Diaminopyrimidines and Severe Cutaneous Adverse Reactions

Abstract

The occurrence of cutaneous adverse reactions with the use of lamotrigine (Lamictal, Glaxo-Wellcome Inc, Research Triangle Park, NC) should prompt a reevaluation of rashes seen with the use of drugs of similar structure, specifically diaminopyrimidines. Trimethoprim and pyrimethamine both contain diaminopyrimidine ring structures. Lamotrigine has a triazine ring structure but is strikingly similar in other respects (Figure). Lamotrigine is currently marketed as an anticonvulsant in the United States and in more than 67 countries worldwide. During premarketing clinical trials of lamotrigine in 3400 subjects, one case of Stevens-Johnson syndrome and one case of toxic epidermal necrolysis were reported.¹ This incidence rate of 2 per 3400 individuals exposed is comparable to (if not greater than) the risks of severe cutaneous adverse reactions reported for the combination products trimethoprim-sulfamethoxazole (1-3 per 100 000 exposed) and pyrimethamine-sulfadoxine (10-20 per 100 000 exposed).^2,3 Pyrimethamine-sulfadoxine is marketed in the United States (Fansidar, Roche