WARNINGS AND PRECAUTIONS
Renal Impairment
Renal impairment, including minimal change nephropathy, acute and chronic interstitial nephritis, and, rarely, renal failure, has been reported in patients taking products such as Asacol HD that contain or are converted to mesalamine.
It is recommended that all patients have an evaluation of renal function prior to initiation of Asacol HD and periodically while on therapy. Exercise caution when using Asacol HD in patients with known renal dysfunction or history of renal disease.
In animal studies (rats, mice, dogs), the kidney was the principal organ for toxicity [see Nonclinical Toxicology ].
Exacerbation of Ulcerative Colitis Symptoms
Exacerbation of the symptoms of colitis has been reported in 2.3% of Asacol HD-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 HD tablets as well as other mesalamine products. Symptoms usually abate when Asacol HD tablets are discontinued.
Hypersensitivity
Some patients who have experienced a hypersensitivity reaction to sulfasalazine may have a similar reaction to Asacol HD tablets or to other compounds that contain or are converted to mesalamine.
Pyloric Stenosis
Patients with pyloric stenosis may have prolonged gastric retention of Asacol HD tablets, which could delay release of mesalamine in the colon.
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 HD to patients with liver disease.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category B: Reproduction studies have been performed in rats at oral doses up to 480 mg/kg/day (about 0.8 times the recommended human treatment dose of 4.8 g/day based on body surface area) and rabbits at oral doses up to 480 mg/kg/day (about 1.6 times the recommended human treatment dose of 4.8 g/day based on body surface area) 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.
Nursing Mothers
Mesalamine and its N-acetyl metabolite have been detected in human breast milk. The clinical significance of this has not been determined. Caution should be exercised when Asacol HD is administered to a nursing woman.
Pediatric Use
Safety and effectiveness of Asacol HD in pediatric patients have not been established.
Geriatric Use
Clinical studies of Asacol HD did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in response 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 HD. Reports from uncontrolled clinical studies and postmarketing reporting systems for Asacol (mesalamine) suggested a higher incidence of blood dyscrasias, i.e., agranulocytosis, neutropenia, pancytopenia, in patients who were 65 years or older. Caution should be taken to closely monitor blood cell counts during mesalamine therapy.
Mesalamine 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. It is recommended that all patients have an evaluation of renal function prior to initiation of Asacol HD therapy and periodically while on Asacol HD therapy [see Warnings and Precautions].
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