{"doi":"10.1111/bcp.15395","title":"Skeletal muscle relaxant drug–drug–drug interactions and unintentional traumatic injury: Screening to detect three‐way drug interaction signals","abstract":"AIM: The aim of this study was to identify skeletal muscle relaxant (SMR) drug-drug-drug interaction (3DI) signals associated with increased rates of unintentional traumatic injury. METHODS: We conducted automated high-throughput pharmacoepidemiologic screening of 2000-2019 healthcare data for members of United States commercial and Medicare Advantage health plans. We performed a self-controlled case series study for each drug triad consisting of an SMR base-pair (i.e., concomitant use of an SMR with another medication), and a co-dispensed medication (i.e., candidate interacting precipitant) taken during ongoing use of the base-pair. We included patients aged ≥16 years with an injury occurring during base-pair-exposed observation time. We used conditional Poisson regression to calculate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for injury with each SMR base-pair + candidate interacting precipitant (i.e., triad) versus the SMR-containing base-pair alone. RESULTS: Among 58 478 triads, 29 were significantly positively associated with injury; confounder-adjusted RRs ranged from 1.39 (95% CI = 1.01-1.91) for tizanidine + omeprazole with gabapentin to 2.23 (95% CI = 1.02-4.87) for tizanidine + diclofenac with alprazolam. Most identified 3DI signals are new and have not been formally investigated. CONCLUSION: We identified 29 SMR 3DI signals associated with increased rates of injury. Future aetiologic studies should confirm or refute these SMR 3DI signals.","journal":"British Journal of Clinical Pharmacology","year":2022,"id":288756,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":356700,"name":"Sean Hennessy","orcid":"0000-0003-4726-9413","position":1,"is_corresponding":false},{"id":362654,"name":"Colleen Brensinger","orcid":null,"position":2,"is_corresponding":false},{"id":360930,"name":"Ghadeer K. Dawwas","orcid":"0000-0002-7982-7419","position":3,"is_corresponding":false},{"id":415459,"name":"Emily K. Acton","orcid":"0000-0002-5150-5995","position":4,"is_corresponding":false},{"id":356701,"name":"Warren B. Bilker","orcid":"0000-0002-2704-7525","position":5,"is_corresponding":false},{"id":494402,"name":"Sophie P. Chung","orcid":"0000-0003-1520-2898","position":6,"is_corresponding":false},{"id":494403,"name":"Sascha Dublin","orcid":"0000-0002-6649-3659","position":7,"is_corresponding":false},{"id":72927,"name":"John R. Horn","orcid":"0000-0003-4525-4250","position":8,"is_corresponding":false},{"id":442245,"name":"Todd A. Miano","orcid":"0000-0002-3832-6212","position":9,"is_corresponding":false},{"id":494401,"name":"Thanh Phuong Pham Nguyen","orcid":"0000-0003-3589-764X","position":10,"is_corresponding":false},{"id":356699,"name":"Samantha E. Soprano","orcid":"0000-0002-9267-4496","position":11,"is_corresponding":false},{"id":356702,"name":"Charles E. Leonard","orcid":"0000-0002-5092-9657","position":12,"is_corresponding":false},{"id":700795,"name":"Cheng Chen","orcid":"0000-0002-3240-8153","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T00:30:14.968626Z","pmid":"35562168","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}