TOLMETIN SODIUM

Clinical summary

Indications and usage INDICATIONS AND USAGE: Carefully consider the potential benefits and risks of TOLECTIN capsules, USP and other treatment options before deciding to use TOLECTIN capsules. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). TOLECTIN capsules are indicated for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis. TOLECTIN capsules are indicated in the treatment of acute flares and the long-term management of the chronic disease. TOLECTIN capsules are also indicated for treatment of juvenile rheumatoid arthritis. The safety and effectiveness of TOLECTIN capsules have not been established in pediatric patients under 2 years of age (see PRECAUTIONS: Pediatric Use and DOSAGE AND ADMINISTRATION ). Dosage and administration DOSAGE AND ADMINISTRATION: Carefully consider the potential benefits and risks of TOLECTIN capsules and other treatment options before deciding to use TOLECTIN capsules. 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 TOLECTIN capsules, the dose and frequency should be adjusted to suit an individual patient’s needs. For the relief of rheumatoid arthritis or osteoarthritis, the recommended starting dose for adults is 400 mg three times daily (1200 mg daily), preferably including a dose on arising and a dose at bedtime. To achieve optimal therapeutic effect the dose should be adjusted according to the patient’s response after 1 or 2 weeks. Control is usually achieved at doses of 600 mg to 1800 mg daily in divided doses (generally t.i.d.). Doses larger than 1800 mg/day have not been studied and are not recommended. For the relief of juvenile rheumatoid arthritis, the recommended starting dose for pediatric patients (2 years and older) is 20 mg/kg/day in divided doses (t.i.d. or q.i.d.). When control has been achieved, the usual dose ranges from 15 to 30 mg/kg/day. Doses higher than 30 mg/kg/day have not been studied, and, therefore, are not recommended. A therapeutic response to TOLECTIN can be expected in a few days to a week. Progressive improvement can be anticipated during succeeding weeks of therapy. If gastrointestinal symptoms occur, TOLECTIN capsules can be administered with antacids other than sodium bicarbonate. TOLECTIN bioavailability and pharmacokinetics are not significantly affected by acute or chronic administration of magnesium and aluminum hydroxides; however, bioavailability is affected by food or milk (see PRECAUTIONS: Drug-Food Interaction ). Warnings and cautions WARNINGS: Cardiovascular Effects: Cardiovascular Thrombotic Events: Clinical trials of several COX-2 selective and nonselective NSAIDs of up to 3 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 TOLECTIN, 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 treat