What are the indications, dosing, administration method, contraindications, adverse effects, counseling points, and alternative therapies for Vivitrol (extended‑release injectable naltrexone) in patients with alcohol or opioid dependence?

Vivitrol (Extended-Release Injectable Naltrexone): Clinical Overview

Indications

Vivitrol is FDA-approved for two primary indications: prevention of relapse to opioid dependence following detoxification and treatment of alcohol dependence in patients who can achieve initial abstinence. 1

Opioid Dependence

• Indicated for highly motivated patients who prefer opioid-free treatment over continuous agonist therapy (methadone or buprenorphine) 1
• Most beneficial in motivated populations such as healthcare professionals and criminal justice populations 1
• Requires complete opioid detoxification before initiation 1, 2

Alcohol Dependence

• Approved for patients with alcohol use disorder who can achieve at least 4 days of initial abstinence 3
• Works by blocking opioid receptors that mediate alcohol-induced reward, reducing cravings and heavy drinking days 1, 4
• Must be combined with comprehensive psychosocial treatment including counseling and support programs 1

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Dosing and Administration

The standard dose is 380 mg administered as a deep intramuscular gluteal injection once every 4 weeks (monthly). 1, 5

Administration Technique

• Deep intramuscular injection into the gluteal muscle 5
• Alternating buttocks for subsequent injections 5
• Must be administered by healthcare provider 5

Oral Naltrexone Alternative

• 50 mg tablets taken daily, or 100 mg on Mondays/Wednesdays and 150 mg on Fridays 1
• Injectable formulation preferred when adherence is a concern 1

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Critical Pre-Treatment Requirements

Patients must be completely opioid-free for 7-14 days before initiating Vivitrol to avoid precipitating severe withdrawal. 2

Opioid-Free Waiting Periods

• Buprenorphine (Suboxone): Wait 7-14 days after last dose 2
• Short-acting opioids (heroin, oxycodone): Wait 7-10 days after last dose 2
• Naltrexone immediately displaces any remaining opioid agonists from receptors, causing acute precipitated withdrawal 2

Baseline Screening Required

• Liver function tests (AST, ALT, bilirubin) 1, 6
• Screen for depression, anxiety, and insomnia 1
• Assess renal function; reduce dose to 25 mg daily (oral) if moderate-to-severe renal impairment 1
• Confirm patient is not pregnant (contraindicated in pregnancy) 1

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Absolute Contraindications

Do not administer Vivitrol in the following situations:

• Current opioid use or positive urine drug screen for opioids 1, 2
• Acute opioid withdrawal 2
• Patients requiring opioid analgesics for pain management (blocks pain relief) 1, 6
• Acute hepatitis or decompensated cirrhosis 6
• Pregnancy or women actively trying to conceive 6
• Patients who have not completed proper detoxification waiting period 2

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Monitoring Requirements

Liver Function Monitoring

Obtain baseline liver function tests and repeat every 3-6 months during treatment. 1, 6

• Hepatotoxicity reported at supratherapeutic doses 1, 4
• At standard 50 mg daily dose, naltrexone does not appear to cause liver injury 1
• Use with extreme caution or avoid in alcoholic liver disease 6

Ongoing Assessment

• Monitor for depression, suicidal ideation, and psychiatric symptoms 1
• Assess treatment response at 12 weeks 1
• Evaluate adherence and engagement with psychosocial treatment 1

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Common Adverse Effects

The most frequently reported side effects are injection site reactions, nausea, and hepatic enzyme elevations. 5

Injection-Related (≥5% incidence)

• Injection site pain, tenderness, induration 5
• These are generally mild and transient 5

Systemic Effects (≥5% incidence)

• Nausea (most common systemic effect) 6, 5
• Hepatic enzyme abnormalities 5
• Nasopharyngitis 5
• Insomnia and sleep disturbances 6, 5
• Headache 5
• Hypertension 5
• Constipation 6
• Dry mouth 6

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Critical Safety Warnings

Overdose Risk After Discontinuation

Patients who discontinue Vivitrol have markedly decreased opioid tolerance and face increased risk of fatal overdose if they return to previous opioid use. 1

• Educate all patients about this increased sensitivity to opioids 1
• Provide naloxone rescue kits and overdose education 1
• Warn that attempting to overcome receptor blockade with high-dose opioids can be fatal 7

Pain Management Considerations

For elective surgery, oral naltrexone should be held 2-3 days prior; extended-release naltrexone requires 24-30 days after last injection. 1

• Coordinate with surgical and anesthesia teams 1
• Alternative non-opioid pain management strategies must be planned 1

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Essential Counseling Points

Vivitrol is only effective when combined with comprehensive behavioral treatment—medication alone is insufficient. 1, 2

Patient Education Topics

• Mechanism: blocks opioid receptors, preventing euphoria from opioids and reducing alcohol cravings 1, 4
• Must maintain complete abstinence from opioids during treatment 1
• For alcohol dependence: strict abstinence recommended, especially with any liver disease 6
• Overdose risk if treatment discontinued and opioid use resumed 1
• Monthly injection schedule and importance of adherence 5
• Cannot use opioid pain medications while on Vivitrol 1, 6

Psychosocial Treatment Integration

• Individual counseling required 1
• Group therapy participation 1
• Family therapy when appropriate 1
• Self-help programs (AA, NA) compatible with Vivitrol 3

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Alternative Pharmacotherapies

For Opioid Dependence

Buprenorphine and methadone are first-line treatments with stronger evidence for preventing relapse than naltrexone. 1

• Buprenorphine: Partial opioid agonist, can be prescribed in office-based settings 1
• Methadone: Full opioid agonist, requires specialized clinic enrollment 1
• Naltrexone reserved for highly motivated patients preferring opioid-free treatment 1

For Alcohol Dependence

Acamprosate and disulfiram are alternative FDA-approved medications for alcohol use disorder. 8

• Acamprosate: Reduces withdrawal symptoms and cravings; safer in liver disease than naltrexone 8, 6
• Disulfiram: Causes aversive reaction with alcohol; poor tolerability limits use 8
• Baclofen: GABA-B agonist; may be preferred in patients with cirrhosis 8, 6
• Topiramate: Off-label use; moderate evidence for reducing heavy drinking 8

Combination Therapy

• Acamprosate plus naltrexone showed benefit in one trial, though evidence is mixed 8
• All pharmacotherapy must be combined with counseling and psychosocial support 8

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Efficacy Evidence

Opioid Dependence

In a 24-week randomized controlled trial, Vivitrol 380 mg monthly significantly increased the median proportion of weeks of confirmed opioid abstinence compared to placebo (primary endpoint). 5

• Significantly higher total confirmed abstinence rates versus placebo 5
• Greater reduction in opioid craving 5
• Longer treatment retention period 5
• Sample size: 250 opioid-detoxified patients 5

Alcohol Dependence

Vivitrol increased initial and 6-month abstinence rates in alcohol-dependent adults with ≥4 days initial abstinence. 3

• Approximately 50% reduction in relapse rates when combined with behavioral therapy 1
• Reduces heavy drinking days and alcohol consumption 3, 4
• fMRI studies show attenuated salience of alcohol cues 3
• Efficacy maintained even during high cue-exposure periods (holidays) 3

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Special Populations and Clinical Scenarios

Alcoholic Liver Disease

Naltrexone carries hepatotoxicity risk and should be avoided in patients with alcoholic liver disease; consider acamprosate or baclofen instead. 6

• If liver function tests show normal or mild elevation without cirrhosis, Vivitrol may proceed with close monitoring 6
• Compensated cirrhosis: assess case-by-case, consider alternatives 6
• Decompensated cirrhosis: absolute contraindication 6

Concurrent Substance Use

Marijuana use does not contraindicate Vivitrol; no documented drug interactions or safety concerns between naltrexone and cannabis. 1

• Screen for all substance use but do not withhold naltrexone based on marijuana alone 1
• Naltrexone does not interact with cannabinoid receptors 1

Pregnancy

Vivitrol is contraindicated in pregnancy; offer buprenorphine (without naloxone) or methadone instead. 1

• Women of reproductive potential must use reliable contraception 6

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Common Clinical Pitfalls

Premature Initiation

• Never administer Vivitrol before completing the required opioid-free waiting period (7-14 days for buprenorphine, 7-10 days for short-acting opioids) 2
• Precipitated withdrawal is severe and can lead to treatment dropout 2

Monotherapy Approach

• Do not prescribe Vivitrol without concurrent comprehensive psychosocial treatment—medication alone is insufficient 1, 2
• Ensure patient is engaged in counseling, group therapy, or support programs 1

Liver Disease Oversight

• Always assess liver function before initiating Vivitrol in patients with alcohol use disorder 6
• Naltrexone may worsen hepatic injury in alcoholic liver disease 6

Pain Management Failure

• Plan ahead for surgical procedures—extended-release naltrexone requires 24-30 days clearance 1
• Coordinate with surgical teams for non-opioid pain strategies 1

Discharge Without Transition Protocol

• Do not discharge patients on Vivitrol without completing proper transition from buprenorphine (requires 3-5 week protocol) 2
• Ensure close outpatient follow-up is arranged 2