Etodolac

Tablet, Film Coated · Oral

Prescription (Rx) Nonsteroidal Anti-inflammatory Drug

Boxed warning. Cardiovascular Thrombotic Events Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [see Warnings and Precautions ]. Etodolac tablets, 400 mg and 500 mg are contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications and Warnings ]. Gastrointestinal Risk NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal (GI) events. (See WARNINGS ).

Uses

Dosage and administration

Carefully consider the potential benefits and risks of etodolac tablets and other treatment options before deciding to use etodolac tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). After observing the response to initial therapy with etodolac tablets, the dose and frequency should be adjusted to suit an individual patient's needs. Dosage adjustment of etodolac tablets is generally not required in patients with mild to moderate renal impairment. Etodolac should be used with caution in such patients, because, as with other NSAIDs, it may further decrease renal function in some patients with impaired renal function (see WARNINGS, Renal Effects ). Analgesia The recommended total daily dose of etodolac for acute pain is up to 1000 mg, given as 200 to 400 mg every 6 to 8 hours. Doses of etodolac greater than 1000 mg/day have not been adequately evaluated in well-controlled trials. Osteoarthritis and Rheumatoid Arthritis The recommended starting dose of etodolac for the management of the signs and symptoms of osteoarthritis or rheumatoid arthritis is: 300 mg b.i.d., t.i.d., or 400 mg b.i.d., or 500 mg b.i.d. A lower dose of 600 mg/day may suffice for long-term administration. Physicians should be aware that doses above 1000 mg/day have not been adequately evaluated in well-controlled clinical trials. 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.

Contraindications

Etodolac tablets are contraindicated in patients with known hypersensitivity to etodolac or other ingredients in etodolac tablets. Etodolac tablets should not be given to patients who have experienced asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS , Anaphylactoid Reactions and PRECAUTIONS , Pre-existing Asthma ). In the setting of coronary artery bypass graft (CABG) surgery [see Warnings ]

Warnings

Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as etodolac, increases the risk of serious gastrointestinal (GI) events [see Warnings ]. Status Post Coronary Artery Bypass Graft (CABG) Surgery Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG [see Contraindications ]. Post-MI Patients Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up. Avoid the use of etodolac tablets in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If etodolac tablets are used in patients with a recent MI, monitor patients for signs of cardiac ischemia. Hypertension NSAIDs, including etodolac, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including etodolac, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy. Heart Failure and Edema The Coxib and traditional NSAID Trialists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death. Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of etodolac may blunt the CV effects of several therapeutic agents used to treat these medical conditions [e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs)] [see Drug Interactions ]. Avoid the use of etodolac tablets in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If etodolac tablets are used in patients with severe heart failure, monitor patients for signs of worsening heart failure. Gastrointestinal Effects—Risk of Ulceration, Bleeding, and Perforation 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. NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease, and/or gastrointestinal bleeding, and who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors.

Precautions

General Etodolac cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered solely if a decision is made to discontinue corticosteroids. The pharmacological activity of etodolac in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions. Hepatic Effects Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including etodolac. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis, and hepatic failure, some of them with fatal outcomes, have been reported. A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with etodolac. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), etodolac should be discontinued. Hematological Effects Anemia is sometimes seen in patients receiving NSAIDs including etodolac. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including etodolac, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia. NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving etodolac who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored. Pre-existing Asthma Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthmas has been associated with severe bronchospasm which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, etodolac should not be administered to patients with this form of aspirin sensitivity and should be used with caution in all patients with pre-existing asthma. Information For Patients Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed. Cardiovascular Thrombotic Events Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately [ see Warnings ]. Etodolac tablets, 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 ). Serious Skin Reactions, including DRESS Advise patients to stop taking tablets immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible [ see WARNINGS ]. Heart Failure And Edema Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur [ see Warnings ]. 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. Patients should be informed of the signs of an anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS ). Fetal Toxicity Inform pregnant women to avoid use of etodolac tablets and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. If treatment with etodolac tablets is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours [see WARNINGS; Fetal Toxicity , PRECAUTIONS; Pregnancy ]. Laboratory Tests Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically for signs or symptoms of anemia. Appropriate measures should be taken in case such signs of anemia occur.

Side effects

In patients taking etodolac or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1 to 10% of patients are: Gastrointestinal experiences including: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal), vomiting. Other events including: abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritis, rashes, tinnitus. Adverse-reaction information for etodolac was derived from 2,629 arthritic patients treated with etodolac tablets in double-blind and open-label clinical trials of 4 to 320 weeks in duration and worldwide postmarketing surveillance studies. In clinical trials, most adverse reactions were mild and transient. The discontinuation rate in controlled clinical trials, because of adverse events, was up to 10% for patients treated with etodolac. New patient complaints (with an incidence greater than or equal to 1%) are listed below by body system. The incidences were determined from clinical trials involving 465 patients with osteoarthritis treated with 300 to 500 mg of etodolac b.i.d. (i.e., 600 to 1000 mg/day). Incidence Greater Than Or Equal To 1% — Probably Causally Related Body as a whole—Chills and fever. 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. Skin and appendages—Pruritus, rash. Special senses—Blurred vision, tinnitus. Urogenital system—Dysuria, urinary frequency. Musculoskeletal—Arthralgia. *Drug-related patient complaints occurring in 3 to 9% of patients treated with etodolac. Drug-related patient-complaints occurring in fewer than 3%, but more than 1%, are unmarked. Incidence Less Than 1%— Probably Causally Related (Adverse reactions reported only in worldwide postmarketing experience, not seen in clinical trials, are considered rarer and are italicized.) Body as a whole— Allergic reaction, anaphylactic/anaphylactoid reactions (including shock). Cardiovascular system—Hypertension, congestive heart failure, flushing, palpitations, syncope, vasculitis (including necrotizing and allergic). Digestive system—Thirst, dry mouth, ulcerative stomatitis, anorexia, eructation, elevated liver enzymes, cholestatic hepatitis, hepatitis, cholestatic jaundice, duodenitis, jaundice, hepatic failure, liver necrosis, peptic ulcer with or without bleeding and/or perforation, intestinal ulceration, pancreatitis. Hemic and lymphatic system—Ecchymosis, anemia, thrombocytopenia, bleeding time increased, agranulocytosis, hemolytic anemia, aplastic anemia, leukopenia, neutropenia, pancytopenia. Metabolic and nutritional—Edema, serum creatinine increase, hyperglycemia in previously controlled diabetic patients. Nervous system—Insomnia, somnolence. Respiratory system—Asthma, pulmonary infiltration with eosinophilia . Skin and appendages—Angioedema, sweating, urticaria, exfoliative dermatitis, vesiculobullous rash, cutaneous vasculitis with purpura, Stevens-Johnson Syndrome, toxic epidermal necrolysis, fixed drug eruption (FDE), leukocytoclastic vasculitis, hyperpigmentation , erythema multiforme. Special senses—Photophobia, transient visual disturbances. Urogenital system— Elevated BUN, renal failure, renal insufficiency, renal papillary necrosis. Incidence Less Than 1% — Causal Relationship Unknown (Medical events occurring under circumstances where causal relationship to etodolac is uncertain. These reactions are listed as alerting information for physicians.) Body as a whole—Infection, headache. Cardiovascular system—Arrhythmias, myocardial infarction, cerebrovascular accident. Digestive system—Esophagitis with or without stricture or cardiospasm, colitis, GI discomfort, burning sensation, blood in stools, gastralgia, upper abdominal discomfort. Metabolic and nutritional—Change in weight. Nervous system—Paresthesia, confusion, irritability. Respiratory system— Bronchitis, bronchospasm, dyspnea, pharyngitis, rhinitis, sinusitis. Skin and appendages—Alopecia, maculopapular rash, photosensitivity, skin peeling. Special senses—Conjunctivitis, deafness, taste perversion, loss of taste. Urogenital system—Cystitis, hematuria, leukorrhea, renal calculus, interstitial nephritis, uterine bleeding irregularities, renal impairment. Musculoskeletal—Muscle pain. Additional Adverse Reactions Reported with NSAIDs Body as a whole—Sepsis, death Cardiovascular system—Tachycardia Digestive system—Gastric ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis Hemic and lymphatic system—Lymphadenopathy Nervous system—Anxiety, dream abnormalities, convulsions, coma, hallucinations, meningitis, tremors, vertigo Respiratory system—Respiratory depression, pneumonia Urogenital system—Oliguria/polyuria, proteinuria

Drug interactions

Drug Interactions ACE-inhibitors Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors (see WARNINGS ). Antacids The concomitant administration of antacids has no apparent effect on the extent of absorption of etodolac. However, antacids can decrease the peak concentration reached by 15% to 20% but have no detectable effect on the time-to-peak. Aspirin When etodolac is administered with aspirin, its protein binding is reduced, although the clearance of free etodolac is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of etodolac and aspirin is not generally recommended because of the potential of increased adverse effects. Cyclosporine, Digoxin, Methotrexate Etodolac, like other NSAIDs, through effects on renal prostaglandins, may cause changes in the elimination of these drugs leading to elevated serum levels of cyclosporine, digoxin, methotrexate, and increased toxicity. Nephrotoxicity associated with cyclosporine may also be enhanced. Patients receiving these drugs who are given etodolac, or any other NSAID, and particularly those patients with altered renal function, should be observed for the development of the specific toxicities of these drugs. NSAIDs, such as etodolac, should not be administered prior to or concomitantly with high doses of methotrexate. NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. In general, caution should be used when NSAIDs are administered concomitantly with methotrexate. Diuretics 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. Glyburide Etodolac has no apparent pharmacokinetic interaction when administered with glyburide. Lithium NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. Careful monitoring of lithium levels is advised in the event NSAID dosage adjustments are required. Phenylbutazone Phenylbutazone causes increase (by about 80%) in the free fraction of etodolac. Although in vivo studies have not been done to see if etodolac clearance is changed by coadministration of phenylbutazone, it is not recommended that they be coadministered. Phenytoin Etodolac has no apparent pharmacokinetic interaction when administered with phenytoin. Warfarin The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than that of users of either drug alone. Short-term pharmacokinetic studies have demonstrated that concomitant administration of warfarin and etodolac tablets results in reduced protein binding of warfarin, but there was no change in the clearance of free warfarin. There was no significant difference in the pharmacodynamic effect of warfarin administered alone and warfarin administered with etodolac as measured by prothrombin time. Thus, concomitant therapy with warfarin and etodolac should not require dosage adjustment of either drug. However, caution should be exercised because there have been a few spontaneous reports of prolonged prothrombin times, with or without bleeding, in etodolac-treated patients receiving concomitant warfarin therapy. Close monitoring of such patients is therefore recommended.

Pregnancy

Pregnancy Risk Summary Use of NSAIDs, including etodolac tablets, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of etodolac tablets use between about 20 and 30 weeks of gestation, and avoid etodolac tablets use at about 30 weeks of gestation and later in pregnancy [ see WARNINGS; Fetal Toxicity ]. Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including etodolac tablets, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. 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. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as etodolac, resulted in increased pre- and post-implantation loss. Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. The estimated background risk of major birth defects and miscarriage for the indicated population(s) 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 Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including etodolac tablets, can cause premature closure of the fetal ductus arteriosus [ see WARNINGS; Fetal Toxicity ]. Oligohydramnios/Neonatal Renal Impairment If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If etodolac tablets treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue etodolac tablets and follow up according to clinical practice [ see WARNINGS; Fetal Toxicity ]. Data Human Data There are no adequate and well-controlled studies in pregnant women. Etodolac tablets should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Premature Closure of Fetal Ductus Arteriosus: Published literature reports that the use of NSAIDs at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment: Published studies and postmarketing reports describe maternal NSAID use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. There have been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. Methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use. Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to NSAIDs through maternal use is uncertain.

Pediatric use

Pediatric Use Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

Geriatric use

Geriatric Use As with any NSAID, caution should be exercised in treating the elderly (65 years and older) and when increasing the dose (see WARNINGS ). In etodolac clinical studies, no overall differences in safety or effectiveness were observed between these patients and younger patients. In pharmacokinetic studies, age was shown not to have any effect on etodolac half-life or protein binding, and there was no change in expected drug accumulation. Therefore, no dosage adjustment is generally necessary in the elderly on the basis of pharmacokinetics (see CLINICAL PHARMACOLOGY , Special Populations ). Elderly patients may be more sensitive to the antiprostaglandin effects of NSAIDs (on the gastrointestinal tract and kidneys) than younger patients (see WARNINGS ). In particular, elderly or debilitated patients who receive NSAID therapy seem to tolerate gastrointestinal ulceration or bleeding less well than other individuals, and most spontaneous reports of fatal GI events are in this population. Etodolac is eliminated primarily by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see WARNINGS, Renal Effects ).

Overdosage

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, 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.

Description

Etodolac is a member of the pyranocarboxylic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Each tablet contains etodolac for oral administration. Etodolac is a racemic mixture of [+]S and [-]R-enantiomers. Etodolac is a white or almost white, crystalline powder, freely soluble in acetone, ethyl acetate and methanol, soluble in dimethyl formamide. 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 17 H 21 NO 3 , and it has the following structural formula: The inactive ingredients in etodolac tablets, USP include: colloidal silicon dioxide, hypromellose, lactose monohydrate, polyethylene glycol, magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate and titanium dioxide. In addition 500 mg tablet contains iron oxide yellow. str

How supplied

Etodolac Tablets, USP are available as: Etodolac Tablets USP, 400 mg are white in color, biconvex oval shaped film-coated tablet, debossed with “ETOT” on one side and “400” on the other side. Bottles of 100 NDC 59651-461-01 Etodolac Tablets USP, 500 mg are yellow in color, biconvex oval shaped film-coated tablet, debossed with “ETOT” on one side and “500” on the other side. Bottles of 100 NDC 59651-462-01 Store at 20 o to 25 o C (68 o to 77 o F) [see USP Controlled Room Temperature]. Store tablets in original container until ready to use. Dispense in light-resistant container. For more information, call Aurobindo Pharma USA, Inc. at 1-866-850-2876. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Issued: November 2025

Patient information

Information For Patients Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed. Cardiovascular Thrombotic Events Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately [ see Warnings ]. Etodolac tablets, 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 ). Serious Skin Reactions, including DRESS Advise patients to stop taking tablets immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible [ see WARNINGS ]. Heart Failure And Edema Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur [ see Warnings ]. 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. Patients should be informed of the signs of an anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS ). Fetal Toxicity Inform pregnant women to avoid use of etodolac tablets and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. If treatment with etodolac tablets is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours [see WARNINGS; Fetal Toxicity , PRECAUTIONS; Pregnancy ].

Label text from the FDA structured product label by Aurobindo Pharma Limited (revised Jul 16, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Etodolac in 103 products

Etodolac NDC products (103)

NDC	Strength & form	Labeler	Type
50090-8037	Etodolac 300 mg/1 Capsule	A-S Medication Solutions	ANDA
50090-6739	Etodolac 500 mg/1 Tablet, Film Coated	A-S Medication Solutions	ANDA
50090-4053	Etodolac 400 mg/1 Tablet, Film Coated	A-S Medication Solutions	ANDA
50090-3974	Etodolac 500 mg/1 Tablet, Film Coated	A-S Medication Solutions	ANDA
50090-3963	Etodolac 400 mg/1 Tablet, Film Coated	A-S Medication Solutions	ANDA
50090-1489	Etodolac 500 mg/1 Tablet, Film Coated	A-S Medication Solutions	ANDA
50090-1790	Etodolac 400 mg/1 Tablet, Film Coated	A-S Medication Solutions	ANDA
50090-2132	Etodolac 300 mg/1 Capsule	A-S Medication Solutions	ANDA
80425-0551	Etodolac 400 mg/1 Tablet, Film Coated	Advanced Rx of Tennessee, LLC	ANDA
80425-0381	Etodolac 600 mg/1 Tablet, Film Coated, Extended Release	Advanced Rx Pharmacy of Tennessee, LLC	ANDA
80425-0190	Etodolac 400 mg/1 Tablet, Film Coated	Advanced Rx Pharmacy of Tennessee, LLC	ANDA
80425-0181	Etodolac 600 mg/1 Tablet, Extended Release	Advanced Rx Pharmacy of Tennessee, LLC	ANDA
80425-0140	Etodolac 400 mg/1 Tablet, Film Coated	Advanced Rx Pharmacy of Tennessee, LLC	ANDA
80425-0126	Etodolac 600 mg/1 Tablet, Extended Release	Advanced Rx Pharmacy of Tennessee, LLC	ANDA
69238-1342	Etodolac 400 mg/1 Tablet, Film Coated	Amneal Pharmaceuticals NY LLC	ANDA
69238-1343	Etodolac 500 mg/1 Tablet, Film Coated	Amneal Pharmaceuticals NY LLC	ANDA
62559-250	Etodolac 200 mg/1 Capsule	ANI Pharmaceuticals, Inc.	ANDA
62559-251	Etodolac 300 mg/1 Capsule	ANI Pharmaceuticals, Inc.	ANDA
71610-859	Etodolac 400 mg/1 Tablet, Film Coated	Aphena Pharma Solutions - Tennessee, LLC	ANDA
71610-816	Etodolac 400 mg/1 Tablet, Film Coated	Aphena Pharma Solutions - Tennessee, LLC	ANDA
71610-804	Etodolac 400 mg/1 Tablet, Film Coated	Aphena Pharma Solutions - Tennessee, LLC	ANDA
71610-795	Etodolac 500 mg/1 Tablet, Film Coated	Aphena Pharma Solutions - Tennessee, LLC	ANDA
71610-794	Etodolac 400 mg/1 Tablet, Film Coated	Aphena Pharma Solutions - Tennessee, LLC	ANDA
71610-779	Etodolac 500 mg/1 Tablet, Film Coated	Aphena Pharma Solutions - Tennessee, LLC	ANDA
60505-0102	Etodolac 500 mg/1 Tablet, Film Coated	Apotex Corp.	ANDA
60505-0039	Etodolac 200 mg/1 Capsule	Apotex Corp.	ANDA
60505-0040	Etodolac 300 mg/1 Capsule	Apotex Corp.	ANDA
60505-0041	Etodolac 400 mg/1 Tablet, Film Coated	Apotex Corp.	ANDA
59651-461	Etodolac 400 mg/1 Tablet, Film Coated	Aurobindo Pharma Limited	ANDA
59651-462	Etodolac 500 mg/1 Tablet, Film Coated	Aurobindo Pharma Limited	ANDA
71335-0126	Etodolac 400 mg/1 Tablet, Film Coated	Bryant Ranch Prepack	ANDA
71335-0399	Etodolac 500 mg/1 Tablet, Film Coated	Bryant Ranch Prepack	ANDA
71335-0982	Etodolac 400 mg/1 Tablet, Film Coated	Bryant Ranch Prepack	ANDA
63629-1935	Etodolac 200 mg/1 Capsule	Bryant Ranch Prepack	ANDA
63629-1936	Etodolac 300 mg/1 Capsule	Bryant Ranch Prepack	ANDA
71335-1230	Etodolac 500 mg/1 Tablet, Film Coated	Bryant Ranch Prepack	ANDA
71335-1958	Etodolac 400 mg/1 Tablet, Film Coated	Bryant Ranch Prepack	ANDA
63629-3641	Etodolac 200 mg/1 Capsule	Bryant Ranch Prepack	ANDA
63629-8598	Etodolac 600 mg/1 Tablet, Film Coated, Extended Release	Bryant Ranch Prepack	ANDA
63629-8805	Etodolac 400 mg/1 Tablet, Film Coated	Bryant Ranch Prepack	ANDA
71335-2259	Etodolac 400 mg/1 Tablet, Film Coated	Bryant Ranch Prepack	ANDA
72162-1757	Etodolac 300 mg/1 Capsule	Bryant Ranch Prepack	ANDA
72162-1756	Etodolac 200 mg/1 Capsule	Bryant Ranch Prepack	ANDA
71335-3119	Etodolac 200 mg/1 Capsule	Bryant Ranch Prepack	ANDA
62135-910	Etodolac 400 mg/1 Tablet, Film Coated	Chartwell RX, LLC	ANDA
62135-911	Etodolac 500 mg/1 Tablet, Film Coated	Chartwell RX, LLC	ANDA
69306-020	Etodolac 400 mg/1 Tablet, Film Coated	Doc Rx	ANDA
42799-111	Etodolac 400 mg/1 Tablet, Film Coated	Edenbridge Pharmaceuticals LLC.	ANDA
42799-112	Etodolac 500 mg/1 Tablet, Film Coated	Edenbridge Pharmaceuticals LLC.	ANDA
60429-313	Etodolac 400 mg/1 Tablet, Extended Release	Golden State Medical Supply, Inc.	ANDA
60429-243	Etodolac 200 mg/1 Capsule	Golden State Medical Supply, Inc.	ANDA
60429-244	Etodolac 300 mg/1 Capsule	Golden State Medical Supply, Inc.	ANDA
60429-311	Etodolac 400 mg/1 Tablet, Film Coated	Golden State Medical Supply, Inc.	ANDA
60429-312	Etodolac 500 mg/1 Tablet, Film Coated	Golden State Medical Supply, Inc.	ANDA
60429-314	Etodolac 500 mg/1 Tablet, Extended Release	Golden State Medical Supply, Inc.	ANDA
83980-032	Etodolac 300 mg/1 Capsule	Ipca Laboratories Limited	ANDA
83980-029	Etodolac 400 mg/1 Tablet	Ipca Laboratories Limited	ANDA
83980-030	Etodolac 500 mg/1 Tablet	Ipca Laboratories Limited	ANDA
83980-031	Etodolac 200 mg/1 Capsule	Ipca Laboratories Limited	ANDA
45865-206	Etodolac 500 mg/1 Tablet, Film Coated	Medsource Pharmaceuticals	ANDA
16714-497	Etodolac 400 mg/1 Tablet, Extended Release	NORTHSTAR RX LLC	ANDA
16714-498	Etodolac 500 mg/1 Tablet, Extended Release	NORTHSTAR RX LLC	ANDA
16714-499	Etodolac 600 mg/1 Tablet, Extended Release	NORTHSTAR RX LLC	ANDA
51655-166	Etodolac 300 mg/1 Capsule	Northwind Health Company, LLC	ANDA
51655-423	Etodolac 400 mg/1 Tablet, Film Coated	Northwind Health Company, LLC	ANDA
51655-735	Etodolac 500 mg/1 Tablet, Film Coated	Northwind Health Company, LLC	ANDA
68071-3731	Etodolac 400 mg/1 Tablet, Film Coated, Extended Release	NuCare Pharmaceuticals, Inc.	ANDA
43063-856	Etodolac 400 mg/1 Tablet, Film Coated	PD-Rx Pharmaceuticals, Inc.	ANDA
43063-671	Etodolac 500 mg/1 Tablet, Film Coated	PD-Rx Pharmaceuticals, Inc.	ANDA
43063-578	Etodolac 400 mg/1 Tablet, Film Coated	PD-Rx Pharmaceuticals, Inc.	ANDA
72789-538	Etodolac 400 mg/1 Tablet, Film Coated	PD-Rx Pharmaceuticals, Inc.	ANDA
68788-7315	Etodolac 400 mg/1 Tablet, Film Coated	Preferred Pharmaceuticals Inc.	ANDA
68788-8673	Etodolac 400 mg/1 Tablet, Film Coated	Preferred Pharmaceuticals Inc.	ANDA
68788-8846	Etodolac 400 mg/1 Tablet, Film Coated	Preferred Pharmaceuticals Inc.	ANDA
71205-140	Etodolac 400 mg/1 Tablet, Film Coated, Extended Release	Proficient Rx LP	ANDA
71205-467	Etodolac 500 mg/1 Tablet, Film Coated	Proficient Rx LP	ANDA
71205-743	Etodolac 200 mg/1 Capsule	Proficient Rx LP	ANDA
63187-793	Etodolac 400 mg/1 Tablet, Extended Release	Proficient Rx LP	ANDA
63187-736	Etodolac 400 mg/1 Tablet, Film Coated	Proficient Rx LP	ANDA
63187-374	Etodolac 400 mg/1 Tablet, Film Coated, Extended Release	Proficient Rx LP	ANDA
70518-4542	Etodolac 400 mg/1 Tablet, Film Coated	REMEDYREPACK INC.	ANDA
70518-3845	Etodolac 500 mg/1 Tablet, Film Coated	REMEDYREPACK INC.	ANDA
70518-4291	Etodolac 500 mg/1 Tablet, Film Coated	REMEDYREPACK INC.	ANDA
60760-298	Etodolac 500 mg/1 Tablet, Film Coated, Extended Release	St. Mary's Medical Park Pharmacy	ANDA
60760-552	Etodolac 400 mg/1 Tablet, Film Coated	St. Marys Medical Park Pharmacy	ANDA
51672-4036	Etodolac 500 mg/1 Tablet, Film Coated	Sun Pharmaceutical Industries, Inc.	ANDA
51672-4016	Etodolac 200 mg/1 Capsule	Sun Pharmaceutical Industries, Inc.	ANDA
51672-4017	Etodolac 300 mg/1 Capsule	Sun Pharmaceutical Industries, Inc.	ANDA
51672-4018	Etodolac 400 mg/1 Tablet, Film Coated	Sun Pharmaceutical Industries, Inc.	ANDA
51672-4051	Etodolac 400 mg/1 Tablet, Extended Release	TaSun Pharmaceutical Industries, Inc.	ANDA
51672-4052	Etodolac 500 mg/1 Tablet, Extended Release	TaSun Pharmaceutical Industries, Inc.	ANDA
51672-4053	Etodolac 600 mg/1 Tablet, Extended Release	TaSun Pharmaceutical Industries, Inc.	ANDA
0093-7172	Etodolac 500 mg/1 Tablet, Film Coated, Extended Release	Teva Pharmaceuticals USA, Inc.	ANDA
0093-1122	Etodolac 400 mg/1 Tablet, Film Coated, Extended Release	Teva Pharmaceuticals USA, Inc.	ANDA
0093-1118	Etodolac 600 mg/1 Tablet, Film Coated, Extended Release	Teva Pharmaceuticals USA, Inc.	ANDA
76385-119	Etodolac 500 mg/1 Tablet, Film Coated	Unichem Pharmaceuticals (USA), Inc.	ANDA
76385-118	Etodolac 400 mg/1 Tablet, Film Coated	Unichem Pharmaceuticals (USA), Inc.	ANDA
65841-777	Etodolac 400 mg/1 Tablet, Film Coated, Extended Release	Zydus Lifesciences Limited	ANDA
65841-778	Etodolac 500 mg/1 Tablet, Film Coated, Extended Release	Zydus Lifesciences Limited	ANDA
65841-779	Etodolac 600 mg/1 Tablet, Film Coated, Extended Release	Zydus Lifesciences Limited	ANDA
68382-273	Etodolac 600 mg/1 Tablet, Film Coated, Extended Release	Zydus Pharmaceuticals USA Inc.	ANDA
68382-272	Etodolac 500 mg/1 Tablet, Film Coated, Extended Release	Zydus Pharmaceuticals USA Inc.	ANDA
68382-271	Etodolac 400 mg/1 Tablet, Film Coated, Extended Release	Zydus Pharmaceuticals USA Inc.	ANDA

Frequently asked questions

What is Etodolac used for?

What are the side effects of Etodolac?

Who makes Etodolac?

Etodolac is listed by 30 labelers in the FDA NDC directory, including A-S Medication Solutions, Advanced Rx of Tennessee, LLC, Advanced Rx Pharmacy of Tennessee, LLC, Amneal Pharmaceuticals NY LLC.