As many as 30% of patients in clinical trials are reported to have discontinued sulfasalazine (SSZ) due to adverse events.1–4 In clinical practice SSZ is generally well-tolerated with the most common side effects being gastrointestinal distress, headache, dizziness, and rash.5 Package inserts for SSZ report the most common side effects, occurring in one-third of people taking sulfasalazine, are anorexia, headache, nausea, vomiting, gastric distress, and low sperm count in men, which is reversible after discontinuation.6 The frequency of these side effects depends on the dosage, the delivery system (enteric coated versus uncoated), and the disease being treated. The medication may be given with meals to minimize the gastrointestinal side effects and because many side effects are dose-related, medication doses can be gradually increased.7 Patients with inflammatory bowel disease generally have higher rates of side effects than patients with rheumatoid arthritis.8 The efficacy and safety profiles of sulfasalazine make it a useful medication for many individuals with inflammatory diseases.
More serious side effects can occur, but uncommonly. Hepatotoxicity was reported to occur at an estimated rate of 0.4% in one case series that identified 10 cases by active surveillance of a large hospital system in the United Kingdom over seven years.9 Abnormal liver function tests occur more frequently (4%).8 Leukopenia was reported to occur in 3.7% of people taking SSZ in one prospective study (n=300),10 but was mild and transient, and neutropenia (2%), thrombocytopenia (1%), hypogammaglobulinemia (1%), and serious agranulocytosis (<1%) have also been reported.4,10
Hypersensitivity reactions have also been reported but are rare.6,8
References
- Scott DL, Dacre JE. Adverse reactions to sulfasalazine: the British experience. J Rheumatol Suppl 1988; 16 : 17-21.
- Erhardt DP, Cannon GW, Teng C-C, Mikuls TR, Curtis JR, Sauer BC. Low Persistence Rates in Rheumatoid Arthritis Patients Treated with Triple Therapy are Attributed to Adverse Drug Events Associated with Sulfasalazine. Arthritis Care Res (Hoboken) September 2018.
- Chen J, Lin S, Liu C. Sulfasalazine for ankylosing spondylitis. Cochrane database Syst Rev 2014;(11): CD004800.
- Amos ARS, Pullar T, Bax DE, Situnayake D, Capell HA, Mcconkey B. Sulphasalazine for rheumatoid arthritis : toxicity in 774 patients monitored for one to 11 years. Br Med J 1986; 293 (6544): 420-423.
- Plosker GL, Croom KF. Sulfasalazine: a review of its use in the management of rheumatoid arthritis. Drugs 2005; 65 (13): 1825-1849.
- Sulfasalazine [package insert]. New York, NY: Pfizer Pharmaceuticals; 2019.
- MacNaughton WK, Sharkey KA. Pharmacotherapy of Inflammatory Bowel Disease. In: Brunton LL, Hilal-Dandan R, Knollmann BC, eds. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics, 13e. New York, NY: McGraw-Hill Education; 2017.
- Sulfasalazine: Adverse effects. Micromedex® (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Updated April 14, 2019. Accessed June 15, 2019.
- Jobanputra P, Amarasena R, Maggs F, et al. Hepatotoxicity associated with sulfasalazine in inflammatory arthritis: A case series from a local surveillance of serious adverse events. BMC Musculoskelet Disord 2008; 9 : 48.
- Farr M, Tunn EJ, Symmons DP, Scott DG, Bacon PA. Sulphasalazine in rheumatoid arthritis: haematological problems and changes in haematological indices associated with therapy. Br J Rheumatol 1989; 28 (2): 134-138.
