In an adult with alcohol use disorder who is opioid‑free and has adequate liver function, what oral and injectable naltrexone dosing schedule and minimum treatment duration are recommended, and which baseline and periodic laboratory tests should be performed to monitor safety?

Naltrexone for Alcohol Use Disorder: Dosing, Duration, and Monitoring

Recommended Dosing Schedule

For adults with alcohol use disorder who are opioid-free and have adequate liver function, initiate naltrexone at 25 mg daily for days 1-3, then increase to 50 mg daily for 3-6 months (up to 12 months), or alternatively use extended-release injectable naltrexone 380 mg intramuscularly once monthly. 1, 2

Oral Naltrexone Dosing

• Start with 25 mg daily for the first 3 days to assess tolerability 1
• Increase to maintenance dose of 50 mg once daily after the initial titration period 1, 2
• The number needed to treat to prevent return to any drinking is approximately 18 patients 3
• The number needed to treat to prevent return to heavy drinking is approximately 11 patients 3

Injectable Naltrexone Dosing

• Extended-release naltrexone (Vivitrol): 380 mg intramuscularly once monthly 1, 2
• Injectable formulation may improve medication adherence compared to daily oral dosing 2
• Injectable naltrexone reduces drinking days by approximately 5 days over a 30-day period compared to placebo 3
• Both oral and injectable formulations show equivalent effectiveness when initiated at hospital discharge, with substantial reductions in heavy drinking days in both groups 4

Critical Timing of Initiation

Naltrexone must be initiated 3-7 days after the last alcohol consumption and only after withdrawal symptoms have completely resolved. 1

• Never start naltrexone during active alcohol withdrawal - it provides no benefit for withdrawal symptoms and delays appropriate benzodiazepine therapy 1
• Naltrexone is contraindicated during the acute withdrawal phase 1
• Benzodiazepines remain the gold standard for managing alcohol withdrawal syndrome before naltrexone can be initiated 1

Minimum Treatment Duration

The recommended treatment duration is 3-6 months, with extension up to 12 months based on clinical response. 1, 2

• Treatment should continue for at least 3 months to achieve meaningful reduction in drinking 1
• Optimal duration extends to 6-12 months for sustained benefit 1
• Shorter duration of naltrexone prescription (≤30 days) is independently associated with increased risk of subsequent hospitalization (hazard ratio 2.50) 5
• Naltrexone is most effective when combined with psychosocial interventions, counseling, and mutual help groups 1, 3

Required Laboratory Testing

Baseline Testing

Obtain liver function tests (AST, ALT) at baseline before initiating naltrexone. 1, 2

• Baseline hepatic panel is mandatory to assess for contraindications 1, 2
• Screen for current opioid use - naltrexone is contraindicated in patients requiring opioid medications 2
• Verify patient is opioid-free to avoid precipitating acute opioid withdrawal 1

Periodic Monitoring

Liver function tests should be repeated every 3-6 months during naltrexone therapy. 1, 2

• Monitor AST and ALT at 3-month intervals initially 1
• Can extend to 6-month intervals if stable 1
• Hepatotoxicity is uncommon at the standard 50 mg dose but requires surveillance 2

Critical Contraindications and Safety Concerns

Absolute Contraindications

Naltrexone is contraindicated in patients with acute hepatitis, decompensated cirrhosis, or alcoholic liver disease. 6, 1

• Naltrexone carries risk of toxic liver injury and is not recommended in patients with alcoholic liver disease 6, 1
• Contraindicated in acute hepatitis or decompensated cirrhosis per FDA labeling 1
• Cannot be used in patients requiring opioid medications for pain control 2

Alternative Medications for Liver Disease

• Baclofen is the only alcohol pharmacotherapy proven safe in cirrhotic patients and should be considered as first-line for patients with liver disease 1
• Acamprosate is a safer alternative for patients with hepatic impairment, as it does not undergo hepatic metabolism 1, 2
• Recent data suggest naltrexone may be safe in compensated cirrhosis with enhanced monitoring, though guidelines remain cautious 1, 5

Common Pitfalls to Avoid

• Do not initiate naltrexone during active withdrawal - this is the most common error and provides no benefit while delaying appropriate benzodiazepine therapy 1
• Do not prescribe naltrexone as monotherapy - it is only effective as part of comprehensive treatment including psychosocial support 1
• Do not use in patients with alcoholic liver disease - choose baclofen or acamprosate instead 6, 1
• Do not forget to hold oral naltrexone 2-3 days before elective procedures if opioids are expected for pain control 2

Expected Adverse Effects

• Gastrointestinal distress is common: nausea (risk ratio 1.73) and vomiting (risk ratio 1.53) compared to placebo 3
• These side effects are generally mild and improve with continued use 3
• Serious hepatotoxicity is rare at standard doses but requires monitoring 2, 5

Evidence Quality Note

The recommendation for 25 mg titration followed by 50 mg maintenance dosing comes from the American College of Gastroenterology guidelines 1, while the 3-6 month minimum duration is supported by both guideline recommendations 1 and high-quality meta-analysis data from JAMA showing number needed to treat of 11-18 for preventing return to drinking 3. The COMBINE study, a large randomized controlled trial, demonstrated that naltrexone with medical management produced better drinking outcomes than placebo 7.