Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines

Background: 5-Aminosalicylates are extensively prescribed for the treatment of ulcerative colitis but have a wide range of described adverse effects. Aims: To determine whether serious adverse effect profiles differ for sulphasalazine and mesalazine. Methods: Analysis of suspected serious adverse reactions reported to the Committee on Safety of Medicines of the UK in 1991-1998. Adverse effect profiles were categorised for interstitial nephritis, pancreatitis, serious skin reactions, hepatitis and hepatic failure, and blood dyscrasias. Report rates were calculated using prescribing data from the Department of Health and compared for mesalazine and sulphasalazine. Further analysis was undertaken for sulphasalazine according to disease indication of inflammatory bowel disease or rheumatoid arthritis. Results: A total of 4.7 million prescriptions were dispensed for sulphasalazine compared with 2.8 million for mesolazine. Interstitial nephritis was only described for mesalazine, with 11.1 reports per million prescriptions. Pancreatitis was reported seven times as frequently for mesalazine (7.5 per million prescriptions) compared with sulphasalazine (1.1 per million prescriptions) (odds ratio (OR) 7.0; 95% confidence interval (CI) 2.6-18.6; p<0.001). There were no reports of serious skin disorders in patients prescribed sulphasalazine for inflammatory bowel disease. Blood dyscrasias were reported significantly more often in patients receiving sulphasalazine for rheumatoid arthritis than for inflammatory bowel disease (OR 5.31; 95% CI 2.6-11.0; p<0.001), and there was a similar trend for hepatic disorders. Conclusions: Spontaneous reports suggest that within the five sets of disorders considered, there is no evidence to indicate a safety advantage of mesalazine over sulphasalazine in the treatment of inflammatory bowel disease. Pancreatitis and interstitial nephritis appear significantly more common with mesalazine, and advice on renal monitoring in patients who receive mesalazine may need reinforcing.