By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Medical Director, Pharmacy, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a new opioid agonist/antagonist product featuring an abuse-deterrent property for the management of pain. This formulation contain pellets of oxycodone, which surround sequestered naltrexone. It is marketed as Troxyca ER.
The combination oxycodone/naltrexone is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.1
The starting dose for opioid-naïve and opioid-non-tolerant patients is 10 mg/1.2 mg every 12 hours.1 Patients may be converted from other oxycodone formulations at one-half the total daily dose as oxycodone/naltrexone every 12 hours. Detail is provided in the prescribing information to convert various oral opioids to oxycodone/naltrexone.
Oxycodone/naltrexone is available as capsules, each containing 10 mg/1.2 mg, 20 mg/2.4 mg, 30 mg/3.6 mg, 40 mg/4.8 mg, 60 mg/7.2 mg, and 80 mg/9.6 mg.
The formulation is expected to help patients reduce abuse when crushed and administered by oral and intranasal routes.1 After crushing the pellets, the sequestered naltrexone releases to counter the effect of oxycodone. This provides another oxycodone formulation with abuse-deterrent features and the addition of naltrexone.
While this formulation is expected to reduce abuse by oral and intranasal routes, it does not preclude oral abuse.1,2,3
The efficacy of oxycodone/naltrexone was evaluated in one randomized, double-blind, placebo-controlled trial in subjects (both opioid-experienced and opioid-naïve) suffering from moderate-to-severe chronic low back pain.1 The study design was an enriched-enrollment with a randomized-withdrawal. Subjects were titrated to effect with oxycodone/naltrexone in the open-label phase; afterward, there was a 12-week double-blind period. Those with adequate pain control were randomized to a 12-week period to continue the drug or to placebo (blind taper of oxycodone/naltrexone).
Two hundred and eighty-one subjects made it to the withdrawal phase out of 410 that entered the titration phase (68.5%). Two-thirds (n = 188) completed the study. The average change in the weekly average pain intensity from baseline was statistically in favor of oxycodone/naltrexone over placebo.
In clinical abuse studies, non-dependent opioid abusers were randomized in three studies to assess the abuse potential of physical manipulation of the oxycodone/naltrexone.1,2 Generally, these abusers preferred crushed oxycodone over oxycodone/naltrexone and were less likely to use the latter again via oral, intranasal, or IV administration. The scores for preference for the drug and “take the drug again” were higher or at least numerically higher than placebo, which means abuse still is possible, particularly oral abuse.
The FDA encourages the development of these formulations to help combat the opioid epidemic. This product is not abuse-proof, and the FDA panel expressed concerns about approving a high-dose opioid product with limited abuse-deterrent properties and the potential for oral abuse.3 Although the agency recommended approval, the FDA also voted against the claim that the drug combination deters oral abuse. The drug’s manufacturer is required to conduct postmarketing studies to quantify the serious risks of misuse, abuse, and addiction associated with long-term use as well as predict opioid overdose and death.4 The cost of oxycodone/naltrexone was not available at the time of this review.
- Troxyca ER Prescribing Information. Pfizer, Inc. August 2016.
- Stenik B, Bass A, Bramson C, et al. Abuse potential study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) compared with immediate-release oxycodone administered orally to nondependent recreational opioid users. Pain Med 2016 Aug 22. pii: pnw178. [Epub ahead of print].
- Reuters. FDA panel backs approval of Pfizer’s opioid painkiller. Available at: . Accessed Sept. 1, 2016.
- Department of Health and Human Services. FDA. NDA approval. Available at: . Accessed Sept. 2, 2016.