Clinical Challenges and Knowledge Gaps Regarding Treatment with Vivitrol

"There are currently no specific clinical guidelines for transitioning patients with opioid use disorder to Vivitrol while minimizing the risk of precipitating withdrawal and relapse.²⁵ However, a number of opioid detoxification and induction strategies are being investigated to assist patients transitioning to Vivitrol.^90,91 The US prescribing recommendation that individuals abstain from opioids for seven to 10 days, combined with conventional methods of opioid-agonist tapering over several days, represents a delay of at least two weeks before Vivitrol can be started.^23,90 In addition, guidance is needed for transitioning patients from oral naltrexone, buprenorphine/naloxone, or methadone to Vivitrol or re-initiating treatment with Vivitrol following discontinuation.²³ Because of the time required for detoxification, current guidelines recommend residential or intensive outpatient settings for initiating treatment with Vivitrol.²

"Pain management is a concern in patients receiving treatment with Vivitrol.^25,92 Patients undergoing emergency or elective surgery will not respond to normal therapeutic doses of opioid analgesics because of the opioid-receptor antagonist mechanism of action of Vivitrol. In addition, re-initiating Vivitrol soon after opioid use may precipitate withdrawal. Therefore, it is recommended that pain be treated with regional or local anesthetic techniques, and non-opioid pharmacologic therapies (including ketorolac and gabapentin).⁹² If non-opioid modalities prove ineffective or are contraindicated, the effects of opioid titration would need to be closely monitored by professionals trained in the management of the effects of high-dose opioids, including assisted ventilation and cardiopulmonary rescucitation.⁹²

"There are currently no recommendations for the duration of treatment with Vivitrol.²⁵ An ongoing trial is assessing the effect of Vivitrol compared with placebo when given for 48 weeks versus 24 weeks in 130 patients addicted to opioids who have completed in-patient treatment.⁹³ Outcome measures include proportion with urine tests positive for opiates and HIV risk behaviours at 12 months.

"Following Vivitrol treatment, opioid tolerance is reduced from the pre-treatment baseline, and patients are vulnerable to potentially fatal overdose, particularly if they take large amounts of opioids in an attempt to overcome the blockade effect of Vivitrol.²³ None of the published phase III trials or studies in real-world settings have investigated the long-term risk of relapse, opioid overdose, and death among those participants who choose not to continue therapy with Vivitrol for longer than 78 months.
Research comparing Vivitrol with oral naltrexone and with opioid agonists (such as methadone or buprenorphine/naloxone) is needed to improve our understanding of its place in therapy for opioid use disorder. One ongoing, randomized, open-label trial is assessing the comparative effectiveness of Vivitrol versus buprenorphine/naloxone in 600 adults with opioid use disorder in the US.⁹⁴ The primary outcome is time to opioid relapse (i.e., loss of persistent abstinence) during the 24-week treatment phase. Secondary outcomes include retention in treatment, opioid abstinence, HIV risk behaviours, quality of life, genetic moderators, and cost-effectiveness. A smaller randomized, open-label trial is also studying Vivitrol versus buprenorphine/naloxone in 180 patients with opioid use disorder in Norway.95 Primary outcomes are abstinence from illicit opioids, as well as retention in treatment. Following the 12-week randomized period, there will be a 36-week period during which participants will continue to receive Vivitrol in order to investigate long-term outcomes. A third trial is investigating whether Vivitrol has greater efficacy and is more cost-effective than oral naltrexone, with or without behavioural therapy and HIV risk reduction counselling, in 320 opiate-dependent patients in Russia.⁹⁶ Primary outcome measures include reductions in HIV risk behaviours, reductions in illicit opiate use, and treatment retention during the six-month treatment phase and the six-month follow-up.

"There has been interest in using Vivitrol in various subpopulations, as agonist therapy with buprenorphine/naloxone or methadone may be less suitable for some patients. Several ongoing phase III and IV trials are evaluating the effect of Vivitrol in people within the criminal justice system, in those living with HIV, and in young adults and adolescents with opioid use disorder. Results from these and future studies will be needed to determine the clinical impact and value of Vivitrol in a broad and diverse population of patients with opioid use disorder."