Cutaneous Adverse Events Caused by Sulfonamide-Containing Drugs: Reality or Perception?

The term "sulfa allergy", originally coined for the sulfonamide antibiotics, has become associated with any drugs that contain a sulfonamide moiety. This raises a question: should medicinal chemists avoid making sulfonamide-containing compounds in drug discovery programs? The negative perception of sulfonamides is not supported by any systematic study or data analysis. To address this gap, an analysis of postmarketing 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. These results strongly suggest that sulfonamide-containing compounds are not at a higher risk of presenting with a cutaneous adverse drug reaction compared with non-sulfonamides and that medicinal chemists should not avoid use of the sulfonamide group.