Sulfasalazine

Sulfasalazine

Sulfasalazine (Azulfidine) is approved for the treatment of rheumatoid arthritis and ulcerative colitis. It is also used to treat ankylosing spondylitis and Crohn’s disease. Comparisons of sulfasalazine with other DMARDs sug-gest that it is more effective than hydroxychloroquine, azathioprine, and oral gold compounds. It is at least as effective as intramuscular gold and penicillamine. It has a greater degree of toxicity than hydroxychloroquine but less than gold compounds and penicillamine. After 5 years, approximately 75% of patients have discontinued sulfasalazine therapy, primarily because of a lack of effi-cacy as opposed to intolerable side effects.

Basic Pharmacology

Sulfasalazine is a prodrug of which 70% is converted by colon bacteria to two active metabolites, sulfapyri-dine and 5-aminosalicylic acid (mesalamine). Sulfa-pyridine has antibacterial activities, and 5-aminosali- cylic acid is antiinflammatory; however, these effects do not account for the ability of this drug to slow the processes of rheumatoid arthritis. Recent research sug-gests additional activities of sulfasalazine that may be relevant to these effects: its ability to increase adeno-sine levels, its inhibitory effects on IL-1 and TNF-αrelease, and its inhibition of NF- B. The pharmacoki-netic data for this and other DMARDs are provided in Table 36.4.

Adverse Effects

Mild to moderate side effects, including nausea, vomit-ing, abdominal pain, diarrhea, anorexia, and headache, occur in up to 33% of patients taking this drug. Skin rash and discoloration, fever, reversible male infertility, and liver enzyme elevation occur less frequently. Rare hematological abnormalities, such as agranulocytosis, aplastic anemia, hemolytic anemia, neutropenia, or other blood dyscrasias, can be fatal. Hypersensitivity re-actions occur rarely.

Contraindications and Drug Interactions

Sulfasalazine is contraindicated in individuals with hy-persensitivity to salicylates, sulfonamides, sulfony-lureas, and certain diuretics (furosemide, thiazides, and carbonic anhydrase inhibitors). Because it can cause kernicterus, sulfasalazine is contraindicated in infants and children under 2 years of age. Sulfasalazine passes into breast milk and is therefore contraindicated for nursing mothers. Similarly, pregnant women near term should not use this drug, although it appears to be the safest of the DMARDs during early pregnancy.

Sulfasalazine can precipitate attacks of porphyria and should not be used by individuals with bowel or urinary obstruction.

Sulfasalazine can inhibit the absorption of cardiac glycosides and folic acid. It may displace certain drugs, including warfarin, phenytoin, methotrexate, tolbu-tamide, chlorpropamide, and oral sulfonylureas, from their protein binding sites. Sulfasalazine can diminish the effectiveness of penicillins and estrogen-containing oral contraceptives.