ETODOLAC
-
etodolac tablet, film coated
Lake Erie Medical DBA Quality Care Products LLC
----------
Etodolac 400 mg DESCRIPTIONCLINICAL PHARMACOLOGY
PharmacodynamicsThe mean oral clearance of etodolac following oral dosing is 49 (± 16) mL/h/kg. Approximately 1% of an etodolac dose is excreted unchanged in the urine with 72% of the dose excreted into urine as parent drug plus metabolite:
- 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 (t1/2) of etodolac is 6.4 hours (22% CV). In patients with severe renal dysfunction or undergoing hemodialysis, dosing adjustment is not generally necessary.
Fecal excretion accounted for 16% of the dose.
Special Populations
GeriatricEtodolac 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 mL/min 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.
CLINICAL STUDIES
AnalgesiaINDICATIONS AND USAGE
Carefully consider the potential benefits and risks of etodolac tablets USP and other treatment options before deciding to use etodolac tablets USP. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).
Etodolac tablets USP are indicated:
Etodolac is contraindicated in patients with known hypersensitivity to etodolac.
Etodolac 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).
Etodolac is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
WARNINGS
Cardiovascular EffectsLong-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greater risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Renal pelvic transitional epithelial hyperplasia, a spontaneous change occurring with variable frequency, was observed with increased frequency in treated male rats in a 2-year chronic study.
Advanced Renal Disease
No information is available from controlled clinical studies regarding the use of etodolac in patients with advanced renal disease. Therefore, treatment with etodolac is not recommended in these patients with advanced renal disease. If etodolac therapy must be initiated, close monitoring of the patient’s renal function is advisable.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).
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.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.
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.
AspirinWhen 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, MethotrexateEtodolac, 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 have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.
DiureticsEtodolac has no apparent pharmacokinetic interaction when administered with furosemide or hydrochlorothiazide. Nevertheless, clinical studies, as well as post-marketing observations have shown that etodolac can reduce the natriuretic effect of furosemide and thiazides in some patients. 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 failure (see WARNINGS, Renal Effects), as well as to assure diuretic efficacy.
GlyburideEtodolac has no apparent pharmacokinetic interaction when administered with glyburide.
LithiumNSAIDs 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.
PhenylbutazonePhenylbutazone 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.
PhenytoinEtodolac has no apparent pharmacokinetic interaction when administered with phenytoin.
WarfarinThe 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 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.
Drug/Laboratory Test InteractionsThe urine of patients who take etodolac can give a false-positive reaction for urinary bilirubin (urobilin) due to the presence of phenolic metabolites of etodolac. Diagnostic dip-stick methodology, used to detect ketone bodies in urine, has resulted in false-positive findings in some patients treated with etodolac. Generally, this phenomenon has not been associated with other clinically significant events. No dose relationship has been observed.
Etodolac treatment is associated with a small decrease in serum uric acid levels. In clinical trials, mean decreases of 1 mg/dL to 2 mg/dL were observed in arthritic patients receiving etodolac (600 mg/day to 1000 mg/day) after 4 weeks of therapy. These levels then remained stable for up to 1 year of therapy.
Carcinogenesis, Mutagenesis, Impairment of FertilityNo carcinogenic effect of etodolac was observed in mice or rats receiving oral doses of 15 mg/kg/day (45 mg/m2 to 89 mg/m2, 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 mcg/mL 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/m2). However, reduced implantation of fertilized eggs occurred in the 8 mg/kg group.
PregnancyTeratogenic EffectsPregnancy Category CIn 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 mg/kg/day 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 EffectsEtodolac should be used during pregnancy only if the potential benefits justify the potential risk to the fetus. Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of the ductus arteriosus), use during pregnancy (particularly during the third trimester) should be avoided.
Labor and DeliveryIn rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition and decreased pup survival occurred. The effects of etodolac on labor and delivery in pregnant women are unknown.
Nursing MothersIt is not known whether etodolac is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from etodolac, 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 UseSafety and effectiveness in pediatric patients below the age of 18 years have not been established.
Geriatric UseAs 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).
ADVERSE REACTIONSIn 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 in double-blind and open-label clinical trials of 4 to 320 weeks in duration and worldwide post-marketing 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 mg to 500 mg of etodolac b.i.d. (i.e., 600 mg/day 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*, constipation, gastritis, melena, vomiting.
Nervous System: Asthenia/malaise*, dizziness*, depression, nervousness.
Skin and Appendages: Pruritus, rash.
Special Senses: Blurred vision, tinnitus.
Urogenital System: Dysuria, urinary frequency.
*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 post-marketing 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, 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, vesiculobullous rash, cutaneous vasculitis with purpura, Stevens-Johnson Syndrome, toxic epidermal necrolysis, 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.
Metabolic and Nutritional: Change in weight.
Nervous System: Paresthesia, confusion.
Respiratory System: Bronchitis, dyspnea, pharyngitis, rhinitis, sinusitis.
Skin and Appendages: Alopecia, maculopapular rash, photosensitivity, skin peeling.
Special Senses: Conjunctivitis, deafness, taste perversion.
Urogenital System: Cystitis, hematuria, leukorrhea, renal calculus, interstitial nephritis, uterine bleeding irregularities.
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
OVERDOSAGESymptoms 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 g to 100 g in adults, 1 g/kg 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.
DOSAGE AND ADMINISTRATIONCarefully consider the potential benefits and risks of etodolac and other treatment options before deciding to use etodolac. 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, the dose and frequency should be adjusted to suit an individual patient’s needs.
Dosage adjustment of etodolac 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).
AnalgesiaThe recommended total daily dose of etodolac for acute pain is up to 1000 mg, given as 200 mg to 400 mg every 6 to 8 hours. Doses of etodolac greater than 1000 mg/day have not been adequately evaluated in well-controlled clinical trials.
Osteoarthritis and Rheumatoid ArthritisThe 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.
HOW SUPPLIEDEtodolac Tablets USP are supplied as follows:
400 mg: White, oval, unscored, film-coated tablets, debossed “E 140” on one side and plain on the other side.
Bottles of 100 Bottles of 500 Bottles of 1000500 mg: White, oval, unscored, film-coated tablets, debossed “E 139” on one side and plain on the other side.
Bottles of 100 Bottles of 500 Bottles of 1000Store at 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature].
Store tablets in original container until ready to use.
Dispense in light-resistant container.
KEEP THIS AND ALL MEDICATION OUT OF REACH OF CHILDREN.
Information for patientsPatients 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.
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. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, etodolac should be discontinued.
InteractionsDrug InteractionsACE-InhibitorsReports 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).
AntacidsThe 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.
AspirinWhen 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, MethotrexateEtodolac, 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 have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.
DiureticsEtodolac has no apparent pharmacokinetic interaction when administered with furosemide or hydrochlorothiazide. Nevertheless, clinical studies, as well as post-marketing observations have shown that etodolac can reduce the natriuretic effect of furosemide and thiazides in some patients. 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 failure (see WARNINGS, Renal Effects), as well as to assure diuretic efficacy.
GlyburideEtodolac has no apparent pharmacokinetic interaction when administered with glyburide.
LithiumNSAIDs 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.
PhenylbutazonePhenylbutazone 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.
PhenytoinEtodolac has no apparent pharmacokinetic interaction when administered with phenytoin.
WarfarinThe 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 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.
Drug/Laboratory Test InteractionsThe urine of patients who take etodolac can give a false-positive reaction for urinary bilirubin (urobilin) due to the presence of phenolic metabolites of etodolac. Diagnostic dip-stick methodology, used to detect ketone bodies in urine, has resulted in false-positive findings in some patients treated with etodolac. Generally, this phenomenon has not been associated with other clinically significant events. No dose relationship has been observed.
Etodolac treatment is associated with a small decrease in serum uric acid levels. In clinical trials, mean decreases of 1 mg/dL to 2 mg/dL were observed in arthritic patients receiving etodolac (600 mg/day to 1000 mg/day) after 4 weeks of therapy. These levels then remained stable for up to 1 year of therapy.
Carcinogenesis, Mutagenesis, Impairment of FertilityNo carcinogenic effect of etodolac was observed in mice or rats receiving oral doses of 15 mg/kg/day (45 mg/m2 to 89 mg/m2, 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 mcg/mL 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/m2). However, reduced implantation of fertilized eggs occurred in the 8 mg/kg group.
PregnancyTeratogenic EffectsPregnancy Category CIn 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 mg/kg/day 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 EffectsEtodolac should be used during pregnancy only if the potential benefits justify the potential risk to the fetus. Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of the ductus arteriosus), use during pregnancy (particularly during the third trimester) should be avoided.
Labor and DeliveryIn rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition and decreased pup survival occurred. The effects of etodolac on labor and delivery in pregnant women are unknown.
Nursing MothersIt is not known whether etodolac is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from etodolac, 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 UseSafety and effectiveness in pediatric patients below the age of 18 years have not been established.
Geriatric UseAs 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).
Cardiovascular Risk
• NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. (See WARNINGS.)
• Etodolac is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. (See 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.)
ETODOLAC - etodolac tablet
Sandoz
Inc
----------
Medication Guide for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)(See the end of this Medication Guide for a list of prescription NSAID medicines.)
What is the most important information I should know about medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
NSAID medicines may increase the chance of a heart attack or stroke that can lead to death. This chance increases:
• with longer use of NSAID medicines • in people who have heart diseaseNSAID medicines should never be used right before or after a heart surgery called a “coronary artery bypass graft (CABG)."
NSAID medicines can cause ulcers and bleeding in the stomach and intestines at any time during treatment. Ulcers and bleeding:
• can happen without warning symptoms • may cause deathThe chance of a person getting an ulcer or bleeding increases with:
• taking medicines called “corticosteroids” and “anticoagulants” • longer use • smoking • drinking alcohol • older age • having poor healthNSAID medicines should only be used:
• exactly as prescribed • at the lowest dose possible for your treatment • for the shortest time neededWhat are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
NSAID medicines are used to treat pain and redness, swelling and heat (inflammation) from medical conditions such as:
• different types of arthritis • menstrual cramps and other types of short-term painWho should not take a Non-Steroidal Anti-Inflammatory Drug (NSAID)?
Do not take an NSAID medicine:
• if you had an asthma attack, hives or other allergic reaction with aspirin or any other NSAID medicine • for pain right before or after heart bypass surgeryTell your healthcare provider:
• about all of your medical conditions. • about all of the medicines you take. NSAIDs and some other medicines can interact with each other and cause serious side effects. Keep a list of your medicines to show to your healthcare provider and pharmacist. • if you are pregnant. NSAID medicines should not be used by pregnant women late in their pregnancy. • if you are breastfeeding. Talk to your doctor.What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
Get emergency help right away if you have any of the following symptoms:
• shortness of breath or trouble breathing • chest pain • weakness in one part or side of your body • slurred speech • swelling of the face or throatStop your NSAID medicine and call your healthcare provider right away if you have any of the following symptoms:
• nausea • more tired or weaker than usual • itching • your skin or eyes look yellow • stomach pain • flu-like symptoms • vomit blood • there is blood in your bowel movement or it is black and sticky like tar • unusual weight gain • skin rash or blisters with fever • swelling of the arms and legs, hands and feetThese are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines.
Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
• Aspirin is an NSAID medicine but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach and intestines. Aspirin can also cause ulcers in the stomach and intestines. • Some of these NSAID medicines are sold in lower doses without a prescription (over–the–counter). Talk to your healthcare provider before using over–the–counter NSAIDs for more than 10 days. NSAID medicines that need a prescriptionThis Medication Guide has been approved by the U.S. Food and Drug Administration.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Sandoz Inc.
Princeton, NJ 08540
Rev 10/08
MF0140REV10/08
OS8660
Revised: 11/2009Sandoz IncImage of label
ETODOLAC
etodolac tablet, film coated |
||||||||||||||||||||||
|
||||||||||||||||||||||
|
||||||||||||||||||||||
|
||||||||||||||||||||||
|
||||||||||||||||||||||
|
Marketing Information | |||
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
ANDA | ANDA074903 | 08/26/2010 |
Labeler - Lake Erie Medical DBA Quality Care Products LLC (831276758) |
Establishment | |||
Name | Address | ID/FEI | Operations |
Snadoz Inc | 614842560 | manufacture |
Establishment | |||
Name | Address | ID/FEI | Operations |
Lake Erie Medical DBA Quality Care Products LLC | 831276758 | repack |