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Comment & Response
September 2015

Prescription Opioid Duration of Action and the Risk of Unintentional Overdose—Reply

Author Affiliations
  • 1Department of Health Sciences, Northeastern University, Boston, Massachusetts
  • 2Department of Health Policy and Management, Harvard School of Public Health, Harvard University, Boston, Massachusetts
  • 3Massachusetts Veterans Epidemiology Research and Information Center, Veterans Affairs Boston Healthcare System, Boston
JAMA Intern Med. 2015;175(9):1583. doi:10.1001/jamainternmed.2015.3259

In Reply We appreciate the opportunity to address the questions that Ruan et al raise with respect to whether the 4802 users of fentanyl patches drove our finding that opioid-naïve patients who initiate long-acting opioid formulations (n = 18 887) appear to be at increased risk of unintentional overdose compared with patients initiating short-acting formulations. Of the 37 overdose events observed in our original cohort of long-acting opioid formulation initiators, 4 events occurred among those initiating fentanyl patches (1 event in the first 14 days after initiation and 3 events after 60 days of therapy). Exclusion of fentanyl initiators from analysis did not materially change our findings. After adjustment for age, sex, opioid dose, and other clinical characteristics, patients receiving long-acting opioid formulations other than fentanyl still had a significantly higher rate of overdose injury than did those receiving short-acting opioid formulations (hazard ratio [HR], 2.24; 95% CI, 1.21-4.14), with risk particularly marked during the first 2 weeks after treatment initiation (HR, 4.97; 95% CI, 1.77-13.96).1

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