Likelihood and Mechanisms of Cross-Allergenicity Between Sulfonamide Antibiotics and Other Drugs Containing a Sulfonamide Functional Group

Authors

  • Dr. Carolyn C. Brackett Pharm.D., BCPS,

    Corresponding author
    1. Division of Pharmacy Practice and Administration, College of Pharmacy, The Ohio State University
      Division of Pharmacy Practice and Administration, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210.
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  • Dr. Harleen Singh Pharm.D.,

    1. Oregon State University College of Pharmacy, Oregon Health and Science University, Portland, Oregon
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  • Dr. John H. Block Ph.D.

    1. Department of Pharmaceutical Sciences, Oregon State University College of Pharmacy, Corvalis, Oregon.
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Division of Pharmacy Practice and Administration, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210.

Abstract

Concerns about cross-allergenicity between sulfonamide antibiotics and nonantibiotic, sulfonamide-containing drugs persist and can complicate patients' drug therapy unnecessarily. No interaction between the human immune system and the sulfonamide functional group has been demonstrated. The immunologic determinant of type I, immediate hypersensitivity responses to sulfonamide antibiotics is the N1 heterocyclic ring. Nonantibiotic sulfonamides do not contain this structural feature. Non-type I hypersensitivity responses to sulfonamide antibiotics are largely attributable to reactive metabolites that may cause either direct cytotoxicity or immunologic response. Formation of these metabolites is a stereospecific process that occurs at the N4 amino nitrogen of the sulfonamide antibiotics, a structure also not found on any nonantibiotic sulfonamide drugs. The stereospecificity of these reactions implies that cross-reactivity with nonantibiotic sulfonamide-containing drugs is highly unlikely; this assertion is supported by recent literature. However, T-cell recognition of unmetabolized, nonhaptenated parent sulfonamide antibiotic appears to occur in a small subset of hypersensitive patients. Several of the severe cutaneous reactions associated with sulfonamide antibiotics are mediated by T cells. It is not known whether T-cell recognition of antibiotic is related to the sulfonamide functional group. Until the mechanism of this recognition is elucidated, cross-reactivity with nonantibiotic sulfonamides appears to remain at least theoretically possible.

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