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Screening to identify signals of opioid drug interactions leading to unintentional traumatic injury - 27/10/20

Doi : 10.1016/j.biopha.2020.110531 
Charles E. Leonard a, b, , Colleen M. Brensinger a, Thanh Phuong Pham Nguyen a, c, John R. Horn d, Sophie Chung e, Warren B. Bilker a, f, Sascha Dublin g, h, Samantha E. Soprano a, Ghadeer K. Dawwas a, David W. Oslin a, f, i, Douglas J. Wiebe j, k, Sean Hennessy a, b, l
a Center for Pharmacoepidemiology Research and Training, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States 
b Center for Therapeutic Effectiveness Research, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States 
c Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States 
d Department of Pharmacy, School of Pharmacy, University of Washington, Seattle, WA, United States 
e AthenaHealth, Inc., Watertown, MA, United States 
f Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States 
g Kaiser Permanente Washington Health Research Institute, Seattle, WA, United States 
h Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States 
i Mental Illness Research, Education, and Clinical Center, Corporal Michael J. Crescenz Veterans Administration Medical Center, Philadelphia, PA, United States 
j Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States 
k Injury Science Center, University of Pennsylvania, Philadelphia, PA, United States 
l Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States 

Corresponding author at: Perelman School of Medicine, University of Pennsylvania, 807 Blockley Hall, 423 Guardian Drive, Philadelphia, PA, 19104, United States.Perelman School of MedicineUniversity of Pennsylvania807 Blockley Hall423 Guardian DrivePhiladelphiaPA19104United States

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Highlights

Opioid drug interactions are a high priority target for minimizing patient harms.
We identified potential opioid drug interactions associated with unintentional injury.
Readers should interpret these drug interaction signals as hypothesis generating.
Among identified signals, most were not documented in drug interaction knowledge bases.
Findings may help researchers target limited available resources to assess etiology.

Le texte complet de cet article est disponible en PDF.

Abstract

Background

Efforts 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.

Objective

To 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.

Setting

Beneficiaries 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. Outcome: Emergency 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.

Results

We 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.

Limitations

Potential 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.

Le texte complet de cet article est disponible en PDF.

Keywords : Drug interactions, Injury, Opioid analgesics, Pharmacoepidemiology, Population health, Self-controlled case series


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