Colazal Warnings, Precautions, Pregnancy, Nursing, Abuse - Balsalazide

Colazal Warnings, Precautions, Pregnancy, Nursing, Abuse - Balsalazide

WARNINGS

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Of the 259 patients treated with COLAZAL 6.75 grams/day in controlled clinical trials of active disease, exacerbation of the symptoms of colitis, possibly related to drug use, has been reported by 3 patients.

General:   Patients with pyloric stenosis may have prolonged gastric retention of COLAZAL Capsules.

Renal:   At doses up to 2000 mg/kg (approximately 21 times the recommended 6.75 grams/day dose on a mg/kg basis for a 70 kg person), COLAZAL had no nephrotoxic effects in rats or dogs. Renal toxicity has been observed in animals and patients given other mesalamine products. Therefore, caution should be exercised when administering COLAZAL to patients with known renal dysfunction or a history of renal disease.

Drug Interactions:   No drug interaction studies have been conducted for COLAZAL ™, however the use of orally administered antibiotics could, theoretically, interfere with the release of mesalamine in the colon.

Carcinogenesis, Mutagenesis, Impairment of Fertility:   In a 24 month rat (Sprague Dawley) carcinogenicity study, oral (dietary) balsalazide disodium at doses up to 2 grams/kg/day was not tumorigenic. For a 50 kg person of average height this dose represents 2.4 times the recommended human dose on a body surface area basis.

Balsalazide disodium was not genotoxic in the following in vitro or in vivo tests: Ames test, human lymphocyte chromosomal aberration test, and mouse lymphoma cell (L5178Y/TK + /-) forward mutation test, or mouse micronucleus test. However, it was genotoxic in the in vitro Chinese hamster lung cell (CH V79/HGPRT) forward mutation test.

4-aminobenzoyl-(beta)-alanine, a metabolite of balsalazide disodium, was not genotoxic in the Ames test and the mouse lymphoma cell (L5178Y/TK + /-) forward mutation test but was positive in the human lymphocyte chromosomal aberration test. N-acetyl-4-aminobenzoyl-(beta)-alanine, a conjugated metabolite of balsalazide disodium, was not genotoxic in Ames test, the mouse lymphoma cell (L5178Y/TK + /-) forward mutation test, or the human lymphocyte chromosomal aberration test. Balsalazide disodium at oral doses up to 2 grams/kg/day, 2.4 times the recommended human dose based on body surface area, was found to have no effect on fertility and reproductive performance in rats.

Pregnancy Teratogenic Effects:   Pregnancy Category B. Reproduction studies were performed in rats and rabbits at oral doses up to 2 grams/kg/day, 2.4 and 4.7 times the recommended human dose based on body surface area for the rat and rabbit, respectively, and revealed no evidence of impaired fertility or harm to the fetus due to balsalazide disodium. 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.

Nursing Mothers:   It is not known whether balsalazide disodium is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when COLAZAL is administered to a nursing woman.

Pediatric Use:   Safety and effectiveness of COLAZAL ™ in pediatric patients have not been established.