Introduction
Vivitrol (naltrexone extended-release injectable suspension) is a long-acting opioid antagonist medication approved by the FDA for the treatment of alcohol dependence and prevention of relapse to opioid dependence. Administered as a monthly intramuscular injection, Vivitrol provides continuous opioid receptor blockade, offering a unique pharmacological approach to addiction treatment that eliminates the need for daily dosing.
Mechanism of Action
Vivitrol contains naltrexone, a competitive opioid receptor antagonist that binds primarily to mu-opioid receptors in the central nervous system. By occupying these receptors, naltrexone blocks the euphoric and sedative effects of opioids. In alcohol dependence, its mechanism is less clearly defined but is thought to involve modulation of the mesolimbic dopamine pathway, reducing the rewarding effects of alcohol and decreasing craving. The extended-release formulation provides sustained receptor blockade for approximately 4 weeks following a single injection.
Indications
- Treatment of alcohol dependence in patients who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment
- Prevention of relapse to opioid dependence following opioid detoxification
Dosage and Administration
Standard dosing: 380 mg administered intramuscularly every 4 weeks (monthly) Administration:- Administer as an intramuscular gluteal injection using the provided prepackaged kit
- The injection should be alternated between the right and left gluteal muscles
- Must be administered by a healthcare professional
- Do not administer intravenously, subcutaneously, or inadvertently into fatty tissue
- Renal impairment: Use with caution in moderate to severe renal impairment
- Hepatic impairment: Contraindicated in acute hepatitis or liver failure
- Elderly: No specific dosage adjustment recommended
- Pediatrics: Safety and effectiveness not established in patients under 18 years
Pharmacokinetics
Absorption: Following IM injection, naltrexone is slowly released from microspheres, with peak concentrations occurring approximately 2-3 days post-injection Distribution: Apparent volume of distribution is approximately 1,350 liters. Naltrexone is 21% bound to plasma proteins Metabolism: Extensively metabolized primarily by dihydrodiol dehydrogenase to 6β-naltrexol (major metabolite) and other minor metabolites Elimination: Mean elimination half-life is 5-10 days for naltrexone and 12-15 days for 6β-naltrexol. Excreted primarily in urine (46-71%) with lesser amounts in feces (11-27%)Contraindications
- Patients receiving opioid analgesics
- Patients with current physiologic opioid dependence
- Patients in acute opioid withdrawal
- Patients who have failed the naloxone challenge test or have positive urine screen for opioids
- Patients with acute hepatitis or liver failure
- Hypersensitivity to naltrexone or any components of the formulation
Warnings and Precautions
Hepatotoxicity: Dose-related hepatocellular injury may occur; monitor liver function tests Injection site reactions: May include induration, tenderness, pain, nodules, swelling, erythema, bruising, or pruritus Precipitation of opioid withdrawal: May occur if administered to opioid-dependent patients Vulnerability to opioid overdose: After opioid blockade discontinuation, patients may have reduced opioid tolerance Depression and suicidality: Monitor patients for development of depression or suicidal thoughts Eosinophilic pneumonia: Rare cases reported; evaluate new or worsening pulmonary symptomsDrug Interactions
Opioid-containing medications: Vivitrol will block the therapeutic effects of opioid medications Opioid dependence treatments: Avoid concomitant use with methadone or buprenorphine Hepatotoxic drugs: Increased risk of liver toxicity when used with other hepatotoxic agents CYP450 interactions: Naltrexone is a minor substrate of CYP450 enzymes; clinical significance unknownAdverse Effects
Common (≥5%): Injection site reactions (85%), nausea (14%), headache (13%), fatigue (8%), insomnia (7%), anxiety (6%), vomiting (5%) Serious:- Hepatotoxicity
- Eosinophilic pneumonia
- Precipitation of opioid withdrawal
- Depression and suicidal ideation
- Hypersensitivity reactions
- Severe injection site reactions including tissue necrosis
Monitoring Parameters
- Liver function tests at baseline and periodically during treatment
- Signs and symptoms of depression or suicidal ideation
- Injection sites for reactions
- Compliance with abstinence from alcohol and opioids
- Signs of opioid withdrawal if recently detoxified
- Respiratory symptoms suggesting eosinophilic pneumonia
- Pregnancy testing in women of childbearing potential
Patient Education
- Vivitrol will block the effects of opioid medications, including prescription pain medications
- Carry medical identification indicating naltrexone use
- Do not attempt to overcome the opioid blockade by taking large amounts of opioids
- Report any injection site reactions that are severe or do not improve
- Seek immediate medical attention for signs of allergic reaction
- Continue participation in counseling and support programs
- Inform all healthcare providers about Vivitrol treatment before receiving any medical care
- Avoid alcohol consumption during treatment
- Report any new or worsening respiratory symptoms
- Notify provider if pregnancy is suspected or planned
References
1. FDA Prescribing Information: Vivitrol (naltrexone for extended-release injectable suspension) 2. Garbutt JC, et al. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA. 2005;293(13):1617-1625. 3. Krupitsky E, et al. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet. 2011;377(9776):1506-1513. 4. Jarvis BP, et al. Extended-release naltrexone for opioid and alcohol use disorders: a systematic review of the literature. Subst Abus. 2018;39(3):275-285. 5. Lee JD, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2018;391(10118):309-318. 6. Tanum L, et al. Effectiveness of injectable extended-release naltrexone vs daily buprenorphine-naloxone for opioid dependence: a randomized clinical noninferiority trial. JAMA Psychiatry. 2017;74(12):1197-1205.