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{"TROLAMINE SALICYLATE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses For the temporarily relief of minor aches and pains of muscles and joint associated with: ♦ simple backache ♦ arthritis ♦ strains ♦ bruises ♦ sprains"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"TROLAMINE SALICYLATE"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': '{"When using this product ♦ Avoid contact with eyes ♦ Do not apply to wounds or damaged skin ♦ Do not bandage tightly ♦ Do not use with heating pads or heating devices ♦ If condition worsens, or if the symptoms persist for more than 7 days or clear up and occur again within a few days, discontinue use of this product and consult a doctor ♦ Avoid contact with the eyes and mucous membranes"}', 'warnings': '{"Warnings For external use only Allergy Alert: if prone to allergic reaction from aspirin or salicylates, consult a doctor before use. When using this product ♦ Avoid contact with eyes ♦ Do not apply to wounds or damaged skin ♦ Do not bandage tightly ♦ Do not use with heating pads or heating devices ♦ If condition worsens, or if the symptoms persist for more than 7 days or clear up and occur again within a few days, discontinue use of this product and consult a doctor ♦ Avoid contact with the eyes and mucous membranes If pregnant or breast-feeding, ask a health professional before use. Keep out of reach of children . If swallowed, 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}

{AMOXICILLIN,"CLAVULANATE POTASSIUM"}

{'contraindications': '{"4 CONTRAINDICATIONS History of a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin and clavulanate potassium for oral suspension or to other beta-lactams (e.g., penicillins or cephalosporins). (4) History of cholestatic jaundice/hepatic dysfunction associated with amoxicillin and clavulanate potassium for oral suspension. (4) 4.1 Serious Hypersensitivity Reactions Amoxicillin and clavulanate potassium for oral suspension is contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin, clavulanate or to other beta-lactam antibacterial drugs (e.g., penicillins and cephalosporins). 4.2 Cholestatic Jaundice/Hepatic Dysfunction Amoxicillin and clavulanate potassium for oral suspension is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with amoxicillin and clavulanate potassium for oral suspension."}', '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) ] Hepatic Dysfunction [see Warnings and Precautions (5.2) ] CDAD [see Warnings and Precautions (5.3) ] The most frequently reported adverse effects were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%) and vaginitis (1%). (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 most frequently reported adverse reactions were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%) and vaginitis (1%). Less than 3% of patients discontinued therapy because of drug-related adverse reactions. The overall incidence of adverse reactions, and in particular diarrhea, increased with the higher recommended dose. Other less frequently reported adverse reactions (<1%) include: Abdominal discomfort, flatulence, and headache. In pediatric patients (aged 2 months to 12 years), 1 U.S./Canadian clinical trial was conducted which compared 45/6.4 mg/kg/day (divided every 12 hours) of amoxicillin and clavulanate potassium for oral suspension for 10 days versus 40/10 mg/kg/day (divided every 8 hours) of amoxicillin and clavulanate potassium for oral suspension for 10 days in the treatment of acute otitis media. A total of 575 patients were enrolled, and only the suspension formulations were used in this trial. Overall, the adverse reactions seen were comparable to that noted above; however, there were differences in the rates of diarrhea, skin rashes/urticaria, and diaper area rashes [see Clinical Studies (14.2) ] . 6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following have been identified during postmarketing use of amoxicillin and clavulanate potassium for oral suspension. 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 and clavulanate potassium for oral suspension. Gastrointestinal: Indigestion, gastritis, stomatitis, glossitis, black “hairy” tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment [see Warnings and Precautions (5.3) ] . Hypersensitivity Reactions: Pruritus, angioedema, serum sickness–like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), erythema multiforme, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, hypersensitivity vasculitis, and cases of exfoliative dermatitis (including toxic epidermal necrolysis) have been reported [see Warnings and Precautions (5.1) ] . Liver: Hepatic dysfunction, including hepatitis and cholestatic jaundice, increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been reported with amoxicillin and clavulanate potassium for oral suspension. It has been reported more commonly in the elderly, in males, or in patients on prolonged treatment. The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular, or mixed cholestatic-hepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. Deaths have been reported [see Contraindications (4.2) , Warnings and Precautions (5.2) ] . Renal: Interstitial nephritis, hematuria, and crystalluria have 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. Thrombocytosis was noted in less than 1% of the patients treated with amoxicillin and clavulanate potassium for oral suspension. There have been reports of increased prothrombin time in patients receiving amoxicillin and clavulanate potassium for oral suspension and anticoagulant therapy concomitantly [see Drug Interactions (7.2) ] . Central Nervous System: Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity 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 probenecid is not recommended. (7.1) Concomitant use of amoxicillin and clavulanate potassium for oral suspension and oral anticoagulants may increase the prolongation of prothrombin time. (7.2) Coadministration with allopurinol increases the risk of rash. (7.3) Amoxicillin and clavulanate potassium for oral suspension may reduce efficacy of oral contraceptives. (7.4) 7.1 Probenecid Probenecid decreases the renal tubular secretion of amoxicillin but does not delay renal excretion of clavulanic acid. Concurrent use with amoxicillin and clavulanate potassium for oral suspension may result in increased and prolonged blood concentrations of amoxicillin. Coadministration of probenecid is not recommended. 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 with amoxicillin and clavulanate potassium for oral suspension. 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 amoxicillin rashes is due to allopurinol or the hyperuricemia present in these patients. 7.4 Oral Contraceptives Amoxicillin and clavulanate potassium for oral suspension may affect intestinal flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives. 7.5 Effects on Laboratory Tests High urine concentrations of amoxicillin 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 and clavulanate potassium for oral suspension, it is recommended that glucose tests based on enzymatic glucose oxidase reactions be used. Following administration of 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 To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and clavulanate potassium for oral suspension, USP and other antibacterial drugs, amoxicillin and clavulanate potassium for oral suspension, USP should be used only to treat 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. Amoxicillin and clavulanate potassium for oral suspension, USP is a combination penicillin-class antibacterial and beta-lactamase inhibitor indicated in the treatment of infections due to susceptible isolates of the designated bacteria in the conditions listed below*: Amoxicillin and clavulanate potassium for oral suspension, USP is a combination penicillin-class antibacterial and beta-lactamase inhibitor indicated for treatment of the following: Lower respiratory tract infections (1.1) Acute bacterial otitis media (1.2) Sinusitis (1.3) Skin and skin structure infections (1.4) Urinary tract infections (1.5) 1.1 Lower Respiratory Tract Infections caused by beta-lactamase–producing isolates of Haemophilus influenzae and Moraxella catarrhalis . 1.2 Acute Bacterial Otitis Media caused by beta-lactamase–producing isolates of H. influenzae and M. catarrhalis . 1.3 Sinusitis caused by beta-lactamase–producing isolates of H. influenzae and M. catarrhalis . 1.4 Skin and Skin Structure Infections caused by beta-lactamase–producing isolates of Staphylococcus aureus , Escherichia coli , and Klebsiella species. 1.5 Urinary Tract Infections caused by beta-lactamase–producing isolates of E. coli , Klebsiella species, and Enterobacter species. 1.6 Limitations of Use When susceptibility test results show susceptibility to amoxicillin, indicating no beta-lactamase production, amoxicillin and clavulanate potassium for oral suspension, USP should not be used."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Serious (including fatal) hypersensitivity reactions: Discontinue amoxicillin and clavulanate potassium for oral suspension if a reaction occurs. (5.1) Hepatic dysfunction and cholestatic jaundice: Discontinue if signs/symptoms of hepatitis occur. Monitor liver function tests in patients with hepatic impairment. (5.2) Clostridium difficile -associated diarrhea (CDAD): Evaluate patients if diarrhea occurs. (5.3) Patients with mononucleosis who receive amoxicillin and clavulanate potassium for oral suspension develop skin rash. Avoid amoxicillin and clavulanate potassium for oral suspension use in these patients. (5.4) Overgrowth: The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. (5.5) 5.1 Hypersensitivity Reactions Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials, including amoxicillin and clavulanate potassium for oral suspension. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Before initiating therapy with amoxicillin and clavulanate potassium for oral suspension, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, amoxicillin and clavulanate potassium for oral suspension should be discontinued and appropriate therapy instituted. 5.2 Hepatic Dysfunction Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of amoxicillin and clavulanate potassium for oral suspension. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment. 5.3 Clostridium difficile -Associated Diarrhea (CDAD) Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including amoxicillin and clavulanate potassium for oral suspension, 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 Skin Rash in Patients with Mononucleosis A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, amoxicillin and clavulanate potassium for oral suspension should not be administered to patients with mononucleosis. 5.5 Potential for Microbial Overgrowth The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. If superinfection occurs, amoxicillin and clavulanate potassium should be discontinued and appropriate therapy instituted. 5.6 Phenylketonurics Each 5 mL of the 200 mg/28.5 mg per 5 mL oral suspension contains 4.42 mg phenylalanine and each 5 mL of the 400 mg/57 mg per 5 mL oral suspension contains 6.35 mg phenylalanine. 5.7 Development of Drug-Resistant Bacteria Prescribing amoxicillin and clavulanate potassium for oral suspension in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient, and increases the risk of the development of drug-resistant bacteria."}', 'overdosage': '{"10 OVERDOSAGE In case of overdosage, discontinue medication, 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 1 . Interstitial nephritis resulting in oliguric renal failure has been reported in patients after overdosage with amoxicillin and clavulanate potassium. Crystalluria, in some cases leading to renal failure, has also been reported after amoxicillin and clavulanate potassium overdosage in adult and pediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxicillin and clavulanate potassium 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 and clavulanate potassium. Amoxicillin and clavulanate potassium may be removed from circulation by hemodialysis [see Dosage and Administration (2.3) ] ."}', 'active_flag': 'Y', 'generic_name': '{"AMOXICILLIN AND CLAVULANATE POTASSIUM"}', '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 17.1 Information for Patients Patients should be informed that amoxicillin and clavulanate potassium for oral suspension may be taken every 8 hours or every 12 hours, depending on the dose prescribed. Each dose should be taken with a meal or snack to reduce the possibility of gastrointestinal upset. Patients should be counseled that antibacterial drugs, including amoxicillin and clavulanate potassium for oral suspension, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When amoxicillin and clavulanate potassium 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 and clavulanate potassium for oral suspension or other antibacterial drugs in the future. Counsel patients that diarrhea is a common problem caused by antibacterials, and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, 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. If diarrhea is severe or lasts more than 2 or 3 days, patients should contact their physician. Patients should be advised to keep suspension refrigerated. Shake well before using. When dosing a child with the suspension (liquid) of amoxicillin and clavulanate potassium for oral suspension, use a dosing spoon or medicine dropper. Be sure to rinse the spoon or dropper after each use. Bottles of suspension of amoxicillin and clavulanate potassium for oral suspension 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 medicine. Patients should be aware that amoxicillin and clavulanate potassium for oral suspension contains a penicillin class drug product that can cause allergic reactions in some individuals. CLINITEST is a registered trademark of Miles, Inc."}', 'pregnancy': '{"8.1 Pregnancy Teratogenic Effects: Pregnancy Category B. Reproduction studies performed in pregnant rats and mice given amoxicillin and clavulanate potassium for oral suspension (2:1 ratio formulation of amoxicillin:clavulanate) at oral doses up to 1200 mg/kg/day revealed no evidence of harm to the fetus due to amoxicillin and clavulanate potassium for oral suspension. The amoxicillin doses in rats and mice (based on body surface area) were approximately 4 and 2 times the maximum recommended adult human oral dose (875 mg every 12 hours). For clavulanate, these dose multiples were approximately 9 and 4 times the maximum recommended adult human oral dose (125 mg every 8 hours). 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."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness of amoxicillin and clavulanate potassium powder for oral suspension and chewable tablets have been established in pediatric patients. Use of amoxicillin and clavulanate potassium for oral suspension in pediatric patients is supported by evidence from studies of amoxicillin and clavulanate potassium tablets in adults with additional data from a study of amoxicillin and clavulanate potassium powder for oral suspension in pediatric patients aged 2 months to 12 years with acute otitis media [see Clinical Studies (14.2) ] . Because of incompletely developed renal function in neonates and young infants, the elimination of amoxicillin may be delayed; clavulanate elimination is unaltered in this age group. Dosing of amoxicillin and clavulanate potassium for oral suspension should be modified in pediatric patients aged <12 weeks (<3 months) [see Dosage and Administration (2.2) ] ."}', 'geriatric_use': '{"8.5 Geriatric Use Of the 3,119 patients in an analysis of clinical studies of amoxicillin and clavulanate potassium for oral suspension, 32% were ≥65 years old, and 14% 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, but 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 adverse 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."}'}

{"MEGESTROL ACETATE"}

{'contraindications': '{"CONTRAINDICATIONS History of hypersensitivity to megestrol acetate or any component of the formulation. Known or suspected pregnancy."}', 'adverse_reactions': '{"ADVERSE REACTIONS Clinical Adverse Events: Adverse events which occurred in at least 5% of patients in any arm of the two clinical efficacy trials and the open trial are listed below by treatment group. All patients listed had at least one post baseline visit during the 12 study weeks. These adverse events should be considered by the physician when prescribing megestrol acetate oral suspension. ADVERSE EVENTS% of Patients Reporting Trial 1 (N = 236) Trail 2 (N=87) Open Label Trial Megestrol Acetate mg/day No. of Patients Placebo 0 N=34 100 N=68 400 N=69 800 N=65 Placebo 0 N=38 800 N=49 1200 N=176 Diarrhea 15 13 8 15 8 6 10 Impotence 3 4 6 14 0 4 7 Rash 9 9 4 12 3 2 6 Flatulence 9 0 1 9 3 10 6 Hypertension 0 0 0 8 0 0 4 Asthenia 3 2 3 6 8 4 5 Insomnia 0 3 4 6 0 0 1 Nausea 9 4 0 5 3 4 5 Anemia 6 3 3 5 0 0 0 Fever 3 6 4 5 3 2 1 Libido Decreased 3 4 0 5 0 2 1 Dyspepsia 0 0 3 3 5 4 2 Hyperglycemia 3 0 6 3 0 0 3 Headache 6 10 1 3 3 0 3 Pain 6 0 0 2 5 6 4 Vomiting 9 3 0 2 3 6 4 Pneumonia 6 0 2 2 3 0 1 Urinary Frequency 0 0 1 2 5 2 1 Adverse events which occurred in 1 to 3% of all patients enrolled in the two clinical efficacy trials with at least one follow-up visit during the first 12 weeks of the study are listed below by body system. Adverse events occurring less than 1% are not included. There were no significant differences between incidence of these events in patients treated with megestrol acetate and patients treated with placebo. Body as a Whole - abdominal pain, chest pain, infection, moniliasis and sarcoma Cardiovascular System - cardiomyopathy and palpitation Digestive System - constipation, dry mouth, hepatomegaly, increased salivation and oral moniliasis Hemic and Lymphatic System - leukopenia Metabolic and Nutritional - LDH increased, edema and peripheral edema Nervous System - paresthesia, confusion, convulsion, depression, neuropathy, hypesthesia and abnormal thinking Respiratory System - dyspnea, cough, pharyngitis and lung disorder Skin and Appendages - alopecia, herpes, pruritus, vesiculobullous rash, sweating and skin disorder Special Senses - amblyopia Urogenital System - albuminuria, urinary incontinence, urinary tract infection and gynecomastia Postmarketing - Postmarketing reports associated with megestrol acetate oral suspension include thromboembolic phenomena including thrombophlebitis and pulmonary embolism and glucose intolerance (see WARNINGS and PRECAUTIONS ). To report SUSPECTED ADVERSE REACTIONS, contact Strides Pharma Inc. at 1-877-244-9825 or go to www.strides.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE Megestrol acetate oral suspension, USP is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS)."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE No serious unexpected side effects have resulted from studies involving megestrol acetate oral suspension administered in dosages as high as 1200 mg/day. In post-marketing experience, limited reports of overdose have been received. Signs and symptoms reported in the context of overdose included diarrhea, nausea, abdominal pain, shortness of breath, cough, unsteady gait, listlessness, and chest pain. There is no specific antidote for overdose with megestrol acetate oral suspension. In case of overdose, appropriate supportive measures should be taken. Megestrol acetate has not been tested for dialyzability, however, due to its low solubility it is postulated that dialysis would not be an effective means of treating overdose"}', 'active_flag': 'Y', 'generic_name': '{"MEGESTROL ACETATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Megestrol acetate may cause fetal harm when administered to a pregnant woman. For animal data on fetal effects, (see PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility: Impairment of Fertility ). There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking (receiving) this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant. Megestrol acetate is not intended for prophylactic use to avoid weight loss. (See also PRECAUTIONS: Carcinogenesis, Mutagenesis, and Impairment of Fertility section.) The glucocorticoid activity of megestrol acetate oral suspension has not been fully evaluated. Clinical cases of new onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, and overt Cushing\'s Syndrome have been reported in association with the chronic use of megestrol acetate. In addition, clinical cases of adrenal insufficiency have been observed in patients receiving or being withdrawn from chronic megestrol acetate therapy in the stressed and non-stressed state. Furthermore, adrenocorticotropin (ACTH) stimulation testing has revealedthe frequent occurrence of asymptomatic pituitary-adrenal suppression in patients treated with chronic megestrol acetate therapy. Therefore, the possibility of adrenal insufficiency should be considered in any patient receiving or being withdrawn from chronic megestrol acetate therapy who presents with symptoms and/or signs suggestive of hypoadrenalism (e.g., hypotension, nausea, vomiting, dizziness, or weakness) in either the stressed or non-stressed state. Laboratory evaluation for adrenal insufficiency and consideration of replacement or stress doses of a rapidly acting glucocorticoid are strongly recommended in such patients. Failure to recognize inhibition of the hypothalamic-pituitary-adrenal axis may result in death. Finally, in patients who are receiving or being withdrawn from chronic megestrol acetate therapy, consideration should be given to the use of empiric therapy with stress doses of a rapidly acting glucocorticoid in conditions of stress or serious intercurrent illness (e.g., surgery, infection)."}', 'precautions': '{"PRECAUTIONS General: Therapy with megestrol acetate oral suspension for weight loss should only be instituted after treatable causes of weight loss are sought and addressed. These treatable causes include possible malignancies, systemic infections, gastrointestinal disorders affecting absorption, endocrine disease and renal or psychiatric diseases. Effects on HIV viral replication have not been determined. Use with caution in patients with a history of thromboembolic disease. Use in Diabetics: Exacerbation of pre-existing diabetes with increased insulin requirements has been reported in association with the use of megestrol acetate. Information for Patients: Patients using megestrol acetate should receive the following instructions: This medication is to be used as directed by the physician. Report any adverse reaction experiences while taking this medication. Use contraception while taking this medication if you are a woman capable of becoming pregnant. Notify your physician if you become pregnant while taking this medication. Drug Interactions: Pharmacokinetic studies show that there are no significant alterations in pharmacokinetic parameters of zidovudine or rifabutin to warrant dosage adjustment when megestrol acetate is administered with these drugs. The effects of zidovudine or rifabutin on the pharmacokinetics of megestrol acetate were not studied. Megestrol acetate may interact with warfarin and increase International Normalized Ratio (INR). Closely monitor INR in patients taking megestrol acetate and warfarin. Animal Toxicology: Long-term treatment with megestrol acetate may increase the risk of respiratory infections. A trend toward increased frequency of respiratory infections, decreased lymphocyte counts, and increased neutrophil counts was observed in a two-year chronic toxicity/carcinogenicity study of megestrol acetate conducted in rats. Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis - Data on carcinogenesis were obtained from studies conducted in dogs, monkeys and rats treated with megestrol acetate at doses 53.2, 26.6 and 1.3 times lower than the proposed dose (13.3 mg/kg/day) for humans. No males were used in the dog and monkey studies. In female beagles, megestrol acetate (0.01, 0.1 or 0.25 mg/kg/day) administered for up to 7 years induced both benign and malignant tumors of the breast. In female monkeys, no tumors were found following 10 years of treatment with 0.01, 0.1 or 0.5 mg/kg/day megestrol acetate. Pituitary tumors were observed in female rats treated with 3.9 or 10 mg/kg/day of megestrol acetate for 2 years. The relationship of these tumors in rats and dogs to humans is unknown but should be considered in assessing the risk-to-benefit ratio when prescribing megestrol acetate oral suspension and in surveillance of patients on therapy. (See WARNINGS .) Mutagenesis - No mutagenesis data are currently available. Impairment of Fertility - Perinatal/postnatal (segment III) toxicity studies were performed in rats at doses (0.05 to 12.5 mg/kg) less than that indicated for humans (13.3 mg/kg); in these low dose studies, the reproductive capability of male offspring of megestrol acetate-treated females was impaired. Similar results were obtained in dogs. Pregnant rats treated with megestrol acetate showed a reduction in fetal weight and number of live births, and feminization of male fetuses. No toxicity data are currently available on male reproduction (spermatogenesis). Pregnancy: No adequate animal teratology information is available at clinically relevant doses. (See WARNINGS and PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility: Impairment of Fertility. ) Nursing Mothers: Because of the potential for adverse effects on the newborn, nursing should be discontinued if megestrol acetate oral suspension is required. Use in Women: Breakthrough bleeding was observed in all 10 female patients participating in the clinical trials. Megestrol acetate oral suspension is a progesterone derivative, which may induce vaginal bleeding in women. Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Geriatric Use: Clinical studies of megestrol acetate oral suspension in the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with AIDS did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients. Other reported clinical experience has not identified differences in responses 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 of other drug therapy. Megestrol acetate 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."}', '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': '{"Use(s) 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 60 MG"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask 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 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}

{TRIMETHOPRIM}

{'contraindications': '{"CONTRAINDICATIONS Trimethoprim is contraindicated in individuals hypersensitive to trimethoprim and in those with documented megaloblastic anemia due to folate deficiency."}', 'adverse_reactions': '{"ADVERSE REACTIONS The adverse effects encountered most often with trimethoprim were rash and pruritus. Dermatologic Rash, pruritus, and phototoxic skin eruptions. At the recommended dosage regimens of 100 mg b.i.d. or 200 mg q.d., each for 10 days, the incidence of rash is 2.9% to 6.7%. In clinical studies which employed high doses of trimethoprim, an elevated incidence of rash was noted. These rashes were maculopapular, morbilliform, pruritic, and generally mild to moderate, appearing 7 to 14 days after the initiation of therapy. Hypersensitivity Rare reports of exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell Syndrome), and anaphylaxis have been received. Gastrointestinal Epigastric distress, nausea, vomiting, and glossitis. Elevation of serum transaminase and bilirubin has been noted, but the significance of this finding is unknown. Cholestatic jaundice has been rarely reported. Hematologic Thrombocytopenia, leukopenia, neutropenia, megaloblastic anemia, and methemoglobinemia. Metabolic Hyperkalemia, hyponatremia. Neurologic Aseptic meningitis has been rarely reported. Miscellaneous Fever, and increases in BUN and serum creatinine levels."}', 'drug_interactions': '{"Drug Interactions Trimethoprim may inhibit the hepatic metabolism of phenytoin. Trimethoprim, given at a common clinical dosage, increased the phenytoin half-life by 51% and decreased the phenytoin metabolic clearance rate by 30%. When administering these drugs concurrently, one should be alert for possible excessive phenytoin effect."}', 'indications_and_usage': '{"INDICATIONS & USAGE To reduce the development of drug-resistant bacteria and maintain the effectiveness of trimethoprim tablets, USP and other antibacterial drugs, trimethoprim tablets, USP 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. For the treatment of initial episodes of uncomplicated urinary tract infections due to susceptible strains of the following organisms: Escherichia coli , Proteus mirabilis , Klebsiella pneumoniae , Enterobacter species, and coagulase-negative Staphylococcus species, including S. saprophyticus . Cultures and susceptibility tests should be performed to determine the susceptibility of the bacteria to trimethoprim. Therapy may be initiated prior to obtaining the results of these tests."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Acute Signs of acute overdosage with trimethoprim may appear following ingestion of 1 gram or more of the drug and include nausea, vomiting, dizziness, headaches, mental depression, confusion, and bone marrow depression (see Chronic subsection). Treatment consists of gastric lavage and general supportive measures. Acidification of the urine will increase renal elimination of trimethoprim. Peritoneal dialysis is not effective and hemodialysis only moderately effective in eliminating the drug. Chronic Use of trimethoprim at high doses and/or for extended periods of time may cause bone marrow depression manifested as thrombocytopenia, leukopenia, and/or megaloblastic anemia. If signs of bone marrow depression occur, trimethoprim should be discontinued and the patient should be given leucovorin; 5 to 15 mg leucovorin daily has been recommended by some investigators."}', 'active_flag': 'Y', 'generic_name': '{TRIMETHOPRIM}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Serious hypersensitivity reactions have been reported rarely in patients on trimethoprim therapy. Trimethoprim has been reported rarely to interfere with hematopoiesis, especially when administered in large doses and/or for prolonged periods. The presence of clinical signs such as sore throat, fever, pallor, or purpura may be early indications of serious blood disorders (see OVERDOSAGE , Chronic ). Complete blood counts should be obtained if any of these signs are noted in a patient receiving trimethoprim and the drug discontinued if a significant reduction in the count of any formed blood element is found. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including trimethoprim tablets, 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 antiobiotic 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 Prescribing trimethoprim tablets, USP 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. Trimethoprim should be given with caution to patients with possible folate deficiency. Folates may be administered concomitantly without interfering with the antibacterial action of trimethoprim. Trimethoprim should also be given with caution to patients with impaired renal or hepatic function (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION ). Information for Patients Patients should be counseled that antibacterial drugs including trimethoprim tablets, USP should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When trimethoprim tablets, USP 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 trimethoprim tablets, 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 and 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. Drug Interactions Trimethoprim may inhibit the hepatic metabolism of phenytoin. Trimethoprim, given at a common clinical dosage, increased the phenytoin half-life by 51% and decreased the phenytoin metabolic clearance rate by 30%. When administering these drugs concurrently, one should be alert for possible excessive phenytoin effect. Drug/Laboratory Test Interactions Trimethoprim can interfere with a serum methotrexate assay as determined by the Competitive Binding Protein Technique (CBPA) when a bacterial dihydrofolate reductase is used as the binding protein. No interference occurs, however, if methotrexate is measured by a radioimmunoassay (RIA). The presence of trimethoprim may also interfere with the Jaffe alkaline picrate reaction assay for creatinine, resulting in overestimations of about 10% in the range of normal values. Carcinogenesis & Mutagenesis & Impairment of Fertility Carcinogenesis Long-term studies in animals to evaluate carcinogenic potential have not been conducted with trimethoprim. Mutagenesis Trimethoprim was demonstrated to be nonmutagenic in the Ames assay. In studies at two laboratories, no chromosomal damage was detected in cultured Chinese hamster ovary cells at concentrations approximately 500 times human plasma levels; at concentrations approximately 1000 times human plasma levels in these same cells, a low level of chromosomal damage was induced at one of the laboratories. No chromosomal abnormalities were observed in cultured human leukocytes at concentrations of trimethoprim up to 20 times human steady-state plasma levels. No chromosomal effects were detected in peripheral lymphocytes of human subjects receiving 320 mg of trimethoprim in combination with up to 1600 mg of sulfamethoxazole per day for as long as 112 weeks. Impairment of Fertility No adverse effects on fertility or general reproductive performance were observed in rats given trimethoprim in oral dosages as high as 70 mg/kg/day for males and 14 mg/kg/day for females. Pregnancy Teratogenic Effects Pregnancy category C Trimethoprim has been shown to be teratogenic in the rat when given in doses 40 times the human dose. In some rabbit studies, the overall increase in fetal loss (dead and resorbed and malformed conceptuses) was associated with doses six times the human therapeutic dose. While there are no large, well-controlled studies on the use of trimethoprim in pregnant women, Brumfitt and Pursell, 3 in a retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or trimethoprim in combination with sulfamethoxazole. The incidence of congenital abnormalities was 4.5% (3 of 66) in those who received placebo and 3.3% (4 of 120) in those receiving trimethoprim and sulfamethoxazole. There were no abnormalities in the 10 children whose mothers received the drug during the first trimester. In a separate survey, Brumfitt and Pursell also found no congenital abnormalities in 35 children whose mothers had received trimethoprim and sulfamethoxazole at the time of conception or shortly thereafter. Because trimethoprim may interfere with folic acid metabolism, trimethoprim should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects The oral administration of trimethoprim to rats at a dose of 70 mg/kg/day commencing with the last third of gestation and continuing through parturition and lactation caused no deleterious effects on gestation or pup growth and survival. Nursing Mothers Trimethoprim is excreted in human milk. Because trimethoprim may interfere with folic acid metabolism, caution should be exercised when trimethoprim is administered to a nursing woman. Pediatric Use Safety and effectiveness in pediatric patients below the age of 2 months have not been established. The effectiveness of trimethoprim as a single agent has not been established in pediatric patients under 12 years of age. Geriatric Use Clinical studies of trimethoprim tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience 4,5 has not identified differences in response 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. Case reports of hyperkalemia in elderly patients receiving trimethoprim-sulfamethoxazole have been published. 6 Trimethoprim 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 potassium concentrations and to monitor renal function by calculating creatinine clearance."}', 'information_for_patients': '{"Information for Patients Patients should be counseled that antibacterial drugs including trimethoprim tablets, USP should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When trimethoprim tablets, USP 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 trimethoprim tablets, 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 and 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 C Trimethoprim has been shown to be teratogenic in the rat when given in doses 40 times the human dose. In some rabbit studies, the overall increase in fetal loss (dead and resorbed and malformed conceptuses) was associated with doses six times the human therapeutic dose. While there are no large, well-controlled studies on the use of trimethoprim in pregnant women, Brumfitt and Pursell, 3 in a retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or trimethoprim in combination with sulfamethoxazole. The incidence of congenital abnormalities was 4.5% (3 of 66) in those who received placebo and 3.3% (4 of 120) in those receiving trimethoprim and sulfamethoxazole. There were no abnormalities in the 10 children whose mothers received the drug during the first trimester. In a separate survey, Brumfitt and Pursell also found no congenital abnormalities in 35 children whose mothers had received trimethoprim and sulfamethoxazole at the time of conception or shortly thereafter. Because trimethoprim may interfere with folic acid metabolism, trimethoprim should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects The oral administration of trimethoprim to rats at a dose of 70 mg/kg/day commencing with the last third of gestation and continuing through parturition and lactation caused no deleterious effects on gestation or pup growth and survival."}', 'pediatric_use': '{"Pediatric Use Safety and effectiveness in pediatric patients below the age of 2 months have not been established. The effectiveness of trimethoprim as a single agent has not been established in pediatric patients under 12 years of age."}', 'geriatric_use': '{"Geriatric Use Clinical studies of trimethoprim tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience 4,5 has not identified differences in response 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. Case reports of hyperkalemia in elderly patients receiving trimethoprim-sulfamethoxazole have been published. 6 Trimethoprim 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 potassium concentrations and to monitor renal function by calculating creatinine clearance."}'}

{"DIPHENHYDRAMINE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use for relief of occasional sleeplessness."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"DIPHENHYDRAMINE HCL"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if sleeplessness persists continuously for more than 2 weeks. Insomnia may be a symptom of a serious underlying medical illness."}', 'do_not_use': '{"Do not use for children under 12 years of age with any other product containing diphenhydramine, even one used on skin"}', 'when_using': '{"When using this product avoid alcoholic drinks."}', 'warnings': '{"Warnings Do not use for children under 12 years of age with any other product containing diphenhydramine, even one used on skin Ask a doctor before use if you have a breathing problem such as emphysema or chronic bronchitis glaucoma trouble urinating due to an enlarged prostate gland Ask a doctor or pharmacist before use if you are taking sedatives or tranquilizers. When using this product avoid alcoholic drinks. Stop use and ask a doctor if sleeplessness persists continuously for more than 2 weeks. Insomnia may be a symptom of a serious underlying medical 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}

{ZONISAMIDE}

{'contraindications': '{"CONTRAINDICATIONS Zonisamide is contraindicated in patients who have demonstrated hypersensitivity to sulfonamides or zonisamide."}', 'adverse_reactions': '{"ADVERSE REACTIONS The most common adverse reactions with zonisamide (an incidence at least 4% greater than placebo) in controlled clinical trials and shown in descending order of frequency were somnolence, anorexia, dizziness, ataxia, agitation/irritability, and difficulty with memory and/or concentration. In controlled clinical trials, 12% of patients receiving zonisamide as adjunctive therapy discontinued due to an adverse reaction compared to 6% receiving placebo. Approximately 21% of the 1,336 patients with epilepsy who received zonisamide in clinical studies discontinued treatment because of an adverse reaction. The most common adverse reactions leading to discontinuation were somnolence, fatigue and/or ataxia (6%), anorexia (3%), difficulty concentrating (2%), difficulty with memory, mental slowing, nausea/vomiting (2%), and weight loss (1%). Many of these adverse reactions were dose-related (see WARNINGS and PRECAUTIONS ). Adverse Reaction Incidence in Controlled Clinical Trials: Table 4 lists adverse reactions that occurred in at least 2% of patients treated with zonisamide in controlled clinical trials that were numerically more common in the zonisamide group. In these studies, either zonisamide or placebo was added to the patient\'s current AED therapy. Table 4. Adverse Reactions in Placebo-Controlled, Add-On Trials (Events that occurred in at least 2% of Zonisamide-treated patients and occurred more frequently in Zonisamide -treated than placebo-treated patients) BODY SYSTEM/PREFERRED TERM ZONISAMIDE (n=269) % PLACEBO (n=230) % BODY AS A WHOLE Headache 10 8 Abdominal Pain 6 3 Flu Syndrome 4 3 DIGESTIVE Anorexia 13 6 Nausea 9 6 Diarrhea 5 2 Dyspepsia 3 1 Constipation 2 1 Dry Mouth 2 1 HEMATOLOGIC AND LYMPHATIC Ecchymosis 2 1 METABOLIC AND NUTRITIONAL Weight Loss 3 2 NERVOUS SYSTEM Dizziness 13 7 Ataxia 6 1 Nystagmus 4 2 Paresthesia 4 1 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-ALTERED COGNITIVE FUNCTION Confusion 6 3 Difficulty Concentrating 6 2 Difficulty with Memory 6 2 Mental Slowing 4 2 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-BEHAVIORAL ABNORMALITIES (NON-PSYCHOSIS-RELATED) Agitation/Irritability 9 4 Depression 6 3 Insomnia 6 3 Anxiety 3 2 Nervousness 2 1 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-BEHAVIORAL ABNORMALITIES (PSYCHOSIS-RELATED) Schizophrenic/Schizophreniform Behavior 2 0 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-CNS DEPRESSION Somnolence 17 7 Fatigue 8 6 Tiredness 7 5 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-SPEECH AND LANGUAGE ABNORMALITIES Speech Abnormalities 5 2 Difficulties in Verbal Expression 2 <1 RESPIRATORY Rhinitis 2 1 SKIN AND APPENDAGES Rash 3 2 SPECIAL SENSES Diplopia 6 3 Taste Perversion 2 0 Other Adverse Reactions in Clinical Trials: Zonisamide has been administered to 1,598 individuals during all clinical trials, only some of which were placebo-controlled. The frequencies represent the proportion of the 1,598 individuals exposed to zonisamide who experienced an event on at least one occasion. All events are included except those already listed in the previous table or discussed in WARNINGS or PRECAUTIONS , trivial events, those too general to be informative, and those not reasonably associated with zonisamide. Events are further classified within each category and listed in order of decreasing frequency as follows: frequent occurring in at least 1:100 patients; infrequent occurring in 1:100 to 1:1,000 patients; rare occurring in fewer than 1:1,000 patients. Body as a Whole : Frequent: Accidental injury, asthenia. Infrequent: Chest pain, flank pain, malaise, allergic reaction, face edema, neck rigidity. Rare: Lupus erythematosus. Cardiovascular : Infrequent: Palpitation, tachycardia, vascular insufficiency, hypotension, hypertension, thrombophlebitis, syncope, bradycardia. Rare: Atrial fibrillation, heart failure, pulmonary embolus, ventricular extrasystoles. Digestive : Frequent: Vomiting. Infrequent: Flatulence, gingivitis, gum hyperplasia, gastritis, gastroenteritis, stomatitis, cholelithiasis, glossitis, melena, rectal hemorrhage, ulcerative stomatitis, gastro-duodenal ulcer, dysphagia, gum hemorrhage. Rare: Cholangitis, hematemesis, cholecystitis, cholestatic jaundice, colitis, duodenitis, esophagitis, fecal incontinence, mouth ulceration. Hematologic and Lymphatic : Infrequent: Leukopenia, anemia, immunodeficiency, lymphadenopathy. Rare: Thrombocytopenia, microcytic anemia, petechia. Metabolic and Nutritional : Infrequent: Peripheral edema, weight gain, edema, thirst, dehydration. Rare: Hypoglycemia, hyponatremia, lactic dehydrogenase increased, SGOT increased, SGPT increased. Musculoskeletal : Infrequent: Leg cramps, myalgia, myasthenia, arthralgia, arthritis. Nervous System : Frequent: Tremor, convulsion, abnormal gait, hyperesthesia, incoordination. Infrequent: Hypertonia, twitching, abnormal dreams, vertigo, libido decreased, neuropathy, hyperkinesia, movement disorder, dysarthria, cerebrovascular accident, hypotonia, peripheral neuritis, reflexes increased. Rare: Dyskinesia, dystonia, encephalopathy, facial paralysis, hypokinesia, hyperesthesia, myoclonus, oculogyric crisis. Behavioral Abnormalities-Non-Psychosis-Related : Infrequent: Euphoria. Respiratory : Frequent: Pharyngitis, cough increased. Infrequent: Dyspnea. Rare: Apnea, hemoptysis. Skin and Appendages : Frequent: Pruritus. Infrequent: Maculopapular rash, acne, alopecia, dry skin, sweating, eczema, urticaria, hirsutism, pustular rash, vesiculobullous rash. Special Senses : Frequent: Amblyopia, tinnitus. Infrequent: Conjunctivitis, parosmia, deafness, visual field defect, glaucoma. Rare: Photophobia, iritis. Urogenital : Infrequent: Urinary frequency, dysuria, urinary incontinence, hematuria, impotence, urinary retention, urinary urgency, amenorrhea, polyuria, nocturia. Rare: Albuminuria, enuresis, bladder pain, bladder calculus, gynecomastia, mastitis, menorrhagia. POST MARKETING EXPERIENCE The following serious adverse reactions have been reported since approval and use of zonisamide worldwide. These reactions are reported voluntarily from a population of uncertain size; therefore, it is not possible to estimate their frequency or establish a causal relationship to drug exposure. Acute pancreatitis, rhabdomyolysis, increased creatine phosphokinase, drug reaction with eosinophilia and systemic symptoms (DRESS), acute myopia and secondary angle closure glaucoma, and hyperammonemia and encephalopathy (see WARNINGS ). To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE Zonisamide is indicated as adjunctive therapy in the treatment of partial seizures in adults with epilepsy."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Human Experience: Experience with zonisamide daily doses over 800 mg/day is limited. During zonisamide clinical development, three patients ingested unknown amounts of zonisamide as suicide attempts, and all three were hospitalized with CNS symptoms. One patient became comatose and developed bradycardia, hypotension, and respiratory depression; the zonisamide plasma level was 100.1 mcg/mL measured 31 hours post-ingestion. Zonisamide plasma levels fell with a half-life of 57 hours, and the patient became alert five days later. Management: No specific antidotes for zonisamide overdosage are available. Following a suspected recent overdose, emesis should be induced or gastric lavage performed with the usual precautions to protect the airway. General supportive care is indicated, including frequent monitoring of vital signs and close observation. Zonisamide has a long half-life (see CLINICAL PHARMACOLOGY section). Due to the low protein binding of zonisamide (40%), renal dialysis may be effective. The effectiveness of renal dialysis as a treatment of overdose has not been formally studied. A poison control center should be contacted for information on the management of zonisamide overdosage."}', 'active_flag': 'Y', 'generic_name': '{ZONISAMIDE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Potentially Fatal Reactions to Sulfonamides: Fatalities have occurred, although rarely, as a result of severe reactions to sulfonamides (zonisamide is a sulfonamide) including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Such reactions may occur when a sulfonamide is readministered irrespective of the route of administration. If signs of hypersensitivity or other serious reactions occur, discontinue zonisamide immediately. Specific experience with sulfonamide-type adverse reaction to zonisamide is described below. Serious Skin Reactions: Consideration should be given to discontinuing zonisamide in patients who develop an otherwise unexplained rash. If the drug is not discontinued, patients should be observed frequently. Seven deaths from severe rash [i.e., Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)] were reported in the first 11 years of marketing in Japan. All of the patients were receiving other drugs in addition to zonisamide. In postmarketing experience from Japan, a total of 49 cases of SJS or TEN have been reported, a reporting rate of 46 per million patient-years of exposure. Although this rate is greater than background, it is probably an underestimate of the true incidence because of under-reporting. There were no confirmed cases of SJS or TEN in the U.S., European, or Japanese development programs. In the U.S. and European randomized controlled trials, 6 of 269 (2.2%) zonisamide patients discontinued treatment because of rash compared to none on placebo. Across all trials during the U.S. and European development, rash that led to discontinuation of zonisamide was reported in 1.4% of patients (12 events per 1,000 patient-years of exposure). During Japanese development, serious rash or rash that led to study drug discontinuation was reported in 2% of patients (27.8 events per 1,000 patient-years). Rash usually occurred early in treatment, with 85% reported within 16 weeks in the U.S. and European studies and 90% reported within two weeks in the Japanese studies. There was no apparent relationship of dose to the occurrence of rash. Serious Hematologic Events: Two confirmed cases of aplastic anemia and one confirmed case of agranulocytosis were reported in the first 11 years of marketing in Japan, rates greater than generally accepted background rates. There were no cases of aplastic anemia and two confirmed cases of agranulocytosis in the U.S., European, or Japanese development programs. There is inadequate information to assess the relationship, if any, between dose and duration of treatment and these events. 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 occurred with zonisamide. 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. Zonisamide should be discontinued if an alternative etiology for the signs or symptoms cannot be established. Oligohidrosis and Hyperthermia in Pediatric Patients: Oligohidrosis, sometimes resulting in heat stroke and hospitalization, is seen in association with zonisamide in pediatric patients. During the pre-approval development program in Japan, one case of oligohidrosis was reported in 403 pediatric patients, an incidence of 1 case per 285 patient-years of exposure. While there were no cases reported in the U.S. or European development programs, fewer than 100 pediatric patients participated in these trials. In the first 11 years of marketing in Japan, 38 cases were reported, an estimated reporting rate of about 1 case per 10,000 patient-years of exposure. In the first year of marketing in the U.S., 2 cases were reported, an estimated reporting rate of about 12 cases per 10,000 patient-years of exposure. These rates are underestimates of the true incidence because of under-reporting. There has also been one report of heat stroke in an 18-year-old patient in the U.S. Decreased sweating and an elevation in body temperature above normal characterized these cases. Many cases were reported after exposure to elevated environmental temperatures. Heat stroke, requiring hospitalization, was diagnosed in some cases. There have been no reported deaths. Pediatric patients appear to be at an increased risk for zonisamide-associated oligohidrosis and hyperthermia. Patients, especially pediatric patients, treated with zonisamide should be monitored closely for evidence of decreased sweating and increased body temperature, especially in warm or hot weather. Caution should be used when zonisamide is prescribed with other drugs that predispose patients to heat-related disorders; these drugs include, but are not limited to, carbonic anhydrase inhibitors and drugs with anticholinergic activity. The practitioner should be aware that the safety and effectiveness of zonisamide in pediatric patients have not been established, and that zonisamide is not approved for use in pediatric patients. Acute Myopia and Secondary Angle Closure Glaucoma: Acute myopia and secondary angle closure glaucoma have been reported in patients receiving zonisamide. Elevated intraocular pressure can lead to serious sequelae, including permanent vision loss, if left untreated. Symptoms in reported cases have included acute onset of decreased visual acuity and/or ocular pain. Ophthalmologic findings can include myopia, anterior chamber shallowing, ocular hyperemia (redness), and increased intraocular pressure. Mydriasis may or may not be present. This syndrome may be associated with ciliochoroidal effusion resulting in anterior displacement of the lens and iris, with secondary angle closure glaucoma. Symptoms typically occur within one month after initiating zonisamide therapy. In contrast to primary narrow angle glaucoma, which is rare under 40 years of age, secondary angle closure glaucoma associated with zonisamide has been reported both in pediatric patients and in adults. The primary treatment to reverse symptoms is discontinuation of zonisamide as rapidly as possible, according to the judgment of the treating physician. Other therapeutic measures, in conjunction with discontinuation of zonisamide, may be helpful. Myopia and secondary angle closure glaucoma usually resolve or improve after discontinuation of zonisamide. Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including zonisamide, 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 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 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1 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 zonisamide 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 (see WARNINGS, Cognitive/Neuropsychiatric Adverse Events subsection below). Metabolic Acidosis: Zonisamide causes hyperchloremic, non-anion gap, metabolic acidosis (i.e., decreased serum bicarbonate below the normal reference range in the absence of chronic respiratory alkalosis) (see PRECAUTIONS, Laboratory Tests subsection). This metabolic acidosis is caused by renal bicarbonate loss due to the inhibitory effect of zonisamide on carbonic anhydrase. Generally, zonisamide-induced metabolic acidosis occurs early in treatment, but it can develop at any time during treatment. Metabolic acidosis generally appears to be dose-dependent and can occur at doses as low as 25 mg daily. Conditions or therapies that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, ketogenic diet, or specific drugs) may be additive to the bicarbonate lowering effects of zonisamide. Some manifestations of acute or chronic metabolic acidosis include hyperventilation, nonspecific symptoms such as fatigue and anorexia, or more severe sequelae including cardiac arrhythmias or stupor. Chronic, untreated, metabolic acidosis may increase the risk for nephrolithiasis or nephrocalcinosis. Nephrolithiasis has been observed in the clinical development program in 4 % of adults treated with zonisamide, has also been detected by renal ultrasound in 8 % of pediatric treated patients who had at least one ultrasound prospectively collected, and was reported as an adverse event in 3 % (4/133) of pediatric patients (see PRECAUTIONS, Kidney Stones subsection). Metabolic acidosis can also increase the risk for hyperammonemia, particularly in the presence of drugs which can cause hyperammonemia. Chronic, untreated metabolic acidosis may result in osteomalacia (referred to as rickets in pediatric patients) and/or osteoporosis with an increased risk for fracture. Of potential relevance, zonisamide treatment was associated with reductions in serum phosphorus and increases in serum alkaline phosphatase, changes that may be related to metabolic acidosis and osteomalacia (see PRECAUTIONS, Laboratory Tests subsection). Chronic, untreated metabolic acidosis in pediatric patients may reduce growth rates. A reduction in growth rate may eventually decrease the maximal height achieved. The effect of zonisamide on growth and bone-related sequelae has not been systematically investigated. Measurement of baseline and periodic serum bicarbonate during treatment is recommended. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing zonisamide (using dose tapering). If the decision is made to continue patients on zonisamide in the face of persistent acidosis, alkali treatment should be considered. Serum bicarbonate was not measured in the adjunctive controlled trials of adults with epilepsy. However, serum bicarbonate was studied in three clinical trials for indications which have not been approved: a placebo-controlled trial for migraine prophylaxis in adults, a controlled trial for monotherapy in epilepsy in adults, and an open label trial for adjunctive treatment of epilepsy in pediatric patients (3 to 16 years). In adults, mean serum bicarbonate reductions ranged from approximately 2 mEq/L at daily doses of 100 mg to nearly 4 mEq/L at daily doses of 300 mg. In pediatric patients, mean serum bicarbonate reductions ranged from approximately 2 mEq/L at daily doses from above 100 mg up to 300 mg, to nearly 4 mEq/L at daily doses from above 400 mg up to 600 mg. In two controlled studies in adults, the incidence of a persistent treatment-emergent decrease in serum bicarbonate to less than 20 mEq/L (observed at 2 or more consecutive visits or the final visit) was dose-related at relatively low zonisamide doses. In the monotherapy trial of epilepsy, the incidence of a persistent treatment-emergent decrease in serum bicarbonate was 21% for daily zonisamide doses of 25 mg or 100 mg, and was 43% at a daily dose of 300 mg. In a placebo-controlled trial for prophylaxis of migraine, the incidence of a persistent treatment-emergent decrease in serum bicarbonate was 7% for placebo, 29% for 150 mg daily, and 34% for 300 mg daily. The incidence of persistent markedly abnormally low serum bicarbonate (decrease to less than 17 mEq/L and more than 5 mEq/L from a pretreatment value of at least 20 mEq/L) in these controlled trials was 2% or less. In the pediatric study, the incidence of persistent, treatment-emergent decreases in serum bicarbonate to levels less than 20 mEq/L was 52% at doses up to 100 mg daily, was 90% for a wide range of doses up to 600 mg daily, and generally appeared to increase with higher doses. The incidence of a persistent markedly abnormally low serum bicarbonate value was 4 % at doses up to 100 mg daily, was 18% for a wide range of doses up to 600 mg daily, and generally appeared to increase with higher doses. Some patients experienced moderately severe serum bicarbonate decrements down to a level as low as 10 mEq/L. The relatively high frequencies of varying severities of metabolic acidosis observed in this study of pediatric patients (compared to the frequency and severity observed in various clinical trial development programs in adults) suggest that pediatric patients may be more likely to develop metabolic acidosis than adults. Seizures on Withdrawal: As with other AEDs, abrupt withdrawal of zonisamide in patients with epilepsy may precipitate increased seizure frequency or status epilepticus. Dose reduction or discontinuation of zonisamide should be done gradually. Teratogenicity: Women of child bearing potential who are given zonisamide should be advised to use effective contraception. Zonisamide was teratogenic in mice, rats, and dogs and embryolethal in monkeys when administered during the period of organogenesis. A variety of fetal abnormalities, including cardiovascular defects, and embryo-fetal deaths occurred at maternal plasma levels similar to or lower than therapeutic levels in humans. These findings suggest that the use of zonisamide during pregnancy in humans may present a significant risk to the fetus (see PRECAUTIONS, Pregnancy subsection). Zonisamide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Cognitive/Neuropsychiatric Adverse Events: Use of zonisamide was frequently associated with central nervous system-related adverse events. The most significant of these can be classified into three general categories: 1) psychiatric symptoms, including depression and psychosis, 2) psychomotor slowing, difficulty with concentration, and speech or language problems, in particular, word-finding difficulties, and 3) somnolence or fatigue. In placebo-controlled trials, 2.2% of patients discontinued zonisamide or were hospitalized for depression compared to 0.4% of placebo patients. Among all epilepsy patients treated with zonisamide, 1.4% were discontinued and 1% were hospitalized because of reported depression or suicide attempts. In placebo-controlled trials, 2.2% of patients discontinued zonisamide or were hospitalized due to psychosis or psychosis-related symptoms compared to none of the placebo patients. Among all epilepsy patients treated with zonisamide, 0.9% were discontinued and 1.4% were hospitalized because of reported psychosis or related symptoms. Psychomotor slowing and difficulty with concentration occurred in the first month of treatment and were associated with doses above 300 mg/day. Speech and language problems tended to occur after 6 to 10 weeks of treatment and at doses above 300 mg/day. Although in most cases these events were of mild to moderate severity, they at times led to withdrawal from treatment. Somnolence and fatigue were frequently reported CNS adverse events during clinical trials with zonisamide. Although in most cases these events were of mild to moderate severity, they led to withdrawal from treatment in 0.2% of the patients enrolled in controlled trials. Somnolence and fatigue tended to occur within the first month of treatment. Somnolence and fatigue occurred most frequently at doses of 300 to 500 mg/day. Patients should be cautioned about this possibility and special care should be taken by patients if they drive, operate machinery, or perform any hazardous task. Hyperammonemia and Encephalopathy: Hyperammonemia and encephalopathy have been reported with the postmarketing use of zonisamide. Zonisamide treatment inhibits carbonic anhydrase activity, which may cause metabolic acidosis that is associated with an increased risk for developing hyperammonemia. Hyperammonemia resulting from zonisamide can also be asymptomatic. The risks of hyperammonemia and various manifestations of encephalopathy may be increased in patients treated with zonisamide and concomitantly taking other medications that can cause hyperammonemia, including valproic acid or topiramate (see PRECAUTIONS ). Patients with inborn errors of metabolism or reduced hepatic mitochondrial activity may be at an increased risk for hyperammonemia with or without encephalopathy and this risk may be increased by zonisamide use. Measure serum ammonia concentration if signs or symptoms (e.g., unexplained change in mental status, vomiting, or lethargy) of encephalopathy occur. Hyperammonemia resulting from zonisamide resolves when zonisamide is discontinued. Hyperammonemia from zonisamide may resolve or decrease in severity with a decrease of the daily dose."}', 'precautions': '{"PRECAUTIONS General: Somnolence is commonly reported, especially at higher doses of zonisamide (see WARNINGS: Cognitive/Neuropsychiatric Adverse Events subsection). Zonisamide is metabolized by the liver and eliminated by the kidneys; caution should therefore be exercised when administering zonisamide to patients with hepatic and renal dysfunction (see CLINICAL PHARMACOLOGY, Specific Populations subsection). Kidney Stones: Among 991 patients treated during the development of zonisamide, 40 patients (4%) with epilepsy receiving zonisamide developed clinically possible or confirmed kidney stones (e.g., clinical symptomatology, sonography, etc.), a rate of 34 per 1,000 patient-years of exposure (40 patients with 1,168 years of exposure). Of these, 12 were symptomatic, and 28 were described as possible kidney stones based on sonographic detection. In nine patients, the diagnosis was confirmed by a passage of a stone or by a definitive sonographic finding. The rate of occurrence of kidney stones was 28.7 per 1,000 patient-years of exposure in the first six months, 62.6 per 1,000 patient-years of exposure between 6 and 12 months, and 24.3 per 1,000 patient-years of exposure after 12 months of use. There are no normative sonographic data available for either the general population or patients with epilepsy. Although the clinical significance of the sonographic findings may not be certain, the development of nephrolithiasis may be related to metabolic acidosis (see WARNINGS, Metabolic Acidosis subsection). The analyzed stones were composed of calcium or urate salts. In general, increasing fluid intake and urine output can help reduce the risk of stone formation, particularly in those with predisposing risk factors. It is unknown, however, whether these measures will reduce the risk of stone formation in patients treated with zonisamide. Although not approved in pediatric patients, sonographic findings consistent with nephrolithiasis were also detected in 8 % of a subset of zonisamide treated pediatric patients who had at least one renal ultrasound prospectively performed in a clinical development program investigating open-label treatment. The incidence of kidney stone as an adverse event was 3 % (see WARNINGS, Metabolic Acidosis subsection) . Effect on Renal Function: In several clinical studies, zonisamide was associated with a statistically significant 8% mean increase from baseline of serum creatinine and blood urea nitrogen (BUN) compared to essentially no change in the placebo patients. The increase appeared to persist over time but was not progressive; this has been interpreted as an effect on glomerular filtration rate (GFR). There were no episodes of unexplained acute renal failure in clinical development in the U.S., Europe, or Japan. The decrease in GFR appeared within the first 4 weeks of treatment. In a 30-day study, the GFR returned to baseline within 2 to 3 weeks of drug discontinuation. There is no information about reversibility, after drug discontinuation, of the effects on GFR after long-term use. Zonisamide should be discontinued in patients who develop acute renal failure or a clinically significant sustained increase in the creatinine/BUN concentration. Zonisamide should not be used in patients with renal failure (estimated GFR < 50 mL/min) as there has been insufficient experience concerning drug dosing and toxicity. Status Epilepticus: Estimates of the incidence of treatment emergent status epilepticus in zonisamide-treated patients are difficult because a standard definition was not employed. Nonetheless, in controlled trials, 1.1% of patients treated with zonisamide had an event labeled as status epilepticus compared to none of the patients treated with placebo. Among patients treated with zonisamide across all epilepsy studies (controlled and uncontrolled), 1% of patients had an event reported as status epilepticus. Information for Patients: Inform patients of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking zonisamide capsules. Instruct patients to take zonisamide capsules only as prescribed. Advise patients as follows: (See Medication Guide) Zonisamide may produce drowsiness, especially at higher doses. Patients should be advised not to drive a car or operate other complex machinery until they have gained experience on zonisamide sufficient to determine whether it affects their performance. Because of the potential of zonisamide to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse events, zonisamide should be used with caution if used in combination with alcohol or other CNS depressants. Patients should contact their physician immediately if a skin rash develops (see WARNINGS, Serious Skin Reactions subsection). Instruct patients to seek immediate medical attention if they experience blurred vision, visual disturbances, or periorbital pain (see WARNINGS, Acute Myopia and Secondary Angle Closure Glaucoma subsection). Patients should contact their physician immediately if they develop signs or symptoms, such as sudden back pain, abdominal pain, and/or blood in the urine, that could indicate a kidney stone. Increasing fluid intake and urine output may reduce the risk of stone formation, particularly in those with predisposing risk factors for stones (see PRECAUTIONS, Kidney Stones subsection). Patients should contact their physician immediately if a child has been taking zonisamide and is not sweating as usual with or without a fever (see WARNINGS, Oligohidrosis and Hyperthermia in Pediatric Patients subsection). Because zonisamide can cause hematological complications, patients should contact their physician immediately if they develop a fever, sore throat, oral ulcers, or easy bruising (see WARNINGS, Serious Hematologic Events subsection). Counsel patients and caregivers that AEDs, including zonisamide, may increase the risk of suicidal thoughts and behavior and advise them 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, Suicidal Behavior and Ideation subsection). Warn patients about the possible development of hyperammonemia with or without encephalopathy. Although hyperammonemia may be asymptomatic, clinical symptoms of hyperammonemic encephalopathy often include acute alterations in level of consciousness and/or cognitive function with lethargy and/or vomiting. Instruct patients to contact their physician if they develop unexplained lethargy, vomiting, or changes in mental status (see WARNINGS, Hyperammonemia and Encephalopathy subsection) Patients should contact their physician immediately if they develop fast breathing, fatigue/tiredness, loss of appetite, or irregular heart beat or palpitations, which are possible manifestations of metabolic acidosis (see WARNINGS, Metabolic Acidosis subsection). As with other AEDs, patients should contact their physician if they intend to become pregnant or are pregnant during zonisamide therapy. Patients should notify their physician if they intend to breast-feed or are breast-feeding an infant (see PRECAUTIONS, Use in Nursing Mothers subsection). 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 antiepileptic drugs during pregnancy. To enroll, patients can call the toll-free number 1-888-233-2334 (see PRECAUTIONS, Pregnancy subsection). Laboratory Tests: In several clinical studies, zonisamide was associated with a mean increase in the concentration of serum creatinine and blood urea nitrogen (BUN) of approximately 8% over the baseline measurement. Consideration should be given to monitoring renal function periodically (see PRECAUTIONS, Effect on Renal Function subsection). Zonisamide increases serum chloride and alkaline phosphatase and decreases serum bicarbonate (see WARNINGS, Metabolic Acidosis subsection), phosphorus, calcium, and albumin. Drug Interactions with CNS Depressants: Concomitant administration of zonisamide and alcohol or other CNS depressant drugs has not been evaluated in clinical studies. Because of the potential of zonisamide to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse events, zonisamide should be used with caution if used in combination with alcohol or other CNS depressants. Other Carbonic Anhydrase Inhibitors: Concomitant use of zonisamide , a carbonic anhydrase inhibitor, with any other carbonic anhydrase inhibitor (e.g., topiramate, acetazolamide or dichlorphenamide), may increase the severity of metabolic acidosis and may also increase the risk of kidney stone formation or the risk of hyperammonemia. Therefore, if zonisamide is given concomitantly with another carbonic anhydrase inhibitor, the patient should be monitored for the appearance or worsening of metabolic acidosis (see CLINICAL PHARMACOLOGY, Interactions of Zonisamide with Other Carbonic Anhydrase Inhibitors subsection and WARNINGS, Metabolic Acidosis subsection and Hyperammonemia and Encephalopathy subsection). Carcinogenicity, Mutagenesis, Impairment of Fertility: No evidence of carcinogenicity was found in mice or rats following dietary administration of zonisamide for two years at doses of up to 80 mg/kg/day. In mice, this dose is approximately equivalent to the maximum recommended human dose (MRHD) of 400 mg/day on a mg/m 2 basis. In rats, this dose is 1 to 2 times the MRHD on a mg/m 2 basis. Zonisamide was mutagenic in an in vitro chromosomal aberration assay in CHL cells. Zonisamide was not mutagenic or clastogenic in other in vitro assays (Ames, mouse lymphoma tk assay, chromosomal aberration in human lymphocytes) or in the in vivo rat bone marrow cytogenetics assay. Rats treated with zonisamide (20, 60, or 200 mg/kg) before mating and during the initial gestation phase showed signs of reproductive toxicity (decreased corpora lutea, implantations, and live fetuses) at all doses. The low dose in this study is approximately 0.5 times the maximum recommended human dose (MRHD) on a mg/m 2 basis. Pregnancy : (see WARNINGS, Teratogenicity subsection): Zonisamide may cause serious adverse fetal effects, based on clinical and nonclinical data. Zonisamide was teratogenic in multiple animal species. Zonisamide treatment causes metabolic acidosis in humans. The effect of zonisamide-induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) may be associated with decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the fetus\'s ability to tolerate labor. Pregnant patients should be monitored for metabolic acidosis and treated as in the non-pregnant state. (See WARNINGS, Metabolic Acidosis subsection.) Newborns of mothers treated with zonisamide should be monitored for metabolic acidosis because of transfer of zonisamide to the fetus and possible occurrence of transient metabolic acidosis following birth. Transient metabolic acidosis has been reported in neonates born to mothers treated during pregnancy with a different carbonic anhydrase inhibitor. Zonisamide was teratogenic in mice, rats, and dogs and embryolethal in monkeys when administered during the period of organogenesis. Fetal abnormalities or embryo-fetal deaths occurred in these species at zonisamide dosage and maternal plasma levels similar to or lower than therapeutic levels in humans, indicating that use of this drug in pregnancy entails a significant risk to the fetus. A variety of external, visceral, and skeletal malformations was produced in animals by prenatal exposure to zonisamide. Cardiovascular defects were prominent in both rats and dogs. Following administration of zonisamide (10, 30, or 60 mg/kg/day) to pregnant dogs during organogenesis, increased incidences of fetal cardiovascular malformations (ventricular septal defects, cardiomegaly, various valvular and arterial anomalies) were found at doses of 30 mg/kg/day or greater. The low effect dose for malformations produced peak maternal plasma zonisamide levels (25 mcg/mL) about 0.5 times the highest plasma levels measured in patients receiving the maximum recommended human dose (MRHD) of 400 mg/day. In dogs, cardiovascular malformations were found in approximately 50% of all fetuses exposed to the high dose, which was associated with maternal plasma levels (44 mcg/mL) approximately equal to the highest levels measured in humans receiving the MRHD. Incidences of skeletal malformations were also increased at the high dose, and fetal growth retardation and increased frequencies of skeletal variations were seen at all doses in this study. The low dose produced maternal plasma levels (12 mcg/mL) about 0.25 times the highest human levels. In cynomolgus monkeys, administration of zonisamide (10 or 20 mg/kg/day) to pregnant animals during organogenesis resulted in embryo-fetal deaths at both doses. The possibility that these deaths were due to malformations cannot be ruled out. The lowest embryolethal dose in monkeys was associated with peak maternal plasma zonisamide levels (5 mcg/mL) approximately 0.1 times the highest levels measured in patients at the MRHD. In a mouse embryo-fetal development study, treatment of pregnant animals with zonisamide (125, 250, or 500 mg/kg/day) during the period of organogenesis resulted in increased incidences of fetal malformations (skeletal and/or craniofacial defects) at all doses tested. The low dose in this study is approximately 1.5 times the MRHD on a mg/m 2 basis. In rats, increased frequencies of malformations (cardiovascular defects) and variations (persistent cords of thymic tissue, decreased skeletal ossification) were observed among the offspring of dams treated with zonisamide (20, 60, or 200 mg/kg/day) throughout organogenesis at all doses. The low effect dose is approximately 0.5 times the MRHD on a mg/m 2 basis. Perinatal death was increased among the offspring of rats treated with zonisamide (10, 30, or 60 mg/kg/day) from the latter part of gestation up to weaning at the high dose, or approximately 1.4 times the MRHD on a mg/m 2 basis. The no effect level of 30 mg/kg/day is approximately 0.7 times the MRHD on a mg/m 2 basis. There are no adequate and well-controlled studies in pregnant women. Zonisamide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. To provide information regarding the effects of in utero exposure to zonisamide, physicians are advised to recommend that pregnant patients taking zonisamide capsules enroll in the 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/. Labor and Delivery : The effect of zonisamide on labor and delivery in humans is not known. Use in Nursing Mothers: Zonisamide is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from zonisamide, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account the importance of the drug to the mother. Pediatric Use: The safety and effectiveness of zonisamide in children under age 16 have not been established. Acute myopia and secondary angle closure glaucoma have been reported in pediatric patients (see WARNINGS, Acute Myopia and Secondary Angle Closure Glaucoma subsection). Cases of oligohidrosis and hyperpyrexia have been reported (see WARNINGS, Oligohidrosis and Hyperthermia in Pediatric Patients subsection). Zonisamide commonly causes metabolic acidosis in pediatric patients (see WARNINGS, Metabolic Acidosis subsection). Hyperammonemia with encephalopathy has been reported in pediatric patients (see WARNINGS, Hyperammonemia and Encephalopathy subsection). Chronic untreated metabolic acidosis in pediatric patients may cause nephrolithiasis and/or nephrocalcinosis, osteoporosis and/or osteomalacia (potentially resulting in rickets), and may reduce growth rates. A reduction in growth rate may eventually decrease the maximal height achieved. The effect of zonisamide on growth and bone-related sequelae has not been systematically investigated. Geriatric Use: Single dose pharmacokinetic parameters are similar in elderly and young healthy volunteers (see CLINICAL PHARMACOLOGY, Specific Populations subsection). Clinical studies of zonisamide 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': '{"Information for Patients: Inform patients of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking zonisamide capsules. Instruct patients to take zonisamide capsules only as prescribed. Advise patients as follows: (See Medication Guide) Zonisamide may produce drowsiness, especially at higher doses. Patients should be advised not to drive a car or operate other complex machinery until they have gained experience on zonisamide sufficient to determine whether it affects their performance. Because of the potential of zonisamide to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse events, zonisamide should be used with caution if used in combination with alcohol or other CNS depressants. Patients should contact their physician immediately if a skin rash develops (see WARNINGS, Serious Skin Reactions subsection). Instruct patients to seek immediate medical attention if they experience blurred vision, visual disturbances, or periorbital pain (see WARNINGS, Acute Myopia and Secondary Angle Closure Glaucoma subsection). Patients should contact their physician immediately if they develop signs or symptoms, such as sudden back pain, abdominal pain, and/or blood in the urine, that could indicate a kidney stone. Increasing fluid intake and urine output may reduce the risk of stone formation, particularly in those with predisposing risk factors for stones (see PRECAUTIONS, Kidney Stones subsection). Patients should contact their physician immediately if a child has been taking zonisamide and is not sweating as usual with or without a fever (see WARNINGS, Oligohidrosis and Hyperthermia in Pediatric Patients subsection). Because zonisamide can cause hematological complications, patients should contact their physician immediately if they develop a fever, sore throat, oral ulcers, or easy bruising (see WARNINGS, Serious Hematologic Events subsection). Counsel patients and caregivers that AEDs, including zonisamide, may increase the risk of suicidal thoughts and behavior and advise them 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, Suicidal Behavior and Ideation subsection). Warn patients about the possible development of hyperammonemia with or without encephalopathy. Although hyperammonemia may be asymptomatic, clinical symptoms of hyperammonemic encephalopathy often include acute alterations in level of consciousness and/or cognitive function with lethargy and/or vomiting. Instruct patients to contact their physician if they develop unexplained lethargy, vomiting, or changes in mental status (see WARNINGS, Hyperammonemia and Encephalopathy subsection) Patients should contact their physician immediately if they develop fast breathing, fatigue/tiredness, loss of appetite, or irregular heart beat or palpitations, which are possible manifestations of metabolic acidosis (see WARNINGS, Metabolic Acidosis subsection). As with other AEDs, patients should contact their physician if they intend to become pregnant or are pregnant during zonisamide therapy. Patients should notify their physician if they intend to breast-feed or are breast-feeding an infant (see PRECAUTIONS, Use in Nursing Mothers subsection). 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 antiepileptic drugs during pregnancy. To enroll, patients can call the toll-free number 1-888-233-2334 (see PRECAUTIONS, Pregnancy subsection)."}', 'pregnancy': '{"Pregnancy : (see WARNINGS, Teratogenicity subsection): Zonisamide may cause serious adverse fetal effects, based on clinical and nonclinical data. Zonisamide was teratogenic in multiple animal species. Zonisamide treatment causes metabolic acidosis in humans. The effect of zonisamide-induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) may be associated with decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the fetus\'s ability to tolerate labor. Pregnant patients should be monitored for metabolic acidosis and treated as in the non-pregnant state. (See WARNINGS, Metabolic Acidosis subsection.) Newborns of mothers treated with zonisamide should be monitored for metabolic acidosis because of transfer of zonisamide to the fetus and possible occurrence of transient metabolic acidosis following birth. Transient metabolic acidosis has been reported in neonates born to mothers treated during pregnancy with a different carbonic anhydrase inhibitor. Zonisamide was teratogenic in mice, rats, and dogs and embryolethal in monkeys when administered during the period of organogenesis. Fetal abnormalities or embryo-fetal deaths occurred in these species at zonisamide dosage and maternal plasma levels similar to or lower than therapeutic levels in humans, indicating that use of this drug in pregnancy entails a significant risk to the fetus. A variety of external, visceral, and skeletal malformations was produced in animals by prenatal exposure to zonisamide. Cardiovascular defects were prominent in both rats and dogs. Following administration of zonisamide (10, 30, or 60 mg/kg/day) to pregnant dogs during organogenesis, increased incidences of fetal cardiovascular malformations (ventricular septal defects, cardiomegaly, various valvular and arterial anomalies) were found at doses of 30 mg/kg/day or greater. The low effect dose for malformations produced peak maternal plasma zonisamide levels (25 mcg/mL) about 0.5 times the highest plasma levels measured in patients receiving the maximum recommended human dose (MRHD) of 400 mg/day. In dogs, cardiovascular malformations were found in approximately 50% of all fetuses exposed to the high dose, which was associated with maternal plasma levels (44 mcg/mL) approximately equal to the highest levels measured in humans receiving the MRHD. Incidences of skeletal malformations were also increased at the high dose, and fetal growth retardation and increased frequencies of skeletal variations were seen at all doses in this study. The low dose produced maternal plasma levels (12 mcg/mL) about 0.25 times the highest human levels. In cynomolgus monkeys, administration of zonisamide (10 or 20 mg/kg/day) to pregnant animals during organogenesis resulted in embryo-fetal deaths at both doses. The possibility that these deaths were due to malformations cannot be ruled out. The lowest embryolethal dose in monkeys was associated with peak maternal plasma zonisamide levels (5 mcg/mL) approximately 0.1 times the highest levels measured in patients at the MRHD. In a mouse embryo-fetal development study, treatment of pregnant animals with zonisamide (125, 250, or 500 mg/kg/day) during the period of organogenesis resulted in increased incidences of fetal malformations (skeletal and/or craniofacial defects) at all doses tested. The low dose in this study is approximately 1.5 times the MRHD on a mg/m 2 basis. In rats, increased frequencies of malformations (cardiovascular defects) and variations (persistent cords of thymic tissue, decreased skeletal ossification) were observed among the offspring of dams treated with zonisamide (20, 60, or 200 mg/kg/day) throughout organogenesis at all doses. The low effect dose is approximately 0.5 times the MRHD on a mg/m 2 basis. Perinatal death was increased among the offspring of rats treated with zonisamide (10, 30, or 60 mg/kg/day) from the latter part of gestation up to weaning at the high dose, or approximately 1.4 times the MRHD on a mg/m 2 basis. The no effect level of 30 mg/kg/day is approximately 0.7 times the MRHD on a mg/m 2 basis. There are no adequate and well-controlled studies in pregnant women. Zonisamide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. To provide information regarding the effects of in utero exposure to zonisamide, physicians are advised to recommend that pregnant patients taking zonisamide capsules enroll in the 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/."}', 'pediatric_use': '{"Pediatric Use: The safety and effectiveness of zonisamide in children under age 16 have not been established. Acute myopia and secondary angle closure glaucoma have been reported in pediatric patients (see WARNINGS, Acute Myopia and Secondary Angle Closure Glaucoma subsection). Cases of oligohidrosis and hyperpyrexia have been reported (see WARNINGS, Oligohidrosis and Hyperthermia in Pediatric Patients subsection). Zonisamide commonly causes metabolic acidosis in pediatric patients (see WARNINGS, Metabolic Acidosis subsection). Hyperammonemia with encephalopathy has been reported in pediatric patients (see WARNINGS, Hyperammonemia and Encephalopathy subsection). Chronic untreated metabolic acidosis in pediatric patients may cause nephrolithiasis and/or nephrocalcinosis, osteoporosis and/or osteomalacia (potentially resulting in rickets), and may reduce growth rates. A reduction in growth rate may eventually decrease the maximal height achieved. The effect of zonisamide on growth and bone-related sequelae has not been systematically investigated."}', 'geriatric_use': '{"Geriatric Use: Single dose pharmacokinetic parameters are similar in elderly and young healthy volunteers (see CLINICAL PHARMACOLOGY, Specific Populations subsection). Clinical studies of zonisamide 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."}'}

{"OLOPATADINE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"USE temporarily relieves itchy eyes due to pollen, ragweed, grass, animal hair and dander"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"OLOPATADINE HYDROCHLORIDE OPHTHALMIC"}', 'route': '{OPHTHALMIC}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"STOP USE AND ASK DOCTOR IF you experience: eye pain changes in vision increased redness of the eye itching worsens or lasts for more than 72 hours"}', 'do_not_use': '{"DO NOT USE if solution changes color or becomes cloudy if you are sensitive to any ingredient in this product to treat contact lens related irritation"}', 'when_using': '{"WHEN USING THIS PRODUCT do not touch tip of container to any surface to avoid contamination remove contact lenses before use wait at least 10 minutes before reinserting contact lenses after use do not wear a contact lens if your eye is red"}', 'warnings': '{"WARNINGS For external use only"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{CALCITRIOL}

{'contraindications': '{"4 CONTRAINDICATIONS None None ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS Most common adverse reactions (incidence > 3%) are hypercalcemia, hypercalciuria, and skin discomfort. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Padagis at 1-866-634-9120 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 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. Calcitriol Ointment was studied in two vehicle-controlled trials and one open label trial, resulting in 743 subjects exposed to Calcitriol Ointment. Table 1 describes adverse events in subjects treated with Calcitriol Ointment twice daily for 8 weeks. The population included subjects ages 13 to 87 years, males (284) and females (135), Caucasians (372) and non-Caucasians (47); with mild (105) to moderate (313) chronic plaque psoriasis. Table 1. Selected Adverse Events Occurring in at least 1% of Subjects in the Two Pooled Vehicle-Controlled Trials Calcitriol Ointment (n=419) Vehicle Ointment (n=420) Discomfort Skin 3% 2% Pruritus 1% 1% Among subjects having laboratory monitoring, hypercalcemia was observed in 24% (18/74) of subjects exposed to active drug and in 16% (13/79) of subjects exposed to vehicle, however the elevation were less than 10% above the upper limit of normal [ see WARNINGS AND PRECAUTIONS ( 5.1 ) ] The open label study enrolled 324 subjects with psoriasis who were then treated for up to 52 weeks and included 239 subjects exposed for 6 months and 116 subjects exposed for one year. Adverse events reported at a rate of greater than or equal to 3% of subjects treated with Calcitriol Ointment were lab test abnormality (8%), urine abnormality (4%), psoriasis (4%), hypercalciuria (3%), and discomfort of skin (3%). Kidney stones were reported in 3 subjects and confirmed in two. 6.2 Postmarketing Experience The following adverse reactions have been identified during the world-wide post-approval use of Calcitriol Ointment: acute blistering dermatitis, erythema,and skin burning sensation. 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."}', 'drug_interactions': None, 'indications_and_usage': '{"1 INDICATIONS AND USAGE Calcitriol Ointment is a vitamin D analog indicated for the topical treatment of mild to moderate plaque psoriasis in adults and pediatric patients 2 years and older ( 1.1 ) Limitations of Use The safety and effectiveness of Calcitriol Ointment in patients with known or suspected disorders of calcium metabolism have not been evaluated. ( 1.2 ) 1.1 Indication Calcitriol Ointment is indicated for the topical treatment of mild to moderate plaque psoriasis in adults and pediatric patients 2 years and older. 1.2 Limitations of Use The safety and effectiveness of Calcitriol Ointment in patients with known or suspected disorders of calcium metabolism have not been evaluated."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Effects on Calcium metabolism: Risk of hypercalcemia. If aberrations in parameters of calcium metabolism are noted discontinue Calcitriol Ointment until these normalize. Increased absorption may occur with occlusive use. ( 5.1 ) Calcitriol Ointment should be used with caution in patients receiving medications known to increase the serum calcium level, such as thiazide diuretics, and in patients receiving calcium supplements or high doses of vitamin D. ( 5.1 ) 5.1 Effects on Calcium Metabolism In controlled clinical trials hypercalcemia was observed in subjects exposed to Calcitriol Ointment. If aberrations in parameters of calcium metabolism occur, treatment should be discontinued until these parameters have normalized. The effects of Calcitriol Ointment on calcium metabolism following treatment durations greater than 52 weeks have not been evaluated. Increased absorption may occur with occlusive use. Calcitriol Ointment should be used with caution in patients receiving medications know to increase the serum calcium level, such as thiazide diuretics, and in patients receiving calcium supplements or high doses of vitamin D."}', 'overdosage': '{"10 OVERDOSAGE Topically applied calcitriol can be absorbed in sufficient amounts to produce systemic effects [ see WARNINGS AND PRECAUTIONS ( 5.1 )]"}', 'active_flag': 'Y', 'generic_name': '{CALCITRIOL}', '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"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Available data from pregnancies that occurred during the clinical development of Calcitriol Ointment and published cases of oral and intravenous calcitriol use in pregnant women have not identified a drug associated risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes. In animal reproduction studies, topical administration of calcitriol to pregnant rabbits during the period organogenesis resulted in an increased incidence of fetal deaths, as well as an increased incidence of minor skeletal abnormalities ( see Data ). The available data do not allow the calculation of relevant comparisons between the systemic exposures of calcitriol observed in animal studies to the systemic exposures that would be expected in humans after topical use of Calcitriol Ointment. 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 miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Embryo-fetal development studies with calcitriol were performed in which rats were treated orally at dosages up to 0.9 mcg/kg/day (5.4 mcg/m 2 /day) and in which rabbits received topical application of calcitriol ointment (3ppm) to 6.4% of the body surface area. No effects on reproductive or fetal parameters were observed in rats. In rabbits, topically applied calcitriol induced a significantly elevated mean post-implantation loss and an increased incidence of minor skeletal abnormalities due to delayed ossification of the pubic bones. A slightly increased incidence of skeletal variation (extra 13th rib, reduced ossification of epiphyses) was also observed. These effects may have been secondary to maternal toxicity."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness of Calcitriol Ointment have been established in pediatric patients age 2 years and older for topical treatment of mild to moderate plaque psoriasis. Use of Calcitriol Ointment in this age group is supported by two adequate and well-controlled 8-week trials and an open label trial in adult subjects, and additional data from trials conducted in pediatric subjects 2 to 17 years of age including: a vehicle controlled 8-week trial in 19 subjects 2 to 12 years of age with mild to moderate plaque psoriasis an open-label 8-week safety and pharmacokinetics (PK) trial in 25 subjects 12 to 17 years of age an open-label 14-day safety and PK trial in 18 subjects 2 to 17 years of age. an open-label 26-week safety and PK trial in 54 subjects 2 to 17 years of age. Data from 63 subjects ages 2 to 12 years, and 42 subjects ages 13 to 17 years showed no significant effects on indices of calcium metabolism. The systemic exposure of calcitriol in the pediatric subjects was generally comparable to the endogenous levels observed at baseline. No new safety signals were identified in subjects 2 to 17 years [see Clinical Studies ( 14 ), Clinical Pharmacology ( 12.3 ) and Adverse Reactions ( 6.1 )]. The safety and effectiveness of Calcitriol Ointment in pediatric subjects below the age of 2 years has not been established."}', 'geriatric_use': '{"8.5 Geriatric Use Clinical studies of Calcitriol Ointment did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported experience has not identified differences in responses between the elderly and younger patients."}'}

{FLUCONAZOLE}

{'contraindications': '{"CONTRAINDICATIONS Fluconazole for oral suspension is contraindicated in patients who have shown hypersensitivity to fluconazole or to any of its excipients. There is no information regarding cross-hypersensitivity between fluconazole and other azole antifungal agents. Caution should be used in prescribing fluconazole for oral suspension to patients with hypersensitivity to other azoles. Coadministration of other drugs known to prolong the QT interval and which are metabolized via the enzyme CYP3A4 such as erythromycin, pimozide, and quinidine are contraindicated in patients receiving fluconazole. (See CLINICAL PHARMACOLOGY: Drug Interaction Studies and PRECAUTIONS .)"}', 'adverse_reactions': '{"ADVERSE REACTIONS Fluconazole is generally well tolerated. In some patients, particularly those with serious underlying diseases such as AIDS and cancer, changes in renal and hematological function test results and hepatic abnormalities have been observed during treatment with fluconazole and comparative agents, but the clinical significance and relationship to treatment is uncertain. In Patients Receiving Multiple Doses: Sixteen percent of over 4000 patients treated with fluconazole in clinical trials of 7 days or more experienced adverse events. Treatment was discontinued in 1.5% of patients due to adverse clinical events and in 1.3% of patients due to laboratory test abnormalities. Clinical adverse events were reported more frequently in HIV infected patients (21%) than in non-HIV infected patients (13%); however, the patterns in HIV infected and non-HIV infected patients were similar. The proportions of patients discontinuing therapy due to clinical adverse events were similar in the two groups (1.5%). The following treatment-related clinical adverse events occurred at an incidence of 1% or greater in 4048 patients receiving fluconazole for 7 or more days in clinical trials: nausea 3.7%, headache 1.9%, skin rash 1.8%, vomiting 1.7%, abdominal pain 1.7%, and diarrhea 1.5%. Hepato-biliary : In combined clinical trials and marketing experience, there have been rare cases of serious hepatic reactions during treatment with fluconazole. (See WARNINGS .) The spectrum of these hepatic reactions has ranged from mild transient elevations in transaminases to clinical hepatitis, cholestasis and fulminant hepatic failure, including fatalities. Instances of fatal hepatic reactions were noted to occur primarily in patients with serious underlying medical conditions (predominantly AIDS or malignancy) and often while taking multiple concomitant medications. Transient hepatic reactions, including hepatitis and jaundice, have occurred among patients with no other identifiable risk factors. In each of these cases, liver function returned to baseline on discontinuation of fluconazole. In two comparative trials evaluating the efficacy of fluconazole for the suppression of relapse of cryptococcal meningitis , a statistically significant increase was observed in median AST (SGOT) levels from a baseline value of 30 IU/L to 41 IU/L in one trial and 34 IU/L to 66 IU/L in the other. The overall rate of serum transaminase elevations of more than 8 times the upper limit of normal was approximately 1% in fluconazole-treated patients in clinical trials. These elevations occurred in patients with severe underlying disease, predominantly AIDS or malignancies, most of whom were receiving multiple concomitant medications, including many known to be hepatotoxic. The incidence of abnormally elevated serum transaminases was greater in patients taking fluconazole concomitantly with one or more of the following medications: rifampin, phenytoin, isoniazid, valproic acid, or oral sulfonylurea hypoglycemic agents. Post-Marketing Experience In addition, the following adverse events have occurred during post-marketing experience. Immunologic: In rare cases, anaphylaxis (including angioedema, face edema and pruritus) has been reported. Body as a Whole : Asthenia, fatigue, fever, malaise. Cardiovascular: QT prolongation, torsade de pointes. (See PRECAUTIONS .) Central Nervous System: Seizures, dizziness. Hematopoietic and Lymphatic: Leukopenia, including neutropenia and agranulocytosis, thrombocytopenia. Metabolic: Hypercholesterolemia, hypertriglyceridemia, hypokalemia. Gastrointestinal: Cholestasis, dry mouth, hepatocellular damage, dyspepsia, vomiting. Other Senses: Taste perversion. Musculoskeletal System: Myalgia. Nervous System: Insomnia, paresthesia, somnolence, tremor, vertigo. Skin and Appendages: Acute generalized exanthematous pustulosis, drug eruption including fixed drug eruption, increased sweating, exfoliative skin disorders including Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS) (See WARNINGS ), alopecia. Adverse Reactions in Pediatric Patients: The pattern and incidence of adverse events and laboratory abnormalities recorded during pediatric clinical trials are comparable to those seen in adults. In Phase II/III clinical trials conducted in the United States and in Europe, 577 pediatric patients, ages 1 day to 17 years were treated with fluconazole at doses up to 15 mg/kg/day for up to 1,616 days. Thirteen percent of pediatric patients experienced treatment-related adverse events. The most commonly reported events were vomiting (5%), abdominal pain (3%), nausea (2%), and diarrhea (2%). Treatment was discontinued in 2.3% of patients due to adverse clinical events and in 1.4% of patients due to laboratory test abnormalities. The majority of treatment-related laboratory abnormalities were elevations of transaminases or alkaline phosphatase. Percentage of Patients With Treatment-Related Side Effects Fluconazole (N=577) Comparative Agents (N=451) With any side effect 13 9.3 Vomiting 5.4 5.1 Abdominal pain 2.8 1.6 Nausea 2.3 1.6 Diarrhea 2.1 2.2 Clinical Trials Experience in Pediatric Patients Safety in Prophylaxis of Invasive Candida Infections in Premature infants weighing less than 750 grams at birth In a Phase 3 clinical trial of pediatric patients (premature infants weighing less than 750 grams at birth), the incidence of intestinal perforation in infants receiving fluconazole prophylaxis was higher compared to infants receiving placebo (see PRECAUTIONS: Pediatric Use ). Safety in Pediatric Patients Receiving ECMO A cohort of 20 pediatric patients (1 day to 17 years of age) on ECMO received fluconazole in a prospective, open-label, single-center safety and PK ECMO study. The adverse reaction profile of fluconazole in these patients was similar to that of adult and pediatric non-ECMO patients (See PRECAUTIONS: Pediatric Use )."}', 'drug_interactions': '{"Drug Interaction Studies (See PRECAUTIONS, Drug Interactions) Oral contraceptives: Oral contraceptives were administered as a single dose both before and after the oral administration of fluconazole 50 mg once daily for 10 days in 10 healthy women. There was no significant difference in ethinyl estradiol or levonorgestrel AUC after the administration of 50 mg of fluconazole. The mean increase in ethinyl estradiol AUC was 6% (range: –47 to 108%) and levonorgestrel AUC increased 17% (range: –33 to 141%). In a second study, twenty-five normal females received daily doses of both 200 mg fluconazole tablets or placebo for two, ten-day periods. The treatment cycles were one month apart with all subjects receiving fluconazole during one cycle and placebo during the other. The order of study treatment was random. Single doses of an oral contraceptive tablet containing levonorgestrel and ethinyl estradiol were administered on the final treatment day (Day 10) of both cycles. Following administration of 200 mg of fluconazole, the mean percentage increase of AUC for levonorgestrel compared to placebo was 25% (range: –12 to 82%) and the mean percentage increase for ethinyl estradiol compared to placebo was 38% (range: –11 to 101%). Both of these increases were statistically significantly different from placebo. A third study evaluated the potential interaction of once-weekly dosing of fluconazole 300 mg to 21 normal females taking an oral contraceptive containing ethinyl estradiol and norethindrone. In this placebo-controlled, double-blind, randomized, two-way crossover study carried out over three cycles of oral contraceptive treatment, fluconazole dosing resulted in small increases in the mean AUCs of ethinyl estradiol and norethindrone compared to similar placebo dosing. The mean AUCs of ethinyl estradiol and norethindrone increased by 24% (95% C.I. range: 18 to 31%) and 13% (95% C.I. range: 8 to 18%), respectively, relative to placebo. Fluconazole treatment did not cause a decrease in the ethinyl estradiol AUC of any individual subject in this study compared to placebo dosing. The individual AUC values of norethindrone decreased very slightly (<5%) in 3 of the 21 subjects after fluconazole treatment. Cimetidine: Fluconazole 100 mg was administered as a single oral dose alone and two hours after a single dose of cimetidine 400 mg to six healthy male volunteers. After the administration of cimetidine, there was a significant decrease in fluconazole AUC and C max . There was a mean ± SD decrease in fluconazole AUC of 13% ± 11% (range: –3.4 to –31%) and C max decreased 19% ± 14% (range: –5 to –40%). However, the administration of cimetidine 600 mg to 900 mg intravenously over a four-hour period (from one hour before to 3 hours after a single oral dose of fluconazole 200 mg) did not affect the bioavailability or pharmacokinetics of fluconazole in 24 healthy male volunteers. Antacid: Administration of Maalox ® (20 mL) to 14 normal male volunteers immediately prior to a single dose of fluconazole 100 mg had no effect on the absorption or elimination of fluconazole. Hydrochlorothiazide: Concomitant oral administration of 100 mg fluconazole and 50 mg hydrochlorothiazide for 10 days in 13 normal volunteers resulted in a significant increase in fluconazole AUC and C max compared to fluconazole given alone. There was a mean ± SD increase in fluconazole AUC and C max of 45% ± 31% (range: 19 to 114%) and 43% ± 31% (range: 19 to 122%), respectively. These changes are attributed to a mean ± SD reduction in renal clearance of 30% ± 12% (range: –10 to –50%). Rifampin: Administration of a single oral 200 mg dose of fluconazole after 15 days of rifampin administered as 600 mg daily in eight healthy male volunteers resulted in a significant decrease in fluconazole AUC and a significant increase in apparent oral clearance of fluconazole. There was a mean ± SD reduction in fluconazole AUC of 23% ± 9% (range: –13 to –42%). Apparent oral clearance of fluconazole increased 32% ± 17% (range: 16 to 72%). Fluconazole half-life decreased from 33.4 ± 4.4 hours to 26.8 ± 3.9 hours. (See PRECAUTIONS .) Warfarin: There was a significant increase in prothrombin time response (area under the prothrombin time-time curve) following a single dose of warfarin (15 mg) administered to 13 normal male volunteers following oral fluconazole 200 mg administered daily for 14 days as compared to the administration of warfarin alone. There was a mean ± SD increase in the prothrombin time response (area under the prothrombin time-time curve) of 7% ± 4% (range: –2 to 13%). (See PRECAUTIONS .) Mean is based on data from 12 subjects as one of 13 subjects experienced a 2-fold increase in his prothrombin time response. Phenytoin: Phenytoin AUC was determined after 4 days of phenytoin dosing (200 mg daily, orally for 3 days followed by 250 mg intravenously for one dose) both with and without the administration of fluconazole (oral fluconazole 200 mg daily for 16 days) in 10 normal male volunteers. There was a significant increase in phenytoin AUC. The mean ± SD increase in phenytoin AUC was 88% ± 68% (range: 16 to 247%). The absolute magnitude of this interaction is unknown because of the intrinsically nonlinear disposition of phenytoin. (See PRECAUTIONS .) Cyclosporine: Cyclosporine AUC and C max were determined before and after the administration of fluconazole 200 mg daily for 14 days in eight renal transplant patients who had been on cyclosporine therapy for at least 6 months and on a stable cyclosporine dose for at least 6 weeks. There was a significant increase in cyclosporine AUC, C max , C min (24-hour concentration), and a significant reduction in apparent oral clearance following the administration of fluconazole. The mean ± SD increase in AUC was 92% ± 43% (range: 18 to 147%). The C max increased 60% ± 48% (range: –5 to 133%). The C min increased 157% ± 96% (range: 33 to 360%). The apparent oral clearance decreased 45% ± 15% (range: –15 to –60%). (See PRECAUTIONS .) Zidovudine: Plasma zidovudine concentrations were determined on two occasions (before and following fluconazole 200 mg daily for 15 days) in 13 volunteers with AIDS or ARC who were on a stable zidovudine dose for at least two weeks. There was a significant increase in zidovudine AUC following the administration of fluconazole. The mean ± SD increase in AUC was 20% ± 32% (range: –27 to 104%). The metabolite, GZDV, to parent drug ratio significantly decreased after the administration of fluconazole, from 7.6 ± 3.6 to 5.7 ± 2.2. Theophylline: The pharmacokinetics of theophylline were determined from a single intravenous dose of aminophylline (6 mg/kg) before and after the oral administration of fluconazole 200 mg daily for 14 days in 16 normal male volunteers. There were significant increases in theophylline AUC, C max , and half-life with a corresponding decrease in clearance. The mean ± SD theophylline AUC increased 21% ± 16% (range: –5 to 48%). The C max increased 13% ± 17% (range: –13 to 40%). Theophylline clearance decreased 16% ± 11% (range: –32 to 5%). The half-life of theophylline increased from 6.6 ± 1.7 hours to 7.9 ± 1.5 hours. (See PRECAUTIONS .) Quinidine: Although not studied in vitro or in vivo , concomitant administration of fluconazole with quinidine may result in inhibition of quinidine metabolism. Use of quinidine has been associated with QT prolongation and rare occurrences of torsade de pointes. Coadministration of fluconazole and quinidine is contraindicated. (See CONTRAINDICATIONS and PRECAUTIONS .) Oral hypoglycemics: The effects of fluconazole on the pharmacokinetics of the sulfonylurea oral hypoglycemic agents tolbutamide, glipizide, and glyburide were evaluated in three placebo-controlled studies in normal volunteers. All subjects received the sulfonylurea alone as a single dose and again as a single dose following the administration of fluconazole 100 mg daily for 7 days. In these three studies, 22/46 (47.8%) of fluconazole-treated patients and 9/22 (40.1%) of placebo-treated patients experienced symptoms consistent with hypoglycemia. (See PRECAUTIONS .) Tolbutamide: In 13 normal male volunteers, there was significant increase in tolbutamide (500 mg single dose) AUC and C max following the administration of fluconazole. There was a mean ± SD increase in tolbutamide AUC of 26% ± 9% (range: 12 to 39%). Tolbutamide C max increased 11% ± 9% (range: –6 to 27%). (See PRECAUTIONS .) Glipizide: The AUC and C max of glipizide (2.5 mg single dose) were significantly increased following the administration of fluconazole in 13 normal male volunteers. There was a mean ± SD increase in AUC of 49% ± 13% (range: 27 to 73%) and an increase in C max of 19% ± 23% (range: –11 to 79%). (See PRECAUTIONS .) Glyburide: The AUC and C max of glyburide (5 mg single dose) were significantly increased following the administration of fluconazole in 20 normal male volunteers. There was a mean ± SD increase in AUC of 44% ± 29% (range: –13 to 115%) and C max increased 19% ± 19% (range: –23 to 62%). Five subjects required oral glucose following the ingestion of glyburide after 7 days of fluconazole administration. (See PRECAUTIONS .) Rifabutin: There have been published reports that an interaction exists when fluconazole is administered concomitantly with rifabutin, leading to increased serum levels of rifabutin. (See PRECAUTIONS .) Tacrolimus: There have been published reports that an interaction exists when fluconazole is administered concomitantly with tacrolimus, leading to increased serum levels of tacrolimus. (See PRECAUTIONS .) Midazolam: The effect of fluconazole on the pharmacokinetics and pharmacodynamics of midazolam was examined in a randomized, cross-over study in 12 volunteers. In the study, subjects ingested placebo or 400 mg fluconazole on Day 1 followed by 200 mg daily from Day 2 to Day 6. In addition, a 7.5 mg dose of midazolam was orally ingested on the first day, 0.05 mg/kg was administered intravenously on the fourth day, and 7.5 mg orally on the sixth day. Fluconazole reduced the clearance of IV midazolam by 51%. On the first day of dosing, fluconazole increased the midazolam AUC and C max by 259% and 150%, respectively. On the sixth day of dosing, fluconazole increased the midazolam AUC and C max by 259% and 74%, respectively. The psychomotor effects of midazolam were significantly increased after oral administration of midazolam but not significantly affected following intravenous midazolam. A second randomized, double-dummy, placebo-controlled, cross over study in three phases was performed to determine the effect of route of administration of fluconazole on the interaction between fluconazole and midazolam. In each phase the subjects were given oral fluconazole 400 mg and intravenous saline; oral placebo and intravenous fluconazole 400 mg; and oral placebo and IV saline. An oral dose of 7.5 mg of midazolam was ingested after fluconazole/placebo. The AUC and C max of midazolam were significantly higher after oral than IV administration of fluconazole. Oral fluconazole increased the midazolam AUC and C max by 272% and 129%, respectively. IV fluconazole increased the midazolam AUC and C max by 244% and 79%, respectively. Both oral and IV fluconazole increased the pharmacodynamic effects of midazolam. (See PRECAUTIONS .) Azithromycin: An open-label, randomized, three-way crossover study in 18 healthy subjects assessed the effect of a single 800 mg oral dose of fluconazole on the pharmacokinetics of a single 1200 mg oral dose of azithromycin as well as the effects of azithromycin on the pharmacokinetics of fluconazole. There was no significant pharmacokinetic interaction between fluconazole and azithromycin. Voriconazole: Voriconazole is a substrate for both CYP2C9 and CYP3A4 isoenzymes. Concurrent administration of oral Voriconazole (400 mg Q12h for 1 day, then 200 mg Q12h for 2.5 days) and oral fluconazole (400 mg on Day 1, then 200 mg Q24h for 4 days) to 6 healthy male subjects resulted in an increase in C max and AUCτ of voriconazole by an average of 57% (90% CI: 20% to 107%) and 79% (90% CI: 40% to 128%), respectively. In a follow-on clinical study involving 8 healthy male subjects, reduced dosing and/or frequency of voriconazole and fluconazole did not eliminate or diminish this effect. (See PRECAUTIONS . ) Tofacitinib: Coadministration of fluconazole (400 mg on Day 1 and 200 mg once daily for 6 days [Days 2 to 7]) and tofacitinib (30 mg single dose on Day 5) in healthy subjects resulted in increased mean tofacitinib AUC and C max values of approximately 79% (90% CI: 64% to 96%) and 27% (90% CI: 12% to 44%), respectively, compared to administration of tofacitinib alone. (See PRECAUTIONS . ) Abrocitinib : When coadministered with fluconazole (inhibitor of CYP2C9, 2C19, and 3A4), the systemic exposure (AUC) of abrocitinib was approximately 4.8-fold higher and the combined exposure (AUC) of abrocitinib and its active metabolites was approximately 2.5-fold higher compared to when abrocitinib was administered alone (See PRECAUTIONS ).","Drug Interactions: (See CONTRAINDICATIONS .) Fluconazole is a moderate CYP2C9 and CYP3A4 inhibitor. Fluconazole is also a strong inhibitor of CYP2C19. Patients treated with fluconazole, who are also concomitantly treated with drugs with a narrow therapeutic window metabolized through CYP2C9 and CYP3A4, should be monitored for adverse reactions associated with the concomitantly administered drugs. In addition to the observed /documented interactions mentioned below, there is a risk of increased plasma concentration of other compounds metabolized by CYP2C9, CYP2C19, and CYP3A4 coadministered with fluconazole. Therefore, caution should be exercised when using these combinations and the patients should be carefully monitored. The enzyme inhibiting effect of fluconazole persists 4 to 5 days after discontinuation of fluconazole treatment due to the long half-life of fluconazole. Clinically or potentially significant drug interactions between fluconazole and the following agents/classes have been observed and are described in greater detail below: Abrocitinib : Drug interaction studies indicate that when coadministered with fluconazole (strong inhibitor of CYP2C19; moderate inhibitor of CYP2C9 and CYP3A4), the systemic exposure of abrocitinib and its active metabolites increased (See CLINICAL PHARMACOLOGY ). Avoid concomitant use of abrocitinib with fluconazole. Refer to the abrocitinib Prescribing Information for additional details. Alfentanil : A study observed a reduction in clearance and distribution volume as well as prolongation of t ½ of alfentanil following concomitant treatment with fluconazole. A possible mechanism of action is fluconazole’s inhibition of CYP3A4. Dosage adjustment of alfentanil may be necessary. Amiodarone : Concomitant administration of fluconazole with amiodarone may increase QT prolongation. Caution must be exercised if the concomitant use of fluconazole and amiodarone is necessary, notably with high-dose fluconazole (800 mg). Amitriptyline, nortriptyline : Fluconazole increases the effect of amitriptyline and nortriptyline. 5-Nortriptyline and/or S-amitriptyline may be measured at initiation of the combination therapy and after 1 week. Dosage of amitriptyline/nortriptyline should be adjusted, if necessary. Amphotericin B : Concurrent administration of fluconazole and amphotericin B in infected normal and immunosuppressed mice showed the following results: a small additive antifungal effect in systemic infection with Candida albicans , no interaction in intracranial infection with Cryptococcus neoformans , and antagonism of the two drugs in systemic infection with A. fumigatus . The clinical significance of results obtained in these studies is unknown. Azithromycin : An open-label, randomized, three-way crossover study in 18 healthy subjects assessed the effect of a single 1200 mg oral dose of azithromycin on the pharmacokinetics of a single 800 mg oral dose of fluconazole as well as the effects of fluconazole on the pharmacokinetics of azithromycin. There was no significant pharmacokinetic interaction between fluconazole and azithromycin. Calcium channel blockers : Certain calcium channel antagonists (nifedipine, isradipine, amlodipine, verapamil, and felodipine) are metabolized by CYP3A4. Fluconazole has the potential to increase the systemic exposure of the calcium channel antagonists. Frequent monitoring for adverse events is recommended. Carbamazepine : Fluconazole inhibits the metabolism of carbamazepine and an increase in serum carbamazepine of 30% has been observed. There is a risk of developing carbamazepine toxicity. Dosage adjustment of carbamazepine may be necessary depending on concentration measurements/effect. Celecoxib : During concomitant treatment with fluconazole (200 mg daily) and celecoxib (200 mg), the celecoxib C max and AUC increased by 68% and 134%, respectively. Half of the celecoxib dose may be necessary when combined with fluconazole. Coumarin-type anticoagulants: Prothrombin time may be increased in patients receiving concomitant fluconazole and coumarin-type anticoagulants. In post-marketing experience, as with other azole antifungals, bleeding events (bruising, epistaxis, gastrointestinal bleeding, hematuria, and melena) have been reported in association with increases in prothrombin time in patients receiving fluconazole concurrently with warfarin. Careful monitoring of prothrombin time in patients receiving fluconazole and coumarin-type anticoagulants is recommended. Dose adjustment of warfarin may be necessary. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies . ) Cyclophosphamide : Combination therapy with cyclophosphamide and fluconazole results in an increase in serum bilirubin and serum creatinine. The combination may be used while taking increased consideration to the risk of increased serum bilirubin and serum creatinine. Cyclosporine: Fluconazole significantly increases cyclosporine levels in renal transplant patients with or without renal impairment. Careful monitoring of cyclosporine concentrations and serum creatinine is recommended in patients receiving fluconazole and cyclosporine. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies . ) This combination may be used by reducing the dosage of cyclosporine depending on cyclosporine concentration. Fentanyl : One fatal case of possible fentanyl-fluconazole interaction was reported. The author judged that the patient died from fentanyl intoxication. Furthermore, in a randomized crossover study with 12 healthy volunteers, it was shown that fluconazole delayed the elimination of fentanyl significantly. Elevated fentanyl concentration may lead to respiratory depression. HMG-CoA reductase inhibitors : The risk of myopathy and rhabdomyolysis increases when fluconazole is coadministered with HMG-CoA reductase inhibitors metabolized through CYP3A4, such as atorvastatin and simvastatin, or through CYP2C9, such as fluvastatin (decreased hepatic metabolism of the statin). If concomitant therapy is necessary, the patient should be observed for symptoms of myopathy and rhabdomyolysis and creatinine kinase should be monitored. HMG-CoA reductase inhibitors should be discontinued if a marked increase in creatinine kinase is observed or myopathy/rhabdomyolysis is diagnosed or suspected. Dose reduction of statins may be needed. Refer to the statin-specific prescribing information for details. Hydrochlorothiazide : In a pharmacokinetic interaction study, coadministration of multiple-dose hydrochlorothiazide to healthy volunteers receiving fluconazole increased plasma concentrations of fluconazole by 40%. An effect of this magnitude should not necessitate a change in the fluconazole dose regimen in subjects receiving concomitant diuretics. Ibrutinib: Moderate inhibitors of CYP3A4 such as fluconazole may increase plasma ibrutinib concentrations and increase risk of adverse reactions associated with ibrutinib. If ibrutinib and fluconazole are concomitantly administered, reduce the dose of ibrutinib as instructed in ibrutinib prescribing information and the patient should be frequently monitored for any adverse reactions associated with ibrutinib. Ivacaftor and fixed dose ivacaftor combinations (e.g.,tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor): Coadministration with ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, increased ivacaftor exposure by 3-fold. If used concomitantly with a moderate inhibitor of CYP3A4, such as fluconazole, a reduction in the dose of ivacaftor (or ivacaftor combination) is recommended as instructed in the ivacaftor (or ivacaftor combination) prescribing information. Lemborexant: Concomitant administration of fluconazole increased lemborexant C max and AUC by approximately 1.6- and 4.2-fold, respectively which is expected to increase risk of adverse reactions, such as somnolence. Avoid concomitant use of fluconazole with lemborexant. Losartan : Fluconazole inhibits the metabolism of losartan to its active metabolite (E-31 74) which is responsible for most of the angiotensin Il-receptor antagonism which occurs during treatment with losartan. Patients should have their blood pressure monitored continuously. Lurasidone: Concomitant use of moderate inhibitors of CYP3A4 such as fluconazole may increase lurasidone plasma concentrations. If concomitant use cannot be avoided, reduce the dose of lurasidone as instructed in the lurasidone prescribing information. Methadone : Fluconazole may enhance the serum concentration of methadone. Dosage adjustment of methadone may be necessary. Non-steroidal anti-inflammatory drugs: The C max and AUC of flurbiprofen were increased by 23% and 81%, respectively, when coadministered with fluconazole compared to administration of flurbiprofen alone. Similarly, the C max and AUC of the pharmacologically active isomer [S-(+)-ibuprofen] were increased by 15% and 82%, respectively, when fluconazole was coadministered with racemic ibuprofen (400 mg) compared to administration of racemic ibuprofen alone. Although not specifically studied, fluconazole has the potential to increase the systemic exposure of other non-steroidal anti-inflammatory drugs (NSAIDs) that are metabolized by CYP2C9 (e.g., naproxen, lornoxicam, meloxicam, diclofenac). Frequent monitoring for adverse events and toxicity related to NSAIDs is recommended. Adjustment of dosage of NSAIDs may be needed. Olaparib: Moderate inhibitors of CYP3A4 such as fluconazole increase olaparib plasma concentrations; concomitant use is not recommended. If the combination cannot be avoided, reduce the dose of olaparib as instructed in the LYNPARZA ® (Olaparib) Prescribing Information. Oral contraceptives : Two pharmacokinetic studies with a combined oral contraceptive have been performed using multiple doses of fluconazole. There were no relevant effects on hormone level in the 50 mg fluconazole study, while at 200 mg daily, the AUCs of ethinyl estradiol and levonorgestrel were increased 40% and 24%, respectively. Thus, multiple-dose use of fluconazole at these doses is unlikely to have an effect on the efficacy of the combined oral contraceptive. Oral hypoglycemics: Clinically significant hypoglycemia may be precipitated by the use of fluconazole with oral hypoglycemic agents; one fatality has been reported from hypoglycemia in association with combined fluconazole and glyburide use. Fluconazole reduces the metabolism of tolbutamide, glyburide, and glipizide and increases the plasma concentration of these agents. When fluconazole is used concomitantly with these or other sulfonylurea oral hypoglycemic agents, blood glucose concentrations should be carefully monitored and the dose of the sulfonylurea should be adjusted as necessary. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies .) Phenytoin: Fluconazole increases the plasma concentrations of phenytoin. Careful monitoring of phenytoin concentrations in patients receiving fluconazole and phenytoin is recommended. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies .) Pimozide : Although not studied in vitro or in vivo , concomitant administration of fluconazole with pimozide may result in inhibition of pimozide metabolism. Increased pimozide plasma concentrations can lead to QT prolongation and rare occurrences of torsade de pointes. Coadministration of fluconazole and pimozide is contraindicated. Prednisone : There was a case report that a liver-transplanted patient treated with prednisone developed acute adrenal cortex insufficiency when a 3 month therapy with fluconazole was discontinued. The discontinuation of fluconazole presumably caused an enhanced CYP3A4 activity which led to increased metabolism of prednisone. Patients on long-term treatment with fluconazole and prednisone should be carefully monitored for adrenal cortex insufficiency when fluconazole is discontinued. Quinidine: Although not studied in vitro or in vivo , concomitant administration of fluconazole with quinidine may result in inhibition of quinidine metabolism. Use of quinidine has been associated with QT prolongation and rare occurrences of torsade de pointes. Coadministration of fluconazole and quinidine is contraindicated. (See CONTRAINDICATIONS . ) Rifabutin: There have been reports that an interaction exists when fluconazole is administered concomitantly with rifabutin, leading to increased serum levels of rifabutin up to 80%. There have been reports of uveitis in patients to whom fluconazole and rifabutin were coadministered. Patients receiving rifabutin and fluconazole concomitantly should be carefully monitored. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies .) Rifampin: Rifampin enhances the metabolism of concurrently administered fluconazole. Depending on clinical circumstances, consideration should be given to increasing the dose of fluconazole when it is administered with rifampin. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies .) Saquinavir : Fluconazole increases the AUC of saquinavir by approximately 50%, C max by approximately 55%, and decreases the clearance of saquinavir by approximately 50% due to inhibition of saquinavir’s hepatic metabolism by CYP3A4 and inhibition of P-glycoprotein. Dosage adjustment of saquinavir may be necessary. Short-acting benzodiazepines: Following oral administration of midazolam, fluconazole resulted in substantial increases in midazolam concentrations and psychomotor effects. This effect on midazolam appears to be more pronounced following oral administration of fluconazole than with fluconazole administered intravenously. If short-acting benzodiazepines, which are metabolized by the cytochrome P450 system, are concomitantly administered with fluconazole, consideration should be given to decreasing the benzodiazepine dosage, and the patients should be appropriately monitored. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies .) Sirolimus : Fluconazole increases plasma concentrations of sirolimus presumably by inhibiting the metabolism of sirolimus via CYP3A4 and P-glycoprotein. This combination may be used with a dosage adjustment of sirolimus depending on the effect/concentration measurements. Tacrolimus: Fluconazole may increase the serum concentrations of orally administered tacrolimus up to 5 times due to inhibition of tacrolimus metabolism through CYP3A4 in the intestines. No significant pharmacokinetic changes have been observed when tacrolimus is given intravenously. Increased tacrolimus levels have been associated with nephrotoxicity. Dosage of orally administered tacrolimus should be decreased depending on tacrolimus concentration. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies .) Theophylline: Fluconazole increases the serum concentrations of theophylline. Careful monitoring of serum theophylline concentrations in patients receiving fluconazole and theophylline is recommended. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies .) Tofacitinib: Systemic exposure to tofacitinib is increased when tofacitinib is coadministered with fluconazole. Reduce the dose of tofacitinib when given concomitantly with fluconazole (i.e., from 5 mg twice daily to 5 mg once daily as instructed in the XELJANZ ® [tofacitinib] label). (See CLINICAL PHARMACOLOGY : Drug Interaction Studies . ) Tolvaptan: Plasma exposure to tolvaptan is significantly increased (200% in AUC; 80% in C max ) when tolvaptan, a CYP3A4 substrate, is coadministered with fluconazole, a moderate CYP3A4 inhibitor. This interaction may result in the risk of a significant increase in adverse reactions associated with tolvaptan, particularly significant diuresis, dehydration, and acute renal failure. If tolvaptan and fluconazole are concomitantly administered, the tolvaptan dose should be reduced as instructed in the tolvaptan prescribing information and the patient should be frequently monitored for any adverse reactions associated with tolvaptan. Triazolam: Fluconazole increases the AUC of triazolam (single dose) by approximately 50%, C max by 20% to 32%, and increases t½ by 25% to 50% due to the inhibition of metabolism of triazolam. Dosage adjustments of triazolam may be necessary. Vinca alkaloids : Although not studied, fluconazole may increase the plasma levels of the vinca alkaloids (e.g., vincristine and vinblastine) and lead to neurotoxicity, which is possibly due to an inhibitory effect on CYP3A4. Vitamin A : Based on a case report in one patient receiving combination therapy with all-trans-retinoid acid (an acid form of vitamin A) and fluconazole, central nervous system (CNS) related undesirable effects have developed in the form of pseudotumor cerebri, which disappeared after discontinuation of fluconazole treatment. This combination may be used but the incidence of CNS related undesirable effects should be borne in mind. Voriconazole: Avoid concomitant administration of voriconazole and fluconazole. Monitoring for adverse events and toxicity related to voriconazole is recommended; especially, if voriconazole is started within 24 h after the last dose of fluconazole. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies . ) Zidovudine : Fluconazole increases the C max and AUC of zidovudine by 84% and 74%, respectively, due to an approximately 45% decrease in oral zidovudine clearance. The half-life of zidovudine was likewise prolonged by approximately 128% following combination therapy with fluconazole. Patients receiving this combination should be monitored for the development of zidovudine-related adverse reactions. Dosage reduction of zidovudine may be considered. Physicians should be aware that interaction studies with medications other than those listed in the CLINICAL PHARMACOLOGY section have not been conducted, but such interactions may occur."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Fluconazole for oral suspension is indicated for the treatment of: Oropharyngeal and esophageal candidiasis. In open noncomparative studies of relatively small numbers of patients, fluconazole for oral suspension was also effective for the treatment of Candida urinary tract infections, peritonitis, and systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia. Cryptococcal meningitis . Before prescribing fluconazole for oral suspension for AIDS patients with cryptococcal meningitis , please see CLINICAL STUDIES section. Studies comparing fluconazole for oral suspension to amphotericin B in non-HIV infected patients have not been conducted. Prophylaxis: Fluconazole for oral suspension is also indicated to decrease the incidence of candidiasis in patients undergoing bone marrow transplantation who receive cytotoxic chemotherapy and/or radiation therapy. Specimens for fungal culture and other relevant laboratory studies (serology, histopathology) should be obtained prior to therapy to isolate and identify causative organisms. Therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, anti-infective therapy should be adjusted accordingly."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE There have been reports of overdose with fluconazole accompanied by hallucination and paranoid behavior. In the event of overdose, symptomatic treatment (with supportive measures and gastric lavage if clinically indicated) should be instituted. Fluconazole is largely excreted in urine. A 3-hour hemodialysis session decreases plasma levels by approximately 50%. In mice and rats receiving very high doses of fluconazole, clinical effects in both species included decreased motility and respiration, ptosis, lacrimation, salivation, urinary incontinence, loss of righting reflex, and cyanosis; death was sometimes preceded by clonic convulsions."}', 'active_flag': 'Y', 'generic_name': '{FLUCONAZOLE}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS (1) Hepatic injury: Fluconazole should be administered with caution to patients with liver dysfunction. Fluconazole has been associated with rare cases of serious hepatic toxicity, including fatalities primarily in patients with serious underlying medical conditions. In cases of fluconazole-associated hepatotoxicity, no obvious relationship to total daily dose, duration of therapy, sex, or age of the patient has been observed. Fluconazole hepatotoxicity has usually, but not always, been reversible on discontinuation of therapy. Patients who develop abnormal liver function tests during fluconazole therapy should be monitored for the development of more severe hepatic injury. Fluconazole should be discontinued if clinical signs and symptoms consistent with liver disease develop that may be attributable to fluconazole. (2) Anaphylaxis: In rare cases, anaphylaxis has been reported. (3) Dermatologic: Exfoliative skin disorders during treatment with fluconazole have been reported. Fatal outcomes have been reported in patients with serious underlying diseases. Patients with deep seated fungal infections who develop rashes during treatment with fluconazole should be monitored closely and the drug discontinued if lesions progress. Fluconazole should be discontinued in patients treated for superficial fungal infection who develop a rash that may be attributed to fluconazole. (4) Potential for fetal harm: There are no adequate and well-controlled clinical trials of fluconazole in pregnant women. Case reports describe a pattern of distinct congenital anomalies in infants exposed in utero to high dose maternal fluconazole (400 to 800 mg/day) during most or all of the first trimester. These reported anomalies are similar to those seen in animal studies. If fluconazole is used during pregnancy or if the patient becomes pregnant while taking the drug, the patient should be informed of the potential hazard to the fetus. Effective contraceptive measures should be considered in women of child-bearing potential who are being treated with fluconazole 400 to 800 mg/day and should continue throughout the treatment period and for approximately 1 week (5 to 6 half-lives) after the final dose. Epidemiological studies suggest a potential risk of spontaneous abortion and congenital abnormalities in infants whose mothers were treated with 150 mg of fluconazole as a single or repeated dose in the first trimester, but these epidemiological studies have limitations and these findings have not been confirmed in controlled clinical trials. (See PRECAUTIONS: Pregnancy . )"}', 'precautions': '{"PRECAUTIONS General Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram. Fluconazole causes QT prolongation via the inhibition of Rectifier Potassium Channel current (Ikr). The QT prolongation caused by other medicinal products (such as amiodarone) may be amplified via the inhibition of cytochrome P450 (CYP) 3A4. (See PRECAUTIONS: Drug Interactions. ) During post-marketing surveillance, there have been rare cases of QT prolongation and torsade de pointes in patients taking fluconazole. Most of these reports involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications that may have been contributory. Patients with hypokalemia and advanced cardiac failure are at an increased risk for the occurrence of life-threatening ventricular arrhythmias and torsade de pointes. Fluconazole should be administered with caution to patients with these potentially proarrhythmic conditions. Concomitant use of fluconazole and erythromycin has the potential to increase the risk of cardiotoxicity (prolonged QT interval, torsade de pointes) and consequently sudden heart death. This combination should be avoided. Fluconazole should be administered with caution to patients with renal dysfunction. Adrenal insufficiency has been reported in patients receiving azoles, including fluconazole. Reversible cases of adrenal insufficiency have been reported in patients receiving fluconazole. Fluconazole for Oral Suspension contains sucrose and should not be used in patients with hereditary fructose, glucose/galactose malabsorption, and sucrase-isomaltase deficiency. When driving vehicles or operating machines, it should be taken into account that occasionally dizziness or seizures may occur. There have been reports of cases of superinfection with Candida species other than C. albicans , which are often inherently not susceptible to fluconazole (e.g., Candida krusei ). Such cases may require alternative antifungal therapy (see CLINICAL PHARMACOLOGY , Microbiology ). Drug Interactions: (See CONTRAINDICATIONS .) Fluconazole is a moderate CYP2C9 and CYP3A4 inhibitor. Fluconazole is also a strong inhibitor of CYP2C19. Patients treated with fluconazole, who are also concomitantly treated with drugs with a narrow therapeutic window metabolized through CYP2C9 and CYP3A4, should be monitored for adverse reactions associated with the concomitantly administered drugs. In addition to the observed /documented interactions mentioned below, there is a risk of increased plasma concentration of other compounds metabolized by CYP2C9, CYP2C19, and CYP3A4 coadministered with fluconazole. Therefore, caution should be exercised when using these combinations and the patients should be carefully monitored. The enzyme inhibiting effect of fluconazole persists 4 to 5 days after discontinuation of fluconazole treatment due to the long half-life of fluconazole. Clinically or potentially significant drug interactions between fluconazole and the following agents/classes have been observed and are described in greater detail below: Abrocitinib : Drug interaction studies indicate that when coadministered with fluconazole (strong inhibitor of CYP2C19; moderate inhibitor of CYP2C9 and CYP3A4), the systemic exposure of abrocitinib and its active metabolites increased (See CLINICAL PHARMACOLOGY ). Avoid concomitant use of abrocitinib with fluconazole. Refer to the abrocitinib Prescribing Information for additional details. Alfentanil : A study observed a reduction in clearance and distribution volume as well as prolongation of t ½ of alfentanil following concomitant treatment with fluconazole. A possible mechanism of action is fluconazole’s inhibition of CYP3A4. Dosage adjustment of alfentanil may be necessary. Amiodarone : Concomitant administration of fluconazole with amiodarone may increase QT prolongation. Caution must be exercised if the concomitant use of fluconazole and amiodarone is necessary, notably with high-dose fluconazole (800 mg). Amitriptyline, nortriptyline : Fluconazole increases the effect of amitriptyline and nortriptyline. 5-Nortriptyline and/or S-amitriptyline may be measured at initiation of the combination therapy and after 1 week. Dosage of amitriptyline/nortriptyline should be adjusted, if necessary. Amphotericin B : Concurrent administration of fluconazole and amphotericin B in infected normal and immunosuppressed mice showed the following results: a small additive antifungal effect in systemic infection with Candida albicans , no interaction in intracranial infection with Cryptococcus neoformans , and antagonism of the two drugs in systemic infection with A. fumigatus . The clinical significance of results obtained in these studies is unknown. Azithromycin : An open-label, randomized, three-way crossover study in 18 healthy subjects assessed the effect of a single 1200 mg oral dose of azithromycin on the pharmacokinetics of a single 800 mg oral dose of fluconazole as well as the effects of fluconazole on the pharmacokinetics of azithromycin. There was no significant pharmacokinetic interaction between fluconazole and azithromycin. Calcium channel blockers : Certain calcium channel antagonists (nifedipine, isradipine, amlodipine, verapamil, and felodipine) are metabolized by CYP3A4. Fluconazole has the potential to increase the systemic exposure of the calcium channel antagonists. Frequent monitoring for adverse events is recommended. Carbamazepine : Fluconazole inhibits the metabolism of carbamazepine and an increase in serum carbamazepine of 30% has been observed. There is a risk of developing carbamazepine toxicity. Dosage adjustment of carbamazepine may be necessary depending on concentration measurements/effect. Celecoxib : During concomitant treatment with fluconazole (200 mg daily) and celecoxib (200 mg), the celecoxib C max and AUC increased by 68% and 134%, respectively. Half of the celecoxib dose may be necessary when combined with fluconazole. Coumarin-type anticoagulants: Prothrombin time may be increased in patients receiving concomitant fluconazole and coumarin-type anticoagulants. In post-marketing experience, as with other azole antifungals, bleeding events (bruising, epistaxis, gastrointestinal bleeding, hematuria, and melena) have been reported in association with increases in prothrombin time in patients receiving fluconazole concurrently with warfarin. Careful monitoring of prothrombin time in patients receiving fluconazole and coumarin-type anticoagulants is recommended. Dose adjustment of warfarin may be necessary. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies . ) Cyclophosphamide : Combination therapy with cyclophosphamide and fluconazole results in an increase in serum bilirubin and serum creatinine. The combination may be used while taking increased consideration to the risk of increased serum bilirubin and serum creatinine. Cyclosporine: Fluconazole significantly increases cyclosporine levels in renal transplant patients with or without renal impairment. Careful monitoring of cyclosporine concentrations and serum creatinine is recommended in patients receiving fluconazole and cyclosporine. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies . ) This combination may be used by reducing the dosage of cyclosporine depending on cyclosporine concentration. Fentanyl : One fatal case of possible fentanyl-fluconazole interaction was reported. The author judged that the patient died from fentanyl intoxication. Furthermore, in a randomized crossover study with 12 healthy volunteers, it was shown that fluconazole delayed the elimination of fentanyl significantly. Elevated fentanyl concentration may lead to respiratory depression. HMG-CoA reductase inhibitors : The risk of myopathy and rhabdomyolysis increases when fluconazole is coadministered with HMG-CoA reductase inhibitors metabolized through CYP3A4, such as atorvastatin and simvastatin, or through CYP2C9, such as fluvastatin (decreased hepatic metabolism of the statin). If concomitant therapy is necessary, the patient should be observed for symptoms of myopathy and rhabdomyolysis and creatinine kinase should be monitored. HMG-CoA reductase inhibitors should be discontinued if a marked increase in creatinine kinase is observed or myopathy/rhabdomyolysis is diagnosed or suspected. Dose reduction of statins may be needed. Refer to the statin-specific prescribing information for details. Hydrochlorothiazide : In a pharmacokinetic interaction study, coadministration of multiple-dose hydrochlorothiazide to healthy volunteers receiving fluconazole increased plasma concentrations of fluconazole by 40%. An effect of this magnitude should not necessitate a change in the fluconazole dose regimen in subjects receiving concomitant diuretics. Ibrutinib: Moderate inhibitors of CYP3A4 such as fluconazole may increase plasma ibrutinib concentrations and increase risk of adverse reactions associated with ibrutinib. If ibrutinib and fluconazole are concomitantly administered, reduce the dose of ibrutinib as instructed in ibrutinib prescribing information and the patient should be frequently monitored for any adverse reactions associated with ibrutinib. Ivacaftor and fixed dose ivacaftor combinations (e.g.,tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor): Coadministration with ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, increased ivacaftor exposure by 3-fold. If used concomitantly with a moderate inhibitor of CYP3A4, such as fluconazole, a reduction in the dose of ivacaftor (or ivacaftor combination) is recommended as instructed in the ivacaftor (or ivacaftor combination) prescribing information. Lemborexant: Concomitant administration of fluconazole increased lemborexant C max and AUC by approximately 1.6- and 4.2-fold, respectively which is expected to increase risk of adverse reactions, such as somnolence. Avoid concomitant use of fluconazole with lemborexant. Losartan : Fluconazole inhibits the metabolism of losartan to its active metabolite (E-31 74) which is responsible for most of the angiotensin Il-receptor antagonism which occurs during treatment with losartan. Patients should have their blood pressure monitored continuously. Lurasidone: Concomitant use of moderate inhibitors of CYP3A4 such as fluconazole may increase lurasidone plasma concentrations. If concomitant use cannot be avoided, reduce the dose of lurasidone as instructed in the lurasidone prescribing information. Methadone : Fluconazole may enhance the serum concentration of methadone. Dosage adjustment of methadone may be necessary. Non-steroidal anti-inflammatory drugs: The C max and AUC of flurbiprofen were increased by 23% and 81%, respectively, when coadministered with fluconazole compared to administration of flurbiprofen alone. Similarly, the C max and AUC of the pharmacologically active isomer [S-(+)-ibuprofen] were increased by 15% and 82%, respectively, when fluconazole was coadministered with racemic ibuprofen (400 mg) compared to administration of racemic ibuprofen alone. Although not specifically studied, fluconazole has the potential to increase the systemic exposure of other non-steroidal anti-inflammatory drugs (NSAIDs) that are metabolized by CYP2C9 (e.g., naproxen, lornoxicam, meloxicam, diclofenac). Frequent monitoring for adverse events and toxicity related to NSAIDs is recommended. Adjustment of dosage of NSAIDs may be needed. Olaparib: Moderate inhibitors of CYP3A4 such as fluconazole increase olaparib plasma concentrations; concomitant use is not recommended. If the combination cannot be avoided, reduce the dose of olaparib as instructed in the LYNPARZA ® (Olaparib) Prescribing Information. Oral contraceptives : Two pharmacokinetic studies with a combined oral contraceptive have been performed using multiple doses of fluconazole. There were no relevant effects on hormone level in the 50 mg fluconazole study, while at 200 mg daily, the AUCs of ethinyl estradiol and levonorgestrel were increased 40% and 24%, respectively. Thus, multiple-dose use of fluconazole at these doses is unlikely to have an effect on the efficacy of the combined oral contraceptive. Oral hypoglycemics: Clinically significant hypoglycemia may be precipitated by the use of fluconazole with oral hypoglycemic agents; one fatality has been reported from hypoglycemia in association with combined fluconazole and glyburide use. Fluconazole reduces the metabolism of tolbutamide, glyburide, and glipizide and increases the plasma concentration of these agents. When fluconazole is used concomitantly with these or other sulfonylurea oral hypoglycemic agents, blood glucose concentrations should be carefully monitored and the dose of the sulfonylurea should be adjusted as necessary. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies .) Phenytoin: Fluconazole increases the plasma concentrations of phenytoin. Careful monitoring of phenytoin concentrations in patients receiving fluconazole and phenytoin is recommended. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies .) Pimozide : Although not studied in vitro or in vivo , concomitant administration of fluconazole with pimozide may result in inhibition of pimozide metabolism. Increased pimozide plasma concentrations can lead to QT prolongation and rare occurrences of torsade de pointes. Coadministration of fluconazole and pimozide is contraindicated. Prednisone : There was a case report that a liver-transplanted patient treated with prednisone developed acute adrenal cortex insufficiency when a 3 month therapy with fluconazole was discontinued. The discontinuation of fluconazole presumably caused an enhanced CYP3A4 activity which led to increased metabolism of prednisone. Patients on long-term treatment with fluconazole and prednisone should be carefully monitored for adrenal cortex insufficiency when fluconazole is discontinued. Quinidine: Although not studied in vitro or in vivo , concomitant administration of fluconazole with quinidine may result in inhibition of quinidine metabolism. Use of quinidine has been associated with QT prolongation and rare occurrences of torsade de pointes. Coadministration of fluconazole and quinidine is contraindicated. (See CONTRAINDICATIONS . ) Rifabutin: There have been reports that an interaction exists when fluconazole is administered concomitantly with rifabutin, leading to increased serum levels of rifabutin up to 80%. There have been reports of uveitis in patients to whom fluconazole and rifabutin were coadministered. Patients receiving rifabutin and fluconazole concomitantly should be carefully monitored. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies .) Rifampin: Rifampin enhances the metabolism of concurrently administered fluconazole. Depending on clinical circumstances, consideration should be given to increasing the dose of fluconazole when it is administered with rifampin. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies .) Saquinavir : Fluconazole increases the AUC of saquinavir by approximately 50%, C max by approximately 55%, and decreases the clearance of saquinavir by approximately 50% due to inhibition of saquinavir’s hepatic metabolism by CYP3A4 and inhibition of P-glycoprotein. Dosage adjustment of saquinavir may be necessary. Short-acting benzodiazepines: Following oral administration of midazolam, fluconazole resulted in substantial increases in midazolam concentrations and psychomotor effects. This effect on midazolam appears to be more pronounced following oral administration of fluconazole than with fluconazole administered intravenously. If short-acting benzodiazepines, which are metabolized by the cytochrome P450 system, are concomitantly administered with fluconazole, consideration should be given to decreasing the benzodiazepine dosage, and the patients should be appropriately monitored. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies .) Sirolimus : Fluconazole increases plasma concentrations of sirolimus presumably by inhibiting the metabolism of sirolimus via CYP3A4 and P-glycoprotein. This combination may be used with a dosage adjustment of sirolimus depending on the effect/concentration measurements. Tacrolimus: Fluconazole may increase the serum concentrations of orally administered tacrolimus up to 5 times due to inhibition of tacrolimus metabolism through CYP3A4 in the intestines. No significant pharmacokinetic changes have been observed when tacrolimus is given intravenously. Increased tacrolimus levels have been associated with nephrotoxicity. Dosage of orally administered tacrolimus should be decreased depending on tacrolimus concentration. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies .) Theophylline: Fluconazole increases the serum concentrations of theophylline. Careful monitoring of serum theophylline concentrations in patients receiving fluconazole and theophylline is recommended. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies .) Tofacitinib: Systemic exposure to tofacitinib is increased when tofacitinib is coadministered with fluconazole. Reduce the dose of tofacitinib when given concomitantly with fluconazole (i.e., from 5 mg twice daily to 5 mg once daily as instructed in the XELJANZ ® [tofacitinib] label). (See CLINICAL PHARMACOLOGY : Drug Interaction Studies . ) Tolvaptan: Plasma exposure to tolvaptan is significantly increased (200% in AUC; 80% in C max ) when tolvaptan, a CYP3A4 substrate, is coadministered with fluconazole, a moderate CYP3A4 inhibitor. This interaction may result in the risk of a significant increase in adverse reactions associated with tolvaptan, particularly significant diuresis, dehydration, and acute renal failure. If tolvaptan and fluconazole are concomitantly administered, the tolvaptan dose should be reduced as instructed in the tolvaptan prescribing information and the patient should be frequently monitored for any adverse reactions associated with tolvaptan. Triazolam: Fluconazole increases the AUC of triazolam (single dose) by approximately 50%, C max by 20% to 32%, and increases t½ by 25% to 50% due to the inhibition of metabolism of triazolam. Dosage adjustments of triazolam may be necessary. Vinca alkaloids : Although not studied, fluconazole may increase the plasma levels of the vinca alkaloids (e.g., vincristine and vinblastine) and lead to neurotoxicity, which is possibly due to an inhibitory effect on CYP3A4. Vitamin A : Based on a case report in one patient receiving combination therapy with all-trans-retinoid acid (an acid form of vitamin A) and fluconazole, central nervous system (CNS) related undesirable effects have developed in the form of pseudotumor cerebri, which disappeared after discontinuation of fluconazole treatment. This combination may be used but the incidence of CNS related undesirable effects should be borne in mind. Voriconazole: Avoid concomitant administration of voriconazole and fluconazole. Monitoring for adverse events and toxicity related to voriconazole is recommended; especially, if voriconazole is started within 24 h after the last dose of fluconazole. (See CLINICAL PHARMACOLOGY : Drug Interaction Studies . ) Zidovudine : Fluconazole increases the C max and AUC of zidovudine by 84% and 74%, respectively, due to an approximately 45% decrease in oral zidovudine clearance. The half-life of zidovudine was likewise prolonged by approximately 128% following combination therapy with fluconazole. Patients receiving this combination should be monitored for the development of zidovudine-related adverse reactions. Dosage reduction of zidovudine may be considered. Physicians should be aware that interaction studies with medications other than those listed in the CLINICAL PHARMACOLOGY section have not been conducted, but such interactions may occur. Carcinogenesis, Mutagenesis, Impairment of Fertility Fluconazole showed no evidence of carcinogenic potential in mice and rats treated orally for 24 months at doses of 2.5 mg/kg/day, 5 mg/kg/day, or 10 mg/kg/day (approximately 2 to 7 times the recommended human dose). Male rats treated with 5 mg/kg/day and 10 mg/kg/day had an increased incidence of hepatocellular adenomas. Fluconazole, with or without metabolic activation, was negative in tests for mutagenicity in four strains of S. typhimurium, and in the mouse lymphoma L5178Y system. Cytogenetic studies in vivo (murine bone marrow cells, following oral administration of fluconazole) and in vitro (human lymphocytes exposed to fluconazole at 1000 mcg/mL) showed no evidence of chromosomal mutations. Fluconazole did not affect the fertility of male or female rats treated orally with daily doses of 5 mg/kg, 10 mg/kg, or 20 mg/kg or with parenteral doses of 5 mg/kg, 25 mg/kg, or 75 mg/kg, although the onset of parturition was slightly delayed at 20 mg/kg PO. In an intravenous perinatal study in rats at 5 mg/kg, 20 mg/kg, and 40 mg/kg, dystocia and prolongation of parturition were observed in a few dams at 20 mg/kg (approximately 5 to 15 times the recommended human dose) and 40 mg/kg, but not at 5 mg/kg. The disturbances in parturition were reflected by a slight increase in the number of still born pups and decrease of neonatal survival at these dose levels. The effects on parturition in rats are consistent with the species specific estrogen-lowering property produced by high doses of fluconazole. Such a hormone change has not been observed in women treated with fluconazole. (See CLINICAL PHARMACOLOGY .) Pregnancy Teratogenic Effects. Potential for Fetal Harm: Use in pregnancy should be avoided except in patients with severe or potentially life-threatening fungal infections in whom fluconazole may be used if the anticipated benefit outweighs the possible risk to the fetus. A few published case reports describe a pattern of distinct congenital anomalies in infants exposed in utero to high dose maternal fluconazole (400 to 800 mg/day) during most or all of the first trimester. These reported anomalies are similar to those seen in animal studies. Effective contraceptive measures should be considered in women of child-bearing potential who are being treated with fluconazole 400 to 800 mg/day and should continue throughout the treatment period and for approximately 1 week (5 to 6 half-lives) after the final dose. If fluconazole is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be informed of the potential hazard to the fetus. Spontaneous abortions and congenital abnormalities have been suggested as potential risks associated with 150 mg of fluconazole as a single or repeated dose in the first trimester of pregnancy based on retrospective epidemiological studies. There are no adequate and well-controlled studies of fluconazole in pregnant women. (See WARNINGS: Potential for Fetal Harm . ) Human Data Case reports describe a distinctive and rare pattern of birth defects among infants whose mothers received high-dose (400 to 800 mg/day) fluconazole during most or all of the first trimester of pregnancy. The features seen in these infants include brachycephaly, abnormal facies, abnormal calvarial development, cleft palate, femoral bowing, thin ribs and long bones, arthrogryposis, and congenital heart disease. These effects are similar to those seen in animal studies. Epidemiological studies suggest a potential risk of spontaneous abortion and congenital abnormalities in infants whose mothers were treated with 150 mg of fluconazole as a single or repeated dose in the first trimester, but these epidemiological studies have limitations and these findings have not been confirmed in controlled clinical trials. Animal Data Fluconazole was administered orally to pregnant rabbits during organogenesis in two studies at doses of 5 mg/kg, 10 mg/kg, and 20 mg/kg and at 5 mg/kg, 25 mg/kg, and 75 mg/kg, respectively. Maternal weight gain was impaired at all dose levels (approximately 0.25 to 4 times the 400 mg clinical dose based on body surface area [BSA] comparison), and abortions occurred at 75 mg/kg (approximately 4 times the 400 mg clinical dose based on BSA); no adverse fetal effects were observed. In several studies in which pregnant rats received fluconazole orally during organogenesis, maternal weight gain was impaired and placental weights were increased at 25 mg/kg. There were no fetal effects at 5 mg/kg or 10 mg/kg; increases in fetal anatomical variants (supernumerary ribs, renal pelvis dilation) and delays in ossification were observed at 25 mg/kg and 50 mg/kg and higher doses. At doses ranging from 80 to 320 mg/kg (approximately 2 to 8 times the 400 mg clinical dose based on BSA), embryolethality in rats was increased and fetal abnormalities included wavy ribs, cleft palate, and abnormal craniofacial ossification. These effects are consistent with the inhibition of estrogen synthesis in rats and may be a result of known effects of lowered estrogen on pregnancy, organogenesis, and parturition. Nursing Mothers Fluconazole was present in low levels in breast milk following administration of a single 150 mg dose, based on data from a study in 10 breastfeeding women who temporarily or permanently discontinued breastfeeding 5 days to 19 months postpartum. The estimated daily infant dose of fluconazole from breast milk (assuming mean milk consumption of 150 mL/kg/day) based on the mean peak milk concentration (2.61 mcg/mL [range: 1.57 to 3.65 mcg/mL] at 5.2 hours post-dose) was 0.39 mg/kg/day, which is approximately 13% of the recommended pediatric dose for oropharyngeal candidiasis. (Labeled pediatric dose is 6 mg/kg/day on the first day followed by 3 mg/kg/day; estimated infant dose is 13% of 3 mg/kg/day maintenance dose). There are no data on fluconazole levels in milk after repeated use or after high-dose fluconazole. A published survey of 96 breastfeeding women who were treated with fluconazole 150 mg every other day (average of 7.3 capsules [range 1 to 29 capsules]) for lactation-associated candida of the breasts reported no serious adverse reactions in infants. Caution should be exercised when fluconazole is administered to a nursing woman. Pediatric Use Use in Pediatric Patients for the Treatment of Oropharyngeal Candidiasis An open-label, randomized, controlled trial has shown fluconazole to be effective in the treatment of oropharyngeal candidiasis in pediatric patients 6 months to 13 years of age. (See CLINICAL STUDIES .) Use in Pediatric Patients for the Treatment of Candida Esophagitis, Systemic Candida Infections, or Cryptococcal Meningitis The use of fluconazole in pediatric patients with cryptococcal meningitis , Candida esophagitis, or systemic Candida infections is supported by the efficacy shown for these indications in adults and by the results from several small noncomparative pediatric clinical studies. In addition, pharmacokinetic studies in pediatric patients (See CLINICAL PHARMACOLOGY ) have established a dose proportionality between pediatric patients and adults. (See DOSAGE AND ADMINISTRATION .) In a noncomparative study of fluconazole administered to pediatric patients (from birth to less than 17 years) with serious systemic fungal infections, most of which were candidemia, the effectiveness of fluconazole was similar to that reported for the treatment of candidemia in adults. Of 17 subjects with culture-confirmed candidemia, 11 of 14 (79%) with baseline symptoms (3 were asymptomatic) had a clinical cure; 13/15 (87%) of evaluable patients had a mycologic cure at the end of treatment but two of these patients relapsed at 10 and 18 days, respectively, following cessation of therapy. The efficacy of fluconazole for the suppression of cryptococcal meningitis was successful in 4 of 5 pediatric patients (4 years to 10 years of age) treated in a compassionate-use study of fluconazole for the treatment of life-threatening or serious mycosis. There are limited clinical data to support the efficacy of fluconazole for the primary treatment of cryptococcal meningitis in pediatric patients. The safety profile of fluconazole has been studied in 577 pediatric patients from 1 day to 17 years of age who received doses ranging from 1 to 15 mg/kg/day for 1 to 1,616 days. (See ADVERSE REACTIONS .) Use in Pediatric Patients on Extracorporeal Membrane Oxygenation (ECMO) A prospective, open-label, single-center study was conducted to determine the PK and safety of fluconazole in pediatric patients (ages: from birth to 17 years of age) on ECMO (see CLINICAL PHARMACOLOGY ). A loading dose of 35 mg/kg is recommended in pediatric patients on ECMO due to increased volume of distribution (see DOSAGE AND ADMINISTRATION ). Use in Prophylaxis of Invasive Candida Infections in Pediatric Patients (premature infants weighing less than 750 grams at birth) Safety and effectiveness of fluconazole for the prophylaxis of invasive candidiasis in pediatric patients (premature infants weighing less than 750 grams at birth) have not been established. A prospective, randomized, double-blind, placebo-controlled, multicenter trial was conducted in premature infants weighing less than 750 grams at birth to evaluate the efficacy and safety of prophylactic fluconazole 6 mg/kg administered twice weekly for 6 weeks versus placebo (NCT00734539). Efficacy was assessed using the endpoint of death or candidiasis by study day 49. The results are summarized in Table 4. Table 4: Death or Candidiasis by Day 49 in Premature Infants Receiving Fluconazole Prophylaxis Fluconazole (N=188) n (%) Placebo (N=173) n (%) P-value Difference (95% CI) Death or candidiasis* 33 (17.6) 38 (22.0) 0.2954 -4.4(-12.6, 3.8) Components of endpoint** Death Candidiasis Missing 27 (14.4) 6 (3.2) 2 (1.0) 25 (14.5) 16 (9.2) 1 (0.5) * Subjects with missing data are imputed as having candidiasis or died. **Subjects may be counted more than once as two fluconazole subjects and four placebo subjects diagnosed with candidiasis subsequently died by day 49. The most common fatal serious adverse reactions in the fluconazole vs placebo arms, respectively, were necrotizing enterocolitis (NEC), 9 (5%) vs 9 (5%); neonatal bacterial sepsis, 6 (3%) vs 7 (4%); and neonatal respiratory failure, 4 (2%) vs 2 (0.6%). The most common serious adverse reactions (>5%), reported in patients receiving fluconazole prophylaxis are displayed in Table 5. Table 5. Serious Adverse Reactions* Occurring in >5% of Infants Receiving Fluconazole Prophylaxis Adverse Reaction Fluconazole (N=188) n(%) Placebo (N=173) n (%) Necrotizing Enterocolitis (NEC) 27 (14) 28 (16) Intestinal Perforation (includes ileal/small intestinal perforation) 13 (7) 7 (4) Neonatal Respiratory Arrest/Neonatal Respiratory Failure 13 (7) 4 (2) Bacterial Sepsis, Neonatal 10 (5) 12 (7) *All serious adverse reactions were assessed and recorded up through 30 days after the final dose of study drug. Serious adverse reactions included both fatal and non-fatal outcomes. Geriatric Use In non-AIDS patients, side effects possibly related to fluconazole treatment were reported in fewer patients aged 65 and older (9%, n=339) than for younger patients (14%, n=2240). However, there was no consistent difference between the older and younger patients with respect to individual side effects. Of the most frequently reported (>1%) side effects, rash, vomiting, and diarrhea occurred in greater proportions of older patients. Similar proportions of older patients (2.4%) and younger patients (1.5%) discontinued fluconazole therapy because of side effects. In post-marketing experience, spontaneous reports of anemia and acute renal failure were more frequent among patients 65 years of age or older than in those between 12 and 65 years of age. Because of the voluntary nature of the reports and the natural increase in the incidence of anemia and renal failure in the elderly, it is however not possible to establish a causal relationship to drug exposure. Controlled clinical trials of fluconazole did not include sufficient numbers of patients aged 65 and older to evaluate whether they respond differently from younger patients in each indication. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Fluconazole is primarily cleared by renal excretion as unchanged drug. Because elderly patients are more likely to have decreased renal function, care should be taken to adjust dose based on creatinine clearance. It may be useful to monitor renal function. (See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION .)"}', 'information_for_patients': None, 'pregnancy': '{"Pregnancy Teratogenic Effects. Potential for Fetal Harm: Use in pregnancy should be avoided except in patients with severe or potentially life-threatening fungal infections in whom fluconazole may be used if the anticipated benefit outweighs the possible risk to the fetus. A few published case reports describe a pattern of distinct congenital anomalies in infants exposed in utero to high dose maternal fluconazole (400 to 800 mg/day) during most or all of the first trimester. These reported anomalies are similar to those seen in animal studies. Effective contraceptive measures should be considered in women of child-bearing potential who are being treated with fluconazole 400 to 800 mg/day and should continue throughout the treatment period and for approximately 1 week (5 to 6 half-lives) after the final dose. If fluconazole is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be informed of the potential hazard to the fetus. Spontaneous abortions and congenital abnormalities have been suggested as potential risks associated with 150 mg of fluconazole as a single or repeated dose in the first trimester of pregnancy based on retrospective epidemiological studies. There are no adequate and well-controlled studies of fluconazole in pregnant women. (See WARNINGS: Potential for Fetal Harm . ) Human Data Case reports describe a distinctive and rare pattern of birth defects among infants whose mothers received high-dose (400 to 800 mg/day) fluconazole during most or all of the first trimester of pregnancy. The features seen in these infants include brachycephaly, abnormal facies, abnormal calvarial development, cleft palate, femoral bowing, thin ribs and long bones, arthrogryposis, and congenital heart disease. These effects are similar to those seen in animal studies. Epidemiological studies suggest a potential risk of spontaneous abortion and congenital abnormalities in infants whose mothers were treated with 150 mg of fluconazole as a single or repeated dose in the first trimester, but these epidemiological studies have limitations and these findings have not been confirmed in controlled clinical trials. Animal Data Fluconazole was administered orally to pregnant rabbits during organogenesis in two studies at doses of 5 mg/kg, 10 mg/kg, and 20 mg/kg and at 5 mg/kg, 25 mg/kg, and 75 mg/kg, respectively. Maternal weight gain was impaired at all dose levels (approximately 0.25 to 4 times the 400 mg clinical dose based on body surface area [BSA] comparison), and abortions occurred at 75 mg/kg (approximately 4 times the 400 mg clinical dose based on BSA); no adverse fetal effects were observed. In several studies in which pregnant rats received fluconazole orally during organogenesis, maternal weight gain was impaired and placental weights were increased at 25 mg/kg. There were no fetal effects at 5 mg/kg or 10 mg/kg; increases in fetal anatomical variants (supernumerary ribs, renal pelvis dilation) and delays in ossification were observed at 25 mg/kg and 50 mg/kg and higher doses. At doses ranging from 80 to 320 mg/kg (approximately 2 to 8 times the 400 mg clinical dose based on BSA), embryolethality in rats was increased and fetal abnormalities included wavy ribs, cleft palate, and abnormal craniofacial ossification. These effects are consistent with the inhibition of estrogen synthesis in rats and may be a result of known effects of lowered estrogen on pregnancy, organogenesis, and parturition."}', 'pediatric_use': '{"Pediatric Use Use in Pediatric Patients for the Treatment of Oropharyngeal Candidiasis An open-label, randomized, controlled trial has shown fluconazole to be effective in the treatment of oropharyngeal candidiasis in pediatric patients 6 months to 13 years of age. (See CLINICAL STUDIES .) Use in Pediatric Patients for the Treatment of Candida Esophagitis, Systemic Candida Infections, or Cryptococcal Meningitis The use of fluconazole in pediatric patients with cryptococcal meningitis , Candida esophagitis, or systemic Candida infections is supported by the efficacy shown for these indications in adults and by the results from several small noncomparative pediatric clinical studies. In addition, pharmacokinetic studies in pediatric patients (See CLINICAL PHARMACOLOGY ) have established a dose proportionality between pediatric patients and adults. (See DOSAGE AND ADMINISTRATION .) In a noncomparative study of fluconazole administered to pediatric patients (from birth to less than 17 years) with serious systemic fungal infections, most of which were candidemia, the effectiveness of fluconazole was similar to that reported for the treatment of candidemia in adults. Of 17 subjects with culture-confirmed candidemia, 11 of 14 (79%) with baseline symptoms (3 were asymptomatic) had a clinical cure; 13/15 (87%) of evaluable patients had a mycologic cure at the end of treatment but two of these patients relapsed at 10 and 18 days, respectively, following cessation of therapy. The efficacy of fluconazole for the suppression of cryptococcal meningitis was successful in 4 of 5 pediatric patients (4 years to 10 years of age) treated in a compassionate-use study of fluconazole for the treatment of life-threatening or serious mycosis. There are limited clinical data to support the efficacy of fluconazole for the primary treatment of cryptococcal meningitis in pediatric patients. The safety profile of fluconazole has been studied in 577 pediatric patients from 1 day to 17 years of age who received doses ranging from 1 to 15 mg/kg/day for 1 to 1,616 days. (See ADVERSE REACTIONS .) Use in Pediatric Patients on Extracorporeal Membrane Oxygenation (ECMO) A prospective, open-label, single-center study was conducted to determine the PK and safety of fluconazole in pediatric patients (ages: from birth to 17 years of age) on ECMO (see CLINICAL PHARMACOLOGY ). A loading dose of 35 mg/kg is recommended in pediatric patients on ECMO due to increased volume of distribution (see DOSAGE AND ADMINISTRATION ). Use in Prophylaxis of Invasive Candida Infections in Pediatric Patients (premature infants weighing less than 750 grams at birth) Safety and effectiveness of fluconazole for the prophylaxis of invasive candidiasis in pediatric patients (premature infants weighing less than 750 grams at birth) have not been established. A prospective, randomized, double-blind, placebo-controlled, multicenter trial was conducted in premature infants weighing less than 750 grams at birth to evaluate the efficacy and safety of prophylactic fluconazole 6 mg/kg administered twice weekly for 6 weeks versus placebo (NCT00734539). Efficacy was assessed using the endpoint of death or candidiasis by study day 49. The results are summarized in Table 4. Table 4: Death or Candidiasis by Day 49 in Premature Infants Receiving Fluconazole Prophylaxis Fluconazole (N=188) n (%) Placebo (N=173) n (%) P-value Difference (95% CI) Death or candidiasis* 33 (17.6) 38 (22.0) 0.2954 -4.4(-12.6, 3.8) Components of endpoint** Death Candidiasis Missing 27 (14.4) 6 (3.2) 2 (1.0) 25 (14.5) 16 (9.2) 1 (0.5) * Subjects with missing data are imputed as having candidiasis or died. **Subjects may be counted more than once as two fluconazole subjects and four placebo subjects diagnosed with candidiasis subsequently died by day 49. The most common fatal serious adverse reactions in the fluconazole vs placebo arms, respectively, were necrotizing enterocolitis (NEC), 9 (5%) vs 9 (5%); neonatal bacterial sepsis, 6 (3%) vs 7 (4%); and neonatal respiratory failure, 4 (2%) vs 2 (0.6%). The most common serious adverse reactions (>5%), reported in patients receiving fluconazole prophylaxis are displayed in Table 5. Table 5. Serious Adverse Reactions* Occurring in >5% of Infants Receiving Fluconazole Prophylaxis Adverse Reaction Fluconazole (N=188) n(%) Placebo (N=173) n (%) Necrotizing Enterocolitis (NEC) 27 (14) 28 (16) Intestinal Perforation (includes ileal/small intestinal perforation) 13 (7) 7 (4) Neonatal Respiratory Arrest/Neonatal Respiratory Failure 13 (7) 4 (2) Bacterial Sepsis, Neonatal 10 (5) 12 (7) *All serious adverse reactions were assessed and recorded up through 30 days after the final dose of study drug. Serious adverse reactions included both fatal and non-fatal outcomes."}', 'geriatric_use': '{"Geriatric Use In non-AIDS patients, side effects possibly related to fluconazole treatment were reported in fewer patients aged 65 and older (9%, n=339) than for younger patients (14%, n=2240). However, there was no consistent difference between the older and younger patients with respect to individual side effects. Of the most frequently reported (>1%) side effects, rash, vomiting, and diarrhea occurred in greater proportions of older patients. Similar proportions of older patients (2.4%) and younger patients (1.5%) discontinued fluconazole therapy because of side effects. In post-marketing experience, spontaneous reports of anemia and acute renal failure were more frequent among patients 65 years of age or older than in those between 12 and 65 years of age. Because of the voluntary nature of the reports and the natural increase in the incidence of anemia and renal failure in the elderly, it is however not possible to establish a causal relationship to drug exposure. Controlled clinical trials of fluconazole did not include sufficient numbers of patients aged 65 and older to evaluate whether they respond differently from younger patients in each indication. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Fluconazole is primarily cleared by renal excretion as unchanged drug. Because elderly patients are more likely to have decreased renal function, care should be taken to adjust dose based on creatinine clearance. It may be useful to monitor renal function. (See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION .)"}'}

{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 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 right away (1-800-222-1222)."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{ACETAMINOPHEN}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses • temporarily relieves minor aches and pains due to: • the common cold • headache • backache • minor pain of arthritis • toothache • muscular aches • premenstrual and menstrual cramps • temporarily reduces fever"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{ACETAMINOPHEN}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if • pain gets worse or lasts more than 10 days • fever gets worse or lasts more than 3 days • new symptoms occur • redness or swelling is present 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 have ever had an allergic reaction to this product or any of its ingredients"}', 'when_using': None, 'warnings': '{"Warnings 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 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."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{GLYCERIN}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses for the temporary relief of burning and irritation due to dryness of the eye. for the temporary relief of discomfort due to minor irritations of the eye or to exposure to wind or sun. for use as a protectant against further irritation or to relieve dryness of the eye. for use as a lubricant to prevent further irritation or to relieve dryness of the eye."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{GLYCERIN}', 'route': '{OPHTHALMIC}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if you experience eye pain, changes in vision, continued redness or irritation of the eye, or if the conditions worsens or persists for more than 72 hours."}', 'do_not_use': '{"Do not use if solution changes color or becomes cloudy. if you are sensitive to any ingredient in this product."}', 'when_using': '{"When using this product to avoid contamination do not touch tip of container to any surface. once opened, discard do not reuse"}', 'warnings': '{"Warnings For external use only Do not use if solution changes color or becomes cloudy. if you are sensitive to any ingredient in this product. When using this product to avoid contamination do not touch tip of container to any surface. once opened, discard do not reuse Stop use and ask a doctor if you experience eye pain, changes in vision, continued redness or irritation of the eye, or if the conditions worsens or persists 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}

{"PROCHLORPERAZINE MALEATE"}

{'contraindications': '{"CONTRAINDICATIONS Do not use in patients with known hypersensitivity to phenothiazines. Do not use in comatose states or in the presence of large amounts of central nervous system depressants (alcohol, barbiturates, narcotics, etc.). Do not use in pediatric surgery. Do not use in pediatric patients under 2 years of age or under 20 lbs. Do not use in children for conditions for which dosage has not been established."}', 'adverse_reactions': '{"ADVERSE REACTIONS Drowsiness, dizziness, amenorrhea, blurred vision, skin reactions and hypotension may occur. Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs (see WARNINGS ). Cholestatic jaundice has occurred. If fever with grippe-like symptoms occurs, appropriate liver studies should be conducted. If tests indicate an abnormality, stop treatment. There have been a few observations of fatty changes in the livers of patients who have died while receiving the drug. No causal relationship has been established. Leukopenia and agranulocytosis have occurred. Warn patients to report the sudden appearance of sore throat or other signs of infection. If white blood cell and differential counts indicate leukocyte depression, stop treatment and start antibiotic and other suitable therapy. Neuromuscular (Extrapyramidal) Reactions These symptoms are seen in a significant number of hospitalized mental patients. They may be characterized by motor restlessness, be of the dystonic type, or they may resemble parkinsonism. Depending on the severity of symptoms, dosage should be reduced or discontinued. If therapy is reinstituted, it should be at a lower dosage. Should these symptoms occur in children or pregnant patients, the drug should be stopped and not reinstituted. In most cases barbiturates by suitable route of administration will suffice. (Or, injectable Benadryl ® ll may be useful). In more severe cases, the administration of an anti-parkinsonism agent, except levodopa (See PDR), usually produces rapid reversal of symptoms. Suitable supportive measures such as maintaining a clear airway and adequate hydration should be employed. 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. These usually subside within a few hours, and almost always within 24 to 48 hours, after the drug has been discontinued. Motor Restlessness: Symptoms may include agitation or jitteriness and sometimes insomnia. These symptoms often disappear spontaneously. At times these symptoms may be similar to the original neurotic or psychotic symptoms. Dosage should not be increased until these side effects have subsided. If these symptoms become too troublesome, they can usually be controlled by a reduction of dosage or change of drug. Treatment with anti-parkinsonian agents, benzodiazepines or propranolol may be helpful. Pseudo-Parkinsonism: Symptoms may include: mask-like facies; drooling; tremors; pillrolling motion; cog-wheel rigidity; and shuffling gait. Reassurance and sedation are important. In most cases these symptoms are readily controlled when an anti-parkinsonism agent is administered concomitantly. Anti- parkinsonism agents should be used only when required. Generally, therapy of a few weeks to 2 or 3 months will suffice. After this time patients should be evaluated to determine their need for continued treatment. (Note: Levodopa has not been found effective in pseudo-parkinsonism). Occasionally it is necessary to lower the dosage of prochlorperazine or to discontinue the drug. Tardive Dyskinesia: As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or may appear after drug therapy has been discontinued. The syndrome can also develop, although much less frequently, after relatively brief treatment periods at low doses. This syndrome appears in all age groups. Although its prevalence appears to be highest among elderly patients, especially elderly women, it is impossible to rely upon prevalence estimates to predict at the inception of antipsychotic treatment which patients are likely to develop the syndrome. The symptoms are persistent and in some patients appear to be irreversible. The syndrome is characterized by rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g., protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes these may be accompanied by involuntary movements of extremities. In rare instances, these involuntary movements of the extremities are the only manifestations of tardive dyskinesia. A variant of tardive dyskinesia, tardive dystonia, has also been described. There is no known effective treatment for tardive dyskinesia; anti-parkinsonism agents do not alleviate the symptoms of this syndrome. It is suggested that all antipsychotic agents be discontinued if these symptoms appear. Should it be necessary to reinstitute treatment, or increase the dosage of the agent, or switch to a different antipsychotic agent, the syndrome may be masked. It has been reported that fine vermicular movements of the tongue may be an early sign of the syndrome and if the medication is stopped at that time the syndrome may not develop. Adverse Reactions Reported with Prochlorperazine or Other Phenothiazine Derivatives: Adverse reactions with different phenothiazines vary in type, frequency and mechanism of occurrence, i.e., some are dose-related, while others involve individual patient sensitivity. Some adverse reactions may be more likely to occur, or occur with greater intensity, in patients with special medical problems, e.g., patients with mitral insufficiency or pheochromocytoma have experienced severe hypotension following recommended doses of certain phenothiazines. Not all of the following adverse reactions have been observed with every phenothiazine derivative, but they have been reported with one or more and should be borne in mind when drugs of this class are administered: extrapyramidal symptoms (opisthotonos, oculogyric crisis, hyperreflexia, dystonia, akathisia, dyskinesia, parkinsonism) some of which have lasted months and even years-particularly in elderly patients with previous brain damage; grand mal and petit mal convulsions, particularly in patients with EEG abnormalities or history of such disorders; altered cerebrospinal fluid proteins; cerebral edema; intensification and prolongation of the action of central nervous system depressants (opiates, analgesics, antihistamines, barbiturates, alcohol), atropine, heat, organophosphorus insecticides; autonomic reactions (dryness of mouth, nasal congestion, headache, nausea, constipation, obstipation, adynamic ileus, ejaculatory disorders/impotence, priapism, atonic colon, urinary retention, miosis and mydriasis); reactivation of psychotic processes, catatonic-like states; hypotension (sometimes fatal); cardiac arrest; blood dyscrasias (pancytopenia, thrombocytopenic purpura, leukopenia, agranulocytosis, eosinophilia, hemolytic anemia, aplastic anemia); liver damage (jaundice, biliary stasis); endocrine disturbances (hyperglycemia, hypoglycemia, glycosuria, lactation, galactorrhea, gynecomastia, menstrual irregularities, false-positive pregnancy tests); skin disorders (photosensitivity, itching, erythema, urticaria, eczema up to exfoliative dermatitis); other allergic reactions (asthma, laryngeal edema, angioneurotic edema, anaphylactoid reactions); peripheral edema; reversed epinephrine effect; hyperpyrexia; mild fever after large I.M. doses; increased appetite; increased weight; a systemic lupus erythematosus-like syndrome; pigmentary retinopathy; with prolonged administration of substantial doses, skin pigmentation, epithelial keratopathy, and lenticular and corneal deposits. EKG changes- particularly nonspecific, usually reversible Q and T wave distortions-have been observed in some patients receiving phenothiazine. Although phenothiazines cause neither psychic nor physical dependence, sudden discontinuance in long-term psychiatric patients may cause temporary symptoms, e.g., nausea and vomiting, dizziness, tremulousness. NOTE: There have been occasional reports of sudden death in patients receiving phenothiazines. In some cases, the cause appeared to be cardiac arrest or asphyxia due to failure of the cough reflex."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE For control of severe nausea and vomiting. For the treatment of schizophrenia. Prochlorperazine is effective for the short-term treatment of generalized non-psychotic anxiety. However, prochlorperazine is not the first drug to be used in therapy for most patients with non-psychotic anxiety, because certain risks associated with its use are not shared by common alternative treatments (e.g., benzodiazepines). When used in the treatment of non-psychotic anxiety, prochlorperazine should not be administered at doses of more than 20 mg per day or for longer than 12 weeks, because the use of prochlorperazine at higher doses or for longer intervals may cause persistent tardive dyskinesia that may prove irreversible (see WARNINGS ). The effectiveness of prochlorperazine as treatment for non-psychotic anxiety was established in 4- week clinical studies of outpatients with generalized anxiety disorder. This evidence does not predict that prochlorperazine will be useful in patients with other non-psychotic conditions in which anxiety, or signs that mimic anxiety, are found (e.g., physical illness, organic mental conditions, agitated depression, character pathologies, etc.). Prochlorperazine has not been shown effective in the management of behavioral complications in patients with mental retardation."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE (See also ADVERSE REACTIONS .) SYMPTOMS -Primarily involvement of the extrapyramidal mechanism producing some of the dystonic reactions described above. Symptoms of central nervous system depression to the point of somnolence or coma. Agitation and restlessness may also occur. Other possible manifestations include convulsions, EKG changes and cardiac arrhythmias, fever and autonomic reactions such as hypotension, dry mouth and ileus. TREATMENT-It is important to determine other medications taken by the patient since multiple-dose therapy is common in overdosage situations. Treatment is essentially symptomatic and supportive. Early gastric lavage is helpful. Keep patient under observation and maintain an open airway, since involvement of the extrapyramidal mechanism may produce dysphagia and respiratory difficulty in severe overdosage. Do not attempt to induce emesis because a dystonic reaction of the head or neck may develop that could result in aspiration of vomitus. Extrapyramidal symptoms may be treated with antiparkinsonism drugs, barbiturates or Benadryl. See prescribing information for these products. Care should be taken to avoid increasing respiratory depression. If administration of a stimulant is desirable, amphetamine, dextroamphetamine or caffeine with sodium benzoate is recommended. Stimulants that may cause convulsions (e.g., picrotoxin or pentylenetetrazol) should be avoided. If hypotension occurs, the standard measures for managing circulatory shock should be initiated. If it is desirable to administer a vasoconstrictor, Levophed and Neo-Synephrine are most suitable. Other pressor agents, including epinephrine, are not recommended because phenothiazine derivatives may reverse the usual elevating action of these agents and cause further lowering of blood pressure. Limited experience indicates that phenothiazines are not dialyzable."}', 'active_flag': 'Y', 'generic_name': '{"PROCHLORPERAZINE MALEATE"}', '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. Prochlorperazine maleate is not approved for the treatment of patients with dementia- related psychosis (see BOXED WARNING ). The extrapyramidal symptoms which can occur secondary to prochlorperazine may be confused with the central nervous system signs of an undiagnosed primary disease responsible for the vomiting, e.g., Reye\'s syndrome or other encephalopathy. The use of prochlorperazine and other potential hepatotoxins should be avoided in children and adolescents whose signs and symptoms suggest Reye\'s syndrome. Tardive Dyskinesia: Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with 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 antipsychotic drug treatment, which patients are likely to develop the syndrome. Whether antipsychotic 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 antipsychotic 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 antipsychotic drug treatment is withdrawn. Antipsychotic drug 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, antipsychotic drugs should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia especially in the elderly. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to antipsychotic 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 antipsychotics, 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 and ADVERSE REACTIONS. Neuroleptic Malignant Syndrome (NMS): A potentially fatal syndrome 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 systems (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. An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN and FBS) has occurred in a few patients treated with lithium plus an antipsychotic. In some instances, the syndrome was followed by irreversible brain damage. Because of a possible causal relationship between these events and the concomitant administration of lithium and antipsychotics, patients receiving such combined therapy should be monitored closely for early evidence of neurologic toxicity and treatment discontinued promptly if such signs appear. This encephalopathic syndrome may be similar to or the same as neuroleptic malignant syndrome (NMS). Patients with bone marrow depression or who have previously demonstrated a hypersensitivity reaction (e.g., blood dyscrasias, jaundice) with a phenothiazine should not receive any phenothiazine, including prochlorperazine, unless in the judgment of the physician the potential benefits of treatment outweigh the possible hazards. Prochlorperazine may impair mental and/or physical abilities, especially during the first few days of therapy. Therefore, caution patients about activities requiring alertness (e.g., operating vehicles or machinery). Phenothiazines may intensify or prolong the action of central nervous system depressants (e.g., alcohol, anesthetics, narcotics). Falls: Prochlorperazine maleate 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: Safety for the use of prochlorperazine during pregnancy has not been established. Therefore, prochlorperazine is not recommended for use in pregnant patients except in cases of severe nausea and vomiting that are so serious and intractable that, in the judgment of the physician, drug intervention is required and potential benefits outweigh possible hazards. There have been reported instances of prolonged jaundice, extrapyramidal signs, hyperreflexia or hyporeflexia in newborn infants whose mothers received phenothiazines. Non-teratogenic Effects Neonates exposed to antipsychotic drugs, during 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. Prochlorperazine maleate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers: There is evidence that phenothiazines are excreted in the breast milk of nursing mothers. Caution should be exercised when prochlorperazine is administered to a nursing woman."}', 'precautions': '{"PRECAUTIONS Leukopenia, Neutropenia and Agranulocytosis: In clinical trial and postmarketing experience, events of leukopenia/neutropenia and agranulocytosis have been reported temporally related to antipsychotic agents. Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia. Patients with a pre-existing 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 prochlorperazine maleate 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 or signs occur. Patients with severe neutropenia (absolute neutrophil count < 1000/mm 3 ) should discontinue prochlorperazine maleate tablets and have their WBC followed until recovery. The antiemetic action of prochlorperazine may mask the signs and symptoms of overdosage of other drugs and may obscure the diagnosis and treatment of other conditions such as intestinal obstruction, brain tumor and Reye\'s syndrome (see WARNINGS ). When prochlorperazine is used with cancer chemotherapeutic drugs, vomiting as a sign of the toxicity of these agents may be obscured by the antiemetic effect of prochlorperazine. Because hypotension may occur, large doses and parenteral administration should be used cautiously in patients with impaired cardiovascular systems. To minimize the occurrence of hypotension after injection, keep patient lying down and observe for at least 1/2 hour. If hypotension occurs after parenteral or oral dosing, place patient in head-low position with legs raised. If a vasoconstrictor is required, Levophed ® * and Neo-Synephrine ® ** are suitable. Other pressor agents, including epinephrine, should not be used because they may cause a paradoxical further lowering of blood pressure. Aspiration of vomitus has occurred in a few post-surgical patients who have received prochlorperazine as an antiemetic. Although no causal relationship has been established, this possibility should be borne in mind during surgical aftercare. Deep sleep, from which patients can be aroused, and coma have been reported, usually with overdosage. Antipsychotic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately 1/3 of human breast cancers are prolactin- dependent in vitro , a factor of potential importance if the prescribing 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 antipsychotic drugs. Neither clinical 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. Chromosomal aberrations in spermatocytes and abnormal sperm have been demonstrated in rodents treated with certain antipsychotics. As with all drugs which exert an anticholinergic effect, and/or cause mydriasis, prochlorperazine should be used with caution in patients with glaucoma. Because phenothiazines may interfere with thermoregulatory mechanisms, use with caution in persons who will be exposed to extreme heat. Phenothiazines can diminish the effect of oral anticoagulants. Phenothiazines can produce alpha-adrenergic blockade. Thiazide diuretics may accentuate the orthostatic hypotension that may occur with phenothiazines. Antihypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concomitantly. Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs. Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary. Potentiation of anticonvulsant effects does not occur. However, it has been reported that phenothiazines may interfere with the metabolism of Dilantin ® *** and thus precipitate Dilantin toxicity. The presence of phenothiazines may produce false-positive phenylketonuria (PKU) test results. Long-Term Therapy: Given the likelihood that some patients exposed chronically to antipsychotics 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. To lessen the likelihood of adverse reactions related to cumulative drug effect, patients with a history of long-term therapy with prochlorperazine and/or other antipsychotics should be evaluated periodically to decide whether the maintenance dosage could be lowered or drug therapy discontinued. Children with acute illnesses (e.g., chickenpox, CNS infections, measles, gastroenteritis) or dehydration seem to be much more susceptible to neuromuscular reactions, particularly dystonias, than are adults. In such patients, the drug should be used only under close supervision. Drugs which lower the seizure threshold, including phenothiazine derivatives should not be used with Amipaque ® §. As with other phenothiazine derivatives, prochlorperazine should be discontinued at least 48 hours before myelography, should not be resumed for at least 24 hours postprocedure, and should not be used for the control of nausea and vomiting occurring either prior to myelography with Amipaque, or post-procedure. Geriatric Use: Clinical studies of prochlorperazine did not include sufficient numbers of subjects aged 65 and over to determine whether elderly subjects respond differently from younger subjects. Geriatric patients are more sensitive to the side effects of antipsychotics, including prochlorperazine. These adverse events include hypotension, anticholinergic effects (such as urinary retention, constipation, and confusion), and neuromuscular reactions (such as parkinsonism and tardive dyskinesia) ( see PRECAUTIONS and ADVERSE REACTIONS ). Also, postmarketing safety experience suggests that the incidence of agranulocytosis may be higher in geriatric patients compared to younger individuals who received prochlorperazine. 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 ( see DOSAGE AND ADMINISTRATION )."}', 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{LISINOPRIL}

{'contraindications': '{"4 CONTRAINDICATIONS Lisinopril is contraindicated in patients with: a history of angioedema or hypersensitivity related to previous treatment with an angiotensin converting enzyme inhibitor hereditary or idiopathic angioedema Do not co-administer aliskiren with lisinopril in patients with diabetes [see Drug Interactions (7.4) ]. Angioedema or a history of hereditary or idiopathic angioedema ( 4 ) Hypersensitivity ( 4 ) Co-administration of aliskiren with lisinopril in patients with diabetes ( 4 , 7.4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS Common adverse reactions (events 2% greater than placebo) by use: Hypertension: headache, dizziness and cough ( 6.1 ) Heart Failure: hypotension and chest pain ( 6.1 ) Acute Myocardial Infarction: hypotension ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Qualitest Pharmaceuticals at 1-800-444-4011 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 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. Hypertension In clinical trials in patients with hypertension treated with lisinopril, 5.7% of patients on lisinopril discontinued with adverse reactions. The following adverse reactions (events 2% greater on lisinopril than on placebo) were observed with lisinopril alone: headache (by 3.8%), dizziness (by 3.5%), cough (by 2.5%). Heart Failure In patients with systolic heart failure treated with lisinopril for up to four years, 11% discontinued therapy with adverse reactions. In controlled studies in patients with heart failure, therapy was discontinued in 8.1% of patients treated with lisinopril for 12 weeks, compared to 7.7% of patients treated with placebo for 12 weeks. The following adverse reactions (events 2% greater on lisinopril than on placebo) were observed with lisinopril: hypotension (by 3.8%), chest pain (by 2.1%). In the two-dose ATLAS trial [see Clinical Studies (14.2) ] in heart failure patients, withdrawals due to adverse reactions were not different between the low and high groups, either in total number of discontinuation (17-18%) or in rare specific reactions (< 1%). The following adverse reactions, mostly related to ACE inhibition, were reported more commonly in the high dose group: Table 1 Dose-related Adverse Drug Reactions: ATLAS trial High Dose (n=1568) Low Dose (n=1596) Dizziness 19% 12% Hypotension 11% 7% Creatinine increased 10% 7% Hyperkalemia 6% 4% Syncope 7% 5% Acute Myocardial Infarction Patients treated with lisinopril had a higher incidence of hypotension (by 5.3%) and renal dysfunction (by 1.3%) compared with patients not taking lisinopril. Other clinical adverse reactions occurring in 1% or higher of patients with hypertension or heart failure treated with lisinopril in controlled clinical trials and do not appear in other sections of labeling are listed below: Body as a whole: Fatigue, asthenia, orthostatic effects. Digestive : Pancreatitis, constipation, flatulence, dry mouth, diarrhea. Hematologic: Rare cases of bone marrow depression, hemolytic anemia, leukopenia/neutropenia and thrombocytopenia. Endocrine : Diabetes mellitus, inappropriate antidiuretic hormone secretion. Metabolic : Gout. Skin : Urticaria, alopecia, photosensitivity, erythema, flushing, diaphoresis, cutaneous pseudolymphoma, toxic epidermal necrolysis, Stevens - Johnson syndrome, and pruritus. Special Senses: Visual loss, diplopia, blurred vision, tinnitus, photophobia, taste disturbances, olfactory disturbance. Urogenital: Impotence. Miscellaneous: A symptom complex has been reported which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia, leukocytosis, paresthesia and vertigo. Rash, photosensitivity or other dermatological manifestations may occur alone or in combination with these symptoms. Clinical Laboratory Test Findings Serum Potassium : In clinical trials hyperkalemia (serum potassium greater than 5.7 mEq/L) occurred in 2.2% and 4.8% of lisinopril-treated patients with hypertension and heart failure, respectively [see Warnings and Precautions (5.5) ]. Creatinine, Blood Urea Nitrogen: Minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 2% of patients with hypertension treated with lisinopril alone. Increases were more common in patients receiving concomitant diuretics and in patients with renal artery stenosis [see Warnings and Precautions (5.4) ] . Reversible minor increases in blood urea nitrogen and serum creatinine were observed in 11.6% of patients with heart failure on concomitant diuretic therapy. Frequently, these abnormalities resolved when the dosage of the diuretic was decreased. Patients with acute myocardial infarction in the GISSI-3 trial treated with lisinopril had a higher (2.4% versus 1.1% in placebo) incidence of renal dysfunction in-hospital and at six weeks (increasing creatinine concentration to over 3 mg/dL or a doubling or more of the baseline serum creatinine concentration). Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.4 g% and 1.3 vol%, respectively) occurred frequently in patients treated with lisinopril but were rarely of clinical importance in patients without some other cause of anemia. In clinical trials, less than 0.1% of patients discontinued therapy due to anemia. 6.2 Post-marketing Experience The following adverse reactions have been identified during post-approval use of lisinopril that are not included in other sections of labeling. 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. Other reactions include: Metabolism and nutrition disorders Hyponatremia [see Warnings and Precautions (5.4) ] , cases of hypoglycemia in diabetic patients on oral antidiabetic agents or insulin [see Drug Interactions (7.2) ] Nervous system and psychiatric disorders Mood alterations (including depressive symptoms), mental confusion, hallucinations Skin and subcutaneous tissue disorders Psoriasis"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Diuretics: Excessive drop in blood pressure ( 7.1 ) NSAIDS: Increased risk of renal impairment and loss of antihypertensive efficacy ( 7.3 ) Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension and hyperkalemia ( 7.4 ) Lithium: Symptoms of lithium toxicity ( 7.5 ) Gold: Nitritoid reactions have been reported ( 7.6 ) 7.1 Diuretics Initiation of lisinopril in patients on diuretics may result in excessive reduction of blood pressure. The possibility of hypotensive effects with lisinopril can be minimized by either decreasing or discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with lisinopril. If this is not possible, reduce the starting dose of lisinopril [see Dosage and Administration (2.2) and Warnings and Precautions (5.4) ] . Lisinopril attenuates potassium loss caused by thiazide-type diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) can increase the risk of hyperkalemia. Therefore, if concomitant use of such agents is indicated, monitor the patient’s serum potassium frequently. 7.2 Antidiabetics Concomitant administration of lisinopril and antidiabetic medicines (insulins, oral hypoglycemic agents) may cause an increased blood-glucose-lowering effect with risk of hypoglycemia. 7.3 Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-\xad2 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 lisinopril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving lisinopril and NSAID therapy. The antihypertensive effect of ACE inhibitors, including lisinopril, may be attenuated by NSAIDs. 7.4 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. The VA NEPHRON trial enrolled 1448 patients with type 2 diabetes, elevated urinary-albumin-to-creatinine ratio, and decreased estimated glomerular filtration rate (GFR 30 to 89.9 ml/min), randomized them to lisinopril or placebo on a background of losartan therapy and followed them for a median of 2.2 years. Patients receiving the combination of losartan and lisinopril did not obtain any additional benefit compared to monotherapy for the combined endpoint of decline in GFR, end state renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney injury compared with the monotherapy group. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on lisinopril and other agents that affect the RAS. Do not co-administer aliskiren with lisinopril in patients with diabetes. Avoid use of aliskiren with lisinopril in patients with renal impairment (GFR <60 ml/min). 7.5 Lithium Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs, which cause elimination of sodium, including ACE inhibitors. Lithium toxicity was usually reversible upon discontinuation of lithium and the ACE inhibitor. Monitor serum lithium levels during concurrent use. 7.6 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 lisinopril. 7.7 mTOR Inhibitors Patients taking concomitant mTOR inhibitor ( e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema [see Warnings and Precautions (5.2) ]."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Lisinopril is an angiotensin converting enzyme (ACE) inhibitor indicated for: Treatment of hypertension in adults and pediatric patients 6 years of age and older ( 1.1 ) Adjunct therapy for heart failure ( 1.2 ) Treatment of Acute Myocardial Infarction ( 1.3 ) 1.1 Hypertension Lisinopril tablets are indicated for the treatment of hypertension in adult patients and pediatric patients 6 years of age and older 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. 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. Lisinopril tablets may be administered alone or with other antihypertensive agents [see Clinical Studies (14.1) ]. 1.2 Heart Failure Lisinopril tablets are indicated to reduce signs and symptoms of systolic heart failure [see Clinical Studies (14.2) ] . 1.3 Reduction of Mortality in Acute Myocardial Infarction Lisinopril tablets are indicated for the reduction of mortality in treatment of hemodynamically stable patients within 24 hours of acute myocardial infarction. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin and beta-blockers [see Clinical Studies (14.3) ] ."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Angioedema: Discontinue lisinopril, provide appropriate therapy and monitor until resolved ( 5.2 ) Renal impairment: Monitor renal function periodically ( 5.3 ) Hypotension: Patients with other heart or renal diseases have increased risk, monitor blood pressure after initiation ( 5.4 ) Hyperkalemia: Monitor serum potassium periodically ( 5.5 ) Cholestatic jaundice and hepatic failure: Monitor for jaundice or signs of liver failure ( 5.6 ) 5.1 Fetal Toxicity Lisinopril tablets can cause fetal harm when administered to a pregnant woman. 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 lisinopril as soon as possible [see Use in specific Populations (8.1) ]. 5.2 Angioedema and Anaphylactoid Reactions Patients taking concomitant mTOR inhibitor ( e.g. temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema [see Drug Interactions (7.7) ] . Angioedema Head and Neck Angioedema Angioedema of the face, extremities, lips, tongue, glottis and/or larynx, including some fatal reactions, have occurred in patients treated with angiotensin converting enzyme inhibitors, including lisinopril, at any time during treatment. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Lisinopril should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms of angioedema has occurred. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor [see Contraindications (4) ]. ACE inhibitors have been associated with a higher rate of angioedema in Black than in non-Black patients. Intestinal Angioedema Intestinal angioedema has occurred 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 C-1 esterase levels were normal. In some cases, the angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Anaphylactoid Reactions Anaphylactoid Reactions During Desensitization Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. Anaphylactoid Reactions During Dialysis Sudden and potentially life threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately, and aggressive therapy for anaphylactoid reactions must be initiated. Symptoms have not been relieved by antihistamines in these situations. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption. 5.3 Impaired Renal Function Monitor renal function periodically in patients treated with lisinopril. Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function may depend in part on the activity of the renin-angiotensin system ( e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-myocardial infarction or volume depletion) may be at particular risk of developing acute renal failure on lisinopril. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on lisinopril [see Adverse Reactions (6.1) , Drug Interactions (7.4) ] . 5.4 Hypotension Lisinopril can cause symptomatic hypotension, sometimes complicated by oliguria, progressive azotemia, acute renal failure or death. Patients at risk of excessive hypotension include those with the following conditions or characteristics: heart failure with systolic blood pressure below 100 mmHg, ischemic heart disease, cerebrovascular disease, hyponatremia, high dose diuretic therapy, renal dialysis, or severe volume and/or salt depletion of any etiology. In these patients, lisinopril 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 lisinopril and/or diuretic is increased. Avoid use of lisinopril in patients who are hemodynamically unstable after acute MI. Symptomatic hypotension is also possible in patients with severe aortic stenosis or hypertrophic cardiomyopathy. Surgery/Anesthesia In patients undergoing major surgery or during anesthesia with agents that produce hypotension, lisinopril 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. 5.5 Hyperkalemia Serum potassium should be monitored periodically in patients receiving lisinopril. Drugs that inhibit the renin angiotensin system can cause hyperkalemia. 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 [see Drug Interactions (7.1) ]. 5.6 Hepatic Failure ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis 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 treatment."}', 'overdosage': '{"10 OVERDOSAGE Following a single oral dose of 20 g/kg no lethality occurred in rats, and death occurred in one of 20 mice receiving the same dose. The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution. Lisinopril can be removed by hemodialysis [see Clinical Pharmacology (12.3) ]."}', 'active_flag': 'Y', 'generic_name': '{LISINOPRIL}', '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 NOTE: 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: Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to notify their healthcare provider with a known or suspected pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ]. Angioedema: Angioedema, including laryngeal edema may occur at any time during treatment with angiotensin converting enzyme inhibitors, including lisinopril. Tell patients 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. Lactation: Advise women not to breastfeed during treatment with lisinopril tablets [see Use in Specific Populations (8.2) ]. Symptomatic Hypotension: Tell patients to report light-headedness especially during the first few days of therapy. If actual syncope occurs, tell the patient to discontinue the drug until they have consulted with the prescribing physician. Tell patients 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; advise patients accordingly. Hyperkalemia : Tell patients not to use salt substitutes containing potassium without consulting their physician. Hypoglycemia: Tell diabetic patients treated with oral antidiabetic agents or insulin starting an ACE inhibitor to monitor for hypoglycaemia closely, especially during the first month of combined use [see Drug Interactions (7.2) ]. Leukopenia/Neutropenia: Tell patients to report promptly any indication of infection ( e.g., sore throat, fever), which may be a sign of leukopenia/neutropenia."}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Lisinopril tablets can cause fetal harm when administered to a pregnant woman. 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. 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. When pregnancy is detected, discontinue lisinopril tablets as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown. In the general U.S. 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. Fetal/Neonatal Adverse Reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death. 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. 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 lisinopril tablets for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occur in neonates with a history of in utero exposure to lisinopril tablets, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function."}', 'pediatric_use': '{"8.4 Pediatric Use Antihypertensive effects and safety of lisinopril have been established in pediatric patients aged 6 to 16 years [see Dosage and Administration (2.1) and Clinical Studies (14.1) ] . No relevant differences between the adverse reaction profile for pediatric patients and adult patients were identified. Safety and effectiveness of lisinopril have not been established in pediatric patients under the age 6 or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73 m 2 [see Dosage and Administration (2.1) , Clinical Pharmacology (12.3) , and Clinical Studies (14.1) ]. Neonates with a history of in utero exposure to lisinopril 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."}', 'geriatric_use': '{"8.5 Geriatric Use No dosage adjustment with lisinopril is necessary in elderly patients. In a clinical study of lisinopril in patients with myocardial infarctions (GISSI-3 Trial) 4,413 (47%) were 65 and over, while 1,656 (18%) were 75 and over. In this study, 4.8% of patients aged 75 years and older discontinued lisinopril treatment because of renal dysfunction vs. 1.3% of patients younger than 75 years. No other differences in safety or effectiveness were observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out."}'}

{"SALICYLIC ACID"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses For the removal of common and plantar warts The common wart is easily recognized by the rough cauliflower-like appearance of the surface. The plantar wart is recognized by its location only on the bottom of the foot, its tenderness, and the interruption of the footprint pattern"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"SALICYLIC ACID"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': '{"DO NOT USE On irritated skin or any area that is infected or reddened. If you are allergic to any of the ingredients in this product."}', 'when_using': None, 'warnings': '{"WARNINGS For external use only,don\'t contact with eyes or swallow. Children should use it under adult supervision. The liquid can get easily volatilized & crystallized,tighten the cap after use. Avoid long term contact with air while using."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"QUININE SULFATE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Fever with neck and back pain*"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"QUININE SULFATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if symptoms persist for more than 3 days or worsen"}', 'do_not_use': None, 'when_using': None, 'warnings': '{""}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"MONTELUKAST SODIUM"}

{'contraindications': '{"4 CONTRAINDICATIONS • Hypersensitivity to any component of this product. • Hypersensitivity to any component of this product (4)."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS Most common adverse reactions (incidence ≥5% and greater than placebo listed in descending order of frequency): upper respiratory infection, fever, headache, pharyngitis, cough, abdominal pain, diarrhea, otitis media, influenza, rhinorrhea, sinusitis, otitis (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 clinical practice. In the following description of clinical trials experience, adverse reactions are listed regardless of causality assessment. The most common adverse reactions (incidence ≥5% and greater than placebo; listed in descending order of frequency) in controlled clinical trials were: upper respiratory infection, fever, headache, pharyngitis, cough, abdominal pain, diarrhea, otitis media, influenza, rhinorrhea, sinusitis, otitis. Adults and Adolescents 15 Years of Age and Older with Asthma Montelukast sodium has been evaluated for safety in approximately 2950 adult and adolescent patients 15 years of age and older in clinical trials. In placebo-controlled clinical trials, the following adverse experiences reported with montelukast sodium occurred in greater than or equal to 1% of patients and at an incidence greater than that in patients treated with placebo: Table 1: Adverse Experiences Occurring in ≥1% of Patients with an Incidence Greater than that in Patients Treated with Placebo Montelukast sodium 10 mg/day) (%) (n=1955) Placebo (%) (n=1180) Body As A Whole Pain, abdominal Asthenia/fatigue Fever 2.9 1.8 1.5 2.5 1.2 0.9 Trauma Digestive System Disorders Dyspepsia 1.0 2.1 0.8 1.1 Pain, dental 1.7 1.0 Gastroenteritis, infectious 1.5 0.5 Nervous System/Psychiatric Headache 18.4 18.1 Dizziness 1.9 1.4 Respiratory System Disorders Influenza 4.2 3.9 Cough 2.7 2.4 Congestion, nasal 1.6 1.3 Skin/Skin Appendages Disorder Rash 1.6 1.2 Laboratory Adverse Experiences * ALT increased 2.1 2.0 AST increased 1.6 1.2 Pyuria 1.0 0.9 *Number of patients tested (montelukast sodium and placebo, respectively): ALT and AST, 1935, 1170; pyuria, 1924, 1159. The frequency of less common adverse events was comparable between montelukast sodium and placebo. The safety profile of montelukast sodium, when administered as a single dose for prevention of EIB in adult and adolescent patients 15 years of age and older, was consistent with the safety profile previously described for montelukast sodium. Cumulatively, 569 patients were treated with montelukast sodium for at least 6 months, 480 for one year, and 49 for two years in clinical trials. With prolonged treatment, the adverse experience profile did not significantly change. Adults and Adolescents 15 Years of Age and Older with Seasonal Allergic Rhinitis Montelukast sodium has been evaluated for safety in 2199 adult and adolescent patients 15 years of age and older in clinical trials. Montelukast sodium administered once daily in the morning or in the evening had a safety profile similar to that of placebo. In placebo-controlled clinical trials, the following event was reported with montelukast sodium with a frequency ≥1% and at an incidence greater than placebo: upper respiratory infection, 1.9% of patients receiving montelukast sodium vs. 1.5% of patients receiving placebo. In a 4-week, placebo-controlled clinical study, the safety profile was consistent with that observed in 2-week studies. The incidence of somnolence was similar to that of placebo in all studies. Adults and Adolescents 15 Years of Age and Older with Perennial Allergic Rhinitis Montelukast sodium has been evaluated for safety in 3357 adult and adolescent patients 15 years of age and older with perennial allergic rhinitis of whom 1632 received montelukast sodium in two, 6-week, clinical studies. Montelukast sodium administered once daily had a safety profile consistent with that observed in patients with seasonal allergic rhinitis and similar to that of placebo. In these two studies, the following events were reported with montelukast sodium with a frequency ≥1% and at an incidence greater than placebo: sinusitis, upper respiratory infection, sinus headache, cough, epistaxis, and increased ALT. The incidence of somnolence was similar to that of placebo. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of montelukast sodium. 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: increased bleeding tendency, thrombocytopenia. Immune system disorders: hypersensitivity reactions including anaphylaxis, hepatic eosinophilic infiltration. Psychiatric disorders: including, but not limited to, agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, dysphemia (stuttering), hallucinations, insomnia, irritability, memory impairment, obsessive-compulsive symptoms, restlessness, somnambulism, suicidal thinking and behavior (including suicide), tic, and tremor [see Boxed Warning, Warnings and Precautions (5.1)]. Nervous system disorders: drowsiness, paraesthesia/hypoesthesia, seizures. Cardiac disorders: palpitations. Respiratory, thoracic and mediastinal disorders: epistaxis, pulmonary eosinophilia. Gastrointestinal disorders: diarrhea, dyspepsia, nausea, pancreatitis, vomiting. Hepatobiliary disorders: Cases of cholestatic hepatitis, hepatocellular liver-injury, and mixed-pattern liver injury have been reported in patients treated with montelukast sodium. Most of these occurred in combination with other confounding factors, such as use of other medications, or when montelukast sodium was administered to patients who had underlying potential for liver disease such as alcohol use or other forms of hepatitis. Skin and subcutaneous tissue disorders: angioedema, bruising, erythema multiforme, erythema nodosum, pruritus, Stevens-Johnson syndrome/toxic epidermal necrolysis, urticaria. Musculoskeletal and connective tissue disorders: arthralgia, myalgia including muscle cramps. Renal and urinary disorders: enuresis in children. General disorders and administration site conditions: edema. Patients with asthma on therapy with montelukast sodium may present with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic corticosteroid therapy. These events have been sometimes associated with the reduction of oral corticosteroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients [see Warnings and Precautions (5.5)]."}', 'drug_interactions': '{"7 DRUG INTERACTIONS No dose adjustment is needed when montelukast sodium is co-administered with theophylline, prednisone, prednisolone, oral contraceptives, terfenadine, digoxin, warfarin, gemfibrozil, itraconazole, thyroid hormones, sedative hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, decongestants, and Cytochrome P450 (CYP) enzyme inducers [see Clinical Pharmacology (12.3)]."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Montelukast sodium tablets are a leukotriene receptor antagonist indicated for: • Prophylaxis and chronic treatment of asthma in patients 15 years of age and older (1.1). • Acute prevention of exercise-induced bronchoconstriction (EIB) in patients 15 years of age and older (1.2). • Relief of symptoms of allergic rhinitis (AR): seasonal allergic rhinitis (SAR) in patients 15 years of age and older, and perennial allergic rhinitis (PAR) in patients 15 years of age and older. Reserve use for patients who have an inadequate response or intolerance to alternative therapies (1.3). 1.1 Asthma Montelukast sodium tablets are indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 15 years of age and older. 1.2 Exercise-Induced Bronchoconstriction (EIB) Montelukast sodium tablets are indicated for prevention of exercise-induced bronchoconstriction (EIB) in patients 15 years of age and older. 1.3 Allergic Rhinitis tablets are indicated for the relief of symptoms of seasonal allergic rhinitis in patients 15 years of age and older and perennial allergic rhinitis in patients of age and older. Because the benefits of montelukast sodium tablets may not outweigh the risk of neuropsychiatric symptoms in patients with reserve use for patients who have an inadequate response or intolerance to alternative therapies. Montelukast sodium tablets are indicated for the relief of symptoms of seasonal allergic rhinitis in patients 15 years of age and older and perennial allergic rhinitis in patients 15 years of age and older. Because the benefits of montelukast sodium tablets may not outweigh the risk of neuropsychiatric symptoms in patients with allergic rhinitis [see warnings and precautions (5.1)], reserve use for patients who have an inadequate response or intolerance to alternative therapies."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Do not prescribe montelukast sodium to treat an acute asthma attack (5.2). • Advise patients to have appropriate rescue medication available (5.2). • Inhaled corticosteroid may be reduced gradually. Do not abruptly substitute montelukast sodium for inhaled or oral corticosteroids (5.3). • Patients with known aspirin sensitivity should continue to avoid aspirin or non-steroidal anti-inflammatory agents while taking montelukast sodium (5.4). • Systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, has been reported. These events have been sometimes associated with the reduction of oral corticosteroid therapy (5.5 and 6.2). 5.1 Neuropsychiatric Events neuropsychiatric (NP) events have been reported with use of montelukast sodium. These postmarketing reports have been highly variable and included, but were not limited to, agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream dysphemia (stuttering), hallucinations, insomnia, irritability, memory impairment, obsessive-compulsive symptoms, restlessness, , suicidal thoughts and behavior (including suicide), tic, and tremor. NP events have been reported in adult, adolescent, and pediatric patients with and without a history of psychiatric disorder. NP events have been reported mostly during montelukast sodium treatment, but some were reported after sodium discontinuation. Animal studies showed that montelukast distributes into the brain in rats however, the mechanisms underlying montelukast sodium-associated NP events are currently not well understood. Based upon the available data, it is difficult to identify risk for or quantify the risk of NP events with montelukast sodium use. of the risk of NP events, the benefits of montelukast sodium may not outweigh the risks in some patients, particularly when the symptoms of disease may be and adequately treated with alternative therapies. Reserve use of montelukast sodium for patients with allergic rhinitis who have an inadequate or intolerance to alternative therapies In patients with asthma or exercise-induced bronchoconstriction, consider the benefits and before prescribing montelukast sodium. the benefits and risks of montelukast sodium use with patients and caregivers when prescribing montelukast sodium. Advise patients and/or caregivers to be for changes in behavior or for new NP symptoms when taking montelukast sodium. If changes in behavior are observed, or if new NP symptoms or suicidal thoughts behavior occur, advise patients to discontinue montelukast sodium and contact a healthcare provider immediately. In many cases, resolved after stopping montelukast sodium therapy; however, in some cases symptoms persisted after discontinuation of montelukast sodium. continue to monitor and provide supportive care until symptoms resolve. Re-evaluate the benefits and risks of restarting treatment with sodium if such events occur. Serious neuropsychiatric (NP) events have been reported with use of montelukast sodium. These postmarketing reports have been highly variable and included, but were not limited to, agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, dysphemia (stuttering), hallucinations, insomnia, irritability, memory impairment, obsessive-compulsive symptoms, restlessness, somnambulism, suicidal thoughts and behavior (including suicide), tic, and tremor. NP events have been reported in adult, adolescent, and pediatric patients with and without a previous history of psychiatric disorder. NP events have been reported mostly during montelukast sodium treatment, but some were reported after montelukast sodium discontinuation. Animal studies showed that montelukast distributes into the brain in rats [see Clinical Pharmacology (12.3)]; however, the mechanisms underlying montelukast sodium-associated NP events are currently not well understood. Based upon the available data, it is difficult to identify risk factors for or quantify the risk of NP events with montelukast sodium use. Because of the risk of NP events, the benefits of montelukast sodium may not outweigh the risks in some patients, particularly when the symptoms of disease may be mild and adequately treated with alternative therapies. Reserve use of montelukast sodium for patients with allergic rhinitis who have an inadequate response or intolerance to alternative therapies [see Indications and Usage (1.3)]. In patients with asthma or exercise-induced bronchoconstriction, consider the benefits and risks before prescribing montelukast sodium. Discuss the benefits and risks of montelukast sodium use with patients and caregivers when prescribing montelukast sodium. Advise patients and/or caregivers to be alert for changes in behavior or for new NP symptoms when taking montelukast sodium. If changes in behavior are observed, or if new NP symptoms or suicidal thoughts and/or behavior occur, advise patients to discontinue montelukast sodium and contact a healthcare provider immediately. In many cases, symptoms resolved after stopping montelukast sodium therapy; however, in some cases symptoms persisted after discontinuation of montelukast sodium. Therefore, continue to monitor and provide supportive care until symptoms resolve. Re-evaluate the benefits and risks of restarting treatment with montelukast sodium if such events occur. 5.2 Acute Asthma Montelukast sodium is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. Patients should be advised to have appropriate rescue medication available. Therapy with montelukast sodium can be continued during acute exacerbations of asthma. Patients who have exacerbations of asthma after exercise should have available for rescue a short-acting inhaled β-agonist. 5.3 Concomitant Corticosteroid Use While the dose of inhaled corticosteroid may be reduced gradually under medical supervision, montelukast sodium should not be abruptly substituted for inhaled or oral corticosteroids. 5.4 Aspirin Sensitivity Patients with known aspirin sensitivity should continue avoidance of aspirin or non-steroidal anti-inflammatory agents while taking montelukast sodium. Although montelukast sodium is effective in improving airway function in asthmatics with documented aspirin sensitivity, it has not been shown to truncate bronchoconstrictor response to aspirin and other non-steroidal anti-inflammatory drugs in aspirin-sensitive asthmatic patients [see Clinical Studies (14.1)]. 5.5 Eosinophilic Conditions Patients with asthma on therapy with montelukast sodium may present with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic corticosteroid therapy. These events have been sometimes associated with the reduction of oral corticosteroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between montelukast sodium and these underlying conditions has not been established [see Adverse Reactions (6.2)]."}', 'overdosage': '{"10 OVERDOSAGE No specific information is available on the treatment of overdosage with montelukast sodium. In the event of overdose, it is reasonable to employ the usual supportive measures; e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required. It is not known whether montelukast is removed by peritoneal dialysis or hemodialysis."}', 'active_flag': 'Y', 'generic_name': '{MONTELUKAST}', '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 For the tablets, advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide). • Advise patients about the potential risk for serious neuropsychiatric symptoms and behavioral changes with montelukast sodium use. • Discuss the benefits and risks of montelukast sodium with patients when prescribing or continuing treatment with montelukast sodium. • Advise patients to monitor for changes in behavior or neuropsychiatric symptoms in patients taking montelukast sodium. • Instruct patients to discontinue montelukast sodium and contact a healthcare provider immediately if changes in behavior or thinking that are not typical for the patient occur, or if the patient develops suicidal ideation or suicidal behavior. • Advise patients to take montelukast sodium daily as prescribed, even when they are asymptomatic, as well as during periods of worsening asthma, and to contact their physicians if their asthma is not well controlled. • Advise Patients that oral montelukast sodium is not for the treatment of acute asthma attacks. They should have appropriate short-acting inhaled β-agonist medication available to treat asthma exacerbations. Patients who have exacerbations of asthma after exercise should be instructed to have available for rescue a short-acting inhaled β-agonist. Daily administration of montelukast sodium for the chronic treatment of asthma has not been established to prevent acute episodes of EIB. • Advise patients to seek medical attention if short-acting inhaled bronchodilators are needed more often than usual, or if more than the maximum number of inhalations of short-acting bronchodilator treatment prescribed for a 24-hour period are needed. • Instruct patients to continue other anti-asthma medications as prescribed unless instructed by a physician. • Instruct patients with known aspirin sensitivity to continue avoidance of aspirin or non-steroidal anti-inflammatory agents while taking montelukast sodium. Manufactured for: Camber Pharmaceuticals, Inc. Piscataway, NJ 08854 By: HETERO TM Hetero Labs Limited, Unit V, Polepally, Jadcherla, Mahabubnagar – 509 301, India. or By: HETERO TM Hetero Labs Limited Jeedimetla, Hyderabad-500 055, India. Revised: 08/2020 camberlogo1"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Available data from published prospective and retrospective cohort studies over decades with montelukast use in pregnant women have not established a drug-associated risk of major birth defects [see Data]. In animal reproduction studies, no adverse developmental effects were observed with oral administration of montelukast to pregnant rats and rabbits during organogenesis at doses approximately 100 and 110 times, respectively, the maximum recommended human daily oral dose (MRHDOD) based on AUCs [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 embryo/fetal risk Poorly or moderately controlled asthma in pregnancy increases the maternal risk of perinatal adverse outcomes such as preeclampsia and infant prematurity, low birth weight, and small for gestational age. Data Human Data Published data from prospective and retrospective cohort studies have not identified an association with montelukast sodium use during pregnancy and major birth defects. Available studies have methodologic limitations, including small sample size, in some cases retrospective data collection, and inconsistent comparator groups. Animal Data In embryo-fetal development studies, montelukast administered to pregnant rats and rabbits during organogenesis (gestation days 6 to 17 in rats and 6 to 18 in rabbits) did not cause any adverse developmental effects at maternal oral doses up to 400 and 300 mg/kg/day in rats and rabbits, respectively (approximately 100 and 110 times the AUC in humans at the MRHDOD, respectively)."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness in pediatric patients below the age of 12 months with asthma, 6 months with perennial allergic rhinitis, and 6 years with exercise-induced bronchoconstriction have not been established."}', 'geriatric_use': '{"8.5 Geriatric Use Of the total number of subjects in clinical studies of montelukast, 3.5% were 65 years of age and over, and 0.4% were 75 years of age and over. 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. The pharmacokinetic profile and the oral bioavailability of a single 10 mg oral dose of montelukast are similar in elderly and younger adults. The plasma half-life of montelukast is slightly longer in the elderly. No dosage adjustment in the elderly is required."}'}

{EDARAVONE}

{'contraindications': '{"4 CONTRAINDICATIONS RADICAVA and RADICAVA ORS are contraindicated in patients with a history of hypersensitivity to edaravone or any of the inactive ingredients in this product. Hypersensitivity reactions and anaphylactic reactions have occurred [see Warnings and Precautions (5.1 , 5.2 )]. Patients with a history of hypersensitivity to edaravone or any of the inactive ingredients in RADICAVA and/or RADICAVA ORS ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: • Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] • Sulfite Allergic Reactions [see Warnings and Precautions (5.2) ] Most common adverse reactions (at least 10% of patients treated with RADICAVA and greater than placebo) are contusion, gait disturbance, and headache ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mitsubishi Tanabe Pharma America, Inc. at 1-888-292-0058 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 randomized, placebo-controlled trials, 184 patients with ALS were administered RADICAVA 60 mg in treatment cycles for 6 months. The population consisted of Japanese patients who had a median age of 60 years (range 29-75) and were 59% male. Most (93%) of these patients were living independently at the time of screening. Most Common Adverse Reactions Observed During Clinical Studies Table 2 lists the adverse reactions that occurred in ≥ 2% of patients in the RADICAVA-treated group and that occurred at least 2% more frequently than in the placebo-treated group in randomized placebo-controlled ALS trials. The most common adverse reactions that occurred in ≥10% of RADICAVA-treated patients were contusion, gait disturbance, and headache. Table 2: Adverse Reactions from Pooled Placebo-Controlled Trials a that Occurred in ≥2% of RADICAVA -Treated Patients and ≥2% More Frequently than in Placebo Patients Adverse Reaction RADICAVA IV (N=184) % Placebo (N=184) % Contusion 15 9 Gait disturbance 13 9 Headache 10 6 Dermatitis 8 5 Eczema 7 4 Respiratory failure, respiratory disorder, hypoxia 6 4 Glycosuria 4 2 Tinea infection 4 2 a Pooled placebo-controlled studies include two additional studies with 231 additional patients, all using the same treatment regimen [see Clinical Studies (14) ]. Additional Adverse Reactions with RADICAVA ORS In an open-label study in patients with ALS (n=185) treated with RADICAVA ORS for 6 months, fatigue was observed in 7.6% of patients. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of RADICAVA. 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. Skin and subcutaneous tissue disorders: Hypersensitivity reactions and anaphylaxis [see Warnings and Precautions (5.1 , 5.2) ]."}', 'drug_interactions': None, 'indications_and_usage': '{"1 INDICATIONS AND USAGE RADICAVA and RADICAVA ORS are indicated for the treatment of amyotrophic lateral sclerosis (ALS). RADICAVA and RADICAVA ORS are indicated for the treatment of amyotrophic lateral sclerosis (ALS). ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Hypersensitivity Reactions: Advise patients to seek immediate medical care ( 5.1 ) • Sulfite Allergic Reactions: RADICAVA and RADICAVA ORS contain sodium bisulfite, which may cause allergic type reactions, including anaphylactic symptoms and asthmatic episodes in susceptible people ( 5.2 ) 5.1 Hypersensitivity Reactions Hypersensitivity reactions (redness, wheals, and erythema multiforme) and cases of anaphylaxis (urticaria, decreased blood pressure, and dyspnea) have been reported in spontaneous postmarketing reports with RADICAVA. Patients should be monitored carefully for hypersensitivity reactions. If hypersensitivity reactions occur, discontinue RADICAVA and/or RADICAVA ORS, treat per standard of care, and monitor until the condition resolves [see Contraindications (4) ]. 5.2 Sulfite Allergic Reactions RADICAVA and RADICAVA ORS contain sodium bisulfite, a sulfite that may cause allergic type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown. Sulfite sensitivity occurs more frequently in asthmatic than non-asthmatic people."}', 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{EDARAVONE}', '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 patients to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Hypersensitivity Reactions Advise patients to seek immediate medical care if they experience signs or symptoms of a hypersensitivity reaction [see Warnings and Precautions (5.1) ]. Sulfite Allergic Reactions Advise patients about potential for sulfite sensitivity. Inform patients that RADICAVA and RADICAVA ORS contain sodium bisulfite, which may cause allergic type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes, and to seek immediate medical care if they experience these signs or symptoms [see Warnings and Precautions (5.2) ]. Pregnancy and Breastfeeding Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during RADICAVA or RADICAVA ORS therapy [see Use in Specific Populations (8.1) ] . Advise patients to notify their healthcare provider if they intend to breastfeed or are breastfeeding an infant [see Use in Specific Populations (8.2) ] . RADICAVA ORS Administration Advise patients to take RADICAVA ORS in the morning on an empty stomach. Instruct patients to fast 8 hours before each dose if they consume a high-fat meal, 4 hours before each dose if they consume a low-fat meal, or 2 hours before each dose if they consume a caloric supplement [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) ] . Also instruct patients to not to consume food for 1 hour after each dose. Advise caregivers, if administering RADICAVA ORS via feeding tube, to use a catheter-tip syringe and flush the feeding tube with approximately 1 ounce (30 mL) of water before and after use (see Instructions for Use ) . Marketed and distributed by: Mitsubishi Tanabe Pharma America, Inc., a US subsidiary of Mitsubishi Tanabe Pharma Corporation Jersey City, NJ 07310 RADICAVA and RADICAVA ORS are registered trademark of Mitsubishi Tanabe Pharma Corporation © 2022 Mitsubishi Tanabe Pharma Corporation 22022-2 Iss. 11/2022 Information for Patients PATIENT INFORMATION RADICAVA (ra di ká vah) (edaravone injection) for intravenous infusion RADICAVA ORS (ra di ká vah o r s) (edaravone oral suspension) administered by mouth or via feeding tube What are RADICAVA and RADICAVA ORS? RADICAVA and RADICAVA ORS are prescription medicines used to treat people with amyotrophic lateral sclerosis (ALS). It is not known if RADICAVA or RADICAVA ORS are safe and effective in children. Do not receive RADICAVA or RADICAVA ORS if you are allergic to edaravone or any of the ingredients in RADICAVA and RADICAVA ORS. See the end of this leaflet for a complete list of ingredients in RADICAVA and RADICAVA ORS. Before you take RADICAVA or RADICAVA ORS, tell your healthcare provider about all of your medical conditions, including if you: • have asthma. • are allergic to other medicines. • are pregnant or plan to become pregnant. It is not known if RADICAVA or RADICAVA ORS will harm your unborn baby. • are breastfeeding or plan to breastfeed. It is not known if RADICAVA or RADICAVA ORS passes into your breastmilk. You and your healthcare provider should decide if you will receive RADICAVA or RADICAVA ORS or breastfeed. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. How will I receive RADICAVA? • You will be prescribed RADICAVA by a healthcare provider and told how often you will receive RADICAVA. • RADICAVA will be given by intravenous (IV) infusion into your vein. • It takes about 1 hour to receive the full dose of RADICAVA. • Your healthcare provider will monitor you closely during your treatment with RADICAVA. How will I take RADICAVA ORS? • See the detailed Instructions for Use on how to take RADICAVA ORS at the end of this Patient Information leaflet. • You will be prescribed RADICAVA ORS by a healthcare provider and told how often you will take RADICAVA ORS. • RADICAVA ORS is to be taken by mouth or by using a feeding tube. • RADICAVA ORS should be taken in the morning on an empty stomach. You should stop eating at bedtime. • Do not eat or drink anything 8 hours before each dose of RADICAVA ORS if you eat a high-fat meal. • Do not eat or drink anything 4 hours before each dose of RADICAVA ORS if you eat a low-fat meal. • Do not eat or drink anything 2 hours before each dose of RADICAVA ORS if you take a calorie supplement. • You should wait at least 1 hour after taking your medicine before eating or drinking anything except water. What are the possible side effects of RADICAVA and RADICAVA ORS? RADICAVA and RADICAVA ORS may cause serious side effects including: 1. Hypersensitivity (allergic) reactions. Hypersensitivity reactions have happened in people receiving RADICAVA or taking RADICAVA ORS and can happen after your medicine has been given. Tell your healthcare provider right away or go to the nearest emergency room if you have any of the following symptoms: 2. Sulfite allergic reactions. RADICAVA and RADICAVA ORS contain sodium bisulfite, a sulfite that may cause a type of allergic reaction that can be serious and life-threatening. Sodium bisulfite can also cause less severe allergic reactions, for example, asthma episodes, in certain people. Sulfite sensitivity can happen more often in people who have asthma than in people who do not have asthma. Tell your healthcare provider right away or go to the nearest emergency room if you have any of the following symptoms: Your healthcare provider will monitor you during treatment to watch for signs and symptoms of all the serious side effects and allergic reactions. The most common side effects of RADICAVA and RADICAVA ORS include bruising (contusion), problems walking (gait disturbance), and headache. These are not all the possible side effects of RADICAVA and RADICAVA ORS. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to www.fda.gov/medwatch or Mitsubishi Tanabe Pharma America, Inc. at 1-888-292-0058. What are the ingredients in RADICAVA and RADICAVA ORS? Active ingredient: edaravone RADICAVA Inactive ingredients: L-cysteine hydrochloride hydrate, sodium bisulfite, sodium chloride, phosphoric acid, and sodium hydroxide. RADICAVA ORS Inactive ingredients: L-cysteine hydrochloride hydrate, polyvinyl alcohol, simethicone emulsion, sodium bisulfite, sorbitol, and xanthan gum. Phosphoric acid and sodium hydroxide are added to adjust to pH 4 Marketed and distributed by: Mitsubishi Tanabe Pharma America, Inc., a US subsidiary of Mitsubishi Tanabe Pharma Corporation, 525 Washington Blvd., Suite 400, Jersey City, NJ 07310 For more information, go to www.Radicava.com or call 1-888-292-0058. This Patient Information has been approved by the U.S. Food and Drug Administration 22022-1 Issued: 05/2022 Instructions for Use INSTRUCTIONS FOR USE RADICAVA (ra di ká vah) ORS (edaravone) oral suspension Read this “Instructions for Use” before you take RADICAVA ORS for the first time and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. Important information about measuring RADICAVA ORS: Always measure your prescribed dose of RADICAVA ORS using the oral syringe provided. Ask your healthcare provider or pharmacist who provided the medicine any questions you have about how to measure your prescribed dose. If you miss a dose, do not take 2 doses of RADICAVA ORS the next day. Do not take a dose of RADICAVA ORS on days 15 through 28. How to prepare RADICAVA ORS : Keep this Instructions for Use handy when preparing the treatment. • If your healthcare provider prescribes a Starter Kit, you will receive 2 bottles of RADICAVA ORS. Each bottle will contain 35 mL of RADICAVA ORS for a total of 70 mL to be used for your first treatment cycle of 14 days. Only open the second bottle when you have finished the first bottle. • If you were not prescribed the Starter Kit, for each treatment cycle you will receive 1 bottle of RADICAVA ORS that contains a total of 50 mL of RADICAVA ORS. After the first treatment cycle, RADICAVA ORS is to be used for 10 days out of 14 day periods. • Only use the bottle adapter and the 2 reusable 5 mL oral syringes provided with the bottle. Do not use a household teaspoon to measure your medicine. How to store RADICAVA ORS: • Store RADICAVA ORS upright at room temperature between 68°F to 77°F (20°C to 25°C). Protect from light. • Opening the bottle: • When you open the bottle of RADICAVA ORS for the first use, write the date you open the bottle on the bottle label. • After opening the bottle of RADICAVA ORS, use within 15 days. • After a bottle of RADICAVA ORS has been opened and used, a white crust may form on the neck or on the side of the bottle. This is due to normal use and RADICAVA ORS can continue to be uses as prescribed. • Keep bottle tightly closed between each use. • Throw away (discard) any RADICAVA ORS that is not used within 15 days after opening the bottle or within 30 days from the date of shipment shown on the carton pharmacy label, whichever happens first. Ask your pharmacist how to properly throw away (discard) RADICAVA ORS you are no longer able to use. • Keep RADICAVA ORS and all medicines out of the reach of children. Each RADICAVA ORS carton contains: • 1 RADICAVA ORS bottle • 1 bottle adapter • 2 (5 mL) reusable oral syringes Use a new 5 mL oral syringe and bottle adapter when using a new bottle of RADICAVA ORS (see Figure A) Figure A Important information: • Keep these instructions for future use. • Do not share RADICAVA ORS with anyone else. • Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. • People who have problems using their hands may need assistance to draw up and give the correct dose of RADICAVA ORS. How to take RADICAVA ORS: Take RADICAVA ORS as prescribed by your healthcare provider. Dosing Information: RADICAVA ORS has 2 different dosing schedules: • For the first treatment cycle, you will take RADICAVA ORS every day for 14 days, followed by 14 days without the medicine. • For the cycles after the first treatment cycle, you will take RADICAVA ORS daily for 10 out of 14 days, followed by 14 days without the medicine. How RADICAVA ORS will be provided: • If your healthcare provider prescribes the Starter Kit, you will receive 2 bottles of RADICAVA ORS. Each bottle contains 35 mL of RADICAVA ORS for a total of 70 mL to deliver 14 doses. o There may be some medicine that remains in each bottle after the dose on day 7 and day 14 of the first treatment cycle. Throw away (discard) any medicine that remains. • If you were not prescribed the starter kit, for each treatment cycle, you will receive 1 bottle of RADICAVA ORS that contains a total of 50 mL of RADICAVA ORS to deliver 10 doses. o There may be some medicine that remains in each bottle after 10 doses. Throw away (discard) any medicine that remains. Fasting Information: • Do not eat or drink anything 8 hours before each dose of RADICAVA ORS if you eat a high-fat meal. • Do not eat or drink anything 4 hours before each dose of RADICAVA ORS if you eat a low-fat meal. • Do not eat or drink anything 2 hours before each dose of RADICAVA ORS if you take a calorie supplement. • You should wait at least 1 hour after taking your medicine before eating or drinking anything except water. Step 1: Before each use of RADICAVA ORS: Before opening the bottle, turn it upside down (invert) and shake vigorously up and down for at least 30 seconds (see Figure B). Look at the liquid medicine to make sure it is mixed well. If you see any small pieces at the bottom of the bottle, invert the bottle and shake it up and down for another 30 seconds or until you can no longer see the pieces at the bottom of the bottle (see Figure B). If the liquid medicine all looks the same, you can proceed to Step 2. Shake up and down for at least 30 seconds Figure B Step 2: Open the bottle by firmly pressing down on the bottle cap and turning it counterclockwise (to the left). Place the open bottle upright on a flat surface. Do not throw away the bottle cap; you will need to replace it after taking each dose. First time use of a bottle only. This must only be done 1 time for each bottle. Insert the ribbed end of the bottle adapter into the bottle by firmly pressing it in as far as it will go (see Figure C). Do not remove the bottle adapter. Figure C Step 3: Remove the oral syringe from plastic wrap and make sure the plunger is inserted all the way into the barrel. Push the oral syringe plunger toward its tip to remove excess air (see Figure D). Insert the oral syringe into the opening of the bottle adapter until it is firmly in place (see Figure E). Turn the bottle upside down and slowly pull the plunger to remove a small amount of liquid (see Figure F). Figure D Figure E Figure F Step 4: Keep the bottle upside down and pull the plunger until it goes up to the last line (5 mL) (see Figure G). While keeping the plunger in the same position, turn the bottle upright, and place it carefully on a flat surface. Remove the oral syringe by gently twisting or pulling it out from the bottle (see Figure H). Check the amount of medicine again before moving on to the next step (see Figure I). Note: Do not remove the oral syringe while the bottle is upside down (medicine may leak out through the adapter). Note: If the dose is not correct, insert the oral syringe tip firmly into the bottle adapter. Push the plunger all the way in so that the medicine flows back into the bottle. Turn the bottle upside down. Repeat Step 4. Figure G Figure H Figure I Step 5: Place the tip of the oral syringe in the mouth and aim towards the inside of the cheek. Slowly press down on the plunger until the oral syringe is empty. Swallow all of the medicine (see Figure J). If needed, you can use up to 8 ounces or 1 cup of water to help swallow the medicine. Note: It is normal for a small amount of medicine to remain in the tip of the syringe after taking. Figure J Step 6: Leave the bottle adapter inside the bottle. Place the bottle cap on the bottle and turn the cap clockwise (to the right). Keep bottle tightly closed between each use (see Figure K). Figure K Step 7: Remove the plunger from the oral syringe barrel by pulling the plunger and the barrel away from each other. Rinse the oral syringe (plunger and barrel) with water only . Allow it to air dry. Figure L Step 8: When the oral syringe (plunger and barrel) is dry, put the plunger back into the oral syringe barrel. Do not throw away the oral syringe . Store the syringe in a clean, dry place. You must complete Steps 1 through 4 under \\"How to take RADICAVA ORS\\" before starting Step 9 under \\"How to take a dose of RADICAVA ORS oral suspension through a feeding tube.\\" How to take a dose of RADICAVA ORS oral suspension through a feeding tube: Step 9: Using a catheter-tip syringe, flush the feeding tube with 1 ounce (30 mL) of water (see Figure M). Figure M Step 10: Place the oral syringe provided (containing the 5 mL of RADICAVA ORS) into the feeding tube. Slowly push down the plunger until the oral syringe is empty (see Figure N). Figure N Step 11: Using a catheter-tip syringe, flush the feeding tube with 1 ounce (30 mL) of water after taking dose of RADICAVA ORS (see Figure O). Figure O Step 12: Leave the adapter in the bottle. Place the bottle cap on the bottle and turn it clockwise (to the right) to close the bottle. Keep the bottle tightly closed between each use (see Figure P). Figure P Step 13: Remove the plunger from the oral syringe barrel by pulling the plunger and barrel away from each other. Rinse the oral syringe (plunger and barrel) with water only (see Figure Q). Allow it to air dry. Figure Q Step 14: When the oral syringe (plunger and barrel) are dry, put the plunger back into the oral syringe barrel. Do not throw away the oral syringe. Store the oral syringe in a clean, dry place. Marketed and distributed by: Mitsubishi Tanabe Pharma America, Inc., a US subsidiary of Mitsubishi Tanabe Pharma Corporation Jersey City, NJ 07310 For more information, go to www.Radicava.com or call 1- 888-292-0058. RADICAVA ORS ® is a registered trademark of Mitsubishi Tanabe Pharma Corporation © 2021 Mitsubishi Tanabe Pharma Corporation. All rights reserved. This Instructions for Use has been approved by the U.S. Food and Drug Administration. 22022-1 Issued: 05/2022 ifu-figure-a ifu-figure-b ifu-figure-c ifu-figure-d ifu-figure-e ifu-figure-f ifu-figure-g ife-figure-h ifu-figure-i ifu-figure-j ifg-figure-k ifu-figure-l ifu-figure-m ifu-figure-n ifu-figure-o ifu-figure-p ifu-figure-q","Information for Patients PATIENT INFORMATION RADICAVA (ra di ká vah) (edaravone injection) for intravenous infusion RADICAVA ORS (ra di ká vah o r s) (edaravone oral suspension) administered by mouth or via feeding tube What are RADICAVA and RADICAVA ORS? RADICAVA and RADICAVA ORS are prescription medicines used to treat people with amyotrophic lateral sclerosis (ALS). It is not known if RADICAVA or RADICAVA ORS are safe and effective in children. Do not receive RADICAVA or RADICAVA ORS if you are allergic to edaravone or any of the ingredients in RADICAVA and RADICAVA ORS. See the end of this leaflet for a complete list of ingredients in RADICAVA and RADICAVA ORS. Before you take RADICAVA or RADICAVA ORS, tell your healthcare provider about all of your medical conditions, including if you: • have asthma. • are allergic to other medicines. • are pregnant or plan to become pregnant. It is not known if RADICAVA or RADICAVA ORS will harm your unborn baby. • are breastfeeding or plan to breastfeed. It is not known if RADICAVA or RADICAVA ORS passes into your breastmilk. You and your healthcare provider should decide if you will receive RADICAVA or RADICAVA ORS or breastfeed. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. How will I receive RADICAVA? • You will be prescribed RADICAVA by a healthcare provider and told how often you will receive RADICAVA. • RADICAVA will be given by intravenous (IV) infusion into your vein. • It takes about 1 hour to receive the full dose of RADICAVA. • Your healthcare provider will monitor you closely during your treatment with RADICAVA. How will I take RADICAVA ORS? • See the detailed Instructions for Use on how to take RADICAVA ORS at the end of this Patient Information leaflet. • You will be prescribed RADICAVA ORS by a healthcare provider and told how often you will take RADICAVA ORS. • RADICAVA ORS is to be taken by mouth or by using a feeding tube. • RADICAVA ORS should be taken in the morning on an empty stomach. You should stop eating at bedtime. • Do not eat or drink anything 8 hours before each dose of RADICAVA ORS if you eat a high-fat meal. • Do not eat or drink anything 4 hours before each dose of RADICAVA ORS if you eat a low-fat meal. • Do not eat or drink anything 2 hours before each dose of RADICAVA ORS if you take a calorie supplement. • You should wait at least 1 hour after taking your medicine before eating or drinking anything except water. What are the possible side effects of RADICAVA and RADICAVA ORS? RADICAVA and RADICAVA ORS may cause serious side effects including: 1. Hypersensitivity (allergic) reactions. Hypersensitivity reactions have happened in people receiving RADICAVA or taking RADICAVA ORS and can happen after your medicine has been given. Tell your healthcare provider right away or go to the nearest emergency room if you have any of the following symptoms: 2. Sulfite allergic reactions. RADICAVA and RADICAVA ORS contain sodium bisulfite, a sulfite that may cause a type of allergic reaction that can be serious and life-threatening. Sodium bisulfite can also cause less severe allergic reactions, for example, asthma episodes, in certain people. Sulfite sensitivity can happen more often in people who have asthma than in people who do not have asthma. Tell your healthcare provider right away or go to the nearest emergency room if you have any of the following symptoms: Your healthcare provider will monitor you during treatment to watch for signs and symptoms of all the serious side effects and allergic reactions. The most common side effects of RADICAVA and RADICAVA ORS include bruising (contusion), problems walking (gait disturbance), and headache. These are not all the possible side effects of RADICAVA and RADICAVA ORS. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to www.fda.gov/medwatch or Mitsubishi Tanabe Pharma America, Inc. at 1-888-292-0058. What are the ingredients in RADICAVA and RADICAVA ORS? Active ingredient: edaravone RADICAVA Inactive ingredients: L-cysteine hydrochloride hydrate, sodium bisulfite, sodium chloride, phosphoric acid, and sodium hydroxide. RADICAVA ORS Inactive ingredients: L-cysteine hydrochloride hydrate, polyvinyl alcohol, simethicone emulsion, sodium bisulfite, sorbitol, and xanthan gum. Phosphoric acid and sodium hydroxide are added to adjust to pH 4 Marketed and distributed by: Mitsubishi Tanabe Pharma America, Inc., a US subsidiary of Mitsubishi Tanabe Pharma Corporation, 525 Washington Blvd., Suite 400, Jersey City, NJ 07310 For more information, go to www.Radicava.com or call 1-888-292-0058. This Patient Information has been approved by the U.S. Food and Drug Administration 22022-1 Issued: 05/2022"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of RADICAVA or RADICAVA ORS in pregnant women. In animal studies, administration of edaravone to pregnant rats and rabbits resulted in adverse developmental effects (increased mortality, decreased growth, delayed sexual development, and altered behavior) at clinically relevant doses. Most of these effects occurred at doses that were also associated with maternal toxicity (see Animal Data ) . 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. The background risk for major birth defects and miscarriage in patients with ALS is unknown. Data Animal Data In rats, intravenous administration of edaravone (0, 3, 30, or 300 mg/kg/day) throughout the period of organogenesis resulted in reduced fetal weight at all doses. In dams allowed to deliver naturally, offspring weight was reduced at the highest dose tested. Maternal toxicity was also observed at the highest dose tested. There were no adverse effects on reproductive function in the offspring. A no-effect dose for embryofetal developmental toxicity was not identified; the low dose is less than the recommended human dose of 60 mg for RADICAVA on a body surface area (mg/m 2 ) basis. In rabbits, intravenous administration of edaravone (0, 3, 20, or 100 mg/kg/day) throughout the period of organogenesis resulted in embryofetal death at the highest dose tested, which was associated with maternal toxicity. The higher no-effect dose for embryofetal developmental toxicity is approximately 6 times the recommended human dose (RHD) for RADICAVA on a body surface area (mg/m 2 ) basis. The effects on offspring of edaravone (0, 3, 20, or 200 mg/kg/day), administered by intravenous injection to rats from GD 17 throughout lactation, were assessed in two studies. In the first study, offspring mortality was observed at the high dose and increased activity was observed at the mid and high doses. In the second study, there was an increase in stillbirths, offspring mortality, and delayed physical development (vaginal opening) at the highest dose tested. Reproduction function in offspring was not affected in either study. Maternal toxicity was evident in both studies at all but the lowest dose tested. The no-effect dose for developmental toxicity (3 mg/kg/day) is less than the RHD on a mg/m 2 basis. Reproductive and developmental toxicology studies of edaravone using the oral route have not been conducted"}', 'pediatric_use': '{"8.4 Pediatric Use Safety and effectiveness of RADICAVA or RADICAVA ORS in pediatric patients have not been established"}', 'geriatric_use': '{"8.5 Geriatric Use Of the 184 patients with ALS who received RADICAVA in 3 placebo-controlled clinical trials, a total of 53 patients were 65 years of age and older, including 2 patients 75 years of age and older. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out."}'}

{OXYGEN}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': None, 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{OXYGEN}', 'route': '{"RESPIRATORY (INHALATION)"}', '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}

{"CAMPHOR (SYNTHETIC)",MENTHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses Temporarily relieves minor aches and pains of muscles and joints associated with: arthritis, simple backaches"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"MENTHOL CAMPHOR"}', '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 on wounds or damaged skin. When using this product: avoid bandaging tightly, avoid contact with eyes, keep out of reach of children. Stop use and ask doctor if: condition worsens, symptoms persist for more than 7 days, clear up and occur again within a few days."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"LOSARTAN POTASSIUM"}

{'contraindications': '{"4 CONTRAINDICATIONS Losartan potassium tablets are contraindicated: In patients who are hypersensitive to any component of this product. For coadministration with aliskiren in patients with diabetes. Hypersensitivity to any component. ( 4 ) Coadministration with aliskiren in patients with diabetes. ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS Most common adverse reactions (incidence ≥2% and greater than placebo) are: dizziness, upper respiratory infection, nasal congestion, and back pain. ( 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. Hypertension Losartan potassium has been evaluated for safety in more than 3300 adult patients treated for essential hypertension and 4058 patients/subjects overall. Over 1200 patients were treated for over 6 months and more than 800 for over one year. Treatment with losartan potassium was well-tolerated with an overall incidence of adverse events similar to that of placebo. In controlled clinical trials, discontinuation of therapy for adverse events occurred in 2.3% of patients treated with losartan potassium and 3.7% of patients given placebo. In 4 clinical trials involving over 1000 patients on various doses (10 to 150 mg) of losartan potassium and over 300 patients given placebo, the adverse events that occurred in ≥2% of patients treated with losartan potassium and more commonly than placebo were: dizziness (3% vs. 2%), upper respiratory infection (8% vs. 7%), nasal congestion (2% vs. 1%), and back pain (2% vs. 1%). The following less common adverse reactions have been reported: Blood and lymphatic system disorders: Anemia. Psychiatric disorders: Depression. Nervous system disorders: Somnolence, headache, sleep disorders, paresthesia, migraine. Ear and labyrinth disorders: Vertigo, tinnitus. Cardiac disorders: Palpitations, syncope, atrial fibrillation, CVA. Respiratory, thoracic and mediastinal disorders: Dyspnea. Gastrointestinal disorders: Abdominal pain, constipation, nausea, vomiting. Skin and subcutaneous tissue disorders: Urticaria, pruritus, rash, photosensitivity. Musculoskeletal and connective tissue disorders: Myalgia, arthralgia. Reproductive system and breast disorders: Impotence. General disorders and administration site conditions: Edema. Cough Persistent dry cough (with an incidence of a few percent) has been associated with ACE-inhibitor use and in practice can be a cause of discontinuation of ACE-inhibitor therapy. Two prospective, parallel-group, double-blind, randomized, controlled trials were conducted to assess the effects of losartan on the incidence of cough in hypertensive patients who had experienced cough while receiving ACE-inhibitor therapy. Patients who had typical ACE-inhibitor cough when challenged with lisinopril, whose cough disappeared on placebo, were randomized to losartan 50 mg, lisinopril 20 mg, or either placebo (one study, n=97) or 25 mg hydrochlorothiazide (n=135). The double-blind treatment period lasted up to 8 weeks. The incidence of cough is shown in Table 1 below. Table 1: * Demographics = (89% Caucasian, 64% female) † Demographics = (90% Caucasian, 51% female) Study 1* HCTZ Losartan Lisinopril Cough 25% 17% 69% Study 2 † Placebo Losartan Lisinopril Cough 35% 29% 62% These studies demonstrate that the incidence of cough associated with losartan therapy, in a population that all had cough associated with ACE-inhibitor therapy, is similar to that associated with hydrochlorothiazide or placebo therapy. Cases of cough, including positive re-challenges, have been reported with the use of losartan in postmarketing experience. Hypertensive Patients with Left Ventricular Hypertrophy In the Losartan Intervention for Endpoint (LIFE) study, adverse reactions with losartan potassium were similar to those reported previously for patients with hypertension. Nephropathy in Type 2 Diabetic Patients In the Reduction of Endpoints in NIDDM with the Angiotensin II Receptor Antagonist Losartan (RENAAL) study involving 1513 patients treated with losartan potassium or placebo, the overall incidences of reported adverse events were similar for the two groups. Discontinuations of losartan potassium because of side effects were similar to placebo (19% for losartan potassium, 24% for placebo). The adverse events, regardless of drug relationship, reported with an incidence of ≥4% of patients treated with losartan potassium and occurring with ≥2% difference in the losartan group vs. placebo on a background of conventional antihypertensive therapy, were asthenia/fatigue, chest pain, hypotension, orthostatic hypotension, diarrhea, anemia, hyperkalemia, hypoglycemia, back pain, muscular weakness, and urinary tract infection. 6.2 Postmarketing Experience The following additional adverse reactions have been reported in postmarketing experience with losartan potassium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure: Digestive: Hepatitis. General Disorders and Administration Site Conditions: Malaise. Hematologic: Thrombocytopenia. Hypersensitivity: Angioedema, including swelling of the larynx and glottis, causing airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue has been reported rarely in patients treated with losartan; some of these patients previously experienced angioedema with other drugs including ACE inhibitors. Vasculitis, including Henoch-Schönlein purpura, has been reported. Anaphylactic reactions have been reported. Metabolic and Nutrition: Hyponatremia. Musculoskeletal: Rhabdomyolysis. Nervous system disorders : Dysgeusia. Skin : Erythroderma."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Agents increasing serum potassium: Risk of hyperkalemia. ( 7.1 ) Lithium: Risk of lithium toxicity. ( 7.2 ) NSAIDs: Increased risk of renal impairment and reduced diuretic, natriuretic, and antihypertensive effects. ( 7.3 ) Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, syncope, and hyperkalemia. ( 7.4 ) 7.1 Agents Increasing Serum Potassium Coadministration of losartan with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients. 7.2 Lithium Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists. Monitor serum lithium levels during concomitant use. 7.3 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) 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 angiotensin II receptor antagonists (including losartan) may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving losartan and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including losartan, may be attenuated by NSAIDs, including selective COX-2 inhibitors. 7.4 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, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial enrolled 1448 patients with type 2 diabetes, elevated urinary-albumin-to-creatinine ratio, and decreased estimated glomerular filtration rate (GFR 30 to 89.9 mL/min), randomized them to lisinopril or placebo on a background of losartan therapy and followed them for a median of 2.2 years. Patients receiving the combination of losartan and lisinopril did not obtain any additional benefit compared to monotherapy for the combined endpoint of decline in GFR, end stage renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney injury compared with the monotherapy group. In most patients no benefit has been associated with using two RAS inhibitors concomitantly. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function, and electrolytes in patients on losartan potassium and other agents that affect the RAS. Do not coadminister aliskiren with losartan potassium in patients with diabetes. Avoid use of aliskiren with losartan potassium in patients with renal impairment (GFR <60 mL/min)."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Losartan potassium tablets are an angiotensin II receptor blocker (ARB) indicated for: Treatment of hypertension, to lower blood pressure in adults and children greater than 6 years old. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. ( 1.1 ) Reduction of the risk of stroke in patients with hypertension and left ventricular hypertrophy. There is evidence that this benefit does not apply to Black patients. ( 1.2 ) Treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria in patients with type 2 diabetes and a history of hypertension. ( 1.3 ) 1.1 Hypertension Losartan potassium tablets are indicated for the treatment of hypertension in adults and pediatric patients 6 years of age and older, to lower blood pressure. Lowering blood pressure lowers the risk of fatal and nonfatal cardiovascular (CV) events, primarily strokes and myocardial infarction. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including losartan. 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. Losartan potassium tablets may be administered with other antihypertensive agents. 1.2 Hypertensive Patients with Left Ventricular Hypertrophy Losartan potassium tablets are indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy, but there is evidence that this benefit does not apply to Black patients [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ]. 1.3 Nephropathy in Type 2 Diabetic Patients Losartan potassium tablets are indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes and a history of hypertension. In this population, losartan potassium tablets reduces the rate of progression of nephropathy as measured by the occurrence of doubling of serum creatinine or end stage renal disease (need for dialysis or renal transplantation) [see Clinical Studies (14.3) ]."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Hypotension: Correct volume or salt depletion prior to administration of losartan potassium. ( 5.2 ) Monitor renal function and potassium in susceptible patients. ( 5.3 , 5.4 ) 5.1 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 losartan potassium as soon as possible [see Use in Specific Populations (8.1) ]. 5.2 Hypotension in Volume- or Salt-Depleted Patients In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with losartan potassium. Correct volume or salt depletion prior to administration of losartan potassium [see Dosage and Administration (2.1) ] . 5.3 Renal Function Deterioration Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on losartan potassium. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on losartan potassium [see Drug Interactions (7.3) and Use in Specific Populations (8.7) ] . 5.4 Hyperkalemia Monitor serum potassium periodically and treat appropriately. Dosage reduction or discontinuation of losartan potassium may be required . Monitor serum potassium periodically and treat appropriately. Dosage reduction or discontinuation of losartan potassium may be required [see Adverse Reactions (6.1) ] . Concomitant use of other drugs that may increase serum potassium may lead hyperkalemia . Concomitant use of other drugs that may increase serum potassium may lead to hyperkalemia [see Drug Interactions (7.1) ] ."}', 'overdosage': '{"10 OVERDOSAGE Significant lethality was observed in mice and rats after oral administration of 1000 mg/kg and 2000 mg/kg, respectively, about 44 and 170 times the maximum recommended human dose on a mg/m 2 basis. Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Neither losartan nor its active metabolite can be removed by hemodialysis."}', 'active_flag': 'Y', 'generic_name': '{"LOSARTAN POTASSIUM"}', '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). Pregnancy Advise female patients of childbearing age about the consequences of exposure to losartan potassium during pregnancy. Discuss treatment options with women planning to become pregnant. Tell patients to report pregnancies to their physicians as soon as possible [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ]. Potassium Supplements Advise patients receiving losartan potassium not to use potassium supplements or salt substitutes containing potassium without consulting their healthcare provider [see Drug Interactions (7.1) ] . Patient Information Losartan Potassium Tablets USP (loe sar\' tan poe tas\' ee um) 25 mg, 50 mg, 100 mg Rx only Read the Patient Information that comes with losartan potassium tablets before you start taking them and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your condition and treatment. What is the most important information I should know about losartan potassium tablets? Losartan potassium tablets can cause harm or death to an unborn baby. Talk to your doctor about other ways to lower your blood pressure if you plan to become pregnant. If you get pregnant while taking losartan potassium tablets, tell your doctor right away. What are losartan potassium tablets? Losartan potassium tablets is a prescription medicine called an angiotensin receptor blocker (ARB). It is used: alone or with other blood pressure medicines to lower high blood pressure (hypertension). to lower the chance of stroke in patients with high blood pressure and a heart problem called left ventricular hypertrophy. Losartan potassium tablets may not help Black patients with this problem. to slow the worsening of diabetic kidney disease (nephropathy) in patients with type 2 diabetes who have or had high blood pressure. Losartan potassium tablets have not been studied in children less than 6 years old or in children with certain kidney problems. High Blood Pressure (hypertension). Blood pressure is the force in your blood vessels when your heart beats and when your heart rests. You have high blood pressure when the force is too much. Losartan potassium tablets can help your blood vessels relax so your blood pressure is lower. Left Ventricular Hypertrophy (LVH) is an enlargement of the walls of the left chamber of the heart (the heart’s main pumping chamber). LVH can happen from several things. High blood pressure is the most common cause of LVH. Type 2 Diabetes with Nephropathy. Type 2 diabetes is a type of diabetes that happens mainly in adults. If you have diabetic nephropathy it means that your kidneys do not work properly because of damage from the diabetes. Who should not take losartan potassium tablets? Do not take losartan potassium tablets if you are allergic to any of the ingredients in losartan potassium tablets. See the end of this leaflet for a complete list of ingredients in losartan potassium tablets. Do not take losartan potassium tablets if you have diabetes and are taking a medicine called aliskiren to reduce blood pressure. What should I tell my doctor before taking losartan potassium tablets? Tell your doctor about all of your medical conditions including if you: are pregnant or planning to become pregnant. See “What is the most important information I should know about losartan potassium tablets?” are breastfeeding. It is not known if losartan potassium passes into your breast milk. You should choose either to take losartan potassium tablets or breastfeed, but not both. are vomiting a lot or having a lot of diarrhea have liver problems have kidney problems Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Losartan potassium tablets and certain other medicines may interact with each other. Especially tell your doctor if you are taking: potassium supplements salt substitutes containing potassium other medicines that may increase serum potassium water pills (diuretics) lithium (a medicine used to treat a certain kind of depression) medicines used to treat pain and arthritis, called non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors other medicines to reduce blood pressure How should I take losartan potassium tablets? Take losartan potassium tablets exactly as prescribed by your doctor. Your doctor may change your dose if needed. Losartan potassium tablets can be taken with or without food. If you miss a dose, take it as soon as you remember. If it is close to your next dose, do not take the missed dose. Just take the next dose at your regular time. If you take too much losartan potassium, call your doctor or Poison Control Center, or go to the nearest hospital emergency room right away. What are the possible side effects of losartan potassium tablets? Losartan potassium tablets may cause the following side effects that may be serious: Injury or death of unborn babies. See “What is the most important information I should know about losartan potassium tablets?” Allergic reaction. Symptoms of an allergic reaction are swelling of the face, lips, throat or tongue. Get emergency medical help right away and stop taking losartan potassium tablets. Low blood pressure (hypotension). Low blood pressure may cause you to feel faint or dizzy. Lie down if you feel faint or dizzy. Call your doctor right away. For people who already have kidney problems, you may see a worsening in how well your kidneys work. Call your doctor if you get swelling in your feet, ankles, or hands, or unexplained weight gain. High blood levels of potassium The most common side effects of losartan potassium tablets in people with high blood pressure are: “colds” (upper respiratory infection) dizziness stuffy nose back pain The most common side effects of losartan potassium tablets in people with type 2 diabetes with diabetic kidney disease are: diarrhea tiredness low blood sugar chest pain high blood potassium low blood pressure Tell your doctor if you get any side effect that bothers you or that won’t go away. This is not a complete list of side effects. For a complete list, ask your doctor or pharmacist. How do I store losartan potassium tablets? Store losartan potassium tablets USP at 59°F to 86°F (15°C to 30°C). Keep losartan potassium tablets in a tightly closed container that protects the medicine from light. Keep losartan potassium tablets and all medicines out of the reach of children. General information about losartan potassium tablets Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use losartan potassium tablets for a condition for which it was not prescribed. Do not give losartan potassium tablets to other people, even if they have the same symptoms that you have. They may harm them. This leaflet summarizes the most important information about losartan potassium tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about losartan potassium tablets that is written for health professionals. What are the ingredients in losartan potassium tablets? Active ingredient: losartan potassium Inactive ingredients: microcrystalline cellulose, lactose monohydrate, pregelatinized starch (maize), low substituted hydroxypropyl cellulose, magnesium stearate, hydroxypropyl cellulose, hypromellose 6 cP, titanium dioxide, FD&C blue #2/indigo carmine aluminum lake, D&C yellow #10 aluminum lake, and purified water. Ora-Plus™ and Ora-Sweet SF™ are the trademarks of Paddock Laboratories, Inc. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 038, India Revised: 03/2019"}', 'pregnancy': '{"8.1 Pregnancy Pregnancy Category D 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 losartan 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 losartan potassium, 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 losartan potassium for hypotension, oliguria, and hyperkalemia [see Use in Specific Populations (8.4) ] . Losartan potassium has been shown to produce adverse effects in rat fetuses and neonates, including decreased body weight, delayed physical and behavioral development, mortality and renal toxicity. With the exception of neonatal weight gain (which was affected at doses as low as 10 mg/kg/day), doses associated with these effects exceeded 25 mg/kg/day (approximately three times the maximum recommended human dose of 100 mg on a mg/m 2 basis). These findings are attributed to drug exposure in late gestation and during lactation. Significant levels of losartan and its active metabolite were shown to be present in rat fetal plasma during late gestation and in rat milk."}', 'pediatric_use': '{"8.4 Pediatric Use Neonates with a history of in utero exposure to losartan potassium: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function. Antihypertensive effects of losartan potassium have been established in hypertensive pediatric patients aged 6 to 16 years. Safety and effectiveness have not been established in pediatric patients under the age of 6 or in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m 2 [see Dosage and Administration (2.1) , Clinical Pharmacology (12.3) , and Clinical Studies (14.1) ] ."}', 'geriatric_use': '{"8.5 Geriatric Use Of the total number of patients receiving losartan potassium in controlled clinical studies for hypertension, 391 patients (19%) were 65 years and over, while 37 patients (2%) were 75 years and over. In a controlled clinical study for renal protection in type 2 diabetic patients with proteinuria, 248 patients (33%) were 65 years and over. In a controlled clinical study for the reduction in the combined risk of cardiovascular death, stroke and myocardial infarction in hypertensive patients with left ventricular hypertrophy, 2857 patients (62%) were 65 years and over, while 808 patients (18%) were 75 years and over. No overall differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out."}'}

{"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 HCL"}', '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}

{"SODIUM CHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses temporary relief of corneal edema"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"SODIUM CHLORIDE"}', 'route': '{OPHTHALMIC}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings For external use only Do not use • except under the advice and supervision of a doctor • if solution changes color or becomes cloudy When using this product • it may cause temporary burning and irritation • to avoid contamination, do not touch tip of container to any surface • replace cap after use Stop use and ask a doctor if • condition worsens or persists for more than 72 hours • you experience eye pain, changes in vision, continued redness or irritation of the eye"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"SOLIFENACIN SUCCINATE"}

{'contraindications': '{"4 CONTRAINDICATIONS Solifenacin succinate tablets are contraindicated in patients: With urinary retention [see Warnings and Precautions ( 5.2 )] , With gastric retention [see Warnings and Precautions ( 5.3 )] , With uncontrolled narrow-angle glaucoma [see Warnings and Precautions ( 5.5 )] , and Who have demonstrated hypersensitivity to solifenacin succinate or the inactive ingredients in solifenacin succinate tablets. Reported adverse reactions have included anaphylaxis and angioedema [see Adverse Reactions ( 6.2 )] . Urinary retention. ( 4 , 5.2 ) Gastric retention. ( 4 , 5.3 ) Uncontrolled narrow-angle glaucoma. ( 4 , 5.5 ) Hypersensitivity to this product or any of its components. ( 4 , 5.1 , 6.2 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The most common adverse reactions (> 4% in solifenacin succinate-treated patients and > placebo-treated patients) were dry mouth and constipation at both 5 mg and 10 mg doses; and urinary tract infection, and blurred vision at the 10 mg dose. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ajanta Pharma USA Inc. at 855-664-7744 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. Solifenacin succinate tablets have been evaluated for safety in 1,811 adult patients in four randomized, placebo-controlled trials (Studies 1-4) [see Clinical Studies ( 14 )] . Expected adverse reactions of antimuscarinic agents are dry mouth, constipation, blurred vision (accommodation abnormalities), urinary retention, and dry eyes. The incidence of dry mouth and constipation in patients treated with solifenacin succinate tablets was higher in the 10 mg dose group compared to the 5 mg dose group. In the four 12-week double-blind clinical trials, severe fecal impaction, colonic obstruction, and intestinal obstruction were reported in one patient each, all in the solifenacin succinate tablets 10 mg group. Angioneurotic edema was reported in one patient taking solifenacin succinate tablets 5 mg. Compared to 12 weeks of treatment with solifenacin succinate tablets, the incidence and severity of adverse reactions were similar in patients who remained on drug for up to 12 months in Study 5 [see Clinical Studies ( 14 )] . The most frequent adverse reaction leading to study discontinuation was dry mouth (1.5%). Table 1 lists the rates of identified adverse reactions, in the four randomized, placebo-controlled trials at an incidence greater than placebo and in 1% or more of patients treated with solifenacin succinate tablets 5 mg or 10 mg once daily for up to 12 weeks. Table 1: Adverse Reactions Reported by ≥ 1% of Patients and Exceeding Placebo in Studies 1, 2, 3 and 4 Placebo (%) Solifenacin succinate tablets 5 mg (%) Solifenacin succinate tablets 10 mg (%) Number of Patients 1,216 578 1,233 GASTROINTESTINAL DISORDERS Dry Mouth 4.2 10.9 27.6 Constipation 2.9 5.4 13.4 Nausea 2.0 1.7 3.3 Dyspepsia 1.0 1.4 3.9 Abdominal Pain Upper 1.0 1.9 1.2 Vomiting NOS 0.9 0.2 1.1 INFECTIONS AND INFESTATIONS Urinary Tract Infection NOS 2.8 2.8 4.8 Influenza 1.3 2.2 0.9 Pharyngitis NOS 1.0 0.3 1.1 NERVOUS SYSTEM DISORDERS Dizziness 1.8 1.9 1.8 EYE DISORDERS Vision Blurred 1.8 3.8 4.8 Dry Eyes NOS 0.6 0.3 1.6 RENAL AND URINARY DISORDERS Urinary Retention 0.6 0 1.4 GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS Edema Lower Limb 0.7 0.3 1.1 Fatigue 1.1 1.0 2.1 PSYCHIATRIC DISORDERS Depression NOS 0.8 1.2 0.8 RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS Cough 0.2 0.2 1.1 VASCULAR DISORDERS Hypertension NOS 0.6 1.4 0.5 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of solifenacin succinate in the U.S. and/or outside of the U.S. 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. General disorders and administration site conditions: peripheral edema, hypersensitivity reactions (including angioedema with airway obstruction, rash, pruritus, urticaria, anaphylactic reaction); Nervous system disorders : dizziness, headache, confusion, hallucinations, delirium, somnolence; Cardiac disorders : QT prolongation, Torsade de Pointes, atrial fibrillation, tachycardia, palpitations; Hepatobiliary disorders : liver disorders mostly characterized by abnormal liver function tests, AST (aspartate aminotransferase), ALT (alanine aminotransferase), GGT (gamma-glutamyl transferase); Renal and urinary disorders : renal impairment, urinary retention; Metabolism and nutrition disorders : decreased appetite, hyperkalemia; Skin and subcutaneous tissue disorders : exfoliative dermatitis, erythema multiforme, dry skin; Eye disorders : glaucoma; Gastrointestinal disorders : gastroesophageal reflux disease, ileus, vomiting, abdominal pain, dysgeusia, sialadenitis; Respiratory, thoracic and mediastinal disorders: dysphonia, nasal dryness; Musculoskeletal and connective tissue disorders : muscular weakness"}', 'drug_interactions': '{"7 DRUG INTERACTIONS CYP3A4 Inhibitors : Do not exceed the 5 mg dose of solifenacin succinate tablets with concomitant use of strong CYP3A4 inhibitors. ( 7.1 ) 7.1 Strong CYP3A4 Inhibitors Solifenacin is a substrate of CYP3A4. Concomitant use of ketoconazole, a strong CYP3A4 inhibitor, significantly increased the exposure of solifenacin [see Clinical Pharmacology ( 12.3 )]. The dosage of solifenacin succinate tablets greater than 5 mg once daily is not recommended when concomitantly used with strong CYP3A4 inhibitors [see Dosage and Administration ( 2.4 )] ."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Solifenacin succinate tablets are indicated for the treatment of adults with overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Solifenacin succinate tablets are a muscarinic antagonist indicated for the treatment of adults with overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Angioedema and Anaphylactic Reactions : Promptly discontinue solifenacin succinate tablets and provide appropriate therapy. ( 5.1 ) Urinary Retention : Solifenacin succinate tablets are not recommended for use in patients with clinically significant bladder outlet obstruction. ( 5.2 ) Gastrointestinal Disorders : Solifenacin succinate tablets are not recommended for use in patients with decreased gastrointestinal motility. ( 5.3 ) Central Nervous System Effects : Somnolence has been reported with solifenacin succinate tablets. Advise patients not to drive or operate heavy machinery until they know how solifenacin succinate tablets affects them. ( 5.4 ) Controlled Narrow-Angle Glaucoma : Use solifenacin succinate tablets with caution in patients being treated for narrow-angle glaucoma. ( 5.5 ) QT Prolongation in Patients at High Risk of QT Prolongation : Solifenacin succinate tablets are not recommended for use in patients at high risk of QT prolongation, including patients with a known history of QT prolongation and patients taking medications known to prolong the QT interval. ( 5.6 ) 5.1 Angioedema and Anaphylactic Reactions Angioedema of the face, lips, tongue, and/or larynx have been reported with solifenacin succinate. In some cases, angioedema occurred after the first dose, however, cases have been reported to occur hours after the first dose or after multiple doses. Anaphylactic reactions have also been reported in patients treated with solifenacin succinate. Angioedema associated with upper airway swelling and anaphylactic reactions may be life-threatening. Solifenacin succinate tablets are contraindicated in patients with a known or suspected hypersensitivity to solifenacin succinate [see Contraindications ( 4 )] . If involvement of the tongue, hypopharynx, or larynx occurs, promptly discontinue solifenacin succinate tablets and provide appropriate therapy and/or measures necessary to ensure a patent airway. 5.2 Urinary Retention The use of solifenacin succinate tablets, like other antimuscarinic drugs, in patients with clinically significant bladder outlet obstruction including patients with urinary retention, may result in further urinary retention and kidney injury. The use of solifenacin succinate tablets are not recommended in patients with clinically significant bladder outlet obstruction and is contraindicated in patients with urinary retention [see Contraindications ( 4 )] . 5.3 Gastrointestinal Disorders The use of solifenacin succinate tablets, like other antimuscarinic drugs, in patients with conditions associated with decreased gastrointestinal motility may result in further decreased gastrointestinal motility. Solifenacin succinate tablets are contraindicated in patients with gastric retention [see Contraindications ( 4 )] . The use of solifenacin succinate tablets are not recommended in patients with conditions associated with decreased gastrointestinal motility. 5.4 Central Nervous System Effects Solifenacin succinate tablets are associated with antimuscarinic central nervous system (CNS) adverse reactions [see Adverse Reactions ( 6.2 )] . A variety of CNS antimuscarinic adverse reactions have been reported, including headache, confusion, hallucinations, and somnolence. Monitor patients for signs of antimuscarinic CNS adverse reactions, particularly after beginning treatment or increasing the dose. Advise patients not to drive or operate heavy machinery until they know how solifenacin succinate tablets affect them. If a patient experiences antimuscarinic CNS adverse reactions, consider dose reduction or drug discontinuation. 5.5 Controlled Narrow-Angle Glaucoma Solifenacin succinate tablets should be used with caution in patients being treated for narrow-angle glaucoma [see Contraindications ( 4 )] . 5.6 QT Prolongation in Patients at High Risk of QT Prolongation In a study of the effect of solifenacin succinate on the QT interval conducted in 76 healthy women [see Clinic al Pharmacology ( 12.2 )] , solifenacin succinate 30 mg (three times the largest maximum recommended dose in adult patients) was associated with a mean increase in the Fridericia-corrected QT interval of 8 msec (90% CI, 4, 13). The QT prolonging effect appeared less with solifenacin succinate 10 mg than with solifenacin succinate 30 mg, and the effect of solifenacin succinate 30 mg did not appear as large as that of the positive control moxifloxacin at its therapeutic dose. The use of solifenacin succinate tablets are not recommended in patients at high risk of QT prolongation, including patients with a known history of QT prolongation and patients who are taking medications known to prolong the QT interval."}', 'overdosage': '{"10 OVERDOSAGE Overdosage with solifenacin succinate tablets can potentially result in severe antimuscarinic effects and should be treated accordingly. The highest dose ingested in an accidental overdose of solifenacin succinate was 280 mg (28 times the maximum dosage) in a 5-hour period. This case was associated with mental status changes. Some cases reported a decrease in the level of consciousness. Intolerable antimuscarinic adverse reactions (fixed and dilated pupils, blurred vision, failure of heel-to-toe exam, tremors, and dry skin) occurred on day 3 in normal volunteers taking 50 mg daily (5 times the maximum recommended therapeutic dose) and resolved within 7 days following discontinuation of drug. In the event of overdose with solifenacin succinate tablets, treat with gastric lavage and appropriate supportive measures. ECG monitoring is also recommended."}', 'active_flag': 'Y', 'generic_name': '{"SOLIFENACIN 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 the patient to read the FDA-approved patient labeling (Patient Information). Angioedema and Anaphylactic Reactions Inform patients that angioedema and anaphylactic reactions have been reported in patients treated with solifenacin succinate tablets. Angioedema and anaphylactic reactions may be life-threatening. Advise patients to promptly discontinue solifenacin succinate tablets therapy and seek immediate attention if they experience edema of the tongue or laryngopharynx, or difficulty breathing [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )]. Urinary Retention Inform patients that solifenacin succinate tablets may cause urinary retention in patients with conditions associated with bladder outlet obstruction [see Warnings and Precautions ( 5.2 )]. Gastrointestinal Disorders Inform patients that solifenacin succinate tablets may cause further decrease in gastrointestinal motility in patients with conditions associated with decreased gastrointestinal motility. Solifenacin succinate tablets has been associated with constipation and dry mouth. Advise patients to contact their health care providers if they experience severe abdominal pain or become constipated for 3 or more days [see Warnings and Precautions ( 5.3 )]. Central Nervous System Effects Because solifenacin succinate tablets, like other antimuscarinic agents, may cause central nervous system effects or blurred vision, advise patients to exercise caution in decisions to engage in potentially dangerous activities until the drug’s effect on the patient has been determined [see Warnings and Precautions ( 5.4 )]. Narrow-Angle Glaucoma Inform patients that solifenacin succinate tablets, like other antimuscarinics, may cause worsening of the glaucoma condition in patients with narrow-angle glaucoma [see Warnings and Precautions ( 5.5 )]. Dry Skin Inform patients that solifenacin succinate tablets, like other antimuscarinics, may cause dry skin due to decreased sweating. Heat prostration due to decreased sweating can occur when solifenacin succinate tablets are used in a hot environment [see Adverse Reactions ( 6.2 )]. Marketed by: Ajanta Pharma USA Inc. Bridgewater, NJ 08807. Made in India. All other trademark names are the property of their respective owners. Patient Information Solifenacin Succinate (SOE-li-FEN-a-sin SUX-i-nate) Tablets Read the Patient Information that comes with solifenacin succinate tablets before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or treatment. What are solifenacin succinate tablets? Solifenacin succinate tablets are a prescription medicine for adults used to treat the following symptoms due to a condition called overactive bladder: Urge urinary incontinence: a strong need to urinate with leaking or wetting accidents Urgency: a strong need to urinate right away Frequency: urinating often Solifenacin succinate 5 mg and 10 mg tablets are not approved for use in children Who should not take solifenacin succinate tablets? Do not take solifenacin succinate tablets if you: are not able to empty your bladder (urinary retention) have delayed or slow emptying of your stomach (gastric retention) have an eye problem called “uncontrolled narrow-angle glaucoma” are allergic to solifenacin succinate or any of the ingredients in solifenacin succinate tablets. See the end of this leaflet for a complete list of ingredients. What should I tell my doctor before taking solifenacin succinate tablets? Before you take solifenacin succinate tablets, tell your doctor if you: have any stomach or intestinal problems or problems with constipation have trouble emptying your bladder or you have a weak urine stream have an eye problem called narrow-angle glaucoma have liver problems have kidney problems have a rare heart problem called “QT prolongation” are pregnant or plan to become pregnant. It is not known if solifenacin succinate tablets will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant. are breastfeeding or plan to breastfeed. It is not known if solifenacin passes into your breast milk. You and your doctor should decide if you will take solifenacin succinate tablets or breastfeed. Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Solifenacin succinate tablets may affect the way other medicines work, and other medicines may affect how solifenacin succinate tablets works. How should I take solifenacin succinate tablets? Take solifenacin succinate tablets exactly as your doctor tells you to take it. You should take 1 solifenacin succinate tablet 1 time a day. You should take solifenacin succinate tablets with water and swallow the tablet whole. You can take solifenacin succinate tablets with or without food. If you miss a dose of solifenacin succinate tablets, begin taking solifenacin succinate tablets again the next day. Do not take 2 doses of solifenacin succinate tablets the same day. If you take too much solifenacin succinate tablets, call your doctor or go to the nearest hospital emergency room right away. What should I avoid while taking solifenacin succinate tablets? Solifenacin succinate tablets can cause blurred vision or drowsiness. Do not drive or operate heavy machinery until you know how solifenacin succinate tablets affects you. What are the possible side effects of solifenacin succinate tablets? Solifenacin succinate tablets may cause serious side effects including: Serious allergic reaction. Stop taking solifenacin succinate tablets and get medical help right away if you have: hives, skin rash or swelling severe itching swelling of your face, mouth or tongue trouble breathing The most common side effects of solifenacin succinate tablets include: dry mouth constipation. Call your doctor if you get severe stomach area (abdominal) pain or become constipated for 3 or more days. urinary tract infection blurred vision Other side effects have been observed with anticholinergic drugs such as solifenacin succinate tablets and may include: dry skin due to decreased sweating. Heat exhaustion or heat stroke can happen due to decreased sweating when solifenacin succinate tablets are used in hot environments. Symptoms may include: decreased sweating dizziness tiredness nausea increase in body temperature These are not all the possible side effects of solifenacin succinate tablets. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. How should I store solifenacin succinate tablets? Solifenacin succinate tablets comes in a child-resistant package. Store solifenacin succinate tablets between 59°F to 86°F (15°C to 30°C). Keep the bottle closed. Safely throw away medicine that is out of date or that you no longer needed. Keep solifenacin succinate tablets and all medicines out of the reach of children. General information about the safe and effective use of solifenacin succinate tablets. Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use solifenacin succinate tablets for a condition for which it was not prescribed. Do not give solifenacin succinate tablets to other people, even if they have the same symptoms you have. It may harm them. This leaflet summarizes the most important information about solifenacin succinate tablets. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about solifenacin succinate tablets that is written for health professionals. What are the ingredients in solifenacin succinate tablets? Active ingredient: solifenacin succinate Inactive ingredients: lactose monohydrate, corn starch, hypromellose, magnesium stearate, talc, polyethylene glycol and titanium dioxide with yellow ferric oxide (5 mg solifenacin succinate tablets) or red ferric oxide (10 mg solifenacin succinate tablets). What is overactive bladder? Overactive bladder occurs when you cannot control your bladder contractions. When these muscle contractions happen too often or cannot be controlled you can get symptoms of overactive bladder, which are urinary frequency, urinary urgency, and urinary incontinence (leakage). Marketed by: Ajanta Pharma USA Inc. Bridgewater, NJ 08807. Made in India. All other trademark names are the property of their respective owners. This Patient Information has been approved by the U.S. Food and Drug Administration Revised: 12/2020"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary There are no studies with the use of solifenacin succinate in pregnant women to inform a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes. No adverse developmental outcomes were observed in animal reproduction studies with oral administration of solifenacin succinate to pregnant mice during the period of organogenesis at a dose resulting in 1.2 times the systemic exposure at the maximum recommended human dose (MRHD) of 10 mg/day. However, administration of doses 3.6 times and greater than the MRHD during organogenesis produced maternal toxicity in the pregnant mice and resulted in developmental toxicity and reduced fetal body weights in offspring [see Data]. In the U.S. general population, the estimated background risk of major birth defects or miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Oral administration of 14 C-solifenacin succinate to pregnant mice resulted in the recovery of radiolabel in the fetus indicating that solifenacin-related product can cross the placental barrier. In pregnant mice, administration of solifenacin succinate at a dose of 250 mg/kg/day (7.9 times the systemic exposure at the MRHD of 10 mg), resulted in an increased incidence of cleft palate and increased maternal lethality. Administration of solifenacin succinate to pregnant mice during organogenesis at greater than or equal to 3.6 times (100 mg/kg/day and greater) the systemic exposure at the MRHD, resulted in reduced fetal body weights and reduced maternal body weight gain. No embryo-fetal toxicity or teratogenicity was observed in fetuses from pregnant mice treated with solifenacin succinate at a dose of 30 mg/kg/day (1.2 times the systemic exposure at the MRHD). Administration of solifenacin succinate to pregnant rats and rabbits at a dose of 50 mg/kg/day (< 1 times and 1.8 times the systemic exposure at the MRHD, respectively), resulted in no findings of embryo-fetal toxicity. Oral pre- and post-natal administration of solifenacin succinate at 100 mg/kg/day (3.6 times the systemic exposure at the MRHD) during the period of organogenesis through weaning, resulted in reduced peripartum and postnatal survival, reduced body weight gain by the pups, and delayed physical development (eye opening and vaginal patency). An increase in the percentage of male offspring was also observed in litters from offspring (F2 generation) exposed to maternal doses of 250 mg/kg/day. There were no effects on natural delivery in mice treated with 1.2 times (30 mg/kg/day) the expected systemic exposure at the MRHD."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness of solifenacin succinate Tablets have not been established in pediatric patients."}', 'geriatric_use': '{"8.5 Geriatric Use In placebo-controlled clinical studies, similar safety and effectiveness were observed between geriatric patients (623 patients ≥ 65 years and 189 patients ≥ 75 years) and younger adult patients (1,188 patients < 65 years) treated with solifenacin succinate tablets [see Clinical Pharmacology ( 12.3 )] ."}'}

{ACETAMINOPHEN,"DIPHENHYDRAMINE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses temporary relief of occasional headaches and minor aches and pains with accompanying sleeplessness"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"ACETAMINOPHEN AND DIPHENHYDRAMINE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if sleeplessness persists continuously for more than 2 weeks. Insomnia may be a symptom of serious underlying medical illness. pain gets worse or lasts more than 10 days fever gets worse or lasts more than 3 days redness or swelling is present new symptoms occur 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. with any product containing diphenhydramine, even one used on skin in children under 12 years of age if you have ever had an allergic reaction to this product or any of its ingredients"}', 'when_using': '{"When using this product drowsiness will occur avoid alcoholic drinks do not drive a motor vehicle or operate machinery"}', 'warnings': '{"Warnings 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 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. with any product containing diphenhydramine, even one used on skin in children under 12 years of age 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 a breathing problem such as emphysema or chronic bronchitis trouble urinating due to an enlarged prostate gland glaucoma Ask a doctor or pharmacist before use if you are taking the blood thinning drug warfarin taking sedatives or tranquilizers When using this product drowsiness will occur avoid alcoholic drinks do not drive a motor vehicle or operate machinery Stop use and ask a doctor if sleeplessness persists continuously for more than 2 weeks. Insomnia may be a symptom of serious underlying medical illness. pain gets worse or lasts more than 10 days fever gets worse or lasts more than 3 days redness or swelling is present new symptoms occur 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 the recommended dose (overdose) may cause liver damage. 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}

{"COAL TAR"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses: Controls scalp itching and flaking due to dandruff"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"COAL TAR"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and consult a doctor if condition worsens or does not improve after regular use."}', 'do_not_use': None, 'when_using': '{"When using this product Do not get into eyse. If contact occurs, rinse eyes thoroughly with water Use caution in exposing the skin to sunlight after using this product. It may increase your tendency to sunburn for up to 24 hours after application."}', 'warnings': '{"Warnings: For external use only Ask A doctor before use if the condition covers a large area of your body with other forms of psoriasis therapy such as prescription drugs or UV radition When using this product Do not get into eyse. If contact occurs, rinse eyes thoroughly with water Use caution in exposing the skin to sunlight after using this product. It may increase your tendency to sunburn for up to 24 hours after application. Stop use and consult a doctor if condition worsens or does not improve after regular use. Keep out of reach of children. If swallowed, get medical help or call a Poison Control Center right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"PYRITHIONE ZINC"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use: controls scalp itching and flaking due to • dandruff • seborrheic dermatitis"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"PYRITHIONE ZINC"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and consult a doctor if condition worsens or does not improve after regular use of this product as directed."}', 'do_not_use': None, 'when_using': '{"When using this product • avoid contact with eyes. If contact occurs, rinse eyes thoroughly with water."}', 'warnings': '{"Warnings: For external use only Ask a doctor before use if you have • serborrheic dermatitis that covers a large area of the body. When using this product • avoid contact with eyes. If contact occurs, rinse eyes thoroughly with water. Stop use and consult a doctor if condition worsens or does not improve after regular use of this product as directed. Keep out of reach of children. If swallowed, get medical help or call a Poison Control Center right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{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"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{GUAIFENESIN}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if cough lasts for more than 1 week, tends to recur, or is accompanied by fever, rash or persistent headache. A persistent cough may be a sign of a serious condition."}', 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings Ask a doctor before use if you have cough that occurs with too much phlegm (mucus) persistent or chronic cough such as occurs with smoking, asthma, chronic bronchitis, or emphysema Stop use and ask a doctor if cough lasts for more than 1 week, tends to recur, 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."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"CALCIUM CARBONATE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses: Relieves Heartburn Sour Stomach Acid indigestion Upset stomach due to these symptoms"}', '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': None, 'warnings': '{"Warnings Do not use if you have ever had an allergic reaction to this product or any of its ingredients"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"SODIUM FLUORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use helps protect against cavities"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"SODIUM FLUORIDE"}', 'route': '{DENTAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings Keep out of reach of children under 6 yrs. of age. If more than used for brushing 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}

{MENTHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses temporarily relieves: cough as may occur with a cold occasional minor irritation and sore throat"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{MENTHOL}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use ask doctor if cough persists for more than 7 days, tends to recur, or is accompanied by fever, rash, or persistent headache. These could be signs of a serius condition. sore throat is severe, or irritation, pain o redness lasts or worsens sore mouth does not improve in 7 days"}', 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings if sore throat is severe, persists for more than 2 days, is accompained or follwed by fever, headache, rash, swelling, nausea, or vomiting, consult a doctor promptly. If sore mouth symptoms do not improve in 7 days, see your dentist or doctor promtly. These symptoms may be serious. Sore throat warning: Ask a doctor before use if you have: persistent or chronic cough such as occurs with smoking, asthma, or emphysema cough accompained by excessive phlegm (mucus) Stop use ask doctor if cough persists for more than 7 days, tends to recur, or is accompanied by fever, rash, or persistent headache. These could be signs of a serius condition. sore throat is severe, or irritation, pain o redness lasts or worsens sore mouth does not improve in 7 days If pregnant or 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}

{"TERBINAFINE HYDROCHLORIDE"}

{'contraindications': '{"4. CONTRAINDICATIONS Terbinafine tablets are contraindicated in patients with: Chronic or active liver disease [see Warnings and Precautions (5.1) ] History of allergic reaction to oral terbinafine because of the risk of anaphylaxis [see Adverse Reactions (6.2) ] Chronic or active liver disease. ( 4 ) History of allergic reaction to oral terbinafine because of the risk of anaphylaxis. ( 4 )"}', 'adverse_reactions': '{"6. ADVERSE REACTIONS Common (greater than 2% of patients treated with Terbinafine tablets) reported adverse events include headache, diarrhea, rash, dyspepsia, liver enzyme abnormalities, pruritus, taste disturbance, nausea, abdominal pain, and flatulence. ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Breckenridge Pharmaceutical, Inc. at 1-800-367-3395, 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 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 frequently reported adverse events observed in the 3 US/Canadian placebo-controlled trials are listed in the Table 1. The adverse events reported encompass gastrointestinal symptoms (including diarrhea, dyspepsia, and abdominal pain), liver test abnormalities, rashes, urticaria, pruritus, and taste disturbances. Changes in the ocular lens and retina have been reported following the use of Terbinafine tablets in controlled trials. The clinical significance of these changes is unknown. In general, the adverse events were mild, transient, and did not lead to discontinuation from study participation. Table 1. Most frequently reported adverse events observed in the 3 US/Canadian placebo-controlled trials Adverse Event Discontinuation Terbinafine tablets (%) n=465 Placebo (%) n=137 Terbinafine tablets (%) n=465 Placebo (%) n=137 Headache 12.9 9.5 0.2 0.0 Gastrointestinal Symptoms: Diarrhea 5.6 2.9 0.6 0.0 Dyspepsia 4.3 2.9 0.4 0.0 Abdominal Pain 2.4 1.5 0.4 0.0 Nausea 2.6 2.9 0.2 0.0 Flatulence 2.2 2.2 0.0 0.0 Dermatological Symptoms: Rash 5.6 2.2 0.9 0.7 Pruritus 2.8 1.5 0.2 0.0 Urticaria 1.1 0.0 0.0 0.0 Liver Enzyme Abnormalities Liver enzyme abnormalities greater than or equal to 2× the upper limit of normal range. 3.3 1.4 0.2 0.0 Taste Disturbance 2.8 0.7 0.2 0.0 Visual Disturbance 1.1 1.5 0.9 0.0 6.2 Postmarketing Experience The following adverse events have been identified during post-approval use of Terbinafine tablets. Because these events 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, agranulocytosis, severe neutropenia, thrombocytopenia, anemia, thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome [see Warnings and Precautions (5.5 , 5.8) ] Immune system disorders: Serious hypersensitivity reactions e.g., angioedema and allergic reactions (including anaphylaxis), precipitation and exacerbation of cutaneous and systemic lupus erythematosus [see Warnings and Precautions (5.7) ] , serum sickness-like reaction Psychiatric disorders: Anxiety and depressive symptoms independent of taste disturbance have been reported with use of Terbinafine tablets. In some cases, depressive symptoms have been reported to subside with discontinuance of therapy and to recur with reinstitution of therapy [see Warnings and Precautions (5.4) ] . Nervous system disorders: Cases of taste disturbance, including taste loss, have been reported with the use of Terbinafine tablets. It can be severe enough to result in decreased food intake, weight loss, anxiety, and depressive symptoms. Cases of smell disturbance, including smell loss, have been reported with the use of Terbinafine tablets [see Warnings and Precautions (5.2 , 5.3) ] . Cases of paresthesia and hypoesthesia have been reported with the use of Terbinafine tablets. Eye disorders: Visual field defects, reduced visual acuity Ear and labyrinth disorders: Hearing impairment, vertigo, tinnitus Vascular disorders: Vasculitis Gastrointestinal disorders: Pancreatitis, vomiting Hepatobiliary disorders: Cases of liver failure some leading to liver transplant or death [see Warnings and Precautions (5.1) ] , idiosyncratic and symptomatic hepatic injury. Cases of hepatitis, cholestasis, and increased hepatic enzymes [see Warnings and Precautions (5.1) ] have been seen with the use of Terbinafine tablets. Skin and subcutaneous tissue disorders: Serious skin reactions [e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, bullous dermatitis, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome] [see Warnings and Precautions (5.6) ] , acute generalized exanthematous pustulosis, psoriasiform eruptions or exacerbation of psoriasis, photosensitivity reactions, hair loss Musculoskeletal and connective tissue disorders: Rhabdomyolysis, arthralgia, myalgia General disorders and administration site conditions: Malaise, fatigue, influenza-like illness, pyrexia Investigations: Altered prothrombin time (prolongation and reduction) in patients concomitantly treated with warfarin and increased blood creatine phosphokinase have been reported."}', 'drug_interactions': '{"7. DRUG INTERACTIONS Terbinafine is an inhibitor of CYP450 2D6 isozyme and has an effect on metabolism of desipramine. Drug interactions have also been noted with cimetidine, fluconazole, cyclosporine, rifampin, and caffeine. ( 7.1 ) 7.1 Drug-Drug Interactions In vivo studies have shown that terbinafine is an inhibitor of the CYP450 2D6 isozyme. Drugs predominantly metabolized by the CYP450 2D6 isozyme include the following drug classes: tricyclic antidepressants, selective serotonin reuptake inhibitors, beta-blockers, antiarrhythmics class 1C (e.g., flecainide and propafenone) and monoamine oxidase inhibitors Type B. Coadministration of Terbinafine tablets should be done with careful monitoring and may require a reduction in dose of the 2D6-metabolized drug. In a study to assess the effects of terbinafine on desipramine in healthy volunteers characterized as normal metabolizers, the administration of terbinafine resulted in a 2-fold increase in C max and a 5-fold increase in area under the curve (AUC). In this study, these effects were shown to persist at the last observation at 4 weeks after discontinuation of Terbinafine tablets. In studies in healthy subjects characterized as extensive metabolizers of dextromethorphan (antitussive drug and CYP2D6 probe substrate), terbinafine increases the dextromethorphan/ dextrorphan metabolite ratio in urine by 16- to 97-fold on average. Thus, terbinafine may convert extensive CYP2D6 metabolizers to poor metabolizer status. In vitro studies with human liver microsomes showed that terbinafine does not inhibit the metabolism of tolbutamide, ethinylestradiol, ethoxycoumarin, cyclosporine, cisapride and fluvastatin. In vivo drug-drug interaction studies conducted in healthy volunteer subjects showed that terbinafine does not affect the clearance of antipyrine or digoxin. Terbinafine decreases the clearance of caffeine by 19%. Terbinafine increases the clearance of cyclosporine by 15%. The influence of terbinafine on the pharmacokinetics of fluconazole, cotrimoxazole (trimethoprim and sulfamethoxazole), zidovudine or theophylline was not considered to be clinically significant. Coadministration of a single dose of fluconazole (100 mg) with a single dose of terbinafine resulted in a 52% and 69% increase in terbinafine C max and AUC, respectively. Fluconazole is an inhibitor of CYP2C9 and CYP3A enzymes. Based on this finding, it is likely that other inhibitors of both CYP2C9 and CYP3A4 (e.g., ketoconazole, amiodarone) may also lead to a substantial increase in the systemic exposure (C max and AUC) of terbinafine when concomitantly administered. There have been spontaneous reports of increase or decrease in prothrombin times in patients concomitantly taking oral terbinafine and warfarin, however, a causal relationship between Terbinafine tablets and these changes has not been established. Terbinafine clearance is increased 100% by rifampin, a CYP450 enzyme inducer, and decreased 33% by cimetidine, a CYP450 enzyme inhibitor. Terbinafine clearance is unaffected by cyclosporine. There is no information available from adequate drug-drug interaction studies with the following classes of drugs: oral contraceptives, hormone replacement therapies, hypoglycemics, phenytoins, thiazide diuretics, and calcium channel blockers. 7.2 Food Interactions An evaluation of the effect of food on Terbinafine tablets was conducted. An increase of less than 20% of the AUC of terbinafine was observed when Terbinafine tablets were administered with food. Terbinafine tablets can be taken with or without food."}', 'indications_and_usage': '{"1. INDICATIONS AND USAGE Terbinafine tablets are indicated for the treatment of onychomycosis of the toenail or fingernail due to dermatophytes (tinea unguium). Prior to initiating treatment, appropriate nail specimens for laboratory testing [potassium hydroxide (KOH) preparation, fungal culture, or nail biopsy] should be obtained to confirm the diagnosis of onychomycosis. Terbinafine tablets are an allylamine antifungal indicated for the treatment of onychomycosis of the toenail or fingernail due to dermatophytes (tinea unguium). ( 1 )"}', 'warnings_and_cautions': '{"5. WARNINGS AND PRECAUTIONS Liver failure, sometimes leading to liver transplant or death, has occurred with the use of oral terbinafine. Obtain pretreatment serum transaminases. Prior to initiating treatment and periodically during therapy, assess liver function tests. Discontinue Terbinafine tablets if liver injury develops. ( 5.1 ) Taste disturbance, including taste loss, has been reported with the use of Terbinafine tablets. Taste disturbance can be severe, may be prolonged, or may be permanent. Discontinue Terbinafine tablets if taste disturbance occurs. ( 5.2 ) Smell disturbance, including loss of smell, has been reported with the use of Terbinafine tablets. Smell disturbance may be prolonged, or may be permanent. Discontinue Terbinafine tablets if smell disturbance occurs. ( 5.3 ) Depressive symptoms have been reported with terbinafine use. Prescribers should be alert to the development of depressive symptoms. ( 5.4 ) Severe neutropenia has been reported. If the neutrophil count is less than or equal to 1000 cells/mm 3 , Terbinafine tablets should be discontinued. ( 5.5 ) Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, bullous dermatitis, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome have been reported with oral terbinafine use. If signs or symptoms of drug reaction occur, treatment with Terbinafine tablets should be discontinued. ( 5.6 ) 5.1 Hepatotoxicity Terbinafine tablets are contraindicated for patients with chronic or active liver disease. Before prescribing Terbinafine tablets, perform liver function tests because hepatotoxicity may occur in patients with and without preexisting liver disease. Cases of liver failure, some leading to liver transplant or death, have occurred with the use of Terbinafine tablets in individuals with and without preexisting liver disease. In the majority of liver cases reported in association with use of Terbinafine tablets, the patients had serious underlying systemic conditions. The severity of hepatic events and/or their outcome may be worse in patients with active or chronic liver disease. Periodic monitoring of liver function tests is recommended. Discontinue Terbinafine tablets if biochemical or clinical evidence of liver injury develops. Warn patients prescribed Terbinafine tablets and/or their caregivers to report immediately to their healthcare providers any symptoms or signs of persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain or jaundice, dark urine, or pale stools. Advise patients with these symptoms to discontinue taking oral terbinafine, and immediately evaluate the patient\'s liver function. 5.2 Taste Disturbance Including Loss of Taste Taste disturbance, including taste loss, has been reported with the use of Terbinafine tablets. It can be severe enough to result in decreased food intake, weight loss, anxiety, and depressive symptoms. Taste disturbance may resolve within several weeks after discontinuation of treatment, but may be prolonged (greater than 1 year), or may be permanent. If symptoms of a taste disturbance occur, Terbinafine tablets should be discontinued. 5.3 Smell Disturbance Including Loss of Smell Smell disturbance, including loss of smell, has been reported with the use of Terbinafine tablets. Smell disturbance may resolve after discontinuation of treatment, but may be prolonged (greater than 1 year), or may be permanent. If symptoms of a smell disturbance occur, Terbinafine tablets should be discontinued. 5.4 Depressive Symptoms Depressive symptoms have occurred during postmarketing use of Terbinafine tablets. Prescribers should be alert to the development of depressive symptoms, and patients should be instructed to report depressive symptoms to their physician. 5.5 Hematologic Effects Transient decreases in absolute lymphocyte counts (ALCs) have been observed in controlled clinical trials. In placebo-controlled trials, 8/465 subjects receiving Terbinafine tablets (1.7%) and 3/137 subjects receiving placebo (2.2%) had decreases in ALC to below 1000/mm 3 on 2 or more occasions. In patients with known or suspected immunodeficiency, physicians should consider monitoring complete blood counts if treatment continues for more than 6 weeks. Cases of severe neutropenia have been reported. These were reversible upon discontinuation of Terbinafine tablets, with or without supportive therapy. If clinical signs and symptoms suggestive of secondary infection occur, a complete blood count should be obtained. If the neutrophil count is less than or equal to 1000 cells/mm 3 , Terbinafine tablets should be discontinued and supportive management started. 5.6 Serious Skin/Hypersensitivity Reactions There have been postmarketing reports of serious skin/hypersensitivity reactions [e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, bullous dermatitis, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome]. Manifestations of DRESS syndrome may include cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, and one or more organ complications such as hepatitis, pneumonitis, nephritis, myocarditis, and pericarditis. If progressive skin rash or signs/symptoms of the above drug reactions occur, treatment with Terbinafine tablets should be discontinued. 5.7 Lupus Erythematosus During postmarketing experience, precipitation and exacerbation of cutaneous and systemic lupus erythematosus have been reported in patients taking Terbinafine tablets. Terbinafine tablets should be discontinued in patients with clinical signs and symptoms suggestive of lupus erythematosus. 5.8 Thrombotic Microangiopathy Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, have been reported with terbinafine. Discontinue terbinafine if clinical symptoms and laboratory findings consistent with TMA occur. The findings of unexplained thrombocytopenia and anemia should prompt further evaluation and consideration of diagnosis of TMA."}', 'overdosage': '{"10 OVERDOSAGE Clinical experience regarding overdose with oral terbinafine is limited. Doses up to 5 grams (20 times the therapeutic daily dose) have been taken without inducing serious adverse reactions. The symptoms of overdose included nausea, vomiting, abdominal pain, dizziness, rash, frequent urination, and headache."}', 'active_flag': 'Y', 'generic_name': '{"TERBINAFINE 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 Medication Guide. Patients taking Terbinafine tablets should receive the following information and instructions: Advise patients to immediately report to their physician or get emergency help if they experience any of the following symptoms: hives, mouth sores, blistering and peeling of skin, swelling of face, lips, tongue, or throat, difficulty swallowing or breathing. Terbinafine tablets treatment should be discontinued. Advise patients to immediately report to their physician any symptoms of persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools. Terbinafine tablets treatment should be discontinued. Advise patients to report to their physician any signs of taste disturbance, smell disturbance and/or depressive symptoms, fever, skin eruption, lymph node enlargement, erythema, scaling, loss of pigment, and unusual photosensitivity that can result in a rash. Terbinafine tablets treatment should be discontinued. Advise patients to minimize exposure to natural and artificial sunlight (tanning beds or UVA/B treatment) while using Terbinafine tablets. Advise patients that if they forget to take Terbinafine tablets, to take their tablets as soon as they remember, unless it is less than 4 hours before the next dose is due. Advise patients to call their physician if they take too many Terbinafine tablets. Advise patients to call their physician if they become pregnant during treatment with Terbinafine Tablets. Dispense with Medication Guide available at: www.bpirx.com/products/patientinformation"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Available data from postmarketing cases on the use of Terbinafine Tablets in pregnant women are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, terbinafine did not cause malformations or any harm to the fetus when administered to pregnant rabbits and rats during the period of organogenesis at oral doses up to 12 and 23 times the maximum recommended human dose (MRHD) of 250 mg/day, respectively (see data ). All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies. Data Animal Data In embryo-fetal development studies in rats and rabbits, pregnant animals received orally (by gavage) doses of terbinafine up to 300 mg/kg/day, during the period of organogenesis. There were no maternal or embryo-fetal effects in either species up to the maximum dose tested. The 300 mg/kg/day dose level in rats and rabbits corresponds to 23 and 12 times the MRHD [based on body surface area (BSA) comparisons], respectively. In a rat peri- and postnatal development study, terbinafine doses of up to 300 mg/kg/day (12 times the MRHD based on BSA comparisons) given by oral gavage during late pregnancy and lactation (Day 15 of gestation to day 20 post-partum) had no adverse effects on parturition and lactation."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and efficacy of Terbinafine tablets have not been established in pediatric patients with onychomycosis."}', 'geriatric_use': '{"8.5 Geriatric Use Clinical studies of Terbinafine tablets did not include sufficient numbers of subjects aged 65 years 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."}'}

{ALCOHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses For Personal hand hygiene to help prevent the spread of bacteria. Can be used in place of hand washing if soap and water are not available."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"ETHYL ALCOHOL"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor If Irritation or redness develops and lasts."}', 'do_not_use': '{"Do not use on children less than 2 months of age on open skin wounds on broken or damaged skin"}', 'when_using': '{"When using this product Avoid contact with eyes. If contact occurs, rinse eyes thoroughly with water. Do not Inhale."}', 'warnings': '{"Warnings For External use only Flammable Keep away from source of heat or fire. When using this product Avoid contact with eyes. If contact occurs, rinse eyes thoroughly with water. Do not Inhale. Do not use on children less than 2 months of age on open skin wounds on broken or damaged skin Stop use and ask a doctor If Irritation or redness develops and lasts. Keep out of reach of children In case of accidental ingestion, get medical help or contact a Poison Control Centre immediately"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"WHITE PETROLATUM"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Directions Apply liberally, as often as necessary."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{PETROLATUM}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if condition worsens or does not improve after 7 days."}', 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings: For external use only Avoid contact with eyes."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{OXYGEN}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': None, 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{OXYGEN}', 'route': '{"RESPIRATORY (INHALATION)"}', '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}

{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 Indoco Remedies Limited at +1-855-642-2594 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 Patients (4 Years to less than 17 Years of Age) The safety of lacosamide injection was evaluated in a multicenter, open-label study of 77 pediatric patients 4 to less than 17 years of age with epilepsy. Infusions were primarily administered over a 30 to 60 minute time period; infusion times less than 30 minutes were not adequately studied in pediatric patients [see Dosage and Administration (2.7)] . Although no serious or severe adverse reactions were noted at the time of infusion in this small study, the adverse reactions associated with lacosamide injection in pediatric patients are expected to be similar to those noted in adults. Additional 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 4 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 4 years of age and older. 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. Additional 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."}', '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 1000 Patients Drug Patients with Events Per 1000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1000 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. 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 (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 (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 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 by calling 1-866-625-1618. 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 to monitor infants for excess sleepiness and to seek medical care if they notice this sign [see Use in Specific Populations (8.2)] . Manufactured By: Indoco Remedies Limited L-32, 33 & 34, Verna Industrial Area, Verna, Goa - 403722, India. Revised: March 2024"}', '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 1-888-233-2334 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 Partial-Onset Seizures Safety and effectiveness of lacosamide for the treatment of partial-onset seizures have been established in pediatric patients 4 to less than 17 years of age. Use of lacosamide in this age group is supported by evidence from adequate and well-controlled studies of lacosamide in adults with partial-onset seizures, pharmacokinetic data from adult and pediatric patients, and safety data in 328 pediatric patients 4 to less than 17 years of age [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3)] . 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. Additional 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)]."}'}

{GUAIFENESIN}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses helps loosen phlegm (mucus) and thin bronchial secretions to make coughs more productive to rid the bronchial passageway of bothersome mucus"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"GUAIFENESIN 400 MG"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if cough lasts for more than 7 days, recurs, or is accompanied by fever, rash, or persistent headache. These could be signs of a serious condition."}', 'do_not_use': None, 'when_using': '{"When using this product do not exceed recommended dosage do not use for more than 7 days"}', 'warnings': '{"Warnings 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 excessive phlegm (mucus) When using this product do not exceed recommended dosage do not use for more than 7 days Stop use and ask a doctor if cough lasts for more than 7 days, recurs, or is 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."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"DOCETAXEL ANHYDROUS"}

{'contraindications': '{"4 CONTRAINDICATIONS Docetaxel Injection is contraindicated in patients with: • neutrophil counts of <1500 cells/mm 3 [ see Warnings and Precautions (5.3) ]. • a history of severe hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80. Severe reactions, including anaphylaxis, have occurred [ see Warnings and Precautions (5.5) ]. • Hypersensitivity to docetaxel or polysorbate 80 ( 4 ) • Neutrophil counts of <1500 cells/mm 3 ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The most serious adverse reactions from docetaxel are: • Toxic Deaths [ see Boxed Warning , Warnings and Precautions (5.1) ] • Hepatic Impairment [ see Boxed Warning , Warnings and Precautions (5.2) ] • Hematologic Effects [ see Boxed Warning , Warnings and Precautions (5.3) ] • Enterocolitis and Neutropenic Colitis [ see Warnings and Precautions (5.4) ] • Hypersensitivity Reactions [ see Boxed Warning , Warnings and Precautions (5.5) ] • Fluid Retention [ see Boxed Warning , Warnings and Precautions (5.6) ] • Second Primary Malignancies [ see Warnings and Precautions (5.7) ] • Cutaneous Reactions [ see Warnings and Precautions (5.8) ] • Neurologic Reactions [ see Warnings and Precautions (5.9) ] • Eye Disorders [ see Warnings and Precautions (5.10) ] • Asthenia [ see Warnings and Precautions (5.11) ] • Alcohol Content [ see Warnings and Precautions (5.13) ] The most common adverse reactions across all docetaxel indications are infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions, and myalgia. Incidence varies depending on the indication. Adverse reactions are described according to indication. 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. Responding patients may not experience an improvement in performance status on therapy and may experience worsening. The relationship between changes in performance status, response to therapy, and treatment-related side effects has not been established. Most common adverse reactions across all docetaxel indications are infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions, and myalgia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Breast Cancer Monotherapy with Docetaxel for Locally Advanced or Metastatic Breast Cancer after Failure of Prior Chemotherapy Docetaxel 100 mg/m 2 : Adverse drug reactions occurring in at least 5% of patients are compared for three populations who received docetaxel administered at 100 mg/m 2 as a 1-hour infusion every 3 weeks: 2045 patients with various tumor types and normal baseline liver function tests; the subset of 965 patients with locally advanced or metastatic breast cancer, both previously treated and untreated with chemotherapy, who had normal baseline liver function tests; and an additional 61 patients with various tumor types who had abnormal liver function tests at baseline. These reactions were described using COSTART terms and were considered possibly or probably related to docetaxel. At least 95% of these patients did not receive hematopoietic support. The safety profile is generally similar in patients receiving docetaxel for the treatment of breast cancer and in patients with other tumor types (see Table 3). Table 3: Summary of Adverse Reactions in Patients Receiving Docetaxel at 100 mg/m 2 Adverse Reaction All Tumor Types Normal LFTs Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN n=2045 % All Tumor Types Elevated LFTs Elevated Baseline LFTs: AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN n=61 % Breast Cancer Normal LFTs n=965 % Hematologic Neutropenia <2000 cells/mm 3 96 96 99 <500 cells/mm 3 75 88 86 Leukopenia <4000 cells/mm 3 96 98 99 <1000 cells/mm 3 32 47 44 Thrombocytopenia <100,000 cells/mm 3 8 25 9 Anemia <11 g/dL 90 92 94 <8 g/dL 9 31 8 Febrile Neutropenia Febrile Neutropenia: ANC grade 4 with fever >38°C with intravenous antibiotics and/or hospitalization 11 26 12 Septic Death 2 5 1 Non-Septic Death 1 7 1 Infections Any 22 33 22 Severe 6 16 6 Fever in Absence of Infection Any 31 41 35 Severe 2 8 2 Hypersensitivity Reactions Regardless of Premedication Any 21 20 18 Severe 4 10 3 With 3-day Premedication n=92 n=3 n=92 Any 15 33 15 Severe 2 0 2 Fluid Retention Regardless of Premedication Any 47 39 60 Severe 7 8 9 With 3-day Premedication n=92 n=3 n=92 Any 64 67 64 Severe 7 33 7 Neurosensory Any 49 34 58 Severe 4 0 6 Cutaneous Any 48 54 47 Severe 5 10 5 Nail Changes Any 31 23 41 Severe 3 5 4 Gastrointestinal Nausea 39 38 42 Vomiting 22 23 23 Diarrhea 39 33 43 Severe 5 5 6 Stomatitis Any 42 49 52 Severe 6 13 7 Alopecia 76 62 74 Asthenia Any 62 53 66 Severe 13 25 15 Myalgia Any 19 16 21 Severe 2 2 2 Arthralgia 9 7 8 Infusion Site Reactions 4 3 4 Hematologic Reactions Reversible marrow suppression was the major dose-limiting toxicity of docetaxel [ see Warnings and Precautions (5.3) ]. The median time to nadir was 7 days, while the median duration of severe neutropenia (<500 cells/mm 3 ) was 7 days. Among 2045 patients with solid tumors and normal baseline LFTs, severe neutropenia occurred in 75.4% and lasted for more than 7 days in 2.9% of cycles. Febrile neutropenia (<500 cells/mm 3 with fever >38°C with intravenous antibiotics and/or hospitalization) occurred in 11% of patients with solid tumors, in 12.3% of patients with metastatic breast cancer, and in 9.8% of 92 breast cancer patients premedicated with 3-day corticosteroids. Severe infectious episodes occurred in 6.1% of patients with solid tumors, in 6.4% of patients with metastatic breast cancer, and in 5.4% of 92 breast cancer patients premedicated with 3-day corticosteroids. Thrombocytopenia (<100,000 cells/mm 3 ) associated with fatal gastrointestinal hemorrhage has been reported. Hypersensitivity Reactions Severe hypersensitivity reactions have been reported [ see Boxed Warning , Warnings and Precautions (5.5) ]. Minor events, including flushing, rash with or without pruritus, chest tightness, back pain, dyspnea, drug fever, or chills, have been reported and resolved after discontinuing the infusion and instituting appropriate therapy. Fluid Retention Fluid retention can occur with the use of docetaxel [ see Boxed Warning , Dosage and Administration (2.6) , Warnings and Precautions (5.6) ]. Cutaneous Reactions Severe skin toxicity is discussed elsewhere in the label [ see Warnings and Precautions (5.8) ]. Reversible cutaneous reactions characterized by a rash including localized eruptions, mainly on the feet and/or hands, but also on the arms, face, or thorax, usually associated with pruritus, have been observed. Eruptions generally occurred within 1 week after docetaxel infusion, recovered before the next infusion, and were not disabling. Severe nail disorders were characterized by hypo- or hyperpigmentation, and occasionally by onycholysis (in 0.8% of patients with solid tumors) and pain. Neurologic Reactions Neurologic reactions are discussed elsewhere in the label [ see Warnings and Precautions (5.9) ]. Gastrointestinal Reactions Nausea, vomiting, and diarrhea were generally mild to moderate. Severe reactions occurred in 3% to 5% of patients with solid tumors and to a similar extent among metastatic breast cancer patients. The incidence of severe reactions was 1% or less for the 92 breast cancer patients premedicated with 3-day corticosteroids. Severe stomatitis occurred in 5.5% of patients with solid tumors, in 7.4% of patients with metastatic breast cancer, and in 1.1% of the 92 breast cancer patients premedicated with 3-day corticosteroids. Cardiovascular Reactions Hypotension occurred in 2.8% of patients with solid tumors; 1.2% required treatment. Clinically meaningful events such as heart failure, sinus tachycardia, atrial flutter, dysrhythmia, unstable angina, pulmonary edema, and hypertension have occurred. Seven of 86 (8.1%) of metastatic breast cancer patients receiving docetaxel 100 mg/m 2 in a randomized trial and who had serial left ventricular ejection fractions assessed developed deterioration of LVEF by ≥10% associated with a drop below the institutional lower limit of normal. Infusion Site Reactions Infusion site reactions were generally mild and consisted of hyperpigmentation, inflammation, redness or dryness of the skin, phlebitis, extravasation, or swelling of the vein. Hepatic Reactions In patients with normal LFTs at baseline, bilirubin values greater than the ULN occurred in 8.9% of patients. Increases in AST or ALT >1.5 times the ULN, or alkaline phosphatase >2.5 times ULN, were observed in 18.9% and 7.3% of patients, respectively. While on docetaxel, increases in AST and/or ALT >1.5 times ULN concomitant with alkaline phosphatase >2.5 times ULN occurred in 4.3% of patients with normal LFTs at baseline. Whether these changes were related to the drug or underlying disease has not been established. Hematologic and Other Toxicity: Relation to Dose and Baseline Liver Chemistry Abnormalities Hematologic and other toxicity is increased at higher doses and in patients with elevated baseline liver function tests (LFTs). In the following tables, adverse drug reactions are compared for three populations: 730 patients with normal LFTs given docetaxel at 100 mg/m 2 in the randomized and single arm studies of metastatic breast cancer after failure of previous chemotherapy; 18 patients in these studies who had abnormal baseline LFTs (defined as AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN); and 174 patients in Japanese studies given docetaxel at 60 mg/m 2 who had normal LFTs (see Tables 4 and 5). Table 4: Hematologic Adverse Reactions in Breast Cancer Patients Previously Treated with Chemotherapy Treated at Docetaxel 100 mg/m 2 with Normal or Elevated Liver Function Tests or 60 mg/m 2 with Normal Liver Function Tests Docetaxel 100 mg/m 2 Docetaxel60 mg/m 2 Adverse Reaction Normal LFTs Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN n=730 % Elevated LFTs Elevated Baseline LFTs: AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN n=18 % Normal LFTs n=174 % Neutropenia Any <2000 cells/mm 3 98 100 95 Grade 4 <500 cells/mm 3 84 94 75 Thrombocytopenia Any <100,000 cells/mm 3 11 44 14 Grade 4 <20,000 cells/mm 3 1 17 1 Anemia <11 g/dL 95 94 65 Infection Incidence of infection requiring hospitalization and/or intravenous antibiotics was 8.5% (n=62) among the 730 patients with normal LFTs at baseline; 7 patients had concurrent grade 3 neutropenia, and 46 patients had grade 4 neutropenia. Any 23 39 1 Grade 3 and 4 7 33 0 Febrile Neutropenia Febrile Neutropenia: For 100 mg/m 2 , ANC grade 4 and fever >38°C with intravenous antibiotics and/or hospitalization; for 60 mg/m 2 , ANC grade 3/4 and fever >38.1°C By Patient 12 33 0 By Course 2 9 0 Septic Death 2 6 1 Non-Septic Death 1 11 0 Table 5: Non-Hematologic Adverse Reactions in Breast Cancer Patients Previously Treated with Chemotherapy Treated at Docetaxel 100 mg/m 2 with Normal or Elevated Liver Function Tests or 60 mg/m 2 with Normal Liver Function Tests NA = not available Docetaxel 100 mg/m 2 Docetaxel 60 mg/m 2 Adverse Reaction Normal LFTs Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN n=730 % Elevated LFTs Elevated Baseline Liver Function: AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN n=18 % Normal LFTs n=174 % Acute Hypersensitivity Reaction Regardless of Premedication Any 13 6 1 Severe 1 0 0 Fluid Retention Fluid Retention includes (by COSTART): edema (peripheral, localized, generalized, lymphedema, pulmonary edema, and edema otherwise not specified) and effusion (pleural, pericardial, and ascites); no premedication given with the 60 mg/m 2 dose Regardless of Premedication Any 56 61 13 Severe 8 17 0 Neurosensory Any 57 50 20 Severe 6 0 0 Myalgia 23 33 3 Cutaneous Any 45 61 31 Severe 5 17 0 Asthenia Any 65 44 66 Severe 17 22 0 Diarrhea Any 42 28 NA Severe 6 11 Stomatitis Any 53 67 19 Severe 8 39 1 In the three-arm monotherapy trial, TAX313, which compared docetaxel 60 mg/m 2 , 75 mg/m 2 and 100 mg/m 2 in advanced breast cancer, grade 3/4 or severe adverse reactions occurred in 49.0% of patients treated with docetaxel 60 mg/m 2 compared to 55.3% and 65.9% treated with 75 mg/m 2 and 100 mg/m 2 , respectively. Discontinuation due to adverse reactions was reported in 5.3% of patients treated with 60 mg/m 2 versus 6.9% and 16.5% for patients treated at 75 mg/m 2 and 100 mg/m 2 , respectively. Deaths within 30 days of last treatment occurred in 4.0% of patients treated with 60 mg/m 2 compared to 5.3% and 1.6% for patients treated at 75 mg/m 2 and 100 mg/m 2 , respectively. The following adverse reactions were associated with increasing docetaxel doses: fluid retention (26%, 38%, and 46% at 60 mg/m 2 , 75 mg/m 2 , and 100 mg/m 2 , respectively), thrombocytopenia (7%, 11% and 12%, respectively), neutropenia (92%, 94%, and 97%, respectively), febrile neutropenia (5%, 7%, and 14%, respectively), treatment-related grade 3/4 infection (2%, 3%, and 7%, respectively) and anemia (87%, 94%, and 97%, respectively). Combination Therapy with Docetaxel in the Adjuvant Treatment of Breast Cancer The following table presents treatment-emergent adverse reactions observed in 744 patients, who were treated with docetaxel 75 mg/m 2 every 3 weeks in combination with doxorubicin and cyclophosphamide (see Table 6). Table 6: Clinically Important Treatment-Emergent Adverse Reactions Regardless of Causal Relationship in Patients Receiving Docetaxel in Combination with Doxorubicin and Cyclophosphamide (TAX316) Docetaxel 75 mg/m 2 + Doxorubicin 50 mg/m 2 + Cyclophosphamide 500 mg/m 2 (TAC) n=744 % Fluorouracil 500 mg/m 2 + Doxorubicin 50 mg/m 2 + Cyclophosphamide 500 mg/m 2 (FAC) n=736 % Adverse Reaction Any Grade 3/4 Any Grade 3/4 Anemia 92 4 72 2 Neutropenia 71 66 82 49 Fever in absence of infection 47 1 17 0 Infection 39 4 36 2 Thrombocytopenia 39 2 28 1 Febrile neutropenia 25 N/A 3 N/A Neutropenic infection 12 N/A 6 N/A Hypersensitivity reactions 13 1 4 0 Lymphedema 4 0 1 0 Fluid Retention COSTART term and grading system for events related to treatment. 35 1 15 0 Peripheral edema 27 0 7 0 Weight gain 13 0 9 0 Neuropathy sensory 26 0 10 0 Neuro-cortical 5 1 6 1 Neuropathy motor 4 0 2 0 Neuro-cerebellar 2 0 2 0 Syncope 2 1 1 0 Alopecia 98 N/A 97 N/A Skin toxicity 27 1 18 0 Nail disorders 19 0 14 0 Nausea 81 5 88 10 Stomatitis 69 7 53 2 Vomiting 45 4 59 7 Diarrhea 35 4 28 2 Constipation 34 1 32 1 Taste perversion 28 1 15 0 Anorexia 22 2 18 1 Abdominal Pain 11 1 5 0 Amenorrhea 62 N/A 52 N/A Cough 14 0 10 0 Cardiac dysrhythmias 8 0 6 0 Vasodilatation 27 1 21 1 Hypotension 2 0 1 0 Phlebitis 1 0 1 0 Asthenia 81 11 71 6 Myalgia 27 1 10 0 Arthralgia 19 1 9 0 Lacrimation disorder 11 0 7 0 Conjunctivitis 5 0 7 0 Of the 744 patients treated with TAC, 36.3% experienced severe treatment-emergent adverse reactions compared to 26.6% of the 736 patients treated with FAC. Dose reductions due to hematologic toxicity occurred in 1% of cycles in the TAC arm versus 0.1% of cycles in the FAC arm. Six percent of patients treated with TAC discontinued treatment due to adverse reactions, compared to 1.1% treated with FAC; fever in the absence of infection and allergy being the most common reasons for withdrawal among TAC-treated patients. Two patients died in each arm within 30 days of their last study treatment; 1 death per arm was attributed to study drugs. Fever and Infection During the treatment period, fever in the absence of infection was seen in 46.5% of TAC-treated patients and in 17.1% of FAC-treated patients. Grade 3/4 fever in the absence of infection was seen in 1.3% and 0% of TAC- and FAC-treated patients, respectively. Infection was seen in 39.4% of TAC-treated patients compared to 36.3% of FAC-treated patients. Grade 3/4 infection was seen in 3.9% and 2.2% of TAC-treated and FAC-treated patients, respectively. There were no septic deaths in either treatment arm during the treatment period. Gastrointestinal Reactions In addition to gastrointestinal reactions reflected in the table above, 7 patients in the TAC arm were reported to have colitis/enteritis/large intestine perforation versus one patient in the FAC arm. Five of the 7 TAC-treated patients required treatment discontinuation; no deaths due to these events occurred during the treatment period. Cardiovascular Reactions More cardiovascular reactions were reported in the TAC arm versus the FAC arm during the treatment period: arrhythmias, all grades (6.2% vs. 4.9%), and hypotension, all grades (1.9% vs. 0.8%). Twenty-six (26) patients (3.5%) in the TAC arm and 17 patients (2.3%) in the FAC arm developed CHF during the study period. All except one patient in each arm were diagnosed with CHF during the follow-up period. Two (2) patients in TAC arm and 4 patients in FAC arm died due to CHF. The risk of CHF was higher in the TAC arm in the first year, and then was similar in both treatment arms. Adverse Reactions during the Follow-Up Period (Median Follow-Up Time of 8 Years) In study TAX316, the most common adverse reactions that started during the treatment period and persisted into the follow-up period in TAC and FAC patients are described below (median follow-up time of 8 years). Nervous System Disorders: In study TAX316, peripheral sensory neuropathy started during the treatment period and persisted into the follow-up period in 84 patients (11.3%) in TAC arm and 15 patients (2%) in FAC arm. At the end of the follow-up period (median follow-up time of 8 years), peripheral sensory neuropathy was observed to be ongoing in 10 patients (1.3%) in TAC arm, and in 2 patients (0.3%) in FAC arm. Skin and Subcutaneous Tissue Disorders: In study TAX316, alopecia persisting into the follow-up period after the end of chemotherapy was reported in 687 of 744 TAC patients (92.3%) and 645 of 736 FAC patients (87.6%). At the end of the follow-up period (actual median follow-up time of 8 years), alopecia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). Reproductive System and Breast Disorders: In study TAX316, amenorrhea that started during the treatment period and persisted into the follow-up period after the end of chemotherapy was reported in 202 of 744 TAC patients (27.2%) and 125 of 736 FAC patients (17.0%). Amenorrhea was observed to be ongoing at the end of the follow-up period (median follow-up time of 8 years) in 121 of 744 TAC patients (16.3%) and 86 FAC patients (11.7%). General Disorders and Administration Site Conditions: In study TAX316, peripheral edema that started during the treatment period and persisted into the follow-up period after the end of chemotherapy was observed in 119 of 744 TAC patients (16.0%) and 23 of 736 FAC patients (3.1%). At the end of the follow-up period (actual median follow-up time of 8 years), peripheral edema was ongoing in 19 TAC patients (2.6%) and 4 FAC patients (0.5%). In study TAX316, lymphedema that started during the treatment period and persisted into the follow-up period after the end of chemotherapy was reported in 11 of 744 TAC patients (1.5%) and 1 of 736 FAC patients (0.1%). At the end of the follow-up period (actual median follow-up time of 8 years), lymphedema was observed to be ongoing in 6 TAC patients (0.8%) and 1 FAC patient (0.1%). In study TAX316, asthenia that started during the treatment period and persisted into the follow-up period after the end of chemotherapy was reported in 236 of 744 TAC patients (31.7%) and 180 of 736 FAC patients (24.5%). At the end of the follow-up period (actual median follow-up time of 8 years), asthenia was observed to be ongoing in 29 TAC patients (3.9%) and 16 FAC patients (2.2%). Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS): AML occurred in the adjuvant breast cancer trial (TAX316). The cumulative risk of developing treatment-related AML at median follow-up time of 8 years in TAX316 was 0.4% for TAC-treated patients and 0.1% for FAC-treated patients. One TAC patient (0.1%) and 1 FAC patient (0.1%) died due to AML during the follow-up period (median follow-up time of 8 years). Myelodysplastic syndrome occurred in 2 of 744 (0.3%) patients who received TAC and in 1 of 736 (0.1%) patients who received FAC. AML occurs at a higher frequency when these agents are given in combination with radiation therapy. Lung Cancer Monotherapy with Docetaxel for Unresectable, Locally Advanced or Metastatic NSCLC Previously Treated with Platinum-Based Chemotherapy Docetaxel 75 mg/m 2 : Treatment-emergent adverse drug reactions are shown in Table 7. Included in this table are safety data for a total of 176 patients with non-small cell lung carcinoma and a history of prior treatment with platinum-based chemotherapy who were treated in two randomized, controlled trials. These reactions were described using NCI Common Toxicity Criteria regardless of relationship to study treatment, except for the hematologic toxicities or where otherwise noted. Table 7: Treatment-Emergent Adverse Reactions Regardless of Relationship to Treatment in Patients Receiving Docetaxel as Monotherapy for Non-small Cell Lung Cancer Previously Treated with Platinum-Based Chemotherapy Normal Baseline LFTs: Transaminases ≤1.5 times ULN or alkaline phosphatase ≤2.5 times ULN or isolated elevations of transaminases or alkaline phosphatase up to 5 times ULN Adverse Reaction Docetaxel 75 mg/m 2 n=176 % Best Supportive Care n=49 % Vinorelbine/ Ifosfamide n=119 % Neutropenia Any 84 14 83 Grade 3/4 65 12 57 Leukopenia Any 84 6 89 Grade 3/4 49 0 43 Thrombocytopenia Any 8 0 8 Grade 3/4 3 0 2 Anemia Any 91 55 91 Grade 3/4 9 12 14 Febrile Neutropenia Febrile Neutropenia: ANC grade 4 with fever >38°C with intravenous antibiotics and/or hospitalization 6 NA Not Applicable 1 Infection Any 34 29 30 Grade 3/4 10 6 9 Treatment Related Mortality 3 NA 3 Hypersensitivity Reactions Any 6 0 1 Grade 3/4 3 0 0 Fluid Retention Any 34 ND Not Done 23 Severe 3 3 Neurosensory Any 23 14 29 Grade 3/4 2 6 5 Neuromotor Any 16 8 10 Grade 3/4 5 6 3 Skin Any 20 6 17 Grade 3/4 1 2 1 Gastrointestinal Nausea Any 34 31 31 Grade 3/4 5 4 8 Vomiting Any 22 27 22 Grade 3/4 3 2 6 Diarrhea Any 23 6 12 Grade 3/4 3 0 4 Alopecia 56 35 50 Asthenia Any 53 57 54 Severe COSTART term and grading system 18 39 23 Stomatitis Any 26 6 8 Grade 3/4 2 0 1 Pulmonary Any 41 49 45 Grade 3/4 21 29 19 Nail Disorder Any 11 0 2 Severe 1 0 0 Myalgia Any 6 0 3 Severe 0 0 0 Arthralgia Any 3 2 2 Severe 0 0 1 Taste Perversion Any 6 0 0 Severe 1 0 0 Combination Therapy with Docetaxel in Chemotherapy-Naïve Advanced Unresectable or Metastatic NSCLC Table 8 presents safety data from two arms of an open label, randomized controlled trial (TAX326) that enrolled patients with unresectable stage IIIB or IV non-small cell lung cancer and no history of prior chemotherapy. Adverse reactions were described using the NCI Common Toxicity Criteria except where otherwise noted. Table 8: Adverse Reactions Regardless of Relationship to Treatment in Chemotherapy-Naïve Advanced Non-small Cell Lung Cancer Patients Receiving Docetaxel in Combination with Cisplatin Adverse Reaction Docetaxel 75 mg/m 2 + Cisplatin 75 mg/m 2 n=406 % Vinorelbine 25 mg/m 2 + Cisplatin 100 mg/m 2 n=396 % Neutropenia Any 91 90 Grade 3/4 74 78 Febrile Neutropenia 5 5 Thrombocytopenia Any 15 15 Grade 3/4 3 4 Anemia Any 89 94 Grade 3/4 7 25 Infection Any 35 37 Grade 3/4 8 8 Fever in absence of infection Any 33 29 Grade 3/4 <1 1 Hypersensitivity Reaction Replaces NCI term “Allergy” Any 12 4 Grade 3/4 3 <1 Fluid Retention COSTART term and grading system Any 54 42 All severe or life-threatening events 2 2 Pleural effusion Any 23 22 All severe or life-threatening events 2 2 Peripheral edema Any 34 18 All severe or life-threatening events <1 <1 Weight gain Any 15 9 All severe or life-threatening events <1 <1 Neurosensory Any 47 42 Grade 3/4 4 4 Neuromotor Any 19 17 Grade 3/4 3 6 Skin Any 16 14 Grade 3/4 <1 1 Nausea Any 72 76 Grade 3/4 10 17 Vomiting Any 55 61 Grade 3/4 8 16 Diarrhea Any 47 25 Grade 3/4 7 3 Anorexia Any 42 40 All severe or life-threatening events 5 5 Stomatitis Any 24 21 Grade 3/4 2 1 Alopecia Any 75 42 Grade 3 <1 0 Asthenia Any 74 75 All severe or life-threatening events 12 14 Nail Disorder Any 14 <1 All severe events <1 0 Myalgia Any 18 12 All severe events <1 <1 Deaths within 30 days of last study treatment occurred in 31 patients (7.6%) in the docetaxel+cisplatin arm and 37 patients (9.3%) in the vinorelbine+cisplatin arm. Deaths within 30 days of last study treatment attributed to study drug occurred in 9 patients (2.2%) in the docetaxel+cisplatin arm and 8 patients (2.0%) in the vinorelbine+cisplatin arm. The second comparison in the study, vinorelbine+cisplatin versus docetaxel+carboplatin (which did not demonstrate a superior survival associated with docetaxel, [ see Clinical Studies (14.3) ]) demonstrated a higher incidence of thrombocytopenia, diarrhea, fluid retention, hypersensitivity reactions, skin toxicity, alopecia and nail changes on the docetaxel+carboplatin arm, while a higher incidence of anemia, neurosensory toxicity, nausea, vomiting, anorexia and asthenia was observed on the vinorelbine+cisplatin arm. Prostate Cancer Combination Therapy with Docetaxel in Patients with Prostate Cancer The following data are based on the experience of 332 patients, who were treated with docetaxel 75 mg/m 2 every 3 weeks in combination with prednisone 5 mg orally twice daily (see Table 9). Table 9: Clinically Important Treatment-Emergent Adverse Reactions (Regardless of Relationship) in Patients with Prostate Cancer who Received Docetaxel in Combination with Prednisone (TAX327) Docetaxel 75 mg/m 2 every 3 weeks + prednisone 5 mg twice daily n=332 % Mitoxantrone 12 mg/m 2 every 3 weeks + prednisone 5 mg twice daily n=335 % Adverse Reaction Any Grade 3/4 Any Grade 3/4 Anemia 67 5 58 2 Neutropenia 41 32 48 22 Thrombocytopenia 3 1 8 1 Febrile Neutropenia 3 N/A 2 N/A Infection 32 6 20 4 Epistaxis 6 0 2 0 Allergic Reactions 8 1 1 0 Fluid Retention Related to treatment 24 1 5 0 Weight Gain 8 0 3 0 Peripheral Edema 18 0 2 0 Neuropathy Sensory 30 2 7 0 Neuropathy Motor 7 2 3 1 Rash/Desquamation 6 0 3 1 Alopecia 65 N/A 13 N/A Nail Changes 30 0 8 0 Nausea 41 3 36 2 Diarrhea 32 2 10 1 Stomatitis/Pharyngitis 20 1 8 0 Taste Disturbance 18 0 7 0 Vomiting 17 2 14 2 Anorexia 17 1 14 0 Cough 12 0 8 0 Dyspnea 15 3 9 1 Cardiac left ventricular function 10 0 22 1 Fatigue 53 5 35 5 Myalgia 15 0 13 1 Tearing 10 1 2 0 Arthralgia 8 1 5 1 Gastric Cancer Combination Therapy with Docetaxel Injection in Gastric Adenocarcinoma Data in the following table are based on the experience of 221 patients with advanced gastric adenocarcinoma and no history of prior chemotherapy for advanced disease who were treated with Docetaxel Injection 75 mg/m 2 in combination with cisplatin and fluorouracil (see Table 10). Table 10: Clinically Important Treatment-Emergent Adverse Reactions Regardless of Relationship to Treatment in the Gastric Cancer Study Docetaxel Injection 75 mg/m 2 + cisplatin 75 mg/m 2 + fluorouracil 750 mg/m 2 n=221 Cisplatin 100 mg/m 2 + fluorouracil 1000 mg/m 2 n=224 Adverse Reaction Any % Grade 3/4 % Any % Grade 3/4 % Anemia 97 18 93 26 Neutropenia 96 82 83 57 Fever in the absence of infection 36 2 23 1 Thrombocytopenia 26 8 39 14 Infection 29 16 23 10 Febrile neutropenia 16 N/A 5 N/A Neutropenic infection 16 N/A 10 N/A Allergic reactions 10 2 6 0 Fluid retention Related to treatment 15 0 4 0 Edema 13 0 3 0 Lethargy 63 21 58 18 Neurosensory 38 8 25 3 Neuromotor 9 3 8 3 Dizziness 16 5 8 2 Alopecia 67 5 41 1 Rash/itch 12 1 9 0 Nail changes 8 0 0 0 Skin desquamation 2 0 0 0 Nausea 73 16 76 19 Vomiting 67 15 73 19 Anorexia 51 13 54 12 Stomatitis 59 21 61 27 Diarrhea 78 20 50 8 Constipation 25 2 34 3 Esophagitis/dysphagia/ odynophagia 16 2 14 5 Gastrointestinal pain/cramping 11 2 7 3 Cardiac dysrhythmias 5 2 2 1 Myocardial ischemia 1 0 3 2 Tearing 8 0 2 0 Altered hearing 6 0 13 2 Clinically important treatment-emergent adverse reactions were determined based upon frequency, severity, and clinical impact of the adverse reaction. Head and Neck Cancer Combination Therapy with Docetaxel Injection in Head and Neck Cancer Table 11 summarizes the safety data obtained from patients that received induction chemotherapy with Docetaxel Injection 75 mg/m 2 in combination with cisplatin and fluorouracil followed by radiotherapy (TAX323; 174 patients) or chemoradiotherapy (TAX324; 251 patients). The treatment regimens are described in Section 14.6. Table 11: Clinically Important Treatment-Emergent Adverse Reactions (Regardless of Relationship) in Patients with SCCHN Receiving Induction Chemotherapy with Docetaxel Injection in Combination with Cisplatin and Fluorouracil Followed by Radiotherapy (TAX323) or Chemoradiotherapy (TAX324) TAX323 (n=355) TAX324 (n=494) Docetaxel Injection arm (n=174) Comparator arm (n=181) Docetaxel Injection arm (n=251) Comparator arm (n=243) Adverse Reaction (by Body System) Any % Grade 3/4 % Any % Grade 3/4 % Any % Grade 3/4 % Any % Grade 3/4 % Neutropenia 93 76 87 53 95 84 84 56 Anemia 89 9 88 14 90 12 86 10 Thrombocytopenia 24 5 47 18 28 4 31 11 Infection 27 9 26 8 23 6 28 5 Febrile neutropenia Febrile neutropenia: grade ≥2 fever concomitant with grade 4 neutropenia requiring intravenous antibiotics and/or hospitalization 5 N/A 2 N/A 12 N/A 7 N/A Neutropenic infection 14 N/A 8 N/A 12 N/A 8 N/A Cancer pain 21 5 16 3 17 9 20 11 Lethargy 41 3 38 3 61 5 56 10 Fever in the absence of infection 32 1 37 0 30 4 28 3 Myalgia 10 1 7 0 7 0 7 2 Weight loss 21 1 27 1 14 2 14 2 Allergy 6 0 3 0 2 0 0 0 Fluid retention Related to treatment 20 0 14 1 13 1 7 2 Edema only 13 0 7 0 12 1 6 1 Weight gain only 6 0 6 0 0 0 1 0 Dizziness 2 0 5 1 16 4 15 2 Neurosensory 18 1 11 1 14 1 14 0 Altered hearing 6 0 10 3 13 1 19 3 Neuromotor 2 1 4 1 9 0 10 2 Alopecia 81 11 43 0 68 4 44 1 Rash/itch 12 0 6 0 20 0 16 1 Dry skin 6 0 2 0 5 0 3 0 Desquamation 4 1 6 0 2 0 5 0 Nausea 47 1 51 7 77 14 80 14 Stomatitis 43 4 47 11 66 21 68 27 Vomiting 26 1 39 5 56 8 63 10 Diarrhea 33 3 24 4 48 7 40 3 Constipation 17 1 16 1 27 1 38 1 Anorexia 16 1 25 3 40 12 34 12 Esophagitis/ dysphagia/ Odynophagia 13 1 18 3 25 13 26 10 Taste, sense of smell altered 10 0 5 0 20 0 17 1 Gastrointestinal pain/cramping 8 1 9 1 15 5 10 2 Heartburn 6 0 6 0 13 2 13 1 Gastrointestinal bleeding 4 2 0 0 5 1 2 1 Cardiac dysrhythmia 2 2 2 1 6 3 5 3 Venous Includes superficial and deep vein thrombosis and pulmonary embolism 3 2 6 2 4 2 5 4 Ischemia myocardial 2 2 1 0 2 1 1 1 Tearing 2 0 1 0 2 0 2 0 Conjunctivitis 1 0 1 0 1 0 0.4 0 Clinically important treatment-emergent adverse reactions based upon frequency, severity, and clinical impact. 6.2 Postmarketing Experience The following adverse reactions have been identified from clinical trials and/or postmarketing surveillance. Because these reactions are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Body as a whole: diffuse pain, chest pain, radiation recall phenomenon, injection site recall reaction (recurrence of skin reaction at a site of previous extravasation following administration of docetaxel at a different site) at the site of previous extravasation. Cardiovascular: atrial fibrillation, deep vein thrombosis, ECG abnormalities, thrombophlebitis, pulmonary embolism, syncope, tachycardia, myocardial infarction. Ventricular arrhythmia, including ventricular tachycardia, in patients treated with docetaxel in combination regimens including doxorubicin, 5-fluorouracil and/or cyclophosphamide may be associated with fatal outcome. Cutaneous: cutaneous lupus erythematosus, bullous eruptions such as erythema multiforme and severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis, scleroderma-like changes (usually preceded by peripheral lymphedema), severe palmar-plantar erythrodysesthesia, and permanent alopecia. Gastrointestinal: enterocolitis, including colitis, ischemic colitis, and neutropenic enterocolitis, which may be fatal. Abdominal pain, anorexia, constipation, duodenal ulcer, esophagitis, gastrointestinal hemorrhage, gastrointestinal perforation, intestinal obstruction, ileus, and dehydration as a consequence of gastrointestinal events. Hearing: ototoxicity, hearing disorders and/or hearing loss, including during use with other ototoxic drugs. Hematologic: bleeding episodes, disseminated intravascular coagulation (DIC), often in association with sepsis or multiorgan failure. Hepatic: hepatitis, sometimes fatal, primarily in patients with pre-existing liver disorders. Hypersensitivity: anaphylactic shock with fatal outcome in patients who received premedication. Severe hypersensitivity reactions with fatal outcome with docetaxel in patients who previously experienced hypersensitivity reactions to paclitaxel. Metabolism and nutrition disorders: electrolyte imbalance, including hyponatremia, hypokalemia, hypomagnesemia, and hypocalcemia. Tumor lysis syndrome, sometimes fatal. Neurologic: confusion, seizures or transient loss of consciousness, sometimes appearing during the infusion of the drug. Ophthalmologic: conjunctivitis, lacrimation or lacrimation with or without conjunctivitis, cystoid macular edema (CME). Excessive tearing which may be attributable to lacrimal duct obstruction. Transient visual disturbances (flashes, flashing lights, scotomata), typically occurring during drug infusion and reversible upon discontinuation of the infusion, in association with hypersensitivity reactions. Respiratory: dyspnea, acute pulmonary edema, acute respiratory distress syndrome/pneumonitis, interstitial lung disease, interstitial pneumonia, respiratory failure, and pulmonary fibrosis, which may be fatal. Radiation pneumonitis in patients receiving concomitant radiotherapy. Renal: renal insufficiency and renal failure, the majority of cases were associated with concomitant nephrotoxic drugs. Second primary malignancies: second primary malignancies, including AML, MDS, NHL, and renal cancer [ see Warnings and Precautions (5.7) ]. Musculoskeletal Disorder: myositis."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Docetaxel is a CYP3A4 substrate. In vitro studies have shown that the metabolism of docetaxel may be modified by the concomitant administration of compounds that induce, inhibit, or are metabolized by cytochrome P450 3A4. In vivo studies showed that the exposure of docetaxel increased 2.2-fold when it was coadministered with ketoconazole, a potent inhibitor of CYP3A4. Protease inhibitors, particularly ritonavir, may increase the exposure of docetaxel. Concomitant use of Docetaxel Injection and drugs that inhibit CYP3A4 may increase exposure to docetaxel and should be avoided. In patients receiving treatment with Docetaxel Injection close monitoring for toxicity and a Docetaxel Injection dose reduction could be considered if systemic administration of a potent CYP3A4 inhibitor cannot be avoided [ see Dosage and Administration (2.7) , Clinical Pharmacology (12.3) ]. • Cytochrome P450 3A4 inducers, inhibitors, or substrates: May alter docetaxel metabolism. ( 7 )"}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Docetaxel Injection is a microtubule inhibitor indicated for: • Breast Cancer (BC): single agent for locally advanced or metastatic BC after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC ( 1.1 ) • Non-small Cell Lung Cancer (NSCLC): single agent for locally advanced or metastatic NSCLC after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC ( 1.2 ) • Castration-Resistant Prostate Cancer (CRPC): with prednisone in metastatic castration-resistant prostate cancer ( 1.3 ) • Gastric Adenocarcinoma (GC): with cisplatin and fluorouracil for untreated, advanced GC, including the gastroesophageal junction ( 1.4 ) • Squamous Cell Carcinoma of the Head and Neck (SCCHN): with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN ( 1.5 ) 1.1 Breast Cancer Docetaxel Injection is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Docetaxel Injection in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer. 1.2 Non-small Cell Lung Cancer Docetaxel Injection as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. Docetaxel Injection in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy for this condition. 1.3 Prostate Cancer Docetaxel Injection in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer. 1.4 Gastric Adenocarcinoma Docetaxel Injection in combination with cisplatin and fluorouracil is indicated for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease. 1.5 Head and Neck Cancer Docetaxel Injection in combination with cisplatin and fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Second primary malignancies: In patients treated with Docetaxel Injection-containing regimens, monitor for delayed AML, MDS, NHL, and renal cancer. ( 5.7 ) • Cutaneous reactions: Reactions including erythema of the extremities with edema followed by desquamation may occur. Severe cutaneous adverse reactions have been reported. Severe skin toxicity may require dose adjustment or permanent treatment discontinuation. ( 5.8 ) • Neurologic reactions: Reactions including paresthesia, dysesthesia, and pain may occur. Severe neurosensory symptoms require dose adjustment or discontinuation if persistent. ( 5.9 ) • Eye disorders: Cystoid macular edema (CME) has been reported and requires treatment discontinuation. ( 5.10 ) • Asthenia: Severe asthenia may occur and may require treatment discontinuation. ( 5.11 ) • Embryo-fetal toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.12 , 8.1 , 8.3 ) • Alcohol content: The alcohol content in a dose of Docetaxel Injection may affect the central nervous system. This may include impairment of a patient’s ability to drive or use machines immediately after infusion. ( 5.13 ) • Tumor lysis syndrome: Tumor lysis syndrome has been reported. Patients at risk should be well hydrated and closely monitored during treatment. ( 5.14 ) 5.1 Toxic Deaths Breast Cancer Docetaxel administered at 100 mg/m 2 was associated with deaths considered possibly or probably related to treatment in 2.0% (19/965) of metastatic breast cancer patients, both previously treated and untreated, with normal baseline liver function and in 11.5% (7/61) of patients with various tumor types who had abnormal baseline liver function (AST and/or ALT >1.5 times ULN together with AP >2.5 times ULN). Among patients dosed at 60 mg/m 2 , mortality related to treatment occurred in 0.6% (3/481) of patients with normal liver function, and in 3 of 7 patients with abnormal liver function. Approximately half of these deaths occurred during the first cycle. Sepsis accounted for the majority of the deaths. Non-small Cell Lung Cancer Docetaxel administered at a dose of 100 mg/m 2 in patients with locally advanced or metastatic non-small cell lung cancer who had a history of prior platinum-based chemotherapy was associated with increased treatment-related mortality (14% and 5% in two randomized, controlled studies). There were 2.8% treatment-related deaths among the 176 patients treated at the 75 mg/m 2 dose in the randomized trials. Among patients who experienced treatment-related mortality at the 75 mg/m 2 dose level, 3 of 5 patients had an ECOG PS of 2 at study entry [ see Dosage and Administration (2.2) , Clinical Studies (14) ]. 5.2 Hepatic Impairment Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of severe neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Avoid Docetaxel Injection in patients with bilirubin > upper limit of normal (ULN), or to patients with AST and/or ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN [ see Warnings and Precautions (5.1) ]. For patients with isolated elevations of transaminase >1.5 × ULN, consider Docetaxel Injection dose modifications [ see Dosage and Administration (2.7) ]. Measure bilirubin, AST or ALT, and alkaline phosphatase prior to each cycle of Docetaxel Injection therapy. 5.3 Hematologic Effects Perform frequent peripheral blood cell counts on all patients receiving Docetaxel Injection. Do not retreat patients with subsequent cycles of Docetaxel Injection until neutrophils recover to a level >1500 cells/mm 3 [ see Contraindications (4) ]. Avoid retreating patients until platelets recover to a level >100,000 cells/mm 3 . A 25% reduction in the dose of Docetaxel Injection is recommended during subsequent cycles following severe neutropenia (<500 cells/mm 3 ) lasting 7 days or more, febrile neutropenia, or a grade 4 infection in a Docetaxel Injection cycle [ see Dosage and Administration (2.7) ]. Neutropenia (<2000 neutrophils/mm 3 ) occurs in virtually all patients given 60 mg/m 2 to 100 mg/m 2 of docetaxel and grade 4 neutropenia (<500 cells/mm 3 ) occurs in 85% of patients given 100 mg/m 2 and 75% of patients given 60 mg/m 2 . Frequent monitoring of blood counts is, therefore, essential so that dose can be adjusted. Docetaxel Injection should not be administered to patients with neutrophils <1500 cells/mm 3 . Febrile neutropenia occurred in about 12% of patients given 100 mg/m 2 but was very uncommon in patients given 60 mg/m 2 . Hematologic responses, febrile reactions and infections, and rates of septic death for different regimens are dose related [ see Adverse Reactions (6.1) , Clinical Studies (14) ]. Three breast cancer patients with severe liver impairment (bilirubin >1.7 times ULN) developed fatal gastrointestinal bleeding associated with severe drug-induced thrombocytopenia. In gastric cancer patients treated with docetaxel in combination with cisplatin and fluorouracil (TCF), febrile neutropenia and/or neutropenic infection occurred in 12% of patients receiving G-CSF compared to 28% who did not. Patients receiving TCF should be closely monitored during the first and subsequent cycles for febrile neutropenia and neutropenic infection [ see Dosage and Administration (2.7) , Adverse Reactions (6) ]. 5.4 Enterocolitis and Neutropenic Colitis Enterocolitis and neutropenic colitis (typhlitis) have occurred in patients treated with Docetaxel Injection alone and in combination with other chemotherapeutic agents, despite the coadministration of G-CSF. Caution is recommended for patients with neutropenia, particularly at risk for developing gastrointestinal complications. Enterocolitis and neutropenic enterocolitis may develop at any time, and could lead to death as early as the first day of symptom onset. Monitor patients closely from onset of any symptoms of gastrointestinal toxicity. Inform patients to contact their healthcare provider with new, or worsening symptoms of gastrointestinal toxicity [ see Dosage and Administration (2) , Warnings and Precautions (5.3) , Adverse Reactions (6.2) ]. 5.5 Hypersensitivity Reactions Monitor patients closely for hypersensitivity reactions, especially during the first and second infusions. Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or fatal anaphylaxis, have been reported in patients premedicated with 3 days of corticosteroids. Severe hypersensitivity reactions require immediate discontinuation of the Docetaxel Injection infusion and aggressive therapy. Do not rechallenge patients with a history of severe hypersensitivity reactions with Docetaxel Injection [ see Contraindications (4) ]. Patients who have previously experienced a hypersensitivity reaction to paclitaxel may develop a hypersensitivity reaction to docetaxel that may include severe or fatal reactions such as anaphylaxis. Monitor patients with a previous history of hypersensitivity to paclitaxel closely during initiation of docetaxel therapy. Hypersensitivity reactions may occur within a few minutes following initiation of a Docetaxel Injection infusion. If minor reactions such as flushing or localized skin reactions occur, interruption of therapy is not required. All patients should be premedicated with an oral corticosteroid prior to the initiation of the infusion of Docetaxel Injection [ see Dosage and Administration (2.6) ]. 5.6 Fluid Retention Severe fluid retention has been reported following docetaxel therapy. Patients should be premedicated with oral corticosteroids prior to each Docetaxel Injection administration to reduce the incidence and severity of fluid retention [ see Dosage and Administration (2.6) ]. Patients with pre-existing effusions should be closely monitored from the first dose for the possible exacerbation of the effusions. When fluid retention occurs, peripheral edema usually starts in the lower extremities and may become generalized with a median weight gain of 2 kg. Among 92 breast cancer patients premedicated with 3-day corticosteroids, moderate fluid retention occurred in 27.2% and severe fluid retention in 6.5%. The median cumulative dose to onset of moderate or severe fluid retention was 819 mg/m 2 . Nine of 92 patients (9.8%) of patients discontinued treatment due to fluid retention: 4 patients discontinued with severe fluid retention; the remaining 5 had mild or moderate fluid retention. The median cumulative dose to treatment discontinuation due to fluid retention was 1021 mg/m 2 . Fluid retention was completely, but sometimes slowly, reversible with a median of 16 weeks from the last infusion of docetaxel to resolution (range: 0 to 42+ weeks). Patients developing peripheral edema may be treated with standard measures, e.g., salt restriction, oral diuretic(s). 5.7 Second Primary Malignancies Second primary malignancies, notably acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), Non-Hodgkin’s Lymphoma (NHL), and renal cancer, have been reported in patients treated with docetaxel-containing regimens. These adverse reactions may occur several months or years after docetaxel-containing therapy. Treatment-related AML or MDS has occurred in patients given anthracyclines and/or cyclophosphamide, including use in adjuvant therapy for breast cancer. In the adjuvant breast cancer trial (TAX316) AML occurred in 3 of 744 patients who received docetaxel, doxorubicin, and cyclophosphamide (TAC) and in 1 of 736 patients who received fluorouracil, doxorubicin, and cyclophosphamide [ see Clinical Studies (14.2) ]. In TAC-treated patients, the risk of delayed myelodysplasia or myeloid leukemia requires hematological follow-up. Monitor patients for second primary malignancies [ see Adverse Reactions (6.1) ]. 5.8 Cutaneous Reactions Localized erythema of the extremities with edema followed by desquamation has been observed. In case of severe skin toxicity, an adjustment in dosage is recommended [ see Dosage and Administration (2.7) ]. The discontinuation rate due to skin toxicity was 1.6% (15/965) for metastatic breast cancer patients. Among 92 breast cancer patients premedicated with 3-day corticosteroids, there were no cases of severe skin toxicity reported and no patient discontinued docetaxel due to skin toxicity. Severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with docetaxel treatment. Patients should be informed about the signs and symptoms of serious skin manifestations and monitored closely. Permanent treatment discontinuation should be considered in patients who experience SCARs. 5.9 Neurologic Reactions Severe neurosensory symptoms (e.g.,paresthesia, dysesthesia, pain) were observed in 5.5% (53/965) of metastatic breast cancer patients, and resulted in treatment discontinuation in 6.1%. When these symptoms occur, dosage must be adjusted. If symptoms persist, treatment should be discontinued [ see Dosage and Administration (2.7) ]. Patients who experienced neurotoxicity in clinical trials and for whom follow-up information on the complete resolution of the event was available had spontaneous reversal of symptoms with a median of 9 weeks from onset (range: 0 to 106 weeks). Severe peripheral motor neuropathy mainly manifested as distal extremity weakness occurred in 4.4% (42/965). 5.10 Eye Disorders Cystoid macular edema (CME) has been reported in patients treated with Docetaxel Injection. Patients with impaired vision should undergo a prompt and comprehensive ophthalmologic examination. If CME is diagnosed, Docetaxel injection treatment should be discontinued and appropriate treatment initiated. Alternative non-taxane cancer treatment should be considered. 5.11 Asthenia Severe asthenia has been reported in 14.9% (144/965) of metastatic breast cancer patients but has led to treatment discontinuation in only 1.8%. Symptoms of fatigue and weakness may last a few days up to several weeks and may be associated with deterioration of performance status in patients with progressive disease. 5.12 Embryo-Fetal Toxicity Based on findings from animal reproduction studies and its mechanism of action, Docetaxel Injection can cause fetal harm when administered to a pregnant woman [ see Clinical Pharmacology (12.1) ]. Available data from case reports in the literature and pharmacovigilance with docetaxel use in pregnant women are not sufficient to inform the drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, administration of docetaxel to pregnant rats and rabbits during the period of organogenesis caused embryo-fetal toxicities, including intrauterine mortality, at doses as low as 0.02 and 0.003 times the recommended human dose based on body surface area, respectively. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify pregnancy status in females of reproductive potential prior to initiating Docetaxel Injection. Advise females of reproductive potential to use effective contraception during treatment and for 2 months after the last dose of Docetaxel Injection. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of Docetaxel Injection [ see Use in Specific Populations (8.1 , 8.3) ]. 5.13 Alcohol Content Cases of intoxication have been reported with some formulations of docetaxel due to the alcohol content. The alcohol content in a dose of Docetaxel Injection may affect the central nervous system and should be taken into account for patients in whom alcohol intake should be avoided or minimized. Consideration should be given to the alcohol content in Docetaxel Injection on the ability to drive or use machines immediately after the infusion. Each administration of Docetaxel Injection at 100 mg/m 2 delivers 1.8 g/m 2 of ethanol. For a patient with a BSA of 2.0 m 2 , this would deliver 3.6 grams of ethanol [ see Description (11) ]. Other docetaxel products may have a different amount of alcohol. 5.14 Tumor Lysis Syndrome Tumor lysis syndrome has been reported with docetaxel [ see Adverse Reactions (6.2) ]. Patients at risk of tumor lysis syndrome (e.g., with renal impairment, hyperuricemia, bulky tumor) should be closely monitored prior to initiating Docetaxel Injection and periodically during treatment. Correction of dehydration and treatment of high uric acid levels are recommended prior to initiation of treatment."}', 'overdosage': '{"10 OVERDOSAGE There is no known antidote for Docetaxel Injection overdosage. In case of overdosage, the patient should be kept in a specialized unit where vital functions can be closely monitored. Anticipated complications of overdosage include: bone marrow suppression, peripheral neurotoxicity, and mucositis. Patients should receive therapeutic G-CSF as soon as possible after discovery of overdose. Other appropriate symptomatic measures should be taken, as needed. In two reports of overdose, one patient received 150 mg/m 2 and the other received 200 mg/m 2 as 1-hour infusions. Both patients experienced severe neutropenia, mild asthenia, cutaneous reactions, and mild paresthesia, and recovered without incident. In mice, lethality was observed following single intravenous doses that were ≥154 mg/kg (about 4.5 times the human dose of 100 mg/m 2 on a mg/m 2 basis); neurotoxicity associated with paralysis, non-extension of hind limbs, and myelin degeneration was observed in mice at 48 mg/kg (about 1.5 times the human dose of 100 mg/m 2 basis). In male and female rats, lethality was observed at a dose of 20 mg/kg (comparable to the human dose of 100 mg/m 2 on a mg/m 2 basis) and was associated with abnormal mitosis and necrosis of multiple organs."}', 'active_flag': 'Y', 'generic_name': '{"DOCETAXEL ANHYDROUS"}', '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 to read the FDA-approved patient labeling (Patient Information). Bone Marrow Suppression Advise patients that periodic assessment of their blood count will be performed to detect neutropenia, thrombocytopenia, and/or anemia [ see Contraindications (4) , Warnings and Precautions (5.3) ]. Instruct patients to monitor their temperature frequently and immediately report any occurrence of fever. Enterocolitis and Neutropenic Colitis Advise patients of the symptoms of colitis, such as abdominal pain or tenderness, and/or diarrhea, with or without fever, and instruct patients to promptly contact their healthcare provider if they experience these symptoms [ see Dosage and Administration (2.7) , Warnings and Precautions (5.4) ]. Hypersensitivity Reactions Ask patients whether they have previously received paclitaxel therapy, and if they have experienced a hypersensitivity reaction to paclitaxel. Instruct patients to immediately report to their healthcare provider signs of a hypersensitivity reaction [ see Contraindications (4) , Warnings and Precautions (5.5) ]. Fluid Retention Advise patients to report signs of fluid retention such as peripheral edema in the lower extremities, weight gain, and dyspnea immediately to their healthcare provider [ see Warnings and Precautions (5.6) ]. Second Primary Malignancies Advise patients on the risk of second primary malignancies during treatment with Docetaxel Injection [ see Warnings and Precautions (5.7) ]. Cutaneous Reactions Advise patients that localized erythema of the extremities and severe skin toxicities may occur. Instruct patients to immediately report severe cutaneous reactions to their healthcare provider [ see Dosage and Administration (2.7) , Warnings and Precautions (5.8) ]. Neurologic Reactions Advise patients that neurosensory symptoms or peripheral neuropathy may occur. Instruct patients to immediately report neurologic reactions to their healthcare provider [ see Dosage and Administration (2.7) , Warnings and Precautions (5.9) ]. Eye Disorders Advise patients that vision disturbances and excessive tearing are associated with Docetaxel Injection administration. Instruct patients to immediately report any vision changes to their healthcare provider [ see Warnings and Precautions (5.10) ]. Gastrointestinal Reactions Explain to patients that nausea, vomiting, diarrhea, and constipation are associated with Docetaxel Injection administration. Instruct patients to report any severe events to their healthcare provider [ see Adverse Reactions (6) ]. Cardiac Disorders Advise patients to report any irregular and/or rapid heartbeat, severe shortness of breath, dizziness, and/or fainting immediately to their healthcare provider [ see Adverse Reactions (6) ]. Other Common Adverse Reactions Advise patients that other common adverse reactions associated with Docetaxel Injection may include alopecia (cases of permanent hair loss have been reported), asthenia, anorexia, dysgeusia, mucositis, myalgia, nail disorders, or pain. Instruct patients to report these reactions to their healthcare provider if serious events occur [ see Adverse Reactions (6) ]. Importance of Corticosteroids Explain the significance of oral corticosteroids such as dexamethasone administration to the patient to help facilitate compliance. Instruct patients to report to their healthcare provider if they were not compliant with the oral corticosteroid regimen [ see Dosage and Administration (2.6) ]. Embryo-Fetal Toxicity Docetaxel Injection can cause fetal harm. Advise patients to inform their healthcare provider of a known or suspected pregnancy. Advise patients to avoid becoming pregnant while receiving this drug. Advise female patients of reproductive potential to use effective contraceptives during treatment and for 2 months after the last dose of Docetaxel Injection. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of Docetaxel Injection [ see Warnings and Precautions (5.12) , Use in Specific Populations (8.1 , 8.3) ]. Lactation Advise women not to breastfeed during Docetaxel Injection treatment and for 1 week after the last dose [ see Use in Specific Populations (8.2) ]. Infertility Advise males of reproductive potential that Docetaxel Injection may impair fertility [ see Nonclinical Toxicology (13.1) ]. Alcohol Content in Docetaxel Injection Explain to patients the possible effects of the alcohol content in Docetaxel Injection, including possible effects on the central nervous system [ see Warnings and Precautions (5.13) ]. Tumor Lysis Syndrome Advise patients of the potential risk of tumor lysis syndrome and to immediately report any signs or symptoms associated with this event (nausea, vomiting, confusion, shortness of breath, seizure, irregular heartbeat, dark or cloudy urine, reduced amount of urine, unusual tiredness, muscle cramps) to their healthcare provider. Advise patients of the importance of keeping scheduled appointment for blood work or other laboratory tests and of drinking adequate fluids to avoid dehydration [ see Warnings and Precautions (5.14) ]. Ability to Drive or Operate Machines Explain to patients that Docetaxel Injection may impair their ability to drive or operate machines due to its side effects [ see Adverse Reactions (6) ] or due to the alcohol content of Docetaxel Injection [ see Warnings and Precautions (5.13) ]. Advise them not to drive or use machines if they experience these side effects during treatment. Drug Interactions Inform patients about the risk of drug interactions and the importance of providing a list of prescription and non-prescription drugs to their healthcare provider [ see Drug Interactions (7) ]. Manufactured for: Mylan Institutional LLC Morgantown, WV 26505 U.S.A. Manufactured by: Mylan Laboratories Limited Bangalore, India"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Based on findings in animal reproduction studies and its mechanism of action, Docetaxel Injection can cause fetal harm when administered to a pregnant woman [ see Clinical Pharmacology (12.1) ]. Available data from case reports in the literature and pharmacovigilance with docetaxel use in pregnant women are not sufficient to inform the drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Docetaxel Injection contains alcohol which can interfere with neurobehavioral development ( see Clinical Considerations ). In animal reproductive studies, administration of docetaxel to pregnant rats and rabbits during the period of organogenesis caused an increased incidence of embryo-fetal toxicities, including intrauterine mortality, at doses as low as 0.02 and 0.003 times the recommended human dose based on body surface area, respectively ( see Data ). Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, miscarriage, 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 Docetaxel Injection contains alcohol [ see Warnings and Precautions (5.13) ]. Published studies have demonstrated that alcohol is associated with fetal harm including central nervous system abnormalities, behavioral disorders, and impaired intellectual development. Data Animal data Intravenous administration of ≥0.3 and 0.03 mg/kg/day docetaxel to pregnant rats and rabbits, respectively, during the period of organogenesis caused an increased incidence of intrauterine mortality, resorptions, reduced fetal weights, and fetal ossification delays. Maternal toxicity was also observed at these doses, which were approximately 0.02 and 0.003 times the daily maximum recommended human dose based on body surface area, respectively."}', 'pediatric_use': '{"8.4 Pediatric Use The alcohol content of Docetaxel Injection should be taken into account when given to pediatric patients [ see Warnings and Precautions (5.13) ]. The efficacy of docetaxel in pediatric patients as monotherapy or in combination has not been established. The overall safety profile of docetaxel in pediatric patients receiving monotherapy or TCF was consistent with the known safety profile in adults. Docetaxel has been studied in a total of 289 pediatric patients: 239 in 2 trials with monotherapy and 50 in combination treatment with cisplatin and 5-fluorouracil (TCF). Docetaxel Monotherapy Docetaxel monotherapy was evaluated in a dose-finding phase 1 trial in 61 pediatric patients (median age 12.5 years, range 1 to 22 years) with a variety of refractory solid tumors. The recommended dose was 125 mg/m 2 as a 1-hour intravenous infusion every 21 days. The primary dose limiting toxicity was neutropenia. The recommended dose for docetaxel monotherapy was evaluated in a phase 2 single-arm trial in 178 pediatric patients (median age 12 years, range 1 to 26 years) with a variety of recurrent/refractory solid tumors. Efficacy was not established with tumor response rates ranging from one complete response (CR) (0.6%) in a patient with undifferentiated sarcoma to four partial responses (2.2%) seen in one patient each with Ewing Sarcoma, neuroblastoma, osteosarcoma, and squamous cell carcinoma. Docetaxel in Combination Docetaxel was studied in combination with cisplatin and 5-fluorouracil (TCF) versus cisplatin and 5-fluorouracil (CF) for the induction treatment of nasopharyngeal carcinoma (NPC) in pediatric patients prior to chemoradiation consolidation. Seventy-five patients (median age 16 years, range 9 to 21 years) were randomized (2:1) to docetaxel (75 mg/m²) in combination with cisplatin (75 mg/m²) and 5-fluorouracil (750 mg/m²) (TCF) or to cisplatin (80 mg/m²) and 5-fluorouracil (1000 mg/m²/day) (CF). The primary endpoint was the CR rate following induction treatment of NPC. One patient out of 50 in the TCF group (2%) had a complete response while none of the 25 patients in the CF group had a complete response. Pharmacokinetics Pharmacokinetic parameters for docetaxel were determined in 2 pediatric solid tumor trials. Following docetaxel administration at 55 mg/m 2 to 235 mg/m 2 in a 1-hour intravenous infusion every 3 weeks in 25 patients aged 1 to 20 years (median 11 years), docetaxel clearance was 17.3±10.9 L/h/m 2 . Docetaxel was administered in combination with cisplatin and 5-fluorouracil (TCF), at dose levels of 75 mg/m 2 in a 1-hour intravenous infusion day 1 in 28 patients aged 10 to 21 years (median 16 years, 17 patients were older than 16). Docetaxel clearance was 17.9±8.75 L/h/m 2 , corresponding to an AUC of 4.20±2.57 mcg•h/mL. In summary, the body surface area adjusted clearance of docetaxel monotherapy and TCF combination in children were comparable to those in adults [ see Clinical Pharmacology (12.3) ]."}', 'geriatric_use': '{"8.5 Geriatric Use In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in elderly patients. Non-small Cell Lung Cancer In a study conducted in chemotherapy-naïve patients with NSCLC (TAX326), 148 patients (36%) in the docetaxel+cisplatin group were 65 years of age or greater. There were 128 patients (32%) in the vinorelbine+cisplatin group 65 years of age or greater. In the docetaxel+cisplatin group, patients less than 65 years of age had a median survival of 10.3 months (95% CI: 9.1 months, 11.8 months) and patients 65 years or older had a median survival of 12.1 months (95% CI: 9.3 months, 14 months). In patients 65 years of age or greater treated with docetaxel+cisplatin, diarrhea (55%), peripheral edema (39%) and stomatitis (28%) were observed more frequently than in the vinorelbine+cisplatin group (diarrhea 24%, peripheral edema 20%, stomatitis 20%). Patients treated with docetaxel+cisplatin who were 65 years of age or greater were more likely to experience diarrhea (55%), infections (42%), peripheral edema (39%) and stomatitis (28%) compared to patients less than the age of 65 administered the same treatment (43%, 31%, 31% and 21%, respectively). When docetaxel was combined with carboplatin for the treatment of chemotherapy-naïve, advanced non-small cell lung carcinoma, patients 65 years of age or greater (28%) experienced higher frequency of infection compared to similar patients treated with docetaxel+cisplatin, and a higher frequency of diarrhea, infection and peripheral edema than elderly patients treated with vinorelbine+cisplatin. Prostate Cancer Of the 333 patients treated with docetaxel every three weeks plus prednisone in the prostate cancer study (TAX327), 209 patients were 65 years of age or greater and 68 patients were older than 75 years. In patients treated with docetaxel every three weeks, the following treatment-emergent adverse reactions occurred at rates ≥10% higher in patients 65 years of age or greater compared to younger patients: anemia (71% vs. 59%), infection (37% vs. 24%), nail changes (34% vs. 23%), anorexia (21% vs. 10%), weight loss (15% vs. 5%), respectively. Breast Cancer In the adjuvant breast cancer trial (TAX316), docetaxel in combination with doxorubicin and cyclophosphamide was administered to 744 patients of whom 48 (6%) were 65 years of age or greater. The number of elderly patients who received this regimen was not sufficient to determine whether there were differences in safety and efficacy between elderly and younger patients. Gastric Cancer Among the 221 patients treated with Docetaxel Injection in combination with cisplatin and fluorouracil in the gastric cancer study, 54 were 65 years of age or older and 2 patients were older than 75 years. In this study, the number of patients who were 65 years of age or older was insufficient to determine whether they respond differently from younger patients. However, the incidence of serious adverse reactions was higher in the elderly patients compared to younger patients. The incidence of the following adverse reactions (all grades, regardless of relationship): lethargy, stomatitis, diarrhea, dizziness, edema, febrile neutropenia/neutropenic infection occurred at rates ≥10% higher in patients who were 65 years of age or older compared to younger patients. Elderly patients treated with TCF should be closely monitored. Head and Neck Cancer Among the 174 and 251 patients who received the induction treatment with Docetaxel Injection in combination with cisplatin and fluorouracil (TPF) for SCCHN in the TAX323 and TAX324 studies, 18 (10%) and 32 (13%) of the patients were 65 years of age or older, respectively. These clinical studies of Docetaxel Injection in combination with cisplatin and fluorouracil in patients with SCCHN did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience with this treatment regimen has not identified differences in responses between elderly and younger patients."}'}

{HYDROCORTISONE}

{'contraindications': '{"CONTRAINDICATIONS Topical corticosteroids are contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation."}', 'adverse_reactions': '{"ADVERSE REACTIONS The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, foliculitiis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE Topical corticosteroids are indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Topically applied corticosteroids can be absorbed in sufficient amounts to produce systems effects (See PRECAUTIONS )."}', 'active_flag': 'Y', 'generic_name': '{HYDROCORTISONE}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': None, 'information_for_patients': '{"Information for the Patient Patients using topical corticosteroids should receive the following information and instructions: 1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes. 2. Patients should be advised not to use this medication for any disorder other than for which it was prescribed. 3. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician. 4. Patients should report any signs of local adverse reactions especially under occlusive dressing. 5. Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on a child being treated in the diaper area, as these garments may constitute occlusive dressings."}', 'pregnancy': '{"Pregnancy: Teratogenic effects - Pregnancy Category C Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time."}', 'pediatric_use': '{"Pediatric Use Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA axis suppression and Cushing’s syndrome than mature patients because of a larger skin surface area to body weight ratio. Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing’s syndrome, and intracranial hypertension have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients include linear growth retardation, delayed weight gain, low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Administration of topical corticosteroids to pediatric patients should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of pediatric patients."}', 'geriatric_use': None}

{CLOTRIMAZOLE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses Proven clinically effective in the treatment of jock itch (tinea cruris). For effective relief of itching, irritation, redness, scaling, cracking, burning, soreness, and discomfort which can accompany these conditions."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{CLOTRIMAZOLE}', '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 on children under two years of age unless directed by a physician. Avoid contact with the eyes. If irritation occurs or if there is no improvement within 2 weeks, discontinue use and consult a physician. Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away. 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}

{ACETAMINOPHEN,CAFFEINE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses temporarily relieves minor aches and pain due to: headache muscular aches"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"ACETAMINOPHEN, CAFFEINE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if any new symptoms occur symptoms do not get better or worsen painful area is red or swollen pain gets worse or lasts for more than 10 days fever gets worse or lasts for more than 3 days"}', 'do_not_use': '{"Do not use with any other drug containing acetaminophen (prescription or nonprescription). Ask a doctor or pharmacist before using with other drugs if you are not sure."}', 'when_using': None, 'warnings': '{"Warnings Liver warning This product contains acetaminophen. Severe liver damage may occur if you take more than 6 caplets in 24 hours, which is the maximum daily amount with other drugs containing acetaminophen 3 or more alcoholic drinks every day while using this product 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 with any other drug containing acetaminophen (prescription or nonprescription). Ask a doctor or pharmacist before using with other drugs if you are not sure. Ask a doctor before use if you have liver disease Ask a doctor or pharmacist if you are taking the blood thinning drug warfarin Stop use and ask a doctor if any new symptoms occur symptoms do not get better or worsen painful area is red or swollen pain gets worse or lasts for more than 10 days fever gets worse or lasts for more than 3 days 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. 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}

{LISINOPRIL}

{'contraindications': '{"4 CONTRAINDICATIONS Lisinopril is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer Lisinopril tablet USP within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor [see Warnings and Precautions (5.2) ]. Lisinopril is contraindicated in patients with: a history of angioedema or hypersensitivity related to previous treatment with an angiotensin converting enzyme inhibitor hereditary or idiopathic angioedema Do not co-administer aliskiren with lisinopril in patients with diabetes [see Drug Interactions (7.4) ]. Angioedema or a history of hereditary or idiopathic angioedema ( 4 ) Hypersensitivity ( 4 ) Co-administration of aliskiren with lisinopril in patients with diabetes ( 4 , 7.4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS Common adverse reactions (events 2% greater than placebo) by use: Hypertension: headache, dizziness and cough ( 6.1 ) Heart Failure: hypotension and chest pain ( 6.1 ) Acute Myocardial Infarction: hypotension ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 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 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. Hypertension In clinical trials in patients with hypertension treated with lisinopril, 5.7% of patients on lisinopril discontinued with adverse reactions. The following adverse reactions (events 2% greater on lisinopril than on placebo) were observed with lisinopril alone: headache (by 3.8%), dizziness (by 3.5%), cough (by 2.5%). Heart Failure In patients with systolic heart failure treated with lisinopril for up to four years, 11% discontinued therapy with adverse reactions. In controlled studies in patients with heart failure, therapy was discontinued in 8.1% of patients treated with lisinopril for 12 weeks, compared to 7.7% of patients treated with placebo for 12 weeks. The following adverse reactions (events 2% greater on lisinopril than on placebo) were observed with lisinopril: hypotension (by 3.8%), chest pain (by 2.1%). In the two-dose ATLAS trial [see Clinical Studies (14.2) ] in heart failure patients, withdrawals due to adverse reactions were not different between the low and high groups, either in total number of discontinuation (17 to 18%) or in rare specific reactions (< 1%). The following adverse reactions, mostly related to ACE inhibition, were reported more commonly in the high dose group: Table 1 Dose-related Adverse Drug Reactions: ATLAS trial High Dose (n=1568) Low Dose (n=1596) Dizziness 19% 12% Hypotension 11% 7% Creatinine increased 10% 7% Hyperkalemia 6% 4% Syncope 7% 5% Acute Myocardial Infarction Patients treated with lisinopril had a higher incidence of hypotension (by 5.3%) and renal dysfunction (by 1.3%) compared with patients not taking lisinopril. Other clinical adverse reactions occurring in 1 % or higher of patients with hypertension or heart failure treated with lisinopril in controlled clinical trials and do not appear in other sections of labeling are listed below: Body as a whole: Fatigue, asthenia, orthostatic effects. Digestive: Pancreatitis, constipation, flatulence, dry mouth, diarrhea. Hematologic: Rare cases of bone marrow depression, hemolytic anemia, leukopenia/neutropenia and thrombocytopenia. Endocrine: Diabetes mellitus, inappropriate antidiuretic hormone secretion. Metabolic: Gout. Skin: Urticaria, alopecia, photosensitivity, erythema, flushing, diaphoresis, cutaneous pseudolymphoma, toxic epidermal necrolysis, Stevens-Johnson syndrome, and pruritus. Special Senses: Visual loss, diplopia, blurred vision, tinnitus, photophobia, taste disturbances, olfactory disturbance. Urogenital: Impotence. Miscellaneous: A symptom complex has been reported which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia, leukocytosis, paresthesia and vertigo. Rash, photosensitivity or other dermatological manifestations may occur alone or in combination with these symptoms. Clinical Laboratory Test Findings Serum Potassium: In clinical trials hyperkalemia (serum potassium greater than 5.7 mEq/L) occurred in 2.2% and 4.8% of lisinopril-treated patients with hypertension and heart failure, respectively [see Warnings and Precautions (5.5) ]. Creatinine, Blood Urea Nitrogen: Minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 2% of patients with hypertension treated with lisinopril alone. Increases were more common in patients receiving concomitant diuretics and in patients with renal artery stenosis [see Warnings and Precautions (5.4) ]. Reversible minor increases in blood urea nitrogen and serum creatinine were observed in 11.6% of patients with heart failure on concomitant diuretic therapy. Frequently, these abnormalities resolved when the dosage of the diuretic was decreased. Patients with acute myocardial infarction in the GISSI-3 trial treated with lisinopril had a higher (2.4% versus 1.1% in placebo) incidence of renal dysfunction in-hospital and at six weeks (increasing creatinine concentration to over 3 mg/dL or a doubling or more of the baseline serum creatinine concentration). Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.4 g% and 1.3 vol%, respectively) occurred frequently in patients treated with lisinopril but were rarely of clinical importance in patients without some other cause of anemia. In clinical trials, less than 0.1% of patients discontinued therapy due to anemia. 6.2 Post-marketing Experience The following adverse reactions have been identified during post-approval use of lisinopril that are not included in other sections of labeling. 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. Other reactions include: Metabolism and Nutrition Disorders Hyponatremia [see Warnings and Precautions (5.4) ], cases of hypoglycemia in diabetic patients on oral antidiabetic agents or insulin [see Drug Interactions (7.2) ] Nervous System and Psychiatric Disorders Mood alterations (including depressive symptoms), mental confusion, hallucinations Skin and Subcutaneous Tissue Disorders Psoriasis"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Diuretics: Excessive drop in blood pressure ( 7.1 ) NSAIDS: Increased risk of renal impairment and loss of antihypertensive efficacy ( 7.3 ) Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension and hyperkalemia ( 7.4 ) Lithium: Symptoms of lithium toxicity ( 7.5 ) Gold: Nitritoid reactions have been reported ( 7.6 ) Concomitant mTOR inhibitor or neprilysin inhibitor use may increase angioedema risk ( 7.7 , 7.8 ) 7.1 Diuretics Initiation of lisinopril in patients on diuretics may result in excessive reduction of blood pressure. The possibility of hypotensive effects with lisinopril can be minimized by either decreasing or discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with lisinopril. If this is not possible, reduce the starting dose of lisinopril tablets [see Dosage and Administration (2.2) and Warnings and Precautions (5.4) ]. Lisinopril attenuates potassium loss caused by thiazide-type diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) can increase the risk of hyperkalemia. Therefore, if concomitant use of such agents is indicated, monitor the patient\'s serum potassium frequently. 7.2 Antidiabetics Concomitant administration of lisinopril and antidiabetic medicines (insulins, oral hypoglycemic agents) may cause an increased blood-glucose-lowering effect with risk of hypoglycemia. 7.3 Non-Steroidal 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 lisinopril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving lisinopril and NSAID therapy. The antihypertensive effect of ACE inhibitors, including lisinopril, may be attenuated by NSAIDs. 7.4 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. The VA NEPHRON trial enrolled 1448 patients with type 2 diabetes, elevated urinary-albumin-to-creatinine ratio, and decreased estimated glomerular filtration rate (GFR 30 to 89.9 ml/min), randomized them to lisinopril or placebo on a background of losartan therapy and followed them for a median of 2.2 years. Patients receiving the combination of losartan and lisinopril did not obtain any additional benefit compared to monotherapy for the combined endpoint of decline in GFR, end state renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney injury compared with the monotherapy group. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on lisinopril and other agents that affect the RAS. Do not co-administer aliskiren with lisinopril in patients with diabetes. Avoid use of aliskiren with lisinopril in patients with renal impairment (GFR <60 ml/min). 7.5 Lithium Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs, which cause elimination of sodium, including ACE inhibitors. Lithium toxicity was usually reversible upon discontinuation of lithium and the ACE inhibitor. Monitor serum lithium levels during concurrent use. 7.6 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 lisinopril. 7.7 mTOR Inhibitors Patients taking concomitant mTOR inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema [see Warnings and Precautions (5.2) ]. 7.8 Neprilysin Inhibitor Patients taking concomitant neprilysin inhibitors may be at increased risk for angioedema. [see Warnings and Precautions (5.2) ]"}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Lisinopril tablets USP is an angiotensin converting enzyme (ACE) inhibitor indicated for: Treatment of hypertension in adults and pediatric patients 6 years of age and older ( 1.1 ) Adjunct therapy for heart failure ( 1.2 ) Treatment of Acute Myocardial Infarction ( 1.3 ) 1.1 Hypertension Lisinopril tablet USP is indicated for the treatment of hypertension in adult patients and pediatric patients 6 years of age and older 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. 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. Lisinopril tablets USP may be administered alone or with other antihypertensive agents [see Clinical Studies (14.1) ]. 1.2 Heart Failure Lisinopril tablet USP is indicated to reduce signs and symptoms of systolic heart failure [see Clinical Studies (14.2) ]. 1.3 Reduction of Mortality in Acute Myocardial Infarction Lisinopril tablet USP is indicated for the reduction of mortality in treatment of hemodynamically stable patients within 24 hours of acute myocardial infarction. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin and beta-blockers [see Clinical Studies (14.3) ]."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Angioedema: Discontinue lisinopril, provide appropriate therapy and monitor until resolved ( 5.2 ) Renal impairment: Monitor renal function periodically ( 5.3 ) Hypotension: Patients with other heart or renal diseases have increased risk, monitor blood pressure after initiation ( 5.4 ) Hyperkalemia: Monitor serum potassium periodically ( 5.5 ) Cholestatic jaundice and hepatic failure: Monitor for jaundice or signs of liver failure ( 5.6 ) 5.1 Fetal Toxicity Lisinopril can cause fetal harm when administered to a pregnant woman. 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 lisinopril as soon as possible [see Use in Specific Populations (8.1) ]. 5.2 Angioedema and Anaphylactoid Reactions Patients taking concomitant mTOR inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema. [see Drug Interactions (7.7 , 7.8) ]. Angioedema Head and Neck Angioedema: Angioedema of the face, extremities, lips, tongue, glottis and/or larynx, including some fatal reactions, have occurred in patients treated with angiotensin converting enzyme inhibitors, including lisinopril, at any time during treatment. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Lisinopril should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms of angioedema has occurred. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor [see Contraindications (4) ]. ACE inhibitors have been associated with a higher rate of angioedema in black than in non-black patients. Intestinal Angioedema : Intestinal angioedema has occurred 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 C-1 esterase levels were normal. In some cases, the angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Anaphylactoid Reactions Anaphylactoid Reactions During Desensitization: Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. Anaphylactoid Reactions During Dialysis: Sudden and potentially life threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately, and aggressive therapy for anaphylactoid reactions must be initiated. Symptoms have not been relieved by antihistamines in these situations. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption. 5.3 Impaired Renal Function Monitor renal function periodically in patients treated with lisinopril. Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-myocardial infarction or volume depletion) may be at particular risk of developing acute renal failure on lisinopril. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on lisinopril [see Adverse Reactions (6.1) , Drug Interactions (7.4) ]. 5.4 Hypotension Lisinopril can cause symptomatic hypotension, sometimes complicated by oliguria, progressive azotemia, acute renal failure or death. Patients at risk of excessive hypotension include those with the following conditions or characteristics: heart failure with systolic blood pressure below 100 mmHg, ischemic heart disease, cerebrovascular disease, hyponatremia, high dose diuretic therapy, renal dialysis, or severe volume and/or salt depletion of any etiology. In these patients, lisinopril 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 lisinopril and/or diuretic is increased. Avoid use of lisinopril in patients who are hemodynamically unstable after acute MI. Symptomatic hypotension is also possible in patients with severe aortic stenosis or hypertrophic cardiomyopathy. Surgery/Anesthesia In patients undergoing major surgery or during anesthesia with agents that produce hypotension, lisinopril 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. 5.5 Hyperkalemia Serum potassium should be monitored periodically in patients receiving lisinopril. Drugs that inhibit the renin angiotensin system can cause hyperkalemia. 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 [see Drug Interactions (7.1) ]. 5.6 Hepatic Failure ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis 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 treatment."}', 'overdosage': '{"10 OVERDOSAGE Following a single oral dose of 20 g/kg no lethality occurred in rats, and death occurred in one of 20 mice receiving the same dose. The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution. Lisinopril can be removed by hemodialysis [see Clinical Pharmacology (12.3) ]."}', 'active_flag': 'Y', 'generic_name': '{LISINOPRIL}', '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 NOTE: 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 Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to notify their healthcare provider with a known or suspected pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ]. Angioedema Angioedema, including laryngeal edema may occur at any time during treatment with angiotensin converting enzyme inhibitors, including lisinopril. Tell patients 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. Lactation Advise women not to breastfeed during treatment with lisinopril [see Use in Specific Populations (8.2) ]. Symptomatic Hypotension Tell patients to report light-headedness especially during the first few days of therapy. If actual syncope occurs, tell the patient to discontinue the drug until they have consulted with the prescribing physician. Tell patients 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; advise patients accordingly. Hyperkalemia Tell patients not to use salt substitutes containing potassium without consulting their physician. Hypoglycemia Tell diabetic patients treated with oral antidiabetic agents or insulin starting an ACE inhibitor to monitor for hypoglycaemia closely, especially during the first month of combined use [see Drug Interactions (7.2) ]. Leukopenia/Neutropenia Tell patients to report promptly any indication of infection (e.g., sore throat, fever), which may be a sign of leukopenia/neutropenia."}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Lisinopril can cause fetal harm when administered to a pregnant woman. 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. 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. When pregnancy is detected, discontinue lisinopril as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown. In the general U.S. 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: 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. Fetal/Neonatal Adverse Reactions: Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death. 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. 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 lisinopril for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occur in neonates with a history of in utero exposure to lisinopril, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function."}', 'pediatric_use': '{"8.4 Pediatric Use Antihypertensive effects and safety of lisinopril have been established in pediatric patients aged 6 to 16 years [see Dosage and Administration (2.1) and Clinical Studies (14.1) ]. No relevant differences between the adverse reaction profile for pediatric patients and adult patients were identified. Safety and effectiveness of lisinopril have not been established in pediatric patients under the age 6 or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73 m 2 [see Dosage and Administration (2.1) , Clinical Pharmacology (12.3) , and Clinical Studies (14.1) ]. Neonates with A History of In Utero Exposure to Lisinopril 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."}', 'geriatric_use': '{"8.5 Geriatric Use No dosage adjustment with lisinopril is necessary in elderly patients. In a clinical study of lisinopril in patients with myocardial infarctions (GISSI-3 Trial) 4,413 (47%) were 65 and over, while 1,656 (18%) were 75 and over. In this study, 4.8 % of patients aged 75 years and older discontinued lisinopril treatment because of renal dysfunction vs. 1.3% of patients younger than 75 years. No other differences in safety or effectiveness were observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out."}'}

{OXYGEN}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': None, 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{OXYGEN}', 'route': '{"RESPIRATORY (INHALATION)"}', '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}

{"FERROSOFERRIC PHOSPHATE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Low Or Mild Fever*"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"FERROSOFERRIC PHOSPHATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if symptoms persist for more than 3 days or worsen"}', 'do_not_use': None, 'when_using': None, 'warnings': '{""}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{ACETAMINOPHEN,CAFFEINE,"PYRILAMINE MALEATE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses for the temporary relief of these symptoms associated with menstrual periods: bloating headache muscle aches cramps backache fatigue water-weight gain"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"ACETAMINOPHEN, CAFFEINE, PYRILAMINE MALEATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if new symptoms occur redness or swelling is present pain gets worse or lasts more than 10 days fever gets worse or lasts more than 3 days 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 have ever had an allergic reaction to this product or any of its ingredients"}', 'when_using': '{"When using this product drowsiness may occur avoid alcoholic beverages alcohol, sedatives, and tranquilizers may increase drowsiness excitability may occur, especially in children use caution when driving a motor vehicle or operating machinery 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 heart rate. The recommended dose of this product contains about as much caffeine as a cup of coffee."}', 'warnings': '{"Warnings 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 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 have ever had an allergic reaction to this product or any of its ingredients Ask a doctor before use if you have difficulty in urination due to enlargement of the prostate gland liver disease a breathing problem such as emphysema or chronic bronchitis glaucoma Ask a doctor or pharmacist before use if you are taking the blood thinning drug warfarin taking sedatives or tranquilizers When using this product drowsiness may occur avoid alcoholic beverages alcohol, sedatives, and tranquilizers may increase drowsiness excitability may occur, especially in children use caution when driving a motor vehicle or operating machinery 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 heart rate. The recommended dose of this product contains about as much caffeine as a cup of coffee. Stop use and ask a doctor if new symptoms occur redness or swelling is present pain gets worse or lasts more than 10 days fever gets worse or lasts more than 3 days 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. Prompt 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}

{"SODIUM NITROPRUSSIDE"}

{'contraindications': '{"CONTRAINDICATIONS Sodium nitroprusside should not be used in the treatment of compensatory hypertension, where the primary hemodynamic lesion is aortic coarctation or arteriovenous shunting. Sodium nitroprusside should not be used to produce hypotension during surgery in patients with known inadequate cerebral circulation, or in moribund patients (A.S.A. Class 5E) coming to emergency surgery. Patients with congenital (Leber\'s) optic atrophy or with tobacco amblyopia have unusually high cyanide/thiocyanate ratios. These rare conditions are probably associated with defective or absent rhodanase, and sodium nitroprusside should be avoided in these patients. Sodium nitroprusside should not be used for the treatment of acute congestive heart failure associated with reduced peripheral vascular resistance such as high-output heart failure that may be seen in endotoxic sepsis."}', 'adverse_reactions': '{"ADVERSE REACTIONS The most important adverse reactions to sodium nitroprusside are the avoidable ones of excessive hypotension and cyanide toxicity, described above under WARNINGS. The adverse reactions described in this section develop less rapidly and, as it happens, less commonly. Methemoglobinemia: As described in CLINICAL PHARMACOLOGY above, sodium nitroprusside infusions can cause sequestration of hemoglobin as methemoglobin. The back-conversion process is normally rapid, and clinically significant methemoglobinemia (>10%) is seen only rarely in patients receiving sodium nitroprusside injection. Even patients congenitally incapable of back-converting methemoglobin should demonstrate 10% methemoglobinemia only after they have received about 10 mg/kg of sodium nitroprusside, and a patient receiving sodium nitroprusside at the maximum recommended rate (10 mcg/kg/min) would take over 16 hours to reach this total accumulated dose. Methemoglobin levels can be measured by most clinical laboratories. The diagnosis should be suspected in patients who have received >10 mg/kg of sodium nitroprusside and who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial pO2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air. When methemoglobinemia is diagnosed, the treatment of choice is 1-2 mg/kg of methylene blue, administered intravenously over several minutes. In patients likely to have substantial amounts of cyanide bound to methemoglobin as cyanmethemoglobin, treatment of methemoglobinemia with methylene blue must be undertaken with extreme caution. Thiocyanate Toxicity: As described in CLINICAL PHARMACOLOGY above, most of the cyanide produced during metabolism of sodium nitroprusside is eliminated in the form of thiocyanate. When cyanide elimination is accelerated by the co-infusion of thiosulfate, thiocyanate production is increased. Thiocyanate is mildly neurotoxic (tinnitus, miosis, hyperreflexia) at serum levels of 1 mmol/L (60 mg/L). Thiocyanate toxicity is life-threatening when levels are 3 or 4 times higher (200 mg/L). The steady-state thiocyanate level after prolonged infusions of sodium nitroprusside is increased with increased infusion rate, and the half-time of accumulation is 3-4 days. To keep the steady-state thiocyanate level below 1 mmol/L, a prolonged infusion of sodium nitroprusside should not be more rapid than 3 mcg/kg/min; in anuric patients, the corresponding limit is just 1 mcg/kg/min. When prolonged infusions are more rapid than these, thiocyanate levels should be measured daily. Physiologic maneuvers (e.g., those that alter the pH of the urine) are not known to increase the elimination of thiocyanate. Thiocyanate clearance rates during dialysis, on the other hand, can approach the blood flow rate of the dialyzer. Thiocyanate interferes with iodine uptake by the thyroid. Abdominal pain, apprehension, diaphoresis, \\"dizziness,\\" headache, muscle twitching, nausea, palpitations, restlessness, retching, and retrosternal discomfort have been noted when the blood pressure was too rapidly reduced. These symptoms quickly disappeared when the infusion was slowed or discontinued, and they did not reappear with a continued (or resumed) slower infusion. Other adverse reactions reported are: Cardiovascular: Bradycardia, electrocardiographic changes, tachycardia. Dermatologic: Rash. Endocrine: Hypothyroidism. Gastrointestinal: Ileus. Hematologic: Decreased platelet aggregation. Neurologic: Increased intracranial pressure. Miscellaneous: Flushing, venous streaking, irritation at the infusion site. To report SUSPECTED ADVERSE REACTIONS, contact Somerset Therapeutics, LLC at 1- 800-417-9175 or FDA at 1-800 -FDA-1088 or www.fda.gov/medwatch"}', 'drug_interactions': '{"Drug Interactions The hypotensive effect of sodium nitroprusside is augmented by that of most other hypotensive drugs, including ganglionic blocking agents, negative inotropic agents, and inhaled anesthetics. Carcinogenesis, Mutagenesis, Impairment of Fertility Animal studies assessing sodium nitroprusside\'s carcinogenicity and mutagenicity have not been conducted. Similarly, sodium nitroprusside has not been tested for effects on fertility."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Sodium nitroprusside is indicated for the immediate reduction of blood pressure of adult and pediatric patients in hypertensive crises. Concomitant longer-acting antihypertensive medication should be administered so that the duration of treatment with sodium nitroprusside can be minimized. Sodium nitroprusside is also indicated for producing controlled hypotension in order to reduce bleeding during surgery. Sodium nitroprusside is also indicated for the treatment of acute congestive heart failure."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Overdosage of nitroprusside can be manifested as excessive hypotension or cyanide toxicity (see WARNINGS ) or as thiocyanate toxicity ( see ADVERSE REACTIONS). The acute intravenous mean lethal doses (LD50) of nitroprusside in rabbits, dogs, mice, and rats are 2.8, 5.0, 8.4, and 11.2 mg/kg, respectively. Treatment of cyanide toxicity: Cyanide levels can be measured by many laboratories, and blood-gas studies that can detect venous hyperoxemia or acidosis are widely available. Acidosis may not appear until more than an hour after the appearance of dangerous cyanide levels, and laboratory tests should not be awaited. Reasonable suspicion of cyanide toxicity is adequate grounds for initiation of treatment. Treatment of cyanide toxicity consists of • discontinuing the administration of sodium nitroprusside; • providing a buffer for cyanide by using sodium nitrite to convert as much hemoglobin into methemoglobin as the patient can safely tolerate; and then • infusing sodium thiosulfate in sufficient quantity to convert the cyanide into thiocyanate. The necessary medications for this treatment are contained in commercially available Cyanide Antidote Kits. Alternatively, discrete stocks of medications can be used. Hemodialysis is ineffective in removal of cyanide, but it will eliminate most thiocyanate. Cyanide Antidote Kits contain both amyl nitrite and sodium nitrite for induction of methemoglobinemia. The amyl nitrite is supplied in the form of inhalant ampoules, for administration in environments where intravenous administration of sodium nitrite may be delayed. In a patient who already has a patent intravenous line, use of amyl nitrite confers no benefit that is not provided by infusion of sodium nitrite. Sodium nitrite is available in a 3% solution, and 4-6 mg/kg (about 0.2 mL/kg) should be injected over 2- 4 minutes. This dose can be expected to convert about 10% of the patient\'s hemoglobin into methemoglobin; this level of methemoglobinemia is not associated with any important hazard of its own. The nitrite infusion may cause transient vasodilatation and hypotension, and this hypotension must, if it occurs, be routinely managed. Immediately after infusion of the sodium nitrite, sodium thiosulfate should be infused. This agent is available in 10% and 25% solutions, and the recommended dose is 150-200 mg/kg; a typical adult dose is 50 mL of the 25% solution. Thiosulfate treatment of an acutely cyanide-toxic patient will raise thiocyanate levels, but not to a dangerous degree. The nitrite/thiosulfate regimen may be repeated, at half the original doses, after two hours."}', 'active_flag': 'Y', 'generic_name': '{"SODIUM NITROPRUSSIDE"}', 'route': '{INTRAVENOUS}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS (See also the boxed warning at the beginning of this insert.) The principal hazards of sodium nitroprusside injection administration are excessive hypotension and excessive accumulation of cyanide ( see also OVERDOSAGE and DOSAGE AND ADMINISTRATION ). Excessive Hypotension: Small transient excesses in the infusion rate of sodium nitroprusside can result in excessive hypotension, sometimes to levels so low as to compromise the perfusion of vital organs. These hemodynamic changes may lead to a variety of associated symptoms; see ADVERSE REACTIONS . Nitroprusside induced hypotension will be self-limited within 1-10 minutes after discontinuation of the nitroprusside infusion; during these few minutes, it may be helpful to put the patient into a head-down (Trendelenburg) position to maximize venous return. If hypotension persists more than a few minutes after discontinuation of the infusion of sodium nitroprusside injection, sodium nitroprusside injection is not the cause, and the true cause must be sought. Cyanide Toxicity: As described in CLINICAL PHARMACOLOGY above, sodium nitroprusside infusions at rates above 2 mcg/kg/min generate cyanide ion (CN - ) faster than the body can normally dispose of it. (When sodium thiosulfate is given, as described under DOSAGE AND ADMINISTRATION, the body\'s capacity for CN - elimination is greatly increased.) Methemoglobin normally present in the body can buffer a certain amount of CN - , but the capacity of this system is exhausted by the CN - produced from about 500 mcg/kg of sodium nitroprusside. This amount of sodium nitroprusside is administered in less than an hour when the drug is administered at 10 mcg/kg/min (the maximum recommended rate). Thereafter, the toxic effects of CN - may be rapid, serious, and even lethal. The true rates of clinically important cyanide toxicity cannot be assessed from spontaneous reports or published data. Most patients reported to have experienced such toxicity have received relatively prolonged infusions, and the only patients whose deaths have been unequivocally attributed to nitroprusside-induced cyanide toxicity have been patients who had received nitroprusside infusions at rates (30-120 mcg/kg/min) much greater than those now recommended. Elevated cyanide levels, metabolic acidosis, and marked clinical deterioration, however, have occasionally been reported in patients who received infusions at recommended rates for only a few hours and even, in one case, for only 35 minutes. In some of these cases, infusion of sodium thiosulfate caused dramatic clinical improvement, supporting the diagnosis of cyanide toxicity. Cyanide toxicity may manifest itself as venous hyperoxemia with bright red venous blood, as cells become unable to extract the oxygen delivered to them; metabolic (lactic) acidosis; air hunger; confusion; and death. Cyanide toxicity due to causes other than nitroprusside has been associated with angina pectoris and myocardial infarction; ataxia, seizures, and stroke; and other diffuse ischemic damage. Hypertensive patients, and patients concomitantly receiving other antihypertensive medications, may be more sensitive to the effects of sodium nitroprusside than normal subjects."}', 'precautions': '{"PRECAUTIONS General Like other vasodilators, sodium nitroprusside can cause increases in intracranial pressure. In patients whose intracranial pressure is already elevated, sodium nitroprusside should be used only with extreme caution. Hepatic: Use caution when administering nitroprusside to patients with hepatic insufficiency. Use in Anesthesia: When sodium nitroprusside (or any other vasodilator) is used for controlled hypotension during anesthesia, the patient\'s capacity to compensate for anemia and hypovolemia may be diminished. If possible, pre-existing anemia and hypovolemia should be corrected prior to administration of sodium nitroprusside injection. Hypotensive anesthetic techniques may also cause abnormalities of the pulmonary ventilation/perfusion ratio. Patients intolerant of these abnormalities may require a higher fraction of inspired oxygen. Extreme caution should be exercised in patients who are especially poor surgical risks (A.S.A. Class 4 and 4E). Laboratory Tests The cyanide-level assay is technically difficult, and cyanide levels in body fluids other than packed red blood cells are difficult to interpret. Cyanide toxicity will lead to lactic acidosis and venous hyperoxemia, but these findings may not be present until an hour or more after the cyanide capacity of the body\'s red-cell mass has been exhausted. Drug Interactions The hypotensive effect of sodium nitroprusside is augmented by that of most other hypotensive drugs, including ganglionic blocking agents, negative inotropic agents, and inhaled anesthetics. Carcinogenesis, Mutagenesis, Impairment of Fertility Animal studies assessing sodium nitroprusside\'s carcinogenicity and mutagenicity have not been conducted. Similarly, sodium nitroprusside has not been tested for effects on fertility. Pregnancy There are no adequate, well-controlled studies of sodium nitroprusside injection in either laboratory animals or pregnant women. It is not known whether sodium nitroprusside injection can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Sodium nitroprusside injection should be given to a pregnant woman only if clearly needed. Nonteratogenic effects: In three studies in pregnant ewes, nitroprusside was shown to cross the placental barrier. Fetal cyanide levels were shown to be dose-related to maternal levels of nitroprusside. The metabolic transformation of sodium nitroprusside given to pregnant ewes led to fatal levels of cyanide in the fetuses. The infusion of 25 mcg/kg/min of sodium nitroprusside for one hour in pregnant ewes resulted in the death of all fetuses. Pregnant ewes infused with 1 mcg/kg/min of sodium nitroprusside for one hour delivered normal lambs. According to one investigator, a pregnant woman at 24 weeks gestation was given sodium nitroprusside to control gestational hypertension secondary to mitral valve disease. Sodium nitroprusside was infused at 3.9 mcg/kg/min for a total of 3.5 mg/kg over 15 hours prior to delivery of a 478 gram stillborn infant without any obvious anomalies. Cyanide levels in the fetal liver were less than 10 mcg/mL. Toxic levels have been reported to be more than 30-40 mcg/mL. The mother demonstrated no cyanide toxicity. The effects of administering sodium thiosulfate in pregnancy, either by itself or as a co-infusion with sodium nitroprusside, are completely unknown. Nursing Mothers It is not known whether sodium nitroprusside and its metabolites are 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 sodium nitroprusside, 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 Efficacy in the pediatric population was established based on adult trials and supported by the dose-ranging trial (Study 1) and an open label trial of at least 12 hour infusion at a rate that achieved adequate MAP control (Study 2) with pediatric patients on sodium nitroprusside. No novel safety issues were seen in these studies in pediatric patients. See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION ."}', 'information_for_patients': None, 'pregnancy': '{"Pregnancy There are no adequate, well-controlled studies of sodium nitroprusside injection in either laboratory animals or pregnant women. It is not known whether sodium nitroprusside injection can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Sodium nitroprusside injection should be given to a pregnant woman only if clearly needed. Nonteratogenic effects: In three studies in pregnant ewes, nitroprusside was shown to cross the placental barrier. Fetal cyanide levels were shown to be dose-related to maternal levels of nitroprusside. The metabolic transformation of sodium nitroprusside given to pregnant ewes led to fatal levels of cyanide in the fetuses. The infusion of 25 mcg/kg/min of sodium nitroprusside for one hour in pregnant ewes resulted in the death of all fetuses. Pregnant ewes infused with 1 mcg/kg/min of sodium nitroprusside for one hour delivered normal lambs. According to one investigator, a pregnant woman at 24 weeks gestation was given sodium nitroprusside to control gestational hypertension secondary to mitral valve disease. Sodium nitroprusside was infused at 3.9 mcg/kg/min for a total of 3.5 mg/kg over 15 hours prior to delivery of a 478 gram stillborn infant without any obvious anomalies. Cyanide levels in the fetal liver were less than 10 mcg/mL. Toxic levels have been reported to be more than 30-40 mcg/mL. The mother demonstrated no cyanide toxicity. The effects of administering sodium thiosulfate in pregnancy, either by itself or as a co-infusion with sodium nitroprusside, are completely unknown."}', 'pediatric_use': '{"Pediatric Use Efficacy in the pediatric population was established based on adult trials and supported by the dose-ranging trial (Study 1) and an open label trial of at least 12 hour infusion at a rate that achieved adequate MAP control (Study 2) with pediatric patients on sodium nitroprusside. No novel safety issues were seen in these studies in pediatric patients. See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION ."}', 'geriatric_use': None}

{"AMPHETAMINE SULFATE"}

{'contraindications': '{"CONTRAINDICATIONS • Known hypersensitivity to amphetamine products. • During or within 14 days following the administration of monoamine oxidase inhibitors(hypertensive crises may result) (see WARNINGS )."}', 'adverse_reactions': '{"ADVERSE REACTIONS Cardiovascular Palpitations, tachycardia, elevation of blood pressure. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use. Central Nervous System Psychotic episodes at recommended doses (rare), overstimulation, restlessness, dizziness, insomnia, euphoria, dyskinesia, dysphoria, tremor, headache, exacerbation of motor and verbal tics and Tourette\'s syndrome. Gastrointestinal Dryness of the mouth, unpleasant taste, diarrhea, constipation, intestinal ischemia and other gastrointestinal disturbances. Anorexia and weight loss may occur as undesirable effects when amphetamines are used for other than the anorectic effect. Allergic Urticaria Endocrine Impotence, changes in libido, and frequent or prolonged erections. Musculoskeletal Rhabdomyolysis"}', 'drug_interactions': '{"Drug Interactions MAO inhibitors - MAOI antidepressants, as well as a metabolic of furazolidone, slow amphetamine metabolism. This slowing potentiates amphetamines, increasing their effect on the release of norepinephrine and other monoamines from adrenergic nerve endings; this can cause headaches and other signs of hypertensive crisis. A variety of neurological toxic effects and malignant hyperpyrexia can occur, sometimes with fatal results. Serotonergic Drugs - The concomitant use of amphetamine sulfate tablets and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during amphetamine sulfate tablets initiation or dosage increase. If serotonin syndrome occurs, discontinue amphetamine sulfate tablets and the concomitant serotonergic drug(s) (see WARNING and PRECAUTIONS). CYP2D6 Inhibitors - The concomitant use of amphetamine sulfate tablets and CYP2D6 inhibitors may increase the exposure of amphetamine sulfate tablets compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during amphetamine sulfate tablets initiation and after a dosage increase. If serotonin syndrome occurs, discontinue amphetamine sulfate tablets and the CYP2D6 inhibitor (see WARNING, OVERDOSAGE). Examples of CYP2D6 Inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir. Acidifying agents - Gastrointestinal acidifying agents (guanethidine, reserpine, glutamic acid HCl, ascorbic acid, fruit juices, etc.) lower absorption of amphetamines. Urinary acidifying agents (ammonium chloride, sodium acid phosphate, etc.) increase concentration of the ionized species of the amphetamine molecule, thereby increasing urinary excretion. Both groups of agents lower blood levels and efficacy of amphetamines. Adrenergic blockers - Adrenergic blockers are inhibited by amphetamines. Alkalinizing agents - Gastrointestinal alkalinizing agents (sodium bicarbonate, etc.) increase absorption of amphetamines. Urinary alkalinizing agents (acetazolamide, some thiazides) increase the concentration of the non-ionized species of the amphetamine molecule, thereby decreasing urinary excretion. Both groups of agents increase blood levels and therefore potentiate the action of amphetamines. Antidepressants tricyclic - Amphetamines may enhance the activity of tricyclic or sympathomimetic agents; d-amphetamine with desipramine or protriptyline and possibly other tricyclics cause striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Antihistamines - Amphetamines may counteract the sedative effect of antihistamines. Antihypertensives - Amphetamines may antagonize the hypotensive effects of antihypertensives. Chlorpromazine - Chlorpromazine blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamine, and can be used to treat amphetamine poisoning. Ethosuximide - Amphetamines may delay intestinal absorption of ethosuximide. Haloperidol - Haloperidol blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamines. Lithium carbonate - The antiobesity and stimulatory effects of amphetamines may be inhibited by lithium carbonate. Meperidine - Amphetamines potentiate the analgesic effect of meperidine. Methenamine therapy - Urinary excretion of amphetamines is increased, and efficacy is reduced by acidifying agents used in methenamine therapy. Norepinephrine - Amphetamines enhance the adrenergic effect of norepinephrine. Phenobarbital - Amphetamines may delay intestinal absorption of Phenobarbital. Co-administration of phenobarbital may produce a synergistic anticonvulsant action. Phenytoin - Amphetamines may delay intestinal absorption of phenytoin; co-administration of phenytoin may produce a synergistic anticonvulsant action. Propoxyphene - In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur. Veratrum alkaloids - Amphetamines inhibit the hypotensive effect of veratrum alkaloids."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Amphetamine sulfate tablets, USP are indicated for: Narcolepsy Attention Deficit Disorder with Hyperactivity 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 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 the 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 not be warranted. Exogenous Obesity as a short term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction for patients refractory to alternative therapy, e.g., repeated diets, group programs, and other drugs. The limited usefulness of amphetamines (see CLINICAL PHARMACOLOGY ) should be weighed against possible risks inherent in use of the drug, such as those described below."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Clinical Effects of Overdose Overdose of CNS stimulants is characterized by the following sympathomimetic effects: o Cardiovascular effects including tachyarrhythmias, and hypertension or hypotension. Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death. Takotsubo cardiomyopathy may develop. o CNS effect including psychomotor agitation, confusion, and hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur. o Life-threatening hyperthermia (temperatures greater than 104°F) and rhabdomyolysis may develop. Overdose Management Consider the possibility of multiple drug ingestion. D-amphetamine is not dialyzable. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations."}', 'active_flag': 'Y', 'generic_name': '{"AMPHETAMINE SULFATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNING Abuse, Misuse, and Addiction Amphetamine sulfate tablet has a high potential for abuse and misuse. The use of amphetamine sulfate tablets exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Amphetamine sulfate can be diverted for non-medical use into illicit channels or distribution (see DRUG ABUSE and DEPENDENCE ). Misuse and abuse of CNS stimulants, including amphetamine sulfate tablets, can result in overdose and death (see OVERDOSAGE ), and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. Before prescribing amphetamine sulfate tablets, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks and proper disposal of any unused drug. Advise patients to store amphetamine sulfate in a safe place, preferably locked, and instruct patients to not give amphetamine sulfate tablets to anyone else. Throughout amphetamine sulfate tablets treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction. Risks to Patients with Serious Cardiac Disease Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended ADHD dosages. Avoid amphetamine sulfate tablets use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. Increased Blood Pressure and Heart Rate CNS stimulants cause an increase in blood pressure (mean increase about 2 to 4 mm Hg) and heart rate (mean increase about 3 to 6 bpm). Monitor all patients for potential tachycardia and hypertension. Psychiatric Adverse Reactions Exacerbation of Pre-Existing Psychosis CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. Induction of a Manic Episode in Patients with Bipolar Disorder CNS stimulants may induce a manic or mixed episode in patients. Prior to initiating amphetamine sulfate tablets, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression). New Psychotic or Manic Symptoms CNS stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS-treated patients, compared with 0% of placebo-treated patients. If such symptoms occur, consider discontinuing amphetamine sulfate tablets. Long-Term Suppression of Growth in Pediatric Patients CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Closely monitor growth (weight and height) in amphetamine sulfate tablets-treated pediatric patients treated with CNS stimulants. Pediatric patients not growing or gaining height or weight as expected may need to have their treatment interrupted (see PRECAUTIONS , PEDIATRIC USE ). 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. Peripheral Vasculopathy, including Raynaud\'s phenomenon Stimulants, including amphetamine sulfate, 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 and at the therapeutic dosages of CNS stimulants in all age groups throughout the course of treatment. Signs and symptoms generally improved after dosage reduction or discontinuation of the CNS stimulant. Careful observation for digital changes is necessary during Amphetamine sulfate tablets treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy. Serotonin Syndrome Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John\'s Wort (see DRUG INTERACTIONS ). The co-administration with cytochrome P450 (CYP2D6) inhibitors may also increase the risk with increased exposure to amphetamine sulfate. In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 (see DRUG INTERACTIONS ). Serotonin syndrome 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). Concomitant use of amphetamine sulfate with MAOI drugs is contraindicated (see CONTRAINDICATIONS ). Discontinue treatment with amphetamine sulfate and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of amphetamine sulfate with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate amphetamine sulfate with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome. Motor and Verbal Tics, and Worsening of Tourette’s Syndrome CNS stimulants, including amphetamine sulfate, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette’s syndrome has also been reported. Assess the family history and clinically evaluate patients for tics or Tourette’s syndrome before initiating amphetamine sulfate tablets. Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome with amphetamine sulfate tablets, and discontinue treatment if clinically appropriate."}', 'precautions': '{"PRECAUTIONS General Caution is to be exercised in prescribing amphetamines for patients with even mild hypertension. Information for Patients Advise the patient to read the FDA-approved patient labeling (Medication Guide). Abuse, Misuse, and Addiction Educate patients and their families about the risks of abuse, misuse, and addiction of amphetamine sulfate tablets, which can lead to overdose and death, and proper disposal of any unused drug (see WARNINGS , DRUG ABUSE AND DEPENDENCE , and OVERDOSAGE ). Advise patients to store amphetamine sulfate tablets in a safe place, preferably locked, and instruct patients to not give amphetamine sulfate tablets to anyone else. Risks to Patients with Serious Cardiac Disease Advise patients that there are potential risks to patients with serious cardiac disease, including sudden death, with amphetamine sulfate tablets use. Instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease (see WARNINGS ). Increased Blood Pressure and Heart Rate Advise patients that amphetamine sulfate tablets can elevate blood pressure and heart rate (see WARNINGS ). Psychiatric Adverse Reactions Advise patients that amphetamine sulfate tablets, at recommended doses, can cause psychotic or manic symptoms, even in patients without prior history of psychotic symptoms or mania (see WARNINGS ). Long-Term Suppression of Growth in Pediatric Patients Advise patients that amphetamine sulfate tablets, may cause slowing of growth including weight loss (see WARNINGS ). Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud\'s phenomenon] • Instruct patients beginning treatment with amphetamine sulfate tablets 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 amphetamine sulfate tablets. • Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. Serotonin Syndrome Caution patients about the risk of serotonin syndrome with concomitant use of amphetamine sulfate tablets and other serotonergic drugs including SSRIs, SNRIs, 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 [see CONTRAINDICATIONS , WARNINGS , and DRUG INTERACTIONS ]. Advise patients to contact their healthcare provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome. Motor and Verbal Tics, and Worsening of Tourette’s Syndrome Advise patients that motor and verbal tics and worsening of Tourette’s Syndrome may occur during treatment with amphetamine sulfate tablets. Instruct the patients to notify their healthcare provider if emergence or worsening of tics or Tourette’s syndrome occurs (see WARNINGS ). Amphetamines may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or vehicle; the patient should therefore be cautioned accordingly. Drug Interactions MAO inhibitors - MAOI antidepressants, as well as a metabolic of furazolidone, slow amphetamine metabolism. This slowing potentiates amphetamines, increasing their effect on the release of norepinephrine and other monoamines from adrenergic nerve endings; this can cause headaches and other signs of hypertensive crisis. A variety of neurological toxic effects and malignant hyperpyrexia can occur, sometimes with fatal results. Serotonergic Drugs - The concomitant use of amphetamine sulfate tablets and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during amphetamine sulfate tablets initiation or dosage increase. If serotonin syndrome occurs, discontinue amphetamine sulfate tablets and the concomitant serotonergic drug(s) (see WARNING and PRECAUTIONS). CYP2D6 Inhibitors - The concomitant use of amphetamine sulfate tablets and CYP2D6 inhibitors may increase the exposure of amphetamine sulfate tablets compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during amphetamine sulfate tablets initiation and after a dosage increase. If serotonin syndrome occurs, discontinue amphetamine sulfate tablets and the CYP2D6 inhibitor (see WARNING, OVERDOSAGE). Examples of CYP2D6 Inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir. Acidifying agents - Gastrointestinal acidifying agents (guanethidine, reserpine, glutamic acid HCl, ascorbic acid, fruit juices, etc.) lower absorption of amphetamines. Urinary acidifying agents (ammonium chloride, sodium acid phosphate, etc.) increase concentration of the ionized species of the amphetamine molecule, thereby increasing urinary excretion. Both groups of agents lower blood levels and efficacy of amphetamines. Adrenergic blockers - Adrenergic blockers are inhibited by amphetamines. Alkalinizing agents - Gastrointestinal alkalinizing agents (sodium bicarbonate, etc.) increase absorption of amphetamines. Urinary alkalinizing agents (acetazolamide, some thiazides) increase the concentration of the non-ionized species of the amphetamine molecule, thereby decreasing urinary excretion. Both groups of agents increase blood levels and therefore potentiate the action of amphetamines. Antidepressants tricyclic - Amphetamines may enhance the activity of tricyclic or sympathomimetic agents; d-amphetamine with desipramine or protriptyline and possibly other tricyclics cause striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Antihistamines - Amphetamines may counteract the sedative effect of antihistamines. Antihypertensives - Amphetamines may antagonize the hypotensive effects of antihypertensives. Chlorpromazine - Chlorpromazine blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamine, and can be used to treat amphetamine poisoning. Ethosuximide - Amphetamines may delay intestinal absorption of ethosuximide. Haloperidol - Haloperidol blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamines. Lithium carbonate - The antiobesity and stimulatory effects of amphetamines may be inhibited by lithium carbonate. Meperidine - Amphetamines potentiate the analgesic effect of meperidine. Methenamine therapy - Urinary excretion of amphetamines is increased, and efficacy is reduced by acidifying agents used in methenamine therapy. Norepinephrine - Amphetamines enhance the adrenergic effect of norepinephrine. Phenobarbital - Amphetamines may delay intestinal absorption of Phenobarbital. Co-administration of phenobarbital may produce a synergistic anticonvulsant action. Phenytoin - Amphetamines may delay intestinal absorption of phenytoin; co-administration of phenytoin may produce a synergistic anticonvulsant action. Propoxyphene - In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur. Veratrum alkaloids - Amphetamines inhibit the hypotensive effect of veratrum alkaloids. Drug/Laboratory Test interactions Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations. Carcinogenesis/Mutagenesis Mutagenicity studies and long term studies in animals to determine the carcinogenic potential of amphetamine sulfate have not been performed. Pregnancy Teratogenic Effects Dextroamphetamine sulfate has been shown to have embryotoxic and teratogenic effects when administered to A/Jax mice and C57BL mice in doses approximately 41 times the maximum human dose. Embryotoxic effects were not seen in New Zealand white rabbits given the drug in doses 7 times the human dose nor in rats given 12.5 times the maximum human dose. There are no adequate and well-controlled studies in pregnant women. Amphetamine sulfate tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude. Nursing Mothers Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing Pediatric Use Long-term effects of amphetamines in children have not been well established. Amphetamines are not recommended for use as anorectic agents in children under 12 years of age, or in children under 3 years of age with Attention Deficit Disorder with Hyperactivity described under INDICATIONS AND USAGE. Clinical experience suggests that in psychotic children, administration of amphetamines may exacerbate symptoms of behavior disturbance and thought disorder. Data is inadequate to determine whether chronic administration of amphetamines may be associated with growth inhibition; therefore growth should be monitored during treatment. Drug Treatment is not indicated in all cases of Attention Deficit Disorder with Hyperactivity and should be considered only in light of the complete history and evaluation of the child. The decision to prescribe amphetamines 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 amphetamines is usually not indicated."}', 'information_for_patients': '{"Information for Patients Advise the patient to read the FDA-approved patient labeling (Medication Guide). Abuse, Misuse, and Addiction Educate patients and their families about the risks of abuse, misuse, and addiction of amphetamine sulfate tablets, which can lead to overdose and death, and proper disposal of any unused drug (see WARNINGS , DRUG ABUSE AND DEPENDENCE , and OVERDOSAGE ). Advise patients to store amphetamine sulfate tablets in a safe place, preferably locked, and instruct patients to not give amphetamine sulfate tablets to anyone else. Risks to Patients with Serious Cardiac Disease Advise patients that there are potential risks to patients with serious cardiac disease, including sudden death, with amphetamine sulfate tablets use. Instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease (see WARNINGS ). Increased Blood Pressure and Heart Rate Advise patients that amphetamine sulfate tablets can elevate blood pressure and heart rate (see WARNINGS ). Psychiatric Adverse Reactions Advise patients that amphetamine sulfate tablets, at recommended doses, can cause psychotic or manic symptoms, even in patients without prior history of psychotic symptoms or mania (see WARNINGS ). Long-Term Suppression of Growth in Pediatric Patients Advise patients that amphetamine sulfate tablets, may cause slowing of growth including weight loss (see WARNINGS ). Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud\'s phenomenon] • Instruct patients beginning treatment with amphetamine sulfate tablets 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 amphetamine sulfate tablets. • Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. Serotonin Syndrome Caution patients about the risk of serotonin syndrome with concomitant use of amphetamine sulfate tablets and other serotonergic drugs including SSRIs, SNRIs, 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 [see CONTRAINDICATIONS , WARNINGS , and DRUG INTERACTIONS ]. Advise patients to contact their healthcare provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome. Motor and Verbal Tics, and Worsening of Tourette’s Syndrome Advise patients that motor and verbal tics and worsening of Tourette’s Syndrome may occur during treatment with amphetamine sulfate tablets. Instruct the patients to notify their healthcare provider if emergence or worsening of tics or Tourette’s syndrome occurs (see WARNINGS ). Amphetamines may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or vehicle; the patient should therefore be cautioned accordingly."}', 'pregnancy': '{"Pregnancy Teratogenic Effects Dextroamphetamine sulfate has been shown to have embryotoxic and teratogenic effects when administered to A/Jax mice and C57BL mice in doses approximately 41 times the maximum human dose. Embryotoxic effects were not seen in New Zealand white rabbits given the drug in doses 7 times the human dose nor in rats given 12.5 times the maximum human dose. There are no adequate and well-controlled studies in pregnant women. Amphetamine sulfate tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude."}', 'pediatric_use': '{"Pediatric Use Long-term effects of amphetamines in children have not been well established. Amphetamines are not recommended for use as anorectic agents in children under 12 years of age, or in children under 3 years of age with Attention Deficit Disorder with Hyperactivity described under INDICATIONS AND USAGE. Clinical experience suggests that in psychotic children, administration of amphetamines may exacerbate symptoms of behavior disturbance and thought disorder. Data is inadequate to determine whether chronic administration of amphetamines may be associated with growth inhibition; therefore growth should be monitored during treatment. Drug Treatment is not indicated in all cases of Attention Deficit Disorder with Hyperactivity and should be considered only in light of the complete history and evaluation of the child. The decision to prescribe amphetamines 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 amphetamines is usually not indicated."}', 'geriatric_use': None}

{LANOLIN,PETROLATUM}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses helps treat and prevent diaper rash temporarily protects minor: cuts scrapes burns temporarily protects and helps relieve chapped, chafed or cracked skin and lips protect chafed skin due to diaper rash and helps seal out wetness"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"LANOLIN AND PETROLATUM"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if condition worsens symptoms last more 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 When using this product do not get into eyes Stop use and ask a doctor if condition worsens symptoms last more than 7 days or clear up and occur again within a few days Do not use on deep or puncture wounds . animal bites serious burns . 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}

{MENTHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses temporarily relieves: cough as may occur with a cold occasional minor irritation and sore throat"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{MENTHOL}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and consult doctor if cough persists for more than 7 days, tends to recur, or is accompanied by fever, rash, or persistent headache. These could be signs of a serious condition. sore throat is severe, or irritation, pain or redness lasts or worsens sore mouth does not improve in 7 days"}', 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings Sore throat warning: if sore throat is severe, persists for more than 2 days, is accompanied or followed by fever, headache, rash, swelling, nausea, or vomiting, consult a doctor promptly. If sore mouth symptoms do not improve in 7 days, see your dentist or doctor promptly. These symptoms may be serious."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{MENTHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses temporarily relieves: cough as may occur with a cold occasional minor irritation and sore throat"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{MENTHOL}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask doctor if cough persists for more than 7 days, tends to recur, or is accompanied by fever, rash, or persistent headache. These could be signs of a serious condition. sore throat is severe, or irritation, pain or redness lasts or worsens sore mouth does not improve in 7 days"}', 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings Sore throat warning: if sore throat is severe, persists for more than 2 days, is accompanied or followed by fever, headache, rash, swelling, nausea, or vomiting, consult a doctor promptly. If sore mouth symptoms do not improve in 7 days, see your dentist or doctor promptly. These symptoms may be serious."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"NAPROXEN SODIUM"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses temporarily relieves minor aches and pains due to: minor pain of arthritis muscular aches backache menstrual cramps headache toothache the common cold temporarily reduces fever"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"NAPROXEN SODIUM"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if side effects occur. You may report side effects to FDA at 1-800-FDA-1088. 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 pain gets worse or lasts more than 10 days fever gets worse or lasts more than 3 days you have difficulty swallowing it feels like the pill is stuck in your throat you develop heartburn redness or swelling is present in the painful area any new symptoms appear"}', 'do_not_use': '{"Do not use if you have ever had an allergic reaction to any other pain reliever/fever reducer right before or after heart surgery"}', 'when_using': '{"When using this product take with food or milk if stomach upset occurs long term continuous use may increase the risk of heart attack or stroke"}', 'warnings': '{"Warnings Allergy alert Naproxen sodium may cause a severe allergic reaction, especially in people allergic to aspirin. Symptoms may include: hives facial swelling asthma (wheezing) shock skin reddening rash blisters If an allergic reaction occurs, stop use and seek medical help right away. 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 Do not use if you have ever had an allergic reaction to any other pain reliever/fever reducer right before or after heart surgery Ask a doctor before use if 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 are taking a diuretic you have asthma you have problems or serious side effects from taking pain relievers or fever reducers Ask a doctor or pharmacist before use if you are under a doctor\'s care for any serious condition taking any other drug When using this product take with food or milk if stomach upset occurs long term continuous use may increase the risk of heart attack or stroke Stop use and ask a doctor if side effects occur. You may report side effects to FDA at 1-800-FDA-1088. 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 pain gets worse or lasts more than 10 days fever gets worse or lasts more than 3 days you have difficulty swallowing it feels like the pill is stuck in your throat you develop heartburn redness or swelling is present in the painful area any new symptoms appear If pregnant or breast-feeding, ask a health professional before use. It is especially important not to use naproxen sodium 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 right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"SODIUM FLUORIDE"}

{'contraindications': '{"CONTRAINDICATIONS Fluoride 1.0 mg Tablets are contraindicated when the fluoride content of drinking water is >0.3 ppm F¯ and should not be administered to pediatric patients under 6 years. Fluoride 0.5 mg Tablets are contraindicated when the fluoride content of drinking water is more than 0.6 ppm F¯ and should not be administered to pediatric patients under age 6 when the fluoride content of drinking water is 0.3 ppm F¯ or more or to pediatric patients under age 3 years. Fluoride 0.25 mg Tablets are contraindicated when the fluoride content of drinking water is more than 0.6 ppm F¯ and should not be administered to pediatric patients under age 3 years when the fluoride content of drinking water is 0.3 ppm F¯ or more. Do not administer Sodium Fluoride Chewable Tablets (any strength) to pediatric patients under age 3 years. Sodium Fluoride Chewable Tablets (any strength) are not indicated for use in adults."}', 'adverse_reactions': '{"ADVERSE REACTIONS Allergic rash and other idiosyncrasies have been rarely reported."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE For once daily self-applied systemic use as a dental caries preventive in pediatric patients. It has been established that ingestion of fluoridated drinking water (1 ppm F¯) during the period of tooth development results in a significant decrease in the incidence of dental caries. Sodium Fluoride Chewable Tablets were developed to provide systemic fluoride for use as a supplement in pediatric patients from age 3 years to age 16 years and older living in areas where the drinking water fluoride contents does not exceed 0.6 ppm F¯."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"SODIUM FLUORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNING Prolonged daily ingestion of quantities greater than the recommended amount may result in various degrees of dental fluorosis in pediatric patients under age 6 years, especially if the water fluoridation exceeds 0.6 ppm. Read directions carefully before using. This product, as all chewable tablets, is not recommended for children under age 3 due to risk of choking. Keep out of the reach of infants and children."}', 'precautions': '{"PRECAUTIONS General Please refer to the CONTRAINDICATIONS , WARNINGS and OVERDOSAGE sections for overdosage concerns. Use in pediatric patients below the age of 3 years is not recommended by current American Dental Associations and American Academy of Pediatrics guidelines. Carcinogenesis, Mutagenesis, Impairment of Fertility In a study conducted in rodents, no carcinogenesis was found in male and female rats treated with fluoride at dose levels ranging from 4.1 to 9.1 mg/kg of body weight. Equivocal evidence of carcinogenesis was reported for male rats treated with 2.5 and 4.1 mg/kg of body weight. In a second study, no carcinogenesis was observed in rats, males or females, treated with fluoride up to 11.3 mg/kg of body weight. This dose is at least 400 times greater than the recommended daily dose of Sodium Fluoride Chewable Tablets. Fluoride ion is not mutagenic in standard bacterial systems. It has been shown that fluoride ion has potential to induce chromosome aberrations in cultured human and rodentcells at does much higher than those to which humans are exposed. In vivo data is conflicting. Some studies report chromosome damage in rodents while other studies using similar protocols report negative results. Potential adverse reproductive effects of fluoride exposure in humans has not been adequately evaluated. Adverse effects on reproduction were reported for rats, mice, fox, and cattle exposed to 100 ppm or greater concentrations of fluoride in their diet or drinking water. Other studies conducted in rats demonstrated that lower doses of fluoride (5 mg/kg of body weight) did not result in impaired fertility and reproductive capabilities. This dose is approximately 200 times greater than the recommended daily dose of Sodium Fluoride Chewable Tablets. Pregnancy Teratogenic Effects Pregnancy Category B It has been shown that fluoride crosses the placenta of rats, but only 0.01% of the amount administered is incorporated in fetal tissue. Animal studies (rats, mice, rabbits) have shown that fluoride is not a teratogen. Maternal exposure to 12.2 mg fluoride/kg of body weight (rats) or 13.1 mg/kg of body weight (rabbits) did not affect the litter size or fetal weight and did not increase the frequency of skeletal or visceral malformations. Epidemiological studies conducted in areas with high levels of naturally fluoridated water showed no increase in birth defects. Heavy exposure to fluoride during in utero development may result in skeletal fluorosis which becomes evident in childhood. Nursing Mothers It is not known if fluoride is excreted in human milk. However, many drugs are excreted in human milk and caution should be exercised when Sodium Fluoride Chewable Tablets are administered to a nursing woman. Reduced milk production was reported in farm raised fox when the animals were fed a diet containing a high concentration of fluoride (98-137 mg/kg of body weight). No adverse effects on parturition, lactation, or offspring were seen in rats administered fluoride up to 5 mg/kg of body weight. This dose is at least 200 times greater than the recommended daily dose of Sodium Fluoride Chewable Tablets. Geriatric Use Sodium Fluoride Chewable Tablets (any strength) are not indicated for use in geriatric patients. Pediatric Use The use of Sodium Fluoride Chewable Tablets as a caries preventive in pediatric age groups 3 years to 16 years is supported by evidence from adequate and well controlled studies on fluoride supplementation from birth through adolescence."}', 'information_for_patients': None, 'pregnancy': '{"Pregnancy Teratogenic Effects Pregnancy Category B It has been shown that fluoride crosses the placenta of rats, but only 0.01% of the amount administered is incorporated in fetal tissue. Animal studies (rats, mice, rabbits) have shown that fluoride is not a teratogen. Maternal exposure to 12.2 mg fluoride/kg of body weight (rats) or 13.1 mg/kg of body weight (rabbits) did not affect the litter size or fetal weight and did not increase the frequency of skeletal or visceral malformations. Epidemiological studies conducted in areas with high levels of naturally fluoridated water showed no increase in birth defects. Heavy exposure to fluoride during in utero development may result in skeletal fluorosis which becomes evident in childhood."}', 'pediatric_use': '{"Pediatric Use The use of Sodium Fluoride Chewable Tablets as a caries preventive in pediatric age groups 3 years to 16 years is supported by evidence from adequate and well controlled studies on fluoride supplementation from birth through adolescence."}', 'geriatric_use': '{"Geriatric Use Sodium Fluoride Chewable Tablets (any strength) are not indicated for use in geriatric patients."}'}

{"NAPROXEN SODIUM"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses ■ temporarily relieves minor aches and pains due to: ■ headache ■ backache ■ muscular aches ■ the common cold ■ toothache ■ menstrual cramps ■ minor pain of arthritis ■ temporarily reduces fever"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"NAPROXEN SODIUM"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if ■ side effects occur. You may report side effects to FDA at 1-800-FDA-1088. ■ 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 ■ pain gets worse or lasts more than 10 days ■ fever gets worse or lasts more than 3 days ■ you have difficulty swallowing ■ it feels like the pill is stuck in your throat ■ redness or swelling is present in the painful area ■ any new symptoms appear"}', 'do_not_use': '{"Do not use ■ if you have ever had an allergic reaction to any other pain reliever/fever reducer ■ right before or after heart surgery"}', 'when_using': '{"When using this product ■ take with food or milk if stomach upset occurs ■ the risk of heart attack or stroke may increase if you use more than directed or for longer than directed"}', 'warnings': '{"Warnings Allergy alert: Naproxen sodium may cause a severe allergic reaction, especially in people allergic to aspirin. Symptoms may include: ■ hives ■ asthma (wheezing) ■ skin reddening ■ facial swelling ■ shock ■ rash ■ blisters If an allergic reaction occurs, stop use and seek medical help right away. 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 Do not use ■ if you have ever had an allergic reaction to any other pain reliever/fever reducer ■ right before or after heart surgery Ask a doctor before use if ■ the 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 are taking a diuretic ■ you have problems or serious side effects from taking pain relievers or fever reducers ■ you have asthma Ask a doctor or pharmacist before use if you are ■ under a doctor\'s care for any serious condition ■ taking any other drug When using this product ■ take with food or milk if stomach upset occurs ■ the risk of heart attack or stroke may increase if you use more than directed or for longer than directed Stop use and ask a doctor if ■ side effects occur. You may report side effects to FDA at 1-800-FDA-1088. ■ 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 ■ pain gets worse or lasts more than 10 days ■ fever gets worse or lasts more than 3 days ■ you have difficulty swallowing ■ it feels like the pill is stuck in your throat ■ redness or swelling is present in the painful area ■ any new symptoms appear If pregnant or breast-feeding , ask a health professional before use. It is especially important not to use naproxen sodium 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 right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{TOLNAFTATE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses ● proven clinically effective in the treatment of most athlete\'s foot (tinea pedis), and ringworm (tinea corporis) ● helps prevent most athlete\'s foot with daily use ● for effective relief of itching, burning and cracking."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{TOLNAFTATE}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings For external use only. When using this product avoid contact with the eyes. Stop use and ask a doctor if ● irritation occurs ● there is no improvement within 4 weeks Do not use on children under 2 years of age except under the advice and supervision of a doctor."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{ALCOHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses For hand washing to decrease the bacteria on skin. Recommended for repeated use"}', '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 condition persists for more than 72 hours"}', 'do_not_use': '{"Do not use in the eyes. In case of contact, flush eyes with water."}', 'when_using': None, 'warnings': '{"Warnings For external use only Flammable, keep away from fire or flame. Do not use in the eyes. In case of contact, flush eyes with water. Stop use and ask a doctor if irritation and redness develop condition persists 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}

{ALCOHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use Hand Sanitizer to help reduce bacteria that potentially can cause disease. For use when soap and water are 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 or rash occurs. These may be signs of a serious condition."}', 'do_not_use': '{"Do not use in children less than 2 months of age on open skin wounds"}', 'when_using': '{"When using this product keep out of eyes, ears, and mouth. In case of contact with eyes, rinse eyes thoroughly with water. Stop use and ask a doctor if irritation or rash occurs. These may be signs of a serious condition. Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away."}', 'warnings': '{"Warnings For external use only. Flammable. Keep away from heat or flame"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{ERYTHROMYCIN}

{'contraindications': '{"CONTRAINDICATIONS Erythromycin Topical Gel USP, 2% is contraindicated in those individuals who have shown hypersensitivity to any of its components."}', 'adverse_reactions': '{"ADVERSE REACTIONS In controlled clinical trials, the incidence of burning associated with erythromycin topical gel USP, 2% was approximately 25%. The following additional local adverse reactions have been reported occasionally: peeling, dryness, itching, erythema, and oiliness. Irritation of the eyes and tenderness of the skin have also been reported with the topical use of erythromycin. A generalized urticarial reaction, possibly related to the use of erythromycin, which required systemic steroid therapy has been reported."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE Erythromycin Topical Gel USP, 2% is indicated for the topical treatment of acne vulgaris."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{ERYTHROMYCIN}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Pseudomembranous colitis has been reported with nearly all antibacterial agents, including erythromycin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of “antibiotic-associated colitis”. After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. 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 topical 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. Avoid contact with eyes and all mucous membranes. The use of antibiotic agents may be associated with the overgrowth of antibiotic-resistant organisms. If this occurs, discontinue use and take appropriate measures. Information For Patients - Patients using Erythromycin Topical Gel USP, 2% should receive the following information and instructions: 1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes, nose, mouth, and all mucous membranes. 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 medication unless otherwise directed by their physician. 4. Patients should report to their physician any signs of local adverse reactions. Carcinogenesis, Mutagenesis, Impairment of Fertility - No animal studies have been performed to evaluate carcinogenic and mutagenic potential, or effects on fertility of topical erythromycin. However, long-term (2-year) oral studies in rats with erythromycin ethylsuccinate and erythromycin base did not provide evidence of tumorigenicity. There was no apparent effect on male or female fertility in rats fed erythromycin (base) at levels up to 0.25% of diet . Pregnancy: Teratogenic Effects: Pregnancy Category B - There was no evidence of teratogenicity or any other adverse effect on reproduction in female rats fed erythromycin base (up to 0.25% of diet) prior to and during mating, during gestation and through weaning of two successive litters. 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 in pregnancy only if clearly needed. Erythromycin has been reported to cross the placental barrier in humans, but fetal plasma levels are generally low. Nursing Women - It is not known whether erythromycin is excreted in human milk after topical application. However, erythromycin is excreted in human milk following oral and parenteral erythromycin administration. Therefore, caution should be exercised when erythromycin is administered to a nursing woman. Pediatric Use - Safety and effectiveness in pediatric patients have not been established. KEEP OUT OF REACH OF CHILDREN."}', 'information_for_patients': '{"Information For Patients - Patients using Erythromycin Topical Gel USP, 2% should receive the following information and instructions: 1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes, nose, mouth, and all mucous membranes. 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 medication unless otherwise directed by their physician. 4. Patients should report to their physician any signs of local adverse reactions."}', 'pregnancy': '{"Pregnancy: Teratogenic Effects: Pregnancy Category B - There was no evidence of teratogenicity or any other adverse effect on reproduction in female rats fed erythromycin base (up to 0.25% of diet) prior to and during mating, during gestation and through weaning of two successive litters. 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 in pregnancy only if clearly needed. Erythromycin has been reported to cross the placental barrier in humans, but fetal plasma levels are generally low."}', 'pediatric_use': '{"Pediatric Use - Safety and effectiveness in pediatric patients have not been established. KEEP OUT OF REACH OF CHILDREN."}', '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, 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 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 right away (1-800-222-1222)."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{LINEZOLID}

{'contraindications': '{"4 CONTRAINDICATIONS • Known hypersensitivity to linezolid or any of the other product components. ( 4.1 ) • Patients taking any monoamine oxidase inhibitors (MAOI) or within two weeks of taking an MAOI. ( 4.2 ) 4.1 Hypersensitivity Linezolid formulations are contraindicated for use in patients who have known hypersensitivity to linezolid or any of the other product components . 4.2 Monoamine Oxidase Inhibitors Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g., phenelzine, isocarboxazid) or within two weeks of taking any such medicinal product."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS Most common adverse reactions (>5% of adult and/or pediatric patients treated with linezolid) include: diarrhea, vomiting, headache, nausea, and anemia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Annora Pharma Private Limited at 1-886-495-1995 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. Adults The safety of linezolid formulations was evaluated in 2,046 adult patients enrolled in seven Phase 3 comparator-controlled clinical trials, who were treated for up to 28 days. Of the patients treated for uncomplicated skin and skin structure infections (uSSSIs), 25.4% of linezolid -treated and 19.6% of comparator-treated patients experienced at least one drug-related adverse event. For all other indications, 20.4% of linezolid -treated and 14.3% of comparator-treated patients experienced at least one drug-related adverse event. Table 2 shows the incidence of all-causality, treatment-emergent adverse reactions reported in at least 1% of adult patients in these trials by dose of linezolid. Table 2. Incidence (%) of Treatment–Emergent Adverse Reactions Occurring in >1% of Adult Patients Treated with Linezolid in Comparator-Controlled Clinical Trials ADVERSE REACTIONS Uncomplicated Skin and Skin Structure Infections All Other Indications Linezolid 400 mg by mouth every 12 hours (n=548) Clarithromycin 250 mg by mouth every 12 hours (n=537) Linezolid 600 mg every 12 hours (n=1498) All Other Comparators * (n=1464) Headache 8.8 8.4 5.7 4.4 Diarrhea 8.2 6.1 8.3 6.4 Nausea 5.1 4.5 6.6 4.6 Vomiting 2 1.5 4.3 2.3 Dizziness 2.6 3 1.8 1.5 Rash 1.1 1.1 2.3 2.6 Anemia 0.4 0 2.1 1.4 Taste alteration 1.8 2 1 0.3 Vaginal moniliasis 1.8 1.3 1.1 0.5 Oral moniliasis 0.5 0 1.7 1 Abnormal liver function tests 0.4 0.2 1.6 0.8 Fungal infection 1.5 0.2 0.3 0.2 Tongue discoloration 1.3 0 0.3 0 Localized abdominal pain 1.3 0.6 1.2 0.8 Generalized abdominal pain 0.9 0.4 1.2 1 * Comparators included cefpodoxime proxetil 200 mg by mouth every 12 hours; ceftriaxone 1 g intravenously every 12 hours; dicloxacillin 500 mg by mouth every 6 hours; oxacillin 2 g intravenously every 6 hours; vancomycin 1 g intravenously every 12 hours. Of the patients treated for uSSSIs, 3.5% of linezolid -treated and 2.4% of comparator-treated patients discontinued treatment due to drug-related adverse events. For all other indications, discontinuations due to drug-related adverse events occurred in 2.1% of linezolid -treated and 1.7% of comparator-treated patients. The most common reported drug-related adverse events leading to discontinuation of treatment were nausea, headache, diarrhea, and vomiting. Pediatric Patients The safety of linezolid formulations was evaluated in 215 pediatric patients ranging in age from birth through 11 years, and in 248 pediatric patients aged 5 through 17 years (146 of these 248 were age 5 through 11 and 102 were age 12 to 17). These patients were enrolled in two Phase 3 comparator-controlled clinical trials and were treated for up to 28 days. In the study of hospitalized pediatric patients (birth through 11 years) with Gram-positive infections, who were randomized 2 to 1 (linezolid: vancomycin), mortality was 6% (13/215) in the linezolid arm and 3 % (3/101) in the vancomycin arm. However, given the severe underlying illness in the patient population, no causality could be established. Of the pediatric patients treated for uSSSIs, 19.2% of linezolid-treated and 14.1% of comparator-treated patients experienced at least one drug-related adverse event. For all other indications, 18.8% of linezolid -treated and 34.3% of comparator-treated patients experienced at least one drug-related adverse event. Table 3 shows the incidence of all-causality, treatment-emergent adverse reactions reported in more than 1% of pediatric patients (and more than 1 patient) in either treatment group in the comparator-controlled Phase 3 trials. Table 3. Incidence (%) of Treatment-Emergent Adverse Reactions Occurring in > 1% of Pediatric Patients (and >1 Patient) in Either Treatment Group in Comparator-Controlled Clinical Trials ADVERSE REACTIONS Uncomplicated Skin and Skin Structure Infections * All Other Indications † Linezolid (n=248) Cefadroxil (n=251) Linezolid (n=215) Vancomycin (n=101) Diarrhea 7.8 8 10.8 12.1 Vomiting 2.9 6.4 9.4 9.1 Headache 6.5 4 0.9 0 Anemia 0 0 5.6 7.1 Thrombocytopenia 0 0 4.7 2 Nausea 3.7 3.2 1.9 0 Generalized abdominal pain 2.4 2.8 0.9 2 Localized abdominal pain 2.4 2.8 0.5 1 Loose stools 1.6 0.8 2.3 3 Eosinophilia 0.4 0.8 1.9 1 Pruritus at non-application site 0.8 0.4 1.4 2 Vertigo 1.2 0.4 0 0 * Patients 5 through 11 years of age received linezolid 1 0 mg/kg by mouth every 12 hours or cefadroxil 15 mg/kg by mouth every 12 hours. Patients 12 years or older received linezolid 600 mg by mouth every 12 hours or cefadroxil 500 mg by mouth every 12 hours. † Patients from birth through 11 years of age received linezolid 10 mg/kg intravenously by mouth every 8 hours or vancomycin 10 to 15 mg/kg intravenously every 6 to 24 hours, depending on age and renal clearance. Of the pediatric patients treated for uSSSIs, 1.6% of linezolid-treated and 2.4% of comparator-treated patients discontinued treatment due to drug-related adverse events. For all other indications, discontinuations due to drug-related adverse events occurred in 0.9% of linezolid-treated and 6.1% of comparator-treated patients. Laboratory Abnormalities Linezolid has been associated with thrombocytopenia when used in doses up to and including 600 mg every 12 hours for up to 28 days. In Phase 3 comparator-controlled trials, the percentage of adult patients who developed a substantially low platelet count (defined as less than 75% of lower limit of normal and/or baseline) was 2.4% (range among studies: 0.3 to 10%) with linezolid and 1.5% (range among studies: 0.4 to 7%) with a comparator. In a study of hospitalized pediatric patients ranging in age from birth through 11 years, the percentage of patients who developed a substantially low platelet count (defined as less than 75% of lower limit of normal and/or baseline) was 12.9% with linezolid and 13.4% with vancomycin. In an outpatient study of pediatric patients aged from 5 through 17 years, the percentage of patients who developed a substantially low platelet count was 0% with linezolid and 0.4% with cefadroxil. Thrombocytopenia associated with the use of linezolid appears to be dependent on duration of therapy (generally greater than 2 weeks of treatment). The platelet counts for most patients returned to the normal range/baseline during the follow-up period. No related clinical adverse events were identified in Phase 3 clinical trials in patients developing thrombocytopenia. Bleeding events were identified in thrombocytopenic patients in a compassionate use program for linezolid; the role of linezolid in these events cannot be determined [ see Warnings and Precautions (5.1) ]. Changes seen in other laboratory parameters, without regard to drug relationship, revealed no substantial differences between linezolid and the comparators. These changes were generally not clinically significant, did not lead to discontinuation of therapy, and were reversible. The incidence of adult and pediatric patients with at least one substantially abnormal hematologic or serum chemistry value is presented in Tables 4, 5, 6, and 7. Table 4. Percent of Adult Patients who Experienced at Least One Substantially Abnormal * Hematology Laboratory Value in Comparator-Controlled Clinical Trials with Linezolid Laboratory Assay Uncomplicated Skin and Skin Structure Infections All Other Indications Linezolid 400 mg every 12 hours Clarithromycin 250 mg every 12 hours Linezolid 600 mg every 12 hours All Other Comparators † Hemoglobin (g/dL) 0.9 0 7.1 6.6 Platelet count (x 10 3 /mm 3 ) 0.7 0.8 3 1.8 WBC (x 10 3 /mm 3 ) 0.2 0.6 2.2 1.3 Neutrophils (x 10 3 /mm 3 ) 0 0.2 1.1 1.2 * < 75% (<50% for neutrophils) of Lower Limit of Normal (LLN) for values normal at baseline; <75% (<50% for neutrophils) of LLN and of baseline for values abnormal at baseline. † Comparators included cefpodoxime proxetil 200 mg by mouth every 12 hours; ceftriaxone 1 g intravenously every 12 hours; dicloxacillin 500 mg by mouth every 6 hours; oxacillin 2 g intravenously every 6 hours; vancomycin 1 g intravenously every 12 hours. Table 5. Percent of Adult Patients who Experienced at Least One Substantially Abnormal * Serum Chemistry Laboratory Value in Comparator-Controlled Clinical Trials with Linezolid Laboratory Assay Uncomplicated Skin and Skin Structure Infections All Other Indications Linezolid 400 mg every 12 hours Clarithromycin 250 mg every 12 hours Linezolid 600 mg every 12 hours All Other Comparators † AST (U/L) 1.7 1.3 5 6.8 ALT (U/L) 1.7 1.7 9.6 9.3 LDH (U/L) 0.2 0.2 1.8 1.5 Alkaline phosphatase (U/L) 0.2 0.2 3.5 3.1 Lipase (U/L) 2.8 2.6 4.3 4.2 Amylase (U/L) 0.2 0.2 2.4 2 Total bilirubin (mg/dL) 0.2 0 0.9 1.1 BUN (mg/dL) 0.2 0 2.1 1.5 Creatinine (mg/dL) 0.2 0 0.2 0.6 * > 2 x Upper Limit of Normal (ULN) for values normal at baseline; > 2 x ULN and >2 x baseline for values abnormal at baseline. † Comparators included cefpodoxime proxetil 200 mg by mouth every 12 hours; ceftriaxone 1 g intravenously every 12 hours; dicloxacillin 500 mg by mouth every 6 hours; oxacillin 2 g intravenously every 6 hours; vancomycin 1 g intravenously every 12 hours. Table 6. Percent of Pediatric Patients who Experienced at Least One Substantially Abnormal * Hematology Laboratory Value in Comparator-Controlled Clinical Trials with Linezolid Laboratory Assay Uncomplicated Skin and Skin Structure Infections † All Other Indications ‡ Linezolid Cefadroxil Linezolid Vancomycin Hemoglobin (g/dL) 0 0 15.7 12.4 Platelet count (x 10 3 /mm 3 ) 0 0.4 12.9 13.4 WBC (x 10 3 /mm 3 ) 0.8 0.8 12.4 10.3 Neutrophils (x 10 3 /mm 3 ) 1.2 0.8 5.9 4.3 * < 75% (<50% for neutrophils) of Lower Limit of Normal (LLN) for values normal at baseline; < 75% (<50% for neutrophils) of LLN and <75% (<50% for neutrophils, <90% for hemoglobin if baseline <LLN) of baseline for values abnormal at baseline. † Patients 5 through 11 years of age received linezolid 10 mg/kg by mouth every 12 hours or cefadroxil 15 mg/kg by mouth every 12 hours. Patients 12 years or older received linezolid 600 mg by mouth every 12 hours or cefadroxil 500 mg by mouth every 12 hours. ‡ Patients from birth through 11 years of age received linezolid 10 mg/kg intravenously by mouth every 8 hours or vancomycin 10 to 15 mg/kg intravenously every 6 to 24 hours, depending on age and renal clearance. Table 7. Percent of Pediatric Patients who Experienced at Least One Substantially Abnormal * Serum Chemistry Laboratory Value in Comparator-Controlled Clinical Trials with Linezolid Laboratory Assay Uncomplicated Skin and Skin Structure Infections † All Other Indications ‡ Linezolid Cefadroxil Linezolid Vancomycin ALT (U/L) 0 0 10.1 12.5 Lipase (U/L) 0.4 1.2 --- --- Amylase (U/L) --- --- 0.6 1.3 Total bilirubin (mg/dL) --- --- 6.3 5.2 Creatinine (mg/dL) 0.4 0 2.4 1 * >2 x Upper Limit of Normal (ULN) for values normal at baseline; >2 x ULN and >2 (>1.5 for total bilirubin) x baseline for values abnormal at baseline. † Patients 5 through 11 years of age received linezolid 10 mg/kg by mouth every 12 hours or cefadroxil 15 mg/kg by mouth every 12 hours. Patients 12 years or older received linezolid 600 mg mouth every 12 hours or cefadroxil 500 mg by mouth every 12 hours. ‡ Patients from birth through 11 years of age received linezolid 10 mg/kg intravenously/by mouth every 8 hours or vancomycin 10 to 15 mg/kg intravenously every 6 to 24 hours, depending on age and renal clearance. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of linezolid. 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: Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia). Thrombocytopenia has been reported more often in patients with severe renal impairment and in patients with moderate to severe hepatic impairment [ see Warnings and Precautions (5.1) ]; sideroblastic anemia. Peripheral neuropathy, and optic neuropathy sometimes progressing to loss of vision [ see Warnings and Precautions (5.2) ]. Lactic acidosis [ see Warnings and Precautions (5.7) ]. Although these reports have primarily been in patients treated for longer than the maximum recommended duration of 28 days, these events have also been reported in patients receiving shorter courses of therapy. Serotonin syndrome has been reported in patients receiving concomitant serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and opioids, and linezolid [ see Warnings and Precautions (5.3) ]. Convulsions [ see Warnings and Precautions (5.8) ]. Anaphylaxis, angioedema, bullous skin disorders including severe cutaneous adverse reactions (SCAR) such as toxic epidermal necrolysis and Stevens-Johnson syndrome, and hypersensitivity vasculitis. Superficial tooth discoloration and tongue discoloration have been reported with the use of linezolid. The tooth discoloration was removable with professional dental cleaning (manual descaling) in cases with known outcome. Hypoglycemia, including symptomatic episodes [ see Warnings and Precautions (5.9) ]. Hyponatremia and/or Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) [ see Warnings and Precautions (5.10) ]."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Monoamine oxidase inhibitors and potential for interaction with adrenergic and serotonergic agents. ( 4.2 , 5.3 , 5.6 , 7 , 12.3 ) 7.1 Monoamine Oxidase Inhibitors Linezolid is a reversible, nonselective inhibitor of monoamine oxidase [ see Contraindications (4.2) and Clinical Pharmacology (12.3) ]. 7.2 Adrenergic and Serotonergic Agents Linezolid has the potential for interaction with adrenergic and serotonergic agents [ see Warnings and Precautions (5.3, 5.6 ) and Clinical Pharmacology (12.3) ]."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Linezolid for oral suspension is an oxazolidinone-class antibacterial indicated in adults and children for the treatment of the following infections caused by susceptible Gram-positive bacteria: Nosocomial pneumonia ( 1.1 ); Community-acquired pneumonia ( 1.2 ); Complicated skin and skin structure infections, including diabetic foot infections, without concomitant osteomyelitis ( 1.3 ); Uncomplicated skin and skin structure infections ( 1.4 ); Vancomycin-resistant Enterococcus faecium infections. ( 1.5 ) Limitations of Use ( 1.6 ): • Linezolid for oral suspension is not indicated for the treatment of Gram-negative infections. • The safety and efficacy of linezolid formulations given for longer than 28 days have not been evaluated in controlled clinical trials. To reduce the development of drug-resistant bacteria and maintain the effectiveness of linezolid formulations and other antibacterial drugs, linezolid should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1.7 ) 1.1 Nosocomial Pneumonia Linezolid for oral suspension is indicated for the treatment of nosocomial pneumonia caused by Staphylococcus aureus (methicillin-susceptible and -resistant isolates) or Streptococcus pneumoniae [ see Clinical Studies (14) ]. 1.2 Community-acquired Pneumonia Linezolid for oral suspension is indicated for the treatment of community-acquired pneumonia caused by Streptococcus pneumoniae , including cases with concurrent bacteremia, or Staphylococcus aureus (methicillin-susceptible isolates only) [ see Clinical Studies (14) ]. 1.3 Complicated Skin and Skin Structure Infections Linezolid for oral suspension is indicated for the treatment of complicated skin and skin structure infections, including diabetic foot infections, without concomitant osteomyelitis, caused by Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus pyogenes , or Streptococcus agalactiae . Linezolid for oral suspension has not been studied in the treatment of decubitus ulcers [ see Clinical Studies (14) ]. 1.4 Uncomplicated Skin and Skin Structure Infections Linezolid for oral suspension is indicated for the treatment of uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible isolates only) or Streptococcus pyogenes [ see Clinical Studies (14) ]. 1.5 Vancomycin-resistant Enterococcus faecium Infections Linezolid for oral suspension is indicated for the treatment of vancomycin-resistant Enterococcus faecium infections, including cases with concurrent bacteremia [ see Clinical Studies (14) ]. 1.6 Limitations of Use Linezolid for oral suspension is not indicated for the treatment of Gram-negative infections. It is critical that specific Gram-negative therapy be initiated immediately if a concomitant Gram-negative pathogen is documented or suspected [ see Warnings and Precautions (5.4) ]. The safety and efficacy of linezolid for oral suspension formulations given for longer than 28 days have not been evaluated in controlled clinical trials [ see Clinical Studies (14) ]. 1.7 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of linezolid for oral suspension and other antibacterial drugs, linezolid for oral suspension 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': '{"5 WARNINGS AND PRECAUTIONS Myelosuppression: Monitor complete blood counts weekly. Thrombocytopenia has been reported more often in patients with severe renal and in patients with moderate to severe hepatic impairment. Consider discontinuation in patients who develop or have worsening myelosuppression. ( 5.1 ) Peripheral and Optic Neuropathy: Reported primarily in patients treated for longer than 28 days. If patients experience symptoms of visual impairment, prompt ophthalmic evaluation is recommended. ( 5.2 ) Serotonin Syndrome: Monitor patients taking serotonergic agents, including antidepressants and opioids, for signs of serotonin syndrome. Patients taking serotonergic antidepressants should receive linezolid for oral suspension only if no other therapies are available. Discontinue serotonergic antidepressants and monitor patients for signs and symptoms of both serotonin syndrome and antidepressant discontinuation. ( 5.3 ) A mortality imbalance was seen in an investigational study in linezolid-treated patients with catheter-related bloodstream infections. ( 5.4 ) Clostridioides difficile- Associated Diarrhea: Evaluate if diarrhea occurs. ( 5.5 ) Potential interactions producing elevation of blood pressure: monitor blood pressure. ( 5.6 ) Hypoglycemia: Postmarketing cases of symptomatic hypoglycemia have been reported in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents. ( 5.9 ) Hyponatremia and/or Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH): Monitor serum sodium levels regularly in patients at risk of hyponatremia and/or SIADH. ( 5.10 ) Phenylketonuria: Linezolid for oral suspension contains phenylalanine which can be harmful to patients with phenylketonuria. ( 5.11 ) 5.1 Myelosuppression Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported in patients receiving linezolid. In cases where the outcome is known, when linezolid was discontinued, the affected hematologic parameters have risen toward pretreatment levels. Thrombocytopenia has been reported more often in patients with severe renal impairment, whether or not on dialysis, and in patients with moderate to severe hepatic impairment.Completeblood counts should be monitored weekly in patients who receive linezolid, particularly in those who receive linezolid for longer than two weeks, those with pre-existing myelosuppression, those with severe renal impairment or moderate to severe hepatic impairment, those receiving concomitant drugs that produce bone marrow suppression, or those with a chronic infection who have received previous or concomitant antibacterial drug therapy. Discontinuation of therapy with linezolid should be considered in patients who develop or have worsening myelosuppression [see Adverse Reactions ( 6.2 )]. 5.2 Peripheral and Optic Neuropathy Peripheral and optic neuropathies have been reported in patients treated with linezolid, primarily in those patients treated for longer than the maximum recommended duration of 28 days. In cases of optic neuropathy that progressed to loss of vision, patients were treated for extended periods beyond the maximum recommended duration. Visual blurring has been reported in some patients treated with linezolid for less than 28 days. Peripheral and optic neuropathy has also been reported in children. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision, or visual field defect, prompt ophthalmic evaluation is recommended. Visual function should be monitored in all patients taking linezolid for extended periods (≥ 3 months) and in all patients reporting new visual symptoms regardless of length of therapy with linezolid. If peripheral or optic neuropathy occurs, the continued use of linezolid in these patients should be weighed against the potential risks. 5.3 Serotonin Syndrome Spontaneous reports of serotonin syndrome including fatal cases associated with the co-administration of linezolid and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs), have been reported. Unless clinically appropriate and patients are carefully observed for signs and/or symptoms of serotonin syndrome or neuroleptic malignant syndrome-like (NMS-like) reactions, linezolid should not be administered to patients with carcinoid syndrome and/or patients taking any of the following medications: serotonin re-uptake inhibitors, tricyclic antidepressants, bupropion, buspirone, serotonin 5-HT1 receptor agonists (triptans), and opioids, including meperidine [see Drug Interactions ( 7 ) and Clinical Pharmacology ( 12.3 )]. In some cases, a patient already receiving a serotonergic antidepressant or buspirone may require urgent treatment with linezolid. If alternatives to linezolid are not available and the potential benefits of linezolid outweigh the risks of serotonin syndrome or NMS-like reactions, the serotonergic antidepressant should be stopped promptly and linezolid administered. The patient should be monitored for two weeks (five weeks if fluoxetine was taken) or until 24 hours after the last dose of linezolid, whichever comes first. Symptoms of serotonin syndrome or NMS-like reactions include hyperthermia, rigidity, myoclonus, autonomic instability, and mental status changes that include extreme agitation progressing to delirium and coma. The patient should also be monitored for discontinuation symptoms of the antidepressant (see package insert of the specified agent(s) for a description of the associated discontinuation symptoms). 5.4 Mortality Imbalance in an Investigational Study in Patients with Catheter-Related Bloodstream Infections, Including Those with Catheter-site Infections An imbalance in mortality was seen in patients treated with linezolid relative to vancomycin/dicloxacillin/oxacillin in an open-label study in seriously ill patients with intravascular catheter-related infections [78/363 (21.5%) vs. 58/363 (16%); odds ratio 1.426, 95% CI 0.970, 2.098]. While causality has not been established, this observed imbalance occurred primarily in linezolid-treated patients in whom either Gram-negative pathogens, mixed Gram-negative and Gram-positive pathogens, or no pathogen were identified at baseline, but was not seen in patients with Gram-positive infections only. Linezolid is not approved and should not be used for the treatment of patients with catheter-related bloodstream infections or catheter-site infections. Linezolid has no clinical activity against Gram-negative pathogens and is not indicated for the treatment of Gram-negative infections. It is critical that specific Gram-negative therapy be initiated immediately if a concomitant Gram-negative pathogen is documented or suspected [ see Indications and Usage (1) ]. 5.5 Clostridioides difficile -Associated Diarrhea Clostridioides difficile- Associated Diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including linezolid, 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 drug 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 antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. 5.6 Potential Interactions Producing Elevation of Blood Pressure Unless patients are monitored for potential increases in blood pressure, linezolid should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis and/or patients taking any of the following types of medications: directly and indirectly acting sympathomimetic agents (e.g., pseudoephedrine), vasopressive agents (e.g., epinephrine, norepinephrine), dopaminergic agents (e.g., dopamine, dobutamine) [ see Drug Interactions (7 ) and Clinical Pharmacology (12.3) ] . 5.7 Lactic Acidosis Lactic acidosis has been reported with the use of linezolid. In reported cases, patients experienced repeated episodes of nausea and vomiting. Patients who develop recurrent nausea or vomiting, unexplained acidosis, or a low bicarbonate level while receiving linezolid should receive immediate medical evaluation. 5.8 Convulsions Convulsions have been reported in patients when treated with linezolid. In some of these cases, a history of seizures or risk factors for seizures was reported. 5.9 Hypoglycemia Postmarketing cases of symptomatic hypoglycemia have been reported in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents when treated with linezolid, a reversible, nonselective MAO inhibitor. Some MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or hypoglycemic agents. While a causal relationship between linezolid and hypoglycemia has not been established, diabetic patients should be cautioned of potential hypoglycemic reactions when treated with linezolid. If hypoglycemia occurs, a decrease in the dose of insulin or oral hypoglycemic agent, or discontinuation of oral hypoglycemic agent, insulin, or linezolid may be required. 5.10 Hyponatremia and/or Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Postmarketing cases of hyponatremia and/or Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) have been observed in patients treated with linezolid. In reported cases, the signs and symptoms included confusion, somnolence, generalized weakness, and in severe cases led to respiratory failure and even death. Monitor serum sodium levels regularly in the elderly, in patients taking diuretics, and in other patients at risk of hyponatremia and/or SIADH while taking linezolid. If signs and symptoms of hyponatremia and/or SIADH occur, discontinue linezolid, and institute appropriate supportive measures. 5.11 Risks in Patients with Phenylketonuria Phenylalanine can be harmful to patients with phenylketonuria (PKU). Linezolid for oral suspension contains phenylalanine, a component of aspartame. Each 5 mL of the 100 mg/5 mL oral suspension contains 20 mg of phenylalanine. Before prescribing linezolid for oral suspension to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including linezolid for oral suspension. The other linezolid formulations do not contain phenylalanine. 5.12 Development of Drug-Resistant Bacteria Prescribing linezolid 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."}', 'overdosage': '{"10 OVERDOSAGE In the event of overdosage, supportive care is advised, with maintenance of glomerular filtration. Hemodialysis may facilitate more rapid elimination of linezolid. In a Phase 1 clinical trial, approximately 30% of a dose of linezolid was removed during a 3-hour hemodialysis session beginning 3 hours after the dose of linezolid was administered. Data are not available for removal of linezolid with peritoneal dialysis or hemoperfusion. Clinical signs of acute toxicity in animals were decreased activity and ataxia in rats and vomiting and tremors in dogs treated with 3,000 mg/kg/day and 2,000 mg/kg/day, respectively."}', 'active_flag': 'Y', 'generic_name': '{LINEZOLID}', '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 Important Administration Instructions Advise patients that linezolid for oral suspension may be taken with or without food. Peripheral and Optic Neuropathy Advise patients to inform their physician if they experience changes in vision while taking linezolid for oral suspension [ see Warnings and Precautions (5.2) ] . Serotonin Syndrome Advise patients to inform their physician if taking serotonergic agents, including serotonin re-uptake inhibitors or other antidepressants and opioids [ see Warnings and Precautions (5.3) ] . Potential Interactions Producing Elevation of Blood Pressure Advise patients to inform their physician if they have a history of hypertension. Advise patients to avoid large quantities of foods or beverages with high tyramine content while taking linezolid for oral suspension. Foods high in tyramine content include those that may have undergone protein changes by aging, fermentation, pickling, or smoking to improve flavor, such as aged cheeses, fermented or air-dried meats, sauerkraut, soy sauce, tap beers, and red wines. The tyramine content of any protein-rich food may be increased if stored for long periods or improperly refrigerated. Advise patients to inform their physician if taking medications containing pseudoephedrine HCl or phenylpropanolamine HCl, such as cold remedies and decongestants [ see Warnings and Precautions (5.6) ]. Lactic Acidosis Advise patients to inform their physician if they experience repeated episodes of nausea or vomiting while receiving linezolid for oral suspension [ see Warnings and Precautions (5.7) ]. Convulsions Advise patients to inform their physician if they have a history of seizures or convulsions [ see Warnings and Precautions (5.8) ]. Hypoglycemia Advise patients to inform their physician if they have diabetes mellitus. Hypoglycemic reactions, such as diaphoresis and tremulousness, along with low blood glucose measurements may occur when treated with linezolid. If such reactions occur, patients should contact a physician or other health professional for proper treatment [ see Warnings and Precautions (5.9) ] . Hyponatremia and/or SIADH Advise patients at risk for hyponatremia to inform their physician if they experience signs and symptoms of hyponatremia and/or SIADH, including confusion, somnolence, generalized weakness, and respiratory distress [ see Warnings and Precautions (5.10) ]. Phenylketonuria Advise patients with phenylketonuria (PKU) that each 5 mL of the 100 mg/5 mL linezolid for oral suspension contains 20 mg phenylalanine. The other linezolid for oral suspension formulations do not contain phenylalanine. Phenylalanine can be harmful to patients with phenylketonuria. Contact your physician or pharmacist when prescribed with linezolid for oral suspension [ see Warnings and Precautions (5.11) ]. Antibacterial Resistance Patients should be counseled that antibacterial drugs including linezolid for oral suspension should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When linezolid 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 linezolid for oral suspension or other antibacterial drugs in the future. Diarrhea 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 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 [ see Warnings and Precautions (5.5) ]. Infertility Advise male patients that linezolid for oral suspension may reversibly impair fertility [ see Use in Specific Populations (8.3) ]. Manufactured for: Camber Pharmaceuticals, Inc. Piscataway, NJ 08854 By: Annora Pharma Pvt. Ltd. Sangareddy - 502313, Telangana, India. Revised: 08/2023"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Available data from published and postmarketing case reports with linezolid use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. When administered during organogenesis, linezolid did not cause malformations in mice, rats, or rabbits at maternal exposure levels approximately 6.5 times (mice), equivalent to (rats), or 0.06 times (rabbits) the clinical therapeutic exposure, based on AUCs. However, embryo-fetal lethality was observed in mice at 6.5 times the estimated human exposure. When female rats were dosed during organogenesis through lactation, postnatal survival of pups was decreased at doses approximately equivalent to the estimated human exposure based on AUCs ( see Data ) . The background risk of major birth defects and miscarriage for the indicated populations 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 In mice, embryo-fetal toxicities were observed only at doses that caused maternal toxicity (clinical signs and reduced body weight gain). An oral dose of 450 mg/kg/day given from Gestation Day (GD) 6 to 16 (6.5 times the estimated human exposure based on AUCs) correlated with increased postimplantational embryo death, including total litter loss, decreased fetal body weights, and an increased incidence of costal cartilage fusion. Neither maternal nor embryo-fetal toxicities were observed at doses up to 150 mg/kg/day. Fetal malformations were not observed. In rats, fetal toxicity was observed at 15 and 50 mg/kg/day administered orally from GD 6 to 17 (exposures 0.22 times to approximately equivalent to the estimated human exposure, respectively, based on AUCs). The effects consisted of decreased fetal body weights and reduced ossification of sternebrae, a finding often seen in association with decreased fetal body weights. Fetal malformations were not observed. Maternal toxicity, in the form of reduced body weight gain, was seen at 50 mg/kg/day. In rabbits, reduced fetal body weight occurred only in the presence of maternal toxicity (clinical signs, reduced body weight gain and food consumption) when administered at an oral dose of 15 mg/kg/day given from GD 6 to 20 (0.06 times the estimated human exposure based on AUCs). Fetal malformations were not observed. When female rats were treated with 50 mg/kg/day (approximately equivalent to the estimated human exposure based on AUCs) of linezolid during pregnancy and lactation (GD 6 through Lactation Day 20), survival of pups was decreased on postnatal days 1 to 4. Male and female pups permitted to mature to reproductive age, when mated, showed an increase in preimplantation loss."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness of linezolid for the treatment of pediatric patients with the following infections are supported by evidence from adequate and well-controlled studies in adults, pharmacokinetic data in pediatric patients, and additional data from a comparator-controlled study of Gram-positive infections in pediatric patients ranging in age from birth through 11 years [ see Indications and Usage (1) , Clinical Pharmacology (12.3) and Clinical Studies (14) ]: nosocomial pneumonia complicated skin and skin structure infections community-acquired pneumonia (also supported by evidence from an uncontrolled study in patients ranging in age from 8 months through 12 years) vancomycin-resistant Enterococcus faecium infections The safety and effectiveness of linezolid for the treatment of pediatric patients with the following infection have been established in a comparator-controlled study in pediatric patients ranging in age from 5 through 17 years [ see Clinical Studies (14) ]: uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible strains only) or Streptococcus pyogenes Pharmacokinetic information generated in pediatric patients with ventriculoperitoneal shunts showed variable cerebrospinal fluid (CSF) linezolid concentrations following single and multiple dosing of linezolid; therapeutic concentrations were not consistently achieved or maintained in the CSF. Therefore, the use of linezolid for the empiric treatment of pediatric patients with central nervous system infections is not recommended. The pharmacokinetics of linezolid have been evaluated in pediatric patients from birth to 17 years of age. In general, weight-based clearance of linezolid gradually decreases with increasing age of pediatric patients. However, in preterm (gestational age < 34 weeks) neonates < 7 days of age, linezolid clearance is often lower than in full-term neonates < 7 days of age. Consequently, preterm neonates < 7 days of age may need an alternative linezolid dosing regimen of 10 mg/kg every 12 hours [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) ]. In limited clinical experience, 5 out of 6 (83%) pediatric patients with infections due to Gram-positive pathogens with minimum inhibitory concentrations (MICs) of 4 mcg/mL treated with linezolid had clinical cures. However, pediatric patients exhibit wider variability in linezolid clearance and systemic exposure (AUC) compared with adults. In pediatric patients with a sub-optimal clinical response, particularly those with pathogens with MIC of 4 mcg/mL, lower systemic exposure, site and severity of infection, and the underlying medical condition should be considered when assessing clinical response [ see Clinical Pharmacology (12.3) and Dosage and Administration (2) ]."}', 'geriatric_use': '{"8.5 Geriatric Use Of the 2,046 patients treated with linezolid in Phase 3 comparator-controlled clinical trials, 589 (29%) were 65 years or older and 253 (12%) were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients, 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."}'}

{PIRFENIDONE}

{'contraindications': '{"4 CONTRAINDICATIONS None. None"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Liver Enzyme Elevations and Drug-Induced Liver Injury [see Warnings and Precautions (5.1) ] Photosensitivity Reaction or Rash [see Warnings and Precautions (5.2) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.3) ] Gastrointestinal Disorders [see Warnings and Precautions (5.4) ] The most common adverse reactions (≥10%) are nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, decreased appetite, dyspepsia, dizziness, vomiting, gastro-esophageal reflux disease, sinusitis, insomnia, weight decreased, and arthralgia. ( 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. The safety of pirfenidone has been evaluated in more than 1400 subjects with over 170 subjects exposed to pirfenidone for more than 5 years in clinical trials. Pirfenidone was studied in 3 randomized, double-blind, placebo-controlled trials (Studies 1, 2, and 3) in which a total of 623 patients received 2403 mg/day of pirfenidone and 624 patients received placebo. Subjects ages ranged from 40 to 80 years (mean age of 67 years). Most patients were male (74%) and Caucasian (95%). The mean duration of exposure to pirfenidone was 62 weeks (range: 2 to 118 weeks) in these 3 trials. At the recommended dosage of 2403 mg/day, 14.6% of patients on pirfenidone compared to 9.6% on placebo permanently discontinued treatment because of an adverse event. The most common (>1%) adverse reactions leading to discontinuation were rash and nausea. The most common (>3%) adverse reactions leading to dosage reduction or interruption were rash, nausea, diarrhea, and photosensitivity reaction. The most common adverse reactions with an incidence of ≥10% and more frequent in the pirfenidone than placebo treatment group are listed in Table 2. Table 2. Adverse Reactions Occurring in ≥10% of pirfenidone -Treated Patients and More Commonly Than Placebo in Studies 1, 2, and 3 Adverse Reaction % of Patients (0 to 118 Weeks) Pirfenidone 2403 mg/day (N = 623) Placebo (N = 624) Nausea 36% 16% Rash 30% 10% Abdominal Pain 1 24% 15% Upper Respiratory Tract Infection 27% 25% Diarrhea 26% 20% Fatigue 26% 19% Headache 22% 19% Decreased Appetite 21% 8% Dyspepsia 19% 7% Dizziness 18% 11% Vomiting 13% 6% Gastro-esophageal Reflux Disease 11% 7% Sinusitis 11% 10% Insomnia 10% 7% Weight Decreased 10% 5% Arthralgia 10% 7% 1 Includes abdominal pain, upper abdominal pain, abdominal distension, and stomach discomfort. Adverse reactions occurring in ≥5 to <10% of pirfenidone-treated patients and more commonly than placebo are photosensitivity reaction (9% vs. 1%), pruritus (8% vs. 5%), asthenia (6% vs. 4%), dysgeusia (6% vs. 2%), and non-cardiac chest pain (5% vs. 4%). 6.2 Postmarketing Experience In addition to adverse reactions identified from clinical trials the following adverse reactions have been identified during post-approval use of pirfenidone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency. Blood and Lymphatic System Disorders: Agranulocytosis Hepatobiliary Disorders: Drug-induced liver injury Immune System Disorders: Angioedema Skin and Subcutaneous Tissue Disorders: Severe Cutaneous Adverse Reactions (SCAR)"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Moderate (e.g., ciprofloxacin) and strong inhibitors of CYP1A2 (e.g., fluvoxamine) increase systemic exposure of pirfenidone and may alter the adverse reaction profile of pirfenidone. Discontinue fluvoxamine prior to administration of pirfenidone or reduce to 267 mg three times a day. Consider dosage reduction with use of ciprofloxacin. ( 7.1 ) 7.1 CYP1A2 Inhibitors Pirfenidone is metabolized primarily (70 to 80%) via CYP1A2 with minor contributions from other CYP isoenzymes including CYP2C9, 2C19, 2D6 and 2E1. Strong CYP1A2 Inhibitors The concomitant administration of pirfenidone and fluvoxamine or other strong CYP1A2 inhibitors (e.g., enoxacin) is not recommended because it significantly increases exposure to pirfenidone [see Clinical Pharmacology (12.3) ]. Use of fluvoxamine or other strong CYP1A2 inhibitors should be discontinued prior to administration of pirfenidone and avoided during pirfenidone treatment. In the event that fluvoxamine or other strong CYP1A2 inhibitors are the only drug of choice, dosage reductions are recommended. Monitor for adverse reactions and consider discontinuation of pirfenidone as needed [ see Dosage and Administration (2.4) ] . Moderate CYP1A2 Inhibitors Concomitant administration of pirfenidone and ciprofloxacin (a moderate inhibitor of CYP1A2) moderately increases exposure to pirfenidone [see Clinical Pharmacology (12.3) ] . If ciprofloxacin at the dosage of 750 mg twice daily cannot be avoided, dosage reductions are recommended [see Dosage and Administration (2.4) ]. Monitor patients closely when ciprofloxacin is used at a dosage of 250 mg or 500 mg once daily. Concomitant CYP1A2 and other CYP Inhibitors Agents or combinations of agents that are moderate or strong inhibitors of both CYP1A2 and one or more other CYP isoenzymes involved in the metabolism of pirfenidone (i.e., CYP2C9, 2C19, 2D6, and 2E1) should be discontinued prior to and avoided during pirfenidone treatment. 7.2 CYP1A2 Inducers The concomitant use of pirfenidone and a CYP1A2 inducer may decrease the exposure of pirfenidone and this may lead to loss of efficacy. Therefore, discontinue use of strong CYP1A2 inducers prior to pirfenidone treatment and avoid the concomitant use of pirfenidone and a strong CYP1A2 inducer [see Clinical Pharmacology (12.3) ] ."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Pirfenidone is indicated for the treatment of idiopathic pulmonary fibrosis (IPF). Pirfenidone is a pyridone indicated for the treatment of idiopathic pulmonary fibrosis (IPF). ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Elevated liver enzymes and drug-induced liver injury: ALT, AST, and bilirubin elevations have occurred with pirfenidone including cases of drug-induced liver injury. In the postmarketing setting, non-serious and serious cases of drug-induced liver injury, including severe liver injury with fatal outcomes, have been reported. Monitor ALT, AST, and bilirubin before and during treatment. Temporary dosage reductions or discontinuations may be required. ( 2.1 , 5.1 ) Photosensitivity and rash: Photosensitivity and rash have been noted with pirfenidone. Avoid exposure to sunlight and sunlamps. Wear sunscreen and protective clothing daily. Temporary dosage reductions or discontinuations may be required. ( 5.2 ) Severe Cutaneous Adverse Reactions (SCAR): Steven-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and systemic symptoms (DRESS) have been reported in association with the use of pirfenidone in the postmarketing setting. Interrupt pirfenidone in case of signs or symptoms of SCAR. Permanently discontinue pirfenidone if a SCAR is confirmed. ( 5.3 ) Gastrointestinal disorders: Nausea, vomiting, diarrhea, dyspepsia, gastroesophageal reflux disease, and abdominal pain have occurred with pirfenidone. Temporary dosage reductions or discontinuations may be required. ( 5.4 ) 5.1 Elevated Liver Enzymes and Drug-Induced Liver Injury Cases of drug-induced liver injury (DILI) have been observed with pirfenidone. In the postmarketing period, non-serious and serious cases of DILI, including severe liver injury with fatal outcome, have been reported. Patients treated with pirfenidone 2403 mg/day in three Phase 3 trials had a higher incidence of elevations in ALT or AST ≥3 × ULN than placebo patients (3.7% vs. 0.8%, respectively). Elevations ≥10 × ULN in ALT or AST occurred in 0.3% of patients in the pirfenidone 2403 mg/day group and in 0.2% of patients in the placebo group. Increases in ALT and AST ≥3 × ULN were reversible with dose modification or treatment discontinuation. Conduct liver function tests (ALT, AST, and bilirubin) prior to the initiation of therapy with pirfenidone, monthly for the first 6 months, every 3 months thereafter, and as clinically indicated. Measure liver function tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Dosage modification or interruption may be necessary for liver enzyme elevations [see Dosage and Administration (2.1 , 2.3) ]. 5.2 Photosensitivity Reaction or Rash Patients treated with pirfenidone 2403 mg/day in the three Phase 3 studies had a higher incidence of photosensitivity reactions (9%) compared with patients treated with placebo (1%). The majority of the photosensitivity reactions occurred during the initial 6 months. Instruct patients to avoid or minimize exposure to sunlight (including sunlamps), to use a sunblock (SPF 50 or higher), and to wear clothing that protects against sun exposure. Additionally, instruct patients to avoid concomitant medications known to cause photosensitivity. Dosage reduction or discontinuation may be necessary in some cases of photosensitivity reaction or rash [see Dosage and Administration (2.3) ] . 5.3Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported in association with the use of pirfenidone in the postmarketing setting. If signs or symptoms of SCAR occur, interrupt pirfenidone treatment until the etiology of the reaction has been determined. Consultation with a dermatologist isrecommended. If a SCAR is confirmed, permanently discontinue pirfenidone. 5.4 Gastrointestinal Disorders In the clinical studies, gastrointestinal events of nausea, diarrhea, dyspepsia, vomiting, gastro-esophageal reflux disease, and abdominal pain were more frequently reported by patients in the pirfenidone treatment groups than in those taking placebo. Dosage reduction or interruption for gastrointestinal events was required in 18.5% of patients in the 2403 mg/day group, as compared to 5.8% of patients in the placebo group; 2.2% of patients in the pirfenidone 2403 mg/day group discontinued treatment due to a gastrointestinal event, as compared to 1.0% in the placebo group. The most common (>2%) gastrointestinal events that led to dosage reduction or interruption were nausea, diarrhea, vomiting, and dyspepsia. The incidence of gastrointestinal events was highest early in the course of treatment (with highest incidence occurring during the initial 3 months) and decreased over time. Dosage modifications may be necessary in some cases of gastrointestinal adverse reactions [see Dosage and Administration (2.3) ] ."}', 'overdosage': '{"10 OVERDOSAGE There is limited clinical experience with overdosage. Multiple dosages of pirfenidone up to a maximum tolerated dose of 4005 mg per day were administered as five 267 mg capsules three times daily to healthy adult volunteers over a 12-day dose escalation. In the event of a suspected overdosage, appropriate supportive medical care should be provided, including monitoring of vital signs and observation of the clinical status of the patient."}', 'active_flag': 'Y', 'generic_name': '{PIRFENIDONE}', '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 ). Liver Enzyme Elevations Advise patients that they may be required to undergo liver function testing periodically. Instruct patients to immediately report any symptoms of a liver problem (e.g., skin or the white of eyes turn yellow, urine turns dark or brown [tea colored], pain on the right side of stomach, bleed or bruise more easily than normal, lethargy) [see Warnings and Precautions (5.1) ] . Photosensitivity Reaction or Rash Advise patients to avoid or minimize exposure to sunlight (including sunlamps) during use of pirfenidone because of concern for photosensitivity reactions or rash. Instruct patients to use a sunblock and to wear clothing that protects against sun exposure. Instruct patients to report symptoms of photosensitivity reaction or rash to their physician. Temporary dosage reductions or discontinuations may be required [see Warnings and Precautions (5.2) ] . Severe Cutaneous Adverse Reactions Advise patients about signs and symptoms of severe cutaneous adverse reactions (SCAR). Advise patients to contact their healthcare provider immediately if they experience signs and symptoms of SCAR [ see Warnings and Precautions (5.3) ]. Gastrointestinal Events Instruct patients to report symptoms of persistent gastrointestinal effects including nausea, diarrhea, dyspepsia, vomiting, gastro-esophageal reflux disease, and abdominal pain. Temporary dosage reductions or discontinuations may be required [see Warnings and Precautions (5.4) ]. Smokers Encourage patients to stop smoking prior to treatment with pirfenidone and to avoid smoking when using pirfenidone [see Clinical Pharmacology (12.3) ] . Take with Food Instruct patients to take pirfenidone with food to help decrease nausea and dizziness. Manufactured by: ScieGen Pharmaceuticals Inc Hauppauge, NY 11788 USA Rev. 3/2023"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary The data with pirfenidone use in pregnant women are insufficient to inform on drug associated risks for major birth defects and miscarriage. In animal reproduction studies, pirfenidone was not teratogenic in rats and rabbits at oral doses up to 3 and 2 times, respectively, the maximum recommended daily dose (MRDD) in adults [see Data] . 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 Animal reproductive studies were conducted in rats and rabbits. In a combined fertility and embryofetal development study, female rats received pirfenidone at oral doses of 0, 50, 150, 450, and 1000 mg/kg/day from 2 weeks prior to mating, during the mating phase, and throughout the periods of early embryonic development from gestation days (GD) 0 to 5 and organogenesis from GD 6 to 17. In an embryofetal development study, pregnant rabbits received pirfenidone at oral doses of 0, 30, 100, and 300 mg/kg/day throughout the period of organogenesis from GD 6 to 18. In these studies, pirfenidone at doses up to 3 and 2 times, respectively, the maximum recommended daily dose (MRDD) in adults (on mg/m 2 basis at maternal oral doses up to 1000 mg/kg/day in rats and 300 mg/kg/day in rabbits, respectively) revealed no evidence of impaired fertility or harm to the fetus due to pirfenidone. In the presence of maternal toxicity, acyclic/irregular cycles (e.g., prolonged estrous cycle) were seen in rats at doses approximately equal to and higher than the MRDD in adults (on a mg/m 2 basis at maternal doses of 450 mg/kg/day and higher). In a pre- and post-natal development study, female rats received pirfenidone at oral doses of 0, 100, 300, and 1000 mg/kg/day from GD 7 to lactation day 20. Prolongation of the gestation period, decreased numbers of live newborn, and reduced pup viability and body weights were seen in rats at an oral dosage approximately 3 times the MRDD in adults (on a mg/m 2 basis at a maternal oral dose of 1000 mg/kg/day)."}', 'pediatric_use': '{"8.4 Pediatric Use Safety and effectiveness of pirfenidone in pediatric patients have not been established."}', 'geriatric_use': '{"8.5 Geriatric Use Of the total number of subjects in the clinical studies receiving pirfenidone, 714 (67%) were 65 years old and over, while 231 (22%) were 75 years old and over. No overall differences in safety or effectiveness were observed between older and younger patients. No dosage adjustment is required based upon age."}'}

{BISACODYL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Directions -detach one suppository from the strip -remove wrapper before inserting into the rectum adults and children 12 years of age and older 1 suppository once daily children 6 to under 12 years 1/2 suppository once daily children under 6 years do not use"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"BISACODYL SUPPOSITORY"}', 'route': '{RECTAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if Stop use and ask a doctor if -you have rectal bleeding -you fail to have a bowel movement after using this product. This may indicate a serious condition"}', 'do_not_use': '{"Do not use Do not use -when abdominal pain, nausea, or vomiting are present -for a period of longer than 1 week"}', 'when_using': '{"When using this product When using this product it may cause abdominal discomfort, faintness, rectal burning and mild cramps"}', 'warnings': '{"Warnings For rectal use only."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"CARVEDILOL PHOSPHATE"}

{'contraindications': '{"4 CONTRAINDICATIONS Carvedilol phosphate extended-release capsules are contraindicated in the following conditions: Bronchial asthma or related bronchospastic conditions. Deaths from status asthmaticus have been reported following single doses of immediate-release carvedilol. Second- or third-degree AV block. Sick sinus syndrome. Severe bradycardia (unless a permanent pacemaker is in place). Patients with cardiogenic shock or who have decompensated heart failure requiring the use of intravenous inotropic therapy. Such patients should first be weaned from intravenous therapy before initiating carvedilol phosphate extended-release capsules. Patients with severe hepatic impairment. Patients with a history of a serious hypersensitivity reaction (e.g., Stevens-Johnson syndrome, anaphylactic reaction, angioedema) to carvedilol or any of the components of carvedilol phosphate extended-release capsules. Bronchial asthma or related bronchospastic conditions. ( 4 ) Second- or third-degree AV block. ( 4 ) Sick sinus syndrome. ( 4 ) Severe bradycardia (unless permanent pacemaker in place). ( 4 ) Patients in cardiogenic shock or decompensated heart failure requiring the use of IV inotropic therapy. ( 4 ) Severe hepatic impairment. ( 2.4 , 4 ) History of serious hypersensitivity reaction (e.g., Stevens-Johnson syndrome, anaphylactic reaction, angioedema) to carvedilol or any of the components of carvedilol phosphate extended-release capsules. ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The safety profile of carvedilol phosphate extended-release capsules was similar to that observed for immediate-release carvedilol. Most common adverse events seen with immediate-release carvedilol ( 6.1 ): Hypertension (>5%): Dizziness. 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Carvedilol has been evaluated for safety in subjects with heart failure (mild, moderate, and severe), in subjects with left ventricular dysfunction following myocardial infarction, and in hypertensive subjects. The observed adverse event profile was consistent with the pharmacology of the drug and the health status of the subjects in the clinical trials. Adverse events reported for each of these populations reflecting the use of either carvedilol phosphate extended-release capsules or immediate-release carvedilol tablets are provided below. Excluded are adverse events considered too general to be informative, and those not reasonably associated with the use of the drug because they were associated with the condition being treated or are very common in the treated population. Rates of adverse events were generally similar across demographic subsets (men and women, elderly and non-elderly, blacks and non-blacks). Carvedilol phosphate extended-release capsules has been evaluated for safety in a 4-week (2 weeks of immediate\xad release carvedilol tablets and 2 weeks of carvedilol phosphate extended-release capsules) clinical trial (n = 187) which included 157 subjects with stable mild, moderate, or severe chronic heart failure and 30 subjects with left ventricular dysfunction following acute myocardial infarction. The profile of adverse events observed with carvedilol phosphate extended-release capsules in this small, short-term trial was generally similar to that observed with immediate-release carvedilol tablets. Differences in safety would not be expected based on the similarity in plasma levels for carvedilol phosphate extended-release capsules and immediate-release carvedilol. Heart Failure The following information describes the safety experience in heart failure with immediate-release carvedilol. Carvedilol has been evaluated for safety in heart failure in more than 4,500 subjects worldwide of whom more than 2,100 participated in placebo-controlled clinical trials. Approximately 60% of the total treated population in placebo-controlled clinical trials received carvedilol for at least 6 months and 30% received carvedilol for at least 12 months. In the COMET trial, 1,511 subjects with mild-to-moderate heart failure were treated with carvedilol for up to 5.9 years (mean 4.8 years). Both in U.S. clinical trials in mild-to-moderate heart failure that compared carvedilol in daily doses up to 100 mg (n = 765) with placebo (n = 437), and in a multinational clinical trial in severe heart failure (COPERNICUS) that compared carvedilol in daily doses up to 50 mg (n = 1,156) with placebo (n = 1,133), discontinuation rates for adverse experiences were similar in carvedilol and placebo subjects. In placebo-controlled clinical trials, the only cause of discontinuation greater than 1% and occurring more often on carvedilol was dizziness (1.3% on carvedilol, 0.6% on placebo in the COPERNICUS trial). Table 2 shows adverse events reported in subjects with mild-to-moderate heart failure enrolled in U.S. placebo-controlled clinical trials, and with severe heart failure enrolled in the COPERNICUS trial. Shown are adverse events that occurred more frequently in drug-treated subjects than placebo-treated subjects with an incidence of greater than 3% in subjects treated with carvedilol regardless of causality. Median trial medication exposure was 6.3 months for both carvedilol and placebo subjects in the trials of mild-to-moderate heart failure and 10.4 months in the trial of subjects with severe heart failure. The adverse event profile of carvedilol observed in the long-term COMET trial was generally similar to that observed in the U.S. Heart Failure Trials. Table 2. Adverse Events (%) Occurring More Frequently with Immediate-Release Carvedilol than with Placebo in Subjects with Mild-to-Moderate Heart Failure (HF) Enrolled in U.S. Heart Failure Trials or in Subjects with Severe Heart Failure in the COPERNICUS Trial (Incidence >3% in Subjects Treated with Carvedilol, Regardless of Causality) Body System/Adverse Event Mild-to-Moderate HF Severe HF Carvedilol Placebo Carvedilol Placebo (n = 765) (n = 437) (n = 1,156) (n = 1,133) Body as a Whole Asthenia 7 7 11 9 Fatigue 24 22 — — Digoxin level increased 5 4 2 1 Edema generalized 5 3 6 5 Edema dependent 4 2 — — Cardiovascular Bradycardia 9 1 10 3 Hypotension 9 3 14 8 Syncope 3 3 8 5 Angina pectoris 2 3 6 4 Central Nervous System Dizziness 32 19 24 17 Headache 8 7 5 3 Gastrointestinal Diarrhea 12 6 5 3 Nausea 9 5 4 3 Vomiting 6 4 1 2 Metabolic Hyperglycemia 12 8 5 3 Weight increase 10 7 12 11 BUN increased 6 5 — — NPN increased 6 5 — — Hypercholesterolemia 4 3 1 1 Edema peripheral 2 1 7 6 Musculoskeletal Arthralgia 6 5 1 1 Respiratory Cough increased 8 9 5 4 Rales 4 4 4 2 Vision Vision abnormal 5 2 — — Cardiac failure and dyspnea were also reported in these trials, but the rates were equal or greater in subjects who received placebo. The following adverse events were reported with a frequency of greater than 1% but less than or equal to 3% and more frequently with carvedilol in either the U.S. placebo-controlled trials in subjects with mild-to-moderate heart failure or in subjects with severe heart failure in the COPERNICUS trial. Incidence greater than 1% to less than or equal to 3% Body as a Whole: Allergy, malaise, hypovolemia, fever, leg edema. Cardiovascular: Fluid overload, postural hypotension, aggravated angina pectoris, AV block, palpitation, hypertension. Central and Peripheral Nervous System: Hypesthesia, vertigo, paresthesia. Gastrointestinal: Melena, periodontitis. Liver and Biliary System: SGPT increased, SGOT increased. Metabolic and Nutritional: Hyperuricemia, hypoglycemia, hyponatremia, increased alkaline phosphatase, glycosuria, hypervolemia, diabetes mellitus, GGT increased, weight loss, hyperkalemia, creatinine increased. Musculoskeletal: Muscle cramps. Platelet, Bleeding and Clotting: Prothrombin decreased, purpura, thrombocytopenia. Psychiatric: Somnolence. Reproductive, male: Impotence. Special Senses: Blurred vision. Urinary System: Renal insufficiency, albuminuria, hematuria. Left Ventricular Dysfunction Following Myocardial Infarction The following information describes the safety experience in left ventricular dysfunction following acute myocardial infarction with immediate-release carvedilol. Carvedilol has been evaluated for safety in survivors of an acute myocardial infarction with left ventricular dysfunction in the CAPRICORN trial which involved 969 subjects who received carvedilol and 980 who received placebo. Approximately 75% of the subjects received carvedilol for at least 6 months and 53% received carvedilol for at least 12 months. Subjects were treated for an average of 12.9 months and 12.8 months with carvedilol and placebo, respectively. The most common adverse events reported with carvedilol in the CAPRICORN trial were consistent with the profile of the drug in the U.S. heart failure trials and the COPERNICUS trial. The only additional adverse events reported in CAPRICORN in >3% of the subjects and more commonly on carvedilol were dyspnea, anemia, and lung edema. The following adverse events were reported with a frequency of >1% but ≤3% and more frequently with carvedilol: flu syndrome, cerebrovascular accident, peripheral vascular disorder, hypotonia, depression, gastrointestinal pain, arthritis, and gout. The overall rates of discontinuations due to adverse events were similar in both groups of subjects. In this database, the only cause of discontinuation >1% and occurring more often on carvedilol was hypotension (1.5% on carvedilol, 0.2% on placebo). Hypertension: Carvedilol phosphate extended-release capsules were evaluated for safety in an 8-week double-blind trial in 337 subjects with essential hypertension. The profile of adverse events observed with carvedilol phosphate extended-release capsules was generally similar to that observed with immediate-release carvedilol tablets. The overall rates of discontinuations due to adverse events were similar between carvedilol phosphate extended-release capsules and placebo. Table 3. Adverse Events (%) Occurring More Frequently with Carvedilol Phosphate Extended-Release Capsules than with Placebo in Subjects with Hypertension (Incidence ≥1% in Subjects Treated with Carvedilol, Regardless of Causality) Adverse Event Carvedilol Phosphate Extended-Release Capsules (n = 253) Placebo (n = 84) Nasopharyngitis 4 0 Dizziness 2 1 Nausea 2 0 Edema peripheral 2 1 Nasal congestion 1 0 Paresthesia 1 0 Sinus congestion 1 0 Diarrhea 1 0 Insomnia 1 0 The following information describes the safety experience in hypertension with immediate-release carvedilol. Carvedilol has been evaluated for safety in hypertension in more than 2,193 subjects in U.S. clinical trials and in 2,976 subjects in international clinical trials. Approximately 36% of the total treated population received carvedilol for at least 6 months. In general, carvedilol was well tolerated at doses up to 50 mg daily. Most adverse events reported during carvedilol therapy were of mild to moderate severity. In U.S. controlled clinical trials directly comparing carvedilol monotherapy in doses up to 50 mg (n = 1,142) with placebo (n = 462), 4.9% of carvedilol subjects discontinued for adverse events versus 5.2% of placebo subjects. Although there was no overall difference in discontinuation rates, discontinuations were more common in the carvedilol group for postural hypotension (1% versus 0). The overall incidence of adverse events in U.S. placebo-controlled trials was found to increase with increasing dose of carvedilol. For individual adverse events this could only be distinguished for dizziness, which increased in frequency from 2% to 5% as total daily dose increased from 6.25 mg to 50 mg as single or divided doses. Table 4 shows adverse events in U.S. placebo-controlled clinical trials for hypertension that occurred with an incidence of ≥1% regardless of causality and that were more frequent in drug-treated subjects than placebo-treated subjects. Table 4. Adverse Events (% Occurrence) in U.S. Placebo-Controlled Hypertension Trials with Immediate-Release Carvedilol Tablets (Incidence ≥1% in Subjects Treated with Carvedilol, Regardless of Causality) Shown are events with rate >1% rounded to nearest integer. Adverse Event Carvedilol (n = 1,142) Placebo (n = 462) Cardiovascular Bradycardia 2 — Postural hypotension 2 — Peripheral edema 1 — Central Nervous System Dizziness 6 5 Insomnia 2 1 Gastrointestinal Diarrhea 2 1 Hematologic Thrombocytopenia 1 — Metabolic Hypertriglyceridemia 1 — Dyspnea and fatigue were also reported in these trials, but the rates were equal or greater in subjects who received placebo. The following adverse events not described above were reported as possibly or probably related to carvedilol in worldwide open or controlled trials with carvedilol in subjects with hypertension or heart failure. Incidence >0.1% to ≤1% Cardiovascular: Peripheral ischemia, tachycardia. Central and Peripheral Nervous System: Hypokinesia. Gastrointestinal: Bilirubinemia, increased hepatic enzymes (0.2% of hypertension patients and 0.4% of heart failure patients were discontinued from therapy because of increases in hepatic enzymes) [see Adverse Reactions (6.2) ]. Psychiatric: Nervousness, sleep disorder, aggravated depression, impaired concentration, abnormal thinking, paroniria, emotional lability. Respiratory System: Asthma [see Contraindications (4) ] . Reproductive, male: Decreased libido. Skin and Appendages: Pruritus, rash erythematous, rash maculopapular, rash psoriaform, photosensitivity reaction. Special Senses: Tinnitus. Urinary System: Micturition frequency increased. Autonomic Nervous System: Dry mouth, sweating increased. Metabolic and Nutritional: Hypokalemia, hypertriglyceridemia. Hematologic: Anemia, leukopenia. The following events were reported in ≤0.1% of subjects and are potentially important: complete AV block, bundle branch block, myocardial ischemia, cerebrovascular disorder, convulsions, migraine, neuralgia, paresis, anaphylactoid reaction, alopecia, exfoliative dermatitis, amnesia, GI hemorrhage, bronchospasm, pulmonary edema, decreased hearing, respiratory alkalosis, increased BUN, decreased HDL, pancytopenia, and atypical lymphocytes. Laboratory Abnormalities Reversible elevations in serum transaminases (ALT or AST) have been observed during treatment with carvedilol. Rates of transaminase elevations (2 to 3 times the upper limit of normal) observed during controlled clinical trials have generally been similar between subjects treated with carvedilol and those treated with placebo. However, transaminase elevations, confirmed by rechallenge, have been observed with carvedilol. In a long-term, placebo-controlled trial in severe heart failure, subjects treated with carvedilol had lower values for hepatic transaminases than subjects treated with placebo, possibly because carvedilol-induced improvements in cardiac function led to less hepatic congestion and/or improved hepatic blood flow. Carvedilol therapy has not been associated with clinically significant changes in serum potassium, total triglycerides, total cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, or creatinine. No clinically relevant changes were noted in fasting serum glucose in hypertensive subjects; fasting serum glucose was not evaluated in the heart failure clinical trials. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of carvedilol tablets or carvedilol phosphate extended-release 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. Blood and Lymphatic System Disorders: Aplastic anemia. Immune System Disorders: Hypersensitivity (e.g., anaphylactic reactions, angioedema, urticaria). Renal and Urinary Disorders: Urinary incontinence. Respiratory, Thoracic, and Mediastinal Disorders: Interstitial pneumonitis. Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme."}', 'drug_interactions': '{"7 DRUG INTERACTIONS CYP P450 2D6 enzyme inhibitors may increase and rifampin may decrease carvedilol levels. ( 7.1 , 7.5 ) Hypotensive agents (e.g., reserpine, MAO inhibitors, clonidine) may increase the risk of hypotension and/or severe bradycardia. ( 7.2 ) Cyclosporine or digoxin levels may increase. ( 7.3 , 7.4 ) Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. ( 7.4 ) Amiodarone may increase carvedilol levels resulting in further slowing of the heart rate or cardiac conduction. ( 7.6 ) Verapamil- or diltiazem-type calcium channel blockers may affect ECG and/or blood pressure. ( 7.7 ) Insulin and oral hypoglycemics action may be enhanced. ( 7.8 ) 7.1 CYP2D6 Inhibitors and Poor Metabolizers Interactions of carvedilol with potent inhibitors of CYP2D6 isoenzyme (such as quinidine, fluoxetine, paroxetine, and propafenone) have not been studied, but these drugs would be expected to increase blood levels of the R(+) enantiomer of carvedilol [see Clinical Pharmacology (12.3) ] . Retrospective analysis of side effects in clinical trials showed that poor 2D6 metabolizers had a higher rate of dizziness during up-titration, presumably resulting from vasodilating effects of the higher concentrations of the alpha-blocking R(+) enantiomer. 7.2 Hypotensive Agents Patients taking a beta-blocker and a drug that can deplete catecholamines (e.g., reserpine and monoamine oxidase inhibitors) should be observed closely for signs of hypotension and/or severe bradycardia. Concomitant administration of clonidine with a beta-blocker may cause hypotension and bradycardia. When concomitant treatment with a beta-blocker and clonidine is to be terminated, the beta-blocker should be discontinued first. Clonidine therapy can then be discontinued several days later by gradually decreasing the dosage. 7.3 Cyclosporine Modest increases in mean trough cyclosporine concentrations were observed following initiation of carvedilol treatment in 21 renal transplant subjects suffering from chronic vascular rejection. In about 30% of subjects, the dose of cyclosporine had to be reduced in order to maintain cyclosporine concentrations within the therapeutic range, while in the remainder no adjustment was needed. On the average for the group, the dose of cyclosporine was reduced about 20% in these subjects. Due to wide interindividual variability in the dose adjustment required, it is recommended that cyclosporine concentrations be monitored closely after initiation of carvedilol therapy and that the dose of cyclosporine be adjusted as appropriate. 7.4 Digitalis Glycosides Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia . Digoxin concentrations are increased by about 15% when digoxin and carvedilol are administered concomitantly. Therefore, increased monitoring of digoxin is recommended when initiating, adjusting, or discontinuing carvedilol phosphate extended-release capsules [see Clinical Pharmacology (12.5) ] . 7.5 Inducers/Inhibitors of Hepatic Metabolism Rifampin reduced plasma concentrations of carvedilol by about 70% [see Clinical Pharmacology (12.5) ] . Cimetidine increased area under the curve (AUC) by about 30% but caused no change in C max [see Clinical Pharmacology (12.5) ] . 7.6 Amiodarone Amiodarone and its metabolite desethyl amiodarone, inhibitors of CYP2C9, and P-glycoprotein increased concentrations of the S(-) enantiomer of carvedilol by at least 2-fold [see Clinical Pharmacology (12.5) ] . The concomitant administration of amiodarone or other CYP2C9 inhibitors such as fluconazole with carvedilol phosphate extended-release capsules may enhance the beta-blocking activity, resulting in further slowing of the heart rate or cardiac conduction. Patients should be observed for signs of bradycardia or heart block, particularly when one agent is added to pre-existing treatment with the other. 7.7 Calcium Channel Blockers Conduction disturbance (rarely with hemodynamic compromise) has been observed when carvedilol phosphate extended-release capsules are co-administered with diltiazem. As with other beta-blockers, if carvedilol phosphate extended-release capsules are administered with calcium channel blockers of the verapamil or diltiazem type, it is recommended that ECG and blood pressure be monitored. 7.8 Insulin or Oral Hypoglycemics Beta-blockers may enhance the blood-sugar-reducing effect of insulin and oral hypoglycemics. Therefore, in patients taking insulin or oral hypoglycemics, regular monitoring of blood glucose is recommended [see Warnings and Precautions (5.6) ] . 7.9 Proton Pump Inhibitors There is no clinically meaningful increase in AUC and C max with concomitant administration of carvedilol phosphate extended-release capsules with pantoprazole. 7.10 Anesthesia If treatment with carvedilol phosphate extended-release capsules is to be continued perioperatively, particular care should be taken when anesthetic agents that depress myocardial function, such as ether, cyclopropane, and trichloroethylene, are used [see Overdosage (10) ]."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Carvedilol phosphate extended-release capsules are an alpha-/beta-adrenergic blocking agent indicated for the treatment of: mild to severe chronic heart failure. ( 1.1 ) left ventricular dysfunction following myocardial infarction in clinically stable patients. ( 1.2 ) hypertension ( 1.3 ) 1.1 Heart Failure Carvedilol phosphate extended-release capsules are indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization [see Drug Interactions (7.4) , Clinical Studies (14.1)]. 1.2 Left Ventricular Dysfunction following Myocardial Infarction Carvedilol phosphate extended-release capsules are indicated to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of less than or equal to 40% (with or without symptomatic heart failure) [see Clinical Studies (14.2)]. 1.3 Hypertension Carvedilol phosphate extended-release capsules are indicated for the management of essential hypertension [see Clinical Studies (14.3 , 14.4 )] . They can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics [see Drug Interactions (7.2) ] ."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS In clinical trials of carvedilol phosphate extended-release capsules in subjects with hypertension (338 subjects) and in subjects with left ventricular dysfunction following a myocardial infarction or heart failure (187 subjects), the profile of adverse events observed with carvedilol phosphate was generally similar to that observed with the administration of immediate-release carvedilol. Therefore, the information included within this section is based on data from controlled clinical trials with carvedilol phosphate extended-release capsules as well as immediate-release carvedilol tablets. This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity. Acute exacerbation of coronary artery disease upon cessation of therapy: Do not abruptly discontinue. ( 5.1 ) Bradycardia, hypotension, worsening heart failure/fluid retention may occur. Reduce the dose as needed. ( 5.2 , 5.3 , 5.4 ) Non-allergic bronchospasm (e.g., chronic bronchitis and emphysema): Avoid beta-blockers. ( 4 ) However, if deemed necessary, use with caution and at lowest effective dose. ( 5.5 ) Diabetes: May mask symptoms of hypoglycemia and alter glucose levels; monitor. ( 5.6 ) 5.1 Cessation of Therapy Patients with coronary artery disease, who are being treated with carvedilol phosphate extended-release capsules, should be advised against abrupt discontinuation of therapy. Severe exacerbation of angina and the occurrence of myocardial infarction and ventricular arrhythmias have been reported in patients with angina following the abrupt discontinuation of therapy with beta-blockers. The last 2 complications may occur with or without preceding exacerbation of the angina pectoris. As with other beta-blockers, when discontinuation of carvedilol phosphate extended-release capsules is planned, the patients should be carefully observed and advised to limit physical activity to a minimum. Carvedilol phosphate extended-release capsules should be discontinued over 1 to 2 weeks whenever possible. If the angina worsens or acute coronary insufficiency develops, it is recommended that carvedilol phosphate extended-release capsules be promptly reinstituted, at least temporarily. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue therapy with carvedilol phosphate extended-release capsules abruptly even in patients treated only for hypertension or heart failure. 5.2 Bradycardia In clinical trials with immediate-release carvedilol, bradycardia was reported in about 2% of hypertensive subjects, 9% of subjects with heart failure, and 6.5% of subjects with myocardial infarction with left ventricular dysfunction. Bradycardia was reported in 0.5% of subjects receiving carvedilol phosphate extended-release capsules in a trial of subjects with heart failure and subjects with myocardial infarction and left ventricular dysfunction. There were no reports of bradycardia in the clinical trial of carvedilol phosphate extended-release capsules in hypertension. However, if pulse rate drops below 55 beats/minute, the dosage of carvedilol phosphate extended-release capsules should be reduced. 5.3 Hypotension In clinical trials of primarily mild-to-moderate heart failure with immediate-release carvedilol, hypotension and postural hypotension occurred in 9.7% and syncope in 3.4% of subjects receiving carvedilol compared with 3.6% and 2.5% of placebo subjects, respectively. The risk for these events was highest during the first 30 days of dosing, corresponding to the up-titration period and was a cause for discontinuation of therapy in 0.7% of carvedilol subjects, compared with 0.4% of placebo subjects. In a long-term, placebo-controlled trial in severe heart failure (COPERNICUS), hypotension and postural hypotension occurred in 15.1% and syncope in 2.9% of subjects with heart failure receiving carvedilol compared with 8.7% and 2.3% of placebo subjects, respectively. These events were a cause for discontinuation of therapy in 1.1% of carvedilol subjects, compared with 0.8% of placebo subjects. In a trial comparing subjects with heart failure switched to carvedilol phosphate extended-release capsules or maintained on immediate-release carvedilol tablets, there was a 2-fold increase in the combined incidence of hypotension, syncope, or dizziness in elderly subjects (older than 65 years) switched from the highest dose of immediate-release carvedilol (25 mg twice daily) to carvedilol phosphate extended-release capsules 80 mg once daily [see Dosage and Administration (2) , Use in Specific Populations (8.5) ] . In the clinical trial of carvedilol phosphate extended-release capsules in hypertensive subjects, syncope was reported in 0.3% of subjects receiving carvedilol phosphate extended-release capsules compared with 0% of subjects receiving placebo. There were no reports of postural hypotension in this trial. Postural hypotension occurred in 1.8% and syncope in 0.1% of hypertensive subjects receiving immediate-release carvedilol, primarily following the initial dose or at the time of dose increase and was a cause for discontinuation of therapy in 1% of subjects. In the CAPRICORN trial of survivors of an acute myocardial infarction with left ventricular dysfunction, hypotension or postural hypotension occurred in 20.2% of subjects receiving carvedilol compared with 12.6% of placebo subjects. Syncope was reported in 3.9% and 1.9% of subjects, respectively. These events were a cause for discontinuation of therapy in 2.5% of subjects receiving carvedilol, compared with 0.2% of placebo subjects. Starting with a low dose, administration with food, and gradual up-titration should decrease the likelihood of syncope or excessive hypotension [see Dosage and Administration (2.1, 2.2, 2.3) ]. During initiation of therapy, the patient should be cautioned to avoid situations such as driving or hazardous tasks, where injury could result should syncope occur. 5.4 Heart Failure/Fluid Retention Worsening heart failure or fluid retention may occur during up-titration of carvedilol. If such symptoms occur, diuretics should be increased and the dose of carvedilol phosphate extended-release capsules should not be advanced until clinical stability resumes [see Dosage and Administration (2) ] . Occasionally it is necessary to lower the dose of carvedilol phosphate extended-release capsules or temporarily discontinue it. Such episodes do not preclude subsequent successful titration of, or a favorable response to, carvedilol phosphate extended-release capsules. In a placebo-controlled trial of subjects with severe heart failure, worsening heart failure during the first 3 months was reported to a similar degree with immediate-release carvedilol and with placebo. When treatment was maintained beyond 3 months, worsening heart failure was reported less frequently in subjects treated with carvedilol than with placebo. Worsening heart failure observed during long-term therapy is more likely to be related to the patients’ underlying disease than to treatment with carvedilol. 5.5 Non-allergic Bronchospasm Patients with bronchospastic disease (e.g., chronic bronchitis, emphysema) should, in general, not receive beta-blockers. Carvedilol phosphate extended-release capsules may be used with caution, however, in patients who do not respond to, or cannot tolerate, other antihypertensive agents. It is prudent, if carvedilol phosphate extended-release capsules are used, to use the smallest effective dose, so that inhibition of endogenous or exogenous beta-agonists is minimized. In clinical trials of subjects with heart failure, subjects with bronchospastic disease were enrolled if they did not require oral or inhaled medication to treat their bronchospastic disease. In such patients, it is recommended that carvedilol phosphate extended-release capsules be used with caution. The dosing recommendations should be followed closely and the dose should be lowered if any evidence of bronchospasm is observed during up-titration. 5.6 Effects on Blood Sugar Betablockers may prevent early warning signs of hypoglycemia, such as tachycardia, and increase the risk for severe or prolonged hypoglycemia at any time during treatment, especially in patients with diabetes mellitus or children and patients who are fasting (i.e., surgery, not eating regularly, or are vomiting). If severe hypoglycemia occurs, patients should be instructed to seek emergency treatment. In patients with heart failure and diabetes, carvedilol therapy may lead to worsening hyperglycemia, which responds to intensification of hypoglycemic therapy. It is recommended that blood glucose be monitored when dosing with carvedilol phosphate extended-release capsules is initiated, adjusted, or discontinued. Trials designed to examine the effects of carvedilol on glycemic control in patients with diabetes and heart failure have not been conducted. In a trial designed to examine the effects of immediate-release carvedilol on glycemic control in a population with mild-to-moderate hypertension and well-controlled type 2 diabetes mellitus, carvedilol had no adverse effect on glycemic control, based on HbA1c measurements [see Clinical Studies (14.4) ] . 5.7 Peripheral Vascular Disease Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. Caution should be exercised in such individuals. 5.8 Deterioration of Renal Function Rarely, use of carvedilol in patients with heart failure has resulted in deterioration of renal function. Patients at risk appear to be those with low blood pressure (systolic blood pressure less than 100 mm Hg), ischemic heart disease and diffuse vascular disease, and/or underlying renal insufficiency. Renal function has returned to baseline when carvedilol was stopped. In patients with these risk factors, it is recommended that renal function be monitored during up-titration of carvedilol phosphate extended-release capsules and the drug discontinued or dosage reduced if worsening of renal function occurs. 5.9 Major Surgery 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. 5.10 Thyrotoxicosis Beta-adrenergic blockade may mask clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of beta-blockade may be followed by an exacerbation of the symptoms of hyperthyroidism or may precipitate thyroid storm. 5.11 Pheochromocytoma In patients with pheochromocytoma, an alpha-blocking agent should be initiated prior to the use of any beta-blocking agent. Although carvedilol has both alpha- and beta-blocking pharmacologic activities, there has been no experience with its use in this condition. Therefore, caution should be taken in the administration of carvedilol to patients suspected of having pheochromocytoma. 5.12 Prinzmetal\'s Variant Angina Agents with non-selective beta-blocking activity may provoke chest pain in patients with Prinzmetal\'s variant angina. There has been no clinical experience with carvedilol in these patients although the alpha-blocking activity may prevent such symptoms. However, caution should be taken in the administration of carvedilol phosphate extended-release capsules to patients suspected of having Prinzmetal\'s variant angina. 5.13 Risk of Anaphylactic Reaction While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction. 5.14 Intraoperative Floppy Iris Syndrome Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients treated with alpha-1 blockers (carvedilol phosphate extended-release capsules are an alpha/beta blocker). 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 the surgical technique, such as 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."}', 'overdosage': '{"10 OVERDOSAGE Overdosage may cause severe hypotension, bradycardia, cardiac insufficiency, cardiogenic shock, and cardiac arrest. Respiratory problems, bronchospasms, vomiting, lapses of consciousness, and generalized seizures may also occur. The patient should be placed in a supine position and, where necessary, kept under observation and treated under intensive-care conditions. The following agents may be administered: For excessive bradycardia: Atropine, 2 mg IV. To support cardiovascular function: Glucagon, 5 to 10 mg IV rapidly over 30 seconds, followed by a continuous infusion of 5 mg/hour; sympathomimetics (dobutamine, isoprenaline, adrenaline) at doses according to body weight and effect. If peripheral vasodilation dominates, it may be necessary to administer adrenaline or noradrenaline with continuous monitoring of circulatory conditions. For therapy-resistant bradycardia, pacemaker therapy should be performed. For bronchospasm, beta-sympathomimetics (as aerosol or IV) or aminophylline IV should be given. In the event of seizures, slow IV injection of diazepam or clonazepam is recommended. NOTE: In the event of severe intoxication where there are symptoms of shock, treatment with antidotes must be continued for a sufficiently long period of time consistent with the 7- to 10-hour half-life of carvedilol. There is no experience of overdosage with carvedilol phosphate extended-release capsules. Cases of overdosage with carvedilol alone or in combination with other drugs have been reported. Quantities ingested in some cases exceeded 1,000 milligrams. Symptoms experienced included low blood pressure and heart rate. Standard supportive treatment was provided and individuals recovered."}', 'active_flag': 'Y', 'generic_name': '{"CARVEDILOL 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). Patients taking carvedilol phosphate extended-release capsules should be advised of the following: Patients should not interrupt or discontinue using carvedilol phosphate extended-release capsules without a physician’s advice. Patients with heart failure should consult their physician if they experience signs or symptoms of worsening heart failure such as weight gain or increasing shortness of breath. Patients may experience a drop in blood pressure when standing, resulting in dizziness and, rarely, fainting. Patients should sit or lie down when these symptoms of lowered blood pressure occur. If experiencing dizziness or fatigue, patients should avoid driving or hazardous tasks. Patients should consult a physician if they experience dizziness or faintness, in case the dosage should be adjusted. Patients should not crush or chew carvedilol phosphate extended-release capsules. Patients should take carvedilol phosphate extended-release capsules with food. Inform patients or caregivers that there is a risk of hypoglycemia when carvedilol tablets are given to patients who are fasting or who are vomiting. Instruct patients or caregivers how to monitor for signs of hypoglycemia [see Warnings and Precautions (5.6)]. Contact lens wearers may experience decreased lacrimation. All trademarks are the property of their respective owners. Manufactured for: Northstar Rx LLC Memphis, TN 38141. Manufactured by: Frontida BioPharm, Inc. Philadelphia, PA 19124. Rev. 02, February 2024"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Available data regarding use of carvedilol phosphate extended-release capsules in pregnant women are insufficient to determine whether there are drug-associated risks of adverse developmental outcomes. There are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy. The use of beta-blockers during the third trimester of pregnancy may increase the risk of hypotension, bradycardia, hypoglycemia, and respiratory depression in the neonate (see Clinical Considerations) . In animal reproduction studies, there was no evidence of adverse developmental outcomes at clinically relevant doses (see Data) . Oral administration of carvedilol to pregnant rats during organogenesis resulted in post-implantation loss, decreased fetal body weight, and an increased frequency of delayed fetal skeletal development at maternally toxic doses that were 50 times the maximum recommended human dose (MRHD). In addition, oral administration of carvedilol to pregnant rabbits during organogenesis resulted in increased post-implantation loss at doses 25 times the MRHD (see Data). 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 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 : 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. Fetal/Neonatal Adverse Reactions : Neonates of women with hypertension who are treated with beta-blockers during the third trimester of pregnancy may be at increased risk for hypotension, bradycardia, hypoglycemia, and respiratory depression. Observe newborns for symptoms of hypotension, bradycardia, hypoglycemia, and respiratory depression and manage accordingly. Data Animal Data: Studies performed in rats and rabbits given carvedilol during fetal organogenesis revealed increased post-implantation loss in rats at a maternally toxic dose of 300 mg/kg/day (50 times the MRHD as mg/m 2 ) and in rabbits (in the absence of maternal toxicity) at doses of 75 mg/kg/day (25 times the MRHD as mg/m 2 ). In the rats, there was also a decrease in fetal body weight at 300 mg/kg/day (50 times the MRHD as mg/m 2 ) accompanied by an increased incidence of fetuses with delayed skeletal development. In rats, the no-effect level for embryo-fetal toxicity was 60 mg/kg/day (10 times the MRHD as mg/m 2 ); in rabbits, it was 15 mg/kg/day (5 times the MRHD as mg/m 2 ). In a pre- and post-natal development study in rats administered carvedilol from late gestation through lactation, increased embryo-lethality was observed at a maternally toxic dose of 200 mg/kg/day (approximately 32 times the MRHD as mg/m 2 ), and pup mortality and delays in physical growth/development were observed at 60 mg/kg/day (10 times the MRHD as mg/m 2 ) in the absence of maternal toxicity. The no-effect level was 12 mg/kg/day (2 times the MRHD as mg/m 2 ). Carvedilol was present in fetal rat tissue."}', 'pediatric_use': '{"8.4 Pediatric Use Effectiveness of carvedilol in patients younger than 18 years has not been established. In a double-blind trial, 161 children (mean age: 6 years; range: 2 months to 17 years; 45% younger than 2 years) with chronic heart failure [NYHA class II-IV, left ventricular ejection fraction less than 40% for children with a systemic left ventricle (LV), and moderate-severe ventricular dysfunction qualitatively by echo for those with a systemic ventricle that was not an LV] who were receiving standard background treatment were randomized to placebo or to 2 dose levels of carvedilol. These dose levels produced placebo-corrected heart rate reduction of 4 to 6 heart beats per minute, indicative of beta-blockade activity. Exposure appeared to be lower in pediatric subjects than adults. After 8 months of follow-up, there was no significant effect of treatment on clinical outcomes. Adverse reactions in this trial that occurred in greater than 10% of subjects treated with immediate-release carvedilol and at twice the rate of placebo-treated subjects included chest pain (17% versus 6%), dizziness (13% versus 2%), and dyspnea (11% versus 0%)."}', 'geriatric_use': '{"8.5 Geriatric Use The initial clinical trials of carvedilol phosphate extended-release capsules in subjects with hypertension, heart failure, and left ventricular dysfunction following myocardial infarction did not include sufficient numbers of subjects aged 65 years or older to determine whether they respond differently from younger patients. A randomized trial (n = 405) comparing subjects with mild to severe heart failure switched to carvedilol phosphate extended-release capsules or maintained on immediate-release carvedilol tablets included 220 subjects who were aged 65 years or older. In this elderly subgroup, the combined incidence of dizziness, hypotension, or syncope was 24% (18/75) in subjects switched from the highest dose of immediate-release carvedilol tablets (25 mg twice daily) to the highest dose of carvedilol phosphate extended-release capsules (80 mg once daily) compared with 11% (4/36) in subjects maintained on immediate-release carvedilol tablets (25 mg twice daily). When switching from the higher doses of immediate-release carvedilol tablets to carvedilol phosphate extended-release capsules, a lower starting dose is recommended for elderly patients [see Dosage and Administration (2.5) ] . The following information is available for trials with immediate-release carvedilol. Of the 765 subjects with heart failure randomized to carvedilol in U.S. clinical trials, 31% (235) were aged 65 years or older, and 7.3% (56) were aged 75 years or older. Of the 1,156 subjects randomized to carvedilol in a long-term, placebo-controlled trial in severe heart failure, 47% (547) were aged 65 years or older, and 15% (174) were aged 75 years or older. Of 3,025 subjects receiving carvedilol in heart failure trials worldwide, 42% were aged 65 years or older. Of the 975 subjects with myocardial infarction randomized to carvedilol in the CAPRICORN trial, 48% (468) were aged 65 years or older, and 11% (111) were aged 75 years or older. Of the 2,065 hypertensive subjects in U.S. clinical trials of efficacy or safety who were treated with carvedilol, 21% (436) were aged 65 years or older. Of 3,722 subjects receiving immediate-release carvedilol in hypertension clinical trials conducted worldwide, 24% were aged 65 years or older. With the exception of dizziness in hypertensive subjects (incidence 8.8% in the elderly versus 6% in younger subjects), no overall differences in the safety or effectiveness (see Figures 2 and 4) were observed between the older subjects and younger subjects in each of these populations. Similarly, 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."}'}

{POVIDONE-IODINE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses Washing whenever a germicidal soap is required Maximum degerming of the hands"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{POVIDONE-IODINE}', '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}

{"ALUMINUM HYDROXIDE",DIMETHICONE,"MAGNESIUM HYDROXIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses relieves heartburn sour stomach acid indigestion the symptoms referred to as gas"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"ALUMINUM HYDROXIDE, MAGNESIUM HYDROXIDE, DIMETHICONE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings Ask a doctor before use if you have • kidney disease • a magnesium-restricted diet Ask a doctor or pharmacist before use if you are taking a prescription drug. Antacids may interact with certain prescription drugs. Stop use and ask a doctor if symptoms last more than 2 weeks If pregnant or 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}

{ALCOHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use(s) To kill bacteria on the skin that could cause disease. Recommended for repeated use."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{ALCOHOL}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop us and ask a doctor if irritation or rash occurs or condition persists for more than 72 hours."}', 'do_not_use': '{"Do not us on open skin wounds or children less than 2 months of age"}', 'when_using': '{"When using this product keep out of eyes. In case of contact with eyes, rinse thoroughly with water."}', 'warnings': '{"Warnings For external use only. Flammable. Keep away from heat or flame Do not us on open skin wounds or children less than 2 months of age When using this product keep out of eyes. In case of contact with eyes, rinse thoroughly with water. Stop us and ask a doctor if irritation or rash occurs or condition persists for more than 72 hours. Keep out of reach of children. If swallowed, 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}

{"SULFACETAMIDE SODIUM",SULFUR}

{'contraindications': '{"CONTRAINDICATIONS: BP 10-1 Wash is contraindicated for use by patients having known hypersensitivity to sulfonamides, sulfur or any other component of this preparation. BP 10-1 Wash is not to be used by patients with kidney disease."}', 'adverse_reactions': '{"ADVERSE REACTIONS: Although rare, sodium sulfacetamide may cause local irritation."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE: BP 10-1 Wash is indicated in the topical control of acne vulgaris, acne rosacea and seborrheic dermatitis."}', 'warnings_and_cautions': '{"WARNINGS: Sensitivity to sodium sulfacetamide may occur, although it is rare. Therefore, caution and careful supervision should be observed when prescribing this drug for patients who may be prone to hypersensitivity to topical sulfonamides. Systemic toxic reactions such as agranulocytosis, acute hemolytic anemia, purpura hemorrhagica, drug fever, jaundice, and contact dermatitis indicate hypersensitivity to sulfonamides. Particular caution should be employed if areas of denuded or abraded skin are involved. FOR EXTERNAL USE ONLY. Keep away from eyes. Keep out of reach of children. Keep tube tightly closed."}', 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"SODIUM SULFACETAMIDE AND SULFUR"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': '{"PRECAUTIONS: General - if irritation occurs, discontinue use of the product and institute appropriate therapy. Patients should be carefully observed for possible local irritation or sensitization during long-term therapy. The object of this therapy is to achieve desquamation without irritation, but sodium sulfacetamide and sulfur can cause reddening and scaling of the epidermis. These side effects are not unusual in the treatment of acne vulgaris, but patients should be cautioned about the possibility."}', 'information_for_patients': None, 'pregnancy': '{"Pregnancy - Category C. Animal reproduction studies have not been conducted with BP 10-1 Wash. It is also not known whether BP 10-1 Wash can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. BP 10-1 Wash should be given to a pregnant woman only if clearly needed."}', 'pediatric_use': '{"Pediatric Use - Safety and effectiveness in children under the age of 12 have not been established."}', 'geriatric_use': None}

{"BUPRENORPHINE HYDROCHLORIDE"}

{'contraindications': '{"4 CONTRAINDICATIONS Buprenorphine sublingual tablets are contraindicated in patients with a history of hypersensitivity to buprenorphine, as serious adverse reactions, including anaphylactic shock, have been reported [see Warnings and Precautions (5.9) ]. Hypersensitivity to buprenorphine. ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1) ] Respiratory and CNS Depression [see Warnings and Precautions (5.2 , 5.3) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.5) ] Adrenal Insufficiency [see Warnings and Precautions (5.6) ] Opioid Withdrawal [see Warnings and Precautions (5.7 , 5.10) ] Hepatitis, Hepatic Events [see Warnings and Precautions (5.8) ] Hypersensitivity Reactions [see Warnings and Precautions (5.9) ] Orthostatic Hypotension [see Warnings and Precautions (5.16) ] Elevation of Cerebrospinal Fluid Pressure [see Warnings and Precautions (5.17) ] Elevation of Intracholedochal Pressure [see Warnings and Precautions (5.18) ] Adverse events commonly observed with administration of buprenorphine are oral hypoesthesia, glossodynia, oral mucosal erythema, headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, pain, and peripheral edema. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Rhodes Pharmaceuticals L.P. at 1-888-827-0616 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 buprenorphine sublingual tablets was supported by clinical trials using buprenorphine sublingual tablets, buprenorphine and naloxone sublingual tablets, and other trials using buprenorphine sublingual solutions. In total, safety data were available from 3214 opioid-dependent subjects exposed to buprenorphine at doses in the range used in treatment of opioid addiction. Few differences in adverse event profile were noted between buprenorphine sublingual tablets or buprenorphine administered as a sublingual solution. The following adverse events were reported to occur by at least 5% of patients in a 4-week study (Table 1). Table 1. Adverse Events ≥ 5% by Body System and Treatment Group in a 4-week study N (%) N (%) Body System/Adverse Event (COSTART Terminology) Buprenorphine sublingual tablets 16 mg/day Placebo N=103 N=107 Body as a Whole Asthenia 5 (4.9%) 7 (6.5%) Chills 8 (7.8%) 8 (7.5%) Headache 30 (29.1%) 24 (22.4%) Infection 12 (11.7%) 7 (6.5%) Pain 19 (18.4%) 20 (18.7%) Pain Abdomen 12 (11.7%) 7 (6.5%) Pain Back 8 (7.8%) 12 (11.2%) Withdrawal Syndrome 19 (18.4%) 40 (37.4%) Cardiovascular System Vasodilation 4 (3.9%) 7 (6.5%) Digestive System Constipation 8 (7.8%) 3 (2.8%) Diarrhea 5 (4.9%) 16 (15.0%) Nausea 14 (13.6%) 12 (11.2%) Vomiting 8 (7.8%) 5 (4.7%) Nervous System Insomnia 22 (21.4%) 17 (15.9%) Respiratory System Rhinitis 10 (9.7%) 14 (13.1%) Skin and Appendages Sweating 13 (12.6%) 11 (10.3%) The adverse event profile of buprenorphine was also characterized in the dose-controlled study of buprenorphine solution, over a range of doses in four months of treatment. Table 2 shows adverse events reported by at least 5% of subjects in any dose group in the dose-controlled study. Table 2. Adverse Events (≥ 5%) by Body System and Treatment Group in a 16-week Study Body System/Adverse Event (COSTART Terminology) Buprenorphine Dose Sublingual solution. Doses in this table cannot necessarily be delivered in tablet form, but for comparison purposes: \\"Very low\\" dose (1 mg solution) would be less than a tablet dose of 2 mg \\"Low\\" dose (4 mg solution) approximates a 6 mg tablet dose \\"Moderate\\" dose (8 mg solution) approximates a 12 mg tablet dose \\"High\\" dose (16 mg solution) approximates a 24 mg tablet dose Very Low (N=184) Low (N=180) Moderate (N=186) High (N=181) Total (N=731) N (%) N (%) N (%) N (%) N (%) Body as a Whole Abscess 9 (5%) 2(1%) 3 (2%) 2 (1%) 16 (2%) Asthenia 26 (14%) 28 (16%) 26 (14%) 24 (13%) 104 (14%) Chills 11 (6%) 12 (7%) 9 (5%) 10 (6%) 42 (6%) Fever 7 (4%) 2 (1%) 2 (1%) 10 (6%) 21 (3%) Flu Syndrome 4 (2%) 13 (7%) 19 (10%) 8 (4%) 44 (6%) Headache 51 (28%) 62 (34%) 54 (29%) 53 (29%) 220 (30%) Infection 32 (17%) 39 (22%) 38 (20%) 40 (22%) 149 (20%) Injury Accidental 5 (3%) 10 (6%) 5 (3%) 5 (3%) 25 (3%) Pain 47 (26%) 37 (21%) 49 (26%) 44 (24%) 177 (24%) Pain Back 18 (10%) 29 (16%) 28 (15%) 27 (15%) 102 (14%) Withdrawal Syndrome 45 (24%) 40 (22%) 41 (22%) 36 (20%) 162 (22%) Digestive System Constipation 10 (5%) 23 (13%) 23 (12%) 26 (14%) 82 (11%) Diarrhea 19 (10%) 8 (4%) 9 (5%) 4 (2%) 40 (5%) Dyspepsia 6 (3%) 10 (6%) 4 (2%) 4 (2%) 24 (3%) Nausea 12 (7%) 22 (12%) 23 (12%) 18 (10%) 75 (10%) Vomiting 8 (4%) 6 (3%) 10 (5%) 14 (8%) 38 (5%) Nervous System Anxiety 22 (12%) 24 (13%) 20 (11%) 25 (14%) 91 (12%) Depression 24 (13%) 16 (9%) 25 (13%) 18 (10%) 83 (11%) Dizziness 4 (2%) 9 (5%) 7 (4%) 11 (6%) 31 (4%) Insomnia 42 (23%) 50 (28%) 43 (23%) 51 (28%) 186 (25%) Nervousness 12 (7%) 11 (6%) 10 (5%) 13 (7%) 46 (6%) Somnolence 5 (3%) 13 (7%) 9 (5%) 11 (6%) 38 (5%) Respiratory System Cough Increase 5 (3%) 11 (6%) 6 (3%) 4 (2%) 26 (4%) Pharyngitis 6 (3%) 7 (4%) 6 (3%) 9 (5%) 28 (4%) Rhinitis 27 (15%) 16 (9%) 15 (8%) 21 (12%) 79 (11%) Skin and Appendages Sweat 23 (13%) 21 (12%) 20 (11%) 23 (13%) 87 (12%) Special Senses Runny Eyes 13 (7%) 9 (5%) 6 (3%) 6 (3%) 34 (5%) 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of buprenorphine. 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 most frequently reported post-marketing adverse events with buprenorphine sublingual tablets not observed in clinical trials, excluding drug exposure during pregnancy, was drug misuse or abuse. Serotonin syndrome : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency : Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Anaphylaxis : Anaphylaxis has been reported with ingredients contained in buprenorphine sublingual tablets. Androgen deficiency : Cases of androgen deficiency have occurred with chronic use of opioids [see Clinical Pharmacology (12.2) ] . Local reactions : dental decay (including caries, tooth fracture, and tooth loss), glossodynia, glossitis, oral mucosal erythema, oral hypoesthesia, and stomatitis."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Table 3 includes clinically significant drug interactions with buprenorphine sublingual tablets. Table 3. Clinically Significant Drug Interactions Benzodiazepines or other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effects, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death. Intervention: Cessation of benzodiazepines or other CNS depressants is preferred in most cases of concomitant use. In some cases, monitoring in a higher level of care for taper may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or CNS depressant or decreasing to the lowest effective dose may be appropriate. Before co-prescribing benzodiazepines for anxiety or insomnia, ensure that patients are appropriately diagnosed and consider alternative medications and non-pharmacologic treatments [see Warnings and Precautions (5.2 , 5.3) ] . If concomitant use is warranted, strongly consider prescribing naloxone for the emergency treatment of opioid overdose, as is recommended for all patients in treatment for opioid use disorder [see Warnings and Precautions (5.2) ]. Examples: Alcohol, benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids. Inhibitors of CYP3A4 Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inhibitors can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after a stable dose of buprenorphine sublingual tablets is achieved. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the buprenorphine plasma concentration will decrease [see Clinical Pharmacology (12.3) ] , potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to buprenorphine. Intervention: If concomitant use is necessary, consider dosage reduction of buprenorphine sublingual tablets until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the buprenorphine sublingual tablets dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inducers can decrease the plasma concentration of buprenorphine [see Clinical Pharmacology (12.3) ] , potentially resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the buprenorphine plasma concentration will increase [see Clinical Pharmacology (12.3) ] , which could increase or prolong both therapeutic effects and adverse reactions and may cause serious respiratory depression. Intervention: If concomitant use is necessary, consider increasing the buprenorphine sublingual tablets dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider buprenorphine sublingual tablets dosage reduction and monitor for signs of respiratory depression. Examples: Rifampin, carbamazepine, phenytoin Antiretrovirals: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Clinical Impact: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are metabolized principally by CYP3A4. Efavirenz, nevirapine, and etravirine are known CYP3A inducers, whereas delavirdine is a CYP3A inhibitor. Significant pharmacokinetic interactions between NNRTIs (e.g., efavirenz and delavirdine) and buprenorphine have been shown in clinical studies, but these pharmacokinetic interactions did not result in any significant pharmacodynamic effects. Intervention: Patients who are on chronic buprenorphine sublingual tablets treatment should have their dose monitored if NNRTIs are added to their treatment regimen. Examples: efavirenz, nevirapine, etravirine, delavirdine Antiretrovirals: Protease inhibitors (PIs) Clinical Impact: Studies have shown some antiretroviral protease inhibitors (PIs) with CYP3A4 inhibitory activity (nelfinavir, lopinavir/ritonavir, ritonavir) have little effect on buprenorphine pharmacokinetic and no significant pharmacodynamic effects. Other PIs with CYP3A4 inhibitory activity (atazanavir and atazanavir/ritonavir) resulted in elevated levels of buprenorphine and norbuprenorphine, and patients in one study reported increased sedation. Symptoms of opioid excess have been found in post-marketing reports of patients receiving buprenorphine and atazanavir with and without ritonavir concomitantly. Intervention: Monitor patients taking buprenorphine sublingual tablets and atazanavir with and without ritonavir, and reduce dose of buprenorphine sublingual tablets if warranted. Examples: atazanavir, ritonavir Antiretrovirals: Nucleoside reverse transcriptase inhibitors (NRTIs) Clinical Impact: Nucleoside reverse transcriptase inhibitors (NRTIs) do not appear to induce or inhibit the P450 enzyme pathway, thus no interactions with buprenorphine are expected. Intervention: None Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue buprenorphine sublingual tablets if serotonin syndrome is suspected. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma). Intervention: The use of buprenorphine sublingual tablets is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. Examples: phenelzine, tranylcypromine, linezolid Muscle Relaxants Clinical Impact: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention: Monitor patients receiving muscle relaxants and buprenorphine sublingual tablets for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of buprenorphine sublingual tablets and/or the muscle relaxant, as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, strongly consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.3) , Warnings and Precautions (5.2 , 5.3) ] . Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Intervention: Monitor patients for signs of urinary retention or reduced gastric motility when buprenorphine sublingual tablets are used concomitantly with anticholinergic drugs. Benzodiazepines : Use caution in prescribing buprenorphine sublingual tablets for patients receiving benzodiazepines or other CNS depressants and warn patients against concomitant self-administration/misuse. ( 7 ) CYP3A4 Inhibitors and Inducers : Monitor patients starting or ending CYP3A4 inhibitors or inducers for potential over- or under- dosing. ( 7 ) Antiretrovirals: Patients who are on chronic buprenorphine treatment should have their dose monitored if NNRTIs are added to their treatment regimen. Monitor patients taking buprenorphine and atazanavir with and without ritonavir, and reduce dose of buprenorphine if warranted. ( 7 ) Serotonergic Drugs : Concomitant use may result in serotonin syndrome. Discontinue buprenorphine sublingual tablets if serotonin syndrome is suspected. ( 7 )"}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Buprenorphine Sublingual Tablets are indicated for the treatment of opioid dependence and are preferred for induction. Buprenorphine sublingual tablets should be used as part of a complete treatment plan to include counseling and psychosocial support. Buprenorphine sublingual tablets contain buprenorphine, a partial opioid agonist, and are indicated for the treatment of opioid dependence and are preferred for induction. ( 1 ) Buprenorphine sublingual tablets should be used as part of a complete treatment plan that includes counseling and psychosocial support. ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse : Buprenorphine can be abused in a similar manner to other opioids. Monitor patients for conditions indicative of diversion or progression of opioid dependence and addictive behaviors. Multiple refills should not be prescribed early in treatment or without appropriate patient follow-up visits. ( 5.1 ) Respiratory Depression : Life-threatening respiratory depression and death have occurred in association with buprenorphine use. Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with buprenorphine sublingual tablets ( 5.2 , 5.3 ) Unintentional Pediatric Exposure : Store buprenorphine sublingual tablets safely out of the sight and reach of children. Buprenorphine can cause severe, possibly fatal, respiratory depression in children. ( 5.4 ) Neonatal Opioid Withdrawal Syndrome : Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy. ( 5.5 ) Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.6 ) Risk of Opioid Withdrawal with Abrupt Discontinuation : If treatment is temporarily interrupted or discontinued, monitor patients for withdrawal and treat appropriately. ( 5.7 ) Risk of Hepatitis, Hepatic Events : Monitor liver function tests prior to initiation and during treatment and evaluate suspected hepatic events. ( 5.8 ) Precipitation of Opioid Withdrawal Signs and Symptoms : An opioid withdrawal syndrome is likely to occur with parenteral misuse of buprenorphine sublingual tablets by individuals physically dependent on full opioid agonists, or by sublingual administration before the agonist effects of other opioids have subsided. ( 5.10 ) Risk of Overdose in Opioid-Naïve Patients : Buprenorphine sublingual tablets are NOT appropriate as an analgesic. There have been reported deaths of opioid naïve individuals who received a 2 mg sublingual dose of buprenorphine. ( 5.11 ) 5.1 Addiction, Abuse, and Misuse Buprenorphine sublingual tablets contain buprenorphine, a Schedule III controlled substance that can be abused in a manner similar to other opioids, legal or illicit. Prescribe and dispense buprenorphine with appropriate precautions to minimize risk of misuse, abuse, or diversion, and ensure appropriate protection from theft, including in the home. Clinical monitoring appropriate to the patient\'s level of stability is essential. Multiple refills should not be prescribed early in treatment or without appropriate patient follow-up visits [see Drug Abuse and Dependence (9.2) ]. 5.2 Risk of Life-Threatening Respiratory and Central Nervous System (CNS) Depression Buprenorphine has been associated with life-threating respiratory depression and death. Many, but not all, post-marketing reports regarding coma and death involved misuses by self-injection or were associated with the concomitant use of benzodiazepines or other CNS depressants, including alcohol. Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with buprenorphine sublingual tablets [see Warning and Precautions (5.3) , Drug Interactions (7) ]. Use buprenorphine sublingual tablets with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Patient Counseling Information (17) ] . Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration (2.10) ]. Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver. Because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose, strongly consider prescribing naloxone for the emergency treatment of opioid overdose, both when initiating and renewing treatment with buprenorphine sublingual tablets. Also consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose [see Dosage and Administration (2.3) ]. Advise patients and caregivers that naloxone may also be administered for a known or suspected overdose with buprenorphine sublingual tablets itself. Higher than normal doses and repeated administration of naloxone may be necessary due to the long duration of action of buprenorphine sublingual tablets and its affinity for the mu opioid receptor [see Overdosage (10) ] . Inform patients and caregivers of their options for obtaining naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program) . Educate patients and caregivers on how to recognize respiratory depression and, if naloxone is prescribed, how to treat with naloxone. Emphasize the importance of calling 911 or getting emergency medical help, even if naloxone is administered [see Patient Counseling Information (17) ]. 5.3 Managing Risks from Concomitant Use of Benzodiazepines or Other CNS Depressants Concomitant use of buprenorphine and benzodiazepines or other CNS depressants increases the risk of adverse reactions including overdose and death. Medication-assisted treatment of opioid use disorder, however, should not be categorically denied to patients taking these drugs. Prohibiting or creating barriers to treatment can pose an even greater risk of morbidity and mortality due to the opioid use disorder alone. As a routine part of orientation to buprenorphine treatment, educate patients about the risks of concomitant use of benzodiazepines, sedatives, opioid analgesics, and alcohol. Develop strategies to manage use of prescribed or illicit benzodiazepines or other CNS depressants at initiation of buprenorphine treatment, or if it emerges as a concern during treatment. Adjustments to induction procedures and additional monitoring may be required. There is no evidence to support dose limitations or arbitrary caps of buprenorphine as a strategy to address benzodiazepine use in buprenorphine-treated patients. However, if a patient is sedated at the time of buprenorphine dosing, delay or omit the buprenorphine dose if appropriate. Cessation of benzodiazepines or other CNS depressants is preferred in most cases of concomitant use. In some cases, monitoring in a higher level of care for taper may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate. For patients in buprenorphine treatment, benzodiazepines are not the treatment of choice for anxiety or insomnia. Before co-prescribing benzodiazepines, ensure that patients are appropriately diagnosed and consider alternative medications and non-pharmacologic treatments to address anxiety or insomnia. Ensure that other healthcare providers prescribing benzodiazepines or other CNS depressants are aware of the patient\'s buprenorphine treatment and coordinate care to minimize the risks associated with concomitant use. If concomitant use is warranted, strongly consider prescribing naloxone for the emergency treatment of opioid overdose, as is recommended for all patients in buprenorphine treatment for opioid use disorder [see Warnings and Precautions (5.2) ]. In addition, take measures to confirm that patients are taking their medications as prescribed and are not diverting or supplementing with illicit drugs. Toxicology screening should test for prescribed and illicit benzodiazepines [see Drug Interactions (7) ]. 5.4 Unintentional Pediatric Exposure Buprenorphine can cause severe, possibly fatal, respiratory depression in children who are accidentally exposed to it. Store buprenorphine-containing medications safely out of the sight and reach of children and destroy any unused medication appropriately [see Patient Counseling (17) ]. 5.5 Neonatal Opioid Withdrawal Syndrome Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy, whether that use is medically-authorized or illicit. Unlike opioid withdrawal syndrome in adults, NOWS may be life-threatening if not recognized and treated in the neonate. Healthcare professionals should observe newborns for signs of NOWS and manage accordingly [see Use in Specific Populations (8.1) ] . Advise pregnant women receiving opioid addiction treatment with buprenorphine sublingual tablets of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations (8.1) ] . This risk must be balanced against the risk of untreated opioid addiction which often results in continued or relapsing illicit opioid use and is associated with poor pregnancy outcomes. Therefore, prescribers should discuss the importance and benefits of management of opioid addiction throughout pregnancy. 5.6 Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency. 5.7 Risk of Opioid Withdrawal with Abrupt Discontinuation Buprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. The withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset [see Drug Abuse and Dependence (9.3) ] . When discontinuing buprenorphine sublingual tablets, gradually taper the dosage [see Dosage and Administration (2.10) ]. 5.8 Risk of Hepatitis, Hepatic Events Cases of cytolytic hepatitis and hepatitis with jaundice have been observed in individuals receiving buprenorphine in clinical trials and through post-marketing adverse event reports. The spectrum of abnormalities ranges from transient asymptomatic elevations in hepatic transaminases to case reports of death, hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy. In many cases, the presence of pre-existing liver enzyme abnormalities, infection with hepatitis B or hepatitis C virus, concomitant usage of other potentially hepatotoxic drugs, and ongoing injecting drug use may have played a causative or contributory role. In other cases, insufficient data were available to determine the etiology of the abnormality. Withdrawal of buprenorphine has resulted in amelioration of acute hepatitis in some cases; however, in other cases no dose reduction was necessary. The possibility exists that buprenorphine had a causative or contributory role in the development of the hepatic abnormality in some cases. Liver function tests, prior to initiation of treatment is recommended to establish a baseline. Periodic monitoring of liver function during treatment is also recommended. A biological and etiological evaluation is recommended when a hepatic event is suspected. Depending on the case, buprenorphine sublingual tablets may need to be carefully discontinued to prevent withdrawal signs and symptoms and a return by the patient to illicit drug use, and strict monitoring of the patient should be initiated. 5.9 Hypersensitivity Reactions Cases of hypersensitivity to buprenorphine products have been reported both in clinical trials and in the post-marketing experience. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported. The most common signs and symptoms include rashes, hives, and pruritus. A history of hypersensitivity to buprenorphine is a contraindication to the use of buprenorphine sublingual tablets. 5.10 Precipitation of Opioid Withdrawal Signs and Symptoms Because of the partial agonist properties of buprenorphine, buprenorphine sublingual tablets may precipitate opioid withdrawal signs and symptoms in individuals physically dependent on full opioid agonists if administered sublingually or parenterally before the agonist effects of other opioids have subsided. 5.11 Risk of Overdose in Opioid Naïve Patients There have been reported deaths of opioid naïve individuals who received a 2 mg dose of buprenorphine as a sublingual tablet for analgesia. Buprenorphine sublingual tablets are not appropriate as an analgesic. 5.12 Use in Patients with Impaired Hepatic Function In a pharmacokinetic study, buprenorphine plasma levels were found to be higher and the half-life was found to be longer in subjects with moderate and severe hepatic impairment, but not in subjects with mild hepatic impairment. For patients with severe hepatic impairment, a dose adjustment is recommended, and patients with moderate or severe hepatic impairment should be monitored for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine [see Dosage and Administration (2.8) , Use in Specific Populations (8.6) ] . 5.13 Dental Adverse Events Cases of dental caries, some severe (i.e., tooth fracture, tooth loss), have been reported following the use of transmucosal buprenorphine-containing products. Reported events include cavities, tooth decay, dental abscesses/infection, rampant caries, tooth erosion, fillings falling out, and, in some cases, total tooth loss. Treatment for these events included tooth extraction, root canal, dental surgery, as well as other restorative procedures (i.e., fillings, crowns, implants, dentures). Multiple cases were reported in individuals without any prior history of dental problems. Refer patients to dental care services and encourage them to have regular dental checkups while taking buprenorphine sublingual tablets. Educate patients to seek dental care and strategies to maintain or improve oral health while being treated with transmucosal buprenorphine-containing products. Strategies include, but are not limited to, gently rinsing the teeth and gums with water and then swallowing after buprenorphine sublingual tablets have been completely dissolved in the oral mucosa. Advise patients to wait for at least one hour after taking buprenorphine sublingual tablets before brushing teeth [see Dosing and Administration (2.6) , Information for Patients (17) , Medication Guide ]. 5.14 QTc Prolongation Thorough QT studies with buprenorphine products have demonstrated QTc prolongation ≤15 msec. This QTc prolongation effect does not appear to be mediated by hERG channels. Based on these two findings, buprenorphine is unlikely to be pro-arrhythmic when used alone in patients without risk factors. The risk of combining buprenorphine with other QT-prolonging agents is not known. Consider these observations in clinical decisions when prescribing buprenorphine sublingual tablets to patients with risk factors such as hypokalemia, bradycardia, recent conversion from atrial fibrillation, congestive heart failure, digitalis therapy, baseline QT prolongation, subclinical long-QT syndrome, or severe hypomagnesemia. 5.15 Impairment of Ability to Drive or Operate Machinery Buprenorphine sublingual tablets may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving a car or operating machinery, especially during treatment induction and dose adjustment. Caution patients about driving or operating hazardous machinery until they are reasonably certain that buprenorphine therapy does not adversely affect his or her ability to engage in such activities. 5.16 Orthostatic Hypotension Like other opioids, buprenorphine sublingual tablets may produce orthostatic hypotension in ambulatory patients. 5.17 Elevation of Cerebrospinal Fluid Pressure Buprenorphine, like other opioids, may elevate cerebrospinal fluid pressure and should be used with caution in patients with head injury, intracranial lesions, and other circumstances when cerebrospinal pressure may be increased. Buprenorphine can produce miosis and changes in the level of consciousness that may interfere with patient evaluation. 5.18 Elevation of Intracholedochal Pressure Buprenorphine has been shown to increase intracholedochal pressure, as do other opioids, and thus should be administered with caution to patients with dysfunction of the biliary tract. 5.19 Effects in Acute Abdominal Conditions As with other opioids, buprenorphine may obscure the diagnosis or clinical course of patients with acute abdominal conditions."}', 'overdosage': '{"10 OVERDOSAGE Clinical Presentation The manifestations of acute overdose include pinpoint pupils, sedation, hypotension, respiratory depression, and death. Treatment of Overdose In the event of overdose, the respiratory and cardiac status of the patient should be monitored carefully. When respiratory or cardiac functions are depressed, primary attention should be given to the re-establishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. Oxygen, IV fluids, vasopressors, and other supportive measures should be employed as indicated. In the case of overdose, the primary management should be the re-establishment of adequate ventilation with mechanical assistance of respiration, if required. Naloxone may be of value for the management of buprenorphine overdose. Higher than normal doses and repeated administration may be necessary. The long duration of action of buprenorphine sublingual tablets should be taken into consideration when determining the length of treatment and medical surveillance needed to reverse the effects of an overdose. Insufficient duration of monitoring may put patients at risk."}', 'active_flag': 'Y', 'generic_name': '{BUPRENORPHINE}', 'route': '{SUBLINGUAL}', '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 read the FDA-approved patient labeling (Medication Guide). Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store buprenorphine sublingual tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home [see Warnings and Precautions (5.1 , 5.4) , Drug Abuse and Dependence (9.2) ] . Inform patients that leaving buprenorphine sublingual tablets unsecured can pose a deadly risk to others in the home. Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused buprenorphine sublingual tablets should be disposed of by flushing the unused medication down the toilet if a drug take-back option is not readily available. Inform patients that they can visit www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines. Safe Use Before initiating treatment with buprenorphine sublingual tablets, explain the points listed below to caregivers and patients. Instruct patients to read the Medication Guide each time buprenorphine sublingual tablets are dispensed because new information may be available. Inform patients and caregivers that potentially fatal additive effects may occur if buprenorphine sublingual tablets are used with benzodiazepines or other CNS depressants, including alcohol. Counsel patients that such medications should not be used concomitantly unless supervised by a health care provider [see Warnings and Precautions (5.2 , 5.3) , Drug Interactions (7) ] . Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Warnings and Precautions (5.2) ]. Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose Because patients being treated for opioid use disorder are at risk for relapse, discuss the importance of having access to naloxone with the patient and caregiver. Also discuss the importance of having access to naloxone if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. Inform patients and caregivers of the options for obtaining naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Educate patients and caregivers on how to recognize the signs and symptoms of an opioid overdose. Explain to patients and caregivers that naloxone\'s effects are temporary, and that they must call 911 or get emergency medical help right away in all cases of known or suspected opioid overdose, even if naloxone is administered. Repeat administration may be necessary, particularly for overdose involving buprenorphine and naloxone sublingual film, because naloxone is often not effective at the doses available for patient access [Dosage and Administration (2.3), Warnings and Precautions (5.2), Overdosage (10)]. If naloxone is prescribed, also advise patients and caregivers: How to treat with naloxone in the event of an opioid overdose To tell family and friends about their naloxone and to keep it in a place where family and friends can easily access it in an emergency To read the Patient Information (or other educational material) that will come with their naloxone. Emphasize the importance of doing this before an opioid emergency happens, so the patient and caregiver will know what to do. Advise patients that buprenorphine sublingual tablets contain an opioid that can be a target for people who abuse prescription medications or street drugs, to keep their tablets in a safe place, and to protect them from theft. Instruct patients to keep buprenorphine sublingual tablets in a secure place, out of the sight and reach of children. Accidental or deliberate ingestion by a child may cause respiratory depression that can result in death. Advise patients to seek medical attention immediately if a child is exposed to buprenorphine sublingual tablets. Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their healthcare providers if they are taking, or plan to take, serotonergic medications [see Drug Interactions (7) ]. Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms [see Warnings and Precautions (5.6) ]. Advise patients to never give buprenorphine sublingual tablets to anyone else, even if he or she has the same signs and symptoms. It may cause harm or death. Advise patients that selling or giving away this medication is against the law. Advise patients that, after buprenorphine sublingual tablets have completely dissolved in the oral mucosa, to take a sip of water, swish it gently around their teeth and gums, and swallow. Advise patients to wait for at least one hour after taking buprenorphine sublingual tablets before brushing teeth [see Warnings and Precautions (5.13) ] . Refer patients to dental care services and encourage them to have regular dental checkups while taking buprenorphine sublingual tablets. Instruct patients to inform their dentist that they have started therapy on buprenorphine sublingual tablets [see Warnings and Precautions (5.13) ] . Caution patients that buprenorphine sublingual tablets may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving or operating hazardous machinery. Caution should be taken especially during drug induction and dose adjustment and until individuals are reasonably certain that buprenorphine therapy does not adversely affect their ability to engage in such activities [see Warnings and Precautions (5.15) ]. Advise patients not to change the dosage of buprenorphine sublingual tablets without consulting their healthcare providers. Advise patients that if they miss a dose of buprenorphine sublingual tablets 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 the regular time. Advise patients to take buprenorphine sublingual tablets once a day. Inform patients that buprenorphine sublingual tablets can cause drug dependence and that withdrawal signs and symptoms may occur when the medication is discontinued. Advise patients seeking to discontinue treatment with buprenorphine for opioid dependence to work closely with their healthcare providers on a tapering schedule and inform them of the potential to relapse to illicit drug use associated with discontinuation of opioid agonist/partial agonist medication-assisted treatment. Advise patients that, like other opioids, buprenorphine sublingual tablets may produce orthostatic hypotension in ambulatory individuals [see Warnings and Precautions (5.16) ]. Advise patients to inform their healthcare providers if any other prescription medications, over-the-counter medications, or herbal preparations are prescribed or currently being used [see Drug Interactions (7) ] . Advise women that if they are pregnant while being treated with buprenorphine sublingual tablets, the baby may have signs of withdrawal at birth and that withdrawal is treatable [see Warnings and Precautions (5.5) , Use in Specific Populations (8.1) ]. Advise women who are breastfeeding to monitor the infant for drowsiness and difficulty breathing [see Use in Specific Populations (8.2) ]. Inform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible [see Use in Specific Populations (8.3) ]. Advise patients to inform their family members that, in the event of emergency, the treating healthcare providers or emergency room staff should be informed that the patient is physically dependent on an opioid and that the patient is being treated with buprenorphine sublingual tablets."}', 'pregnancy': '{"8.1 Pregnancy Risk Summary The data on use of buprenorphine, the active ingredient in buprenorphine sublingual tablets, in pregnancy, are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure. There are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations [see Data ] . Observational studies have reported on congenital malformations among buprenorphine-exposed pregnancies, but were also not designed appropriately to assess the risk of congenital malformations specifically due to buprenorphine exposure [see Data ]. Reproductive and developmental studies in rats and rabbits identified adverse events at clinically relevant and higher doses. Embryofetal death was observed in both rats and rabbits administered buprenorphine during the period of organogenesis at doses approximately 6 and 0.3 times, respectively, the human sublingual dose of 16 mg/day of buprenorphine. Pre- and post-natal development studies in rats demonstrated increased neonatal deaths at 0.3 times and above and dystocia at approximately 3 times the human sublingual dose of 16 mg/day of buprenorphine. No clear teratogenic effects were seen when buprenorphine was administered during organogenesis with a range of doses equivalent to or greater than the human sublingual dose of 16 mg/day of buprenorphine. However, increases in skeletal abnormalities were noted in rats and rabbits administered buprenorphine daily during organogenesis at doses approximately 0.6 times and approximately equal to the human sublingual dose of 16 mg/day of buprenorphine, respectively. In a few studies, some events such as acephalus and omphalocele were also observed but these findings were not clearly treatment-related [see Data ] . Based on animal data, advise pregnant women of the potential risk to a fetus. 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. Clinical Considerations Disease-associated maternal and embryo-fetal risk Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. In addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. Dose Adjustment during Pregnancy and the Postpartum Period Dosage adjustments of buprenorphine may be required during pregnancy, even if the patient was maintained on a stable dose prior to pregnancy. Withdrawal signs and symptoms should be monitored closely and the dose adjusted as necessary. Fetal/neonatal adverse reactions Neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with buprenorphine sublingual tablets. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight. Signs of neonatal withdrawal usually occur in the first days after birth. The duration and severity of neonatal opioid withdrawal syndrome may vary. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.5) ] . Labor or Delivery Opioid-dependent women on buprenorphine maintenance therapy may require additional analgesia during labor. Data Human Data Studies have been conducted to evaluate neonatal outcomes in women exposed to buprenorphine during pregnancy. Limited data from trials, observational studies, case series, and case reports on buprenorphine use in pregnancy do not indicate an increased risk of major malformations specifically due to buprenorphine. Several factors may complicate the interpretation of investigations of the children of women who take buprenorphine during pregnancy, including maternal use of illicit drugs, late presentation for prenatal care, infection, poor compliance, poor nutrition, and psychosocial circumstances. Interpretation of data is complicated further by the lack of information on untreated opioid-dependent pregnant women, who would be the most appropriate group for comparison. Rather, women on another form of opioid medication-assisted treatment, or women in the general population are generally used as the comparison group. However, women in these comparison groups may be different from women prescribed buprenorphine-containing products with respect to maternal factors that may lead to poor pregnancy outcomes. In a multicenter, double-blind, randomized, controlled trial [Maternal Opioid Treatment: Human Experimental Research (MOTHER)] designed primarily to assess neonatal opioid withdrawal effects, opioid-dependent pregnant women were randomized to buprenorphine (n=86) or methadone (n=89) treatment, with enrollment at an average gestational age of 18.7 weeks in both groups. A total of 28 of the 86 women in the buprenorphine group (33%) and 16 of the 89 women in the methadone group (18%) discontinued treatment before the end of pregnancy. Among women who remained in treatment until delivery, there was no difference between buprenorphine-treated and methadone-treated groups in the number of neonates requiring NOWS treatment or in the peak severity of NOWS. Buprenorphine-exposed neonates required less morphine (mean total dose, 1.1 mg vs. 10.4 mg), had shorter hospital stays (10.0 days vs. 17.5 days), and shorter duration of treatment for NOWS (4.1 days vs. 9.9 days) compared to the methadone-exposed group. There were no differences between groups in other primary outcomes (neonatal head circumference) or secondary outcomes (weight and length at birth, preterm birth, gestational age at delivery, and 1-minute and 5-minute Apgar scores), or in the rates of maternal or neonatal adverse events. The outcomes among mothers who discontinued treatment before delivery and may have relapsed to illicit opioid use are not known. Because of the imbalance in discontinuation rates between the buprenorphine and methadone groups, the study findings are difficult to interpret. Animal Data The exposure margins listed below are based on body surface area comparisons (mg/m 2 ) to the human sublingual dose of 16 mg buprenorphine via buprenorphine sublingual tablets. No definitive drug-related teratogenic effects were observed in rats and rabbits at IM doses up to 30 mg/kg/day (estimated exposure approximately 20 times and 35 times, respectively, the human sublingual dose of 16 mg). Maternal toxicity resulting in mortality was noted in these studies in both rats and rabbits. Acephalus was observed in one rabbit fetus from the low-dose group and omphalocele was observed in two rabbit fetuses from the same litter in the mid-dose group; no findings were observed in fetuses from the high-dose group. Maternal toxicity was seen in the high-dose group but not at the lower doses where the findings were observed. Following oral administration of buprenorphine to rats, dose-related post-implantation losses, evidenced by increases in the numbers of early resorptions with consequent reductions in the numbers of fetuses, were observed at doses of 10 mg/kg/day or greater (estimated exposure approximately 6 times the human sublingual dose of 16 mg). In the rabbit, increased post-implantation losses occurred at an oral dose of 40 mg/kg/day. Following IM administration in the rat and the rabbit, post-implantation losses, as evidenced by decreases in live fetuses and increases in resorptions, occurred at 30 mg/kg/day. Buprenorphine was not teratogenic in rats or rabbits after IM or subcutaneous (SC) doses up to 5 mg/kg/day (estimated exposure was approximately 3 and 6 times, respectively, the human sublingual dose of 16 mg), after IV doses up to 0.8 mg/kg/day (estimated exposure was approximately 0.5 times and equal to, respectively, the human sublingual dose of 16 mg), or after oral doses up to 160 mg/kg/day in rats (estimated exposure was approximately 95 times the human sublingual dose of 16 mg) and 25 mg/kg/day in rabbits (estimated exposure was approximately 30 times the human sublingual dose of 16 mg). Significant increases in skeletal abnormalities (e.g., extra thoracic vertebra or thoraco-lumbar ribs) were noted in rats after SC administration of 1 mg/kg/day and up (estimated exposure was approximately 0.6 times the human sublingual dose of 16 mg), but were not observed at oral doses up to 160 mg/kg/day. Increases in skeletal abnormalities in rabbits after IM administration of 5 mg/kg/day (estimated exposure was approximately 6 times the human sublingual dose of 16 mg) in the absence of maternal toxicity or oral administration of 1 mg/kg/day or greater (estimated exposure was approximately equal to the human sublingual dose of 16 mg) were not statistically significant. In rabbits, buprenorphine produced statistically significant pre-implantation losses at oral doses of 1 mg/kg/day or greater and post-implantation losses that were statistically significant at IV doses of 0.2 mg/kg/day or greater (estimated exposure approximately 0.3 times the human sublingual dose of 16 mg). No maternal toxicity was noted at doses causing post-implantation loss in this study. Dystocia was noted in pregnant rats treated intramuscularly with buprenorphine from Gestation Day 14 through Lactation Day 21 at 5 mg/kg/day (approximately 3 times the human sublingual dose of 16 mg). Fertility, and pre- and post-natal development studies with buprenorphine in rats indicated increases in neonatal mortality after oral doses of 0.8 mg/kg/day and up (approximately 0.5 times the human sublingual dose of 16 mg), after IM doses of 0.5 mg/kg/day and up (approximately 0.3 times the human sublingual dose of 16 mg), and after SC doses of 0.1 mg/kg/day and up (approximately 0.06 times the human sublingual dose of 16 mg). An apparent lack of milk production during these studies likely contributed to the decreased pup viability and lactation indices. Delays in the occurrence of righting reflex and startle response were noted in rat pups at an oral dose of 80 mg/kg/day (approximately 50 times the human sublingual dose of 16 mg)."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness of buprenorphine sublingual tablets have not been established in pediatric patients."}', 'geriatric_use': '{"8.5 Geriatric Use Clinical studies of buprenorphine sublingual tablets, buprenorphine and naloxone sublingual film, or buprenorphine and naloxone sublingual tablet did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Due to possible decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in geriatric patients, the decision to prescribe buprenorphine sublingual tablets should be made cautiously in individuals 65 years of age or older and these patients should be monitored for signs and symptoms of toxicity or overdose."}'}

{"FLUDROCORTISONE ACETATE"}

{'contraindications': '{"CONTRAINDICATIONS Corticosteroids are contraindicated in patients with systemic fungal infections and in those with a history of possible or known hypersensitivity to these agents."}', 'adverse_reactions': '{"ADVERSE REACTIONS Most adverse reactions are caused by the drug’s mineralocorticoid activity (retention of sodium and water) and include hypertension, edema, cardiac enlargement, congestive heart failure, potassium loss, and hypokalemic alkalosis. When fludrocortisone is used in the small dosages recommended, the glucocorticoid side effects often seen with cortisone and its derivatives are not usually a problem; however the following untoward effects should be kept in mind, particularly when fludrocortisone is used over a prolonged period of time or in conjunction with cortisone or a similar glucocorticoid. 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, and spontaneous fractures. Gastrointestinal —peptic ulcer with possible perforation and hemorrhage, pancreatitis, abdominal distention, and ulcerative esophagitis. Dermatologic —impaired wound healing, thin fragile skin, bruising, petechiae and ecchymoses, facial erythema, increased sweating, subcutaneous fat atrophy, purpura, striae, hyperpigmentation of the skin and nails, hirsutism, acneiform eruptions and hives; reactions to skin tests may be suppressed. Neurological —convulsions, increased intracranial pressure with papilledema (psuedo-tumor cerebri) usually after treatment, vertigo, headache, and severe mental disturbances. Endocrine —menstrual irregularities; development of the cushingoid state; suppression of growth in children; secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress (e.g., trauma, surgery, or illness); decreased carbohydrate tolerance; manifestations of latent diabetes mellitus; and increased requirements for insulin or oral hypoglycemic agents in diabetics. Ophthalmic —posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and exophthalmos. Metabolic —hyperglycemia, glycosuria, and negative nitrogen balance due to protein catabolism. Allergic Reactions —allergic skin rash, maculopapular rash, and urticaria. Other adverse reactions that may occur following the administration of a corticosteroid are necrotizing angiitis, thrombophlebitis, aggravation or masking of infections, insomnia, syncopal episodes, and anaphylactoid reactions. To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch."}', 'drug_interactions': '{"Drug Interactions When administered concurrently, the following drugs may interact with adrenal corticosteroids. Amphotericin B or potassium-depleting diuretics (benzothiadiazines and related drugs, ethacrynic acid and furosemide)—enhanced hypokalemia. Check serum potassium levels at frequent intervals; use potassium supplements if necessary (see WARNINGS ). Digitalis glycosides — enhanced possibility of arrhythmias or digitalis toxicity associated with hypokalemia. Monitor serum potassium levels; use potassium supplements if necessary. Oral anticoagulants — decreased prothrombin time response. Monitor prothrombin levels and adjust anticoagulant dosage accordingly. Antidiabetic drugs (oral agents and insulin)—diminished antidiabetic effect. Monitor for symptoms of hyperglycemia; adjust dosage of antidiabetic drug upward if necessary. Aspirin — increased ulcerogenic effect; decreased pharmacologic effect of aspirin. Rarely salicylate toxicity may occur in patients who discontinue steroids after concurrent high-dose aspirin therapy. Monitor salicylate levels or the therapeutic effect for which aspirin is given; adjust salicylate dosage accordingly if effect is altered (see PRECAUTIONS, General ). Barbiturates, phenytoin, or rifampin —increased metabolic clearance of fludrocortisone acetate because of the induction of hepatic enzymes. Observe the patient for possible diminished effect of steroid and increase the steroid dosage accordingly. Anabolic steroids (particularly C-17 alkylated androgens such as oxymetholone, methandrostenolone, norethandrolone, and similar compounds)—enhanced tendency toward edema. Use caution when giving these drugs together, especially in patients with hepatic or cardiac disease. Vaccines —neurological complications and lack of antibody response (see WARNINGS ). Estrogen —increased levels of corticosteroid-binding globulin thereby increasing the bound (inactive) fraction; this effect is at least balanced by decreased metabolism of corticosteroids. When estrogen therapy is initiated, a reduction in corticosteroid dosage may be required, and increased amounts may be required when estrogen is terminated."}', 'indications_and_usage': '{"INDICATIONS AND USAGE Fludrocortisone acetate tablets, 0.1 mg are indicated as partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison’s disease and for the treatment of salt-losing adrenogenital syndrome."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Development of hypertension, edema, hypokalemia, excessive increase in weight, and increase in heart size are signs of overdosage of fludrocortisone acetate. When these are noted, administration of drugs should be discontinued, after which the symptoms will usually subside within several days; subsequent treatment with fludrocortisone acetate should be with a reduced dose. Muscular weakness may develop due to excessive potassium loss and can be treated by administering a potassium supplement. Regular monitoring of blood pressure and serum electrolytes can help to prevent overdosage (see WARNINGS )."}', 'active_flag': 'Y', 'generic_name': '{"FLUDROCORTISONE ACETATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS BECAUSE OF ITS MARKED EFFECT ON SODIUM RETENTION THE USE OF FLUDROCORTISONE ACETATE IN THE TREATMENT OF CONDITIONS OTHER THAN THOSE INDICATED HEREIN IS NOT ADVISED. 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. If an infection occurs during fludrocortisone acetate therapy, it should be promptly controlled by suitable antimicrobial therapy. 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. 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. However, since fludrocortisone acetate is a potent mineralocorticoid, both the dosage and salt intake should be carefully monitored in order to avoid the development of hypertension, edema or weight gain. Periodic checking of serum electrolyte levels is advisable during prolonged therapy; dietary salt restriction and potassium supplementation may be necessary . All corticosteroids increase calcium excretion. Patients should not be vaccinated against smallpox while on corticosteroid therapy. 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 fludrocortisone acetate in patients with 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 antituberculous regimen. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary since 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. Chicken pox 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 variicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If chicken pox develops, treatment with antiviral agents may be considered."}', 'precautions': '{"PRECAUTIONS General Adverse reactions to corticosteroids may be produced by too rapid withdrawal or by continued use of large doses. To avoid drug-induced adrenal insufficiency, supportive dosage may be required in times of stress (such as trauma, surgery, or severe illness) both during treatment with fludrocortisone acetate and for a year afterwards. There is an enhanced corticosteroid effect in 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 being treated. A gradual reduction in dosage should be made when possible. Psychic derangements may appear when corticosteroids are used. These may range from euphoria, insomnia, mood swings, personality changes, and severe depression to frank psychotic manifestations. Existing emotional instability or psychotic tendencies may also be aggravated by corticosteroids. Aspirin should be used cautiously in conjunction with corticosteroids in patients with hypoprothrombinemia. Corticosteroids should be used with caution in patients with nonspecific ulcerative colitis if there is a probability of impending perforation, abscess, or other pyogenic infection. Corticosteroids should also be used cautiously in patients with diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, renal insufficiency, hypertension, osteoporosis, and myasthenia gravis. Information for Patients The physician should advise the patient to report any medical history of heart disease, high blood pressure, or kidney or liver disease and to report current use of any medicines to determine if these medicines might interact adversely with fludrocortisone acetate (see Drug Interactions ). Patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chicken pox or measles and, if exposed, to obtain medical advice. The patient’s understanding of his steroid-dependent status and increased dosage requirement under widely variable conditions of stress is vital. Advise the patient to carry medical identification indicating his dependence on steroid medication and, if necessary, instruct him to carry an adequate supply of medication for use in emergencies. Stress to the patient the importance of regular follow-up visits to check his progress and the need to promptly notify the physician of dizziness, severe or continuing headaches, swelling of feet or lower legs, or unusual weight gain. Advise the patient to use the medicine only as directed, to take a missed dose as soon as possible, unless it is almost time for the next dose, and not to double the next dose. Inform the patient to keep this medication and all drugs out of the reach of children. Laboratory Tests Patients should be monitored regularly for blood pressure determinations and serum electrolyte determinations (see WARNINGS ). Drug Interactions When administered concurrently, the following drugs may interact with adrenal corticosteroids. Amphotericin B or potassium-depleting diuretics (benzothiadiazines and related drugs, ethacrynic acid and furosemide)—enhanced hypokalemia. Check serum potassium levels at frequent intervals; use potassium supplements if necessary (see WARNINGS ). Digitalis glycosides — enhanced possibility of arrhythmias or digitalis toxicity associated with hypokalemia. Monitor serum potassium levels; use potassium supplements if necessary. Oral anticoagulants — decreased prothrombin time response. Monitor prothrombin levels and adjust anticoagulant dosage accordingly. Antidiabetic drugs (oral agents and insulin)—diminished antidiabetic effect. Monitor for symptoms of hyperglycemia; adjust dosage of antidiabetic drug upward if necessary. Aspirin — increased ulcerogenic effect; decreased pharmacologic effect of aspirin. Rarely salicylate toxicity may occur in patients who discontinue steroids after concurrent high-dose aspirin therapy. Monitor salicylate levels or the therapeutic effect for which aspirin is given; adjust salicylate dosage accordingly if effect is altered (see PRECAUTIONS, General ). Barbiturates, phenytoin, or rifampin —increased metabolic clearance of fludrocortisone acetate because of the induction of hepatic enzymes. Observe the patient for possible diminished effect of steroid and increase the steroid dosage accordingly. Anabolic steroids (particularly C-17 alkylated androgens such as oxymetholone, methandrostenolone, norethandrolone, and similar compounds)—enhanced tendency toward edema. Use caution when giving these drugs together, especially in patients with hepatic or cardiac disease. Vaccines —neurological complications and lack of antibody response (see WARNINGS ). Estrogen —increased levels of corticosteroid-binding globulin thereby increasing the bound (inactive) fraction; this effect is at least balanced by decreased metabolism of corticosteroids. When estrogen therapy is initiated, a reduction in corticosteroid dosage may be required, and increased amounts may be required when estrogen is terminated. Drug/Laboratory Test Interactions Corticosteroids may affect the nitrobluetetrazolium test for bacterial infection and produce false-negative results. Carcinogenesis, Mutagenesis, Impairment of Fertility Adequate studies have not been performed in animals to determine whether fludrocortisone acetate has carcinogenic or mutagenic activity or whether it affects fertility in males or females. Pregnancy: Teratogenic Effects: Category C Adequate animal reproduction studies have not been conducted with fludrocortisone acetate. However, many corticosteroids have been shown to be teratogenic in laboratory animals at low doses. Teratogenicity of these agents in man has not been demonstrated. It is not known whether fludrocortisone acetate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Fludrocortisone acetate should be given to a pregnant woman only if clearly needed. Pregnancy: Nonteratogenic Effects Infants born of mothers who have received substantial doses of fludrocortisone acetate during pregnancy should be carefully observed for signs of hypoadrenalism. Maternal treatment with corticosteroids should be carefully documented in the infant’s medical records to assist in follow up. Nursing Mothers Corticosteroids are found in the breast milk of lactating women receiving systemic therapy with these agents. Caution should be exercised when fludrocortisone acetate is administered to a nursing woman. Pediatric Use Safety and effectiveness in children have not been established. Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed."}', 'information_for_patients': '{"Information for Patients The physician should advise the patient to report any medical history of heart disease, high blood pressure, or kidney or liver disease and to report current use of any medicines to determine if these medicines might interact adversely with fludrocortisone acetate (see Drug Interactions ). Patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chicken pox or measles and, if exposed, to obtain medical advice. The patient’s understanding of his steroid-dependent status and increased dosage requirement under widely variable conditions of stress is vital. Advise the patient to carry medical identification indicating his dependence on steroid medication and, if necessary, instruct him to carry an adequate supply of medication for use in emergencies. Stress to the patient the importance of regular follow-up visits to check his progress and the need to promptly notify the physician of dizziness, severe or continuing headaches, swelling of feet or lower legs, or unusual weight gain. Advise the patient to use the medicine only as directed, to take a missed dose as soon as possible, unless it is almost time for the next dose, and not to double the next dose. Inform the patient to keep this medication and all drugs out of the reach of children."}', 'pregnancy': '{"Pregnancy: Teratogenic Effects: Category C Adequate animal reproduction studies have not been conducted with fludrocortisone acetate. However, many corticosteroids have been shown to be teratogenic in laboratory animals at low doses. Teratogenicity of these agents in man has not been demonstrated. It is not known whether fludrocortisone acetate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Fludrocortisone acetate should be given to a pregnant woman only if clearly needed.","Pregnancy: Nonteratogenic Effects Infants born of mothers who have received substantial doses of fludrocortisone acetate during pregnancy should be carefully observed for signs of hypoadrenalism. Maternal treatment with corticosteroids should be carefully documented in the infant’s medical records to assist in follow up."}', 'pediatric_use': '{"Pediatric Use Safety and effectiveness in children have not been established. Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed."}', 'geriatric_use': None}

{TOLNAFTATE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses cures most athlete\'s foot (tinea pedis), ringworm (tinea corporis) and jock itch (tinea cruris) can prevent recurrence of most athlete\'s foot relieves symptoms of athlete\'s foot, including itching, burning, crcaking, and chafing associated with jock itch"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"TOLNAFTATE POWDER SPRAY"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if irritation occurs no improvement within 2 weeks"}', 'do_not_use': '{"Do not use on children under 2 years of age unless directed by a doctor."}', 'when_using': '{"When using this product avoid contact with the eyes or mouth use only as directed"}', 'warnings': '{"Warnings For external use only. Flammable: Do not use while smoking or flame. Do not puncture or incinerate. Contents under pressure. Do not store at temperature above 120ºF. Intentional misuse by deliberately concentrating and inhaling contents can be harmful or fatal. When using this product avoid contact with the eyes or mouth use only as directed Stop use and ask a doctor if irritation occurs no improvement within 2 weeks Do not use on children under 2 years of age unless directed by 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}

{HYDROCORTISONE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"USES For temporary external feminine itching"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"HYDROCORTISONE 0.5%"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': '{"Stop use and ask a doctor if you have a vaginal discharge. Consult a physician. condition worsens, or if symptoms persist for more than 7 days, or clear up and occur again in a few days."}', 'when_using': None, 'warnings': '{"WARNINGS For External Use Only Avoid Contact with eyes"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"SALICYLIC ACID"}

{'contraindications': '{"CONTRAINDICATIONS: KERALYT SHAMPOO should not be used in any patient known to be sensitive to salicylic acid or any other listed ingredient. KERALYT SHAMPOO should not be used in children under 2 years of age."}', 'adverse_reactions': '{"ADVERSE REACTIONS: Excessive erythema and scaling conceivably could result from use on open skin lesions."}', 'drug_interactions': '{"Drug Interactions. (The following interactions are from a published review ⁵ and include reports concerning both oral and topical salicylate administration. The relationship of these interactions to the use of KERALYT SHAMPOO is not known.) I. Due to the competition of salicylate with other drugs for binding to serum albumin the following drug interactions may occur: Drug Description of Interaction Tolbutamide; Sulfonylureas Hypoglycemia potentiated Methotrexate Decreases tubular reabsorption; clinical toxicity from methotrexate can result Oral Anticoagulant Increased bleeding II. Drugs changing salicylate levels by altering renal tubular reabsorption: Drug Description Corticosteroids Decreases plasma salicylate level; Tapering doses of steroids may promote salicylism Ammonium Sulfate Increases plasma salicylate level III. Drugs with complicated interactions with salicylates: Drug Description Heparin Salicylate decreases platelet adhesiveness and interferes with hemostasis in heparin-treated patients Pyrazinamide Inhibits pyrazinamide-induced hyperuricemia Uricosuric Agents Effect of probenecid, sulfinpyrazone and phenylbutazone inhibited The following alterations of laboratory tests have been reported during salicylate therapy ⁶ : Laboratory Tests Effect of Salicylates Thyroid Function Decreased PBI; increased T 3 uptake Urinary Sugar False negative with glucose oxidase; false positive with Clinitest with high-dose salicylate therapy (2-5 g qd) 5 Hydroxyindole acetic acid False negative with fluorometric test Acetone, Ketone Bodies False positive FeCl 3 in Gerhardt reaction; red color persists with boiling 17-OH corticosteroids False reduced values with >4.8 g qd salicylate Vanilmandelic Acid False reduced values Uric Acid May increase or decrease depending on dose Prothrombin Decreased levels; slightly increased prothrombin time"}', 'indications_and_usage': '{"INDICATIONS AND USAGE - For the removal of excess keratin in hyperkeratotic disorders, including scaling associated with scalp psoriasis or thickened skin of palms and soles, corns and calluses."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE - See WARNINGS"}', 'active_flag': 'Y', 'generic_name': '{"SALICYLIC ACID"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS: Prolonged use over large areas, especially in children and those patients with significant renal or hepatic impairment, could result in salicylism. Concomitant use of other drugs which may contribute to elevated serum salicylate levels should be avoided where the potential for toxicity is present. In children under 12 years of age and those patients with renal or hepatic impairment, the area to be treated should be limited and the patient monitored closely for signs of salicylate toxicity: nausea, vomiting, dizziness, loss of hearing, tinnitus, lethargy, hyperpnoea, diarrhea, psychic disturbances. In the event of salicylic acid toxicity, the use of KERALYT SHAMPOO should be discontinued. Fluids should be administered to promote urinary excretion. Treat- ment with sodium bicarbonate (oral or intravenous) should be instituted as appropriate. Considering the potential risk of developing Reye’s Syndrome, salicylate products should not be administered to children or teenagers with varicella or influenza, unless directed by a physician."}', 'precautions': '{"PRECAUTIONS: For external use only. Avoid contact with eyes and other mucous membranes. Mild burning or stinging may occur. Peeling of the skin may increase as the salicylic acid works to loosen excess keratin. If excessive burning, stinging or peeling occurs, discontinue use and consult your physician. Keep this and all medications out of reach of children. Drug Interactions. (The following interactions are from a published review ⁵ and include reports concerning both oral and topical salicylate administration. The relationship of these interactions to the use of KERALYT SHAMPOO is not known.) I. Due to the competition of salicylate with other drugs for binding to serum albumin the following drug interactions may occur: Drug Description of Interaction Tolbutamide; Sulfonylureas Hypoglycemia potentiated Methotrexate Decreases tubular reabsorption; clinical toxicity from methotrexate can result Oral Anticoagulant Increased bleeding II. Drugs changing salicylate levels by altering renal tubular reabsorption: Drug Description Corticosteroids Decreases plasma salicylate level; Tapering doses of steroids may promote salicylism Ammonium Sulfate Increases plasma salicylate level III. Drugs with complicated interactions with salicylates: Drug Description Heparin Salicylate decreases platelet adhesiveness and interferes with hemostasis in heparin-treated patients Pyrazinamide Inhibits pyrazinamide-induced hyperuricemia Uricosuric Agents Effect of probenecid, sulfinpyrazone and phenylbutazone inhibited The following alterations of laboratory tests have been reported during salicylate therapy ⁶ : Laboratory Tests Effect of Salicylates Thyroid Function Decreased PBI; increased T 3 uptake Urinary Sugar False negative with glucose oxidase; false positive with Clinitest with high-dose salicylate therapy (2-5 g qd) 5 Hydroxyindole acetic acid False negative with fluorometric test Acetone, Ketone Bodies False positive FeCl 3 in Gerhardt reaction; red color persists with boiling 17-OH corticosteroids False reduced values with >4.8 g qd salicylate Vanilmandelic Acid False reduced values Uric Acid May increase or decrease depending on dose Prothrombin Decreased levels; slightly increased prothrombin time Pregnancy (Category C): Salicylic acid has been shown to be teratogenic in rats and monkeys. It is difficult to extrapolate from oral doses of acetyl salicylic acid used in these studies to topical administration as the oral dose to monkeys may represent 4 times the maximum daily human dose of salicylic acid (as supplied in one bottle, 8 oz. of KERALYT SHAMPOO) when applied topically over a large body surface. There are no adequate and well-controlled studies in pregnant women. KERALYT SHAMPOO should be used during pregnancy only if the potential benefit justifies the risk to the fetus. Nursing Mothers: Because of the potential for serious adverse reactions in nursing infants from the mother’s use of KERALYT SHAMPOO, 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. If used by nursing mothers, it should not be in the chest area in order to avoid accidental exposure to a nursing child. Carcinogenesis, Mutagenesis, Impairment of Fertility: No data are available concerning potential carcinogenic or reproductive effects of KERALYT SHAMPOO. It has been shown to lack mutagenic potential in the Ames Salmonella test."}', 'information_for_patients': None, 'pregnancy': '{"Pregnancy (Category C): Salicylic acid has been shown to be teratogenic in rats and monkeys. It is difficult to extrapolate from oral doses of acetyl salicylic acid used in these studies to topical administration as the oral dose to monkeys may represent 4 times the maximum daily human dose of salicylic acid (as supplied in one bottle, 8 oz. of KERALYT SHAMPOO) when applied topically over a large body surface. There are no adequate and well-controlled studies in pregnant women. KERALYT SHAMPOO should be used during pregnancy only if the potential benefit justifies the risk to the fetus."}', 'pediatric_use': None, 'geriatric_use': None}

{"BENZYL ALCOHOL","LIDOCAINE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"USES Temporary relief of minor pain"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"LIDOCAINE HYDROCHLORIDE, BENZYL ALCOHOL"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"STOP USE AND ASK A DOCTOR IF skin reactions occur, such as rash, itching, redness, irritation, pain, swelling and blistering conditions worsen symptoms persist for more than 7 days symptoms clear up and occur again within a few days"}', 'do_not_use': '{"DO NOT USE on wounds or damaged skin in large quantities with a heating pad if you are allergic to any ingredients of this product"}', 'when_using': '{"WHEN USING THIS PRODUCT use only as directed avoid contact with the eyes, mucous membranes or rashes do not bandage tightly"}', 'warnings': '{"WARNINGS For external use only FLAMMABLE :Keep away from fire or flame DO NOT USE on wounds or damaged skin in large quantities with a heating pad if you are allergic to any ingredients of this product WHEN USING THIS PRODUCT use only as directed avoid contact with the eyes, mucous membranes or rashes do not bandage tightly STOP USE AND ASK A DOCTOR IF skin reactions occur, such as rash, itching, redness, irritation, pain, swelling and blistering conditions worsen symptoms persist for more than 7 days symptoms clear up and occur again within a few days IF PREGNANT OR BREAST-FEEDING , ask a health professional before use. KEEP OUT OF REACH OF CHILDREN AND PETS. 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}

{TADALAFIL}

{'contraindications': '{"4 CONTRAINDICATIONS Administration of tadalafil to patients using any form of organic nitrate is contraindicated. Tadalafil was shown to potentiate the hypotensive effect of nitrates ( 4.1 ). History of known serious hypersensitivity reaction to Tadalafil or ADCIRCA ® ( 4.2 ). Administration with guanylate cyclase (GC) stimulators, such as riociguat ( 4.3 ). 4.1 Nitrates Administration of tadalafil to patients who are using any form of organic nitrate, either regularly and/or intermittently, is contraindicated. In clinical pharmacology studies, tadalafil was shown to potentiate the hypotensive effect of nitrates [see Clinical Pharmacology ( 12.2 )] . 4.2 Hypersensitivity Reactions Tadalafil is contraindicated in patients with a known serious hypersensitivity to tadalafil (Tadalafil tablets or ADCIRCA ® ). Hypersensitivity reactions have been reported, including Stevens-Johnson syndrome and exfoliative dermatitis [see Adverse Reactions ( 6.2 )] . 4.3 Concomitant Guanylate Cyclase (GC) Stimulators Do not use Tadalafil in patients who are using a GC stimulator, such as riociguat. PDE5 inhibitors, including Tadalafil, may potentiate the hypotensive effects of GC stimulators."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS Most common adverse reactions (greater than or equal to 2%) include headache, dyspepsia, back pain, myalgia, nasal congestion, flushing, and pain in limb ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Ajanta Pharma USA Inc. at 1-855-664-7744 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. Tadalafil was administered to over 9000 men during clinical trials worldwide. In trials of tadalafil tablets for once daily use, a total of 1434, 905, and 115 were treated for at least 6 months, 1 year, and 2 years, respectively. For tadalafil tablets for use as needed, over 1300 and 1000 subjects were treated for at least 6 months and 1 year, respectively. Tadalafil tablets for Use as Needed for ED In eight primary placebo-controlled clinical studies of 12 weeks duration, mean age was 59 years (range 22 to 88) and the discontinuation rate due to adverse events in patients treated with tadalafil 10 or 20 mg was 3.1%, compared to 1.4% in placebo treated patients. When taken as recommended in the placebo-controlled clinical trials, the following adverse reactions were reported ( see Table 1) for tadalafil tablets for use as needed: Table 1: Treatment-Emergent Adverse Reactions Reported by greater than or equal to 2% of Patients Treated with Tadalafil tablets (10 mg or 20 mg) and More Frequent on Drug than Placebo in the Eight Primary Placebo-Controlled Clinical Studies (Including a Study in Patients with Diabetes) for Tadalafil tablets for Use as Needed for ED a The term flushing includes: facial flushing and flushing Adverse Reaction Placebo (N=476) Tadalafil 5 mg (N=151) Tadalafil 10 mg (N=394) Tadalafil 20 mg (N=635) Headache 5% 11% 11% 15% Dyspepsia 1% 4% 8% 10% Back pain 3% 3% 5% 6% Myalgia 1% 1% 4% 3% Nasal congestion 1% 2% 3% 3% Flushing a 1% 2% 3% 3% Pain in limb 1% 1% 3% 3% Tadalafil tablets for Once Daily Use for ED In three placebo-controlled clinical trials of 12 or 24 weeks duration, mean age was 58 years (range 21 to 82) and the discontinuation rate due to adverse events in patients treated with tadalafil was 4.1%, compared to 2.8% in placebo-treated patients. The following adverse reactions were reported ( see Table 2) in clinical trials of 12 weeks duration: Table 2: Treatment-Emergent Adverse Reactions Reported by greater than or equal to 2% of Patients Treated with Tadalafil for Once Daily Use (2.5 mg or 5 mg) and More Frequent on Drug than Placebo in the Three Primary Placebo-Controlled Phase 3 Studies of 12 weeks Treatment Duration (Including a Study in Patients with Diabetes) for Tadalafil tablets for Once Daily Use for ED Adverse Reaction Placebo (N=248) Tadalafil 2.5 mg (N=196) Tadalafil 5 mg (N=304) Headache 5% 3% 6% Dyspepsia 2% 4% 5% Nasopharyngitis 4% 4% 3% Back pain 1% 3% 3% Upper respiratory tract infection 1% 3% 3% Flushing 1% 1% 3% Myalgia 1% 2% 2% Cough 0% 4% 2% Diarrhea 0% 1% 2% Nasal congestion 0% 2% 2% Pain in extremity 0% 1% 2% Urinary tract infection 0% 2% 0% Gastroesophageal reflux disease 0% 2% 1% Abdominal pain 0% 2% 1% The following adverse reactions were reported ( see Table 3) over 24 weeks treatment duration in one placebo-controlled clinical study: Table 3: Treatment-Emergent Adverse Reactions Reported by greater than or equal to 2% of Patients Treated with Tadalafil tablets for Once Daily Use (2.5 mg or 5 mg) and More Frequent on Drug than Placebo in One Placebo-Controlled Clinical Study of 24 Weeks Treatment Duration for Tadalafil tablets for Once Daily Use for ED Adverse Reaction Placebo (N=94) Tadalafil 2.5 mg (N=96) Tadalafil 5 mg (N=97) Nasopharyngitis 5% 6% 6% Gastroenteritis 2% 3% 5% Back pain 3% 5% 2% Upper respiratory tract infection 0% 3% 4% Dyspepsia 1% 4% 1% Gastroesophageal reflux disease 0% 3% 2% Myalgia 2% 4% 1% Hypertension 0% 1% 3% Nasal congestion 0% 0% 4% Tadalafil tablets for Once Daily Use for BPH and for ED and BPH In three placebo-controlled clinical trials of 12 weeks duration, two in patients with BPH and one in patients with ED and BPH, the mean age was 63 years (range 44 to 93) and the discontinuation rate due to adverse events in patients treated with tadalafil was 3.6% compared to 1.6% in placebo-treated patients. Adverse reactions leading to discontinuation reported by at least 2 patients treated with tadalafil included headache, upper abdominal pain, and myalgia. The following adverse reactions were reported ( see Table 4). Table 4: Treatment-Emergent Adverse Reactions Reported by greater than or equal to 1% of Patients Treated with Tadalafil tablets for Once Daily Use (5 mg) and More Frequent on Drug than Placebo in Three Placebo-Controlled Clinical Studies of 12 Weeks Treatment Duration, including Two Studies for Tadalafil tablets for Once Daily Use for BPH and One Study for ED and BPH Adverse Reaction Placebo (N=576) Tadalafil 5 mg (N=581) Headache 2.3% 4.1% Dyspepsia 0.2% 2.4% Back pain 1.4% 2.4% Nasopharyngitis 1.6% 2.1% Diarrhea 1.0% 1.4% Pain in extremity 0.0% 1.4% Myalgia 0.3% 1.2% Dizziness 0.5% 1.0% Additional, less frequent adverse reactions (less than 1%) reported in the controlled clinical trials of Tadalafil for BPH or ED and BPH included: gastroesophageal reflux disease, upper abdominal pain, nausea, vomiting, arthralgia, and muscle spasm. Back pain or myalgia was reported at incidence rates described in Tables 1 through 4. In tadalafil clinical pharmacology trials, back pain or myalgia generally occurred 12 to 24 hours after dosing and typically resolved within 48 hours. The back pain/myalgia associated with tadalafil treatment was characterized by diffuse bilateral lower lumbar, gluteal, thigh, or thoracolumbar muscular discomfort and was exacerbated by recumbency. In general, pain was reported as mild or moderate in severity and resolved without medical treatment, but severe back pain was reported with a low frequency (less than 5% of all reports). When medical treatment was necessary, acetaminophen or non-steroidal anti-inflammatory drugs were generally effective; however, in a small percentage of subjects who required treatment, a mild narcotic (e.g., codeine) was used. Overall, approximately 0.5% of all subjects treated with tadalafil for on demand use discontinued treatment as a consequence of back pain/myalgia. In the 1-year open label extension study, back pain and myalgia were reported in 5.5% and 1.3% of patients, respectively. Diagnostic testing, including measures for inflammation, muscle injury, or renal damage revealed no evidence of medically significant underlying pathology. Incidence rates for tadalafil for once daily use for ED, BPH and BPH/ED are described in Tables 2, 3 and 4. In studies of tadalafil for once daily use, adverse reactions of back pain and myalgia were generally mild or moderate with a discontinuation rate of less than 1% across all indications. Across placebo-controlled studies with tadalafil for use as needed for ED, diarrhea was reported more frequently inpatients 65 years of age and older who were treated with tadalafil (2.5% of patients) [see Use in Specific Populations ( 8.5 )] . Across all studies with any tadalafil dose, reports of changes in color vision were rare (less than 0.1% of patients). The following section identifies additional, less frequent events (less than 2%) reported in controlled clinical trials of tadalafil for once daily use or use as needed. A causal relationship of these events to tadalafil is uncertain. Excluded from this list are those events that were minor, those with no plausible relation to drug use, and reports too imprecise to be meaningful: Body as a Whole — asthenia, face edema, fatigue, pain, peripheral edema Cardiovascular — angina pectoris, chest pain, hypotension, myocardial infarction, postural hypotension, palpitations, syncope, tachycardia Digestive — abnormal liver function tests, dry mouth, dysphagia, esophagitis, gastritis, GGTP increased, loose stools, nausea, upper abdominal pain, vomiting, gastroesophageal reflux disease, hemorrhoidal hemorrhage, rectal hemorrhage Musculoskeletal — arthralgia, neck pain Nervous — dizziness, hypesthesia, insomnia, paresthesia, somnolence, vertigo Renal and Urinary — renal impairment Respiratory — dyspnea, epistaxis, pharyngitis Skin and Appendages — pruritus, rash, sweating Ophthalmologic — blurred vision, changes in color vision, conjunctivitis (including conjunctival hyperemia), eye pain, lacrimation increase, swelling of eyelids Otologic — sudden decrease or loss of hearing, tinnitus Urogenital — erection increased, spontaneous penile erection 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of tadalafil. 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 events have been chosen for inclusion either due to their seriousness, reporting frequency, lack of clear alternative causation, or a combination of these factors. Cardiovascular and Cerebrovascular — Serious cardiovascular events, including myocardial infarction, sudden cardiac death, stroke, chest pain, palpitations, and tachycardia, have been reported postmarketing in temporal association with the use of tadalafil. Most, but not all, of these patients had preexisting cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of tadalafil without sexual activity. Others were reported to have occurred hours to days after the use of tadalafil and sexual activity. It is not possible to determine whether these events are related directly to tadalafil, to sexual activity, to the patient’s underlying cardiovascular disease, to a combination of these factors, or to other factors [see Warnings and Precautions ( 5.1 )] . Body as a Whole — hypersensitivity reactions including urticaria, Stevens-Johnson syndrome, and exfoliative dermatitis Nervous — migraine, seizure and seizure recurrence, transient global amnesia Ophthalmologic — visual field defect, retinal vein occlusion, retinal artery occlusion 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 tadalafil. 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 )] . Otologic — Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including tadalafil. In some of the 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 tadalafil, to the patient’s underlying risk factors for hearing loss, a combination of these factors, or to other factors [see Warnings and Precautions ( 5.5 )] . Urogenital — priapism [see Warnings and Precautions ( 5.3 )]."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Tadalafil can potentiate the hypotensive effects of nitrates, alpha-blockers, antihypertensives or alcohol ( 7.1 ). CYP3A4 inhibitors (e.g. ketoconazole, ritonavir) increase tadalafil exposure ( 2.7 , 5.10 , 7.2 ) requiring dose adjustment: Tadalafil for use as needed: no more than 10 mg every 72 hours Tadalafil for once daily use: dose not to exceed 2.5 mg CYP3A4 inducers (e.g. rifampin) decrease tadalafil exposure ( 7.2 ). 7.1 Potential for Pharmacodynamic Interactions with Tadalafil Nitrates — Administration of tadalafil to patients who are using any form of organic nitrate, is contraindicated. In clinical pharmacology studies tadalafil was shown to potentiate the hypotensive effect of nitrates. In a patient who has taken tadalafil, where nitrate administration is deemed medically necessary in a life-threatening situation, at least 48 hours should elapse after the last dose of tadalafil before nitrate administration is considered. In such circumstances, nitrates should still only be administered under close medical supervision with appropriate hemodynamic monitoring [see Dosage and Administration ( 2.7 ), Contraindications ( 4.1 ), and Clinical Pharmacology ( 12.2 )] . Alpha-Blockers — Caution is advised when PDE5 inhibitors are coadministered with alpha-blockers. PDE5 inhibitors, including tadalafil, 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 tadalafil with doxazosin, tamsulosin or alfuzosin. [see Dosage and Administration ( 2.7 ), Warnings and Precautions ( 5.6 ), and Clinical Pharmacology ( 12.2 )] . Antihypertensives — PDE5 inhibitors, including tadalafil, are mild systemic vasodilators. Clinical pharmacology studies were conducted to assess the effect of tadalafil on the potentiation of the blood-pressure-lowering effects of selected antihypertensive medications (amlodipine, angiotensin II receptor blockers, bendrofluazide, enalapril, and metoprolol). Small reductions in blood pressure occurred following coadministration of tadalafil with these agents compared with placebo. [see Warnings and Precautions ( 5.6 ) and Clinical Pharmacology ( 12.2 )] . Alcohol — Both alcohol and tadalafil, a PDE5 inhibitor, act as mild vasodilators. When mild vasodilators are taken in combination, blood-pressure-lowering effects of each individual compound may be increased. Substantial consumption of alcohol (e.g., 5 units or greater) in combination with tadalafil can increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache. Tadalafil did not affect alcohol plasma concentrations and alcohol did not affect tadalafil plasma concentrations. [see Warnings and Precautions ( 5.9 ) and Clinical Pharmacology ( 12.2 )] . 7.2 Potential for Other Drugs to Affect Tadalafil [See Dosage and Administration ( 2.7 ) and Warnings and Precautions ( 5.10 )] . Antacids — Simultaneous administration of an antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil reduced the apparent rate of absorption of tadalafil without altering exposure (AUC) to tadalafil. H2 Antagonists (e.g. Nizatidine ) — An increase in gastric pH resulting from administration of nizatidine had no significant effect on pharmacokinetics. Cytochrome P450 Inhibitors — Tadalafil is a substrate of and predominantly metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase tadalafil exposure. CYP3A4 (e.g., Ketoconazole) — Ketoconazole (400 mg daily), a selective and potent inhibitor of CYP3A4, increased tadalafil 20 mg single-dose exposure (AUC) by 312% and Cmax by 22%, relative to the values for tadalafil 20 mg alone. Ketoconazole (200 mg daily) increased tadalafil 10-mg single-dose exposure (AUC) by 107% and Cmax by 15%, relative to the values for tadalafil 10 mg alone [see Dosage and Administration ( 2.7 )] . Although specific interactions have not been studied, other CYP3A4 inhibitors, such as erythromycin, itraconazole, and grapefruit juice, would likely increase tadalafil exposure. HIV Protease inhibitor — Ritonavir (500 mg or 600 mg twice daily at steady state), an inhibitor of CYP3A4, CYP2C9, CYP2C19, and CYP2D6, increased tadalafil 20-mg single-dose exposure (AUC) by 32% with a 30% reduction in C max , relative to the values for tadalafil 20 mg alone. Ritonavir (200 mg twice daily), increased tadalafil 20-mg single-dose exposure (AUC) by 124% with no change in Cmax , relative to the values for tadalafil 20 mg alone. Although specific interactions have not been studied, other HIV protease inhibitors would likely increase tadalafil exposure [see Dosage and Administration ( 2.7 )] . Cytochrome P450 Inducers — Studies have shown that drugs that induce CYP3A4 can decrease tadalafil exposure. CYP3A4 (e.g., Rifampin) — Rifampin (600 mg daily), a CYP3A4 inducer, reduced tadalafil 10-mg single-dose exposure (AUC) by 88% and Cmax by 46%, relative to the values for tadalafil 10 mg alone. Although specific interactions have not been studied, other CYP3A4 inducers, such as carbamazepine, phenytoin, and phenobarbital, would likely decrease tadalafil exposure. No dose adjustment is warranted. The reduced exposure of tadalafil with the coadministration of rifampin or other CYP3A4 inducers can be anticipated to decrease the efficacy of tadalafil for once daily use; the magnitude of decreased efficacy is unknown. 7.3 Potential for Tadalafil to Affect Other Drugs Aspirin — Tadalafil did not potentiate the increase in bleeding time caused by aspirin. Cytochrome P450 Substrates — Tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of drugs metabolized by cytochrome P450 (CYP) isoforms. Studies have shown that tadalafil does not inhibit or induce P450 isoforms CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP2E1. CYP1A2 (e.g. Theophylline) — Tadalafil had no significant effect on the pharmacokinetics of theophylline. When tadalafil was administered to subjects taking theophylline, a small augmentation (3 beats per minute) of the increase in heart rate associated with theophylline was observed. CYP2C9 (e.g. Warfarin) — Tadalafil had no significant effect on exposure (AUC) to S-warfarin or R-warfarin, nor did tadalafil affect changes in prothrombin time induced by warfarin. CYP3A4 (e.g. Midazolam or Lovastatin) — Tadalafil had no significant effect on exposure (AUC) to midazolam or lovastatin. P-glycoprotein (e.g. Digoxin ) — Coadministration of tadalafil (40 mg once per day) for 10 days did not have a significant effect on the steady-state pharmacokinetics of digoxin (0.25 mg/day) in healthy subjects."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of: erectile dysfunction (ED) ( 1.1 ) the signs and symptoms of benign prostatic hyperplasia (BPH) ( 1.2 ) ED and the signs and symptoms of BPH (ED/BPH) ( 1.3 ) If tadalafil is used with finasteride to initiate BPH treatment, such use is recommended for up to 26 weeks ( 1.4 ). 1.1 Erectile Dysfunction Tadalafil tablets are indicated for the treatment of erectile dysfunction (ED). 1.2 Benign Prostatic Hyperplasia Tadalafil tablets are indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). 1.3 Erectile Dysfunction and Benign Prostatic Hyperplasia Tadalafil tablets are indicated for the treatment of ED and the signs and symptoms of BPH (ED/BPH). 1.4 Limitation of Use If tadalafil is used with finasteride to initiate BPH treatment, such use is recommended for up to 26 weeks because the incremental benefit of tadalafil decreases from 4 weeks until 26 weeks, and the incremental benefit of tadalafil beyond 26 weeks is unknown [see Clinical Studies ( 14.3 )] ."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Evaluation of erectile dysfunction and BPH should include an appropriate medical assessment to identify potential underlying causes, as well as treatment options. Before prescribing tadalafil tablets, it is important to note the following: Patients should not use tadalafil if sex is inadvisable due to cardiovascular status ( 5.1 ). Use of tadalafil with alpha-blockers, antihypertensives or substantial amounts of alcohol (greater than or equal to 5 units) may lead to hypotension ( 5.6 , 5.9 ). Tadalafil is not recommended in combination with alpha-blockers for the treatment of BPH because efficacy of the combination has not been adequately studied and because of the risk of blood pressure lowering. Caution is advised when tadalafil is used as a treatment for ED in men taking alpha-blockers. ( 2.7 , 5.6 , 7.1 , 12.2 ) Patients should seek emergency treatment if an erection lasts greater than 4 hours. Use tadalafil with caution in patients predisposed to priapism ( 5.3 ). Patients should stop tadalafil and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of non-arteritic anterior ischemic optic neuropathy (NAION). Tadalafil 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 ). Patients should stop tadalafil and seek prompt medical attention in the event of sudden decrease or loss of hearing ( 5.5 ). Prior to initiating treatment with tadalafil for BPH, consideration should be given to other urological conditions that may cause similar symptoms ( 5.14 ). 5.1 Cardiovascular Physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. Therefore, treatments for erectile dysfunction, including tadalafil, should not be used in men for whom sexual activity is inadvisable as a result of their underlying cardiovascular status. Patients who experience symptoms upon initiation of sexual activity should be advised to refrain from further sexual activity and seek immediate medical attention. Physicians should discuss with patients the appropriate action in the event that they experience anginal chest pain requiring nitroglycerin following intake of tadalafil. In such a patient, who has taken tadalafil, where nitrate administration is deemed medically necessary for a life-threatening situation, at least 48 hours should have elapsed after the last dose of tadalafil tablets before nitrate administration is considered. In such circumstances, nitrates should still only be administered under close medical supervision with appropriate hemodynamic monitoring. Therefore, patients who experience anginal chest pain after taking tadalafil tablets should seek immediate medical attention. [see Contraindications ( 4.1 ) and Patient Counseling Information ( 17.1 )] . Patients with left ventricular outflow obstruction, (e.g., aortic stenosis and idiopathic hypertrophic subaortic stenosis) can be sensitive to the action of vasodilators, including PDE5 inhibitors. The following groups of patients with cardiovascular disease were not included in clinical safety and efficacy trials for tadalafil, and therefore until further information is available, tadalafil is not recommended for the following groups of patients: myocardial infarction within the last 90 days unstable angina or angina occurring during sexual intercourse New York Heart Association Class 2 or greater heart failure in the last 6 months uncontrolled arrhythmias, hypotension (less than 90/50 mm Hg), or uncontrolled hypertension stroke within the last 6 months. As with other PDE5 inhibitors, tadalafil has mild systemic vasodilatory properties that may result in transient decreases in blood pressure. In a clinical pharmacology study, tadalafil 20 mg resulted in a mean maximal decrease in supine blood pressure, relative to placebo, of 1.6/0.8 mm Hg in healthy subjects [see Clinical Pharmacology ( 12.2 )] . While this effect should not be of consequence in most patients, prior to prescribing tadalafil tablets, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects. Patients with severely impaired autonomic control of blood pressure may be particularly sensitive to the actions of vasodilators, including PDE5 inhibitors. 5.2 Potential for Drug Interactions When Taking Tadalafil tablets for Once Daily Use Physicians should be aware that tadalafil tablets for once daily use provides continuous plasma tadalafil levels and should consider this when evaluating the potential for interactions with medications (e.g., nitrates, alpha-blockers, antihypertensives and potent inhibitors of CYP3A4) and with substantial consumption of alcohol [see Drug Interactions ( 7.1 , 7.2 , 7.3 ) ]. 5.3 Prolonged Erection 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. Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. Patients who have an erection lasting greater than 4 hours, whether painful or not, should seek emergency medical attention. Tadalafil should be used with caution in patients who have conditions that might predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia), or in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie’s disease). 5.4 Effects on the Eye Physicians should advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including tadalafil, and seek medical attention in the event of a 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 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 greater than or equal to 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 tadalafil, 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 tadalafil, for this uncommon condition. Patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa, were not included in the clinical trials, and use in these patients is not recommended. 5.5 Sudden Hearing Loss Physicians should advise patients to stop taking PDE5 inhibitors, including tadalafil, 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 tadalafil. 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 ( 6.1 , 6.2 )] . 5.6 Alpha-blockers and Antihypertensives Physicians should discuss with patients the potential for tadalafil to augment the blood-pressure-lowering effect of alpha-blockers and antihypertensive medications [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.2 )] . Caution is advised when PDE5 inhibitors are coadministered with alpha-blockers. PDE5 inhibitors, including tadalafil, 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 [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.2 )] , which may lead to symptomatic hypotension (e.g., fainting). Consideration should be given to the following: ED • 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 dose. • 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 when 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 antihypertensive drugs. [see Dosage and Administration ( 2.7 ) and Drug Interactions ( 7.1 )] . BPH • The efficacy of the coadministration of an alpha-blocker and tadalafil for the treatment of BPH has not been adequately studied, and due to the potential vasodilatory effects of combined use resulting in blood pressure lowering, the combination of tadalafil and alpha-blockers is not recommended for the treatment of BPH. [see Dosage and Administration ( 2.7 ), Drug Interactions ( 7.1 ), and Clinical Pharmacology ( 12.2 .)] . • Patients on alpha-blocker therapy for BPH should discontinue their alpha-blocker at least one day prior to starting tadalafil for once daily use for the treatment of BPH. 5.7 Renal Impairment Tadalafil tablets for Use as Needed Tadalafil should be limited to 5 mg not more than once in every 72 hours in patients with creatinine clearance less than 30 mL/min or end-stage renal disease on hemodialysis. The starting dose of tadalafil in patients with creatinine clearance 30 mL/min to 50 mL/min should be 5 mg not more than once per day, and the maximum dose should be limited to 10 mg not more than once in every 48 hours. [see Use in Specific Populations ( 8.7 )] . Tadalafil tablets for Once Daily Use ED Due to increased tadalafil exposure (AUC), limited clinical experience, and the lack of ability to influence clearance by dialysis, tadalafil tablets for once daily use is not recommended in patients with creatinine clearance less than 30 mL/min [see Use in Specific Populations ( 8.7 )] . BPH and ED/BPH Due to increased tadalafil exposure (AUC), limited clinical experience, and the lack of ability to influence clearance by dialysis, tadalafil for once daily use is not recommended in patients with creatinine clearance less than 30 mL/min. In patients with creatinine clearance 30 mL/min to 50 mL/min, start dosing at 2.5 mg once daily, and increase the dose to 5 mg once daily based upon individual response [see Dosage and Administration ( 2.6 ), Use in Specific Populations ( 8.7 ), and Clinical Pharmacology ( 12.3 )] . 5.8 Hepatic Impairment Tadalafil tablets for Use as Needed In patients with mild or moderate hepatic impairment, the dose of tadalafil tablets should not exceed 10 mg. Because of insufficient information in patients with severe hepatic impairment, use of tadalafil in this group is not recommended [see Use in Specific Populations ( 8.6 )] . Tadalafil tablets for Once Daily Use Tadalafil tablets for once daily use has not been extensively evaluated in patients with mild or moderate hepatic impairment. Therefore, caution is advised if tadalafil tablets for once daily use is prescribed to these patients. Because of insufficient information in patients with severe hepatic impairment, use of tadalafil in this group is not recommended [see Use in Specific Populations ( 8.6 )] . 5.9 Alcohol Patients should be made aware that both alcohol and tadalafil, a PDE5 inhibitor, act as mild vasodilators. When mild vasodilators are taken in combination, blood-pressure-lowering effects of each individual compound may be increased. Therefore, physicians should inform patients that substantial consumption of alcohol (e.g., 5 units or greater) in combination with tadalafil can increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache [see Clinical Pharmacology ( 12.2 )] . 5.10 Concomitant Use of Potent Inhibitors of Cytochrome P450 3A4 (CYP3A4) Tadalafil is metabolized predominantly by CYP3A4 in the liver. The dose of tadalafil tablets for use as needed should be limited to 10 mg no more than once every 72 hours in patients taking potent inhibitors of CYP3A4 such as ritonavir, ketoconazole, and itraconazole [see Drug Interactions ( 7.2 )] . In patients taking potent inhibitors of CYP3A4 and tadalafil tablets for once daily use, the maximum recommended dose is 2.5 mg [see Dosage and Administration ( 2.7 )] . 5.11 Combination With Other PDE5 Inhibitors or Erectile Dysfunction Therapies The safety and efficacy of combinations of tadalafil and other PDE5 inhibitors or treatments for erectile dysfunction have not been studied. Inform patients not to take tadalafil with other PDE5 inhibitors, including ADCIRCA. 5.12 Effects on Bleeding Studies in vitro have demonstrated that tadalafil is a selective inhibitor of PDE5. PDE5 is found in platelets. When administered in combination with aspirin, tadalafil 20 mg did not prolong bleeding time, relative to aspirin alone. Tadalafil has not been administered to patients with bleeding disorders or significant active peptic ulceration. Although tadalafil has not been shown to increase bleeding times in healthy subjects, use in patients with bleeding disorders or significant active peptic ulceration should be based upon a careful risk-benefit assessment and caution. 5.13 Counseling Patients About Sexually Transmitted Diseases The use of tadalafil offers no protection against sexually transmitted diseases. Counseling patients about the protective measures necessary to guard against sexually transmitted diseases, including Human Immunodeficiency Virus (HIV) should be considered. 5.14 Consideration of Other Urological Conditions Prior to Initiating Treatment for BPH Prior to initiating treatment with tadalafil for BPH, consideration should be given to other urological conditions that may cause similar symptoms. In addition, prostate cancer and BPH may coexist. 5.15 Risk of Allergic Reactions due to Tartrazine Tadalafil Tablets contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity."}', 'overdosage': '{"10 OVERDOSAGE Single doses up to 500 mg have been given to healthy subjects, and multiple daily doses up to 100 mg have been given to patients. Adverse events were similar to those seen at lower doses. In cases of overdose, standard supportive measures should be adopted as required. Hemodialysis contributes negligibly to tadalafil elimination."}', 'active_flag': 'Y', 'generic_name': '{TADALAFIL}', '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)” 17.1 Nitrates Physicians should discuss with patients the contraindication of tadalafil with regular and/or intermittent use of organic nitrates. Patients should be counseled that concomitant use of tadalafil with nitrates could cause blood pressure to suddenly drop to an unsafe level, resulting in dizziness, syncope, or even heart attack or stroke. Physicians should discuss with patients the appropriate action in the event that they experience anginal chest pain requiring nitroglycerin following intake of tadalafil. In such a patient, who has taken tadalafil, where nitrate administration is deemed medically necessary for a life-threatening situation, at least 48 hours should have elapsed after the last dose of tadalafil before nitrate administration is considered. In such circumstances, nitrates should still only be administered under close medical supervision with appropriate hemodynamic monitoring. Therefore, patients who experience anginal chest pain after taking tadalafil should seek immediate medical attention [see Contraindications ( 4.1 ) and Warnings and Precautions ( 5.1 )] . 17.2 Guanylate Cyclase (GC) Stimulators Physicians should discuss with patients the contraindication of tadalafil with any use of a GC stimulator, such as riociguat, for pulmonary arterial hypertension. Patients should be counseled that the concomitant use of tadalafil with GC stimulators may cause blood pressure to drop to an unsafe level. 17.3 Cardiovascular Considerations Physicians should consider the potential cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Physicians should advise patients who experience symptoms upon initiation of sexual activity to refrain from further sexual activity and seek immediate medical attention [see Warnings and Precautions ( 5.1 )] . 17.4 Concomitant Use with Drugs Which Lower Blood Pressure Physicians should discuss with patients the potential for tadalafil to augment the blood-pressure-lowering effect of alpha-blockers, and antihypertensive medications [see Warnings and Precautions ( 5.6 ), Drug Interactions ( 7.1 ), and Clinical Pharmacology ( 12.2 )] . 17.5 Potential for Drug Interactions When Taking tadalafil tablets for Once Daily Use Physicians should discuss with patients the clinical implications of continuous exposure to tadalafil when prescribing tadalafil for once daily use, especially the potential for interactions with medications (e.g., nitrates, alpha-blockers, antihypertensives and potent inhibitors of cytochrome P450 3A4) and with substantial consumption of alcohol. [see Dosage and Administration ( 2.7 ), Warnings and Precautions ( 5.6 ), Drug Interactions ( 7.1 , 7.2 ), Clinical Pharmacology ( 12.2 ), and Clinical Studies (14.2)] . 17.6 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. Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. Physicians should advise patients who have an erection lasting greater than 4 hours, whether painful or not, to seek emergency medical attention. 17.7 Sudden Loss of Vision Physicians should advise patients to stop use of all PDE5 inhibitors, including tadalafil, and seek medical attention in the event of a 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 possible permanent loss of vision, that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors. Physicians should 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 inhibitors, including tadalafil, for this uncommon condition [see Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.2 )] . 17.8 Sudden Hearing Loss Physicians should advise patients to stop taking PDE5 inhibitors, including tadalafil, 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 tadalafil. 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 ( 6.1 , 6.2 )] . 17.9 Alcohol Patients should be made aware that both alcohol and tadalafil, a PDE5 inhibitor, act as mild vasodilators. When mild vasodilators are taken in combination, blood-pressure-lowering effects of each individual compound may be increased. Therefore, physicians should inform patients that substantial consumption of alcohol (e.g., 5 units or greater) in combination with tadalafil can increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache [see Warnings and Precautions ( 5.9 ), Drug Interactions ( 7.1 ), and Clinical Pharmacology ( 12.2 )] . 17.10 Sexually Transmitted Disease The use of tadalafil offers no protection against sexually transmitted diseases. Counseling of patients about the protective measures necessary to guard against sexually transmitted diseases, including Human Immunodeficiency Virus (HIV) should be considered. 17.11 Recommended Administration Physicians should instruct patients on the appropriate administration of tadalafil to allow optimal use. For tadalafil for use as needed in men with ED, patients should be instructed to take one tablet at least 30 minutes before anticipated sexual activity. In most patients, the ability to have sexual intercourse is improved for up to 36 hours. For tadalafil for once daily use in men with ED or ED/BPH, patients should be instructed to take one tablet at approximately the same time every day without regard for the timing of sexual activity. Tadalafil is effective at improving erectile function over the course of therapy. For tadalafil for once daily use in men with BPH, patients should be instructed to take one tablet at approximately the same time every day. Revised: 08/2022 Marketed by: Ajanta Pharma USA Inc. Bridgewater, NJ 08807. Made in INDIA."}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Tadalafil is not indicated for use in females. There are no data with the use of tadalafil in pregnant women to inform any drug-associated risks for adverse developmental outcomes. In animal reproduction studies, no adverse developmental effects were observed with oral administration of tadalafil to pregnant rats or mice during organogenesis at exposures up to 11 times the maximum recommended human dose (MRHD) of 20 mg/day (see Data). Data Animal Data Animal reproduction studies showed no evidence of teratogenicity, embryotoxicity, or fetotoxicity when tadalafil was given orally to pregnant rats or mice at exposures up to 11 times the maximum recommended human dose (MRHD) of 20 mg/day during organogenesis. In a prenatal/postnatal developmental studies in rats, postnatal pup survival decreased following maternal exposure to tadalafil doses greater than 10 times the MRHD based on AUC. Signs of maternal toxicity occurred at doses greater than 16 times the MRHD based on AUC. Surviving offspring had normal development and reproductive performance. In another rat prenatal and postnatal development study at doses of 60 mg/kg, 200 mg/kg, and 1000 mg/kg, a reduction in postnatal survival of pups was observed. The no observed effect level (NOEL) for maternal toxicity was 200 mg/kg/day and for developmental toxicity was 30 mg/kg/day. This gives approximately 16 and 10 fold exposure multiples, respectively, of the human AUC for the MRHD of 20 mg. Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats."}', 'pediatric_use': '{"8.4 Pediatric Use Tadalafil is not indicated for use in pediatric patients. Safety and efficacy in patients below the age of 18 years have not been established. A randomized, double-blind, placebo-controlled trial in pediatric patients (7 to 14 years of age) with Duchenne muscular dystrophy, who received tadalafil 0.3 mg/kg, tadalafil 0.6 mg/kg, or placebo daily for 48 weeks failed to demonstrate any benefit of treatment with tadalafil on a range of assessments of muscle strength and performance. Juvenile Animal Study No adverse effects were observed in a study in which tadalafil was administered orally at doses of 60 mg/kg/day, 200 mg/kg/day, and 1000 mg/kg/day to juvenile rats on postnatal days 14 to 90. The highest plasma tadalafil exposures (AUC) achieved were approximately 10-fold that observed at the MRHD."}', 'geriatric_use': '{"8.5 Geriatric Use Of the total number of subjects in ED clinical studies of tadalafil, approximately 19 percent were 65 and over, while approximately 2 percent were 75 and over. Of the total number of subjects in BPH clinical studies of tadalafil (including the ED/BPH study), approximately 40 percent were over 65, while approximately 10 percent were 75 and over. In these clinical trials, no overall differences in efficacy or safety were observed between older (greater than 65 and greater than or equal to75 years of age) and younger subjects (less than or equal to 65 years of age). However, in placebo-controlled studies with tadalafil for use as needed for ED, diarrhea was reported more frequently in patients 65 years of age and older who were treated with tadalafil (2.5% of patients) [see Adverse Reactions ( 6.1 )] . No dose adjustment is warranted based on age alone. However, a greater sensitivity to medications in some older individuals should be considered. [see Clinical Pharmacology ( 12.3 )] ."}'}

{ALCOHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use Decreases bacteria on hands."}', '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': None, 'when_using': '{"When using this product keep out of eyes. Stop use and ask a doctor if irritation or redness develops."}', 'warnings': '{"Warnings Flammable: Keep away from flame or high heat.","For external use only."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{GEMFIBROZIL}

{'contraindications': '{"CONTRAINDICATIONS 1. Hepatic or severe renal dysfunction, including primary biliary cirrhosis. 2. Preexisting gallbladder disease (see WARNINGS ). 3. Hypersensitivity to gemfibrozil. 4. Combination therapy of gemfibrozil with simvastatin (see WARNINGS and PRECAUTIONS ). 5. Combination therapy of gemfibrozil with repaglinide (see PRECAUTIONS ). 6. Combination therapy of gemfibrozil with dasabuvir (see PRECAUTIONS ). 7. Combination therapy of gemfibrozil with selexipag (see PRECAUTIONS )."}', 'adverse_reactions': '{"ADVERSE REACTIONS In the double-blind controlled phase of the primary prevention component of the Helsinki Heart Study, 2046 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: 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 versus 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: Additional adverse reactions that have been reported include cholecystitis and cholelithiasis ( see WARNINGS). Adverse Reactions Additional Adverse Reactions"}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE Gemfibrozil Tablets are indicated as adjunctive therapy to diet for: 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 2000 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 1000 mg/dL are unlikely to present a risk of pancreatitis. Gemfibrozil therapy may be considered for those subjects with triglyceride elevations between 1000 and 2000 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 1000 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. 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, 1000 subjects with previous myocardial infarction were treated for five years with clofibrate. There was no difference in mortality between the clofibrate-treated subjects and 3000 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), 5000 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 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, 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 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 ). Avoid concomitant use of gemfibrozil with rosuvastatin. If concomitant use cannot be avoided, initiate rosuvastatin at 5 mg once daily. The dose of rosuvastatin should not exceed 10 mg once daily. 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 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 2–3) 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 C max (ratios: 11.3 and 2.01, respectively) due to CYP2C8 inhibition. Increased dasabuvir exposure may increase the risk of QT prolongation, therefore, co-administration of gemfibrozil with dasabuvir is contraindicated (see CONTRAINDICATIONS ). Selexipag: Co-administration of gemfibrozil with selexipag doubled exposure to selexipag and increased exposure to the active metabolite by approximately 11-fold. Concomitant administration of gemfibrozil with selexipag 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 - 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 long-term 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}

{POVIDONE-IODINE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses prepping intact skin and mucous membranes prior to surgery"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"POVIDONE IODINE"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop using this product and ask a doctor if Skin shows symptoms of irritation, sensitivity, redness, pain or swelling"}', 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings For external use only Avoid use on persons allergic to iodine"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"DOCUSATE SODIUM"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses relieves occasional constipation (irregularity) generally produces bowel movement in 12 to 72 hours"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"DOCUSATE SODIUM"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings Ask a doctor before use if you have stomach pain, nausea or vomiting have a sudden change in bowel habits that persists over a period of 2 weeks are presently taking mineral oil Stop use and ask a doctor if you need to use a laxative longer than 1 week you have rectal bleeding or fail to have a bowel movement. 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}

{LIDOCAINE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use helps relieve the pain, itching and burning associated with hemorrhoids and other anorectal disorders."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{LIDOCAINE}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if rectal bleeding occurs condition worsens or does not improve within 7 days allergic reaction occurs to ingredients in this product symptom being treated does not subside or if redness, irritation, swelling, pain or other symptoms develop or increase symptoms clear up and return within a few days"}', 'do_not_use': None, 'when_using': '{"When using this product avoid contact with the eyes do not exceed the recommended daily dosage unless directed by a doctor do not put into the rectum by using fingers or any mechanical device or applicator"}', 'warnings': '{"Warnings For external use only. When using this product avoid contact with the eyes do not exceed the recommended daily dosage unless directed by a doctor do not put into the rectum by using fingers or any mechanical device or applicator Stop use and ask a doctor if rectal bleeding occurs condition worsens or does not improve within 7 days allergic reaction occurs to ingredients in this product symptom being treated does not subside or if redness, irritation, swelling, pain or other symptoms develop or increase symptoms clear up and return within a few days If pregnant or breastfeeding ask a health professional before use. 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}

{CLOTRIMAZOLE}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses For relief of most fungal skin infection symptoms."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{CLOTRIMAZOLE}', '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 on children under two years of age unless directed by a physician. Avoid contact with the eyes. If irritation occurs or if there is no improvement within 4 weeks, discontinue use and consult a physician. Keep out of reach of children . If swallowed, call poison control or seek medical help."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{ALCOHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Directions 1. Open the cover, Pick as much as you needs, Wipe your body gently. 2. Put sticker after using. There is risk of drying. 3. Use it as soon as possible after opening. ※ Supervise children under 6 years of age when using this product to avoid swallowing"}', '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': None, 'when_using': '{"3. Avoid contact with eyes. In case of contact, rinse eyes thoroughly with water Do not dispose used tissue in the flushing toilet. Do not put used tissue into pack again. There is the risk of degeneration."}', 'warnings': '{"Warning! 6. Flammable. Keep away from heat or flame. Use only as intended and according to the directions of use."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"ERYTHROMYCIN ETHYLSUCCINATE"}

{'contraindications': '{"CONTRAINDICATIONS Erythromycin is contraindicated in patients with known hypersensitivity to this antibiotic. Erythromycin is contraindicated in patients taking terfenadine, astemizole, pimozide, or cisapride (see PRECAUTIONS - Drug Interactions ). Do not use erythromycin concomitantly with HMG CoA reductase inhibitors (statins) that are extensively metabolized by CYP 3A4 (lovastatin or simvastatin), due to the increased risk of myopathy, including rhabdomyolysis."}', 'adverse_reactions': '{"ADVERSE REACTIONS The most frequent side effects of oral erythromycin preparations are gastrointestinal and are dose-related. They include nausea, vomiting, abdominal pain, diarrhea and anorexia. Symptoms of hepatitis, hepatic dysfunction and/or abnormal liver function test results may occur (see WARNINGS section). Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment (See WARNINGS section). Erythromycin has been associated with QT prolongation and ventricular arrhythmias, including ventricular tachycardia and torsades de pointes (see WARNINGS ). Allergic reactions ranging from urticaria to anaphylaxis have occurred. Skin reactions ranging from mild eruptions to erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely. There have been reports of interstitial nephritis coincident with erythromycin use. There have been rare reports of pancreatitis and convulsions. There have been isolated reports of reversible hearing loss occurring chiefly in patients with renal insufficiency and in patients receiving high doses of erythromycin."}', 'drug_interactions': '{"Drug Interactions Theophylline Erythromycin use in patients who are receiving high doses of theophylline may be associated with an increase in serum theophylline levels and potential theophylline toxicity. In case of theophylline toxicity and/or elevated serum theophylline levels, the dose of theophylline should be reduced while the patient is receiving concomitant erythromycin therapy. There have been published reports suggesting that when oral erythromycin is given concurrently with theophylline there is a decrease in erythromycin serum concentrations of approximately 35%. The mechanism by which this interaction occurs is unknown. The decrease in erythromycin concentrations due to co-administration of theophylline could result in subtherapeutic concentrations of erythromycin. Verapamil Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving concurrent verapamil, belonging to the calcium channel blockers drug class. Digoxin Concomitant administration of erythromycin and digoxin has been reported to result in elevated digoxin serum levels. Anticoagulants There have been reports of increased anticoagulant effects when erythromycin and oral anticoagulants were used concomitantly. Increased anticoagulation effects due to interactions of erythromycin with various oral anticoagulants may be more pronounced in the elderly. Erythromycin is a substrate and inhibitor of the 3A isoform subfamily of the cytochrome p450 enzyme system (CYP3A). Coadministration of erythromycin and a drug primarily metabolized by CYP3A may be associated with elevations in drug concentrations that could increase or prolong both the therapeutic and adverse effects of the concomitant drug. Dosage adjustments may be considered, and when possible, serum concentrations of drugs primarily metabolized by CYP3A should be monitored closely in patients concurrently receiving erythromycin. The following are examples of some clinically significant CYP3A based drug interactions. Interactions with other drugs metabolized by the CYP3A isoform are also possible. The following CYP3A based drug interactions have been observed with erythromycin products in post-marketing experience: Ergotamine/dihydroergotamine Post-marketing reports indicate that coadministration of erythromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system. Concomitant administration of erythromycin with ergotamine or dihydroergotamine is contraindicated (see CONTRAINDICATIONS ). Triazolobenzodiazepines (such as triazolam and alprazolam) and related benzodiazepines Erythromycin has been reported to decrease the clearance of triazolam and midazolam, and thus, may increase the pharmacologic effect of these benzodiazepines. HMG-CoA Reductase Inhibitors Erythromycin has been reported to increase concentrations of HMG-CoA reductase inhibitors (e.g., lovastatin and simvastatin). Rare reports of rhabdomyolysis have been reported in patients taking these drugs concomitantly. Sildenafil (Viagra) Erythromycin has been reported to increase the systemic exposure (AUC) of sildenafil. Reduction of sildenafil dosage should be considered. (See Viagra package insert.) There have been spontaneous or published reports of CYP3A based interactions of erythromycin with cyclosporine, carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine, methylprednisolone, cilostazol, vinblastine, and bromocriptine. Concomitant administration of erythromycin with cisapride, pimozide, astemizole, or terfenadine is contraindicated (see CONTRAINDICATIONS ). In addition, there have been reports of interactions of erythromycin with drugs not thought to be metabolized by CYP3A, including hexobarbital, phenytoin, and valproate. Erythromycin has been reported to significantly alter the metabolism of the nonsedating antihistamines terfenadine and astemizole when taken concomitantly. Rare cases of serious cardiovascular adverse events, including electrocardiographic QT/QT c interval prolongation, cardiac arrest, torsades de pointes, and other ventricular arrhythmias have been observed (see CONTRAINDICATIONS ). In addition, deaths have been reported rarely with concomitant administration of terfenadine and erythromycin. There have been post-marketing reports of drug interactions when erythromycin is co-administered with cisapride, resulting in QT prolongation, cardiac arrhythmias, ventricular tachycardia, ventricular fibrillation, and torsades de pointes, most likely due to inhibition of hepatic metabolism of cisapride by erythromycin. Fatalities have been reported (see CONTRAINDICATIONS ). Colchicine Colchicine is a substrate for both CYP3A4 and the efflux transporter P-glycoprotein (P-gp). Erythromycin is considered a moderate inhibitor of CYP3A4. A significant increase in colchicine plasma concentration is anticipated when co-administered with moderate CYP3A4 inhibitors such as erythromycin. If co-administration of colchicine and erythromycin is necessary, the starting dose of colchicine may need to be reduced, and the maximum colchicine dose should be lowered. Patients should be monitored for clinical symptoms of colchicine toxicity (see WARNINGS )."}', 'indications_and_usage': '{"INDICATIONS AND USAGE To reduce the development of drug-resistant bacteria and maintain the effectiveness of erythromycin ethylsuccinate tablets, USP and other antibacterial drugs, erythromycin ethylsuccinate tablets, USP 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. Erythromycin ethylsuccinate tablets, USP are indicated in the treatment of infections caused by susceptible strains of the designated organisms in the diseases listed below: Upper respiratory tract infections of mild to moderate degree caused by Streptococcus pyogenes , Streptococcus pneumoniae , or Haemophilus influenzae (when used concomitantly with adequate doses of sulfonamides, since many strains of H. influenzae are not susceptible to the erythromycin concentrations ordinarily achieved). (See appropriate sulfonamide labeling for prescribing information.) Lower-respiratory tract infections of mild to moderate severity caused by S treptococcus pneumoniae or Streptococcus pyogenes . Listeriosis caused by Listeria monocytogenes . Pertussis (whooping cough) caused by Bordetella pertussis . Erythromycin is effective in eliminating the organism from the nasopharynx of infected individuals rendering them noninfectious. Some clinical studies suggest that erythromycin may be helpful in the prophylaxis of pertussis in exposed susceptible individuals. Respiratory tract infections due to Mycoplasma pneumoniae . Skin and skin structure infections of mild to moderate severity caused by Streptococcus pyogenes or Staphylococcus aureus (resistant staphylococci may emerge during treatment). Diphtheria: Infections due to Corynebacterium diphtheriae , as an adjunct to antitoxin, to prevent establishment of carriers and to eradicate the organism in carriers. Erythrasma: In the treatment of infections due to Corynebacterium minutissimum . Intestinal amebiasis caused by Entamoeba histolytica (oral erythromycins only). Extraenteric amebiasis requires treatment with other agents. Acute pelvic inflammatory disease caused by Neisseria gonorrhoeae : As an alternative drug in treatment of acute pelvic inflammatory disease caused by N. gonorrhoeae in female patients with a history of sensitivity to penicillin. Patients should have a serologic test for syphilis before receiving erythromycin as treatment of gonorrhea and a follow-up serologic test for syphilis after 3 months. Syphilis caused by Treponema pallidum : Erythromycin is an alternate choice of treatment for primary syphilis in patients allergic to the penicillins. In treatment of primary syphilis, spinal fluid examinations should be done before treatment and as part of follow-up after therapy. Erythromycins are indicated for the treatment of the following infections caused by Chlamydia trachomatis : conjunctivitis of the newborn, pneumonia of infancy, and urogenital infections during pregnancy. When tetracyclines are contraindicated or not tolerated, erythromycin is indicated for the treatment of uncomplicated urethral, endocervical, or rectal infections in adults due to Chlamydia trachomatis. When tetracyclines are contraindicated or not tolerated, erythromycin is indicated for the treatment of nongonococcal urethritis caused by Ureaplasma urealyticum. Legionnaires\' Disease caused by Legionella pneumophila : Although no controlled clinical efficacy studies have been conducted, in vitro and limited preliminary clinical data suggest that erythromycin may be effective in treating Legionnaires\' Disease. Prophylaxis Prevention of Initial Attacks of Rheumatic Fever Penicillin is considered by the American Heart Association to be the drug of choice in the prevention of initial attacks of rheumatic fever (treatment of Streptococcus pyogenes infections of the upper respiratory tract, e.g., tonsillitis or pharyngitis). Erythromycin is indicated for the treatment of penicillin-allergic patients. 1 The therapeutic dose should be administered for 10 days. Prevention of Recurrent Attacks of Rheumatic Fever Penicillin or sulfonamides are considered by the American Heart Association to be the drugs of choice in the prevention of recurrent attacks of rheumatic fever. In patients who are allergic to penicillin and sulfonamides, oral erythromycin is recommended by the American Heart Association in the long-term prophylaxis of streptococcal pharyngitis (for the prevention of recurrent attacks of rheumatic fever). 1"}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE In case of overdosage, erythromycin should be discontinued. Overdosage should be handled with the prompt elimination of unabsorbed drug and all other appropriate measures should be instituted. Erythromycin is not removed by peritoneal dialysis or hemodialysis."}', 'active_flag': 'Y', 'generic_name': '{"ERYTHROMYCIN ETHYLSUCCINATE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Hepatotoxicity There have been reports of hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, occurring in patients receiving oral erythromycin products. QT Prolongation Erythromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving erythromycin. Fatalities have been reported. Erythromycin should be avoided in patients with known prolongation of the QT interval, patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval. Syphilis in Pregnancy There have been reports suggesting that erythromycin does not reach the fetus in adequate concentration to prevent congenital syphilis. Infants born to women treated during pregnancy with oral erythromycin for early syphilis should be treated with an appropriate penicillin regimen. Clostridium difficile Associated Diarrhea Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Erythromycin Ethylsuccinate Tablets, 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. Drug Interactions Serious adverse reactions have been reported in patients taking erythromycin concomitantly with CYP3A4 substrates. These include colchicine toxicity with colchicine; rhabdomyolysis with simvastatin, lovastatin, and atorvastatin; and hypotension with calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem) (see PRECAUTIONS-Drug Interactions ). There have been post-marketing reports of colchicine toxicity with concomitant use of erythromycin and colchicine. This interaction is potentially life-threatening, and may occur while using both drugs at their recommended doses (see PRECAUTIONS-Drug Interactions ). Rhabdomyolysis with or without renal impairment has been reported in seriously ill patients receiving erythromycin concomitantly with lovastatin. Therefore, patients receiving concomitant lovastatin and erythromycin should be carefully monitored for creatine kinase (CK) and serum transaminase levels. (See package insert for lovastatin.)"}', 'precautions': '{"PRECAUTIONS General Prescribing erythromycin ethylsuccinate tablets 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. Since erythromycin is principally excreted by the liver, caution should be exercised when erythromycin is administered to patients with impaired hepatic function (see CLINICAL PHARMACOLOGY and WARNINGS sections). Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome have been reported in patients receiving erythromycin therapy. There have been reports of infantile hypertrophic pyloric stenosis (IHPS) occurring in infants following erythromycin therapy. In one cohort of 157 newborns who were given erythromycin for pertussis prophylaxis, seven neonates (5%) developed symptoms of non-bilious vomiting or irritability with feeding and were subsequently diagnosed as having IHPS requiring surgical pyloromyotomy. A possible dose-response effect was described with an absolute risk of IHPS of 5.1% for infants who took erythromycin for 8 to 14 days and 10% for infants who took erythromycin for 15 to 21 days. 2 Since erythromycin may be used in the treatment of conditions in infants which are associated with significant mortality or morbidity (such as pertussis or neonatal Chlamydia trachomatis infections), the benefit of erythromycin therapy needs to be weighed against the potential risk of developing IHPS. Parents should be informed to contact their physician if vomiting or irritability with feeding occurs. Prolonged or repeated use of erythromycin may result in an overgrowth of nonsusceptible bacteria or fungi. If superinfection occurs, erythromycin should be discontinued and appropriate therapy instituted. When indicated, incision and drainage or other surgical procedures should be performed in conjunction with antibiotic therapy. Information for Patients Patients should be counseled that antibacterial drugs, including erythromycin ethylsuccinate tablets, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When erythromycin ethylsuccinate tablets 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 erythromycin ethylsuccinate tablets 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. Drug Interactions Theophylline Erythromycin use in patients who are receiving high doses of theophylline may be associated with an increase in serum theophylline levels and potential theophylline toxicity. In case of theophylline toxicity and/or elevated serum theophylline levels, the dose of theophylline should be reduced while the patient is receiving concomitant erythromycin therapy. There have been published reports suggesting that when oral erythromycin is given concurrently with theophylline there is a decrease in erythromycin serum concentrations of approximately 35%. The mechanism by which this interaction occurs is unknown. The decrease in erythromycin concentrations due to co-administration of theophylline could result in subtherapeutic concentrations of erythromycin. Verapamil Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving concurrent verapamil, belonging to the calcium channel blockers drug class. Digoxin Concomitant administration of erythromycin and digoxin has been reported to result in elevated digoxin serum levels. Anticoagulants There have been reports of increased anticoagulant effects when erythromycin and oral anticoagulants were used concomitantly. Increased anticoagulation effects due to interactions of erythromycin with various oral anticoagulants may be more pronounced in the elderly. Erythromycin is a substrate and inhibitor of the 3A isoform subfamily of the cytochrome p450 enzyme system (CYP3A). Coadministration of erythromycin and a drug primarily metabolized by CYP3A may be associated with elevations in drug concentrations that could increase or prolong both the therapeutic and adverse effects of the concomitant drug. Dosage adjustments may be considered, and when possible, serum concentrations of drugs primarily metabolized by CYP3A should be monitored closely in patients concurrently receiving erythromycin. The following are examples of some clinically significant CYP3A based drug interactions. Interactions with other drugs metabolized by the CYP3A isoform are also possible. The following CYP3A based drug interactions have been observed with erythromycin products in post-marketing experience: Ergotamine/dihydroergotamine Post-marketing reports indicate that coadministration of erythromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system. Concomitant administration of erythromycin with ergotamine or dihydroergotamine is contraindicated (see CONTRAINDICATIONS ). Triazolobenzodiazepines (such as triazolam and alprazolam) and related benzodiazepines Erythromycin has been reported to decrease the clearance of triazolam and midazolam, and thus, may increase the pharmacologic effect of these benzodiazepines. HMG-CoA Reductase Inhibitors Erythromycin has been reported to increase concentrations of HMG-CoA reductase inhibitors (e.g., lovastatin and simvastatin). Rare reports of rhabdomyolysis have been reported in patients taking these drugs concomitantly. Sildenafil (Viagra) Erythromycin has been reported to increase the systemic exposure (AUC) of sildenafil. Reduction of sildenafil dosage should be considered. (See Viagra package insert.) There have been spontaneous or published reports of CYP3A based interactions of erythromycin with cyclosporine, carbamazepine, tacrolimus, alfentanil, disopyramide, rifabutin, quinidine, methylprednisolone, cilostazol, vinblastine, and bromocriptine. Concomitant administration of erythromycin with cisapride, pimozide, astemizole, or terfenadine is contraindicated (see CONTRAINDICATIONS ). In addition, there have been reports of interactions of erythromycin with drugs not thought to be metabolized by CYP3A, including hexobarbital, phenytoin, and valproate. Erythromycin has been reported to significantly alter the metabolism of the nonsedating antihistamines terfenadine and astemizole when taken concomitantly. Rare cases of serious cardiovascular adverse events, including electrocardiographic QT/QT c interval prolongation, cardiac arrest, torsades de pointes, and other ventricular arrhythmias have been observed (see CONTRAINDICATIONS ). In addition, deaths have been reported rarely with concomitant administration of terfenadine and erythromycin. There have been post-marketing reports of drug interactions when erythromycin is co-administered with cisapride, resulting in QT prolongation, cardiac arrhythmias, ventricular tachycardia, ventricular fibrillation, and torsades de pointes, most likely due to inhibition of hepatic metabolism of cisapride by erythromycin. Fatalities have been reported (see CONTRAINDICATIONS ). Colchicine Colchicine is a substrate for both CYP3A4 and the efflux transporter P-glycoprotein (P-gp). Erythromycin is considered a moderate inhibitor of CYP3A4. A significant increase in colchicine plasma concentration is anticipated when co-administered with moderate CYP3A4 inhibitors such as erythromycin. If co-administration of colchicine and erythromycin is necessary, the starting dose of colchicine may need to be reduced, and the maximum colchicine dose should be lowered. Patients should be monitored for clinical symptoms of colchicine toxicity (see WARNINGS ). Drug/Laboratory Test Interactions Erythromycin interferes with the fluorometric determination of urinary catecholamines. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term oral dietary studies conducted with erythromycin stearate in rats up to 400 mg/kg/day and in mice up to about 500 mg/kg/day (approximately 1 to 2 fold of the maximum human dose on a body surface area basis) did not provide evidence of tumorigenicity. Erythromycin stearate did not show genotoxic potential in the Ames, and mouse lymphoma assays or induce chromosomal aberrations in CHO cells. There was no apparent effect on male or female fertility in rats treated with erythromycin base by oral gavage at 700 mg/kg/day (approximately 3 times the maximum human dose on a body surface area basis). Pregnancy Teratogenic Effects There is no evidence of teratogenicity or any other adverse effect on reproduction in female rats fed erythromycin base by oral gavage at 350 mg/kg/day (approximately twice the maximum recommended human dose on a body surface area) prior to and during mating, during gestation, and through weaning. No evidence of teratogenicity or embryotoxicity was observed when erythromycin base was given by oral gavage to pregnant rats and mice at 700 mg/kg/day and to pregnant rabbits at 125 mg/kg/day (approximately 1 to 3 times the maximum recommended human dose). Labor and Delivery The effect of erythromycin on labor and delivery is unknown. Nursing Mothers Erythromycin is excreted in human milk. Caution should be exercised when erythromycin is administered to a nursing woman. Pediatric Use See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION sections. Geriatric Use Elderly patients, particularly those with reduced renal or hepatic function, may be at increased risk for developing erythromycin-induced hearing loss (see ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION ). Elderly patients may be more susceptible to the development of torsades de pointes arrhythmias than younger patients (see WARNINGS ). Elderly patients may experience increased effects of oral anticoagulant therapy while undergoing treatment with erythromycin (see PRECAUTIONS – Drug Interactions ). Erythromycin Ethylsuccinate Tablets (400 mg) contain 47 mg (2 mEq) of sodium and 9.2 mg (0.3 mEq) of potassium per tablet. 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 erythromycin ethylsuccinate tablets, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When erythromycin ethylsuccinate tablets 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 erythromycin ethylsuccinate tablets 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 There is no evidence of teratogenicity or any other adverse effect on reproduction in female rats fed erythromycin base by oral gavage at 350 mg/kg/day (approximately twice the maximum recommended human dose on a body surface area) prior to and during mating, during gestation, and through weaning. No evidence of teratogenicity or embryotoxicity was observed when erythromycin base was given by oral gavage to pregnant rats and mice at 700 mg/kg/day and to pregnant rabbits at 125 mg/kg/day (approximately 1 to 3 times the maximum recommended human dose)."}', 'pediatric_use': '{"Pediatric Use See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION sections."}', 'geriatric_use': '{"Geriatric Use Elderly patients, particularly those with reduced renal or hepatic function, may be at increased risk for developing erythromycin-induced hearing loss (see ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION ). Elderly patients may be more susceptible to the development of torsades de pointes arrhythmias than younger patients (see WARNINGS ). Elderly patients may experience increased effects of oral anticoagulant therapy while undergoing treatment with erythromycin (see PRECAUTIONS – Drug Interactions ). Erythromycin Ethylsuccinate Tablets (400 mg) contain 47 mg (2 mEq) of sodium and 9.2 mg (0.3 mEq) of potassium per tablet. 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."}'}

{ALCOHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use Hand Sanitizer to help reduce bacteria that potentially can cause disease. For use when soap and water are 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 or rash occurs. These may be signs of a serious condition."}', 'do_not_use': '{"Do not use in children less than 2 months of age on open skin wounds"}', 'when_using': '{"When using this product keep out of eyes, ears, and mouth. In case of contact with eyes, rinse eyes thoroughly with water. Stop use and ask a doctor if irritation or rash occurs. These may be signs of a serious condition. Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away."}', 'warnings': '{"Warnings For external use only. Flammable. Keep away from heat or flame"}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{HYDROCORTISONE}

{'contraindications': '{"CONTRAINDICATIONS Topical corticosteroids are contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation."}', 'adverse_reactions': '{"ADVERSE REACTIONS The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS AND USAGE Topical corticosteroids are indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects (see PRECAUTIONS )."}', 'active_flag': 'Y', 'generic_name': '{HYDROCORTISONE}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': None, 'precautions': '{"PRECAUTIONS General Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing\'s syndrome, hyperglycemia, and glucosuria in some patients. Conditions which augment systemic absorption include the application of the more potent steroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression by using the urinary free cortisol and ACTH stimulation tests. If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the drug. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids. Children may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity (see PRECAUTIONS-Pediatric Use ). If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted. In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, the corticosteroid should be discontinued until the infection has been adequately controlled. Information for the Patient Patients using topical corticosteroids should receive the following information and instructions: This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes. Patients should be advised not to use this medication for any disorder other than for which it was prescribed. The treated skin area should not be bandaged or otherwise covered or wrapped so as to be occlusive unless directed by the physician. Patients should report any signs of local adverse reactions, especially under occlusive dressing. Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on a child being treated in the diaper area, as these garments may constitute occlusive dressings. Laboratory Tests The following tests may be helpful in evaluating HPA axis suppression: Urinary free cortisol test ACTH stimulation test Carcinogenesis, Mutagenesis, and Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of topical corticosteroids. Studies to determine mutagenicity with prednisolone and hydrocortisone have revealed negative results. Pregnancy Teratogenic Effects Pregnancy Category C Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time. Nursing Mothers It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk in quantities not likely to have a deleterious effect on the infant. Nevertheless, caution should be exercised when topical corticosteroids are administered to a nursing woman. Pediatric Use Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced hypothalamic-pituitary-adrenal (HPA) axis suppression and Cushing\'s syndrome than mature patients because of a larger skin surface area to body weight ratio. Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing\'s syndrome, and intracranial hypertension have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients include linear growth retardation, delayed weight gain, low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Administration of topical corticosteroids to pediatric patients should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of pediatric patients."}', 'information_for_patients': '{"Information for the Patient Patients using topical corticosteroids should receive the following information and instructions: This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes. Patients should be advised not to use this medication for any disorder other than for which it was prescribed. The treated skin area should not be bandaged or otherwise covered or wrapped so as to be occlusive unless directed by the physician. Patients should report any signs of local adverse reactions, especially under occlusive dressing. Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on a child being treated in the diaper area, as these garments may constitute occlusive dressings."}', 'pregnancy': '{"Pregnancy Teratogenic Effects Pregnancy Category C Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time."}', 'pediatric_use': '{"Pediatric Use Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced hypothalamic-pituitary-adrenal (HPA) axis suppression and Cushing\'s syndrome than mature patients because of a larger skin surface area to body weight ratio. Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing\'s syndrome, and intracranial hypertension have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients include linear growth retardation, delayed weight gain, low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Administration of topical corticosteroids to pediatric patients should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of pediatric patients."}', 'geriatric_use': None}

{"METOPROLOL TARTRATE"}

{'contraindications': '{"4 CONTRAINDICATIONS Metoprolol tartrate tablets are contraindicated in severe bradycardia, second or third degree heart block, cardiogenic shock, systolic blood pressure <100, decompensated heart 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: Greater than first degree heart block, or sick sinus syndrome without a pacemaker. ( 4 ) Cardiogenic shock or decompensated heart failure. ( 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) ]. \xadMost common adverse reactions: tiredness, dizziness, depression, shortness of breath, bradycardia, hypotension, diarrhea, pruritus, rash. ( 6.1 ) 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. 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. Hypertension and Angina Most adverse effects have been mild and transient. Central Nervous System: Tiredness and dizziness have occurred in about 10% of patients. Depression has been reported in about 5 of 100 patients. Mental confusion and short-term memory loss have been reported. Headache, nightmares, and insomnia have also been reported. Cardiovascular: Shortness of breath and bradycardia have occurred in approximately 3% of patients. Cold extremities; arterial insufficiency, usually of the Raynaud type; palpitations; heart failure exacerbations; peripheral edema; and hypotension have been reported in about 1% of patients. Gangrene in patients with pre-existing severe peripheral circulatory disorders has also been reported. [see Contraindications (4) and Warnings and Precautions (5.2) ]. Respiratory: Wheezing (bronchospasm) and dyspnea have been reported in about 1% of patients [see Warnings and Precautions (5.3) ] . Rhinitis has also been reported. Gastrointestinal: Diarrhea has occurred in about 5% of patients. Nausea, dry mouth, gastric pain, constipation, flatulence, and heartburn have been reported in about 1% of patients. Vomiting was a common occurrence. Hypersensitive Reactions: Pruritus or rash have occurred in about 5% of patients. Photosensitivity and worsening of psoriasis has been reported. Miscellaneous: Peyronie’s disease, musculoskeletal pain, blurred vision, and tinnitus has been reported. Myocardial Infarction In general, the adverse reactions observed in trials with metoprolol in MI are consistent with the hypertension and angina experience. In a randomized comparison of metoprolol and placebo in the setting of acute MI the following adverse reactions were reported: Metoprolol Placebo Hypotension (systolic BP < 90 mm Hg) 27.4% 23.2% Bradycardia (heart rate < 40 beats/min) 15.9% 6.7% Second- or third-degree heart block 4.7% 4.7% First-degree heart block (P-R ≥ 0.26 sec) 5.3% 1.9% Heart failure 27.5% 29.6% 6.2 Post-Marketing Experience The following adverse reactions have been identified during post approval use of drug X. 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. 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, slightly clouded sensorium, and decreased performance on neuropsychometrics. Cardiovascular: Intensification of AV block [see Contraindications (4) ]. Hematologic: Agranulocytosis, nonthrombocytopenic purpura and thrombocytopenic purpura. Hypersensitive Reactions: Fever combined with aching and sore throat, laryngospasm and respiratory distress. Laboratory Findings : Increase in blood triglycerides, elevated transaminase and decrease in High Density Lipoprotein (HDL)"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Catecholamine-depleting drugs may have an additive effect when given with beta-blocking agents. ( 7.1 ) Patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction. ( 7.2 ) CYP2D6 Inhibitors are likely to increase metoprolol concentration. ( 7.3 ) Concomitant use of glycosides, clonidine, and diltiazem and verapamil with beta-blockers can increase the risk of bradycardia. ( 7.4 ) Beta-blockers including metoprolol, may exacerbate the rebound hypertension that can follow the withdrawal of clonidine. ( 7.4 ) 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 plus a catecholamine depletor for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension. 7.2 Epinephrine 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. 7.3 CYP2D6 Inhibitors Drugs that are strong inhibitors of CYP2D6 such as quinidine, fluoxetine, paroxetine, and propafenone were shown to double metoprolol concentrations. While there is no information about moderate or weak inhibitors, these too are likely to increase metoprolol concentration. Increases in plasma concentration decrease the cardioselectivity of metoprolol [see Clinical Pharmacology (12.3) ]. Monitor patients closely, when the combination cannot be avoided. 7.4 Negative Chronotropes 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 ."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Metoprolol tartrate tablets are a beta-adrenergic blocker 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 ) Myocardial Infarction, to reduce the risk of cardiovascular mortality when used in conjunction with intravenous metoprolol therapy in patients with definite or suspected acute myocardial infarction in hemodynamically stable patients ( 1.3 ) 1.1 Hypertension Metoprolol tartrate tablets are indicated for the treatment of hypertension in adult patients, 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 tartrate tablets may be administered with other antihypertensive agents. 1.2 Angina Pectoris Metoprolol tartrate tablets are indicated in the long-term treatment of angina pectoris, to reduce angina attacks and to improve exercise tolerance. 1.3 Myocardial Infarction Metoprolol tartrate tablets are indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality when used alone or in conjunction with intravenous metoprolol."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Abrupt cessation may exacerbate myocardial ischemia. ( 5.1 ) Heart Failure: Worsening cardiac failure may occur. ( 5.2 ) Bronchospastic Disease: Avoid beta-blockers. ( 5.3 ) Pheochromocytoma: Initiate therapy with an alpha blocker. ( 5.4 ) Major Surgery: Avoid initiation of high-dose extended-release metoprolol in patients undergoing non-cardiac surgery. Do not routinely withdraw chronic beta-blocker therapy prior to surgery. ( 5.5 , 6.1 ) Diabetes: May mask symptoms of hypoglycemia.( 5.6 ) Thyrotoxicosis: Abrupt withdrawal in patients with thyrotoxicosis might precipitate a thyroid storm. ( 5.7 ) Peripheral Vascular Disease: Can aggravate symptoms of arterial insufficiency. ( 5.9 ) 5.1 Abrupt Cessation of Therapy 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, particularly in patients with ischemic heart disease, gradually reduce the dosage over a period of 1 to 2 weeks and monitor the patient. If angina markedly worsens or acute coronary ischemia develops, promptly reinstate metoprolol, 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 in patients treated only for hypertension. 5.2 Heart Failure Worsening cardiac failure may occur during up-titration of metoprolol. If such symptoms occur, increase diuretics and restore clinical stability before advancing the dose of metoprolol [see Dosage and Administration (2) ]. It may be necessary to lower the dose of metoprolol or temporarily discontinue it. Such episodes do not preclude subsequent successful titration of metoprolol. 5.3 Bronchospastic Disease Patients with bronchospastic disease, should in general, not receive beta-blockers, including metoprolol. Because of its relative beta 1 cardio-selectivity, however, metoprolol 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. Bronchodilators, including beta 2 -agonists, should be readily available or administered concomitantly [see Dosage and Administration (2) ]. 5.4 Pheochromocytoma If metoprolol 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 beta-blocker therapy 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 Hypoglycemia Beta-blockers may prevent early warning signs of hypoglycemia, such as tachycardia, and increase the risk for severe or prolonged hypoglycemia at any time during treatment, especially in patients with diabetes mellitus or children and patients who are fasting (i.e., surgery, not eating regularly, or are vomiting). If severe hypoglycemia occurs, patients should be instructed to seek emergency treatment. 5.7 Thyrotoxicosis Beta-adrenergic blockade may mask certain clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of beta-blockade may precipitate a thyroid storm. 5.8 Risk of Anaphylactic Reactions While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction. 5.9 Peripheral Vascular Disease Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease."}', 'overdosage': '{"10 OVERDOSAGE Signs and Symptoms - Overdosage of metoprolol 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. 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. Hemodialysis is unlikely to make a useful contribution to metoprolol elimination [see Clinical Pharmacology (12.3) ]. 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 TARTRATE"}', '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 tartrate 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 tartrate 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 tartrate 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 tartrate tablets. Inform patients or caregivers that there is a risk of hypoglycemia when metoprolol tartrate tablets are given to patients who are fasting or who are vomiting. Instruct patients or caregivers how to monitor for signs of hypoglycemia [see Warnings and Precautions (5.6) ] . Repackaged By / Distributed By: RemedyRepack Inc. 625 Kolter Drive, Indiana, PA 15701 (724) 465-8762"}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Available data from published observational studies have not demonstrated an association of adverse developmental outcomes with maternal use of metoprolol during pregnancy ( see Data). Untreated hypertension and myocardial infarction during pregnancy can lead to adverse outcomes for the mother and the fetus (see Clinical Considerations). In animal reproduction studies, metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, approximately 11 times the daily dose of 450 mg in a 60-kg patient on a mg/m 2 basis. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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 consideration 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. Fetal/Neonatal adverse reactions Metoprolol crosses the placenta. Neonates born to mothers who are receiving metoprolol during pregnancy, may be at risk for hypotension, hypoglycemia, bradycardia, and respiratory depression. Observe neonates and manage accordingly. Data Human Data Data from published observational studies did not demonstrate an association of major congenital malformations and use of metoprolol in pregnancy. The published literature has reported inconsistent findings of intrauterine growth retardation, preterm birth and perinatal mortality with maternal use of metoprolol during pregnancy; however, these studies have methodological limitations hindering interpretation. Methodological limitations include retrospective design, concomitant use of other medications, and other unadjusted confounders that may account for the study findings including the underlying disease in the mother. These observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. Animal Data Metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, i.e. 11 times, on a mg/m 2 basis, the daily dose of 450 mg in a 60-kg patient. No fetal abnormalities were observed when pregnant rats received metoprolol orally up to a dose of 200 mg/kg/day, i.e. 4 times, the daily dose of 400 mg in a 60-kg patient."}', 'pediatric_use': '{"8.4 Pediatric Use Safety and effectiveness of metoprolol have not been established in pediatric patients."}', 'geriatric_use': '{"8.5 Geriatric Use Clinical studies of metoprolol 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. In worldwide clinical trials of metoprolol in myocardial infarction, where approximately 478 patients were over 65 years of age (0 over 75 years of age), no age-related differences in safety and effectiveness were found. Other reported clinical experience in myocardial infarction has not identified differences in response between the elderly 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."}'}

{"SODIUM FLUORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use - aids in the prevention of dental cavities"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"MIPASTE ONE KIDS COTTON CANDY"}', 'route': '{DENTAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"Warning Keep out of reach of children under 6 years of age. If more than the recommended amount of paste used for brushing is accidentally swallowed, get medical help or contact a Poison Control Center right away. Do not use on patients with a milk protein or hydroxybenzoates allergy. In case of allergic reaction, stop use, rinse mouth with water and seek medical advice."}', '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': '{"Use helps eliminate bacteria on hands"}', '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': '{"When using this product do not use in near the eyes. In case of contact, rinse eyes throughly with water."}', 'warnings': '{"Warnings For external use only When using this product do not use in near the eyes. In case of contact, rinse eyes throughly with water. Keep out of the reach of children, except under adult supervision. 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}

{"METOCLOPRAMIDE HYDROCHLORIDE"}

{'contraindications': '{"CONTRAINDICATIONS Metoclopramide should not be used whenever stimulation of gastrointestinal motility might be dangerous, e.g., in the presence of gastrointestinal hemorrhage, mechanical obstruction or perforation. Metoclopramide is contraindicated in patients with pheochromocytoma because the drug may cause a hypertensive crisis, probably due to release of catecholamines from the tumor. Such hypertensive crises may be controlled by phentolamine. Metoclopramide is contraindicated in patients with known sensitivity or intolerance to the drug. Metoclopramide should not be used in epileptics or patients receiving other drugs which are likely to cause extrapyramidal reactions, since the frequency and severity of seizures or extrapyramidal reactions may be increased."}', 'adverse_reactions': '{"ADVERSE REACTIOS In general, the incidence of adverse reactions correlates with the dose and duration of metoclopramide administration. The following reactions have been reported, although in most instances, data do not permit an estimate of frequency. CNS Effects Restlessness, drowsiness, fatigue and lassitude may occur in patients receiving the recommended prescribed dosage of metoclopramide injection. Insomnia, headache, confusion, dizziness, or mental depression with suicidal ideation also may occur (see WARNINGS ). In cancer chemotherapy patients being treated with 1 to 2 mg/kg per dose, incidence of drowsiness is about 70%. There are isolated reports of convulsive seizures without a clear-cut relationship to metoclopramide. Rarely, hallucinations have been reported. Extrapyramidal Reactions (EPS) Acute dystonic reactions, the most common type of EPS associated with metoclopramide, occur in approximately 0.2% of patients (1 in 500) treated with 30 to 40 mg of metoclopramide per day. In cancer chemotherapy patients receiving 1 to 2 mg/kg per dose, the incidence is 2% in patients over the ages of 30 to 35, and 25% or higher in pediatric patients and adult patients less than 30 years of age who have not had prophylactic administration of diphenhydramine. Symptoms include involuntary movements of limbs, facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, opisthotonus (tetanus-like reactions) and rarely, stridor and dyspnea, possibly due to laryngospasm; ordinarily these symptoms are readily reversed by diphenhydramine (see WARNINGS ). Parkinsonian-like symptoms may include bradykinesia, tremor, cogwheel rigidity, mask-like facies (see WARNINGS ). Tardive dyskinesia most frequently is characterized by involuntary movements of the tongue, face, mouth or jaw, and sometimes by involuntary movements of the trunk and/or extremities; movements may be choreoathetotic in appearance (see WARNINGS ). Motor restlessness (akathisia) may consist of feelings of anxiety, agitation, jitteriness, and insomnia, as well as inability to sit still, pacing, and foot tapping. These symptoms may disappear spontaneously or respond to a reduction in dosage. Neuroleptic Malignant Syndrome Rare occurrences of neuroleptic malignant syndrome (NMS) have been reported. This potentially fatal syndrome is comprised of the symptom complex of hyperthermia, muscular rigidity, altered consciousness, and autonomic instability (see WARNINGS ). Endocrine Disturbances Galactorrhea, amenorrhea, gynecomastia, impotence secondary to hyperprolactinemia (see PRECAUTIONS). Fluid retention secondary to transient elevation of aldosterone (see CLINICAL PHARMACOLOGY ). Cardiovascular Hypotension, hypertension, supraventricular tachycardia, bradycardia, fluid retention, acute congestive heart failure, and possible atrioventricular (AV) block (see CONTRAINDICATIONS and PRECAUTIONS ). Gastrointestinal Nausea and bowel disturbances, primarily diarrhea. Hepatic Rarely, cases of hepatotoxicity, characterized by such findings as jaundice and altered liver function tests, when metoclopramide was administered with other drugs with known hepatotoxic potential. Renal Urinary frequency and incontinence. Hematologic A few cases of neutropenia, leukopenia, or agranulocytosis, generally without a clear-cut relationship to metoclopramide. Methemoglobinemia, in adults and especially with overdosage in neonates (see OVERDOSAGE ). Sulfhemoglobinemia in adults. Allergic Reactions A few cases of rash, urticaria, or bronchospasm, especially in patients with a history of asthma. Rarely, angioneurotic edema, including glossal or laryngeal edema. Miscellaneous Visual disturbances, Porphyria. Transient flushing of the face and upper body, without alterations in vital signs, following high doses intravenously."}', 'drug_interactions': None, 'indications_and_usage': '{"INDICATIONS & USAGE Diabetic Gastroparesis (Diabetic Gastric Stasis) Metoclopramide is indicated for the relief of symptoms associated with acute and recurrent diabetic gastric stasis. The Prevention of Nausea and Vomiting Associated with Emetogenic Cancer Chemotherapy Metoclopramide Injection, USP is indicated for the prophylaxis of vomiting associated with emetogenic cancer chemotherapy. The Prevention of Postoperative Nausea and Vomiting Metoclopramide Injection, USP is indicated for the prophylaxis of postoperative nausea and vomiting in those circumstances where nasogastric suction is undesirable. Small Bowel Intubation Metoclopramide Injection, USP may be used to facilitate small bowel intubation in adults and pediatric patients in whom the tube does not pass the pylorus with conventional maneuvers. Radiological Examination Metoclopramide Injection, USP may be used to stimulate gastric emptying and intestinal transit of barium in cases where delayed emptying interferes with radiological examination of the stomach and/or small intestine."}', 'warnings_and_cautions': None, 'overdosage': '{"OVERDOSAGE Symptoms of overdosage may include drowsiness, disorientation and extrapyramidal reactions. Anticholinergic or antiparkinson drugs or antihistamines with anticholinergic properties may be helpful in controlling the extrapyramidal reactions. Symptoms are self-limiting and usually disappear within 24 hours. Hemodialysis removes relatively little metoclopramide, probably because of the small amount of the drug in blood relative to tissues. Similarly, continuous ambulatory peritoneal dialysis does not remove significant amounts of drug. It is unlikely that dosage would need to be adjusted to compensate for losses through dialysis. Dialysis is not likely to be an effective method of drug removal in overdose situations. Unintentional overdose due to misadministration has been reported in infants and children with the use of metoclopramide syrup. While there was no consistent pattern to the reports associated with these overdoses, events included seizures, extrapyramidal reactions and lethargy. Methemoglobinemia has occurred in premature and full-term neonates who were given overdoses of metoclopramide (1 to 4 mg/kg/day orally, intramuscularly or intravenously for 1 to 3 or more days). Methemoglobinemia can be reversed by the intravenous administration of methylene blue. However, methylene blue may cause hemolytic anemia in patients with G6PD deficiency, which may be fatal (see PRECAUTIONS – Other Special Populations)."}', 'active_flag': 'Y', 'generic_name': '{METOCLOPRAMIDE}', 'route': '{INTRAMUSCULAR,INTRAVENOUS}', 'product_type': '{"HUMAN PRESCRIPTION DRUG"}', 'stop_use': None, 'do_not_use': None, 'when_using': None, 'warnings': '{"WARNINGS Neuroleptic Malignant Syndrome (NMS) There have been rare reports of an uncommon but potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) associated with metoclopramide. Clinical manifestations of NMS include hyperthermia, muscle rigidity, altered consciousness, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac arrhythmias). 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, malignant hyperthermia, drug fever and primary central nervous system (CNS) pathology. The management of NMS should include 1) immediate discontinuation of metoclopramide 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. Bromocriptine and dantrolene sodium have been used in treatment of NMS, but their effectiveness have not been established (see ADVERSE REACTIONS ). Extrapyramidal Symptoms (EPS) Acute Dystonic Reactions Acute dystonic reactions occur in approximately 1 in 500 patients treated with the usual adult dosages of 30 to 40 mg/day of metoclopramide. These usually are seen during the first 24 to 48 hours of treatment with metoclopramide, occur more frequently in pediatric patients and adult patients less than 30 years of age and are even more frequent at the higher doses used in prophylaxis of vomiting due to cancer chemotherapy. These symptoms may include involuntary movements of limbs and facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, or dystonic reactions resembling tetanus. Rarely, dystonic reactions may present as stridor and dyspnea, possibly due to laryngospasm. If these symptoms should occur, inject 50 mg Benadryl® (diphenhydramine hydrochloride) intramuscularly, and they usually will subside. Cogentin® (benztropine mesylate), 1 to 2 mg intramuscularly, may also be used to reverse these reactions. Tardive Dyskinesia (see BOXED WARNINGS ) Treatment with metoclopramide can cause tardive dyskinesia (TD), a potentially irreversible and disfiguring disorder characterized by involuntary movements of the face, tongue, or extremities. The risk of tardive dyskinesia increases with the duration of treatment and the total cumulative dose. An analysis of utilization patterns showed that about 20% of patients who used metoclopramide took it longer than 12 weeks. Treatment with metoclopramide for longer than the recommended 12 weeks should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risk of developing TD. Although the risk of developing TD in the general population may be increased among the elderly, women, and diabetics, it is not possible to predict which patients will develop metoclopramide-induced TD. Both the risk of developing TD and the likelihood that TD will become irreversible increase with duration of treatment and total cumulative dose. Metoclopramide should be discontinued in patients who develop signs or symptoms of TD. There is no known effective treatment for established cases of TD, although in some patients, TD may remit, partially or completely, within several weeks to months after metoclopramide is withdrawn. Metoclopramide itself may suppress, or partially suppress, the signs of TD, thereby masking the underlying disease process. The effect of this symptomatic suppression upon the long-term course of TD is unknown. Therefore, metoclopramide should not be used for the symptomatic control of TD. Parkinsonian-like Symptoms Parkinsonian-like symptoms, including bradykinesia, tremor, cogwheel rigidity, or mask-like facies, have occurred, more commonly within the first 6 months after beginning treatment with metoclopramide, but occasionally after longer periods. These symptoms generally subside within 2 to 3 months following discontinuance of metoclopramide. Patients with pre-existing Parkinson\'s disease should be given metoclopramide cautiously, if at all, since such patients may experience exacerbation of parkinsonian symptoms when taking metoclopramide. Depression Mental depression has occurred in patients with and without prior history of depression. Symptoms have ranged from mild to severe and have included suicidal ideation and suicide. Metoclopramide should be given to patients with a prior history of depression only if the expected benefits outweigh the potential risks."}', 'precautions': '{"PRECAUTIONS General In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines, hence, caution should be exercised when metoclopramide is used in patients with hypertension. Intravenous injections of undiluted metoclopramide should be made slowly allowing 1 to 2 minutes for 10 mg since a transient but intense feeling of anxiety and restlessness, followed by drowsiness, may occur with rapid administration. Because metoclopramide produces a transient increase in plasma aldosterone, certain patients, especially those with cirrhosis or congestive heart failure, may be at risk of developing fluid retention and volume overload. If these side effects occur at any time during metoclopramide therapy, the drug should be discontinued. Intravenous administration of Metoclopramide Injection, USP, diluted in a parenteral solution should be made slowly over a period of not less than 15 minutes. Giving a promotility drug such as metoclopramide theoretically could put increased pressure on suture lines following a gut anastomosis or closure. This possibility should be considered and weighed when deciding whether to use metoclopramide or nasogastric suction in the prevention of postoperative nausea and vomiting. Information for Patients A patient Medication Guide is available for metoclopramide. 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. Refer to the accompanying Medication Guide. Metoclopramide may impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle. The ambulatory patient should be cautioned accordingly. Drug Interactions The effects of metoclopramide on gastrointestinal motility are antagonized by anticholinergic drugs and narcotic analgesics. Additive sedative effects can occur when metoclopramide is given with alcohol, sedatives, hypnotics, narcotics or tranquilizers. The finding that metoclopramide releases catecholamines in patients with essential hypertension suggests that it should be used cautiously, if at all, in patients receiving monoamine oxidase inhibitors. Absorption of drugs from the stomach may be diminished (e.g., digoxin) by metoclopramide, whereas the rate and/or extent of absorption of drugs from the small bowel may be increased (e.g., acetaminophen, tetracycline, levodopa, ethanol, cyclosporine). Gastroparesis (gastric stasis) may be responsible for poor diabetic control in some patients. Exogenously administered insulin may begin to act before food has left the stomach and lead to hypoglycemia. Because the action of metoclopramide will influence the delivery of food to the intestines and thus the rate of absorption, insulin dosage or timing of dosage may require adjustment. Carcinogenesis, Mutagenesis, Impairment of Fertility A 77-week study was conducted in rats with oral doses up to about 40 times the maximum recommended human daily dose. Metoclopramide elevates prolactin levels and 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 metoclopramide is contemplated in a patient with previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported with prolactin-elevating drugs, 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 prolactin-stimulating neuroleptic drugs and metoclopramide. 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 too limited to be conclusive at this time. An Ames mutagenicity test performed on metoclopramide was negative. Pregnancy Reproduction studies performed in rats, mice, and rabbits by the IM, IV, subcutaneous (SC), and oral routes at maximum levels ranging from 12 to 250 times the human dose have demonstrated no impairment of fertility or significant harm to the fetus due to metoclopramide. 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 Metoclopramide is excreted in human milk. Caution should be exercised when metoclopramide is administered to a nursing mother. Pediatric Use Safety and effectiveness in pediatric patients have not been established except as stated to facilitate small bowel intubation (see OVERDOSAGE and DOSAGE & ADMINISTRATION ). Care should be exercised in administering metoclopramide to neonates since prolonged clearance may produce excessive serum concentrations (see CLINICAL PHARMACOLOGY – Pharmacokinetics). In addition, neonates have reduced levels of NADH-cytochrome b5 reductase which, in combination with the aforementioned pharmacokinetic factors, make neonates more susceptible to methemoglobinemia (see OVERDOSAGE ). The safety profile of metoclopramide in adults cannot be extrapolated to pediatric patients. Dystonias and other extrapyramidal reactions associated with metoclopramide are more common in the pediatric population than in adults (see WARNINGS and ADVERSE REACTIONS – Extrapyramidal Reactions (EPS)). Geriatric Use Clinical studies of metoclopramide did not include sufficient numbers of subjects aged 65 and over to determine whether elderly subjects respond differently from younger subjects. The risk of developing parkinsonian-like side effects increases with ascending dose. Geriatric patients should receive the lowest dose of metoclopramide that is effective. If parkinsonian-like symptoms develop in a geriatric patient receiving metoclopramide, metoclopramide should generally be discontinued before initiating any specific anti-parkinsonian agents (see WARNINGS ). The elderly may be at greater risk for tardive dyskinesia (see WARNINGS – Tardive Dyskinesia). Sedation has been reported in metoclopramide users. Sedation may cause confusion and manifest as over-sedation in elderly (see CLINICAL PHARMACOLOGY , PRECAUTIONS – Information for Patients and ADVERSE REACTIONS – CNS Effects). Metoclopramide 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 (see DOSAGE & ADMINISTRATION – Use in Patients with Renal or Hepatic Impairment). For these reasons, 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 renal function, concomitant disease, or other drug therapy in the elderly (see DOSAGE & ADMINISTRATION – Use in Patients with Renal or Hepatic Impairment). Other Special Populations Patients with NADH-cytochrome b5 reductase deficiency are at an increased risk of developing methemoglobinemia and/or sulfhemoglobinemia when metoclopramide is administered. In patients with G6PD deficiency who experience metoclopramide-induced methemoglobinemia, methylene blue treatment is not recommended (see OVERDOSAGE )."}', 'information_for_patients': '{"MEDICATION GUIDE Metoclopramide Injection, USP You or your caregiver should read the Medication Guide before you start receiving metoclopramide injection and before you get another dose of metoclopramide injection. There may be new information. If you take another product that contains metoclopramide (such as metoclopramide tablets, metoclopramide orally disintegrating tablets, or metoclopramide oral solution), you should read the Medication Guide that comes with that product. Some of the information may be different. This Medication Guide does not take the place of talking to your doctor about your medical condition or your treatment. What is the most important information I should know about metoclopramide? Metoclopramide can cause serious side effects, including: Abnormal muscle movements called tardive dyskinesia (TD). These movements happen mostly in the face muscles. You can not control these movements. They may not go away even after stopping metoclopramide. There is no treatment for TD, but symptoms may lessen or go away over time after you stop taking metoclopramide. Your chances for getting TD go up: • the longer you take metoclopramide and the more metoclopramide you take. You should not take metoclopramide for more than 12 weeks. • if you are older, especially if you are a woman • if you have diabetes It is not possible for your doctor to know if you will get TD if you take metoclopramide. Call your doctor right away if you get movements you can not stop or control, such as: • lip smacking, chewing, or puckering up your mouth • frowning or scowling • sticking out your tongue • blinking and moving your eyes • shaking of your arms and legs See the section \\"What are the possible side effects of metoclopramide?\\" for more information about side effects. What is metoclopramide? Metoclopramide is a prescription medicine used to: • relieve symptoms of slow stomach emptying in people with diabetes • prevent nausea and vomiting that can happen with cancer chemotherapy • prevent nausea and vomiting that may happen after surgery, if your doctor decides that you should not be treated with a stomach tube and suction • help make it easier to insert a tube into the small intestine in both adults and children, if the tube does not pass into the stomach normally. • to help empty stomach contents or to help barium move through your intestine, when you get an X-ray examination of the stomach or small intestine. It is not known if metoclopramide is safe and works in children except when used to help insert a tube into the small intestine. Who should not receive metoclopramide? Do not receive metoclopramide if you: • have stomach or intestine problems that could get worse with metoclopramide, such as bleeding, blockage or a tear in your stomach or bowel wall • have an adrenal gland tumor called pheochromocytoma • are allergic to metoclopramide or anything in it. See the end of this Medication Guide for a list of ingredients in metoclopramide. • take medicines that can cause uncontrolled movements, such as medicines for mental illness • have seizures What should I tell my doctor before receiving metoclopramide? Tell your doctor about all of your medical conditions, including if you have: • depression • Parkinson\'s disease • high blood pressure • kidney problems. Your doctor may start with a lower dose. • liver problems or heart failure. Metoclopramide may cause your body to hold fluids. • diabetes. Your dose of insulin may need to be changed. • breast cancer • you are pregnant or plan to become pregnant. It is not known if metoclopramide will harm your unborn child. • you are breastfeeding. Metoclopramide is passed into human milk and may harm your baby. Talk with your doctor about the best way to feed your baby if you take metoclopramide. Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Metoclopramide and some other medicines can affect each other and may not work as well, or cause possible side effects. Do not start any new medicines while receiving metoclopramide until you talk with your doctor. Especially tell your doctor if you take: • another medicine that contains metoclopramide, such as metoclopramide tablets, metoclopramide orally disintegrating tablets, or metoclopramide oral solution • a blood pressure medicine • a medicine for depression, especially a Monoamine Oxidase Inhibitor (MAOI) • insulin • a medicine that can make you sleepy, such as anti-anxiety medicine, sleep medicines, and narcotics. If you are not sure if your medicine is one listed above, ask your doctor or pharmacist. Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine. How will I receive metoclopramide? • Metoclopramide will be given to you by intravenous (IV) infusion into your vein or by intramuscular (IM) injection into a large muscle. Where and how you receive your metoclopramide injection (IV or IM) will depend on why you are receiving it. • Certain side effects can happen if metoclopramide is given too fast. See the section \\" What are the possible side effects of metoclopramide?\\" • You should not take or receive metoclopramide for more than 12 weeks. What should I avoid while receiving metoclopramide? • Do not drink alcohol while receiving metoclopramide. Alcohol may make some side effects of metoclopramide worse, such as feeling sleepy. • Do not drive, work with machines, or do dangerous tasks until you know how metoclopramide affects you. Metoclopramide may cause sleepiness. What are the possible side effects of metoclopramide? Metoclopramide can cause serious side effects, including: • Abnormal muscle movements. See the section \\" What is the most important information I should know about metoclopramide?\\" • Uncontrolled spasms of your face and neck muscles, or muscles of your body, arms, and legs (dystonia). These muscle spasms can cause abnormal movements and body positions. These spasms usually start within the first 2 days of treatment. These spasms happen more often in children and adults under age 30. • Depression, thoughts about suicide, and suicide. Some people who take metoclopramide become depressed. You may have thoughts about hurting or killing yourself. Some people who take metoclopramide have ended their own lives (suicide). • Neuroleptic Malignant Syndrome (NMS). NMS is a very rare but very serious condition that can happen with metoclopramide. NMS can cause death and must be treated in a hospital. Symptoms of NMS include: high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating. • Parkinsonism. Symptoms include slight shaking, body stiffness, trouble moving or keeping your balance. If you already have Parkinson\'s disease, your symptoms may become worse while you are receiving metoclopramide. Call your doctor and get medical help right away if you: • feel depressed or have thoughts about hurting or killing yourself • have high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating • have muscle movements you can not stop or control • have muscle movements that are new or unusual Common side effects of metoclopramide include: • feeling restless, sleepy, tired, dizzy, or exhausted • headache • confusion • trouble sleeping Infusion related side effects can happen if metoclopramide is given too fast. You may feel very anxious and restless for a short time, and then become sleepy while you are receiving a dose of metoclopramide. Tell your doctor or nurse right away if this happens. You may have more side effects the longer you take metoclopramide and the more metoclopramide you take. Tell your doctor about any side effects that bother you or do not go away. These are not all the possible side effects of metoclopramide. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about metoclopramide Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. This Medication Guide summarizes the most important information about metoclopramide. If you would like more information about metoclopramide, talk with your doctor. You can ask your doctor or pharmacist for information about metoclopramide that is written for healthcare professionals. For more information go to www.hospira.com or call 1-800-615-0187. What are the ingredients in metoclopramide? Active ingredient: metoclopramide Inactive ingredients: sodium chloride, water, hydrochloric acid or sodium hydroxide This Medication Guide has been approved by the U.S. Food and Drug Administration. Distributed by Hospira, Inc., Lake Forest, IL 60045 USA LAB-1291-1.0 Revised: 4/2018 MED GUIDE LOGO"}', 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"MECLIZINE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses for prevention and treatment of these symptoms associated with motion sickness: nausea vomiting dizziness"}', 'warnings_and_cautions': None, 'overdosage': '{"In case of overdose, get medical help or contact a Poison Control Center (1-800-222-1222) immediately."}', 'active_flag': 'Y', 'generic_name': '{"MECLIZINE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': None, 'do_not_use': None, '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': '{"Do not give to children under 12 years of age unless directed by a doctor. Ask a doctor before use if you have a breathing problem such as emphysema or chronic bronchitis glaucoma trouble urinating due to an enlarged prostate gland Ask a doctor or pharmacist before use if you are taking sedatives or tranquilizers. 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 If pregnant or breast-feeding , ask a doctor before use. Keep out of reach of children . In case of overdose, get medical help or contact a Poison Control Center (1-800-222-1222) immediately."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"TRIMETHOBENZAMIDE HYDROCHLORIDE"}

{'contraindications': '{"4 CONTRAINDICATIONS Trimethobenzamide hydrochloride capsules are contraindicated in patients with known hypersensitivity to trimethobenzamide [see Adverse Reactions ( 6 )] . Known hypersensitivity to trimethobenzamide ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following adverse reactions from voluntary reports or clinical studies have been reported with trimethobenzamide. Because many of these reactions were 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: Parkinson-like symptoms, coma, convulsions, opisthotonos, dizziness, drowsiness, headache, [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 )] Psychiatric disorders: disorientation, depression of mood Eye disorders: blurred vision Hematologic disorders: blood dyscrasias Hepatobiliary disorders: jaundice [see Warnings and Precautions ( 5.4 )] Immune system disorders: hypersensitivity, including angioedema and allergic-type skin reactions Gastrointestinal disorders: diarrhea Musculoskeletal disorders: muscle cramps Adverse reactions include hypersensitivity reactions and Parkinson-like symptoms; blood dyscrasias, blurring of vision, coma, convulsions, depression of mood, diarrhea, disorientation, dizziness, drowsiness, headache, jaundice, muscle cramps, and opisthotonos. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc. at 1-866-901-DRUG (3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch."}', 'drug_interactions': '{"7 DRUG INTERACTIONS Alcohol : May cause drowsiness; avoid concomitant use. ( 7.1 ) Other Drugs that Cause CNS Depression or EPS: Either trimethobenzamide hydrochloride capsules or the other interacting drug should be chosen, depending on the importance of the drug to the patient. If CNS-acting drugs cannot be avoided, monitor patients for CNS adverse reactions. ( 7.2 ) 7.1 Alcohol Alcohol may increase the CNS depressant effects of trimethobenzamide hydrochloride capsules and may cause drowsiness [see Warnings and Precautions ( 5.3 , 5.5 )] . Avoid concomitant use of trimethobenzamide hydrochloride capsules with alcohol. 7.2 Other Drugs that Cause CNS Depression or EPS The concurrent use of trimethobenzamide hydrochloride capsules with other drugs that cause CNS depression or EPS (e.g., sedatives, hypnotics, opiates, anxiolytics, antipsychotics, and anticholinergics, may potentiate the effects of trimethobenzamide hydrochloride capsules [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 , 5.5 )] . Either trimethobenzamide hydrochloride capsules or the other interacting drug should be chosen, depending on the importance of the drug to the patient. If CNS-acting drugs cannot be avoided, monitor patients for CNS adverse reactions."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Trimethobenzamide hydrochloride capsules are indicated in adults for the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis. Limitation of Use: Trimethobenzamide hydrochloride capsules are not recommended for use in pediatric patients due to the risk of extrapyramidal signs and symptoms and other serious central nervous system (CNS) effects, and the risk of exacerbation of the underlying disease in pediatric patients with Reye’s syndrome or other hepatic impairment. Trimethobenzamide hydrochloride capsules are an antiemetic indicated in adults for the treatment of postoperative nausea and vomiting and for nausea associated with gastroenteritis. ( 1 ) Limitation of Use: Trimethobenzamide hydrochloride capsule is not recommended for use in pediatric patients due to the risk of extrapyramidal signs and symptoms and other serious central nervous system (CNS) effects and the risk of exacerbation of the underlying disease in pediatric patients with Reye’s syndrome or other hepatic impairment. ( 1 , 8.4 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Acute Dystonic Reactions and Other Extrapyramidal Symptoms (EPS): Depending on the severity of symptoms, reduce the dosage or discontinue the drug. Treat acute dystonic reactions with anticholinergics. Avoid trimethobenzamide hydrochloride capsules in patients receiving other drugs that are likely to cause EPS. ( 5.1 , 7.2 ) Masking of Other Serious Disorders: EPS and other CNS symptoms in patients treated with trimethobenzamide hydrochloride capsules may be confused with CNS signs of undiagnosed primary disease (e.g., encephalopathy, metabolic imbalance, Reye’s Syndrome). If CNS symptoms occur, evaluate the risks and benefits of continuing trimethobenzamide hydrochloride capsules. ( 5.2 , 7.2 ) Other CNS Reactions: Coma, depression of mood, disorientation, and seizures have been reported. The recent use of other drugs that cause CNS depression or EPS symptoms may also increase the risk; consider reducing the dosage or discontinuing the drug. ( 5.3 , 7.1 , 7.2 ) Hepatotoxicity: Avoid use in patients whose signs and symptoms suggest the presence of hepatic impairment. Discontinue trimethobenzamide hydrochloride capsules in patients who develop impaired liver function while on treatment. ( 5.4 , 8.7 ) Effects on the Ability to Drive or Operate Machinery: Mental and/or physical abilities may be impaired. Concomitant use of other drugs that cause CNS depression or EPS symptoms may increase this effect; either trimethobenzamide hydrochloride capsules or the other interacting drug should be chosen, depending on the importance of the drug to the patient. ( 5.5 , 7.1 , 7.2 ) 5.1 Acute Dystonic Reactions and Other Extrapyramidal Symptoms (EPS) Extrapyramidal symptoms (EPS), manifested primarily as acute dystonic reactions, may occur with trimethobenzamide hydrochloride capsules. Dystonic reactions may include sudden onset of muscular spasms, especially in the head and neck or opisthotonos. Other EPS include laryngospasm, dysphagia, and oculogyric crisis. Involuntary spasms of the tongue and mouth may lead to difficulty in speaking and swallowing. Anticholinergic drugs can be used to treat acute dystonic reactions. EPS may also include akathisia, restlessness, akinesia, and other parkinsonian-like symptoms (e.g., tremor). Depending on the severity of symptoms, reduce the daily dosage of trimethobenzamide hydrochloride capsules by increasing the dosing interval or discontinue trimethobenzamide hydrochloride capsules [see Dosage and Administration ( 2.1 )] . Avoid trimethobenzamide hydrochloride capsules in patients receiving other drugs that are likely to cause EPS (e.g. antipsychotics) [see Drug Interactions ( 7.2 )] . 5.2 Masking of Other Serious Disorders EPS and other CNS symptoms which can occur in patients treated with trimethobenzamide hydrochloride capsules may be confused with CNS signs of undiagnosed primary disease (e.g., encephalopathy, metabolic imbalance, Reye’s syndrome) [see Warnings and Precautions ( 5.1 , 5.3 )] . If CNS symptoms occur, evaluate the risks and benefits of continuing trimethobenzamide hydrochloride capsules for each patient. 5.3 Other CNS Reactions Other serious CNS adverse reactions such as coma, depression of mood, disorientation, and seizures have been reported with trimethobenzamide hydrochloride capsules administration. The recent use of other drugs that cause CNS depression or EPS symptoms (e.g., alcohol, sedatives, hypnotics, opiates, anxiolytics, antipsychotics, and anticholinergics) may also increase the risk for these serious CNS reactions [see Warnings and Precautions ( 5.1 , 5.5 )] . Consider reducing the daily dosage of trimethobenzamide hydrochloride capsules by increasing the dosing interval or discontinuing the drug [see Dosage and Administration ( 2.1 ), Drug Interactions ( 7.1 , 7.2 )] . 5.4 Hepatotoxicity Trimethobenzamide hydrochloride is potentially hepatotoxic [see Adverse Reactions ( 6 )] . Avoid use of Trimethobenzamide hydrochloride capsules in patients whose signs and symptoms suggest the presence of hepatic impairment. Discontinue trimethobenzamide hydrochloride capsules in patients who develop impaired liver function while taking trimethobenzamide hydrochloride capsules. 5.5 Effects on the Ability to Drive or Operate Machinery Trimethobenzamide hydrochloride capsules can cause drowsiness and may impair the mental and/or physical abilities required for the performance of hazardous tasks such as driving a motor vehicle or operating machinery [see Warnings and Precautions ( 5.1 , 5.3 )] . Concomitant use of other drugs that cause CNS depression or EPS symptoms (e.g., alcohol, sedatives, hypnotics, opiates, anxiolytics, antipsychotics, and anticholinergics) may increase this effect. Either trimethobenzamide hydrochloride or the other interacting drug should be chosen, depending on the importance of the drug to the patient [Drug Interactions ( 7.1 , 7.2 )] . Inform patients not to operate motor vehicles or other dangerous machinery until they are reasonably certain that trimethobenzamide hydrochloride capsules does not affect them adversely."}', 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"TRIMETHOBENZAMIDE 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': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"DOCUSATE SODIUM",SENNOSIDES}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses relieves occasional constipation (irregularity) generally produces bowel movement in 6 to12 hours"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"DOCUSATE SODIUM AND 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}

{DIMETHICONE,"LOPERAMIDE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses relieves symptoms of diarrhea plus bloating, pressure and cramps, commonly referred to as gas"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"LOPERAMIDE HYDROCHLORIDE, SIMETHICONE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if • symptoms get worse • diarrhea lasts for more than 2 days • you get abdominal swelling or bulging. These may be signs of a serious condition. • you have difficulty swallowing the caplet"}', 'do_not_use': '{"Do not use • if you have bloody or black stool • if you have difficulty swallowing"}', 'when_using': '{"When using this product tiredness, drowsiness or dizziness may occur. Be careful when driving or operating machinery."}', 'warnings': '{"Warnings Allergy alert: Do not use if you have ever had a rash or other allergic reaction to loperamide HCl Heart alert: Taking more than directed can cause serious heart problems or death Do not use • if you have bloody or black stool • if you have difficulty swallowing Ask a doctor before use if you have • fever • mucus in the stool • a history of liver disease • a history of abnormal heart rhythm Ask a doctor or pharmacist before use if you are taking a prescription drug. Loperamide may interact with certain prescription drugs. When using this product tiredness, drowsiness or dizziness may occur. Be careful when driving or operating machinery. Stop use and ask a doctor if • symptoms get worse • diarrhea lasts for more than 2 days • you get abdominal swelling or bulging. These may be signs of a serious condition. • you have difficulty swallowing the caplet 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}

{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 (1-800-222-1222) right away."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"DIPHENHYDRAMINE HYDROCHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses • for the relief of occasional sleeplessness • reduces time to fall asleep if you have difficulty falling asleep"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"DIPHENHYDRAMINE HYDROCHLORIDE"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if sleeplessness persists continuously for more than 2 weeks. Insomnia may be a symptom of serious underlying medical illness."}', 'do_not_use': '{"Do not use • for children under 12 years of age • with any other product containing diphenhydramine, even one used on skin."}', 'when_using': '{"When using this product • avoid alcoholic beverages"}', 'warnings': '{"Warnings Do not use • for children under 12 years of age • with any other product containing diphenhydramine, even one used on skin. Ask a doctor before use if you have • a breathing problem such as emphysema or chronic bronchitis • glaucoma • difficulty in urination due to enlargement of the prostate gland Ask a doctor or pharmacist before use if you are taking sedatives or tranquilizers When using this product • avoid alcoholic beverages Stop use and ask a doctor if sleeplessness persists continuously for more than 2 weeks. Insomnia may be a symptom of serious underlying medical 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}

{"BENZALKONIUM CHLORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses For hand sanitizing to decrease the bacteria on skin. Recommended for repeated use."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"BENZALKONIUM CHLORIDE"}', 'route': '{TOPICAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if irritation or redness develops, or if condition persists for more than 72 hours."}', 'do_not_use': None, 'when_using': '{"When using this product avoid contact with eyes. In case of eye contact, flush eyes with water."}', 'warnings': '{"Warnings For external use only When using this product avoid contact with eyes. In case of eye contact, flush eyes with water. Stop use and ask a doctor if irritation or redness develops, or if condition persists 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}

{MENTHOL}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses temporarily relieves: cough as may occur with a cold occasional minor irritation and sore throat"}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{MENTHOL}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask doctor if cough persists for more than 7 days, tends to recur, or is accompanied by fever, rash, or persistent headache. These could be signs of a serious condition. sore throat is severe, or irritation, pain or redness lasts or worsens sore mouth does not improve in 7 days"}', 'do_not_use': None, 'when_using': None, 'warnings': '{"Warnings Sore throat warning: if sore throat is severe, persists for more than 2 days, is accompanied or followed by fever, headache, rash, swelling, nausea, or vomiting, consult a doctor promptly. If sore mouth symptoms do not improve in 7 days, see your dentist or doctor promptly. These symptoms may be serious."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"TRAMADOL HYDROCHLORIDE"}

{'contraindications': '{"4 CONTRAINDICATIONS Tramadol hydrochloride tablets are contraindicated for: • all children younger than 12 years of age [see Warnings and Precautions (5.4)] . • postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Warnings and Precautions (5.4)]. Tramadol hydrochloride tablets are also contraindicated in patients with: • Significant respiratory depression [see Warnings and Precautions (5.3)] . • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.12)] . • Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.15)] . • Hypersensitivity to tramadol, any other component of this product or opioids [see Warnings and Precautions (5.16)] . • Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days [see Drug Interactions (7)]. • Children younger than 12 years of age (4). • Post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy (4) . • Significant respiratory depression (4) . • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (4) . • Known or suspected gastrointestinal obstruction, including paralytic ileus (4) . • Hypersensitivity to tramadol, any other component of this product or opioids (4) . • Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days (4) ."}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following serious adverse reactions are described, or described in greater detail, in other sections: • Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)] • Life-Threatening Respiratory Depression [see Warnings and Precautions (5.3)] • Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-threatening Respiratory Depression in Children [see Warnings and Precautions (5.4)] • Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.5)] • Interactions with Benzodiazepines or Other CNS Depressants [see Warnings and Precautions (5.7)] • Serotonin Syndrome [see Warnings and Precautions (5.8)] • Seizures [see Warnings and Precautions (5.9)] • Suicide [see Warnings and Precautions (5.10)] • Adrenal Insufficiency [see Warnings and Precautions (5.11)] • Severe Hypotension [see Warnings and Precautions (5.13)] • Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.15)] • Hypersensitivity Reactions [see Warnings and Precautions (5.16)] • Withdrawal [see Warnings and Precautions (5.17)] The most common incidence of treatment-emergent adverse events (≥15.0%) in patients from clinical trials were dizziness/vertigo, nausea, constipation, headache, somnolence, vomiting and pruritus (6) . To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-406-7984 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. Tramadol hydrochloride tablets were administered to 550 patients during the double-blind or open-label extension periods in U.S. studies of chronic nonmalignant pain. Of these patients, 375 were 65 years old or older. Table 1 reports the cumulative incidence rate of adverse reactions by 7, 30 and 90 days for the most frequent reactions (5% or more by 7 days). The most frequently reported events were in the central nervous system and gastrointestinal system. Although the reactions listed in the table are felt to be probably related to tramadol hydrochloride tablets administration, the reported rates also include some events that may have been due to underlying disease or concomitant medication. The overall incidence rates of adverse experiences in these trials were similar for tramadol hydrochloride tablets and the active control groups, TYLENOL with Codeine #3 (acetaminophen 300 mg with codeine phosphate 30 mg), and aspirin 325 mg with codeine phosphate 30 mg, however, the rates of withdrawals due to adverse events appeared to be higher in the tramadol hydrochloride tablets groups. Table 1: Cumulative Incidence of Adverse Reactions for Tramadol Hydrochloride Tablets in Chronic Trials of Nonmalignant Pain (N=427) Up to 7 Days Up to 30 Days Up to 90 Days Dizziness/Vertigo 26% 31% 33% Nausea 24% 34% 40% Constipation 24% 38% 46% Headache 18% 26% 32% Somnolence 16% 23% 25% Vomiting 9% 13% 17% Pruritus 8% 10% 11% “CNS Stimulation” 1 7% 11% 14% Asthenia 6% 11% 12% Sweating 6% 7% 9% Dyspepsia 5% 9% 13% Dry Mouth 5% 9% 10% Diarrhea 5% 6% 10% 1 “CNS Stimulation” is a composite of nervousness, anxiety, agitation, tremor, spasticity, euphoria, emotional lability and hallucinations Incidence 1% to Less than 5% Possibly Causally Related The following lists adverse reactions that occurred with an incidence of 1% to less than 5% in clinical trials, and for which the possibility of a causal relationship with tramadol hydrochloride tablets exist. Body as a Whole : Malaise. Cardiovascular : Vasodilation. Central Nervous System : Anxiety, Confusion, Coordination disturbance, Euphoria, Miosis, Nervousness, Sleep disorder. Gastrointestinal : Abdominal pain, Anorexia, Flatulence. Musculoskeletal : Hypertonia. Skin : Rash. Special Senses : Visual disturbance. Urogenital : Menopausal symptoms, Urinary frequency, Urinary retention. Incidence Less than 1%, Possibly Causally Related The following lists adverse reactions that occurred with an incidence of less than 1% in clinical trials of tramadol and/or reported in postmarketing experience with tramadol-containing products. Body as a Whole : Accidental injury, Allergic reaction, Anaphylaxis, Death, Suicidal tendency, Weight loss, Serotonin syndrome (mental status change, hyperreflexia, fever, shivering, tremor, agitation, diaphoresis, seizures and coma). Cardiovascular : Orthostatic hypotension, Syncope, Tachycardia. Central Nervous System : Abnormal gait, Amnesia, Cognitive dysfunction, Depression, Difficulty in concentration, Hallucinations, Paresthesia, Seizure, Tremor. Respiratory : Dyspnea. Skin : Stevens-Johnson syndrome/Toxic epidermal necrolysis, Urticaria, Vesicles. Special Senses : Dysgeusia. Urogenital : Dysuria, Menstrual disorder. Other Adverse Experiences, Causal Relationship Unknown A variety of other adverse events were reported infrequently in patients taking tramadol hydrochloride tablets during clinical trials and/or reported in postmarketing experience. A causal relationship between tramadol hydrochloride tablets and these events has not been determined. However, the most significant events are listed below as alerting information to the physician. Cardiovascular : Abnormal ECG, Hypertension, Hypotension, Myocardial ischemia, Palpitations, Pulmonary edema, Pulmonary embolism. Central Nervous System : Migraine. Gastrointestinal : Gastrointestinal bleeding, Hepatitis, Stomatitis, Liver failure. Laboratory Abnormalities : Creatinine increase, Elevated liver enzymes, Hemoglobin decrease, Proteinuria. Sensory : Cataracts, Deafness, Tinnitus. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of tramadol hydrochloride 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. Serotonin syndrome : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency : Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Androgen deficiency : Cases of androgen deficiency have occurred with chronic use of opioids [see Clinical Pharmacology (12.2)] . QT prolongation/torsade de pointes : Cases of QT prolongation and/or torsade de pointes have been reported with tramadol use. Many of these cases were reported in patients taking another drug labeled for QT prolongation, in patients with a risk factor for QT prolongation (e.g., hypokalemia), or in the overdose setting. Eye disorders – mydriasis Metabolism and nutrition disorders – Hyponatremia: Cases of severe hyponatremia and/or SIADH have been reported in patients taking tramadol, most often in females over the age of 65, and within the first week of therapy [see Warnings and Precautions (5.19)] . Hypoglycemia: Cases of hypoglycemia have been reported in patients taking tramadol. Most reports were in patients with predisposing risk factors, including diabetes or renal insufficiency, or in elderly patients [see Warnings and Precautions (5.20)] . Nervous system disorders – movement disorder, speech disorder Psychiatric disorders – delirium"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Table 2: Clinically Significant Drug Interactions with Tramadol Hydrochloride Tablets Inhibitors of CYP2D6 Clinical Impact: The concomitant use of tramadol hydrochloride tablets and CYP2D6 inhibitors may result in an increase in the plasma concentration of tramadol and a decrease in the plasma concentration of M1, particularly when an inhibitor is added after a stable dose of tramadol hydrochloride tablets is achieved. Since M1 is a more potent µ-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who had developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. After stopping a CYP2D6 inhibitor, as the effects of the inhibitor decline, the tramadol plasma concentration will decrease and the M1 plasma concentration will increase. This could increase or prolong therapeutic effects but also increase adverse reactions related to opioid toxicity, such as potentially fatal respiratory depression [see Clinical Pharmacology (12.3)] . Intervention: If concomitant use of a CYP2D6 inhibitor is necessary, follow patients closely for adverse reactions including opioid withdrawal, seizures and serotonin syndrome. If a CYP2D6 inhibitor is discontinued, consider lowering tramadol hydrochloride tablets dosage until stable drug effects are achieved. Follow patients closely for adverse events including respiratory depression and sedation. Examples: Quinidine, fluoxetine, paroxetine and bupropion Inhibitors of CYP3A4 Clinical Impact: The concomitant use of tramadol hydrochloride tablets and CYP3A4 inhibitors can increase the plasma concentration of tramadol and may result in a greater amount of metabolism via CYP2D6 and greater levels of M1. Follow patients closely for increased risk of serious adverse events including seizures and serotonin syndrome, and adverse reactions related to opioid toxicity including potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of tramadol hydrochloride tablets is achieved. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the tramadol plasma concentration will decrease [see Clinical Pharmacology (12.3)] , resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to tramadol. Intervention: If concomitant use is necessary, consider dosage reduction of tramadol hydrochloride tablets until stable drug effects are achieved. Follow patients closely for seizures and serotonin syndrome, and signs of respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the tramadol hydrochloride tablets dosage until stable drug effects are achieved and follow patients for signs and symptoms of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The concomitant use of tramadol hydrochloride tablets and CYP3A4 inducers can decrease the plasma concentration of tramadol [see Clinical Pharmacology (12.3)] , resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to tramadol. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the tramadol plasma concentration will increase [see Clinical Pharmacology (12.3)] , which could increase or prolong both the therapeutic effects and adverse reactions, and may cause seizures, serotonin syndrome, and/or potentially fatal respiratory depression. Intervention: If concomitant use is necessary, consider increasing the tramadol hydrochloride tablets dosage until stable drug effects are achieved. Follow patients for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider tramadol hydrochloride tablets dosage reduction and monitor for seizures and serotonin syndrome, and signs of sedation and respiratory depression. Patients taking carbamazepine, a CYP3A4 inducer, may have a significantly reduced analgesic effect of tramadol. Because carbamazepine increases tramadol metabolism and because of the seizure risk associated with tramadol, concomitant administration of tramadol hydrochloride tablets and carbamazepine is not recommended. Examples: Rifampin, carbamazepine, phenytoin Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death. Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation [see Warnings and Precautions ( 5.7 )] . If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2), Warnings and Precautions ( 5.1 , 5.3 , 5.7 )]. Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, and alcohol. Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue tramadol hydrochloride tablets immediately if serotonin syndrome is suspected. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome [see Warnings and Precautions (5.9)] or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5.3)]. Intervention: Do not use tramadol hydrochloride tablets in patients taking MAOIs or within 14 days of stopping such treatment. Examples: phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of tramadol hydrochloride tablets and/or precipitate withdrawal symptoms. Intervention: Avoid concomitant use. Examples: butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants Clinical Impact: Tramadol may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention: Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of tramadol hydrochloride tablets and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration ( Error! Hyperlink reference not valid. ), Warnings and Precautions ( 5.3 , 5.7 )]. Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Intervention: Monitor patients for signs of urinary retention or reduced gastric motility when tramadol hydrochloride tablets are used concomitantly with anticholinergic drugs. Digoxin Clinical Impact: Post-marketing surveillance of tramadol has revealed rare reports of digoxin toxicity. Intervention: Follow patients for signs of digoxin toxicity and adjust dosage of digoxin as needed. Warfarin Clinical Impact: Post-marketing surveillance of tramadol has revealed rare reports of alteration of warfarin effect, including elevation of prothrombin times. Intervention: Monitor the prothrombin time of patients on warfarin for signs of an interaction and adjust the dosage of warfarin as needed. Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics : Avoid use with tramadol hydrochloride tablets because they may reduce analgesic effect of tramadol hydrochloride tablets or precipitate withdrawal symptoms (7)."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Tramadol hydrochloride tablets are indicated in adults for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see Warnings and Precautions (5.1) ] , reserve tramadol hydrochloride tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]: • Have not been tolerated or are not expected to be tolerated. • Have not provided adequate analgesia or are not expected to provide adequate analgesia. Tramadol hydrochloride tablets are an opioid agonist indicated in adults for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate (1) . Limitations of Use (1) Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses (5.1) , reserve tramadol hydrochloride tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]: • Have not been tolerated or are not expected to be tolerated. • Have not provided adequate analgesia, or are not expected to provide adequate analgesia."}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS • Serotonin Syndrome : May be life-threatening. Can occur with use of tramadol alone, with concomitant use of serotonergic drugs, with drugs that impair metabolism of serotonin or tramadol (5.8) . • Risk of Seizure : Can occur at the recommended dose of tramadol. Concomitant use with other drugs may increase seizure risk. Risk may increase in patients with epilepsy, a history of seizures, and in patients with a recognized risk for seizures (5.9) . • Risk of Suicide : Do not prescribe for suicidal or addiction-prone patients (5.10) . • Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off the opioid (5.11) . • Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients : Monitor closely, particularly during initiation and titration (5.12) . • Severe Hypotension : Monitor during dosage initiation and titration. Avoid use of tramadol hydrochloride tablets in patients with circulatory shock (5.13) . • Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness : Monitor for sedation and respiratory depression. Avoid use of tramadol hydrochloride tablets in patients with impaired consciousness or coma (5.14) . 5.1 Addiction, Abuse and Misuse Tramadol hydrochloride tablets contain tramadol, a Schedule IV controlled substance. As an opioid, tramadol hydrochloride tablets expose users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9)] . Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed tramadol hydrochloride tablets. Addiction can occur at recommended dosages and if the drug is misused or abused. Assess each patient\'s risk for opioid addiction, abuse, or misuse prior to prescribing tramadol hydrochloride tablets, and monitor all patients receiving tramadol hydrochloride tablets for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as tramadol hydrochloride tablets, but use in such patients necessitates intensive counseling about the risks and proper use of tramadol hydrochloride tablets along with intensive monitoring for signs of addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration ( Error! Hyperlink reference not valid. ), Warnings and Precautions ( 5.3 )]. Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing tramadol hydrochloride tablets. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counselling Information (17)] . Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. 5.2 Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following: • Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain. • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG . • Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them. • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities. To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint. 5.3 Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient\'s clinical status [see Overdosage (10)]. Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of tramadol hydrochloride tablets, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with and following dosage increases of tramadol hydrochloride tablets. To reduce the risk of respiratory depression, proper dosing and titration of tramadol hydrochloride tablets are essential [see Dosage and Administration (2)] . Overestimating the tramadol hydrochloride tablets dosage when converting patients from another opioid product can result in a fatal overdose with the first dose. Accidental ingestion of even one dose of tramadol hydrochloride tablets, especially by children, can result in respiratory depression and death due to an overdose of tramadol. Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Patient Counseling Information ( 17 )]. Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration ( 2.5 )] . Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with tramadol hydrochloride tablets. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help, even if naloxone is administered [see Patient Counseling Information ( 17 )]. Consider prescribing naloxone, based on the patient\'s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. However, the presence of risk factors for overdose should not prevent the proper management of pain in any given patient. Also consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental exposure or overdose. If naloxone is prescribed, educate patients and caregivers on how to treat with naloxone. [see Warnings and Precautions ( 5.1 , 5.7 ), Patient Counseling Information ( 17 )]. 5.4 Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-threatening Respiratory Depression in Children Life-threatening respiratory depression and death have occurred in children who received tramadol. Tramadol and codeine are subject to variability in metabolism based upon CYP2D6 genotype (described below), which can lead to increased exposure to an active metabolite. Based upon postmarketing reports with tramadol or with codeine, children younger than 12 years of age may be more susceptible to the respiratory depressant effects of tramadol. Furthermore, children with obstructive sleep apnea who are treated with opioids for post-tonsillectomy and/or adenoidectomy pain may be particularly sensitive to their respiratory depressant effect. Because of the risk of life-threatening respiratory depression and death: • Tramadol hydrochloride tablets are contraindicated for all children younger than 12 years of age [see Contraindications (4)]. • Tramadol hydrochloride tablets are contraindicated for postoperative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Contraindications (4)]. • Avoid the use of tramadol hydrochloride tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol unless the benefits outweigh the risks. Risk factors include conditions associated with hypoventilation such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression. • As with adults, when prescribing opioids for adolescents, healthcare providers should choose the lowest effective dose for the shortest period of time and inform patients and caregivers about these risks and the signs of opioid overdose [see Use in Specific Populations (8.4) , Overdosage (10)] . Nursing Mothers Tramadol is subject to the same polymorphic metabolism as codeine, with ultra-rapid metabolizers of CYP2D6 substrates being potentially exposed to life-threatening levels of the active metabolite O-desmethyltramadol (M1). At least one death was reported in a nursing infant who was exposed to high levels of morphine in breast milk because the mother was an ultra-rapid metabolizer of codeine. A baby nursing from an ultra-rapid metabolizer mother taking tramadol hydrochloride tablets could potentially be exposed to high levels of M1, and experience life-threatening respiratory depression. For this reason, breastfeeding is not recommended during treatment with tramadol hydrochloride tablets [see Use in Specific Populations (8.2)] . CYP2D6 Genetic Variability: Ultra-rapid Metabolizer Some individuals may be ultra-rapid metabolizers because of a specific CYP2D6 genotype (e.g., gene duplications denoted as *1/*1xN or *1/*2xN). The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 1 to 10% for Whites (European, North American), 3 to 4% for Blacks (African Americans), 1 to 2% for East Asians (Chinese, Japanese, Korean), and may be greater than 10% in certain racial/ethnic groups (i.e., Oceanian, Northern African, Middle Eastern, Ashkenazi Jews, Puerto Rican). These individuals convert tramadol into its active metabolite, O-desmethyltramadol (M1), more rapidly and completely than other people. This rapid conversion results in higher than expected serum M1 levels. Even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may have life-threatening or fatal respiratory depression or experience signs of overdose (such as extreme sleepiness, confusion, or shallow breathing) [see Overdosage (10)] . Therefore, individuals who are ultra-rapid metabolizers should not use tramadol hydrochloride tablets. 5.5 Neonatal Opioid Withdrawal Syndrome Prolonged use of tramadol hydrochloride tablets during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life- threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations (8.1) and Patient Counseling Information (17)]. 5.6 Risks of Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors on levels of tramadol and M1 from tramadol hydrochloride tablets are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol hydrochloride tablets require careful consideration of the effects on the parent drug, tramadol which is a weak serotonin and norepinephrine reuptake inhibitor and μ-opioid agonist, and the active metabolite, M1, which is more potent than tramadol in μ-opioid receptor binding [see Drug Interactions (7)] . Risks of Concomitant Use or Discontinuation of Cytochrome P450 2D6 Inhibitors The concomitant use of tramadol hydrochloride tablets with all cytochrome P450 2D6 inhibitors (e.g., amiodarone, quinidine) may result in an increase in tramadol plasma levels and a decrease in the levels of the active metabolite, M1. A decrease in M1 exposure in patients who have developed physical dependence to tramadol, may result in signs and symptoms of opioid withdrawal and reduced efficacy. The effect of increased tramadol levels may be an increased risk for serious adverse events including seizures and serotonin syndrome. Discontinuation of a concomitantly used cytochrome P450 2D6 inhibitor may result in a decrease in tramadol plasma levels and an increase in active metabolite M1 levels, which could increase or prolong adverse reactions related to opioid toxicity and may cause potentially fatal respiratory depression. Follow patients receiving tramadol hydrochloride tablets and any CYP2D6 inhibitor for the risk of serious adverse events including seizures and serotonin syndrome, signs and symptoms that may reflect opioid toxicity, and opioid withdrawal when tramadol hydrochloride tablets are used in conjunction with inhibitors of CYP2D6 [see Drug Interactions (7)] . Cytochrome P450 3A4 Interaction The concomitant use of tramadol hydrochloride tablets with cytochrome P450 3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir) or discontinuation of a cytochrome P450 3A4 inducer such as rifampin, carbamazepine, and phenytoin, may result in an increase in tramadol plasma concentrations, which could increase or prolong adverse reactions, increase the risk for serious adverse events including seizures and serotonin syndrome, and may cause potentially fatal respiratory depression. The concomitant use of tramadol hydrochloride tablets with all cytochrome P450 3A4 inducers or discontinuation of a cytochrome P450 3A4 inhibitor may result in lower tramadol levels. This may be associated with a decrease in efficacy, and in some patients, may result in signs and symptoms of opioid withdrawal. Follow patients receiving tramadol hydrochloride tablets and any CYP3A4 inhibitor or inducer for the risk for serious adverse events including seizures and serotonin syndrome, signs and symptoms that may reflect opioid toxicity and opioid withdrawal when tramadol hydrochloride tablets are used in conjunction with inhibitors and inducers of CYP3A4 [see Drug Interactions (7)] . 5.7 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of tramadol hydrochloride tablets with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use 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 opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions (7)] . If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration ( Error! Hyperlink reference not valid. ), Warnings and Precautions ( 5.3 )]. Advise both patients and caregivers about the risks of respiratory depression and sedation when tramadol hydrochloride tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see Drug Interactions (7) ; and Patient Counseling Information (17 )]. 5.8 Serotonin Syndrome Risk Cases of serotonin syndrome, a potentially life-threatening condition, have been reported with the use of tramadol, particularly during concomitant use with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) [see Drug Interactions (7) ] . This may occur within the recommended dosage range. 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, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that. Discontinue tramadol hydrochloride tablets if serotonin syndrome is suspected. 5.9 Increased Risk of Seizure Seizures have been reported in patients receiving tramadol hydrochloride tablets within the recommended dosage range. Spontaneous postmarketing reports indicate that seizure risk is increased with doses of tramadol hydrochloride tablets above the recommended range. Concomitant use of tramadol hydrochloride tablets increase the seizure risk in patients taking [see Drug Interactions (7)] : • Selective serotonin re-uptake inhibitors (SSRI antidepressants or anorectics), • Tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), • Other opioids, • MAO inhibitors [see Warnings and Precautions (5.8) ; Drug Interactions (7)] . • Neuroleptics, or • Other drugs that reduce the seizure threshold. Risk of seizure may also increase in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (such as head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections). In tramadol hydrochloride tablets overdose, naloxone administration may increase the risk of seizure. 5.10 Suicide Risk Do not prescribe tramadol hydrochloride tablets for patients who are suicidal or addiction-prone. • Consideration should be given to the use of non-narcotic analgesics in patients who are suicidal or depressed [see Drug Abuse and Dependence (9)] . • Prescribe tramadol hydrochloride tablets with caution for patients with a history of misuse and/or are currently taking CNS-active drugs including tranquilizers or antidepressant drugs, alcohol in excess, and patients who suffer from emotional disturbance or depression [see Drug Interactions (7)] . • Inform patients not to exceed the recommended dose and to limit their intake of alcohol [see Dosage and Administration (2), Warnings and Precautions (5.7)]. 5.11 Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency. 5.12 Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients The use of tramadol hydrochloride tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated. Patients with Chronic Pulmonary Disease Tramadol hydrochloride tablets -treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosage of tramadol hydrochloride tablets [see Warnings and Precautions (5.3) ] . Elderly, Cachectic, or Debilitated Patients Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [see Warnings and Precautions (5.3)] . Monitor such patients closely, particularly when initiating and titrating tramadol hydrochloride tablets and when tramadol hydrochloride tablets are given concomitantly with other drugs that depress respiration [see Warnings and Precautions (5.7) ; Drug Interactions (7)]. Alternatively, consider the use of non-opioid analgesics in these patients. 5.13 Severe Hypotension Tramadol hydrochloride tablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g. phenothiazines or general anesthetics) [see Drug Interactions (7) ] . Monitor these patients for signs of hypotension after initiating or titrating the dosage of tramadol hydrochloride tablets. In patients with circulatory shock, tramadol hydrochloride tablets may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of tramadol hydrochloride tablets in patients with circulatory shock. 5.14 Risks of use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness In patients who may be susceptible to the intracranial effects of CO 2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), tramadol hydrochloride tablets may reduce respiratory drive, and the resultant CO 2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with tramadol hydrochloride tablets. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of tramadol hydrochloride tablets in patients with impaired consciousness or coma. 5.15 Risks of Use in Patients with Gastrointestinal Conditions Tramadol hydrochloride tablets are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see Contraindications (4)] . The tramadol in tramadol hydrochloride tablets may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms. 5.16 Anaphylaxis and Other Hypersensitivity Reactions Serious and rarely fatal anaphylactic reactions have been reported in patients receiving therapy with tramadol hydrochloride tablets. When these events do occur it is often following the first dose. Other reported allergic reactions include pruritus, hives, bronchospasm, angioedema, toxic epidermal necrolysis and Stevens-Johnson syndrome. Patients with a history of hypersensitivity reactions to tramadol and other opioids may be at increased risk and therefore should not receive tramadol hydrochloride tablets [see Contraindications (4)] . If anaphylaxis or other hypersensitivity occurs, stop administration of tramadol hydrochloride tablets immediately, discontinue tramadol hydrochloride tablets permanently, and do not rechallenge with any formulation of tramadol. Advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. [see Contraindications (4) ; Patient Counselling Information (17)]. 5.17 Withdrawal Do not abruptly discontinue tramadol hydrochloride tablets in a patient physically dependent on opioids. When discontinuing tramadol hydrochloride tablets in a physically dependent patient, gradually taper the dosage. Rapid tapering of tramadol in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see Dosage and Administration ( 2.5 ), Drug Abuse and Dependence ( 9.3 )]. Additionally, avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including tramadol hydrochloride tablets. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [see Drug Interactions (7)] . 5.18 Driving and Operating Machinery Tramadol hydrochloride tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of tramadol hydrochloride tablets and know how they will react to the medication [see Patient Counselling Information (17)]. 5.19 Hyponatremia Hyponatremia (serum sodium < 135 mmol/L) has been reported with the use of tramadol, and many cases are severe (sodium level < 120 mmol/L). Most cases of hyponatremia occurred in females over the age of 65 and within the first week of therapy. In some reports, hyponatremia resulted from the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Monitor for signs and symptoms of hyponatremia (e.g., confusion, disorientation), during treatment with tramadol hydrochloride tablets, especially during initiation of therapy. If signs and symptoms of hyponatremia are present, initiate appropriate treatment (e.g., fluid restriction) and discontinue tramadol hydrochloride tablets [see Dosage and Administration: Safe Reduction or Discontinuation of Tramadol Hydrochloride Tablets (2.5)]. 5.20 Hypoglycemia Cases of tramadol-associated hypoglycemia have been reported, some resulting in hospitalization. In most cases, patients had predisposing risk factors (e.g. diabetes). If hypoglycemia is suspected, monitor blood glucose levels and consider drug discontinuation as appropriate [see Dosage and Administration: Safe Reduction or Discontinuation of Tramadol Hydrochloride Tablets (2.5)] ."}', 'overdosage': '{"10 OVERDOSAGE Clinical Presentation Acute overdosage with tramadol hydrochloride tablets can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, QT prolongation, hypotension, partial or complete airway obstruction, atypical snoring, seizures, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations. Deaths due to overdose have been reported with abuse and misuse of tramadol [ see Warnings and Precautions (5.1) ; Drug Abuse and Dependence (9.2)] . Review of case reports has indicated that the risk of fatal overdose is further increased when tramadol is abused concurrently with alcohol or other CNS depressants, including other opioids. Treatment of Overdose In case of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or serious arrhythmias will require advanced life-supporting measures. Opioid antagonists, such as naloxone, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to opioid overdose, administer an opioid antagonist. While naloxone will reverse some, but not all, symptoms caused by overdosage with tramadol, the risk of seizures is also increased with naloxone administration. In animals, convulsions following the administration of toxic doses of tramadol hydrochloride tablets could be suppressed with barbiturates or benzodiazepines but were increased with naloxone. Naloxone administration did not change the lethality of an overdose in mice. Hemodialysis is not expected to be helpful in an overdose because it removes less than 7% of the administered dose in a 4-hour dialysis period. Because the duration of opioid reversal is expected to be less than the duration of action of tramadol in tramadol hydrochloride tablets, carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product\'s prescribing information. In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist."}', 'active_flag': 'Y', 'generic_name': '{"TRAMADOL 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). Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store tramadol hydrochloride tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home [see Warnings and Precautions (5.1 , 5.17) , Drug Abuse and Dependence (9.2) ] . Inform patients that leaving tramadol hydrochloride tablets unsecured can pose a deadly risk to others in the home. Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Inform patients that medicine take-back options are the preferred way to safely dispose of most types of unneeded medicines. If no take back programs or Drug Enforcement Administration (DEA)-registered collectors are available, instruct patients to dispose of tramadol hydrochloride tablets by following these four steps: • Mix tramadol hydrochloride tablets (do not crush) with an unpalatable substance such as dirt, cat litter, or used coffee grounds; • Place the mixture in a container such as a sealed plastic bag; • Throw the container in the household trash; • Delete all personal information on the prescription label of the empty bottle. Inform patients that they can visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines. Addiction, Abuse, and Misuse Inform patients that the use of tramadol hydrochloride tablets, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see Warnings and Precautions (5.1)] . Instruct patients not to share tramadol hydrochloride tablets with others and to take steps to protect tramadol hydrochloride tablets from theft or misuse. Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting tramadol hydrochloride tablets or when the dosage is increased, and that it can occur even at recommended dosages. Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Warnings and Precautions (5.3)]. Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss with the patient and caregiver the availability of naloxone for the emergency treatment of opioid overdose, both when initiating and renewing treatment with tramadol hydrochloride tablets. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program) Error! Hyperlink reference not valid. Warnings and Precautions (5.3) ]. Educate patients and caregivers on how to recognize the signs and symptoms of an overdose. Explain to patients and caregivers that naloxone\'s effects are temporary, and that they must call 911 or get emergency medical help right away in all cases of known or suspected opioid overdose, even if naloxone is administered [see Overdosage (10)]. If naloxone is prescribed, also advise patients and caregivers: • How to treat with naloxone in the event of an opioid overdose • To tell family and friends about their naloxone and to keep it in a place where family and friends can access it in an emergency • To read the Patient Information (or other educational material) that will come with their naloxone. Emphasize the importance of doing this before an opioid emergency happens, so the patient and caregiver will know what to do. Accidental Ingestion Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see Warnings and Precautions (5.3)] . Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-threatening Respiratory Depression in Children Advise caregivers that tramadol hydrochloride tablets are contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Advise caregivers of children ages 12 to 18 years of age receiving tramadol hydrochloride tablets to monitor for signs of respiratory depression [see Warnings and Precautions (5.4)] . Interactions with Benzodiazepines and Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if tramadol hydrochloride tablets are used with benzodiazepines, CNS depressants, including alcohol, or some illicit drugs and not to use these concomitantly unless supervised by a healthcare provider [see Warnings and Precautions (5.7) ; Drug Interactions (7)] . Serotonin Syndrome Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome, and to seek medical attention right away if symptoms develop. Instruct patients to inform their healthcare provider if they are taking, or plan to take serotonergic medications [see Warnings and Precautions (5.8)] . Seizures Inform patients that tramadol hydrochloride tablets may cause seizures with concomitant use of serotonergic agents (including SSRIs, SNRIs, and triptans) or drugs that significantly reduce the metabolic clearance of tramadol [see Warnings and Precautions (5.9)] . MAOI Interaction Inform patients not to take tramadol hydrochloride tablets while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking tramadol hydrochloride tablets [see Drug Interactions (7)] . Adrenal Insufficiency Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms [see Warnings and Precautions (5.11)] . Important Administration Instructions • Instruct patients how to properly take tramadol hydrochloride tablets. [see Dosage and Administration (2)] . • Advise patients not to adjust the dose of tramadol hydrochloride tablets without consulting with a physician or other healthcare professional. Important Discontinuation Instructions In order to avoid developing withdrawal symptoms, instruct patients not to discontinue tramadol hydrochloride tablets without first discussing a tapering plan with the prescriber [see Dosage and Administration ( 2.5 )] . Hypotension Inform patients that tramadol hydrochloride tablets may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position) [see Warnings and Precautions (5.13)] . Anaphylaxis Inform patients that anaphylaxis has been reported with ingredients contained in tramadol hydrochloride tablets. Advise patients how to recognize such a reaction and when to seek medical attention [see Contraindications (4) ; Warnings and Precautions (5.16) ; Adverse Reactions (6)] . Pregnancy Neonatal Opioid Withdrawal Syndrome Inform female patients of reproductive potential that prolonged use of tramadol hydrochloride tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated and that the patient should inform their healthcare provider if they have used opioids at any time during their pregnancy, especially near the time of birth. [ see Warnings and Precautions (5.5) ; Use in Specific Populations (8.1)] . Embryo-Fetal Toxicity Inform female patients of reproductive potential that tramadol hydrochloride tablets may cause fetal harm and to inform the healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1)] . Lactation Advise women that breastfeeding is not recommended during treatment with tramadol hydrochloride tablets [see Warnings and Precautions (5.4); Use in Specific Populations (8.2)] . Infertility Inform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible [see Use in Specific Populations (8.3)] . Driving or Operating Heavy Machinery Inform patients that tramadol hydrochloride tablets may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication [see Warnings and Precautions (5.18)] . Constipation Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see Adverse Reactions (6)] . Maximum single-dose and 24-hour dose Advise patients not to exceed the single-dose and 24-hour dose limit and the time interval between doses, since exceeding these recommendations can result in respiratory depression, seizures and death [see Dosage and Administration (2) ; Warnings and Precautions (5.3)] . Dispense with Medication Guide available at https://www.sunpharma.com/usa/products Manufactured By: Sun Pharmaceutical Industries Ltd. Survey No. 259/15, Dadra-396 191, (U.T. of D & NH), India. Distributed By: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 5224039 Rev. 10/2021 Repackaged By: Preferred Pharmaceuticals Inc."}', 'pregnancy': '{"8.1 Pregnancy Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. Available data with tramadol hydrochloride tablets in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, tramadol administration during organogenesis decreased fetal weights and reduced ossification in mice, rats, and rabbits at 1.4, 0.6, and 3.6 times the maximum recommended human daily dosage (MRHD). Tramadol decreased pup body weight and increased pup mortality at 1.2 and 1.9 times the MRHD [see Data] . Based on animal data, advise pregnant women of the potential risk to a 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 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 Fetal/Neonatal Adverse Reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in respiratory depression and physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome can present as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms and signs of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.5 )] . Neonatal seizures, neonatal withdrawal syndrome, fetal death and still birth have been reported during postmarketing. Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Tramadol hydrochloride tablets are not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including tramadol hydrochloride tablets, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Tramadol has been shown to cross the placenta. The mean ratio of serum tramadol in the umbilical veins compared to maternal veins was 0.83 for 40 women given tramadol during labor. The effect of tramadol hydrochloride tablets, if any, on the later growth, development, and functional maturation of the child is unknown. Data Animal Data Tramadol has been shown to be embryotoxic and fetotoxic in mice, (120 mg/kg), rats (25 mg/kg) and rabbits (75 mg/kg) at maternally toxic dosages, but was not teratogenic at these dose levels. These doses on a mg/m 2 basis are 1.4, 0.6, and 3.6 times the maximum recommended human daily dosage (MRHD) for mouse, rat and rabbit, respectively. No drug-related teratogenic effects were observed in progeny of mice (up to 140 mg/kg), rats (up to 80 mg/kg) or rabbits (up to 300 mg/kg) treated with tramadol by various routes. Embryo and fetal toxicity consisted primarily of decreased fetal weights, decreased skeletal ossification and increased supernumerary ribs at maternally toxic dose levels. Transient delays in developmental or behavioral parameters were also seen in pups from rat dams allowed to deliver. Embryo and fetal lethality were reported only in one rabbit study at 300 mg/kg, a dose that would cause extreme maternal toxicity in the rabbit. The dosages listed for mouse, rat and rabbit are 1.7, 1.9 and 14.6 times the MRHD, respectively. Tramadol was evaluated in pre- and post-natal studies in rats. Progeny of dams receiving oral (gavage) dose levels of 50 mg/kg 1.2 times the MRHD) or greater had decreased weights, and pup survival was decreased early in lactation at 80 mg/kg (1.9 times the MRHD)."}', 'pediatric_use': '{"8.4 Pediatric Use The safety and effectiveness of tramadol hydrochloride tablets in pediatric patients have not been established. Life-threatening respiratory depression and death have occurred in children who received tramadol [see Warnings and Precautions (5.4) ] . In some of the reported cases, these events followed tonsillectomy and/or adenoidectomy, and one of the children had evidence of being an ultra-rapid metabolizer of tramadol (i.e., multiple copies of the gene for cytochrome P450 isoenzyme 2D6). Children with sleep apnea may be particularly sensitive to the respiratory depressant effects of tramadol. Because of the risk of life-threatening respiratory depression and death: • Tramadol hydrochloride tablets are contraindicated for all children younger than 12 years of age [ see Contraindications (4) ] . • Tramadol hydrochloride tablets are contraindicated for post-operative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy [ see Contraindications (4) ] . Avoid the use of tramadol hydrochloride tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol unless the benefits outweigh the risks. Risk factors include conditions associated with hypoventilation such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression."}', 'geriatric_use': '{"8.5 Geriatric Use A total of 455 elderly (65 years of age or older) subjects were exposed to tramadol hydrochloride tablets in controlled clinical trials. Of those, 145 subjects were 75 years of age and older. In studies including geriatric patients, treatment-limiting adverse events were higher in subjects over 75 years of age compared to those under 65 years of age. Specifically, 30% of those over 75 years of age had gastrointestinal treatment-limiting adverse events compared to 17% of those under 65 years of age. Constipation resulted in discontinuation of treatment in 10% of those over 75. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of tramadol hydrochloride tablets slowly in geriatric patients starting at the low end of the dosing range and monitor closely for signs of central nervous system and respiratory depression [ see Warnings and Precautions (5.12) ] . Tramadol is known to be substantially excreted by the kidney, and the risk of adverse 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."}'}

{"SODIUM FLUORIDE"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Use 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': '{"Warning 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}

{"DOCUSATE SODIUM"}

{'contraindications': None, 'adverse_reactions': None, 'drug_interactions': None, 'indications_and_usage': '{"Uses For the relief of occasional constipation. Helps to prevent dry, hard stools. This product generally produces a bowel movement within 12 to 72 hours."}', 'warnings_and_cautions': None, 'overdosage': None, 'active_flag': 'Y', 'generic_name': '{"DOCUSATE SODIUM"}', 'route': '{ORAL}', 'product_type': '{"HUMAN OTC DRUG"}', 'stop_use': '{"Stop use and ask a doctor if you have rectal bleeding or you fail to have a bowel movement after use."}', 'do_not_use': '{"Do not use: If you are currently taking mineral oil, unless directed by a doctor. When abdominal pain, nausea, or vomiting are present. For longer than one week unless directed by a doctor."}', 'when_using': None, 'warnings': '{"Warnings Do not use: If you are currently taking mineral oil, unless directed by a doctor. When abdominal pain, nausea, or vomiting are present. For longer than one week unless directed by a doctor."}', 'precautions': None, 'information_for_patients': None, 'pregnancy': None, 'pediatric_use': None, 'geriatric_use': None}

{"POTASSIUM CHLORIDE"}

{'contraindications': '{"4 CONTRAINDICATIONS Potassium chloride is contraindicated in patients on triamterene and amiloride. Concomitant use with triamterene and amiloride ( 4 )"}', 'adverse_reactions': '{"6 ADVERSE REACTIONS The following adverse reactions have been identified with use of oral potassium salts. 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 most common adverse reactions to oral potassium salts are nausea, vomiting, flatulence, abdominal pain/discomfort, and diarrhea. There have been reports hyperkalemia and of upper and lower gastrointestinal condition including obstruction, bleeding, ulceration, perforation. Skin rash has been reported rarely. The most common adverse reactions are nausea, vomiting, flatulence, abdominal pain/discomfort and diarrhea. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Upsher-Smith Laboratories, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch"}', 'drug_interactions': '{"7 DRUG INTERACTIONS Triamterene and amiloride: Concomitant use is contraindicated ( 7.1 ) Renin-angiotensin-aldosterone inhibitors: Monitor for hyperkalemia ( 7.2 ) Nonsteroidal anti-inflammatory drugs: Monitor for hyperkalemia ( 7.3 ) 7.1 Triamterene or amiloride Use with triamterene or amiloride can produce severe hyperkalemia. Concomitant use is contraindicated [see Contraindications (4) ] . 7.2 Renin-angiotensin-aldosterone Inhibitors Drugs that inhibit the renin-angiotensin-aldosterone system (RAAS) including angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), spironolactone, eplerenone, or aliskiren produce potassium retention by inhibiting aldosterone production. Closely monitor potassium in patients on concomitant RAAS inhibitors. 7.3 Nonsteroidal Anti-inflammatory Drugs (NSAIDs) NSAIDs may produce potassium retention by reducing renal synthesis of prostaglandin E and impairing the renin-angiotensin system. Closely monitor potassium in patients on concomitant NSAIDs."}', 'indications_and_usage': '{"1 INDICATIONS AND USAGE Klor-Con is indicated for the treatment and prophylaxis of hypokalemia with or without metabolic alkalosis, in patients for whom dietary management with potassium-rich foods or diuretic dose reduction is insufficient. KLOR-CON is a potassium salt, indicated for the treatment and prophylaxis of hypokalemia with or without metabolic alkalosis in patients for whom dietary management with potassium-rich foods or diuretic dose reduction is insufficient. ( 1 )"}', 'warnings_and_cautions': '{"5 WARNINGS AND PRECAUTIONS Gastrointestinal Irritation: Take with meals. ( 5.1 ) 5.1 Gastrointestinal Adverse Reactions Solid oral dosage forms of potassium chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract, particularly if the drug maintains contact with the gastrointestinal mucosa for prolonged periods. Consider the use of liquid potassium in patients with dysphagia, swallowing disorders, or severe gastrointestinal motility disorders. If severe vomiting, abdominal pain, distention, or gastrointestinal bleeding occurs, discontinue Klor-Con extended-release tablets and consider possibility of ulceration, obstruction or perforation. Klor-Con extended-release tablets should not be taken on an empty stomach because of its potential for gastric irritation [see Dosage and Administration (2.1) ] ."}', 'overdosage': '{"10 OVERDOSAGE 10.1 Symptoms The administration of oral potassium salts to persons with normal excretory mechanisms for potassium rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired, potentially fatal hyperkalemia can result [see Contraindications and Warnings ] . It is important to recognize that hyperkalemia is usually asymptomatic and may be manifested only by an increased serum potassium concentration (6.5 mEq/L to 8.0 mEq/L) and characteristic electrocardiographic changes (peaking of T-waves, loss of P-wave, depression of S-T segment and prolongation of the QT interval). Late manifestations include muscle paralysis and cardiovascular collapse from cardiac arrest (9 to 12 mEq/L). 10.2 Treatment Treatment measures for hyperkalemia include the following: Elimination of foods and medications containing potassium and of any agents with potassium-sparing properties. Intravenous administration of 300 mL/hr to 500 mL/hr of 10% dextrose solution containing 10 to 20 units of crystalline insulin per 1,000 mL. Correction of acidosis, if present, with intravenous sodium bicarbonate. Use of exchange resins, hemodialysis or peritoneal dialysis. In treating hyperkalemia, it should be recalled that in patients who have been stabilized on digitalis, too rapid a lowering of the serum potassium concentration can produce digitalis toxicity. The extended-release feature means that absorption and toxic effects may be delayed for hours. Consider standard measures to remove any unabsorbed drug."}', 'active_flag': 'Y', 'generic_name': '{"POTASSIUM CHLORIDE"}', '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 Inform patients to take each dose with meals and with a full glass of water or other liquid, and to not crush, chew, or suck the tablets. Inform patients that the wax matrix is not absorbed and is excreted in the feces; in some instances the empty matrices may be noticeable in the stool. Advise patients seek medical attention if tarry stools or other evidence of gastrointestinal bleeding is noticed."}', 'pregnancy': '{"8.1 Pregnancy Risk Summary There are no human data related to use of Klor-Con during pregnancy, and animal reproduction studies have not been conducted. Potassium supplementation that does not lead to hyperkalemia is not expected to cause fetal harm. The background risk for major birth defects and miscarriage in 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."}', 'pediatric_use': '{"8.4 Pediatric Use Safety and effectiveness in the pediatric population have not been established."}', 'geriatric_use': '{"8.5 Geriatric Use Clinical studies of Klor-Con extended-release 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."}'}