s The Metabolic Rationale for a Lack of Cross-reactivity Between Sulfonamide Antimicrobials and Other Sulfonamide-containing Drugs

Sulfonamide antimicrobials (sulfamethoxazole) contain an arylamine group, oxidized by CYP2C9 to the hydroxylamine with subsequent auto-oxidation to a highly reactive [-nitroso-] intermediate is a necessary (if not sufficient) cause of drug hypersensitivity. Accordingly, xenobiotics that do not contain an arylamine cannot generate this reactive intermediate and do not cross react with sulfonamide antimicrobials. Despite this well-attested observation, product labeling and direct-to-consumer advertising for non-arylamine therapeutic classes of drugs containing the sulfonamido- functional group persist with a warning of the potential for cross-reactivity. It is hoped that by offering an explicit rationale for the lack of cross-reactivity will provide medical practitioners with a level comfort to proceed with prescribing medications such as thiazide diuretics and celecoxib for patients with a history of hypersensitivity to sulfonamide antimicrobials.