Last updated: October 22, 2014
Trade Names: Azulfidine, Azulfidine EN-tabs
Synonyms: Salazopyrin; 5-aminosalicylic acid plus sulfapyridine
Drug Class: Sulfonamide/salicylate congener, DMARD
Tablet: 500 mg
Tablet, enteric coated: 500 mg
Dose: In rheumatic diseases, 2–3 g/day in two or three divided doses. Initial dose of 500 mg daily is increased by 500-mg increments weekly as tolerated. Usual maintenance dose is 2–3 g/day. Higher doses may be associated with greater GI toxicity.
Mechanism of Action: Unknown; the sulfonamide component is thought to be more active in the treatment of rheumatic diseases than the 5-aminosalicylic component.
Contraindications: Hypersensitivity to sulfonamides or salicylates, porphyria, GI/genitourinary obstruction
Precautions: Use caution in impaired renal function; it may cause hemolysis in G6PD deficiency.
Monitoring: Hematologic adverse effects are most likely in the first 6 months. CBC every 2–3 weeks for first 3 months, then gradually decrease frequency to every 3 months. Periodic LFTs (3- to 6-month intervals).
Pregnancy Risk: B (D at term)
Common: GI side effects (nausea, vomiting, diarrhea, cramps), rash, itch, dizziness, headache
Less common: Reversible oligospermia, neutropenia, aplastic anemia, agranulocytosis, hemolysis, Stevens-Johnson syndrome and other hypersensitivity reactions, photosensitivity, SLE-like syndrome, nephrotic syndrome, orange-yellow discoloration of urine, hepatitis
Warfarin: Resistance to warfarin described, monitor international normalized ratio for change
Patient Instructions: May cause orange-yellow discoloration of skin, urine, and contact lenses. Beware of photosensitive reactions to prolonged sunlight exposure.
Comments: GI intolerance is often prominent when starting treatment. Thus, start with a low dose and work up. Some evidence indicates that the enteric coated tablets are better tolerated. Efficacy in RA appears similar to that of methotrexate (MTX), but there may be more minor side effects. Widely used in combination with MTX and hydroxychloroquine (triple therapy) in patients with RA not responding to MTX alone. Efficacy in ankylosing spondylitis, reactive arthritis, and psoriatic arthritis is variable, probably greatest in those with peripheral arthropathy (rather than axial disease alone), and less than that of anti-TNFs. It may cause folate deficiency (consider supplementation with folate, 1 mg/day).
Clinical Pharmacology: The azo bond joining 5-aminosalicylic and sulfapyridine is broken by bacteria in the colon. Approximately 15%–30% is absorbed; hepatic metabolism; renal excretion. Half-life is 6–10 hours. Slow acetylators have higher sulfapyridine blood levels and perhaps more minor side effects, but acetylator status need not be routinely determined.
Cost: Generic, $$; enteric coated, $$$
O'Dell JR, Mikuls TR, Taylor TH, et al. Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med 2013;369:307-18. PMID: 23755969.