June 2003 • Volume 124 • Number 7
Selected summary
James D. Lewis, M.D., MSCE1

Ransford RAJ, Langman MJS (Queen Elizabeth Hospital, Birmingham, UK). Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines. Gut 2002;51:536-539.

Sulfasalazine (sulphasalazine) and mesalamine (mesalazine) each deliver 5-aminosalicylic acid (5-ASA) to the colon. These topical anti-inflammatory compounds have become standard therapy for inflammatory bowel disease, particularly ulcerative colitis. Sulfasalazine has a 5-ASA molecule bound to sulfapyridine. Because sulfapyridine contributes to toxicity in selected patients but does not have activity against colonic inflammation, several new systems were designed to deliver 5-ASA to the bowel without sulfapyridine. Today, these mesalamine compounds are prescribed more commonly than sulfasalazine in many parts of the world (Gut 2002;51:548-549). Their popularity is largely based on perceived better tolerance rather than documented improved efficacy, particularly for ulcerative colitis (BMJ 1989;298:82-86, Ann Intern Med 1993;118:540-549). Recently, concern has been raised about the safety of mesalamine, particularly with regards to renal toxicity and pancreatitis. In contrast, sulfasalazine has been implicated as causing blood dyscrasias. Because of the rarity of these events, proof of the proposed associations has been difficult. To attempt to answer these questions, Ransford and Langman analyzed data from spontaneous reports to the Committee on Safety of Medicines (CSM) in the United Kingdom (Gut 2002;51:536-539).
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In conclusion, Ransford and Langman have used spontaneous reporting data to support an association between mesalamine exposure and pancreatitis and interstitial nephritis. Sulfasalazine seemed to be associated with blood dyscrasias, but this was limited to patients with rheumatoid arthritis. Their work was based on data from spontaneous reports of suspected serious adverse events. Although their data alone are insufficient to make a definitive statement of causality, it provides compelling evidence to support the hypothesis and highlights the need for further observational studies. In addition, it highlights the need for active utilization of existing spontaneous reporting systems around the world. In the United States, suspected adverse events from medications can be reported to the FDA through the MedWatch system at their website www.fda.gov/medwatch or by phone (1-800-FDA-1088) or by fax (1-800-FDA-0178)