Review of Opioid Abuse-Deterrent Formulations: Impact and Barriers to Access

Abstract

The misuse and abuse of opioid analgesics continue to pose a serious public health concern, but for some patients, opioids remain an important analgesic option. Extended-release (ER) opioid formulations are effective for treating chronic pain and are supported by multiple 12-week efficacy studies. ER opioids often contain a high opioid content, and similar to immediate-release (IR) formulations, are subject to abuse, misuse, and diversion. Unintentional misuse may also occur when ER formulations are manipulated for medicinal administration, such as crushing a dose for easier oral intake. As part of a multipronged strategy designed to fight the opioid epidemic, abuse-deterrent formulations (ADFs) were developed to deter misuse, abuse, and diversion of opioids by making manipulation more difficult and nonoral routes of administration less rewarding. Although ADF opioids have been shown to decrease rates of abuse and diversion, they are not equally effective in terms of deterring manipulation for abuse or misuse. Xtampza ER utilizes DETERx technology, which allows it to retain ER characteristics when chewed or crushed, making it the only ER opioid without a boxed warning against these types of manipulation. OxyContin was also developed as an ADF but uses RESISTEC technology, making the tablet hard to crush and viscous in aqueous solutions. ADF utilization has been hampered by patient access issues, including high prices due to lack of insurance coverage. Postmarket real-world studies demonstrate lower rates of abuse, misuse, and diversion for ADF ER opioids compared with non-ADF formulations. However, similar studies comparing abuse-related effectiveness and health care costs for ADF opioids are warranted if clinicians are expected to utilize these potentially safer opioid formulations. These studies would support further education surrounding the benefits and utilization of ADFs and manipulation potential of different ADFs.

Keywords: abuse-deterrent; chronic pain; extended release; opioid analgesics; opioid crisis; tamper.

Figure 1

The mean plasma oxycodone concentration over time following oral administration of Xtampza ER (intact and crushed; left panel), OxyContin (intact and crushed; right panel), and crushed oxycodone IR. In an open-label, randomized, active-controlled, 5-treatment, 5-period, naltrexone-blocked crossover comparison study, blood samples were collected from healthy participants to compare the pharmacokinetics profile of Xtampza ER with OxyContin. IR oxycodone crushed, n=38; Xtampza ER intact, n=38; Xtampza crushed ER, n=40; Oxycontin intact, n=39; OxyContin crushed, n=39. Used with permission of Future Medicine Ltd, from Brennan MJ, Kopecky EA, Marseilles A, O’Connor M, Fleming AB. The comparative pharmacokinetics of physical manipulation by crushing of Xtampza® ER compared with OxyContin®. Pain Manag. 2017;7(6):461–472; permission conveyed through Copyright Clearance Center, Inc.

Figure 2

OxyContin abusers and their route of administration. A sentinel surveillance sample of 140,496 individuals assessed for substance abuse treatment at 357 US centers between June 1, 2009, and March 31, 2012, was examined. Data on the route of administration used (percent) by OxyContin abusers (N=1705) after the introduction of reformulated OxyContin are shown. Adapted from J Pain, volume 14(4), Butler SF, Cassidy TA, Chilcoat H, et al. Abuse rates and routes of administration of reformulated extended-release oxycodone: initial findings from a sentinel surveillance sample of individuals assessed for substance abuse treatment. 351–358, Copyright 2013, with permission from Elsevier.