General: Patients with pyloric stenosis may have prolonged gastric retention of Asacol tablets which could delay release of mesalamine in the colon.
Exacerbation of the symptoms of colitis has been reported in 3% of Asacol-treated patients in controlled clinical trials. This acute reaction, characterized by cramping, abdominal pain, bloody diarrhea, and occasionally by fever, headache, malaise, pruritus, rash, and conjunctivitis, has been reported after the initiation of Asacol tablets as well as other mesalamine products. Symptoms usually abate when Asacol tablets are discontinued.
Some patients who have experienced a hypersensitivity reaction to sulfasalazine may have a similar reaction to Asacol tablets or to other compounds which contain or are converted to mesalamine.
Renal: Renal impairment, including minimal change nephropathy, acute and chronic interstitial nephritis, and, rarely, renal failure has been reported in patients taking Asacol tablets as well as other compounds which contain or are converted to mesalamine. In animal studies (rats, dogs), the kidney is the principal target organ for toxicity. At doses of approximately 750 mg/kg to 1000 mg/kg [15 to 20 times the administered recommended human dose (based on a 50 kg person) on a mg/kg basis and 3 to 4 times on a mg/m2 basis], mesalamine causes renal papillary necrosis. Therefore, caution should be exercised when using Asacol (or other compounds which contain or are converted to mesalamine or its metabolites) in patients with known renal dysfunction or history of renal disease. It is recommended that all patients have an evaluation of renal function prior to initiation of Asacol tablets and periodically while on Asacol therapy.
Use in Hepatic Impairment: There have been reports of hepatic failure in patients with pre-existing liver disease who have been administered mesalamine. Caution should be exercised when administering Asacol to patients with liver disease.
CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY
Dietary mesalamine was not carcinogenic in rats at doses as high as 480 mg/kg/day, or in mice at 2000 mg/kg/day. These doses are 2.4 and 5.1 times the maximum recommended human maintenance dose of Asacol of 1.6 g/day (32 mg/kg/day if 50 kg body weight assumed or 1184 mg/m2), respectively, based on body surface area. Mesalamine was negative in the Ames assay for mutagenesis, negative for induction of sister chromatid exchanges (SCE) and chromosomal aberrations in Chinese hamster ovary cells in vitro, and negative for induction of micronuclei (MN) in mouse bone marrow polychromatic erythrocytes. Mesalamine, at oral doses up to 480 mg/kg/day (about 1.6 times the recommended human treatment dose on a body surface area basis), was found to have no effect on fertility or reproductive performance of male and female rats.
Teratogenic Effects: Pregnancy Category B: Reproduction studies have been performed in rats at oral doses up to 480 mg/kg/day (about 1.6 times the recommended human treatment dose on a body surface area basis) and rabbits at oral doses up to 480 mg/kg/day (about 3.2 times the recommended human treatment dose on a body surface area basis) 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.
Low concentrations of mesalamine and higher concentrations of its N-acetyl metabolite have been detected in human breast milk. While the clinical significance of this has not been determined, caution should be exercised when mesalamine is administered to a nursing woman.
Safety and effectiveness of Asacol tablets in pediatric patients have not been established.
Clinical studies of Asacol did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in elderly patients should be considered when prescribing Asacol. Reports from uncontrolled clinical studies and post-marketing reporting systems suggest a higher incidence of blood dyscrasias, i.e., agranulocytosis, neutropenia, pancytopenia, in subjects receiving Asacol who are 65 years or older. Caution should be taken to closely monitor blood cell counts during drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken when prescribing this drug therapy. As stated in the PRECAUTIONS section, it is recommended that all patients have an evaluation of renal function prior to initiation of Asacol tablets and periodically while on Asacol therapy.