Drug/Laboratory Test Interactions
The presence of sulfasalazine or its metabolites in body fluids has not been reported to interfere with laboratory test procedures.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Two-year oral carcinogenicity studies were conducted in male and female F344/N rats and B6C3F1 mice. Sulfasalazine was tested at 84 (496 mg/m2), 168 (991 mg/m2), and 337.5 (1991 mg/m2) mg/kg/day doses in rats. A statistically significant increase in the incidence of urinary bladder transitional cell papillomas was observed in male rats. In female rats, two (4%) of the 337.5 mg/kg rats had transitional cell papilloma of the kidney. The increased incidence of neoplasms in the urinary bladder and kidney of rats was also associated with an increase in the renal calculi formation and hyperplasia of transitional cell epithelium. For the mouse study, sulfasalazine was tested at 675 (2025 mg/m2), 1350 (4050 mg/m2), and 2700 (8100 mg/m2) mg/kg/day. The incidence of hepatocellular adenoma or carcinoma in male and female mice was significantly greater than the control at all doses tested.
Sulfasalazine did not show mutagenicity in the bacterial reverse mutation assay (Ames test) and in L51784 mouse lymphoma cell assay at the HGPRT gene. However, sulfasalazine showed equivocal mutagenic response in the micronucleus assay of mouse and rat bone marrow and mouse peripheral RBC and in the sister chromatid exchange, chromosomal aberration, and micronucleus assays in lymphocytes obtained from humans.
Impairment of male fertility was observed in reproductive studies performed in rats at a dose of 800 mg/kg/day (4800 mg/m2). Oligospermia and infertility have been described in men treated with sulfasalazine. Withdrawal of the drug appears to reverse these effects.
Pregnancy Category B
Reproduction studies have been performed in rats and rabbits at doses up to 6 times the human dose and have revealed no evidence of impaired female fertility or harm to the fetus due to sulfasalazine. 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.
A national survey evaluated the outcome of pregnancies associated with inflammatory bowel disease (IBD). In a group of 186 women treated with sulfasalazine alone or sulfasalazine and concomitant steroid therapy, the incidence of fetal morbidity and mortality was comparable to that for 245 untreated IBD pregnancies as well as to pregnancies in the general population.1 A study of 1,455 pregnancies associated with exposure to sulfonamides indicated that this group of drugs, including sulfasalazine, did not appear to be associated with fetal malformation.2 A review of the medical literature covering 1,155 pregnancies in women with ulcerative colitis suggested that the outcome was similar to that expected in the general population.3
No clinical studies have been performed to evaluate the effect of sulfasalazine on the growth development and functional maturation of children whose mothers received the drug during pregnancy.