Sulfonamide cross-reactivity: is there evidence to support broad cross-allergenicity?

Am J Health Syst Pharm. 2013 Sep 1;70(17):1483-94. doi: 10.2146/ajhp120291.


Purpose: Published and manufacturer-provided data regarding potential cross-reactivity between antibacterial and nonantibacterial sulfonamide agents are reviewed.

Summary: An estimated 3-6% of the general population is allergic to sulfonamides and thus at risk for type I and other hypersensitivity reactions to sulfamethoxazole and other sulfonamide antibacterial agents. Concerns have been raised that a history of sulfa allergy may be associated with an increased risk of adverse reactions to a wide range of nonantibacterial sulfonamides, including certain antivirals, carbonic anhydrase inhibitors, cyclooxygenase-2- selective nonsteroidal antiinflammatory drugs, loop and thiazide diuretics, and sulfonylureas; concerns have also been raised that patients who have experienced an allergic reaction to one nonantibacterial sulfonamide may be at risk for an adverse reaction to others. Structurally, none of the nonantibiotic sulfonamides exhibit both of the features shown to be responsible for sulfonamide reactions (i.e., an N-containing ring attached to the N1 nitrogen of the sulfonamide group and an arylamine group at the N4 position), and only two agents (amprenavir and fosamprenavir) have the latter characteristic. A comprehensive literature search (1966-December 2011) identified nine case reports indicating possible cross-reactivity to sulfonamide medications; however, in most cases, adequate patient testing was not conducted to firmly establish either sulfa allergy or sulfonamide cross-sensitivity. The weight of evidence suggests that withholding nonantibacterial sulfonamides from patients with prior reactions to antibacterial sulfonamides or other nonantibacterial sulfonamides is not clinically justified.

Conclusion: A review of the professional literature and manufacturer-provided data did not find convincing evidence of broad cross-reactivity between antibacterial and nonantibacterial sulfonamide agents.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / chemistry
  • Cross Reactions
  • Drug Hypersensitivity / diagnosis*
  • Drug Hypersensitivity / epidemiology*
  • Humans
  • Sulfonamides / adverse effects*
  • Sulfonamides / chemistry


  • Anti-Bacterial Agents
  • Sulfonamides