What is the recommended naltrexone dosage and treatment schedule for an adult with alcohol use disorder after detoxification, including duration, monitoring, and safety precautions?

Naltrexone Dosing for Alcohol Use Disorder

For alcohol use disorder after detoxification, 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, 3

Critical Timing: Naltrexone is NOT for Withdrawal

Naltrexone must NEVER be started during active alcohol withdrawal—it provides zero benefit for withdrawal symptoms and delays appropriate benzodiazepine therapy. 1

• Benzodiazepines are the gold standard for managing alcohol withdrawal syndrome, reducing withdrawal symptoms and preventing seizures and delirium tremens 1
• Long-acting benzodiazepines (diazepam, chlordiazepoxide) provide superior protection against seizures and delirium 1
• Initiate naltrexone only 3-7 days after the last alcohol consumption and only after withdrawal symptoms have completely resolved 1

Standard Dosing Protocol

Oral Naltrexone

• Days 1-3: 25 mg once daily 1, 3
• Day 4 onward: 50 mg once daily 1, 2, 3
• Duration: 3-6 months, with consideration for extension up to 12 months 1, 2
• The 50 mg daily dose was validated in placebo-controlled trials demonstrating efficacy for up to 12 weeks 3

Injectable Extended-Release Naltrexone (Vivitrol)

• 380 mg intramuscularly once monthly 1, 4, 2
• May improve adherence compared to daily oral dosing 2
• Particularly useful for patients with adherence concerns 4

Mechanism and Expected Efficacy

• Naltrexone functions as a competitive mu-opioid receptor antagonist, blocking the euphoric effects of alcohol and reducing cravings 4, 2
• Number needed to treat is approximately 20 to prevent return to any drinking 1, 2
• Effect size ranges from 0.15-0.2, which is modest but clinically meaningful 1, 2
• Clinical trials show reduction in relapse rates from 54-60% to 23-31% when combined with psychosocial treatment 1

Mandatory Safety Monitoring

Hepatotoxicity Screening

Obtain liver function tests at baseline and every 3-6 months due to potential hepatotoxicity. 1, 4, 2

Contraindications - DO NOT USE naltrexone in:

• Acute hepatitis or decompensated cirrhosis 1, 4
• Active alcohol withdrawal 1
• Patients requiring opioid medications for pain 4, 2
• Patients who have used opioids (including tramadol) within 7-10 days 3

Special Populations Requiring Alternative Medications

• Patients with alcoholic liver disease: Consider baclofen (the only alcohol pharmacotherapy proven safe in cirrhotic patients) or acamprosate instead 1
• Patients with compensated cirrhosis may be considered for naltrexone with enhanced monitoring on a case-by-case basis 1
• Patients with moderate-to-severe renal impairment should have dose reduced to 25 mg daily 4

Essential Treatment Context

Naltrexone is only effective as part of comprehensive treatment including psychosocial support, counseling, and mutual help groups like Alcoholics Anonymous. 1, 4

• Medication alone is insufficient 4
• Factors associated with good outcomes include: type, intensity, and duration of treatment; appropriate management of comorbid conditions; use of community-based support groups; and good medication compliance 3
• Implement compliance-enhancing techniques for all treatment components 3

Pre-Treatment Requirements

Ensure Opioid-Free Status

• Minimum 7-10 day opioid-free interval for patients previously dependent on short-acting opioids 3
• Patients transitioning from buprenorphine or methadone may be vulnerable to precipitated withdrawal for up to 2 weeks 3
• Consider naloxone challenge test if any question of occult opioid dependence exists 3

Screen for Contraindications

• Screen for depression, anxiety, and insomnia before initiation, as naltrexone may cause or worsen depression 4
• Verify no acute hepatitis or liver failure 1
• Confirm patient is not pregnant (naltrexone is not recommended during pregnancy) 4

Common Pitfalls to Avoid

• Never start naltrexone during active withdrawal—this is the most critical error 1
• Do not prescribe to patients with alcoholic liver disease without considering safer alternatives like baclofen or acamprosate 1
• Do not fail to obtain baseline liver function tests 1, 4
• Do not prescribe without ensuring comprehensive psychosocial treatment is in place 1, 4
• Warn patients who discontinue naltrexone about increased risk of opioid overdose due to decreased tolerance if they return to opioid use 4

Surgical Considerations

• Hold oral naltrexone for 2-3 days prior to elective procedures if opioids are expected 4, 2
• Hold extended-release naltrexone for 24-30 days after last injection before elective procedures 4