Hospitalized patients were monitored during 2,118 courses of therapy with sulfisoxazole, sulfamethoxazole, or nitrofurantoin. Overall frequency of adverse reactions severe enough to require discontinuation of the responsible drug was 3.1% for sulfisoxazole, 3.3% for sulfamethoxazole, and 9.2% for nitrofurantoin. Reaction rates were highly dependent on the duration of therapy. Toxic reactions were far more common to nitrofurantoin (5.1%) than to the sulfonamides (0.3%). They consisted mainly of gastrointestinal disturbances, were more common in women, and their frequency increased sharply with daily dose per patient weight. Sulfisoxazole was associated with allergic reactions in 2.8% of patients, sulfamethoxazole in 3.0%, and nitrofurantoin in 4.1%. Skin rashes, eosinophilia, and drug fever were the common manifestations. Serious reactions to all three drugs were rare (0.14%) and renal toxicity or immediate-type hypersensitivity reactions were not observed.
Koch-Weser J, Sidel VW, Dexter M, Parish C, Finer DC, Kanarek P. Adverse Reactions to Sulfisoxazole, Sulfamethoxazole, and NitrofurantoinManifestations and Specific Reaction Rates During 2,118 Courses of Therapy. Arch Intern Med. 1971;128(3):399-404. doi:10.1001/archinte.1971.00310210075006