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Cohort studyClinical drug investigation · 2026

Signals of Venous Thromboembolism Risk from Drug-Drug Interactions Involving Benzodiazepines and Other Sedative Hypnotics: Self-Controlled Case Series Analyses.

Fengge Wang, Lin-Chieh Meng, Kacie Bogar … Charles E Leonard

Internal MedicineCohort study

Gabapentin combined with a benzodiazepine or z-drug may raise venous thromboembolism risk 3.5-fold

Signals of Venous Thromboembolism Risk from Drug-Drug Interactions Involving Benzodiazepines and Other Sedative Hypnotics: Self-Controlled Case Series Analyses.

Fengge Wang … Charles E Leonard

Clinical drug investigation · 2026

Background

Benzodiazepines and sedative hypnotics such as zolpidem ("z-drugs") are commonly prescribed for anxiety and sleep disorders.

Purpose

We investigated venous thromboembolism risk among concomitant users of individual benzodiazepines/z-drugs (examined separately) with other prescription medications to generate data-driven hypotheses about drug interactions resulting in clinically meaningful harm to inform future etiologic studies of specific drug combinations.

Methods

We conducted a series of self-controlled case series studies within a 50% random sample of US Medicaid and Medicare data.

n = 8853 individuals

Results

3.5-fold

combining them may raise clot risk, not just gabapentin alone

n = 8853 individuals

More results

Among 1590 self-controlled case series studies involving 8853 individuals with venous thromboembolism, 38 (2.4%) potential drug interaction signals were identified before calibration.

More results

After adjustment for multiple testing and negative control findings, five (0.3%) signals remained, involving gabapentin combined with eszopiclone, lorazepam, clonazepam, or alprazolam, and apixaban combined with diazepam (ratio of incidence rate ratio range: 1.92-3.57).

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Conclusion · 1 of 2

Most benzodiazepine/z-drug combinations conferred no increased venous thromboembolism risk. However, concurrent use of a benzodiazepine/z-drug with gabapentin may increase the relative rate of venous thromboembolism up to 3.5-fold.

Conclusion · 2 of 2

As this work was hypothesis generating, a future etiologic study should confirm this potential drug interaction.

Post

Signals of Venous Thromboembolism Risk from Drug-Drug Interactions Involving Benzodiazepines and Other Sedative Hypnotics: Self-Controlled Case Series Analyses.

Gabapentin combined with a benzodiazepine or z-drug may raise venous thromboembolism risk 3.5-fold

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