Propoxyphene and the risk of out-of-hospital death
Version of Record online: 14 FEB 2013
Copyright © 2013 John Wiley & Sons, Ltd.
Pharmacoepidemiology and Drug Safety
Volume 22, Issue 4, pages 403–412, April 2013
How to Cite
Ray, W. A., Murray, K. T., Kawai, V., Graham, D. J., Cooper, W. O., Hall, K. and Michael Stein, C. (2013), Propoxyphene and the risk of out-of-hospital death. Pharmacoepidem. Drug Safe., 22: 403–412. doi: 10.1002/pds.3411
- Issue online: 1 APR 2013
- Version of Record online: 14 FEB 2013
- Manuscript Accepted: 2 JAN 2013
- Manuscript Revised: 20 DEC 2012
- Manuscript Received: 4 SEP 2012
- sudden death
The opioid analgesic propoxyphene was withdrawn from the US market in 2010, motivated by concerns regarding fatality in overdose and adverse cardiac effects, including prolongation of the QT interval. These concerns were based on case reports, summary vital statistics, and surrogate endpoint studies.
Using the linked Tennessee Medicaid database (1992–2007), we conducted a retrospective cohort study that compared risk of sudden cardiac, medication toxicity, and total out-of-hospital death for propoxyphene users with that for comparable nonusers of any prescribed opioid analgesic and users of hydrocodone, an opioid with similar indications. Cohort members had 1 873 500 propoxyphene prescriptions, 1 873 500 matched nonuser control periods, and 936 750 matched hydrocodone prescriptions.
Current propoxyphene users had no increased risk for sudden cardiac death (versus nonusers: hazard ratio [HR] = 1.00 [0.81–1.23]; versus current hydrocodone users: HR = 0.91 [0.68–1.21]) but did have increased risk for medication toxicity deaths (versus nonusers: HR = 1.85 [1.07–3.19], p = 0.027; versus current hydrocodone users: HR = 2.10 [0.87–5.10], p = 0.100). Because toxicity deaths were a small proportion of study deaths, total out-of-hospital mortality differed by less than 10% between the study groups and was not significantly elevated for propoxyphene (versus nonusers: HR = 1.09 [0.95–1.25]; versus current hydrocodone users: HR = 1.06 [0.87–1.29] ).
Our findings support the concern that propoxyphene has greater toxicity in overdose but do not provide evidence that it increases the risk of sudden cardiac death. Copyright © 2013 John Wiley & Sons, Ltd.