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Azulfidine (Sulfasalazine) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drug/Laboratory Test Interactions

Several reports of possible interference with measurements, by liquid chromatography, of urinary normetanephrine causing a false-positive test result have been observed in patients exposed to sulfasalazine or its metabolite, mesalamine/mesalazine.

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

Pregnancy Category B

There are no adequate and well-controlled studies of sulfasalazine in pregnant women. Reproduction studies have been performed in rats and rabbits at doses up to 6 times the human maintenance dose of 2 g/day based on body surface area and have revealed no evidence of impaired female fertility or harm to the fetus due to sulfasalazine. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

There have been case reports of neural tube defects (NTDs) in infants born to mothers who were exposed to sulfasalazine during pregnancy, but the role of sulfasalazine in these defects has not been established. However, oral sulfasalazine inhibits the absorption and metabolism of folic acid which may interfere with folic acid supplementation (see Drug Interactions) and diminish the effect of periconceptional folic acid supplementation that has been shown to decrease the risk of NTDs.

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.

OVERDOSAGE

There is evidence that the incidence and severity of toxicity following overdosage are directly related to the total serum sulfapyridine concentration. Symptoms of overdosage may include nausea, vomiting, gastric distress, and abdominal pains. In more advanced cases, central nervous system symptoms such as drowsiness, convulsions, etc., may be observed. Serum sulfapyridine concentrations may be used to monitor the progress of recovery from overdosage.

There are no documented reports of deaths due to ingestion of large single doses of sulfasalazine.

Doses of Azulfidine tablets of 16 g per day have been given to patients without mortality. A single oral dose of 12 g/kg was not lethal to mice.

Instructions for Overdosage

Gastric lavage or emesis plus catharsis as indicated. Alkalinize urine. If kidney function is normal, force fluids. If anuria is present, restrict fluids and salt, and treat appropriately. Catheterization of the ureters may be indicated for complete renal blockage by crystals. The low molecular weight of sulfasalazine and its metabolites may facilitate their removal by dialysis.

CONTRAINDICATIONS

AZULFIDINE Tablets are contraindicated in:

  •  Patients with intestinal or urinary obstruction,
  •  Patients with porphyria as sulfonamides have been reported to precipitate an acute attack,
  •  Patients hypersensitive to sulfasalazine, its metabolites, sulfonamides, or salicylates.

DRUG ABUSE AND DEPENDENCE

None reported.

REFERENCES

  1. Mogadam M, et al. Pregnancy in inflammatory bowel disease: effect of sulfasalazine and corticosteroids on fetal outcome. Gastroenterology 1981;80:72–6.
  2. Kaufman DW, editor. Birth defects and drugs during pregnancy. Littleton, MA: Publishing Sciences Group, Inc, 1977: 296–313.
  3. Jarnerot G. Fertility, sterility and pregnancy in chronic inflammatory bowel disease. Scand J Gastroenterol 1982;17:1–4.
  4. Korelitz B, et al. Desensitization to sulfasalazine in allergic patients with IBD: an important therapeutic modality. Gastroenterology 1982;82:1104.
  5. Holdworth CG. Sulphasalazine desensitization. Br Med J 1981;282:110.
  6. Taffet SL, Das KM. Desensitization of patients with inflammatory bowel disease to sulfasalazine. Am J Med 1982;73:520–4.

This product's label may have been updated. For current full prescribing information, please visit www.pfizer.com.

LAB-0241-8.0

February 2014

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