"In the 12 months after a nonfatal overdose, 2040 persons (11%) enrolled in MMT for a median of 5 months (interquartile range, 2 to 9 months), 3022 persons (17%) received buprenorphine for a median of 4 months (interquartile range, 2 to 8 months), and 1099 persons (6%) received naltrexone for a median of 1 month (interquartile range, 1 to 2 months). Among the entire cohort, all-cause mortality was 4.7 deaths (95% CI, 4.4 to 5.0 deaths) per 100 person-years and opioid-related mortality was 2.1 deaths (CI, 1.9 to 2.4 deaths) per 100 person-years.

"VIVITROL injections may be followed by pain, tenderness, induration, swelling, erythema, bruising, or pruritus; however, in some cases injection site reactions may be very severe. In the clinical trials, one patient developed an area of induration that continued to enlarge after 4 weeks, with subsequent development of necrotic tissue that required surgical excision. In the postmarketing period, additional cases of injection site reaction with features including induration, cellulitis, hematoma, abscess, sterile abscess, and necrosis, have been reported.

"Vulnerability to Opioid Overdose

"Precipitation of Opioid Withdrawal

"What is VIVITROL?
"VIVITROL is a prescription injectable medicine used to:
"• treat alcohol dependence. You should stop drinking before starting VIVITROL.
"• prevent relapse to opioid dependence, after opioid detoxification.
"This means that if you take opioids or opioid-containing medicines, you must stop taking them before you start receiving VIVITROL. See “What is the most important information I should know about 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.

"This large multicentre, randomised, controlled, comparative effectiveness trial had five major findings. First, it was more difficult to start XR-NTX [Extended-release naltrexone] treatment than BUP-NX [sublingual buprenorphine-naloxone] treatment: 28% dropped out of treatment before XR-NTX induction versus only 6% before BUP-NX induction. Second, nearly all induction failures had early relapse. Third, in the intention-to-treat population of all patients who were randomly assigned, XR-NTX had lower relapse-free survival than BUP-NX, directly related to early induction failure.

"Naltrexone is a long acting opioid receptor antagonist used in drug rehabilitation programmes to maintain opioid abstinence. However, when consumed in conjunction with an opioid substance, prolonged opioid withdrawal will be precipitated resulting in unpredictable and life threatening medical consequences."

"The risk of severe precipitated opioid withdrawal (POW) is amplified when precipitated by a long-acting opioid antagonist. IM [intramuscular] extended release naltrexone (XRNTX; Vivitrol®) is an FDA approved therapy to prevent relapse of opioid and alcohol abuse. Two cases of precipitated opioid withdrawal from XRNTX are presented that illustrate different patient reactions to POW. A 56-year-old woman developed a hypertensive emergency and required continuous intravenous vasodilator, clonidine, and intensive care monitoring after re-initiation of XRNTX following opioid relapse.

"However, one problem markedly reduces naltrexone’s efficacy and has limited its use for treating heroin and other forms of opioid dependence worldwide: patients often do not like it and do not take it on a daily basis.