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ADVERSE DRUG REACTIONS

Sulfonamide Cross-Reactivity: Fact or Fiction?

at time of writing, Adult Internal Medicine Pharmacy Resident, Department of Pharmacy Services, Virginia Commonwealth University Medical Center—Medical College of Virginia (MCV) Campus, Richmond, VA; now, Clinical Pharmacist, Cardiology and Critical Care, Lutheran General Hospital, Park Ridge, IL

David L Green, PharmD

at time of writing, Critical Care Pharmacy Resident, Department of Pharmacy Services, Virginia Commonwealth University Medical Center—MCV Campus; now, Clinical Specialist, Critical Care, Sherman Hospital, Elgin, IL

Jason P Rife, PhD

Assistant Professor, Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond

Lynn Limon, PharmD

Drug Information Specialist, Department of Pharmacy Services, Virginia Commonwealth University Medical Center, Medical College of Virginia (MCV) Campus

Reprints: Dr. Limon, Department of Pharmacy Services, Virginia Commonwealth University Medical Center, 401 N. 12th St., B306, Box 980042, Richmond, VA 23298-0042, fax 804/628-3919, llimon{at}hsc.vcu.edu

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.

Key Words: cross-reaction, hypersensitivity, sulfonamide

Published Online, January 11, 2005. www.theannals.com, DOI 10.1345/aph.1E350

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