Inability to interpret toxic salicylate levels in patients taking aspirin and diflunisal

Diflunisal, a nonsteroidal antiinflammatory drug, is not metabolized to the free salicylate moiety, but yields serum salicylate levels. We describe 2 patients who unexpectedly had toxic range serum salicylate levels while taking diflunisal and aspirin for rheumatoid arthritis. Diflunisal is measured by standard salicylate assays, a fact not widely appreciated. Serum salicylate levels by these assays cannot be used to determine salicylate toxicity when a patient is taking both aspirin and diflunisal. High pressure liquid chromatography can be used to distinguish true salicylate toxicity from interference with diflunisal.