Work

Comparative risk of injury among users of benzodiazepines and related drugs concomitantly with clarithromycin versus azithromycin: a retrospective cohort study of US Medicaid enrollees

Year: 2026

Type: article

Abstract: Background/Objectives Drug interactions with benzodiazepines and related drugs (collectively referred to within as BZDs) are a significant public health concern. Several commonly co-prescribed drugs may exacerbate BZDs’ central nervous system depressant effects by inhibiting BZDs’ metabolic degradation in the liver. In a previous pharmacoepidemiologic screening study of potential drug–drug interactions involving BZDs, concomitant use of clarithromycin with either alprazolam or zolpidem was associated with a higher risk of unintentional injury. Methods To validate these findings, we used 1999–2012 US Medicaid claims data to conduct six cohort studies of adult users of six common BZDs: alprazolam, clonazepam, diazepam, lorazepam, temazepam and zolpidem. Each cohort consisted exclusively of person-time concomitantly exposed to each BZD plus either clarithromycin (the precipitant of interest) or azithromycin (the prespecified active comparator). Propensity scores, calculated from baseline covariates, were used to estimate overlap weights. Weighted Cox proportional hazard models were used to estimate adjusted hazard ratios and 95% CIs for the risk of unintentional injury in each BZD cohort comparing concurrent users of clarithromycin versus azithromycin. Results We found that concomitant use of zolpidem+clarithromycin (HR=1.24, 95% CI 1.00 to 1.55, p=0.05) and temazepam+clarithromycin (HR=1.38, 95% CI 1.00 to 1.92, p=0.05) may be associated with an increased risk of hospital presentation for unintentional injury. Conclusions These findings suggest that certain BZD-macrolide combinations may increase the risk of unintentional traumatic injury.

Source: BMJ Open

DOI: 10.1136/bmjopen-2025-109127