Difference in Risks of Allergic Reaction to Sulfonamide Drugs Based on Chemical Structure

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Abstract
Background: The chemical structure of sulfonamide antibiotics and sulfonamide nonantibiotics can affect the potential for adverse reactions. Objective: To assess whether differences in chemical structure of the various sulfonamide drugs influence the risk of allergic events. Methods: A case–control study was conducted among patients with diabetes mellitus (DM) using data from the General Practice Research Database. Cases were defined as patients with a diagnosis of hypersensitivity or allergic reaction. The date of the last event was the index date. Controls were matched on practice, type of DM, and index date. Current use of sulfonamides was defined as use in a 14 day time window before the index date. Sulfonamides were classified according to the presence/absence of an N1 substituent (N1+/-) and/or an arylamine (N4+/-). Conditional logistic regression was used to estimate strength of association and expressed as odds ratios and 95% confidence intervals. Results: Overall, current use of N1+ N4+ sulfonamide drugs was associated with the outcome (adjusted OR 3.71; 95% Cl 1.40 to 9.81). Current use of N1+ N4- and N1- N4- sulfonamide drugs was also associated with the occurrence of allergic reactions, although not as strongly: adjusted OR 2.48 (95% Cl 2.12 to 2.89) and 2.07 (95% Cl 1.74 to 2.46), respectively. Sex and age seemed to be effect modifiers. There was no clear evidence for effect modification by immune disease state. Conclusions: Although we did not identify major differences between the groups, we believe that this approach is an innovative manner to examine adverse drug reactions by using chemical structure instead of therapeutic drug classes to classify exposure.