Signals of Muscle Relaxant Drug Interactions Associated with Unintentional Traumatic Injury: A Population-Based Screening Study

Ghadeer K Dawwas; Sean Hennessy; Colleen M Brensinger; Emily K Acton; Warren B Bilker; Sophie Chung; Sascha Dublin; John R Horn; Melanie M Manis; Todd A Miano; David W Oslin; Thanh Phuong Pham Nguyen; Samantha E Soprano; Douglas J Wiebe; Charles E Leonard

doi:10.1007/s40263-022-00909-1

Signals of Muscle Relaxant Drug Interactions Associated with Unintentional Traumatic Injury: A Population-Based Screening Study

CNS Drugs. 2022 Apr;36(4):389-400. doi: 10.1007/s40263-022-00909-1. Epub 2022 Mar 6.

Authors

Ghadeer K Dawwas^{1

2

3}, Sean Hennessy^{1

2

3

4}, Colleen M Brensinger^{1

2}, Emily K Acton^{1

2

5}, Warren B Bilker^{1

6}, Sophie Chung⁷, Sascha Dublin^{8

9}, John R Horn¹⁰, Melanie M Manis¹¹, Todd A Miano^{1

2}, David W Oslin^{1

6

12}, Thanh Phuong Pham Nguyen^{1

2

5

13}, Samantha E Soprano^{1

2}, Douglas J Wiebe^{2

3

14}, Charles E Leonard^{15

16

17}

Affiliations

¹ Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA.
² Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³ Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, USA.
⁴ Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁵ Translational Center of Excellence for Neuroepidemiology and Neurology Outcomes Research, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁶ Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁷ AthenaHealth, Inc., Watertown, MA, USA.
⁸ Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
⁹ Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
¹⁰ Department of Pharmacy, School of Pharmacy, University of Washington, Seattle, WA, USA.
¹¹ Department of Pharmacy Practice, McWhorter School of Pharmacy, Samford University, Birmingham, AL, USA.
¹² Mental Illness Research, Education, and Clinical Center, Corporal Michael J. Crescenz Veterans Administration Medical Center, Philadelphia, PA, USA.
¹³ Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
¹⁴ Penn Injury Science Center, University of Pennsylvania, Philadelphia, PA, USA.
¹⁵ Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA. celeonar@pennmedicine.upenn.edu.
¹⁶ Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. celeonar@pennmedicine.upenn.edu.
¹⁷ Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, USA. celeonar@pennmedicine.upenn.edu.

Abstract

Background: Use of muscle relaxants is rapidly increasing in the USA. Little is understood about the role of drug interactions in the known association between muscle relaxants and unintentional traumatic injury, a clinically important endpoint causing substantial morbidity, disability, and death.

Objective: We examined potential associations between concomitant drugs (i.e., precipitants) taken with muscle relaxants (affected drugs, i.e., objects) and hospital presentation for unintentional traumatic injury.

Methods: In a series of self-controlled case series studies, we screened to identify drug interaction signals for muscle relaxant + precipitant pairs and unintentional traumatic injury. We used Optum's de-identified Clinformatics^® Data Mart Database, 2000-2019. We included new users of a muscle relaxant, aged 16-90 years, who were dispensed at least one precipitant drug and experienced an unintentional traumatic injury during the observation period. We classified each observation day as precipitant exposed or precipitant unexposed. The outcome was an emergency department or inpatient discharge diagnosis for unintentional traumatic injury. We used conditional Poisson regression to estimate rate ratios adjusting for time-varying confounders and then accounted for multiple estimation via semi-Bayes shrinkage.

Results: We identified 74,657 people who initiated muscle relaxants and experienced an unintentional traumatic injury, in whom we studied concomitant use of 2543 muscle relaxant + precipitant pairs. After adjusting for time-varying confounders, 16 (0.6%) pairs were statistically significantly and positively associated with injury, and therefore deemed signals of a potential drug interaction. Among signals, semi-Bayes shrunk, confounder-adjusted rate ratios ranged from 1.29 (95% confidence interval 1.04-1.62) for baclofen + sertraline to 2.28 (95% confidence interval 1.14-4.55) for methocarbamol + lamotrigine.

Conclusions: Using real-world data, we identified several new signals of potential muscle relaxant drug interactions associated with unintentional traumatic injury. Only one among 16 signals is currently reported in a major drug interaction knowledge base. Future studies should seek to confirm or refute these signals.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Bayes Theorem
Databases, Factual
Drug Interactions
Emergency Service, Hospital*
Humans
Muscles*

Abstract

Publication types

MeSH terms

Grants and funding