Sulfonamide cross-reactivity: fact or fiction?

Ann Pharmacother. 2005 Feb;39(2):290-301. doi: 10.1345/aph.1E350. Epub 2005 Jan 11.


Objective: To provide a critical and comprehensive review of the literature, specifically case reports and observational studies used to support the concept of cross-reactivity between sulfonylarylamines and non-sulfonylarylamines.

Data sources: A list of medications was formulated from several different review articles. A MEDLINE/PubMed search was conducted (1966-March 2004) using the individual medications and the MeSH terms of drug hypersensitivity/etiology, sulfonamides/adverse effects, and/or cross-reaction.

Study selection and data extraction: A critical review of the methodology and conclusions for each article found in the search was conducted. The manufacturer's package insert (MPI) for each drug was examined for a statement concerning possible cross-reactivity in patients with a sulfonamide allergy. If indicated, the manufacturers were contacted to obtain any clinical data supporting the statement.

Data synthesis: A total of 33 medications were identified. Seventeen (51.5%) of the MPIs contained statements of varying degrees concerning use in patients with a "sulfonamide" allergy; 21 case series, case reports, and other articles were found.

Conclusions: After a thorough critique of the literature, it appears that the dogma of sulfonylarylamine cross-reactivity with non-sulfonylarylamines is not supported by the data. While many of the case reports on the surface support the concept of cross-reactivity, on closer examination the level of evidence in many of the cases does not conclusively support either a connection or an association between the observed cause and effect.

Publication types

  • Review

MeSH terms

  • Cyclooxygenase Inhibitors / adverse effects
  • Cyclooxygenase Inhibitors / chemistry
  • Diuretics / adverse effects
  • Diuretics / chemistry
  • Drug Hypersensitivity / etiology
  • Drug Interactions
  • Drug Labeling
  • Humans
  • Sulfonamides / adverse effects
  • Sulfonamides / chemistry*


  • Cyclooxygenase Inhibitors
  • Diuretics
  • Sulfonamides