Opioid tolerance and urine drug testing among initiates of extended-release or long-acting opioids in Food and Drug Administration's Sentinel System


  • Marc R. Larochelle, MD, MPH
  • Noelle M. Cocoros, DSc, MPH
  • Jennifer Popovic, DVM, MA
  • Elizabeth C. Dee, MPH
  • Cynthia Kornegay, PhD
  • Jing Ju, PharmD, PhD
  • Judith A. Racoosin, MD, MPH




opioid analgesics, opioid tolerance, urine drug testing


Objective: A risk evaluation and mitigation strategy for extended-release and long-acting (ER/LA) opioid analgesics was approved by the Food and Drug Administration in 2012. Our objective was to assess frequency of opioid tolerance and urine drug testing for individuals initiating ER/LA opioid analgesics.

Design: Retrospective cohort study.

Setting: Sentinel, a distributed database with electronic healthcare data on >190 million predominantly commercially insured members.

Patients, participants: Members under age 65 initiating ER/LA opioid analgesics between January 2009 and December 2013.

Main outcome measure(s): We examined the proportion of opioid-tolerantonly ER/LA opioid analgesic initiates meeting tolerance criteria: receipt of 30 mg oxycodone equivalents per day in 7 days prior to the first opioid-tolerant-only dispensing. We separately examined the proportion of new users of extended-release oxycodone (ERO) and other ER/LA opioid analgesics with a claim for a urine drug test in the 30 days prior to, and separately for the 183 days after, dispensing.

Results: We identified 79,824 ERO, 7,343 extended-release hydromorphone, and 91,778 transdermal fentanyl opioid-tolerant-only episodes. Tolerance criteria were met in 64 percent of ERO, 64 percent of extended-release hydromorphone and 40 percent of transdermal fentanyl episodes. We identified 210,581 incident ERO and 311,660 other ER/LA opioid analgesic episodes. Use of urine drug testing for ERO compared with other ER/LA opioid analgesics was: 4 percent vs 14 percent respectively in the 30 days prior to initiation and 9 percent vs 23 percent respectively in the 183 days following initiation.

Conclusions: These results suggest potential areas for improving appropriate ER/LA opioid analgesic prescribing practices.

Author Biographies

Marc R. Larochelle, MD, MPH

Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Section of General Internal Medicine, Boston, Massachusetts

Noelle M. Cocoros, DSc, MPH

Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts

Jennifer Popovic, DVM, MA

Program for Health Data and Standardized Methods, RTI International, Waltham, Massachusetts

Elizabeth C. Dee, MPH

Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts

Cynthia Kornegay, PhD

Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland

Jing Ju, PharmD, PhD

Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland

Judith A. Racoosin, MD, MPH

Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland


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How to Cite

Larochelle, MD, MPH, M. R., N. M. Cocoros, DSc, MPH, J. Popovic, DVM, MA, E. C. Dee, MPH, C. Kornegay, PhD, J. Ju, PharmD, PhD, and J. A. Racoosin, MD, MPH. “Opioid Tolerance and Urine Drug Testing Among Initiates of Extended-Release or Long-Acting Opioids in Food and Drug Administration’s Sentinel System”. Journal of Opioid Management, vol. 13, no. 5, Sept. 2017, pp. 315-27, doi:10.5055/jom.2017.0407.

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