Should celecoxib be contraindicated in patients who are allergic to sulfonamides? Revisiting the meaning of 'sulfa' allergy

Celecoxib, a selective cyclo-oxygenase-2 inhibitor, is a diaryl-substituted pyr azole derivative containing a sulfonamide substituent. Because of this structural component, celecoxib is contraindicated for use in patients who have demonstrated allergic reactions to sulfonamides. However, there is a lack of data demonstrating cross-reactivity among sulfonamide medications. A sulfonamide is any compound with an SO2NH2 moiety. The major difference b etween sulfonamide antimicrobials and other sulfonamide-containing medicati ons such as furosemide, thiazide diuretics and celecoxib, is that sulfonami de antimicrobials contain an aromatic amine group at the N4 position. This allows for division of the sulfonamides into 2 groups: aromatic amines (i.e ., sulfonamide antimicrobials) and nonaromatic amines. In addition, sulfona mide antimicrobials contain a substituted ring at the N1-position; this gro up is not found with nonaromatic amine-containing sulfonamides. Adverse reactions to sulfonamide antimicrobials include type II or immunogl obulin (Ig) E-mediated reactions, hypersensitivity syndrome reactions, and severe skin reactions such as toxic epidermal necrolysis. The aromatic amin e portion of the sulfonamide antimicrobial is considered to be critical in the development of latter 2 reactions. In susceptible individuals, the hydr oxylamine metabolite is unable to be detoxified leading to a cascade of cyt otoxic and immunological events that eventually results in the adverse reac tion. Since celecoxib does not contain the aromatic amine, adverse reaction s such as hypersensitivity syndrome reactions and toxic epidermal necrolysi s would not be expected to occur at the same frequency as they do with sulf onamide antimicrobials. Similarly, for IgE-mediated reactions, the N1-subst ituent and not the sulphonamide moiety is important in determining specific ity to antibodies. Celecoxib and other nonaromatic amine-containing sulfona mide medications do not contain the N1-substituent. Cross-reactivity among the various sulfonamide-containing medications hasal so not been substantiated by published case reports. In fact, conflicting i nformation exists in the literature. Reports showing lack of crass-reactivi ty balance the few case reports suggesting cross-reactivity. Cross-reactivity between sulfonamide medications should be based on scienti fic data, including chemistry, metabolism, immune responses and clinical da ta. Based on the current information, there is no documentation for cross-r eactivity between sulfonamide antimicrobials and other sulfonamide medicati ons, such as celecoxib.