ArticleScientific reports2022
Population-based screening to detect benzodiazepine drug-drug-drug interaction signals associated with unintentional traumatic injury.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Signals of Venous Thromboembolism Risk from Drug-Drug Interactions Involving Benzodiazepines and Other Sedative Hypnotics: Self-Controlled Case Series Analyses.Clinical drug investigation · 2026Article
- Exploring Risks of Adverse Drug Events From Single Drug to Three-Drug Combination.Clinical and translational science · 2026Article
- Drug-Drug Interaction Signals for Major Bleeding in Nursing Home Residents: High-Throughput Screening of Clopidogrel and Oral Anticoagulants.Pharmacoepidemiology and drug safety · 2026Article
- Potential Drug Dose-Specific Adverse Three-Drug Combinations: A US Insurance Claims Data-Based Study.Pharmacoepidemiology and drug safety · 2025Article
- Thinking Three-Dimensionally: A Self- and Externally-Controlled Approach to Screening for Drug-Drug-Drug Interactions Among High-Risk Populations.Clinical pharmacology and therapeutics · 2024Article
- Antidepressant drug-drug-drug interactions associated with unintentional traumatic injury: Screening for signals in real-world data.Clinical and translational science · 2023Article
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Authors and funding
11 authors.
Funding
Abstract
Drug interactions involving benzodiazepines and related drugs (BZDs) are increasingly recognized as a contributor to increased risk of unintentional traumatic injury. Yet, it remains unknown to what extent drug interaction triads (3DIs) may amplify BZDs' inherent injury risk. We identified BZD 3DI signals associated with increased injury rates by conducting high-throughput pharmacoepidemiologic screening of 2000-2019 Optum's health insurance data. Using self-controlled case series design, we included patients aged ≥ 16 years with an injury while using a BZD + co-dispensed medication (i.e., base pair). During base pair-exposed observation time, we identified other co-dispensed medications as candidate interacting precipitants. Within each patient, we compared injury rates during time exposed to the drug triad versus to the base pair only using conditional Poisson regression, adjusting for time-varying covariates. We calculated rate ratios (RRs) with 95% confidence intervals (CIs) and accounted for multiple estimation via semi-Bayes shrinkage. Among the 65,123 BZD triads examined, 79 (0.1%) were associated with increased injury rates and considered 3DI signals. Adjusted RRs for signals ranged from 3.01 (95% CI = 1.53-5.94) for clonazepam + atorvastatin with cefuroxime to 1.42 (95% CI = 1.00-2.02, p = 0.049) for alprazolam + hydrocodone with tizanidine. These signals may help researchers prioritize future etiologic studies to investigate higher-order BZD interactions.
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