Risk of drug eruption associated with the use of tetracyclines, macrolides, and fluoroquinolones: real-world evidence from a pharmacovigilance study utilizing the FDA adverse event reporting system

Recently, concerns regarding the risk of drug eruption associated with the use of tetracyclines were raised by the United States Food and Drug Administration (U.S. FDA). Therefore, it is necessary to reevaluate this risk. This study aimed to quantify the signal of drug eruption associated with the use of tetracyclines. Also, the signal of drug eruption with the use of two other antimicrobial drugs-macrolides and fluoroquinolones-was investigated for comparison. A pharmacovigilance case/noncase study was conducted using the U.S. FDA Adverse Event Reporting System (FAERS). Reports of drug eruptions using the preferred term were retrieved from the database from 2020-2025 quarter 1. The associations between the risk of drug eruption and the three antibiotic classes were quantified using disproportionality analysis utilizing both Bayesian and traditional statistical analyses, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), empirical Bayes geometric mean (EBGM) and information component (IC). All three antibiotic classes were significantly associated with the risk of drug eruption. However, compared with fluoroquinolones and macrolides, tetracyclines were more strongly associated with drug eruption. Disproportionality analysis revealed that the ROR for tetracycline was 6.65 (95% confidence interval (CI), 4.00-11.09) in 2020; in 2024, it was 30.75 (95% CI, 24.46-38.67). For macrolides, the RORs were 2.16 (95% CI, 1.20-3.92) and 10.12 (95% CI, 7.16-14.31) in 2020 and 2024, respectively. The RORs for fluoroquinolones were 4.57 (95% CI, 3.20-6.52) in 2020 and 2.27 (95% CI, 1.31-3.92) in 2024. Males were predominant in the tetracycline group (74%), and females were predominant in the macrolide group (56%). Approximately 41% and 40% of patients in the fluoroquinolone and macrolide classes, respectively, were hospitalized. All three antibiotic classes were associated with the signal of drug eruption. The signal of drug eruption occurred across all age groups with all three antibiotics. Also, the signal has affected both males and females across the years studied. However, there is no specific pattern for the signal.