 1 mg twice daily following initial dosage titration, the incidence of nausea was 30% compared with 10% in patients taking a comparable placebo regimen. In patients taking varenicline tablets 0.5 mg twice daily following initial titration, the incidence was 16% compared with 11% for placebo. Approximately 3% of patients treated with varenicline tablets 1 mg twice daily in studies involving 12 weeks of treatment discontinued treatment prematurely because of nausea. For patients with intolerable nausea, a dose reduction should be considered"}', 'overdosage': '{"10 OVERDOSAGE In case of overdose, standard supportive measures should be instituted as required. Varenicline has been shown to be dialyzed in patients with end-stage renal disease [see Clinical Pharmacology ( 12.3 )] , however, there is no experience in dialysis following overdose."}', 'active_flag': 'Y', 'generic_name': '{VARENICLINE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Medication Guide) Initiate Treatment and Continue to Attempt to Quit if Lapse Instruct patients to set a date to quit smoking and to initiate varenicline tablet treatment one week before the quit date. Alternatively, the patient can begin varenicline tablet dosing and then set a date to quit smoking between days 8 and 35 of treatment. Encourage patients to continue to attempt to quit if they have early lapses after quit day [see Dosage and Administration ( 2.1 )]. For patients who are sure that they are not able or willing to quit abruptly, a gradual approach to quitting smoking with varenicline tablets may be considered. Patients should begin varenicline tablets dosing and reduce smoking during the first 12 weeks of treatment, then quit by the end of that period and continue treatment for an additional 12 weeks for a total of 24 weeks [see Dosage and Administration ( 2.1 )]. Encourage patients who are motivated to quit and who did not succeed in stopping smoking during prior varenicline tablets therapy for reasons other than intolerability due to adverse events, or who relapsed after treatment to make another attempt with varenicline tablets once factors contributing to the failed attempt have been identified and addressed [see Dosage and Administration ( 2.1 ), Clinical Studies ( 14.6 )]. How to Take Advise patients that varenicline tablets should be taken orally after eating, and with a full glass of water [see Dosage and Administration ( 2.1 )]. Starting Week Dosage Instruct patients on how to titrate varenicline tablets, beginning at a dose of 0.5 mg/day. Explain that one 0.5 mg tablet should be taken daily for the first three days, and that for the next four days, one 0.5 mg tablet should be taken in the morning and one 0.5 mg tablet should be taken in the evening [see Dosage and Administration ( 2.1 )] . Continuing Weeks Dosage Advise patients that, after the first seven days, the dose should be increased to one 1 mg tablet in the morning and one 1 mg tablet in the evening [see Dosage and Administration ( 2.1 )]. Dosage Adjustment for Varenicline Tablets or Other Drugs Inform patients that nausea and insomnia are side effects of varenicline tablets and are usually transient; however, advise patients that if they are persistently troubled by these symptoms, they should notify the prescribing physician so that a dose reduction can be considered. Inform patients that some drugs may require dose adjustment after quitting smoking [see Dosage and Administration (2.1) ]. Counseling and Support Provide patients with educational materials and necessary counseling to support an attempt at quitting smoking [see Dosage and Administration (2.1) ]. Neuropsychiatric Adverse Events Inform patients that some patients have experienced changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation and suicide when attempting to quit smoking while taking varenicline tablets. Instruct patients to discontinue varenicline tablets and contact a healthcare professional if they experience such symptoms [see Warnings and Precautions (5.1) , Adverse Reactions (6.2) ]. History of Psychiatric Illness Encourage patients to reveal any history of psychiatric illness prior to initiating treatment. Nicotine Withdrawal Inform patients that quitting smoking, with or without varenicline tablets, may be associated with nicotine withdrawal symptoms (including depression or agitation) or exacerbation of pre-existing psychiatric illness. Seizures Encourage patients to report any history of seizures or other factors that can lower seizure threshold. Instruct patients to discontinue varenicline tablets and contact a healthcare provider immediately if they experience a seizure while on treatment [see Warnings and Precautions ( 5.2 )]. Interaction with Alcohol Advise patients to reduce the amount of alcohol they consume while taking varenicline tablets until they know whether varenicline tablets affect their tolerance for alcohol [see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6.2 )]. Driving or Operating Machinery Advise patients to use caution driving or operating machinery until they know how quitting smoking and/or varenicline may affect them [see Warnings and Precautions ( 5.4 )]. Cardiovascular Events Patients should be instructed to notify their healthcare providers of symptoms of new or worsening cardiovascular events and to seek immediate medical attention if they experience signs and symptoms of myocardial infarction or stroke [see Warnings and Precautions ( 5.5 ), Adverse Reactions ( 6.1 )]. Somnambulism Patients should be instructed to discontinue varenicline tablets and notify their healthcare providers if they experience somnambulism [see Warnings and Precautions ( 5.6 )]. Angioedema Inform patients that there have been reports of angioedema, with swelling of the face, mouth (lip, gum, tongue) and neck (larynx and pharynx) that can lead to life-threatening respiratory compromise. Instruct patients to discontinue varenicline tablets and immediately seek medical care if they experience these symptoms [see Warnings and Precautions (5.7) , and Adverse Reactions (6.2) ]. Serious Skin Reactions Inform patients that serious skin reactions, such as Stevens-Johnson Syndrome and erythema multiforme, were reported by some patients taking varenicline tablets. Advise patients to stop taking varenicline tablets at the first sign of rash with mucosal lesions or skin reaction and contact a healthcare provider immediately [see Warnings and Precautions (5.8) , Adverse Reactions (6.2) ]. Vivid, Unusual, or Strange Dreams Inform patients that they may experience vivid, unusual or strange dreams during treatment with varenicline tablets. Pregnancy and Lactation Patients who are pregnant or breastfeeding or planning to become pregnant should be advised of: the risks of smoking to a pregnant mother and her developing baby, the potential risks of varenicline tablet use during pregnancy and breastfeeding, and the benefits of smoking cessation with and without varenicline tablets. Advise breastfeeding women to monitor the infant for seizures and vomiting [see Use in Specific Populations (8.1 and 8.2) ]. Rx only APOTEX INC. VARENICLINE TABLETS 0.5 mg and 1 mg Manufactured by: Manufactured for: Apotex Inc. Apotex Corp. Toronto, Ontario Weston, Canada M9L 1T9 Florida 33326 Rev. 3"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Available data have not suggested an increased risk for major birth defects following exposure to varenicline in pregnancy, compared with women who smoke [see Data]. Smoking during pregnancy is associated with maternal, fetal, and neonatal risks (see Clinical Considerations). In animal studies, varenicline did not result in major malformations but caused decreased fetal weights in rabbits when dosed during organogenesis at exposures equivalent to 50 times the exposure at the maximum recommended human dose (MRHD). Additionally, administration of varenicline to pregnant rats during organogenesis through lactation produced developmental toxicity in offspring at maternal exposures equivalent to 36 times human exposure at the MRHD [see Data] . The estimated background risk of oral clefts is increased by approximately 30% in infants of women who smoke during pregnancy, compared to pregnant women who do not smoke. The background risk of other major birth defects and miscarriage for the indicated population are unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Smoking during pregnancy causes increased risks of orofacial clefts, premature rupture of membranes, placenta previa, placental abruption, ectopic pregnancy, fetal growth restriction and low birth weight, stillbirth, preterm delivery and shortened gestation, neonatal death, sudden infant death syndrome and reduction of lung function in infants. It is not known whether quitting smoking with varenicline tablets during pregnancy reduces these risks. Data Human Data A population-based observational cohort study using the national registers of Denmark and Sweden compared pregnancy and birth outcomes among women exposed to varenicline (N=335, includes 317 first trimester exposed) with women who smoked during pregnancy (N=78,412) and with non-smoking pregnant women (N=806,438). The prevalence of major malformations, the primary outcome, was similar in all groups, including between smoking and non-smoking groups. The prevalence of adverse perinatal outcomes in the varenicline-exposed cohort was not greater than in the cohort of women who smoked, and differed somewhat between the three cohorts. The prevalences of the primary and secondary outcomes are shown in Table 6. Table 6. Summary of Primary and Secondary Outcomes for Three Birth Cohorts Outcome Varenicline Cohort (n=335) Smoking Cohort (n=78,412) Non-Smoking Cohort (n=806,438) Major congenital malformation* 12 / 334 (3.6%) 3,382 / 78,028 (4.3%) 33,950 /804,020 (4.2%) Stillbirth 1 (0.3%) 384 (0.5%) 2,418 (0.3%) Small for gestational age 42 (12.5%) 13,433 (17.1%) 73,135 (9.1%) Preterm birth 25 (7.5%) 6,173 (7.9%) 46,732 (5.8%) Premature rupture of membranes 12 (3.6%) 4,246 (5.4%) 30,641 (3.8%) Sudden infant death syndrome** 0/307 (0.0%) 51/71,720 (0.1%) 58/755,939 (<0.1%) *Included only live births in the cohorts. Prevalence among first trimester varenicline-exposed pregnancies (11/317 [3.5%]). **There was a lag in death data in Denmark, so the cohorts were smaller. The study limitations include the inability to capture malformations in pregnancies that do not result in a live birth, and possible misclassification of outcome and of exposure to varenicline or to smoking. Other small epidemiological studies of pregnant women exposed to varenicline did not identify an association with major malformations, consistent with the Danish and Swedish observational cohort study. Methodological limitations of these studies include small samples and lack of adequate controls. Overall, available studies cannot definitely establish or exclude any varenicline-associated risk during pregnancy. Animal Data Pregnant rats and rabbits received varenicline succinate during organogenesis at oral doses up to 15 and 30 mg/kg/day, respectively. While no fetal structural abnormalities occurred in either species, maternal toxicity characterized by reduced body weight gain, and reduced fetal weights occurred in rabbits at the highest dose (exposures 50 times the human exposure at the MRHD of 1 mg twice daily based on AUC). Fetal weight reduction did not occur in rabbits at exposures 23 times the human exposure at the MRHD based on AUC. In a pre- and postnatal development study, pregnant rats received up to 15 mg/kg/day of oral varenicline succinate from organogenesis through lactation. Maternal toxicity, characterized by a decrease in body weight gain was observed at 15 mg/kg/day (36 times the human exposure at the MRHD based on AUC). However, decreased fertility and increased auditory startle response occurred in offspring at the highest maternal dose of 15 mg/kg/day."}', 'pediatric_use': '{"8.4 Pediatric Use Varenicline tablets are not recommended for use in pediatric patients 16 years of age or younger because its efficacy in this population was not demonstrated. Single and multiple-dose pharmacokinetics of varenicline have been investigated in pediatric patients aged 12 to 17 years old (inclusive) and were approximately dose-proportional over the 0.5 mg to 2 mg daily dose range studied. Steady-state systemic exposure in adolescent patients of bodyweight >55 kg, as assessed by AUC (0-24), was comparable to that noted for the same doses in the adult population. When 0.5 mg BID was given, steady-state daily exposure of varenicline was, on average, higher (by approximately 40%) in adolescent patients with bodyweight ≤ 55 kg compared to that noted in the adult population. The efficacy and safety of varenicline was evaluated in a randomized, double-blind, placebo-controlled study of 312 patients aged 12 to 19 years, who smoked an average of at least 5 cigarettes per day during the 30 days prior to recruitment, had a score of at least 4 on the Fagerstrom Test for Nicotine Dependence scale, and at least one previous failed quit attempt. Patients were stratified by age (12 to 16 years of age, n = 216 and 17 to 19 years of age, n = 96) and by body weight (≤55 kg and >55 kg). Patients were randomized to one of two doses of varenicline, adjusted by weight to provide plasma levels in the efficacious range (based on adult studies) and placebo. Patients received treatment for 12 weeks, followed by a non-treatment period of 40 weeks, along with age-appropriate counseling throughout the study. Results from this study showed that varenicline, at either dose studied, did not improve continuous abstinence rates at weeks 9 through 12 of treatment compared with placebo in subjects 12 to 19 years of age. The varenicline safety profile in this study was consistent with that observed in adult studies."}', 'geriatric_use': '{"8.5 Geriatric Use A combined single- and multiple-dose pharmacokinetic study demonstrated that the pharmacokinetics of 1 mg varenicline given once daily or twice daily to 16 healthy elderly male and female smokers (aged 65 to 75 yrs) for 7 consecutive days was similar to that of younger subjects. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Varenicline is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Dosage and Administration ( 2.2 )]. No dosage adjustment is recommended for elderly patients."}'}

{"CETIRIZINE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses temporarily relieves these symptoms due to hay fever or other upper respiratory allergies: • runny nose • sneezing • itchy, watery eyes • itching of the nose or throat"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"CETIRIZINE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if an allergic reaction to this product occurs. Seek medical help right away."}', 'do_not_use': '{"Do not use if you have ever had an allergic reaction to this product or any of its ingredients or to an antihistamine containing hydroxyzine."}', 'when_using': '{"When using this product • drowsiness may occur • avoid alcoholic drinks • alcohol, sedatives, and tranquilizers may increase drowsiness • be careful when driving a motor vehicle or operating machinery"}', 'warnings': '{"Warnings Do not use if you have ever had an allergic reaction to this product or any of its ingredients or to an antihistamine containing hydroxyzine. Ask a doctor before use if you have liver or kidney disease. Your doctor should determine if you need a different dose. Ask a doctor or pharmacist before use if you are taking tranquilizers or sedatives. When using this product • drowsiness may occur • avoid alcoholic drinks • alcohol, sedatives, and tranquilizers may increase drowsiness • be careful when driving a motor vehicle or operating machinery Stop use and ask a doctor if an allergic reaction to this product occurs. Seek medical help right away. If pregnant or breast-feeding: • if breast-feeding: not recommended • if pregnant: ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away. (1-800-222-1222)"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{LACOSAMIDE}

{'contraindications': '{"4 CONTRAINDICATIONS None. None ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.1 )] Dizziness and Ataxia [see Warnings and Precautions ( 5.2 )] Cardiac Rhythm and Conduction Abnormalities [see Warnings and Precautions ( 5.3 )] Syncope [see Warnings and Precautions ( 5.4 )] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions [see Warnings and Precautions ( 5.6 )] Adjunctive therapy: Most common adverse reactions in adults (≥10% and greater than placebo) are diplopia, headache, dizziness, nausea, and somnolence ( 6.1 ) Monotherapy: Most common adverse reactions are similar to those seen in adjunctive therapy studies ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Laboratory Abnormalities Abnormalities in liver function tests have occurred in controlled trials with lacosamide in adult patients with partial-onset seizures who were taking 1 to 3 concomitant anti-epileptic drugs. Elevations of ALT to ≥3x ULN occurred in 0.7% (7/935) of lacosamide patients and 0% (0/356) of placebo patients. One case of hepatitis with transaminases >20x ULN occurred in one healthy subject 10 days after lacosamide treatment completion, along with nephritis (proteinuria and urine casts). Serologic studies were negative for viral hepatitis. Transaminases returned to normal within one month without specific treatment. At the time of this event, bilirubin was normal. The hepatitis/nephritis was interpreted as a delayed hypersensitivity reaction to lacosamide. Other Adverse Reactions The following is a list of adverse reactions reported by patients treated with lacosamide in all clinical trials in adult patients, including controlled trials and long-term open-label extension trials. Adverse reactions addressed in other tables or sections are not listed here. Blood and lymphatic system disorders: neutropenia, anemia Cardiac disorders: palpitations Ear and labyrinth disorders: tinnitus Gastrointestinal disorders: constipation, dyspepsia, dry mouth, oral hypoaesthesia General disorders and administration site conditions: irritability, pyrexia, feeling drunk Injury, poisoning, and procedural complications: fall Musculoskeletal and connective tissue disorders: muscle spasms Nervous system disorders: paresthesia, cognitive disorder, hypoaesthesia, dysarthria, disturbance in attention, cerebellar syndrome Psychiatric disorders: confusional state, mood altered, depressed mood Lacosamide Injection Adult Patients (17 Years and Older) Adverse reactions with intravenous administration to adult patients with partial-onset seizures generally were similar to those that occurred with the oral formulation, although intravenous administration was associated with local adverse reactions such as injection site pain or discomfort (2.5%), irritation (1%), and erythema (0.5%). One case of profound bradycardia (26 bpm: BP 100/60 mmHg) occurred in a patient during a 15-minute infusion of 150 mg lacosamide. This patient was on a beta-blocker. Infusion was discontinued and the patient experienced a rapid recovery. The safety of a 15-minute loading dose administration of lacosamide injection 200 mg to 400 mg followed by oral administration of lacosamide given twice daily at the same total daily dose as the initial intravenous infusion was assessed in an open-label study in adult patients with partial-onset seizures. Patients had to have been maintained on a stable dose regimen of 1 to 2 marketed antiepileptics for at least 28 days prior to treatment assignment. Treatment groups were as follows: Single dose of intravenous lacosamide injection 200 mg followed by oral lacosamide 200 mg/day (100 mg every 12 hours) Single dose of intravenous lacosamide injection 300 mg followed by oral lacosamide 300 mg/day (150 mg every 12 hours) Single dose of intravenous lacosamide injection 400 mg followed by oral lacosamide 400 mg/day (200 mg every 12 hours). Table 5 gives the incidence of adverse reactions that occurred in ≥5% of adult patients in any lacosamide dosing group. Table 5: Adverse Reactions in a 15-minute Infusion Study in Adult Patients with Partial-Onset Seizures Adverse Reaction Lacosamide 200 mg N=25 % Lacosamide 300 mg N=50 % Lacosamide 400 mg N=25 % Lacosamide Total N=100 % Eye disorders Diplopia 4 6 20 9 Blurred Vision 0 4 12 5 Gastrointestinal disorders Nausea 0 16 24 14 Dry mouth 0 6 12 6 Vomiting 0 4 12 5 Oral Paresthesia 4 4 8 5 Oral Hypoesthesia 0 6 8 5 Diarrhea 0 8 0 4 General disorders/administration site conditions Fatigue 0 18 12 12 Gait disturbance 8 2 0 3 Chest pain 0 0 12 3 Nervous system disorders Dizziness 20 46 60 43 Somnolence 0 34 36 26 Headache 8 4 16 8 Paresthesia 8 6 4 6 Tremor 0 6 4 4 Abnormal Coordination 0 6 0 3 Skin & subcutaneous tissue disorders Pruritus 0 6 4 4 Hyperhidrosis 0 0 8 2 Adverse reactions that occurred with infusion of lacosamide 200 mg over 15-minutes followed by lacosamide 100 mg administered orally twice per day were similar in frequency to those that occurred in 3-month adjunctive therapy-controlled trials. Considering the difference in period of observations (1 week vs. 3 months), the incidence of CNS adverse reactions, such as dizziness, somnolence, and paresthesia may be higher with 15-minute administration of lacosamide injection than with administration over a 30-to 60-minute period. The adverse reactions associated with lacosamide injection in adult patients with primary generalized tonic-clonic seizures are expected to be similar to those seen in adults with partial-onset seizures. Pediatric use information is approved for UCB, Inc.’s VIMPAT ® (lacosamide) injection. However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of lacosamide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and lymphatic system disorders: Agranulocytosis Psychiatric disorders: Aggression, agitation, hallucination, insomnia, psychotic disorder Skin and subcutaneous tissue disorders: Angioedema, rash, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis. Neurologic disorders: Dyskinesia, new or worsening seizures"}', 'drug_interactions': '{"7 DRUG INTERACTIONS 7.1 Strong CYP3A4 or CYP2C9 Inhibitors Patients with renal or hepatic impairment who are taking strong inhibitors of CYP3A4 and CYP2C9 may have a significant increase in exposure to lacosamide. Dose reduction may be necessary in these patients. 7.2 Concomitant Medications that Affect Cardiac Conduction Lacosamide should be used with caution in patients on concomitant medications that affect cardiac conduction (sodium channel blockers, beta-blockers, calcium channel blockers, potassium channel blockers) including those that prolong PR interval (including sodium channel blocking AEDs), because of a risk of AV block, bradycardia, or ventricular tachyarrhythmia. In such patients, obtaining an ECG before beginning lacosamide, and after lacosamide is titrated to steady-state, is recommended. In addition, these patients should be closely monitored if they are administered lacosamide through the intravenous route [see Warnings and Precautions ( 5.3 )]."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Lacosamide injection is indicated for: Treatment of partial-onset seizures in patients 17 years of age and older ( 1.1 ) Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients 4 years of age and older ( 1.2 ) 1.1 Partial-Onset Seizures Lacosamide injection is indicated for the treatment of partial-onset seizures in patients 17 years of age and older. Pediatric use information is approved for UCB, Inc.’s VIMPAT ® (lacosamide) injection. However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information. 1.2 Primary Generalized Tonic-Clonic Seizures Lacosamide injection is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients 4 years of age and older."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Monitor patients for suicidal behavior and ideation ( 5.1 ) Lacosamide may cause dizziness and ataxia ( 5.2 ) Cardiac Rhythm and Conduction Abnormalities: Obtaining ECG before beginning and after titration to steady-state maintenance is recommended in patients with underlying proarrhythmic conditions or on concomitant medications that affect cardiac conduction; closely monitor these patients ( 5.3 , 7.2 ) Lacosamide may cause syncope ( 5.4 ) Lacosamide should be gradually withdrawn to minimize the potential of increased seizure frequency ( 5.5 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/ Multi-Organ Hypersensitivity: Discontinue if no alternate etiology ( 5.6 ) 5.1 Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including lacosamide, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number of events is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Table 3 shows absolute and relative risk by indication for all evaluated AEDs. Table 3: Risk by Indication for Antiepileptic Drugs in the Pooled Analysis Indication Placebo Patients with Events Per 1,000 Patients Drug Patients with Events Per 1,000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1,000Patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar. Anyone considering prescribing lacosamide or any other AED must balance this risk with the risk of untreated illness. Epilepsy and many other illnesses for which antiepileptics are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. 5.2 Dizziness and Ataxia Lacosamide may cause dizziness and ataxia in adult and pediatric patients. In adult patients with partial-onset seizures taking 1 to 3 concomitant AEDs, dizziness was experienced by 25% of patients randomized to the recommended doses (200 to 400 mg/day) of lacosamide injection (compared with 8% of placebo patients) and was the adverse reaction most frequently leading to discontinuation (3%). Ataxia was experienced by 6% of patients randomized to the recommended doses (200 to 400 mg/day) of lacosamide injection (compared to 2% of placebo patients). The onset of dizziness and ataxia was most commonly observed during titration. There was a substantial increase in these adverse reactions at doses higher than 400 mg/day [see Adverse Reactions ( 6.1 )]. If a loading dose is clinically indicated, administer with medical supervision because of the possibility of increased incidence of adverse reactions, including CNS adverse reactions such as dizziness and ataxia. 5.3 Cardiac Rhythm and Conduction Abnormalities PR Interval Prolongation, Atrioventricular Block, and Ventricular Tachyarrhythmia Dose-dependent prolongations in PR interval with lacosamide have been observed in clinical studies in adult patients and in healthy volunteers [see Clinical Pharmacology ( 12.2 )] . In adjunctive clinical trials in adult patients with partial-onset seizures, asymptomatic first-degree atrioventricular (AV) block was observed as an adverse reaction in 0.4% (4/944) of patients randomized to receive lacosamide and 0% (0/364) of patients randomized to receive placebo. One case of profound bradycardia was observed in a patient during a 15-minute infusion of 150 mg lacosamide. When lacosamide is given with other drugs that prolong the PR interval, further PR prolongation is possible. In the postmarketing setting, there have been reports of cardiac arrhythmias in patients treated with lacosamide, including bradycardia, AV block, and ventricular tachyarrhythmia, which have rarely resulted in asystole, cardiac arrest, and death. Most, although not all, cases have occurred in patients with underlying proarrhythmic conditions, or in those taking concomitant medications that affect cardiac conduction or prolong the PR interval. These events have occurred with both oral and intravenous routes of administration and at prescribed doses as well as in the setting of overdose [see Overdosage ( 10 )]. In all patients for whom a loading dose is clinically indicated, administer the loading dose with medical supervision because of the possibility of increased incidence of adverse reactions, including cardiovascular adverse reactions. Lacosamide should be used with caution in patients with underlying proarrhythmic conditions such as known cardiac conduction problems (e.g., marked first-degree AV block, second-degree or higher AV block and sick sinus syndrome without pacemaker), severe cardiac disease (such as myocardial ischemia or heart failure, or structural heart disease), and cardiac sodium channelopathies (e.g., Brugada Syndrome). Lacosamide should also be used with caution in patients on concomitant medications that affect cardiac conduction, including sodium channel blockers, beta-blockers, calcium channel blockers, potassium channel blockers, and medications that prolong the PR interval [see Drug Interactions ( 7.2 )]. In such patients, obtaining an ECG before beginning lacosamide, and after lacosamide is titrated to steady-state maintenance dose, is recommended. In addition, these patients should be closely monitored if they are administered lacosamide through the intravenous route [see Adverse Reactions ( 6.1 ) and Drug Interactions ( 7.2 )]. Atrial Fibrillation and Atrial Flutter In the short-term investigational trials of lacosamide injection in adult patients with partial-onset seizures there were no cases of atrial fibrillation or flutter. Both atrial fibrillation and atrial flutter have been reported in open label partial-onset seizure trials and in postmarketing experience. In adult patients with diabetic neuropathy, for which lacosamide is not indicated, 0.5% of patients treated with lacosamide experienced an adverse reaction of atrial fibrillation or atrial flutter, compared to 0% of placebo-treated patients. Lacosamide administration may predispose to atrial arrhythmias (atrial fibrillation or flutter), especially in patients with diabetic neuropathy and/or cardiovascular disease. 5.4 Syncope In the short-term controlled trials of lacosamide in adult patients with partial-onset seizures with no significant system illnesses, there was no increase in syncope compared to placebo. In the short-term controlled trials in adult patients with diabetic neuropathy, for which lacosamide is not indicated, 1.2% of patients who were treated with lacosamide reported an adverse reaction of syncope or loss of consciousness, compared with 0% of placebo-treated patients with diabetic neuropathy. Most of the cases of syncope were observed in patients receiving doses above 400 mg/day. The cause of syncope was not determined in most cases. However, several were associated with either changes in orthostatic blood pressure, atrial flutter/fibrillation (and associated tachycardia), or bradycardia. Cases of syncope have also been observed in open-label clinical partial-onset seizure studies in adult and pediatric patients. These cases were associated with a history of risk factors for cardiac disease and the use of drugs that slow AV conduction. 5.5 Withdrawal of Antiepileptic Drugs (AEDs) As with all AEDs, lacosamide should be withdrawn gradually (over a minimum of 1 week) to minimize the potential of increased seizure frequency in patients with seizure disorders. 5.6 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity, has been reported in patients taking antiepileptic drugs, including lacosamide. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection. Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Lacosamide should be discontinued if an alternative etiology for the signs or symptoms cannot be established."}', 'overdosage': '{"10 OVERDOSAGE Events reported after an intake of more than 800 mg (twice the maximum recommended daily dosage) of lacosamide include dizziness, nausea, and seizures (generalized tonic-clonic seizures, status epilepticus). Cardiac conduction disorders, confusion, decreased level of consciousness, cardiogenic shock, cardiac arrest, and coma have also been observed. Fatalities have occurred following lacosamide overdoses of several grams. There is no specific antidote for overdose with lacosamide. Standard decontamination procedures should be followed. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of patient. A Certified Poison Control Center should be contacted for up to date information on the management of overdose with lacosamide. Standard hemodialysis procedures result in significant clearance of lacosamide (reduction of systemic exposure by 50% in 4 hours). Hemodialysis may be indicated based on the patient\'s clinical state or in patients with significant renal impairment."}', 'active_flag': 'Y', 'generic_name': '{LACOSAMIDE}', 'route': '{INTRAVENOUS}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide). The Medication Guide accompanies the product and can also be accessed on www.apotex.com or by calling 1-800-706-5575. Suicidal Thinking and Behavior Patients, their caregivers, and families should be counseled that AEDs, including lacosamide, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers [see Warnings and Precautions ( 5.1 )]. Dizziness and Ataxia Patients should be counseled that lacosamide use may cause dizziness, double vision, abnormal coordination and balance, and somnolence. Patients taking lacosamide should be advised not to drive, operate complex machinery, or engage in other hazardous activities until they have become accustomed to any such effects associated with lacosamide [see Warnings and Precautions ( 5.2 )]. Cardiac Rhythm and Conduction Abnormalities Patients should be counseled that lacosamide is associated with electrocardiographic changes that may predispose to irregular heart beat and syncope. Cardiac arrest has been reported. This risk is increased in patients with underlying cardiovascular disease, with heart conduction problems, or who are taking other medications that affect the heart. Patients should be made aware of and report cardiac signs or symptoms to their healthcare provider right away. Patients who develop syncope should lay down with raised legs and contact their health care provider [see Warnings and Precautions ( 5.3 )]. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity Patients should be aware that lacosamide may cause serious hypersensitivity reactions affecting multiple organs such as the liver and kidney. Lacosamide should be discontinued if a serious hypersensitivity reaction is suspected. Patients should also be instructed to report promptly to their physicians any symptoms of liver toxicity (e.g., fatigue, jaundice, dark urine) [see Warnings and Precautions ( 5.6 )]. Pregnancy Registry Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during lacosamide therapy. Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry if they become pregnant. This registry is collecting information about the safety of AEDs during pregnancy [see Use in Specific Populations ( 8.1 )]. Lactation Advise breastfeeding women using lacosamide injection to monitor infants for excess sleepiness and to seek medical care if they notice this sign [see Use in Specific Populations ( 8.2 )]. Rx Only APOTEX INC. LACOSAMIDE INJECTION, USP 200 mg/ 20mL Manufactured by: Manufactured for: Maiva Pharma Pvt. Ltd. Apotex Corp. No 32, Sipcot Industrial Complex, Phase I, Hosur, Weston, Florida Tamilnadu 635126, India (IND) USA 33326 Revision: 7"}', 'pregnancy': '{"8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as lacosamide, during pregnancy. Encourage women who are taking lacosamide during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry by calling 1-888\xad 233-2334 or visiting http://www.aedpregnancyregistry.org/. Risk Summary Available data from the North American Antiepileptic Drug (NAAED) pregnancy registry, a prospective cohort study, case reports, and a case series with lacosamide use in pregnant women are insufficient to identify a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Lacosamide produced developmental toxicity (increased embryofetal and perinatal mortality, growth deficit) in rats following administration during pregnancy. Developmental neurotoxicity was observed in rats following administration during a period of postnatal development corresponding to the third trimester of human pregnancy. These effects were observed at doses associated with clinically relevant plasma exposures (see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Oral administration of lacosamide to pregnant rats (20, 75, or 200 mg/kg/day) and rabbits (6.25, 12.5, or 25 mg/kg/day) during the period of organogenesis did not produce any effects on the incidences of fetal structural abnormalities. However, the maximum doses evaluated were limited by maternal toxicity in both species and embryofetal death in rats. These doses were associated with maternal plasma lacosamide exposures (AUC) approximately 2 and 1 times (rat and rabbit, respectively) that in humans at the maximum recommended human dose (MRHD) of 400 mg/day. In two studies in which lacosamide (25, 70, or 200 mg/kg/day and 50, 100, or 200 mg/kg/day) was orally administered to rats throughout pregnancy and lactation, increased perinatal mortality and decreased body weights in the offspring were observed at the highest dose tested. The no-effect dose for pre- and postnatal developmental toxicity in rats (70 mg/kg/day) was associated with a maternal plasma lacosamide AUC similar to that in humans at the MRHD. Oral administration of lacosamide (30, 90, or 180 mg/kg/day) to rats during the neonatal and juvenile periods of development resulted in decreased brain weights and long-term neurobehavioral changes (altered open field performance, deficits in learning and memory). The early postnatal period in rats is generally thought to correspond to late pregnancy in humans in terms of brain development. The no-effect dose for developmental neurotoxicity in rats was associated with a plasma lacosamide AUC less than that in humans at the MRHD. In Vitro Data Lacosamide has been shown in vitro to interfere with the activity of collapsin response mediator protein-2 (CRMP-2), a protein involved in neuronal differentiation and control of axonal outgrowth. Potential adverse effects on CNS development related to this activity cannot be ruled out."}', 'pediatric_use': '{"8.4 Pediatric Use Safety and effectiveness in pediatric patients below 1 month of age have not been established. Primary Generalized Tonic-Clonic Seizures Safety and effectiveness of lacosamide as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in pediatric patients with idiopathic generalized epilepsy 4 years of age and older was established in a 24-week double-blind, randomized, placebo-controlled, parallel-group, multi-center study (Study 5), which included 37 pediatric patients 4 years to less than 17 years of age [see Adverse Reactions ( 6.1 ) and Clinical Studies ( 14.3 )] . Safety and effectiveness in pediatric patients below the age of 4 years have not been established. Animal Data Lacosamide has been shown in vitro to interfere with the activity of collapsin response mediator protein-2 (CRMP-2), a protein involved in neuronal differentiation and control of axonal outgrowth. Potential related adverse effects on CNS development cannot be ruled out. Administration of lacosamide to rats during the neonatal and juvenile periods of postnatal development (approximately equivalent to neonatal through adolescent development in humans) resulted in decreased brain weights and long-term neurobehavioral changes (altered open field performance, deficits in learning and memory). The no-effect dose for developmental neurotoxicity in rats was associated with a plasma lacosamide exposure (AUC) less than that in humans at the maximum recommended human dose of 400 mg/day. Pediatric use information is approved for UCB, Inc.’s VIMPAT ® (lacosamide) injection. However, due to UCB, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information."}', 'geriatric_use': '{"8.5 Geriatric Use There were insufficient numbers of elderly patients enrolled in partial-onset seizure trials (n=18) to adequately determine whether they respond differently from younger patients. No lacosamide dose adjustment based on age is necessary. In elderly patients, dose titration should be performed with caution, usually starting at the lower end of the dosing range, reflecting the greater frequency of decreased hepatic function, decreased renal function, increased cardiac conduction abnormalities, and polypharmacy [see Dosage and Administration ( 2.1 , 2.4, 2.5) and Clinical Pharmacology ( 12.3 )]."}'}

{"CHLORPHENIRAMINE MALEATE","DEXTROMETHORPHAN HYDROBROMIDE","PHENYLEPHRINE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"USE For temporary relief of runny nose, sneezing,itching of the nose or throat and itchy watery eyes due to hay fever. Temporarily relieves cough due to minor throat and bronchial irritation as may occur with the common cold. Temporarily restores freer breathing through the nose"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"CHLORPHENIRAMINE MALEATE, DEXTROMETHORPHAN HYDROBROMIDE, AND PHENYLEPHRINE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"STOP USE AND ASK A DOCTOR IF you get nervous, dizzy, or sleepless. cough last more than 7 day, comes back, or is accompanied by fever, rash or persistent headaches. These could be signs of a serious condition."}', 'do_not_use': '{"DO NOT USE to sedate a child or to make a child sleepy If you are now taking a prescription monoamine oxidase inhibitor (MAOI) ( certain drugs for depression, psychiatric or emotional conditions or parkinson\'s disease) or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product."}', 'when_using': '{"When using this product DO NOT EXCEED RECOMMENDED DOSAGE may cause marked drowsiness avoid alcoholic beverages Alcohol, sedatives, and tranquilizers may cause increased drowsiness be careful when driving a motor vehicle or operating machinery excitability may occur, especially with children."}', 'warnings': '{"WARNINGS DO NOT USE to sedate a child or to make a child sleepy If you are now taking a prescription monoamine oxidase inhibitor (MAOI) ( certain drugs for depression, psychiatric or emotional conditions or parkinson\'s disease) or for 2 weeks after stopping the MAOI drug. If you do not know if your prescription drug contains an MAOI, ask a doctor or pharmacist before taking this product. ASK A DOCTOR BEFORE USE IF YOU HAVE heart disease thyroid disease trouble urinating due to enlarged prostate gland glaucoma cough that occurs with too much phlegm (mucus) a breathing problems or chronic cough that lasts such as occurs with smoking, asthma, chronic bronchitis or emphysema ASK A DOCTOR OR PHARMACIST BEFORE USE IF YOU ARE taking sedatives or tranquilizers When using this product DO NOT EXCEED RECOMMENDED DOSAGE may cause marked drowsiness avoid alcoholic beverages Alcohol, sedatives, and tranquilizers may cause increased drowsiness be careful when driving a motor vehicle or operating machinery excitability may occur, especially with children. STOP USE AND ASK A DOCTOR IF you get nervous, dizzy, or sleepless. cough last more than 7 day, comes back, or is accompanied by fever, rash or persistent headaches. These could be signs of a serious condition. IF PREGNANT OR BREAST FEEDING ask a health professional before use. KEEP OUT OF REACH OF CHILDREN . in case of accidental overdose, get medical help or contact a poison control Center right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"TRAZODONE HYDROCHLORIDE"}

{'contraindications': '{"4 CONTRAINDICATIONS Trazodone hydrochloride tablets are contraindicated in: Patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (MAOIs), including MAOIs such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome [see Warnings and Precautions ( 5.2 ), Drug Interactions ( 7.1 )]. Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping MAOIs ( 4 )."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Suicidal Thoughts and Behavior in Children, Adolescents and Young Adults [see Boxed Warning and Warnings and Precautions ( 5.1 )] Serotonin Syndrome [see Warnings and Precautions ( 5.2 )] Cardiac Arrythmias (see Warnings and Precautions ( 5.3 )] Orthostatic Hypotension and Syncope [see Warnings and Precautions ( 5.4 )] Increased Risk of Bleeding [see Warnings and Precautions ( 5.5 )] Priapism [see Warnings and Precautions ( 5.6 )] Activation of Mania or Hypomania [see Warnings and Precautions ( 5.7 )] Discontinuation Syndrome [see Warnings and Precautions ( 5.8 )] Potential for Cognitive and Motor Impairment [see Warnings and Precautions ( 5.9 ) ] Angle-Closure Glaucoma [see Warnings and Precautions ( 5.10 )] Hyponatremia [see Warnings and Precautions ( 5.11 )] Most common adverse reactions (incidence ≥ 5% and twice that of placebo) are: edema, blurred vision, syncope, drowsiness, fatigue, diarrhea, nasal congestion, weight loss ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals USA, Inc. at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Table 2: Common Adverse Reactions Occurring in ≥ 2% of Trazodone Hydrochloride Tablets-treated Patients and Greater than the Rate of Placebo-Treated Patients as Observed in Controlled Clinical Studies Inpatients Outpatients Trazodone Hydrochloride Tablets Placebo Trazodone Hydrochloride Tablets Placebo N =142 N=95 N =157 N=158 Allergic 3% 1% 7% 1% Skin Condition/Edema Autonomic Blurred Vision 6% 4% 15% 4% Constipation 7% 4% 8% 6% Dry Mouth 15% 8% 34% 20% Cardiovascular Hypertension 20% 1% 1% * Hypotension 7% 1% 4% 0 Syncope 3% 2% 5% 1% CNS Confusion 5% 0 6% 8% Decreased Concentration 3% 2% 1% 0 Disorientation 2% 0 * 0 Dizziness/Light-Headedness 20% 5% 28% 15% Drowsiness 24% 6% 41% 20% Fatigue 11% 4% 6% 3% Headache 10% 5% 20% 16% Nervousness 15% 11% 6% 8% Gastrointestinal Abdominal/Gastric Disorder 4% 4% 6% 4% Diarrhea 0 1% 5% 1% Nausea/Vomiting 10% 1% 13% 10% Musculoskeletal Aches/Pains 6% 3% 5% 3% Neurological Incoordination 5% 0 2% * Tremors 3% 1% 5% 4% Other Eyes Red/Tired/Itching 3% 0 0 0 Head Full-Heavy 3% 0 0 0 Malaise 3% 0 0 0 Nasal/Sinus Congestion 3% 0 6% 3% Weight Gain 1% 0 5% 2% Weight Loss * 3% 6% 3% Other adverse reactions occurring at an incidence of <2% with the use of trazodone hydrochloride in the controlled clinical studies: akathisia, allergic reaction, anemia, chest pain, delayed urine flow, early menses, flatulence, hallucinations/delusions, hematuria, hypersalivation, hypomania, impaired memory, impaired speech, impotence, increased appetite, increased libido, increased urinary frequency, missed periods, muscle twitches, numbness, paresthesia, retrograde ejaculation, shortness of breath, and tachycardia/palpitations. Occasional sinus bradycardia has occurred in long-term studies. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of trazodone hydrochloride tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure: Blood and lymphatic system disorders: hemolytic anemia, leukocytosis Cardiac disorders: cardiospasm, congestive heart failure, conduction block, orthostatic hypotension and syncope, palpitations, bradycardia, atrial fibrillation, myocardial infarction, cardiac arrest, arrhythmia, ventricular ectopic activity, including ventricular tachycardia and QT prolongation. Prolonged QT interval, torsade de pointes, and ventricular tachycardia have been reported at doses of 100 mg per day or less [see Warnings and Precautions ( 5.3 )]. Endocrine disorders: inappropriate ADH syndrome Eye disorders: diplopia Gastrointestinal disorders: increased salivation, nausea/vomiting General disorders and administration site conditions: chills, edema, unexplained death, weakness Hepatobiliary disorders: cholestasis, jaundice, hyperbilirubinemia, liver enzyme alterations Investigations: increased amylase Metabolism and nutrition disorders: methemoglobinemia Nervous system disorders: aphasia, ataxia, cerebrovascular accident, extrapyramidal symptoms, grand mal seizures, paresthesia, tardive dyskinesia, vertigo Psychiatric disorders: abnormal dreams, agitation, anxiety, hallucinations, insomnia, paranoid reaction, psychosis, stupor Renal and urinary disorders: urinary incontinence, urinary retention Reproductive system and breast disorders: breast enlargement or engorgement, clitorism, lactation, priapism [see Warnings and Precautions ( 5.6 )] Respiratory, thoracic and mediastinal disorders: apnea Skin and subcutaneous tissue disorders: alopecia, hirsutism, leukonychia, pruritus, psoriasis, rash, urticaria Vascular disorders: vasodilation"}', 'drug_interactions': '{"7 DRUG INTERACTIONS • CNS Depressants: Trazodone hydrochloride tablets may enhance effects of alcohol, barbiturates, or other CNS depressants ( 7 ). • CYP3A4 Inhibitors: Consider trazodone hydrochloride tablets dose reduction based on tolerability ( 2.5 , 7 ). • CYP3A4 Inducers: Increase in trazodone hydrochloride tablets dosage may be necessary ( 2.5 , 7 ). • Digoxin or Phenytoin: Monitor for increased digoxin or phenytoin serum levels ( 7 ). • Warfarin: Monitor for increased or decreased prothrombin time ( 7 ). 7.1 Drugs Having Clinically Important Interactions with Trazodone Hydrochloride Tablets Table 3: Clinically Important Drug Interactions with Trazodone Hydrochloride Tablets Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: The concomitant use of MAOIs and serotonergic drugs including trazodone hydrochloride tablets increases the risk of serotonin syndrome. Intervention: Trazodone hydrochloride tablets are contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Contraindications (4), Dosage and Administration ( 2.3 , 2.4 ), and Warnings and Precautions ( 5.2 )]. Examples: isocarboxazid, moclobemide, phenelzine, selegiline, tranylcypromine Other Serotonergic Drugs Clinical Impact: The concomitant use of serotonergic drugs including trazodone hydrochloride tablets and other serotonergic drugs increases the risk of serotonin syndrome. Intervention: Monitor patients for signs and symptoms of serotonin syndrome, particularly during trazodone hydrochloride tablets initiation. If serotonin syndrome occurs, consider discontinuation of trazodone hydrochloride tablets and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.2 )]. Examples: triptans, antidepressants (tricyclic and serotonin uptake inhibitors), fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John\'s Wort Antiplatelet Agents and Anticoagulants Clinical Impact: Serotonin release by platelets plays an important role in hemostasis. The concurrent use of an antiplatelet agent or anticoagulant with trazodone hydrochloride tablets may potentiate the risk of bleeding. Intervention: Inform patients of the increased risk of bleeding with the concomitant use of trazodone hydrochloride tablets and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio (INR) when initiating or discontinuing trazodone hydrochloride tablets [see Warnings and Precautions ( 5.5 )]. Examples: warfarin, rivaroxaban, dabigatran, clopidogrel Strong CYP3A4 Inhibitors Clinical Impact: The concomitant use of trazodone hydrochloride tablets and strong CYP3A4 inhibitors increased the exposure of trazodone compared to the use of trazodone hydrochloride tablets alone. Intervention: If trazodone hydrochloride tablets is used with a potent CYP3A4 inhibitor, the risk of adverse reactions, including cardiac arrhythmias, may be increased and a lower dose of trazodone hydrochloride tablets should be considered [see Dosage and Administration ( 2.5 ), Warnings and Precautions ( 5.3 )]. Examples: itraconazole, ketoconazole, clarithromycin, indinavir Strong CYP3A4 Inducers Clinical Impact: The concomitant use of trazodone hydrochloride tablets and strong CYP3A4 inducers decreased the exposure of trazodone compared to the use of trazodone hydrochloride tablets alone. Intervention: Patients should be closely monitored to see if there is a need for an increased dose of trazodone hydrochloride tablets when taking CYP3A4 inducers [see Dosage and Administration ( 2.5 )]. Examples: rifampin, carbamazepine, phenytoin, St. John’s wort Digoxin and Phenytoin Clinical Impact: Digoxin and phenytoin are narrow therapeutic index drugs. Concomitant use of trazodone hydrochloride tablets can increase digoxin or phenytoin concentrations. Intervention: Measure serum digoxin or phenytoin concentrations before initiating concomitant use of trazodone hydrochloride tablets. Continue monitoring and reduce digoxin or phenytoin dose as necessary. Examples: digoxin, phenytoin Central Nervous System (CNS) Depressants Clinical Impact: Trazodone hydrochloride tablets may enhance the response CNS depressants. Intervention: Patients should be counseled that trazodone hydrochloride tablets may enhance the response to alcohol, barbiturates, and other CNS depressants. Examples: alcohol, barbiturates QT Interval Prolongation Clinical Impact: Concomitant use of drugs that prolong the QT interval may add to the QT effects of trazodone hydrochloride tablets and increase the risk of cardiac arrhythmia. Intervention: Avoid the use of trazodone hydrochloride tablets in combination with other drugs known to prolong QTc [see Warnings and Precautions ( 5.3 )]. Examples: Class 1A antiarrhythmics: quinidine, procainamide, disopyramide; Class 3 antiarrhythmics: amiodarone, sotalol; Antipsychotics: ziprasidone, chlorpromazine, thioridazine; Antibiotics: gatifloxacin"}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Trazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (MDD) in adults. Trazodone hydrochloride tablets are a selective serotonin reuptake inhibitor indicated for the treatment of major depressive disorder (MDD) ( 1 )."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents (e.g., SSRI, SNRI, triptans), but also when taken alone. If it occurs, discontinue trazodone hydrochloride tablets and initiate supportive treatment ( 5.2 ). • Cardiac Arrhythmias: Increases the QT interval. Avoid use with drugs that also increase the QT interval and in patients with risk factors for prolonged QT interval ( 5.3 ) • Orthostatic Hypotension and Syncope: Warn patients of risk and symptoms of hypotension ( 5.4 ). • Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk ( 5.5 ). • Priapism: Cases of painful and prolonged penile erections and priapism have been reported. Immediate medical attention should be sought if signs and symptoms of prolonged penile erections or priapism are observed ( 5.6 ). • Activation of Mania or Hypomania: Screen for bipolar disorder and monitor for mania or hypomania ( 5.7 ). • Potential for Cognitive and Motor Impairment: Has potential to impair judgment, thinking, and motor skills. Advise patients to use caution when operating machinery ( 5.9 ). • Angle-Closure Glaucoma: Avoid use of antidepressants, including trazodone hydrochloride tablets, in patients with untreated anatomically narrow angles. ( 5.10 ). 5.1 Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and over 4,400 pediatric patients, the incidence of suicidal thoughts and behaviors in pediatric and young adult patients was greater in antidepressant-treated patients than in placebo-treated patients. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 1. No suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the number was not sufficient to reach any conclusion about antidepressant drug effect on suicide. Table 1: Risk Differences of the Number of Cases of Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range (years) Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1000 Patients Treated Increases Compared to Placebo < 18 14 additional patients 18 to 24 5 additional patients Decreases Compared to Placebo 25 to 64 1 fewer patient ≥ 65 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in pediatric and young adult patients extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression. Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing trazodone hydrochloride tablets, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome Serotonin-norepinephrine reuptake inhibitors (SNRIs) and SSRIs, including trazodone hydrochloride tablets, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications ( 4 ), Drug Interactions ( 7.1 )]. Serotonin syndrome can also occur when these drugs are used alone. Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of trazodone hydrochloride tablets with MAOIs is contraindicated. In addition, do not initiate trazodone hydrochloride tablets in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking trazodone hydrochloride tablets, discontinue trazodone hydrochloride tablets before initiating treatment with the MAOI [see Contraindications ( 4 ), Drug Interactions ( 7.1 )]. Monitor all patients taking trazodone hydrochloride tablets for the emergence of serotonin syndrome. Discontinue treatment with trazodone hydrochloride tablets and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of trazodone hydrochloride tablets with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.3 Cardiac Arrhythmias Clinical studies indicate that trazodone hydrochloride may be arrhythmogenic in patients with preexisting cardiac disease. Arrhythmias identified include isolated PVCs, ventricular couplets, tachycardia with syncope, and torsade de pointes. Postmarketing events, including torsade de pointes have been reported at doses of 100 mg or less with the immediate-release form of trazodone hydrochloride. Trazodone hydrochloride should also be avoided in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval. Trazodone hydrochloride is not recommended for use during the initial recovery phase of myocardial infarction. Caution should be used when administering trazodone hydrochloride to patients with cardiac disease and such patients should be closely monitored, since antidepressant drugs (including trazodone hydrochloride ) may cause cardiac arrhythmias [see Adverse Reactions ( 6.2 )]. Trazodone hydrochloride prolongs the QT/QTc interval. The use of trazodone hydrochloride should be avoided in patients with known QT prolongation or in combination with other drugs that are inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, voriconazole), or known to prolong QT interval including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), certain antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), and certain antibiotics (e.g., gatifloxacin). Concomitant administration of drugs may increase the risk of cardiac arrhythmia [see Drug Interactions ( 7.1 )]. 5.4 Orthostatic Hypotension and Syncope Hypotension, including orthostatic hypotension and syncope has been reported in patients receiving trazodone hydrochloride. Concomitant use with an antihypertensive may require a reduction in the dose of the antihypertensive drug. 5.5 Increased Risk of Bleeding Drugs that interfere with serotonin reuptake inhibition, including trazodone hydrochloride, increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to drugs that interfere with serotonin reuptake have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages. Inform patients about the risk of bleeding associated with the concomitant use of trazodone hydrochloride and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing trazodone hydrochloride. 5.6 Priapism Cases of priapism (painful erections greater than 6 hours in duration) have been reported in men receiving trazodone hydrochloride tablets. Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. Men who have an erection lasting greater than 4 hours, whether painful or not, should immediately discontinue the drug and seek emergency medical attention [see Adverse Reactions ( 6.2 ), Overdosage ( 10 )]. Trazodone hydrochloride tablets should be used with caution in men who have conditions that might predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, or leukemia), or in men with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, or Peyronie’s disease). 5.7 Activation of Mania or Hypomania In patients with bipolar disorder, treating a depressive episode with trazodone hydrochloride tablets or another antidepressant may precipitate a mixed/manic episode. Activation of mania/hypomania has been reported in a small proportion of patients with major affective disorder who were treated with antidepressants. Prior to initiating treatment with trazodone hydrochloride tablets, screen patients for any personal or family history of bipolar disorder, mania, or hypomania [see Dosage and Administration ( 2.3 )]. 5.8 Discontinuation Syndrome Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible [See Dosage and Administration ( 2.6 )]. 5.9 Potential for Cognitive and Motor Impairment Trazodone hydrochloride tablets may cause somnolence or sedation and may impair the mental and/or physical ability required for the performance of potentially hazardous tasks. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that the drug treatment does not affect them adversely. 5.10 Angle-Closure Glaucoma The pupillary dilation that occurs following use of many antidepressant drugs including trazodone hydrochloride tablets may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of antidepressants, including trazodone hydrochloride tablets, in patients with untreated anatomically narrow angles. 5.11 Hyponatremia Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including trazodone hydrochloride tablets. Cases with serum sodium lower than 110 mmol/L have been reported. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In patients with symptomatic hyponatremia, discontinue trazodone hydrochloride tablets and institute appropriate medical intervention. Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with SSRIs and SNRIs [see Use in Specific Populations ( 8.5 )]."}', 'overdosage': '{"10 OVERDOSAGE Death from overdose has occurred in patients ingesting trazodone hydrochloride and other CNS depressant drugs concurrently (alcohol; alcohol and chloral hydrate and diazepam; amobarbital; chlordiazepoxide; or meprobamate). The most severe reactions reported to have occurred with overdose of trazodone hydrochloride alone have been priapism, respiratory arrest, seizures, and ECG changes, including QT prolongation. The reactions reported most frequently have been drowsiness and vomiting. Overdosage may cause an increase in incidence or severity of any of the reported adverse reactions. There is no specific antidote for trazodone hydrochloride overdose. In managing overdosage, consider the possibility of multiple drug involvement. For current information on the management of poisoning or overdose, contact a poison control center (1-800-222-1222 or www.poison.org)."}', 'active_flag': 'Y', 'generic_name': '{"TRAZODONE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Suicidal Thoughts and Behaviors Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and when the dosage is adjusted up or down and instruct them to report such symptoms to the healthcare provider [see Box Warning and Warnings and Precautions ( 5.1 )]. Dosage and Administration Advise patients that trazodone hydrochloride tablets should be taken shortly after a meal or light snack. Advise patients regarding the importance of following dosage titration instructions [see Dosage and Administration ( 2 )]. Serotonin Syndrome Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of trazodone hydrochloride tablets with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid). Patients should contact their health care provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome [see Warnings and Precautions ( 5.2 ) and Drug Interactions ( 7 )]. Activation of Mania/Hypomania Advise patients and their caregivers to observe for signs of activation of mania/hypomania and instruct them to report such symptoms to the healthcare provider [see Warnings and Precautions ( 5.7 )] . Increased Risk of Bleeding Inform patients about the concomitant use of trazodone hydrochloride tablets with aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other anticoagulants because the combined use of drugs that interfere with serotonin reuptake and these medications has been associated with an increased risk of bleeding. Advise them to inform their health care providers if they are taking or planning to take any prescription or over-the-counter medications that increase the risk of bleeding [see Warnings and Precautions ( 5.5 )]. Discontinuation Syndrome Advise patients not to abruptly discontinue trazodone hydrochloride tablets and to discuss any tapering regimen with their healthcare provider. Adverse reactions can occur when trazodone hydrochloride tablets is discontinued [see Warnings and Precautions ( 5.8 )]. Concomitant Medications Advise patients to inform their health care providers if they are taking, or plan to take any prescription or over-the-counter medications since there is a potential for interactions [see Drug Interactions ( 7.1 )]. Pregnancy Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during therapy with trazodone hydrochloride tablets. Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to trazodone hydrochloride tablets during pregnancy [see Use in Special Populations ( 8.1 )]. Manufactured In Croatia By: Pliva Hrvatska d.o.o. Zagreb, Croatia Manufactured For: Teva Pharmaceuticals USA, Inc. Parsippany, NJ 07054 Repackaged By: Proficient Rx LP Thousand Oaks, CA 91320 Rev. I 7/2020"}', 'pregnancy': '{"8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/ Risk Summary Published prospective cohort studies, case series, and case reports over several decades with trazodone hydrochloride use in pregnant women have not identified any drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). Trazodone hydrochloride has been shown to cause increased fetal resorption and other adverse effects on the fetus in the rat when given at dose levels approximately 7.3 to 11 times the maximum recommended human dose (MRHD) of 400 mg/day in adults on a mg/m 2 basis. There was also an increase in congenital anomalies in the rabbit at approximately 7.3 to 22 times the MRHD on a mg/m 2 basis (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryofetal risk A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression that women who continued antidepressants. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Data Human Data While available studies cannot definitively establish the absence of risk, published data from prospective cohort studies, case series, and case reports over several decades have not identified an association with trazodone use during pregnancy and major birth defects, miscarriage, or other adverse maternal or fetal outcomes. All available studies have methodological limitations, including small sample size and inconsistent comparator groups. Animal Data No teratogenic effects were observed when trazodone was given to pregnant rats and rabbits during the period of organogenesis at oral doses up to 450 mg/kg/day. This dose is 11 and 22 times, in rats and rabbits, respectively, the maximum recommended human dose (MRHD) of 400 mg/day in adults on a mg/m 2 basis. Increased fetal resorption and other adverse effects on the fetus in rats at 7.3 to 11 times the MRHD and increase in congenital anomalies in rabbits at 7.3 to 22 times the MRHD on a mg/m 2 basis were observed. No further details on these studies are available."}', 'pediatric_use': '{"8.4 Pediatric Use Safety and effectiveness in the pediatric population have not been established. Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning, Warnings and Precautions ( 5.1 )] ."}', 'geriatric_use': '{"8.5 Geriatric Use Reported clinical literature and experience with trazodone has not identified differences in responses between elderly and younger patients. However, as experience in the elderly with trazodone hydrochloride is limited, it should be used with caution in geriatric patients. Serotonergic antidepressants have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see Warnings and Precautions ( 5.11 )]."}'}

{"MECLIZINE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses prevents and treats nausea, vomiting or dizziness associated with motion sickness"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"MECLIZINE HCL 25MG"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': '{"When using this product do not exceed recommended dosage drowsiness may occur alcohol, sedatives, and tranquilizers may increase drowsiness avoid alcoholic drinks be careful when driving a motor vehicle or operating machinery"}', 'warnings': '{"Warnings Do not use for children under 12 years of age unless directed by a doctor. Do not take unless directed by a doctor if you have glaucoma trouble urinating due to an enlarged prostate gland a breathing problem such as emphysema or chronic bronchitis Do not take if you are taking sedatives or tranquilizers, without first consulting your doctor. When using this product do not exceed recommended dosage drowsiness may occur alcohol, sedatives, and tranquilizers may increase drowsiness avoid alcoholic drinks be careful when driving a motor vehicle or operating machinery If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{DIMETHICONE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses for the relief of pressure, bloating, and fullness commonly referred to as gas"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{SIMETHICONE}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings If pregnant of breast-feeding, ask a health professional before use. Keep out of reach of children."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{INDOMETHACIN}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': None, 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{INDOMETHACIN}', 'route': '{RECTAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"DOXYCYCLINE HYCLATE"}

{'contraindications': '{"CONTRAINDICATIONS This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines."}', 'adverse_reactions': '{"ADVERSE REACTIONS Due to oral doxycycline’s virtually complete absorption, side effects of the lower bowel, particularly diarrhea, have been infrequent. The following adverse reactions have been observed in patients receiving tetracyclines: Gastrointestinal: anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, inflammatory lesions (with monilial overgrowth) in the anogenital region, and pancreatitis. Hepatotoxicity has been reported rarely. These reactions have been caused by both the oral and parenteral administration of tetracyclines. Superficial discoloration of the adult permanent dentition, reversible upon drug discontinuation and professional dental cleaning has been reported. Permanent tooth discoloration and enamel hypoplasia may occur with drugs of the tetracycline class when used during tooth development. (See WARNINGS .) Rare instances of esophagitis and esophageal ulcerations have been reported in patients receiving capsule and tablet forms of the drugs in the tetracycline class. Most of these patients took medications immediately before going to bed. (See DOSAGE AND ADMINISTRATION .) Skin: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, skin hyperpigmentation, maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Photosensitivity is discussed above. (See WARNINGS . ) Renal toxicity: Rise in BUN has been reported and is apparently dose related. (See WARNINGS . ) Immune: Hypersensitivity reactions including urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, exacerbation of systemic lupus erythematosus, and drug reaction with eosinophilia and systemic symptoms (DRESS), and Jarisch-Herxheimer reaction has been reported in the setting of spirochete infections treated with doxycycline. Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported. Other: Bulging fontanels in infants and intracranial hypertension in adults. (See WARNINGS . ) When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of the thyroid gland. No abnormalities of thyroid function studies are known to occur. To report SUSPECTED ADVERSE EVENTS, contact Actavis at 1-888-838-2872 or FDA at 1-800-FDA-1088 or http://www.fda.gov/ for voluntary reporting of adverse reactions."}', 'drug_interactions': '{"Drug Interactions Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracyclines in conjunction with penicillin. Absorption of tetracyclines is impaired by antacids containing aluminum, calcium, or magnesium, and iron-containing preparations. Absorption of tetracyclines is impaired by bismuth subsalicylate. Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline. The concurrent use of tetracycline and Penthrane ® (methoxyflurane) has been reported to result in fatal renal toxicity. Concurrent use of tetracycline may render oral contraceptives less effective."}', 'indications_and_usage': '{"INDICATIONS AND USAGE To reduce the development of drug-resistant bacteria and maintain effectiveness of doxycycline hyclate and other antibacterial drugs, doxycycline hyclate should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Treatment : Doxycycline is indicated for the treatment of the following infections: Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae. Respiratory tract infections caused by Mycoplasma pneumoniae . Lymphogranuloma venereum caused by Chlamydia trachomatis . Psittacosis (ornithosis) caused by Chlamydophila psittaci . Trachoma caused by Chlamydia trachomatis , although the infectious agent is not always eliminated, as judged by immunofluorescence. Inclusion conjunctivitis caused by Chlamydia trachomatis . Uncomplicated urethral, endocervical, or rectal infections in adults caused by Chlamydia trachomatis . Nongonococcal urethritis caused by Ureaplasma urealyticum . Relapsing fever due to Borrelia recurrentis . Doxycycline is also indicated for the treatment of infections caused by the following gram-negative microorganisms: Chancroid caused by Haemophilus ducreyi . Plague due to Yersinia pestis . Tularemia due to Francisella tularensis . Cholera caused by Vibrio cholerae . Campylobacter fetus infections caused by Campylobacter fetus . Brucellosis due to Brucella species (in conjunction with streptomycin). Bartonellosis due to Bartonella bacilliformis . Granuloma inguinale caused by Klebsiella granulomatis . Because many strains of the following groups of microorganisms have been shown to be resistant to doxycycline, culture and susceptibility testing are recommended. Doxycycline is indicated for treatment of infections caused by the following gram-negative bacteria, when bacteriologic testing indicates appropriate susceptibility to the drug: Escherichia coli . Enterobacter aerogenes . Shigella species. Acinetobacter species. Respiratory tract infections caused by Haemophilus influenzae . Respiratory tract and urinary tract infections caused by Klebsiella species. Doxycycline is indicated for treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug: Upper respiratory infections caused by Streptococcus pneumoniae . Anthrax due to Bacillus anthracis , including inhalational anthrax (post-exposure): to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis . When penicillin is contraindicated, doxycycline is an alternative drug in the treatment of the following infections: Uncomplicated gonorrhea caused by Neisseria gonorrhoeae . Syphilis caused by Treponema pallidum . Yaws caused by Treponema pallidum subspecies pertenue . Listeriosis due to Listeria monocytogenes . Vincent’s infection caused by Fusobacterium fusiforme . Actinomycosis caused by Actinomyces isr aelii . Infections caused by Clostridium species. In acute intestinal amebiasis, doxycycline may be a useful adjunct to amebicides. In severe acne, doxycycline may be useful adjunctive therapy. Prophylaxis: Doxycycline is indicated for the prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (<4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains. (See DOSAGE AND ADMINISTRATION section and Information for Patients subsection of the PRECAUTIONS section.)"}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures. Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage."}', 'active_flag': 'Y', 'generic_name': '{"DOXYCYCLINE HYCLATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS The use of drugs of the tetracycline class during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the drugs, but it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Use doxycycline in pediatric patients 8 years of age or less only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including doxycycline, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following the use of antibacterial drugs. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing use of antibacterial drugs not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. Severe skin reactions, such as exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients receiving doxycycline. (See ADVERSE REACTIONS .) If severe skin reactions occur, doxycycline should be discontinued immediately and appropriate therapy should be instituted. Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines including doxycycline. Clinical manifestations of IH include headache, blurred vision, diplopia, and vision loss; papilledema can be found on fundoscopy. Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH. Concomitant use of isotretinoin and doxycycline should be avoided because isotretinoin is also known to cause pseudotumor cerebri. Although IH typically resolves after discontinuation of treatment, the possibility for permanent visual loss exists. If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Since intracranial pressure can remain elevated for weeks after drug cessation patients should be monitored until they stabilize. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in prematures given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryotoxicity has also been noted in animals treated early in pregnancy. If any tetracycline is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. The antianabolic action of the tetracyclines may cause an increase in BUN. Studies to date indicate that this does not occur with the use of doxycycline in patients with impaired renal function. Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema."}', 'precautions': '{"PRECAUTIONS General As with other antibacterial drugs, use of doxycycline may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, doxycycline should be discontinued and appropriate therapy instituted. Incision and drainage or other surgical procedures should be performed in conjunction with antibacterial therapy, when indicated. Doxycycline offers substantial but not complete suppression of the asexual blood stages of Plasmodium strains. Doxycycline does not suppress P. falciparum’ s sexual blood stage gametocytes. Subjects completing this prophylactic regimen may still transmit the infection to mosquitoes outside endemic areas. Prescribing doxycycline hyclate in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Information For Patients Patients taking doxycycline for malaria prophylaxis should be advised: - that no present-day antimalarial agent, including doxycycline, guarantees protection against malaria. - to avoid being bitten by mosquitoes by using personal protective measures that help avoid contact with mosquitoes, especially from dusk to dawn (e.g., staying in well-screened areas, using mosquito nets, covering the body with clothing, and using an effective insect repellent). - that doxycycline prophylaxis: - should begin 1 to 2 days before travel to the malarious area, - should be continued daily while in the malarious area and after leaving the malarious area, - should be continued for 4 further weeks to avoid development of malaria after returning from an endemic area, - should not exceed 4 months. All patients taking doxycycline should be advised: - to avoid excessive sunlight or artificial ultraviolet light while receiving doxycycline and to discontinue therapy if phototoxicity (e.g., skin eruption, etc.) occurs. Sunscreen or sunblock should be considered. (See WARNINGS . ) - to drink fluids liberally along with doxycycline to reduce the risk of esophageal irritation and ulceration. (See ADVERSE REACTIONS . ) - that the absorption of tetracyclines is reduced when taken with foods, especially those which contain calcium. However, the absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk. (See DRUG INTERACTIONS .) - that the absorption of tetracyclines is reduced when taking bismuth subsalicylate. (See DRUG INTERACTIONS .) - that the use of doxycycline might increase the incidence of vaginal candidiasis. Patients should be counseled that antibacterial drugs, including doxycycline hyclate should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When doxycycline hyclate is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by doxycycline hyclate or other antibacterial drugs in the future. Diarrhea is a common problem caused by antibacterial drugs, which usually ends when the antibacterials are discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible. Laboratory Tests In venereal disease, when co-existent syphilis is suspected, dark field examinations should be done before treatment is started and the blood serology repeated monthly for at least 4 months. In long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic, renal, and hepatic studies, should be performed. Drug Interactions Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracyclines in conjunction with penicillin. Absorption of tetracyclines is impaired by antacids containing aluminum, calcium, or magnesium, and iron-containing preparations. Absorption of tetracyclines is impaired by bismuth subsalicylate. Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline. The concurrent use of tetracycline and Penthrane ® (methoxyflurane) has been reported to result in fatal renal toxicity. Concurrent use of tetracycline may render oral contraceptives less effective. Drug/Laboratory Test Interactions False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals to evaluate carcinogenic potential of doxycycline have not been conducted. However, there has been evidence of oncogenic activity in rats in studies with the related antibacterial drugs, oxytetracycline (adrenal and pituitary tumors), and minocycline (thyroid tumors). Likewise, although mutagenicity studies of doxycycline have not been conducted, positive results in in vitro mammalian cell assays have been reported for related antibacterial drugs (tetracycline, oxytetracycline). Doxycycline administered orally at dosage levels as high as 250 mg/kg/day had no apparent effect on the fertility of female rats. Effect on male fertility has not been studied. Pregnancy : Teratogenic Effects. There are no adequate and well-controlled studies on the use of doxycycline in pregnant women. The vast majority of reported experience with doxycycline during human pregnancy is short-term, first trimester exposure. There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women, such as that proposed for treatment of anthrax exposure. An expert review of published data on experiences with doxycycline use during pregnancy by TERIS – the Teratogen Information System – concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (the quantity and quality of data were assessed as limited to fair), but the data are insufficient to state that there is no risk. 1 A case-control study (18,515 mothers of infants with congenital anomalies and 32,804 mothers of infants with no congenital anomalies) shows a weak but marginally statistically significant association with total malformations and use of doxycycline anytime during pregnancy. Sixty-three (0.19%) of the controls and fifty-six (0.30%) of the cases were treated with doxycycline. This association was not seen when the analysis was confined to maternal treatment during the period of organogenesis (i.e., in the second and third months of gestation) with the exception of a marginal relationship with neural tube defect based on only two exposed cases. 2 A small prospective study of 81 pregnancies describes 43 pregnant women treated for 10 days with doxycycline during early first trimester. All mothers reported their exposed infants were normal at 1 year of age. 3 Nonteratogenic Effects: (See WARNINGS .) Labor and Delivery The effect of tetracyclines on labor and delivery is unknown. Nursing Mothers Tetracyclines are excreted in human milk; however, the extent of absorption of tetracyclines, including doxycycline, by the breastfed infant is not known. Short-term use by lactating women is not necessarily contraindicated; however, the effects of prolonged exposure to doxycycline in breast milk are unknown. 4 Because of the potential for serious adverse reactions in nursing infants from doxycycline, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. (See WARNINGS . ) Pediatric Use Because of the effects of drugs of the tetracycline-class on tooth development and growth, use doxycycline in pediatric patients 8 years of age or less only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies. (See WARNINGS and DOSAGE AND ADMINISTRATION .)"}', 'information_for_patients': '{"Information For Patients Patients taking doxycycline for malaria prophylaxis should be advised: - that no present-day antimalarial agent, including doxycycline, guarantees protection against malaria. - to avoid being bitten by mosquitoes by using personal protective measures that help avoid contact with mosquitoes, especially from dusk to dawn (e.g., staying in well-screened areas, using mosquito nets, covering the body with clothing, and using an effective insect repellent). - that doxycycline prophylaxis: - should begin 1 to 2 days before travel to the malarious area, - should be continued daily while in the malarious area and after leaving the malarious area, - should be continued for 4 further weeks to avoid development of malaria after returning from an endemic area, - should not exceed 4 months. All patients taking doxycycline should be advised: - to avoid excessive sunlight or artificial ultraviolet light while receiving doxycycline and to discontinue therapy if phototoxicity (e.g., skin eruption, etc.) occurs. Sunscreen or sunblock should be considered. (See WARNINGS . ) - to drink fluids liberally along with doxycycline to reduce the risk of esophageal irritation and ulceration. (See ADVERSE REACTIONS . ) - that the absorption of tetracyclines is reduced when taken with foods, especially those which contain calcium. However, the absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk. (See DRUG INTERACTIONS .) - that the absorption of tetracyclines is reduced when taking bismuth subsalicylate. (See DRUG INTERACTIONS .) - that the use of doxycycline might increase the incidence of vaginal candidiasis. Patients should be counseled that antibacterial drugs, including doxycycline hyclate should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When doxycycline hyclate is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by doxycycline hyclate or other antibacterial drugs in the future. Diarrhea is a common problem caused by antibacterial drugs, which usually ends when the antibacterials are discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible."}', 'pregnancy': '{"Pregnancy : Teratogenic Effects. There are no adequate and well-controlled studies on the use of doxycycline in pregnant women. The vast majority of reported experience with doxycycline during human pregnancy is short-term, first trimester exposure. There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women, such as that proposed for treatment of anthrax exposure. An expert review of published data on experiences with doxycycline use during pregnancy by TERIS – the Teratogen Information System – concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (the quantity and quality of data were assessed as limited to fair), but the data are insufficient to state that there is no risk. 1 A case-control study (18,515 mothers of infants with congenital anomalies and 32,804 mothers of infants with no congenital anomalies) shows a weak but marginally statistically significant association with total malformations and use of doxycycline anytime during pregnancy. Sixty-three (0.19%) of the controls and fifty-six (0.30%) of the cases were treated with doxycycline. This association was not seen when the analysis was confined to maternal treatment during the period of organogenesis (i.e., in the second and third months of gestation) with the exception of a marginal relationship with neural tube defect based on only two exposed cases. 2 A small prospective study of 81 pregnancies describes 43 pregnant women treated for 10 days with doxycycline during early first trimester. All mothers reported their exposed infants were normal at 1 year of age. 3 Nonteratogenic Effects: (See WARNINGS .)"}', 'pediatric_use': '{"Pediatric Use Because of the effects of drugs of the tetracycline-class on tooth development and growth, use doxycycline in pediatric patients 8 years of age or less only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies. (See WARNINGS and DOSAGE AND ADMINISTRATION .)"}', 'geriatric_use': None}

{PETROLATUM}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use helps treat and prevent diaper rash protects chafed skin due to diaper rash helps seal out wetness"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"WHITE PETROLATUM"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if condition worsens systems last longer than 7 days or clear up and occur again within a few days"}', 'do_not_use': '{"Do not use on deep or puncture wounds animal bites serious burns"}', 'when_using': '{"When using this product do not get into eyes"}', 'warnings': '{"Warnings For external use only"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"ESOMEPRAZOLE MAGNESIUM DIHYDRATE"}

{'contraindications': '{"4 CONTRAINDICATIONS Esomeprazole magnesium is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions ( 5.2 ), Adverse Reactions ( 6.2 )]. For information about contraindications of amoxicillin and clarithromycin, indicated in combination with esomeprazole magnesium for H. pylori eradication to reduce the risk of duodenal ulcer recurrence, refer to the Contraindications section of the respective prescribing information. Proton pump inhibitors (PPIs), including esomeprazole magnesium, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions ( 7 )]. Known hypersensitivity to substituted benzimidazoles or any component of the formulation. ( 4 ) Patients receiving rilpivirine-containing products. ( 4 , 7 ) Refer to the Contraindications section of the prescribing information for amoxicillin and clarithromycin, when administered in combination with esomeprazole magnesium. ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in labeling: Acute Tubulointerstitial Nephritis [see Warnings and Precautions ( 5.2 )] Clostridium difficile -Associated Diarrhea [see Warnings and Precautions ( 5.3 )] Bone Fracture [see Warnings and Precautions ( 5.4 )] Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5.5 )] Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions ( 5.6 )] Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions ( 5.8 )] Hypomagnesemia and Mineral Metabolism [see Warnings and Precautions ( 5.9 )] Fundic Gland Polyps [see Warnings and Precautions ( 5.13 )] Most common adverse reactions ( 6.1 ): Adults (≥ 18 years) (≥ 1%) are: headache, diarrhea, nausea, flatulence, abdominal pain, constipation, and dry mouth. Pediatrics (1 year to 17 years) (≥ 2%) are: headache, diarrhea, abdominal pain, nausea, and somnolence. To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults The safety of esomeprazole magnesium delayed-release capsules was evaluated in over 15,000 patients (aged 18 years to 84 years) in clinical trials worldwide including over 8,500 patients in the United States and over 6,500 patients in Europe and Canada. Over 2,900 patients were treated in long-term studies for up to 6 months to 12 months. The safety in the treatment of healing of EE in adults was assessed in four randomized comparative clinical trials, which included 1,240 patients on esomeprazole magnesium 20 mg, 2,434 patients on esomeprazole magnesium 40 mg, and 3,008 patients on omeprazole 20 mg once daily. The most frequently occurring adverse reactions (at least 1%) in all three groups were headache (5.5%, 5%, and 3.8%, respectively) and diarrhea (no difference among the three groups). Nausea, flatulence, abdominal pain, constipation, and dry mouth occurred at similar rates among patients taking esomeprazole magnesium or omeprazole. Less common adverse reactions with an incidence of less than 1% are listed below by body system: Body as a Whole Abdomen enlarged, allergic reaction, asthenia, back pain, chest pain, substernal chest pain, facial edema, peripheral edema, hot flushes, fatigue, fever, flu-like disorder, generalized edema, leg edema, malaise, pain, rigors; Cardiovascular Flushing, hypertension, tachycardia; Endocrine Goiter; Gastrointestinal Bowel irregularity, constipation aggravated, dyspepsia, dysphagia, dysplasia GI, epigastric pain, eructation, esophageal disorder, frequent stools, gastroenteritis, GI hemorrhage, GI symptoms not otherwise specified, hiccup, melena, mouth disorder, pharynx disorder, rectal disorder, serum gastrin increased, tongue disorder, tongue edema, ulcerative stomatitis, vomiting; Hearing Earache, tinnitus; Hematologic Anemia, anemia hypochromic, cervical lymphadenopathy, epistaxis, leukocytosis, leukopenia, thrombocytopenia; Hepatic Bilirubinemia, hepatic function abnormal, SGOT increased, SGPT increased; Metabolic/Nutritional Glycosuria, hyperuricemia, hyponatremia, increased alkaline phosphatase, thirst, vitamin B12 deficiency, weight increase, weight decrease; Musculoskeletal Arthralgia, arthritis aggravated, arthropathy, cramps, fibromyalgia syndrome, hernia, polymyalgia rheumatica; Nervous System/Psychiatric Anorexia, apathy, appetite increased, confusion, depression aggravated, dizziness, hypertonia, nervousness, hypoesthesia, impotence, insomnia, migraine, migraine aggravated, paresthesia, sleep disorder, somnolence, tremor, vertigo, visual field defect; Reproductive Dysmenorrhea, menstrual disorder, vaginitis; Respiratory Asthma aggravated, coughing, dyspnea, larynx edema, pharyngitis, rhinitis, sinusitis; Skin and Appendages Acne, angioedema, dermatitis, pruritus, pruritus ani, rash, rash erythematous, rash maculo-papular, skin inflammation, sweating increased, urticaria; Special Senses Otitis media, parosmia, taste loss, taste perversion; Urogenital Abnormal urine, albuminuria, cystitis, dysuria, fungal infection, hematuria, micturition frequency, moniliasis, genital moniliasis, polyuria; Visual Conjunctivitis, vision abnormal. The following potentially clinically significant laboratory changes in clinical trials, irrespective of relationship to esomeprazole magnesium, were reported in 1% or less of patients: increased creatinine, uric acid, total bilirubin, alkaline phosphatase, ALT, AST, hemoglobin, white blood cell count, platelets, serum gastrin, potassium, sodium, thyroxine and thyroid stimulating hormone [see Clinical Pharmacology ( 12 )]. Decreases were seen in hemoglobin, white blood cell count, platelets, potassium, sodium, and thyroxine. Endoscopic findings that were reported as adverse reactions include: duodenitis, esophagitis, esophageal stricture, esophageal ulceration, esophageal varices, gastric ulcer, gastritis, hernia, benign polyps or nodules, Barrett\'s esophagus, and mucosal discoloration. The incidence of adverse reactions during 6-month trials for the maintenance of healing of EE with esomeprazole magnesium 20 mg once daily was similar to placebo. There were no differences in types of adverse reactions seen during maintenance treatment up to 12 months compared to short-term treatment. Two placebo-controlled studies were conducted in 710 adults patients for the treatment of symptomatic GERD. adverse reactions that were reported were: diarrhea (4%), headache (4%), and abdominal pain (4%). Combination Treatment with Esomeprazole Magnesium, Amoxicillin and Clarithromycin In clinical trials of H. pylori eradication of to reduce duodenal ulcer recurrence, no additional adverse reactions specific to the combination of esomeprazole magnesium delayed-release capsules, amoxicillin and clarithromycin were observed and were similar to those observed with esomeprazole magnesium, amoxicillin, or clarithromycin alone. The most frequently reported adverse reactions for patients who received esomeprazole magnesiu, amoxicillin and clarithromycin for 10 days were diarrhea (9%), taste perversion (4%), and abdominal pain (4%). No adverse reactions were observed at higher rates with esomeprazole magnesium, amoxicillin and clarithromycin than were observed with esomeprazole magnesium alone. In clinical trials using of esomeprazole magnesium, amoxicillin and clarithromycin, no additional increased laboratory abnormalities particular to these drug combinations were observed. For more information on adverse reactions and laboratory changes with amoxicillin or clarithromycin, refer to Adverse Reactions section of the respective prescribing information. Pediatrics 1 Year to 17 Years of Age The safety of esomeprazole magnesium delayed-release capsules was evaluated in 316 pediatric and adolescent patients aged 1 year to 17 years in four clinical trials for the treatment of symptomatic GERD [see Clinical Studies ( 14.3 )]. In 109 pediatric patients aged 1 year to 11 years, the most frequently reported (at least 1%) treatment-related adverse reactions in these patients were diarrhea (3%), headache (2%) and somnolence (2%). In 149 pediatric patients aged 12 years to 17 years the most frequently reported adverse reactions (at least 2%) were headache (8%), abdominal pain (3%), diarrhea (2%), and nausea (2%). 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of esomeprazole magnesium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reports are listed below by body system: Blood and Lymphatic Agranulocytosis, pancytopenia; Eye Blurred vision; Gastrointestinal Pancreatitis; stomatitis; microscopic colitis; fundic gland polyps; Hepatobiliary Hepatic failure, hepatitis with or without jaundice; Immune System Anaphylactic reaction/shock; systemic lupus erythematosus; Infections and Infestations GI candidiasis; Clostridium difficile- associated diarrhea; Metabolism and nutritional disorders Hypomagnesemia (may lead to hypocalcemia and/or hypokalemia) [see Warnings and Precautions ( 5.9 )] Musculoskeletal and Connective Tissue Muscular weakness, myalgia, bone fracture; Nervous System Hepatic encephalopathy, taste disturbance; Psychiatric Aggression, agitation, depression, hallucination; Renal and Urinary Interstitial nephritis; Reproductive System and Breast Gynecomastia, erectile dysfunction; Respiratory, Thoracic, and Mediastinal Bronchospasm; Skin and Subcutaneous Tissue Alopecia, erythema multiforme, hyperhidrosis, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), cutaneous lupus erythematosus. Adverse reactions associated with omeprazole may also be expected to occur with esomeprazole. See the full prescribing information for omeprazole for complete safety information."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Tables 3 and 4 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with esomeprazole and instructions for preventing or managing them. Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs. Table 3 Clinically Relevant Interactions Affecting Drugs Co-Administered with Esomeprazole and Interaction with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with esomeprazole may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology ( 12.3 )]. Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with esomeprazole may increase toxicity [see Clinical Pharmacology ( 12.3 )]. There are other antiretroviral drugs which do not result in clinically relevant interactions with esomeprazole. Intervention: Rilpivirine-containing products: Concomitant use with esomeprazole magnesium is contraindicated [see Contraindications ( 4 )] . Atazanavir: See prescribing information for atazanavir for dosing information. Nelfinavir: Avoid concomitant use with esomeprazole magnesium. See prescribing information for nelfinavir. Saquinavir: See the prescribing information for saquinavir for monitoring of potential saquinavir-related toxicities. Other antiretrovirals: See prescribing information for specific antiretroviral drugs Warfarin Clinical Impact: Increased INR and prothrombin time in patients receiving PPIs, including esomeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Intervention: Monitor INR and prothrombin time and adjust the dose of warfarin, if needed, to maintain the target INR range. Methotrexate Clinical Impact: Concomitant use of esomeprazole with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [see Warnings and Precautions ( 5.12 )]. Intervention: A temporary withdrawal of esomeprazole magnesium may be considered in some patients receiving high-dose methotrexate. 2C19 Substrates (e.g., clopidogrel, citalopram, cilostazol) Clopidogrel Clinical Impact: Concomitant use of esomeprazole 40 mg resulted in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition [see Clinical Pharmacology ( 12.3 )]. There are no adequate combination studies of a lower dose of esomeprazole or a higher dose of clopidogrel in comparison with the approved dose of clopidogrel . Intervention: Avoid concomitant use with esomeprazole magnesium. Consider use of alternative anti-platelet therapy [see Warnings and Precautions ( 5.7 )]. Citalopram Clinical Impact: Increased exposure of citalopram leading to an increased risk of QT prolongation [see Clinical Pharmacology ( 12.3 )]. Intervention: Limit the dose of citalopram to a maximum of 20 mg per day. See prescribing information for citalopram. Cilostazol Clinical Impact: Increased exposure of cilostazol and one of its active metabolites (3,4-dihydro-cilostazol) [see Clinical Pharmacology ( 12.3 )]. Intervention: Consider reducing the dose of cilostazol to 50 mg twice daily. See prescribing information for cilostazol. Digoxin Clinical Impact: Potential for increased exposure of digoxin [see Clinical Pharmacology ( 12.3 )]. Intervention: Monitor digoxin concentrations and adjust the dose, if needed, to maintain therapeutic drug concentrations. See prescribing information for digoxin. Combination Therapy with Clarithromycin and Amoxicillin Clinical Impact: Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated. Amoxicillin also has drug interactions. Intervention: See Contraindications, Warnings and Precautions in prescribing information for clarithromycin. See Drug Interactions in prescribing information for amoxicillin. Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Impact: Esomeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity Intervention: Mycophenolate mofetil (MMF): Co-administration of omeprazole, of which esomeprazole is an enantiomer, in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving esomeprazole magnesium and MMF. Use esomeprazole magnesium with caution in transplant patients receiving MMF [see Clinical Pharmacology ( 12.3 )] . See the prescribing information for other drugs dependent on gastric pH for absorption. Tacrolimus Clinical Impact: Potentially increased exposure of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19 . Intervention: Monitor tacrolimus whole blood concentrations and consider reducing the dose, if needed, to maintain therapeutic drug concentrations. See prescribing information for tacrolimus. Interactions with Investigations of Neuroendocrine Tumors Clinical Impact: Serum chromogranin A (CgA) levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors [see Warnings and Precautions ( 5.11 ), Clinical Pharmacology ( 12.2 )]. Intervention: Discontinue esomeprazole magnesium at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary. Interaction with Secretin Stimulation Test Clinical Impact: Hyper-response in gastrin secretion in response to secretin stimulation test, falsely suggesting gastrinoma. Intervention: Discontinue esomeprazole magnesium 4 weeks prior to testing [see Clinical Pharmacology ( 12.2 )] False Positive Urine Tests for THC Clinical Impact: There have been reports of false positive urine screening test for tetrahydrocannabinol (THC) in patients receiving PPIs. Intervention: An alternative confirmatory method should be considered to verify positive results. Table 4 Clinically Relevant Interactions Affecting Esomeprazole When Co-Administered with Other Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact: Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology ( 12.3 )]. Intervention: St. John\'s Wort, rifampin: Avoid concomitant use with [see Warnings and Precautions ( 5.10 )]. Ritonavir-containing products: see prescribing information for specific drugs Voriconazole Clinical Impact: Increased exposure of esomeprazole [see Clinical Pharmacology ( 12.3 )]. Intervention: Dose adjustment of esomeprazole magnesium is not normally required. However, in patients with Zollinger-Ellison syndrome, who may require higher doses, dosage adjustment may be considered. See prescribing information for voriconazole. See full prescribing information for a list of clinically important drug interactions. ( 7 )"}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Esomeprazole magnesium delayed-release capsules are proton pump inhibitor (PPI). Esomeprazole magnesium delayed-release capsules are indicated for the: Short-term treatment in the healing of erosive esophagitis (EE) in adults and pediatric patients 12 years to 17 years of age. ( 1.1 ) Maintenance of healing of EE in adults. ( 1.2 ) Short-term treatment of heartburn and other symptoms associated GERD in adults and pediatric patients 12 years to 17 years of age. ( 1.3 ) Risk reduction of nonsteroidal anti-inflammatory drugs (NSAID)-associated gastric ulcer in adults at risk for developing gastric ulcers due to age (60 years and older) and/or documented history of gastric ulcers. ( 1.4 ) Helicobacter pylori eradication in adult patients to reduce the risk of duodenal ulcer recurrence in combination with amoxicillin and clarithromycin. ( 1.5 ) Long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome in adults. ( 1.6 ) 1.1 Healing of Erosive Esophagitis (EE) Adults Esomeprazole magnesium delayed-release capsules are indicated for the short-term treatment (4 weeks to 8 weeks) in the healing and symptomatic resolution of diagnostically confirmed EE in adults. For those patients who have not healed after 4 to 8 weeks of treatment, an additional 4 week to 8 week course of esomeprazole magnesium delayed-release capsules may be considered. Pediatric Patients 12 Years to 17 Years of Age Esomeprazole magnesium delayed-release capsules are indicated for the short-term treatment (4 weeks to 8 weeks) for the healing of EE in pediatric patients 12 years to 17 years of age. 1.2 Maintenance of Healing of EE Esomeprazole magnesium delayed-release capsules are indicated for the maintenance of healing of EE in adults. Controlled studies do not extend beyond 6 months. 1.3 Treatment of Symptomatic GERD Adults Esomeprazole magnesium delayed-release capsules are indicated for short-term treatment (4 weeks to 8 weeks) of heartburn and other symptoms associated with GERD in adults. Pediatric Patients 12 Years to 17 Years of Age Esomeprazole magnesium delayed-release capsules are indicated for short-term treatment (4 weeks) of heartburn and other symptoms associated with GERD in pediatric patients 12 years to 17 years of age. 1.4 Risk Reduction of Nonsteroidal Anti-Inflammatory Drugs (NSAID) Associated Gastric Ulcer Esomeprazole magnesium delayed-release capsules are indicated for the reduction in the occurrence of gastric ulcers associated with continuous NSAID therapy in adult patients at risk for developing gastric ulcers. Patients are considered to be at risk due to their age (60 years and older) and/or documented history of gastric ulcers. Controlled studies do not extend beyond 6 months. 1.5 Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. Triple Therapy Esomeprazole magnesium delayed-release capsules in combination with amoxicillin and clarithromycin is indicated for the treatment of adult patients with H. pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori . In patients who fail therapy, susceptibility testing should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted [see Clinical Pharmacology ( 12.4 ) and the prescribing information for clarithromycin]. 1.6 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome Esomeprazole magnesium delayed-release capsules are indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison Syndrome, in adults."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Gastric Malignancy: In adults, symptomatic response does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing. ( 5.1 ) Acute Tubulointerstitial Nephritis: Discontinue treatment and evaluate patients. ( 5.2 ) Clostridium difficile -Associated Diarrhea: PPI therapy may be associated with increased risk. ( 5.3 )\uf020 Bone Fracture: Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. ( 5.4 ) Severe Cutaneous Adverse Reactions: Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. ( 5.5 ) Cutaneous and Systemic Lupus Erythematosus: Mostly cutaneous; new onset or exacerbation of existing disease; discontinue esomeprazole magnesium and refer to specialist for evaluation. ( 5.6 ) Interaction with Clopidogrel: Avoid concomitant use of esomeprazole magnesium. ( 5.7 ) Cyanocobalamin (Vitamin B-12) Deficiency: Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin. ( 5.8 ) Hypomagnesemia and Mineral Metabolism: Reported rarely with prolonged treatment with PPIs. ( 5.9 ) Interaction with St. John\'s Wort or Rifampin: Avoid concomitant use of esomeprazole. 5.10 , 7.3 ) Interactions with Diagnostic Investigations for Neuroendocrine Tumors: Increased chromogranin A (CgA) levels may interfere with diagnostic investigations for neuroendocrine tumors, temporarily stop esomeprazole at least 14 days before assessing CgA levels. ( 5.11 , 12.2 ) Interaction with Methotrexate: Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. With high dose methotrexate administration, consider temporary withdrawal of esomeprazole. ( 5.12 , 7 ) Fundic Gland Polyps: Risk increases with long-term use, especially beyond one year. Use the shortest duration of therapy. ( 5.13 ) 5.1 Presence of Gastric Malignancy In adults, symptomatic response to therapy with esomeprazole magnesium does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy. 5.2 Acute Tubulointerstitial Nephritis Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to nonspecific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue esomeprazole magnesium delayed-release capsules and evaluate patients with suspected acute TIN [see Contraindications ( 4 )]. 5.3 Clostridium difficile-Associated Diarrhea Published observational studies suggest that PPI therapy like esomeprazole magnesium may be associated with an increased risk of Clostridium difficile -associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions ( 6.2 )] . Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Clostridium difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with esomeprazole magnesium, refer to Warnings and Precautions section of the corresponding prescribing information. 5.4 Bone Fracture Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration ( 2 ) and Adverse Reactions ( 6.2 )]. 5.5 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs [see Adverse Reactions ( 6.2 )] . Discontinue esomeprazole magnesium at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. 5.6 Cutaneous and Systemic Lupus Erythematosus Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including esomeprazole. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases were CLE. The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement. Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported. Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving esomeprazole magnesium, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g., ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations. 5.7 Interaction with Clopidogrel Avoid concomitant use of esomeprazole magnesium with clopidogrel. Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications, such as esomeprazole, that inhibit CYP2C19 activity. Concomitant use of clopidogrel with 40 mg esomeprazole reduces the pharmacological activity of clopidogrel. When using esomeprazole magnesium consider alternative anti-platelet therapy [see Drug Interactions ( 7 )]. 5.8 Cyanocobalamin (Vitamin B-12) Deficiency Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed. 5.9 Hypomagnesemia and Mineral Metabolism Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions ( 6.2 )]. Consider monitoring magnesium and calcium levels prior to initiation of esomeprazole magnesium and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium, as necessary. If hypocalcemia is refractory to treatment, consider discontinuing the PPI. 5.10 Interaction with St. John’s Wort or Rifampin Drugs which induce CYP2C19 or CYP3A4 (such as St. John\'s Wort or rifampin) can substantially decrease esomeprazole concentrations [see Drug Interactions ( 7 )] . Avoid concomitant use of esomeprazole magnesium with St. John\'s Wort or rifampin. 5.11 Interactions with Diagnostic Investigations for Neuroendocrine Tumors Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop esomeprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary [see Clinical Pharmacology ( 12.2 )] . 5.12 Interaction with Methotrexate Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions ( 7 )] . 5.13 Fundic Gland Polyps PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated."}', 'overdosage': '{"10 OVERDOSAGE Manifestations in patients exposed to omeprazole, the racemic mixture, at doses up to 2,400 mg (120 times the usual recommended clinical dose) include confusion, drowsiness, blurred vision, tachycardia, nausea, diaphoresis, flushing, headache, dry mouth, and other adverse reactions similar to those seen at recommended dosages. See the full prescribing information for omeprazole for complete safety information. No specific antidote for esomeprazole is known. Since esomeprazole is extensively protein bound, it is not expected to be removed by dialysis. In the event of overdosage, treatment should be symptomatic and supportive. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage."}', 'active_flag': 'Y', 'generic_name': '{"ESOMEPRAZOLE MAGNESIUM"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Acute Tubulointerstitial Nephritis Advise the patient or caregiver to call the patient\'s healthcare provider immediately if they experience signs and/or symptoms associated with suspected acute TIN [see Warnings and Precautions ( 5.2 )]. Clostridium difficile-Associated Diarrhea Advise the patient or caregiver to immediately call the patient\'s healthcare provider if they experience diarrhea that does not improve [see Warnings and Precautions ( 5.3 )]. Bone Fracture Advise the patient or caregiver to report any fractures, especially of the hip, wrist or spine, to the patient\'s healthcare provider [see Warnings and Precautions ( 5.4 )]. Severe Cutaneous Adverse Reactions Advise the patient or caregiver to discontinue esomeprazole magnesium delayed-release capsules and immediately call the patient\'s healthcare provider for at first appearance of a severe cutaneous adverse reaction or other sign of hypersensitivity signs or symptoms associated with Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5.5 )] Cutaneous and Systemic Lupus Erythematosus Advise the patient or caregiver to immediately call the patient\'s healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus [see Warnings and Precautions ( 5.6 )]. Cyanocobalamin (Vitamin B-12) Deficiency Advise the patient or caregiver to report any clinical symptoms that may be associated with cyanocobalamin deficiency to the patient\'s healthcare provider if they have been receiving esomeprazole magnesium for longer than 3 years [see Warnings and Precautions ( 5.8 )]. Hypomagnesemia and Mineral Metabolism Advise the patient or caregiver to report any clinical symptoms that may be associated with hypomagnesemia, hypocalcemia, and/or hypokalemia to the patient\'s healthcare provider, if they have been receiving esomeprazole magnesium for at least 3 months [see Warnings and Precautions ( 5.9 )]. Drug Interactions Advise the patient or caregiver to report to their healthcare provider if starting treatment with rilpivirine-containing products, clopidogrel, St. John\'s Wort or rifampin; or, if they take high-dose methotrexate [see Contraindications ( 4 ), Warnings and Precautions ( 5.7 , 5.10 , 5.12 )]. Administration Take esomeprazole magnesium delayed-release capsules at least one hour before meals. Antacids may be used concomitantly with esomeprazole magnesium. Swallow esomeprazole magnesium delayed-release capsules whole; do not chew or crush the capsules. For patients who have difficulty swallowing capsules, esomeprazole magnesium delayed-release capsules can be opened, and the contents sprinkled on applesauce. Use with other foods is not recommended. Add one tablespoon of applesauce to an empty bowl. The applesauce used should not be hot and should be soft enough to be swallowed without chewing. Open the esomeprazole magnesium delayed-release capsule and carefully empty the granules inside the capsule onto the applesauce. Mix the granules with the applesauce. Administer the mixture immediately. Do not chew or crush the granules Discard any remaining mixture. Do not store the mixture for future use. Esomeprazole magnesium delayed-release capsules can also be administered via a nasogastric tube, as described in the Instructions for Use. Medication Guide available at www.zydususa.com/medguides or call 1-877-993-8779."}', 'pregnancy': '{"8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies with esomeprazole in pregnant women. Esomeprazole is the S-isomer of omeprazole. Available epidemiologic data fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use (see Data) . Reproduction studies in rats and rabbits resulted in dose-dependent embryo-lethality at omeprazole doses that were approximately 3.4 to 34 times an oral human dose of 40 mg (based on a body surface area for a 60 kg person). Teratogenicity was not observed in animal reproduction studies with administration of oral esomeprazole magnesium in rats and rabbits with doses about 68 times and 42 times, respectively, an oral human dose of 40 mg (based on a body surface area basis for a 60 kg person). Changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg. When maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age (see Data). The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Esomeprazole is the S-isomer of omeprazole. Four epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with the frequency of abnormalities among infants of women exposed to H 2 -receptor antagonists or other controls. A population-based retrospective cohort epidemiological study from the Swedish Medical Birth Registry, covering approximately 99% of pregnancies, from 1995 to 1999, reported on 955 infants (824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131 exposed after the first trimester) whose mothers used omeprazole during pregnancy. The number of infants exposed in utero to omeprazole that had any malformation, low birth weight, low Apgar score, or hospitalization was similar to the number observed in this population. The number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed infants than the expected number in this population. A population-based retrospective cohort study covering all live births in Denmark from 1996 to 2009, reported on 1,800 live births whose mothers used omeprazole during the first trimester of pregnancy and 837,317 live births whose mothers did not use any proton pump inhibitor. The overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole was 2.9% and 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. A retrospective cohort study reported on 689 pregnant women exposed to either H 2 -blockers or omeprazole in the first trimester (134 exposed to omeprazole) and 1,572 pregnant women unexposed to either during the first trimester. The overall malformation rate in offspring born to mothers with first trimester exposure to omeprazole, an H 2 -blocker, or were unexposed was 3.6%, 5.5%, and 4.1% respectively. A small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy (89% with first trimester exposures). The reported rate of major congenital malformations was 4% in the omeprazole group, 2% in controls exposed to non-teratogens, and 2.8% in disease paired controls. Rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight were similar among the groups. Several studies have reported no apparent adverse short-term effects on the infant when single dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. Animal Data Omeprazole Reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) and in rabbits at doses up to 69.1 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) during organogenesis did not disclose any evidence for a teratogenic potential of omeprazole. In rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis) administered during organogenesis produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. In rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at 13.8 to 138.0 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis), administered prior to mating through the lactation period. Esomeprazole No effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats at oral doses up to 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) or in rabbits at oral doses up to 86 mg/kg/day (about 41 times an oral human dose of 40 mg on a body surface area basis) administered during organogenesis. A pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with esomeprazole magnesium at oral doses of 14 to 280 mg/kg/day (about 3.4 to 68 times an oral human dose of 40 mg on a body surface area basis). Neonatal/early postnatal (birth to weaning) survival was decreased at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis). Body weight and body weight gain were reduced and neurobehavioral or general developmental delays in the immediate post-weaning timeframe were evident at doses equal to or greater than 69 mg/kg/day (about 17 times an oral human dose of 40 mg on a body surface area basis). In addition, decreased femur length, width and thickness of cortical bone, decreased thickness of the tibial growth plate and minimal to mild bone marrow hypocellularity were noted at doses equal to or greater than 14 mg/kg/day (about 3.4 times an oral human dose of 40 mg on a body surface area basis). Physeal dysplasia in the femur was observed in offspring of rats treated with oral doses of esomeprazole magnesium at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis). Effects on maternal bone were observed in pregnant and lactating rats in a pre- and postnatal toxicity study when esomeprazole magnesium was administered at oral doses of 14 to 280 mg/kg/day (about 3.4 to 68 times an oral human dose of 40 mg on a body surface area basis). When rats were dosed from gestational day 7 through weaning on postnatal day 21, a statistically significant decrease in maternal femur weight of up to 14% (as compared to placebo treatment) was observed at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis). A pre- and postnatal development study in rats with esomeprazole strontium (using equimolar doses compared to esomeprazole magnesium study) produced similar results in dams and pups as described above. A follow up developmental toxicity study in rats with further time points to evaluate pup bone development from postnatal day 2 to adulthood was performed with esomeprazole magnesium at oral doses of 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) where esomeprazole administration was from either gestational day 7 or gestational day 16 until parturition. When maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age."}', 'pediatric_use': '{"8.4 Pediatric Use Healing of EE Pediatric Patients 1 Year to 17 Years of Age The safety and effectiveness of esomeprazole magnesium delayed-release capsules have been established in pediatric patients 12 years to 17 years for short-term treatment (4 weeks to 8 weeks) for healing of EE [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14.4 )] . Symptomatic GERD Pediatric Patients 1 Year to 17 Years of Age The safety and effectiveness of esomeprazole magnesium delayed-release capsules have been established in pediatric patients 12 years to 17 years of age for the short-term treatment (4 weeks) of heartburn and other symptoms associated with GERD [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14.4 )]. Other Conditions The safety and effectiveness of esomeprazole magensium for the risk reduction of NSAID-associated gastric ulcer, H. pylori eradication to reduce the risk of duodenal ulcer recurrence and treatment of pathological hypersecretory conditions have not been established in pediatric patients. Juvenile Animal Toxicity Studies In a juvenile rat toxicity study, esomeprazole was administered with both magnesium and strontium salts at oral doses about 34 to 68 times a daily human dose of 40 mg based on body surface area. Increases in death were seen at the high dose, and at all doses of esomeprazole, there were decreases in body weight, body weight gain, femur weight and femur length, and decreases in overall growth [see Nonclinical Toxicology ( 13.2 )]."}', 'geriatric_use': '{"8.5 Geriatric Use Of the total number of patients who received esomeprazole magnesium in clinical trials, 1,459 were 65 years to 74 years of age and 354 patients were 75 years of age and older. No overall differences in safety and efficacy were observed between the elderly and younger individuals, and other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out."}'}

{"CYCLOBENZAPRINE HYDROCHLORIDE"}

{'contraindications': '{"CONTRAINDICATIONS Hypersensitivity to any component of this product. Concomitant use of monoamine oxidase (MAO) inhibitors or within 14 days after their discontinuation. Hyperpyretic crisis seizures and deaths have occurred in patients receiving cyclobenzaprine (or structurally similar tricyclic antidepressants) concomitantly with MAO inhibitor drugs. Acute recovery phase of myocardial infarction, and patients with arrhythmias, heart block or conduction disturbances, or congestive heart failure. Hyperthyroidism."}', 'adverse_reactions': '{"ADVERSE REACTIONS Incidence of most common adverse reactions in the two double-blind*, placebo-controlled 5 mg studies (incidence of > 3% on cyclobenzaprine hydrochloride 5 mg): Cyclobenzaprine Hydrochloride 5 mg Cyclobenzaprine Hydrochloride 10 mg Placebo N = 464 N = 249 N = 469 Drowsiness 29% 38% 10% Dry Mouth 21% 32% 7% Fatigue 6% 6% 3% Headache 5% 5% 8% *Note: Cyclobenzaprine hydrochloride 10 mg data are from one clinical trial. Cyclobenzaprine hydrochloride 5 mg and placebo data are from two studies. Adverse reactions which were reported in 1% to 3% of the patients were: abdominal pain, acid regurgitation, constipation, diarrhea, dizziness, nausea, irritability, mental acuity decreased, nervousness, upper respiratory infection, and pharyngitis. The following list of adverse reactions is based on the experience in 473 patients treated with cyclobenzaprine hydrochloride 10 mg in additional controlled clinical studies, 7,607 patients in the postmarketing surveillance program, and reports received since the drug was marketed. The overall incidence of adverse reactions among patients in the surveillance program was less than the incidence in the controlled clinical studies. The adverse reactions reported most frequently with cyclobenzaprine were drowsiness, dry mouth and dizziness. The incidence of these common adverse reactions was lower in the surveillance program than in the controlled clinical studies: Clinical Studies with Cyclobenzaprine hydrochloride 10 mg Surveillance Program with Cyclobenzaprine hydrochloride 10 mg Drowsiness 39% 16% Dry Mouth 27% 7% Dizziness 11% 3% Among the less frequent adverse reactions, there was no appreciable difference in incidence in controlled clinical studies or in the surveillance program. Adverse reactions which were reported in 1% to 3% of the patients were: fatigue/tiredness, asthenia, nausea, constipation, dyspepsia, unpleasant taste, blurred vision, headache, nervousness, and confusion. The following adverse reactions have been reported in postmarketing experience or with an incidence of less than 1% of patients in clinical trials with the 10 mg tablet: Body as a Whole: Syncope; malaise. Cardiovascular: Tachycardia; arrhythmia; vasodilatation; palpitation; hypotension. Digestive: Vomiting; anorexia; diarrhea; gastrointestinal pain; gastritis; thirst; flatulence; edema of the tongue; abnormal liver function and rare reports of hepatitis, jaundice and cholestasis. Hypersensitivity: Anaphylaxis; angioedema; pruritus; facial edema; urticaria; rash. Musculoskeletal: Local weakness. Nervous System and Psychiatric: Seizures; ataxia; vertigo; dysarthria; tremors; hypertonia; convulsions; muscle twitching; disorientation; insomnia; depressed mood; abnormal sensations; anxiety; agitation; psychosis; abnormal thinking and dreaming; hallucinations; excitement; paresthesia; diplopia, serotonin syndrome. Skin: Sweating. Special Senses: Ageusia; tinnitus. Urogenital: Urinary frequency and/or retention. Causal Relationship Unknown Other reactions, reported rarely for cyclobenzaprine under circumstances where a causal relationship could not be established or reported for other tricyclic drugs, are listed to serve as alerting information to physicians: Body as a Whole: Chest pain; edema. Cardiovascular: Hypertension; myocardial infarction; heart block; stroke. Digestive: Paralytic ileus; tongue discoloration; stomatitis; parotid swelling. Endocrine: Inappropriate ADH syndrome. Hematic and Lymphatic: Purpura; bone marrow depression; leukopenia; eosinophilia; thrombocytopenia. Metabolic, Nutritional and Immune: Elevation and lowering of blood sugar levels; weight gain or loss. Musculoskeletal: Myalgia. Nervous System and Psychiatric: Decreased or increased libido; abnormal gait; delusions; aggressive behavior; paranoia; peripheral neuropathy; Bell\'s palsy; alteration in EEG patterns; extrapyramidal symptoms. Respiratory: Dyspnea. Skin: Photosensitization; alopecia. Urogenital: Impaired urination; dilatation of urinary tract; impotence; testicular swelling; gynecomastia; breast enlargement; galactorrhea."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE Cyclobenzaprine hydrochloride tablets, USP are indicated as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions. Improvement is manifested by relief of muscle spasm and its associated signs and symptoms, namely, pain, tenderness, limitation of motion, and restriction in activities of daily living. Cyclobenzaprine hydrochloride tablets should be used only for short periods (up to 2 or 3 weeks) because adequate evidence of effectiveness for more prolonged use is not available and because muscle spasm associated with acute, painful musculoskeletal conditions is generally of short duration and specific therapy for longer periods is seldom warranted. Cyclobenzaprine hydrochloride tablets have not been found effective in the treatment of spasticity associated with cerebral or spinal cord disease, or in children with cerebral palsy."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Although rare, deaths may occur from overdosage with cyclobenzaprine. Multiple drug ingestion (including alcohol) is common in deliberate cyclobenzaprine overdose. As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment . Signs and symptoms of toxicity may develop rapidly after cyclobenzaprine overdose; therefore, hospital monitoring is required as soon as possible. The acute oral LD 50 of cyclobenzaprine is approximately 338 and 425 mg/kg in mice and rats, respectively. Manifestations The most common effects associated with cyclobenzaprine overdose are drowsiness and tachycardia. Less frequent manifestations include tremor, agitation, coma, ataxia, hypertension, slurred speech, confusion, dizziness, nausea, vomiting, and hallucinations. Rare but potentially critical manifestations of overdose are cardiac arrest, chest pain, cardiac dysrhythmias, severe hypotension, seizures, and neuroleptic malignant syndrome. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of cyclobenzaprine toxicity. Other potential effects of overdosage include any of the symptoms listed under ADVERSE REACTIONS. Management General As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. In order to protect against the rare but potentially critical manifestations described above, obtain an ECG and immediately initiate cardiac monitoring. Protect the patient\'s airway, establish an intravenous line and initiate gastric decontamination. Observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary. If signs of toxicity occur at any time during this period, extended monitoring is required. Monitoring of plasma drug levels should not guide management of the patient. Dialysis is probably of no value because of low plasma concentrations of the drug. Gastrointestinal Decontamination All patients suspected of an overdose with cyclobenzaprine should receive gastrointestinal decontamination. This should include large volume gastric lavage followed by activated charcoal. If consciousness is impaired, the airway should be secured prior to lavage and emesis is contraindicated. Cardiovascular A maximal limb-lead QRS duration of ≥ 0.10 seconds may be the best indication of the severity of the overdose. Serum alkalinization, to a pH of 7.45 to 7.55, using intravenous sodium bicarbonate and hyperventilation (as needed), should be instituted for patients with dysrhythmias and/or QRS widening. A pH > 7.60 or a pCO 2 < 20 mmHg is undesirable. Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine, bretylium or phenytoin. Type 1A and 1C antiarrhythmics are generally contraindicated (e.g., quinidine, disopyramide, and procainamide). CNS In patients with CNS depression, early intubation is advised because of the potential for abrupt deterioration. Seizures should be controlled with benzodiazepines or, if these are ineffective, other anticonvulsants (e.g., phenobarbital, phenytoin). Physostigmine is not recommended except to treat life-threatening symptoms that have been unresponsive to other therapies, and then only in close consultation with a poison control center. Psychiatric Follow-up Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Psychiatric referral may be appropriate. Pediatric Management The principles of management of child and adult overdosages are similar. It is strongly recommended that the physician contact the local poison control center for specific pediatric treatment."}', 'active_flag': 'Y', 'generic_name': '{"CYCLOBENZAPRINE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Serotonin Syndrome The development of a potentially life-threatening serotonin syndrome has been reported with cyclobenzaprine hydrochloride when used in combination with other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or (MAO) inhibitors. The concomitant use of cyclobenzaprine hydrochloride with MAO inhibitors is contraindicated (see CONTRAINDICATIONS ). Serotonin syndrome symptoms may include mental status changes (e.g., confusion, agitation, hallucinations), autonomic instability (e.g., diaphoresis, tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g., tremor, ataxia, hyperreflexia, clonus, muscle rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Treatment with cyclobenzaprine hydrochloride and any concomitant serotonergic agents should be discontinued immediately if the above reactions occur and supportive symptomatic treatment should be initiated. If concomitant treatment with cyclobenzaprine hydrochloride and other serotonergic drugs is clinically warranted, careful observation is advised, particularly during treatment initiation or dose increases (see PRECAUTIONS: Drug Interactions ). Cyclobenzaprine is closely related to the tricyclic antidepressants, e.g., amitriptyline and imipramine. In short term studies for indications other than muscle spasm associated with acute musculoskeletal conditions, and usually at doses somewhat greater than those recommended for skeletal muscle spasm, some of the more serious central nervous system reactions noted with the tricyclic antidepressants have occurred (see WARNINGS , below, and ADVERSE REACTIONS ). Tricyclic antidepressants have been reported to produce arrhythmias, sinus tachycardia, prolongation of the conduction time leading to myocardial infarction and stroke. Cyclobenzaprine may enhance the effects of alcohol, barbiturates, and other CNS depressants."}', 'precautions': '{"PRECAUTIONS General Because of its atropine-like action, cyclobenzaprine should be used with caution in patients with a history of urinary retention, angle-closure glaucoma, increased intraocular pressure, and in patients taking anticholinergic medication. Impaired Hepatic Function The plasma concentration of cyclobenzaprine is increased in patients with hepatic impairment (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Hepatic Impairment ). These patients are generally more susceptible to drugs with potentially sedating effects, including cyclobenzaprine. Cyclobenzaprine hydrochloride should be used with caution in subjects with mild hepatic impairment starting with a 5 mg dose and titrating slowly upward. Due to the lack of data in subjects with more severe hepatic insufficiency, the use of cyclobenzaprine in subjects with moderate to severe impairment is not recommended. Information for Patients Cyclobenzaprine, especially when used with alcohol or other CNS depressants, may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle. In the elderly, the frequency and severity of adverse events associated with the use of cyclobenzaprine, with or without concomitant medications, is increased. In elderly patients, cyclobenzaprine hydrochloride should be initiated with a 5 mg dose and titrated slowly upward. Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of cyclobenzaprine hydrochloride and other drugs, such as SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, verapamil or MAO inhibitors. Patients should be advised of the signs and symptoms of serotonin syndrome, and be instructed to seek medical care immediately if they experience these symptoms (see WARNINGS and PRECAUTIONS: Drug Interactions ). Drug Interactions Cyclobenzaprine may have life-threatening interactions with MAO inhibitors (see CONTRAINDICATIONS ). Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine hydrochloride and other drugs, such as SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, verapamil or MAO inhibitors. If concomitant treatment with cyclobenzaprine hydrochloride and other serotonergic drugs is clinically warranted, careful observation is advised, particularly during treatment initiation or dose increases (see WARNINGS ). Cyclobenzaprine may enhance the effects of alcohol, barbiturates, and other CNS depressants. Tricyclic antidepressants may block the antihypertensive action of guanethidine and similarly acting compounds. Tricyclic antidepressants may enhance the seizure risk in patients taking tramadol. Carcinogenesis, Mutagenesis, Impairment of Fertility In rats treated with cyclobenzaprine for up to 67 weeks at doses of approximately 5 to 40 times the maximum recommended human dose, pale, sometimes enlarged, livers were noted and there was a dose-related hepatocyte vacuolation with lipidosis. In the higher dose groups this microscopic change was seen after 26 weeks and even earlier in rats which died prior to 26 weeks; at lower doses, the change was not seen until after 26 weeks. Cyclobenzaprine did not affect the onset, incidence or distribution of neoplasia in an 81-week study in the mouse or in a 105-week study in the rat. At oral doses of up to 10 times the human dose, cyclobenzaprine did not adversely affect the reproductive performance or fertility of male or female rats. Cyclobenzaprine did not demonstrate mutagenic activity in the male mouse at dose levels of up to 20 times the human dose. Pregnancy Teratogenic Effects. Pregnancy Category B Reproduction studies have been performed in rats, mice and rabbits at doses up to 20 times the human dose, and have revealed no evidence of impaired fertility or harm to the fetus due to cyclobenzaprine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing Mothers It is not known whether this drug is excreted in human milk. Because cyclobenzaprine is closely related to the tricyclic antidepressants, some of which are known to be excreted in human milk, caution should be exercised when cyclobenzaprine hydrochloride is administered to a nursing woman. Pediatric Use Safety and effectiveness of cyclobenzaprine in pediatric patients below 15 years of age have not been established. Use in the Elderly The plasma concentration of cyclobenzaprine is increased in the elderly (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Elderly ). The elderly may also be more at risk for CNS adverse events such as hallucinations and confusion, cardiac events resulting in falls or other sequelae, drug-drug and drug-disease interactions. For these reasons, in the elderly, cyclobenzaprine should be used only if clearly needed. In such patients cyclobenzaprine hydrochloride should be initiated with a 5 mg dose and titrated slowly upward."}', 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}