Cheng Chen1,2, Sean Hennessy1,2,3,4, Colleen M Brensinger1,2, Ghadeer K Dawwas1,2,3, Emily K Acton1,2,5, Warren B Bilker1,6, Sophie P Chung7, Sascha Dublin8,9, John R Horn10, Todd A Miano1,2, Thanh Phuong Pham Nguyen1,5,11, Samantha E Soprano1,2, Charles E Leonard1,2,3. 1. Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, United States. 2. Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. 3. Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, United States. 4. Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. 5. Translational Center of Excellence for Neuroepidemiology and Neurology Outcomes Research, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. 6. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. 7. AthenaHealth, Inc, Watertown, MA, United States. 8. Kaiser Permanente Washington Health Research Institute, Seattle, WA, United States. 9. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States. 10. Department of Pharmacy, School of Pharmacy, University of Washington, Seattle, WA, United States. 11. Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.
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.
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.
Authors: Charles E Leonard; Meijia Zhou; Colleen M Brensinger; Warren B Bilker; Samantha E Soprano; Thanh Phuong Pham Nguyen; Young Hee Nam; Jordana B Cohen; Sean Hennessy Journal: Clin Pharmacol Ther Date: 2019-07-04 Impact factor: 6.875
Authors: Charles E Leonard; Colleen M Brensinger; Thanh Phuong Pham Nguyen; John R Horn; Sophie Chung; Warren B Bilker; Sascha Dublin; Samantha E Soprano; Ghadeer K Dawwas; David W Oslin; Douglas J Wiebe; Sean Hennessy Journal: Biomed Pharmacother Date: 2020-07-30 Impact factor: 6.529
Authors: Charles E Leonard; Colleen M Brensinger; Emily K Acton; Todd A Miano; Ghadeer K Dawwas; John R Horn; Sophie Chung; Warren B Bilker; Sascha Dublin; Samantha E Soprano; Thanh Phuong Pham Nguyen; Melanie M Manis; David W Oslin; Douglas J Wiebe; Sean Hennessy Journal: Clin Pharmacol Ther Date: 2021-03-14 Impact factor: 6.903
Authors: Aidan G Cashin; Thiago Folly; Matthew K Bagg; Michael A Wewege; Matthew D Jones; Michael C Ferraro; Hayley B Leake; Rodrigo R N Rizzo; Siobhan M Schabrun; Sylvia M Gustin; Richard Day; Christopher M Williams; James H McAuley Journal: BMJ Date: 2021-07-07