Opioid Dependence: Vivitrol Proves Effective in Decreasing Rate of Relapse

Tuesday, August 9, 2016
Author: 

R.L. Wynn

In a recent study, extended-release naltrexone — or Vivitrol — resulted in a decreased rate of opioid dependency relapse when compared with the rate when using the usual treatment in a predominantly male and minority population. The study subjects were all outpatient, voluntary participants with criminal justice involvement and opioid abstinence at baseline.

What Is Vivitrol?

Extended-release naltrexone was approved in 2010 for the prevention of relapse to opioid dependence. Vivitrol is a sustained-release monthly injectable formulation of naltrexone, a full opioid antagonist. It has no known abuse potential and is not a controlled substance.

Naltrexone has gained acceptance in the criminal justice system as a tool for prevention of relapse to opioid dependence. This extended-release opioid antagonist is particularly appealing to patients and providers who are unlikely to access opioid-agonist maintenance treatment such as methadone therapy, or methadone-buprenorphine (Suboxone) therapy and who prefer a relapse-prevention medication.

Vivitrol is especially formulated to gradually release naltrexone to block any effect of opioids for up to one month after a single intramuscular injection. Naltrexone is manufactured with incorporation into polymeric microspheres. These microspheres consist of two different types of polymers (long-chain molecules) known as poly lactic acid (PLA) and poly lactic co-glycolic acid (PLGA). The release pattern after intramuscular injection is a result of absorbing water and swelling immediately after injection where the near surface drug is released first. As water absorption continues, hydrolysis of the polymers starts, and afterwards, several days’ degradation of the microspheres begins. More drug diffuses into surrounding tissues resulting in sustained release of drug molecules as polymer hydrolysis continues. After several days, physical erosion of the microspheres begins and drug continues to diffuse from eroding microspheres into surrounding tissues over a four-week period.

The NIH Study

The National Institute on Drug Abuse, a government organization that is part of the National Institutes of Health (NIH) co-sponsored a large, multisite, randomized trial to test the effectiveness of extended-release naltrexone among community-dwelling criminal justice offenders who were at high risk for opioid relapse and other related adverse outcomes. The co-sponsor was Alkermes, the manufacturer of the product.

The report can be accessed at: Lee JD et al. “Extended-release naltrexone to prevent opioid relapse in criminal justice offenders.” N Eng J Med 2016; 374:1232-42.

The authors stated that opioid dependence disproportionately affects U.S. criminal justice system populations. Relapse back to drug addiction and opioid overdose deaths occur at higher rates after release from incarceration.

Methods

The trial involved five sites, all independently funded and using a common collaborative protocol. The sites were:

  1. University of Pennsylvania
  2. New York University School of Medicine and Bellevue Hospital Center
  3. Brown University and Rhode Island Hospital
  4. Columbia University and Medical Center
  5. Friends Research Institute, Baltimore

The trial was open-label (no placebo control) and randomized. It evaluated a 24-week course of extended-release naltrexone (Vivitrol) compared with the usual treatment, consisting of brief counseling and referrals for community treatment programs for the prevention of opioid relapse among adult criminal justice offenders who had a history of opioid dependence and a preference for opioid-free rather than opioid maintenance treatments and who were abstinent from opioids at the time of inclusion into the study.

The primary outcome was the time to an opioid-relapse event defined as 10 or more days of opioid use in a 28-day period as assessed by self-reporting or by testing urine samples obtained every two weeks. A positive or missing urine sample was computed as five days of opioid use.

Secondary outcomes of interest included rates of alcohol and non-opioid drug use, HIV risk behaviors, rearrests and re-incarcerations, and adverse events including opioid overdose.

Recruitment

The study recruited community-dwelling adult volunteers who were criminal justice offenders with a history of opioid dependence. It included 153 subjects that were assigned to the Vivitrol group and 155 that were assigned to usual treatment group.

The mean age of total subjects was 44 years, and 85% of subjects were male. All subjects reported a history of opioid dependence, and 34% reported the use of heroin or any other opioid in the previous 30 days.

Physicians or nurses administered extended-release naltrexone by injection and provided medication-management counseling. The drug was administered at a dose of 380 mg intramuscularly once every four weeks. A standard naloxone challenge to assess opioid withdrawal symptoms had to be negative prior to initial Vivitrol injection. Participants in the usual treatment group received similar counseling focused on adverse events, the prevention of relapse and overdose, and support for community treatment involvement.

Visits occurred at screening, randomization, and then every two weeks for 24 weeks during treatment phase. Post-treatment follow-up occurred at weeks 27, 52, and 78 and included urine toxicology screening and self-reporting of opioid, cocaine, alcohol, and intravenous drug use.

Study results

  1. During the 24-week treatment phase (dosing once every 4 weeks with Vivitrol), the time to relapse to opioid dependence was significantly longer (10.5 weeks) in the Vivitrol group than in the usual treatment group (5.0 weeks).
  2. A relapse event was detected in 66 subjects assigned to the Vivitrol group (43%), as compared to 99 assigned to usual treatment group (64%).
  3. The percent of opioid-negative urine samples during the 24-week treatment phase was 74% in the Vivitrol group and 56% in the usual treatment group. At week 78 (approximately one year after the end of the treatment phase), rates of opioid-negative urine samples were equal (46% in each group).
  4. Rates of other secondary outcome measures, i.e. self-reported cocaine, alcohol, and intravenous drug use, unsafe sex and re-incarceration, were not significantly lower with the Vivitrol treatment than with usual treatment.
  5. Over the 78 weeks observed, there were no opioid overdose events in the Vivitrol group, while there were seven overdose events in the usual treatment group.

Summary

This multisite trial showed that extended-release naltrexone (Vivitrol) resulted in a lower rate of opioid relapse than the rate with usual treatment in a predominantly male and minority population of outpatient, voluntary participants with criminal justice involvement and opioid abstinence at baseline. The trial did not directly compare extended-release naltrexone with the standard of opioid-agonist maintenance treatment (i.e., methadone maintenance). According to the authors, that comparison is being assessed in an ongoing trial.

Some notes on intra-muscular extended-release naltrexone:

  • The clinician is reminded that IM Vivitrol has no analgesic properties.
  • IM Vivitrol is not a DEA controlled substance. It has no addictive/dependence properties. IM Vivitrol blocks any effects of an opioid agonist such as oxycodone and hydrocodone.
  • Patients on IM Vivitrol will most likely have a history of opioid dependence. Any controlled substances, such as opiate pain relievers or tranquilizers, are contraindicated in this population.
  • In treating patients currently undergoing IM Vivitrol treatment or with the drug in their system, any necessary postoperative acute pain management should occur with NSAIDs and/or acetaminophen, not an opiate.
  • IM Vivitrol is indicated for treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids. Dosing is 380 mg intramuscularly every 4 weeks.
  • IM Vivitrol utilizes microsphere technology to provide long acting duration.

Richard L. Wynn, BS Pharm, PhD, is professor of pharmacology at the Baltimore College of Dental Surgery, Dental School, University of Maryland Baltimore.

Want to learn more about this topic? Check out these RxPerts Academy features on opioid topics:

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