What are the guidelines for using Vivitrol (naltrexone) in patients with opioid or alcohol dependence?

Vivitrol (Extended-Release Injectable Naltrexone) Guidelines

Formulation and Dosing

Vivitrol is administered as a 380 mg intramuscular injection once monthly and is FDA-approved for both opioid dependence and alcohol dependence. 1

• The injectable formulation provides reliable therapeutic naltrexone levels over 4 weeks, significantly improving medication adherence compared to daily oral dosing (50 mg tablets). 2, 3
• For oral naltrexone, the standard dose is 50 mg daily, or alternatively 100 mg on Mondays/Wednesdays and 150 mg on Fridays. 2

Mechanism of Action

• Naltrexone functions as a competitive mu-opioid receptor antagonist, blocking the euphoric effects of opioids and dampening alcohol's activation of the reward pathway by reducing dopamine concentration in the brain. 2, 3
• This blockade prevents the "high" from opioids and reduces alcohol cravings, thereby decreasing excessive drinking and relapse rates. 2, 4

Critical Pre-Treatment Requirements

Patients MUST be completely opioid-free for a minimum of 7-10 days before starting naltrexone to avoid precipitating severe withdrawal. 1

• For patients transitioning from buprenorphine or methadone, they may be vulnerable to precipitated withdrawal for up to 2 weeks. 2, 1
• Consider performing a naloxone challenge test if there is any question of occult opioid dependence, but do NOT perform this test in patients showing clinical signs of withdrawal or with opioids in their urine. 1
• Precipitated withdrawal can be severe enough to require hospitalization and is distinctly different from spontaneous withdrawal. 1

Patient Selection

For Opioid Dependence:

• Vivitrol is most beneficial for highly motivated patients who cannot or do not wish to take continuous opioid agonist therapy (like methadone or buprenorphine). 2
• Criminal justice populations show significant benefit from extended-release naltrexone. 2
• Healthcare professionals and other highly motivated populations demonstrate excellent outcomes with naltrexone maintenance. 2

For Alcohol Dependence:

• Naltrexone combined with psychosocial support reduces relapse to heavy drinking by approximately 50% compared to placebo. 5, 6
• The number needed to treat to prevent return to any drinking is approximately 20, with a modest effect size of 0.15-0.2. 3
• Naltrexone is more effective at reducing heavy drinking than achieving complete abstinence. 7

Absolute Contraindications

Do NOT use naltrexone in the following situations:

• Patients requiring opioid medications for pain control—naltrexone will completely block pain relief from opioid agonists. 2, 4
• Patients with alcoholic liver disease (ALD) due to risk of hepatotoxicity. 8, 4
• Patients with acute hepatitis or decompensated cirrhosis (10-fold increase in naltrexone AUC). 1
• Current opioid use or dependence without adequate detoxification period. 1

Monitoring Requirements

• Obtain baseline liver function tests before initiating treatment. 2, 4
• Monitor liver function tests every 3-6 months during treatment due to potential hepatotoxicity at supratherapeutic doses. 2, 4
• While hepatotoxicity is uncommon at the standard 50 mg dose, it becomes a concern at higher doses. 4, 7

Perioperative Management

For patients on naltrexone requiring elective surgery with expected opioid use:

• Hold oral naltrexone for 2-3 days prior to the procedure. 2
• Hold extended-release naltrexone (Vivitrol) for 24-30 days after the last injection. 2
• Be aware that greater-than-usual opioid doses may be required, and resulting respiratory depression may be deeper and more prolonged. 1

Treatment Duration and Efficacy

• The FDA-approved trials demonstrating efficacy used naltrexone 50 mg daily for up to 12 weeks for alcohol dependence. 1
• Many clinicians recommend one year of treatment, though optimal duration has not been well-studied. 7
• In opioid dependence trials, 24-week treatment with Vivitrol 380 mg monthly significantly increased the median proportion of weeks of confirmed abstinence compared to placebo. 9

Essential Counseling Points

Patients must understand these critical safety issues:

• Increased sensitivity to opioids after naltrexone discontinuation creates significant overdose risk due to decreased opioid tolerance. 2, 1
• Attempting to overcome the opioid blockade by using large doses of heroin or other opioids may lead to serious injury, coma, or death. 1
• Patients should carry identification indicating they are on naltrexone therapy for emergency situations. 1
• Family members must be informed of the increased overdose risk if the patient returns to opioid use after treatment. 1

Combination with Psychosocial Treatment

Naltrexone should NEVER be used as monotherapy—it must be combined with comprehensive psychosocial support. 1

• Effective components include individual counseling, cognitive behavioral therapy, group therapy (such as Alcoholics Anonymous), and family therapy. 8, 5
• The addition of psychosocial care significantly reduces dropout rates and substance use during treatment. 2
• Appropriate compliance-enhancing techniques should be implemented for all treatment components, especially medication adherence. 1

Common Adverse Effects

• Most common side effects (≥5% incidence) include nausea, vomiting, hepatic enzyme abnormalities, nasopharyngitis, insomnia, hypertension, and injection-site pain. 9, 6
• Nausea is the most frequently reported adverse effect but is generally mild and transient. 6, 7
• Monitor for depression during treatment, as patients may experience depressive symptoms while on naltrexone. 1

Alternative Medications for Specific Populations

• For patients with liver cirrhosis requiring medication to maintain alcohol abstinence, baclofen may be a better alternative than naltrexone. 4
• Acamprosate is a safer option for patients with liver disease concerns, as it helps reduce withdrawal symptoms and maintain abstinence without hepatotoxicity risk. 4
• Consider these alternatives particularly in patients with any degree of alcoholic liver disease where strict abstinence is mandatory. 4

Critical Pitfall to Avoid

Never initiate naltrexone in patients with subclinical opioid dependence or inadequate opioid-free period—this will precipitate severe withdrawal that may require hospitalization. 1 Always verify opioid-free status through patient history, urine drug screening, and consider naloxone challenge testing when in doubt. 1