UMEM Educational Pearls

Category: Toxicology

Title: Mythbuster: No Cross-Reactivity Between Sulfonamide Antibiotics and Non-Antibiotics

Keywords: sulfonamide, antibiotic, cross-reactivity (PubMed Search)

Posted: 8/15/2013 by Bryan Hayes, PharmD (Updated: 1/29/2014)
Click here to contact Bryan Hayes, PharmD

There is minimal evidence of cross-reactivity between sulfonamide antibiotics and non-antibiotics [1-4]. Despite this, the U.S. FDA-approved product information for many non-antibiotic sulfonamide drugs contains warnings concerning possible cross-reactions.

Key Findings from a New Review Article [5]:

  • An estimated 3-6% of the general population is allergic to sulfonamides.
  • Structurally, none of the non-antibiotic 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).
  • A comprehensive literature search (1966-December 2011) identified only 9 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.

Bottom line: You can feel safe prescribing furosemide, glyburide, and hydrochlorothiazide to your patient with an allergy to sulfamethoxazole/trimethoprim.

Other blog reference on this topic:


  1. Strom BL, et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med 2003;349(17):1628-35. [PMID 14573734]
  2. Hemstreet BA, et al. Sulfonamide allergies and outcomes related to use of potentially cross-reactive drugs in hospitalized patients. Pharmacotherapy 2006;26(4):551-7. [PMID 16553515]
  3. Lee AG, et al. Presumed "sulfa allergy" in patients with intracranial hypertension treated with acetazolamide or furosemide: cross-reactivity, myth or reality? Am J Ophthalmol 2004;138(1):114-8. [PMID 15234289]
  4. Johnson KK, et al. Sulfonamide cross-reactivity: fact or fiction? Ann Pharmacother 2005;39(2):290-301. [PMID 15644481]
  5. Wulf NR, et al. Sulfonamide cross-reactivity: Is there evidence to support broad cross-allergenicity? Am J Health-Syst Pharm 2013;70(17):1483-94. [PMID 23943179]

Follow me on Twitter (@PharmERToxGuy)