Mesalamine Delayed-release Tablets

SECTION 2: Hazards identification

Dose and Mesalamine Delayed-release Tablets 1.2 g are pale red-brown, oval- Administration shaped, biconvex, bevel film-coated tablets debossed with the ‘711’ on one side and plain on other side – each containing 1.2 g Mesalamine. The recommended dosage for the induction of remission in adult patients with active, mild to moderate ulcerative colitis is two to four 1.2 g tablets taken once daily with a meal for a total daily dose of 2.4 g or 4.8 g. The recommended dosage for the maintenance of remission is two 1.2 g tablets taken once daily with a meal for a total daily dose of 2.4 g. Adverse Effects The following reactions have been reported during treatment with mesalamine. Renal Impairment Renal impairment, including minimal change nephropathy, acute and chronic interstitial nephritis and rarely renal failure has been reported in patients given products such as mesalamine delayed-release tablets that contain mesalamine or are converted to mesalamine. It is recommended that patients have an evaluation of renal function prior to initiation of mesalamine delayed-release tablets therapy and periodically while on therapy. Exercise caution when using mesalamine delayed-release tablets in patients with known renal dysfunction or a history of renal disease. In animal studies, the kidney was the principal organ for toxicity Mesalamine-Induced Acute Intolerance Syndrome Mesalamine has been associated with an acute intolerance syndrome that may be difficult to distinguish from an exacerbation of ulcerative colitis. Although the exact frequency of occurrence has not been determined, it has occurred in 3% of patients in controlled clinical trials of mesalamine or sulfasalazine. Symptoms include cramping, acute abdominal pain and bloody diarrhea, and sometimes fever, headache and rash. Observe patients closely for worsening of these symptoms while on treatment. If acute intolerance syndrome is suspected, promptly discontinue treatment with mesalamine delayed- release tablets. Hypersensitivity Reactions Some patients who have experienced a hypersensitivity reaction to sulfasalazine may have a similar reaction to mesalamine delayed- release tablets or to other compounds that contain or are converted to mesalamine. Mesalamine-induced cardiac hypersensitivity reactions (myocarditis and pericarditis) have been reported with mesalamine delayed- release tablets and other mesalamine medications. Caution should be taken in prescribing this medicine to patients with conditions predisposing them to the development of myocarditis or pericarditis. Hepatic Impairment There have been reports of hepatic failure in patients with preexisting liver disease who have been administered mesalamine. Caution should be exercised when administering mesalamine delayed-release tablets to patients with liver disease. Upper GI Tract Obstruction Pyloric stenosis or other organic or functional obstruction in the upper gastrointestinal tract may cause prolonged gastric retention of mesalamine delayed-release tablets which would delay mesalamine release in the colon. Interference with Laboratory Tests Use of mesalamine may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection because of the similarity in the chromatograms of normetanephrine and mesalamine’s main metabolite, N-acetylaminosalicylic acid (N-Ac-5-ASA). An alternative, selective assay for normetanephrine should be considered. Over Dose Effect Mesalamine is an aminosalicylate, and symptoms of salicylate toxicity may include tinnitus, vertigo, headache, confusion, drowsiness, sweating, seizures, hyperventilation, dyspnea, vomiting, and diarrhea. Severe intoxication may lead to disruption of electrolyte balance and blood-pH, hyperthermia, dehydration, and end organ damage. There is no specific known antidote for mesalamine overdose; however, conventional therapy for salicylate toxicity may be beneficial in the event of acute over dosage. Fluid and electrolyte imbalance should be corrected by the administration of appropriate intravenous therapy. Adequate renal function should be maintained. Contraindications Mesalamine delayed-release tablets are contraindicated in patients with known hypersensitivity to salicylates or aminosalicylates or to any of the ingredients of mesalamine delayed-release tablets. Renal impairment may occur. Assess renal function at the beginning of treatment and periodically during treatment. Mesalamine-induced acute intolerance syndrome has been reported. Observe patients closely for worsening of these symptoms while on treatment. Use caution when treating patients who are hypersensitive to sulfasalazine. Mesalamine-induced cardiac hypersensitivity reactions (myocarditis and pericarditis) have been reported. Hepatic failure has been reported in patients with pre-existing liver disease. Use caution when treating patients with liver disease. Upper GI tract obstruction may delay onset of action. Use of mesalamine may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection. Pregnancy Comments Pregnancy Category B Reproduction studies with mesalamine have been performed in rats at doses up to 1000 mg/kg/day (1.8 times the maximum recommended human dose based on a body surface area comparison) and rabbits at doses up to 800 mg/kg/day (2.9 times the maximum recommended human dose based on a body surface area comparison) and have revealed no evidence of impaired fertility or harm to the fetus due to mesalamine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Mesalamine is known to cross the placental barrier.