Clinically, a controversial issue in the administration of furosemide is the incidence of cross-reactivity with sulfonamide-containing antibiotics because of the sulfonamide moiety that furosemide contains (Fig. 16.1). The clinical issue centers on the administration of furosemide to a patient with documented sulfa allergy. Opinions differ on the believed hypersensitivity cross-reaction that may manifest itself as anaphylaxis, dermatitis, urticaria, eczema, Stevens-Johnson syndrome, rash, or fever within 30 days, but current literature states that the lack of published clinical evidence for the allergic reactions is noteworthy. The authors of a recently published review of the literature on this topic state that much of the evidence used to provide support for the theory is in fact not conclusive and does not implicate appropriate causation. Detractors of the belief of a legitimate cross-reactivity also cite that sulfonamide nonantibiotics lack the aromatic amine group at the N4 position of sulfonamide-containing antibiotics, believed to be the cause of sulfonamide antibiotic hypersensitivity.