Interpreting labels of abuse-deterrent opioid analgesics


  • Lynn R. Webster, MD, FACPM, FASAM



opioid analgesics, opioid-related disorders, opioid mixed agonist-antagonists, pain management, pain


Objective: To provide an overview of available abuse-deterrent opioids (ADOs) and the labeling text that describes abuse-deterrent (AD) properties. Design: A nonsystematic review of ADO literature and regulatory documents guiding their development.

Outcome Measures/Results: A critical assessment and discussion of common routes of opioid abuse, AD methods and properties, US Food and Drug Administration (FDA) study requirements to achieve AD labeling, and brief guide to understanding AD labels.

Conclusions: The FDA has issued guidance as incentive and direction to industry to develop ADOs as one component of a multi-pronged public-health strategy to combat opioid abuse and misuse. The guidance describes separate categories of premarket and postmarket studies and makes recommendations for claims that may be made based on study findings. Ten ADOs have FDA-approved labeling attesting to AD properties. Available formulations that fail to conform to FDA guidance in study and labeling recommendations cannot be considered ADO. Formulations with AD properties are expected to reduce risk compared to the same agents without AD properties but cannot prevent all abuse and adverse clinical outcomes.

Author Biography

Lynn R. Webster, MD, FACPM, FASAM

Vice President of Scientific Affairs, Early Development Services, PRA Health Sciences, Salt Lake City, Utah


Rudd RA, Seth P, David F, Scholl L: Increases in Drug and Opioid-Involved Overdose Deaths - United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016; 65(5051): 1445-1452.

U.S. Food and Drug Administration, Center for Drug Evaluation and Research (CDER): Abuse-Deterrent Opioids—Evaluation and Labeling: Guidance for Industry. April 2015; Available at Accessed November 24, 2017..

Califf RM, Woodcock J, Ostroff S: A Proactive Response to Prescription Opioid Abuse. N Engl J Med. 2016; 374(15): 1480-1485.

Vowles KE, McEntee ML, Julnes PS, et al.: Rates of opioid misuse, abuse, and addiction in chronic pain: A systematic review and data synthesis. Pain. 2015; 156(4): 569-576.

Han B, Compton WM, Blanco C, et al.: Prescription Opioid Use, Misuse, and Use Disorders in U.S. Adults: 2015 National Survey on Drug Use and Health. Ann Intern Med. 2017; 167(5): 293-301.

Volkow ND, McLellan AT: Opioid abuse in chronic pain—misconceptions and mitigation strategies. N Engl J Med. 2016; 374(13): 1253-1263.

Butler SF: Reply to commentary. J Pain. 2013; 14(4): 361-362.

Dart R: Public Health Need for Abuse-Deterrent ER Morphine. Egalet Presentations for the August 4, 2016 Joint Meeting of the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee. 2016; Silver Spring, MD.

Gasior M, Bond M, Malamut R: Routes of abuse of prescription opioid analgesics: a review and assessment of the potential impact of abuse-deterrent formulations. Postgrad Med. 2016; 128(1): 85-96.

California Health Benefits Review Program: Analysis of California Assembly Bill AB 623 Abuse-Deterrent Opioid Analgesics. 2015.

Butler SF, Budman SH, Licari A, et al.: National addictions vigilance intervention and prevention program (NAVIPPRO): A real-time, product-specific, public health surveillance system for monitoring prescription drug abuse. Pharmacoepidemiol Drug Saf. 2008; 17(12): 1142-1154.

Severtson SG, Ellis MS, Kurtz SP, et al.: Sustained reduction of diversion and abuse after introduction of an abuse deterrent formulation of extended release oxycodone. Drug Alcohol Depend. 2016; 168: 219-229.

Jones CM, Paulozzi LJ, Mack KA: Alcohol involvement in opioid pain reliever and benzodiazepine drug abuse-related emergency department visits and drug-related deaths - United States,

MMWR Morb Mortal Wkly Rep. 2014; 63(40): 881-885.

Gomes T, Juurlink DN, Antoniou T, et al.: Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study. PLoS Med. 2017; 14(10): e1002396.

Crane EH: The CBHSQ Report: Emergency Department Visits Involving Narcotic Pain Relievers. Rockville, MD: Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality; 2015.

Peacock A, Bruno R, Larance B, et al.: Same-day use of opioids and other central nervous system depressants amongst people who tamper with pharmaceutical opioids: A retrospective 7-day diary study. Drug Alcohol Depend. 2016; 166: 125-133.

Cicero TJ, Ellis MS, Kasper ZA: Relative preferences in the abuse of immediate-release versus extended-release opioids in a sample of treatment-seeking opioid abusers. Pharmacoepidemiol Drug Saf. 2017; 26(1): 56-62.

Green JL, Bucher Bartelson B, Le Lait MC, et al.: Medical outcomes associated with prescription opioid abuse via oral and non-oral routes of administration. Drug Alcohol Depend. 2017; 175: 140-145.

Webster LR, Markman J, Cone EJ, et al.: Current and future development of extended-release, abuse-deterrent opioid formulations in the United States. Postgrad Med. 2017; 129(1): 102-110.

U.S. Drug Enforcement Administration: Drug Scheduling. Availabe at Accessed November 17, 2017.

U.S. Food and Drug Administration: FDA Briefing Document: Joint Meeting of Anesthetic and Analgesic Drug Products Advisory Committee and Drug Safety and Risk Management Advisory Committee. April 5, 2017; Available at Accessed October 13, 2017.

U.S. Food and Drug Administration: Impact of Exclusivity on Approval of Arymo ER. January 9, 2017; Available at Accessed October 12, 2017.

U.S. Food and Drug Administration, Center for Drug Evaluation and Research (CDER): FDA Briefing Document: Joint Meeting of Anesthetic and Analgesic Drug Products Advisory Committee and Drug Safety and Risk Management Advisory Committee to Discuss NDA 209777. April 5, 2017.

Coplan PM, Chilcoat HD, Butler SF, et al.: The effect of an abuse-deterrent opioid formulation (OxyContin) on opioid abuse-related outcomes in the postmarketing setting. Clin Pharmacol Ther. 2016; 100(3): 275-286.

Eaton TA, Comer SD, Revicki DA, et al.: Determining the clinically important difference in visual analog scale scores in abuse liability studies evaluating novel opioid formulations. Qual Life Res. 2012; 21(6): 975-981.

White AG, LeCates J, Birnbaum HG, et al.: Positive subjective measures in abuse liability studies and real-world nonmedical use: Potential impact of abuse-deterrent opioids on rates

of nonmedical use and associated healthcare costs. J Opioid Manag. 2015; 11(3): 199-210.

Institute for Clinical and Economic Review (ICER): Abuse deterrent formulations of opioids: effectiveness and value: draft evidence report. Prepared for: New England Comparative Effectiveness Public Advisory Council; May 5, 2017.

Skinner BJ: Societal cost savings from abuse deterrent formulations for prescription opioids in Canada. Canadian Health Policy: Canadian Health Policy Institute; May 29, 2017.



How to Cite

Webster, MD, FACPM, FASAM, L. R. “Interpreting Labels of Abuse-Deterrent Opioid Analgesics”. Journal of Opioid Management, vol. 13, no. 6, Dec. 2017, pp. 415-23, doi:10.5055/jom.2017.0418.