FDA Approves Long-Acting Injectable Naltrexone for Opioid Dependence
In October 2010, the Food and Drug Administration (FDA) approved a long-acting injectable formulation of naltrexone (XR-NTX) for the prevention of relapse to opioid dependence following opioid detoxification. This approval was based, in part, on a 24-week double-blind randomized controlled trial comparing 380-mg XR-NTX with placebo among 250 subjects with opioid dependence conducted at 13 clinical sites in Russia. Both groups received 12 counseling sessions (1 every 2 weeks). The primary outcome was abstinence confirmed by self-report and urine drug tests. The study population was 88% male, 41% HIV-infected, and 91% hepatitis-C antibody positive and had a mean of 9–10 years of opioid dependence.
- The trial was completed by 46% of the subjects: 53% in the XR-NTX group and 38% in the control group (p=0.02).
- Confirmed abstinence for weeks 5–24 was 36% in the XR-NTX group compared with 23% in the placebo group (p=0.02).
- Secondary outcomes of opioid craving, number of days retained in treatment, and receipt of all injections were better in the XR-NTX group compared with placebo.
- Serious adverse events were uncommon, although any adverse event was reported by 50% of the XR-NTX group and 32% of the placebo group (p=0.001). Only 2 subjects in each group discontinued the trial because of adverse events.
Comments:This study provides support for the use XR-NTX in places where opioid agonist treatment (methadone or buprenorphine) is not available or in patients who cannot tolerate or prefer not to take these treatments. FDA approval based on data from 1 industry-sponsored and designed study, conducted in a setting where treatment conditions are substantially different from the US, has been questioned because of generalizability concerns, because less than half of the subjects completed the trial, and because there was no surveillance for overdose (a known risk among detoxified opioid dependent patients). Before wide dissemination in the US, a trial comparing XR-NTX with opioid agonist treatment, the current standard of care, is warranted. Alexander Y. Walley, MD, MSc
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