The sulfonamide antibiotics, which are based upon a 4-aminobenzene sulfonamide core structure, have helped to revolutionize the treatment of bacterial infections in the 20th century. However, despite being effective antibacterial agents, these drugs are often associated with cutaneous adverse events (AEs), including rare but serious reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). It is estimated that 3-6% of the general population exhibit an “allergy to sulfonamides”, also known as “sulfa allergy”, with the frequency of serious adverse drug reactions (ADRs) being much lower. Over time the legitimate concerns about these cutaneous ADRs with sulfonamide antibiotics became associated with any compounds that contain the sulfonamide group and often these non-antibiotic sulfonamide drugs are often contraindicated in patients with a history of “sulfa allergies”. The perceived risk of cutaneous AEs associated with sulfonamides raises a question: should chemists avoid making sulfonamide-containing compounds in discovery programs? Surprisingly, there are no systematic study or data analysis to support this negative perception of sulfonamides containing drugs. To address this gap, an analysis of post-marketing reports of cutaneous AEs for drugs with and without a sulfonamide group was conducted. The analysis revealed no evidence of association between the presence of a sulfonamide moiety and a high reporting rate of cutaneous AEs and indicated that the risk of such AEs was associated with the presence of certain structural alerts and higher daily doses. The presentation will describe the results of this analysis and the extension of the methodology to evaluate the relationships between chemical structure and other ADRs.

Cutaneous adverse events caused by sulfonamide-containing drugs: Reality or Perception

ACS Fall 2020 Virtual Meeting

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