THE TOXICITY PROFILE OF TRIMETHOPRIM/SULPHAMETHOXAZOLE AFTER FOUR YEARS OF WIDESPREAD USE

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Abstract
The pattern of adverse reactions associated with the administration of sulphonamides is already well known, although it required 30 years for its definition. The combination of trimethoprim with sulphamethoxazole has been available for medical use since October, 1968, since when approximately 25,000,000 standard treatment courses have been given. As the real pattern of adverse reactions to a new drug can only be assessed after a drug has become generally available, the Wellcome Foundation has kept close surveillance of the situation. Within 18 months, all types of adverse reactions associated with sulphonamides were recorded, and the nature and incidence of these correspond with that expected from a sulphonamide of relatively low toxicity. Sensitivity reactions and gastrointestinal symptoms comprised nearly three‐quarters of the adverse reactions reported. Isolated cases of severe skin and systemic sensitivity reactions have occurred. Hæmatological changes reported have been rare, but these have included thrombocytopenia, leucopenia and agranulocytosis. Changes resulting from the trimethoprim component are more likely to be apparent as a result of long‐term use of the combination. Data presented elsewhere are reassuring, and do not suggest that serious adverse effects are to be predicted. Possible immunosuppressive effects have been reported, and are being further investigated. Possible adverse effects on renal function have been reported in one study, but other workers have not observed similar changes. Pregnant patients have been treated with TMP/SMX without teratogenic result. Nevertheless, the combination cannot yet be recommended for use in pregnancy.