Label: ETODOLAC capsule
NDC Code(s): 66267-575-30
Packager: NuCare Pharmaceuticals,Inc.
The chemical name is (±) 1,8-diethyl-1,3,4,9-tetrahydropyrano-[3,4-b]indole-1-acetic acid. The molecular weight of the base is 287.37. It has a pKa of 4.65 and an n-octanol:water partition coefficient of 11.4 at pH 7.4. The molecular formula for etodolac is C 17H 21NO 3, and it has the following structural formula:
Each etodolac capsule, USP is for oral administration, contains 200 mg or 300 mg of etodolac. In addition, each capsule contains the following inactive ingredients: black iron oxide, black SW-9008/SW-9009, colloidal silicon dioxide, croscarmellose sodium, gelatin, lactose monohydrate, sodium lauryl sulfate, stearic acid, talc and titanium dioxide.
The systemic bioavailability of etodolac is 100% as compared to solution and at least 80% as determined from mass balance studies. Etodolac is well absorbed and had a relative bioavailability of 100% when 200 mg capsules were compared with a solution of etodolac. Based on mass balance studies, the systemic availability of etodolac from either the tablet or capsule formulation is at least 80%. Etodolac does not undergo significant first-pass metabolism following oral administration. Mean (± 1 SD) peak plasma concentrations (C max) range from approximately 14 ± 4 to 37 ± 9 mcg/mL after 200 to 600 mg single doses and are reached in 80 ± 30 minutes (see Table 1 for summary of pharmacokinetic parameters). The dose-proportionality based on the area under the plasma concentration-time curve (AUC) is linear following doses up to 600 mg every 12 hours. Peak concentrations are dose proportional for both total and free etodolac following doses up to 400 mg every 12 hours, but following a 600 mg dose, the peak is about 20% higher than predicted on the basis of lower doses. The extent of absorption of etodolac is not affected when etodolac is administered after a meal. Food intake, however, reduces the peak concentration reached by approximately one-half and increases the time to peak concentration by 1.4 to 3.8 hours.
PKParameters Normal Healthy
Adults (18-65)*
(n=179) Healthy Males
(n=176) Healthy Females
(n=9) Renal Impairment
(n=10) Hepatic Impairment
T max, h 1.4
(61%) † 1.4
(8%) 414
† % Coefficient of variation
* Age Range (years)
— etodolac, unchanged 1%
— etodolac glucuronide 13%
— hydroxylated metabolites (6-, 7-, and 8-OH) 5%
— hydroxylated metabolite glucuronides 20%
— unidentified metabolites 33%
Although renal elimination is a significant pathway of excretion for etodolac metabolites, no dosing adjustment in patients with mild to moderate renal dysfunction is generally necessary. The terminal half-life (t ½) of etodolac is 6.4 hours (22% CV). In patients with severe renal dysfunction or undergoing hemodialysis, dosing adjustment is not generally necessary.
Etodolac pharmacokinetics have been investigated in subjects with renal insufficiency. Etodolac renal clearance was unchanged in the presence of mild-to-moderate renal failure (creatinine clearance 37 to 88 mL/min). Furthermore, there were no significant differences in the disposition of total and free etodolac in these patients. However, etodolac should be used with caution in such patients because, as with other NSAIDs, it may further decrease renal function in some patients. In patients undergoing hemodialysis, there was a 50% greater apparent clearance of total etodolac, due to a 50% greater unbound fraction. Free etodolac clearance was not altered, indicating the importance of protein binding in etodolac's disposition. Etodolac is not significantly removed from the blood in patients undergoing hemodialysis.
Etodolac capsules are indicated:
• For acute and long-term use in the management of signs and symptoms of the following:
• For the management of acute pain
Etodolac is contraindicated in patients with known hypersensitivity to etodolac or other ingredients in etodolac capsules.
In the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS)
NSAIDs, including etodolac, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. Physicians should inform patients about the signs and/or symptoms of serious GI toxicity and what steps to take if they occur.
In late pregnancy, the third trimester, as with other NSAIDs, etodolac should be avoided because it may cause premature closure of the ductus arteriosus (see PRECAUTIONS, Pregnancy, Nonteratogenic Effects).
Etodolac, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS, Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation).
Etodolac, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.
Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.
In late pregnancy, the third trimester, as with other NSAIDs, etodolac should be avoided because it may cause premature closure of the ductus arteriosus.
Etodolac has no apparent pharmacokinetic interaction when administered with furosemide or hydrochlorothiazide. Nevertheless, clinical studies, as well as postmarketing observations have shown that etodolac can reduce the natriuretic effect of furosemide and thiazides in some patients with possible loss of blood pressure control. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal insufficiency or failure (see WARNINGS, Renal Effects), as well as to assure diuretic efficacy.
No carcinogenic effect of etodolac was observed in mice or rats receiving oral doses of 15 mg/kg/day (45 to 89 mg/m 2, respectively) or less for periods of 2 years or 18 months, respectively. Etodolac was not mutagenic in in vitro tests performed with S. typhimurium and mouse lymphoma cells as well as in an in vivo mouse micronucleus test. However, data from the in vitro human peripheral lymphocyte test showed an increase in the number of gaps (3.0 to 5.3% unstained regions in the chromatid without dislocation) among the etodolac-treated cultures (50 to 200 mcg/mL) compared to negative controls (2.0%); no other difference was noted between the controls and drug-treated groups. Etodolac showed no impairment of fertility in male and female rats up to oral doses of 16 mg/kg (94 mg/m 2). However, reduced implantation of fertilized eggs occurred in the 8 mg/kg group.
Teratogenic Effects - Pregnancy Category C
In teratology studies, isolated occurrences of alterations in limb development were found and included polydactyly, oligodactyly, syndactyly, and unossified phalanges in rats and oligodactyly and synostosis of metatarsals in rabbits. These were observed at dose levels (2 to 14 mg/kg/day) close to human clinical doses. However, the frequency and the dosage group distribution of these findings in initial or repeated studies did not establish a clear drug or dose-response relationship. Animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Etodolac should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects
Etodolac should be used during pregnancy only if the potential benefits justify the potential risk to the fetus. Because of the known effects of NSAIDs on the fetal cardiovascular system (closure of the ductus arteriosus), use during pregnancy (particularly during the third trimester) should be avoided.
Digestive system - Dyspepsia (10%), abdominal pain*, diarrhea*, flatulence*, nausea*, abdominal distension, epigastric pain, abnormal stools, constipation, gastritis, melena, vomiting.
Nervous system - Asthenia/malaise*, dizziness*, depression, nervousness, fatigue.
Musculoskeletal - Arthralgia
*Drug-related patient complaints occurring in 3 to 9% of patients treated with etodolac.
Digestive system - Thirst, dry mouth, ulcerative stomatitis, anorexia, eructation, elevated liver enzymes, cholestatic hepatitis, hepatitis , cholestatic jaundice, duodenitis, jaundice, hepatic failure, liver necrosis, fatal fulminant hepatitis, peptic ulcer with or without bleeding and/or perforation , intestinal ulceration, pancreatitis.
Musculoskeletal - Muscle pain.
Hemic and lymphatic system – Lymphadenopathy
Symptoms following acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur and coma has occurred following massive ibuprofen or mefenamic-acid overdose. Hypertension/hypotension, acute renal failure, and respiratory depression may occur but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following overdose.
Patients should be managed by symptomatic and supportive care following an NSAID overdose. There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalinization of the urine, hemodialysis, or hemoperfusion would probably not be useful due to etodolac's high protein binding.
After observing the response to initial therapy with etodolac, the dose and frequency should be adjusted to suit an individual patient's needs.
In chronic conditions, a therapeutic response to therapy with etodolac is sometimes seen within one week of therapy, but most often is observed by two weeks. After a satisfactory response has been achieved, the patient's dose should be reviewed and adjusted as required.
300 mg capsules (Hard gelatin capsules with a white opaque body and a light gray cap. APO 040 is imprinted on each capsules in black ink)
Store at controlled room temperature 20° to 25°C (68° to 77°F); excursions permitted from 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from moisture.
Dispense in tight, light-resistant container [see USP].
ETODOLAC CAPSULES, USP
200 mg and 300 mg
Manufactured for:
Revised: July 2016
Rev. 5
Increased risk of heart attack or stroke that can lead to death. This risk may happen early in treatment and may increase:
Do not take NSAIDs right before or after heart surgery called a "coronary artery bypass graft (CABG)". Avoid taking NSAIDs after a recent heart attack, unless your healthcare provider tells you to. You may have an increased risk of another heart attack if you take NSAIDs after a recent heart attack.
Increased risk of bleeding, ulcers and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach and intestines:
at anytime during use
if you had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAIDs.
NSAIDs can cause serious side effects including:
Other side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting, and dizziness
Stop taking NSAID and call your healthcare provider right away if you get any of the following symptoms:
Other information about NSAIDs:
PRINCIPAL DISPLAY PANEL - 300 mg
etodolac capsule
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:66267-575(NDC:60505-0040)
FERROSOFERRIC OXIDE (UNII: XM0M87F357)
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)
GELATIN (UNII: 2G86QN327L)
LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)
SODIUM LAURYL SULFATE (UNII: 368GB5141J)
STEARIC ACID (UNII: 4ELV7Z65AP)
TALC (UNII: 7SEV7J4R1U)
Color white (opaque body) , gray (light gray cap) Score no score
Shape CAPSULE Size 23mm
Flavor Imprint Code APO;040
NDC:66267-575-30 30 in 1 BOTTLE; Type 0: Not a Combination Product 04/04/2019
Labeler - NuCare Pharmaceuticals,Inc. (010632300)
NuCare Pharmaceuticals,Inc. 010632300 repack(66267-575)
1 197685 etodolac 300 MG Oral Capsule PSN
2 197685 etodolac 300 MG Oral Capsule SCD
https://dailymed.nlm.nih.gov/dailymed/labelrss.cfm?setid=85b6254b-21da-ea85-e053-2991aa0a7d51
1 66267-575-30