Etodolac ER

Indications and Usage Section INDICATIONS AND USAGE Carefully consider the potential benefits and risks of etodolac extended-release tablets and other treatment options before deciding to use etodolac extended-release tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS). Etodolac extended-release tablets are indicated: * For relief of signs and symptoms of juvenile arthritis * For relief of the signs and symptoms of rheumatoid arthritis * For relief of the signs and symptoms of osteoarthritis

Dosage and Administration Carefully consider the potential benefits and risks of etodolac extended-release tablets and other treatment options before deciding to use etodolac extended-release 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 extended-release tablets, the dose and frequency should be adjusted to suit an individual patient's needs. Juvenile Rheumatoid Arthritis For the relief of the signs and symptoms of juvenile rheumatoid arthritis in patients 6 to 16 years of age, the recommended dose given orally once per day should be based on body weight, according to the following table: Body Weight Range (kg) Dose 20 to 30 400 mg Tablet × 1 31 to 45 600 mg Tablet × 1 46 to 60 400 mg Tablet × 2 >60 500 mg Tablet × 2 Rheumatoid Arthritis and Osteoarthritis For the relief of the signs and symptoms of osteoarthritis or rheumatoid arthritis, the recommended starting dose of etodolac extended-release tablets is 400 to 1000 mg given orally once per day. As with other NSAIDs, the lowest effective dose should be sought for each patient. In chronic conditions, a therapeutic response to therapy with etodolac extended-release tablets is sometimes seen within one week of therapy, but most often is observed by two weeks.

Warnings Cardiovascular Effects 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 extended-release tablets in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If etodolac extended-release tablets are used in patients with a recent MI, monitor patients for signs of cardiac ischemia. Hypertension NSAIDs, including etodolac extended-release tablets, can lead to onset of new hypertension or worsening of preexisting 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 extended-release tablets, 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, hospit…

Contraindications Etodolac extended-release tablets are contraindicated in patients with known hypersensitivity to etodolac. Etodolac extended-release tablets should not be given to patients who have experienced asthma, urticaria, or 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, PREEXISTING ASTHMA). Etodolac extended-release tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

Adverse Reactions A total of 1552 patients were exposed to etodolac extended-release tablets in controlled clinical studies of at least 4 weeks in length and using daily doses in the range of 400 to 1200 mg. In the tabulations below, adverse event rates are generally categorized based on the incidence of events in the first 30 days of treatment with etodolac extended-release tablets. As with other NSAIDs, the cumulative adverse event rates may increase significantly over time with extended therapy. In patients taking NSAIDs, including etodolac extended-release tablets, the most frequently reported adverse experiences occurring in approximately 1 to 10% of patients are: gastrointestinal experiences including: abdominal pain constipation diarrhea dyspepsia flatulence GI ulcers (gastric/duodenal)* gross bleeding/perforation * nausea vomiting other events including: abnormal renal function* anemia* asthenia dizziness edema* elevated liver enzymes* headaches hypertension increased bleeding time* infection pharyngitis pruritus rashes rhinitis tinnitus* *Adverse events that were observed in < 1% of patients in the first 30 days of treatment with etodolac extended-release tablets in clinical trials. Additional NSAID Adverse Experiences Reported Occasionally with NSAIDs or Etodolac Extended-Release Tablets Include Body as a whole - allergic reaction, anaphylactic/anaphylactoid reactions (including shock), chills, fever, sepsis Cardiovascular system - congestive heart failure, flushing, palpitations, tachycardia, syncope, vasculitis (including necrotizing and allergic) Digestive system - anorexia, cholestatic hepatitis, cholestatic jaundice, dry mouth, duodenitis, eructation, esophagitis, gastritis, gastric/peptic ulcers, glossitis, hepatic failure, hepatitis, hematemesis, intestinal ulceration, jaundice, liver necrosis, melena, pancreatitis, rectal bleeding, stomatitis Hemic and lymphatic system - agranulocytosis, ecchymosis, eosinophilia, hemolytic anemia, leukopenia, neutropenia, pancytopenia, purpura, thrombocytopenia Metabolic and nutritional - hyperglycemia in previously controlled diabetic patients Nervous system - anxiety, confusion, depression, dream abnormalities, insomnia, nervousness, paresthesia, somnolence, tremors, vertigo Respiratory system - asthma, dyspnea, pulmonary infiltration with eosinophilia Skin and appendages - angioedema, cutaneous vasculitis with purpura, erythema multiforme, hyperpigmentation, sweating, urticaria, vesiculobullous rash Special senses - blurred vision, photophobia, transient visual disturbances Urogenital system - dysuria, elevated BUN, oliguria/polyuria, proteinuria, renal failure, renal insufficiency, renal papillary necrosis, serum creatinine increase, urinary frequency Other NSAID Adverse Reactions, Which Occur Rarely Are Body as a whole - anaphylactic reactions, appetite changes, death Cardiovascular system - arrhythmia, cerebrovascular accident, hypotension, myocardial infarction Digestive system - colitis, esophagitis with or without stricture or cardiospasm, thirst, ulcerative stomatitis Hemic and lymphatic system - aplastic anemia, lymphadenopathy Metabolic and nutritional - change in weight Nervous system - coma, convulsions, hallucinations, meningitis Respiratory - bronchitis, pneumonia, respiratory depression, sinusitis Skin and appendages - alopecia, exfoliative dermatitis, maculopapular rash, photosensitivity, skin peeling, Stevens-Johnson syndrome, toxic epidermal necrosis Special senses - conjunctivitis, deafness, hearing impairment, taste perversion Urogenital system - cystitis, hematuria, interstitial nephritis, leukorrhea, renal calculus, uterine bleeding irregularities