Dataset Information

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.

SUBMITTER: Chen C

PROVIDER: S-EPMC9560998 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Skeletal muscle relaxant drug-drug-drug interactions and unintentional traumatic injury: Screening to detect three-way drug interaction signals.

Chen Cheng C Hennessy Sean S Brensinger Colleen M CM Dawwas Ghadeer K GK Acton Emily K EK Bilker Warren B WB Chung Sophie P SP Dublin Sascha S Horn John R JR Miano Todd A TA Pham Nguyen Thanh Phuong TP Soprano Samantha E SE Leonard Charles E CE

British journal of clinical pharmacology 20220601 11

<h4>Aim</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 35562168

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Project description:BackgroundUse 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.ObjectiveWe 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.MethodsIn 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.ResultsWe 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.ConclusionsUsing 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.

Project description:BackgroundEfforts to minimize harms from opioid drug interactions may be hampered by limited evidence on which drugs, when taken concomitantly with opioids, result in adverse clinical outcomes.ObjectiveTo identify signals of opioid drug interactions by identifying concomitant medications (precipitant drugs) taken with individual opioids (object drugs) that are associated with unintentional traumatic injury DESIGN: We conducted pharmacoepidemiologic screening of Optum Clinformatics Data Mart, identifying drug interaction signals by performing confounder-adjusted self-controlled case series studies for opioid + precipitant pairs and injury.SettingBeneficiaries of a major United States-based commercial health insurer during 2000-2015 PATIENTS: Persons aged 16-90 years co-dispensed an opioid and ≥1 precipitant drug(s), with an unintentional traumatic injury event during opioid therapy, as dictated by the case-only design EXPOSURE: Precipitant-exposed (vs. precipitant-unexposed) person-days during opioid therapy.OutcomeEmergency department or inpatient International Classification of Diseases discharge diagnosis for unintentional traumatic injury. We used conditional Poisson regression to generate confounder adjusted rate ratios. We accounted for multiple estimation via semi-Bayes shrinkage.ResultsWe identified 25,019, 12,650, and 10,826 new users of hydrocodone, tramadol, and oxycodone who experienced an unintentional traumatic injury. Among 464, 376, and 389 hydrocodone-, tramadol-, and oxycodone-precipitant pairs examined, 20, 17, and 16 (i.e., 53 pairs, 34 unique precipitants) were positively associated with unintentional traumatic injury and deemed potential drug interaction signals. Adjusted rate ratios ranged from 1.23 (95 % confidence interval: 1.05-1.44) for hydrocodone + amoxicillin-clavulanate to 4.21 (1.88-9.42) for oxycodone + telmisartan. Twenty (37.7 %) of 53 signals are currently reported in a major drug interaction knowledgebase.LimitationsPotential for reverse causation, confounding by indication, and chance CONCLUSIONS: We identified previously undescribed and/or unappreciated signals of opioid drug interactions associated with unintentional traumatic injury. Subsequent etiologic studies should confirm (or refute) and elucidate these potential drug interactions.

Dataset Information

Skeletal muscle relaxant drug-drug-drug interactions and unintentional traumatic injury: Screening to detect three-way drug interaction signals.

Aim

Methods

Results

Conclusion

Publications

Skeletal muscle relaxant drug-drug-drug interactions and unintentional traumatic injury: Screening to detect three-way drug interaction signals.

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