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We performed a self\u2010controlled case series study for each drug triad consisting of an SMR base\u2010pair (i.e., concomitant use of an SMR with another medication), and a co\u2010dispensed medication (i.e., candidate interacting precipitant) taken during ongoing use of the base\u2010pair. We included patients aged \u226516\u2009years with an injury occurring during base\u2010pair\u2010exposed observation time. We used conditional Poisson regression to calculate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for injury with each SMR base\u2010pair + candidate interacting precipitant (i.e., triad) versus the SMR\u2010containing base\u2010pair alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 58\u2009478 triads, 29 were significantly positively associated with injury; confounder\u2010adjusted RRs ranged from 1.39 (95% CI\u2009=\u20091.01\u20131.91) for tizanidine + omeprazole with gabapentin to 2.23 (95% CI\u2009=\u20091.02\u20134.87) for tizanidine + diclofenac with alprazolam. Most identified 3DI signals are new and have not been formally investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identified 29 SMR 3DI signals associated with increased rates of injury. Future aetiologic studies should confirm or refute these SMR 3DI signals.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15395","type":"journal-article","created":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T01:38:34Z","timestamp":1652492314000},"page":"4773-4783","source":"Crossref","is-referenced-by-count":9,"title":["Skeletal muscle relaxant drug\u2013drug\u2013drug interactions and unintentional traumatic injury: Screening to detect three\u2010way drug interaction signals"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3240-8153","authenticated-orcid":false,"given":"Cheng","family":"Chen","sequence":"first","affiliation":[{"name":"Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics University of Pennsylvania  Philadelphia PA United States"},{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine University of Pennsylvania  Philadelphia PA United 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