Drug-associated road traffic accidents: insights from an analysis of the FDA adverse event reporting system (FAERS) database

Objective Drug-related road traffic accidents (RTAs) represent a significant public health concern, yet large-scale real-world evidence on high-risk medications remains limited. This study aimed to characterize the landscape and quantify signals of drug-associated RTAs using the U.S. FDA Adverse Event Reporting System (FAERS).Methods A retrospective study was conducted on FAERS reports (Q1 2004–Q2 2025). Dispro­portionality analyses were performed using the Reporting Odds Ratio (ROR) and the Bayesian Confidence Propagation Neural Network (BCPNN) for the top 50 most frequently reported drugs. Gender differences and time-to-onset profiles were also analyzed.Results Among 22,775,812 total adverse event reports, we identified 38,760 RTA cases. The three most reported drugs were adalimumab (n = 2,278), oxycodone (n = 1,898), and etanercept (n = 1,087). Disproportionality analysis showed that 41 of the top 50 drugs (82.0%) generated positive safety signals for RTAs. Nervous system agents (36.6%) and antineoplastic/immunomodulating agents (34.1%) comprised the majority of signal-positive drugs. Zolpidem demonstrated the strongest signal (IC025 = 4.42), followed by alendronic acid (IC025 = 2.77) and buprenorphine/naloxone (IC025 = 2.64). Gender-stratified analysis of these 41 signal-positive drugs found that males had a significantly higher reporting risk for 26 drugs, whereas females had a higher risk for 6 drugs.Conclusion This analysis identifies drugs most frequently associated with RTAs using real-world data, providing evidence for risk assessment and patient guidance. However, the FAERS database has inherent limitations, such as unadjusted confounders, missing data on alcohol or substance use, and incomplete accident outcomes. Thus, further clinical validation is warranted to confirm these associations.