Screening to identify signals of opioid drug interactions leading to unintentional traumatic injury
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
• 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.
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.