Injectable extended-release naltrexone (XR-NTX) for opioid dependence: long-term safety and effectiveness

Addiction. 2013 Sep;108(9):1628-37. doi: 10.1111/add.12208. Epub 2013 May 24.


Aims: To describe drug use and safety with intramuscular injectable extended-release naltrexone (XR-NTX) in opioid dependence during a 1-year open-label extension phase.

Design: Following 6 months of randomized, double-blind, placebo (PBO)-controlled injections given every 28 days, patients receiving XR-NTX 380 mg continued and PBO patients were switched to open-label XR-NTX, with monthly individual drug counseling, for a further year.

Setting: Thirteen clinical sites in Russia.

Participants: Adult opioid-dependent outpatients.

Measurements: Monthly urine samples; reports of craving and functioning; adverse events.

Findings: For the open-label extension (n = 114), 67 continued on XR-NTX and 47 switched from PBO during the double-blind phase to XR-NTX during the open-label phase. Overall, 62.3% (95% CI: 52.7%, 71.2%) completed the extension. Discontinuation occurred most commonly because of withdrawal of consent (18.4%) and loss to follow-up (11.4%); two patients discontinued as a result of lack of efficacy and one because of adverse events. Urine testing revealed that 50.9% (41.5%, 60.4%) were abstinent from opioids at all assessments during the 1-year open-label phase. Adverse events reported by 21.1% of patients were judged to be study drug-related. Injection site reactions were infrequent (6.1%) and the majority were mild. Elevations in liver function tests occurred for 16.7% of patients, but none of these elevations was judged to be clinically significant. No patients died, overdosed or discontinued as a result of severe adverse events.

Conclusions: During a 1-year open-label extension phase of injectable XR-NTX for the prevention of relapse in opioid dependence, 62.3% of patients completed the phase and 50.9% were abstinent from opioids. No new safety concerns were evident.

Trial registration: NCT00678418.

Keywords: Craving; depot naltrexone; extended-release naltrexone; heroin dependence; injectable naltrexone; long-term safety; naltrexone; opioid dependence; sustained release formulations.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Delayed-Action Preparations
  • Double-Blind Method
  • Female
  • Humans
  • Injections, Intramuscular
  • Male
  • Medication Adherence
  • Naltrexone / administration & dosage*
  • Naltrexone / adverse effects
  • Narcotic Antagonists / administration & dosage*
  • Narcotic Antagonists / adverse effects
  • Opioid-Related Disorders / rehabilitation*
  • Secondary Prevention
  • Self Report


  • Delayed-Action Preparations
  • Narcotic Antagonists
  • Naltrexone

Associated data