What are the recommended oral and injectable naltrexone dosing regimens, contraindications, and monitoring (including liver function tests) for a patient after opioid detoxification or with alcohol use disorder?

Naltrexone Treatment for Opioid and Alcohol Use Disorders

Dosing Regimens

For alcohol use disorder, prescribe oral naltrexone 50 mg once daily, or injectable naltrexone (Vivitrol) 380 mg intramuscularly once monthly, both combined with comprehensive psychosocial treatment. 1, 2, 3

Oral Naltrexone Dosing

• Standard regimen: 50 mg once daily for alcohol use disorder 1, 2, 3
• Alternative supervised dosing: 100 mg on Mondays and Wednesdays, 150 mg on Fridays 1
• For opioid dependence: Start with 25 mg on day 1; if no withdrawal occurs, advance to 50 mg daily thereafter 2, 3
• Treatment duration: 3-6 months up to 12 months based on clinical trials 4

Injectable Naltrexone (Vivitrol)

• Dose: 380 mg intramuscularly once monthly 1, 2
• FDA-approved for both alcohol and opioid dependence 1
• Preferred when adherence is a concern due to monthly administration 1

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, 2, 3

Opioid-Free Period

• Minimum 7-10 days opioid-free for short-acting opioids 2, 3
• Up to 2 weeks may be required for patients transitioning from buprenorphine or methadone 2, 3
• Consider naloxone challenge test if occult opioid dependence is suspected 2, 3
• Do not perform challenge in patients showing clinical withdrawal signs or with opioids in urine 2, 3

Alcohol Use Disorder Initiation

• Wait 3-7 days after last alcohol consumption and only after withdrawal symptoms have completely resolved 4
• Never start during active withdrawal—naltrexone provides no benefit for withdrawal symptoms and delays appropriate benzodiazepine therapy 4
• Complete alcohol detoxification required as naltrexone is for relapse prevention, not acute detoxification 4, 5

Absolute Contraindications

Naltrexone is absolutely contraindicated in patients with acute hepatitis, decompensated cirrhosis, current opioid use, or those requiring opioid analgesics. 1, 4

Hepatic Contraindications

• Acute hepatitis (absolute contraindication) 4, 5
• Decompensated cirrhosis (absolute contraindication) 4
• Active alcoholic hepatitis (absolute contraindication) 5
• Alcoholic liver disease—not recommended due to hepatotoxicity risk 4

Opioid-Related Contraindications

• Current opioid use or dependence 1, 2, 3
• Patients requiring opioid analgesics—naltrexone blocks pain relief from opioid agonists 1
• Acute opioid withdrawal symptoms present 2, 3

Surgical Planning

• Hold oral naltrexone 2-3 days before elective procedures if opioids expected 1
• Hold injectable naltrexone 24-30 days after last injection before elective procedures 1

Liver Function Monitoring Protocol

Obtain baseline liver function tests before starting naltrexone and repeat every 3-6 months during treatment. 1, 4

Baseline Assessment

• Check transaminases (AST, ALT), alkaline phosphatase, bilirubin, and INR before initiation 4, 5
• Screen for alcoholic liver disease, cirrhosis, and acute hepatitis 4, 5

Ongoing Monitoring

• Repeat liver function tests every 3-6 months during treatment 1, 4
• Monthly monitoring recommended for patients with compensated cirrhosis 4
• Hepatotoxicity is uncommon at standard 50 mg dose but has been reported at supratherapeutic doses 1, 6, 7

Special Populations with Liver Disease

• Compensated cirrhosis: May consider naltrexone with enhanced monthly monitoring, though recent data suggest safety 4, 8, 9
• Any liver disease: Consider safer alternatives first—baclofen or acamprosate 4, 5

Alternative Medications for Patients with Liver Disease

For patients with alcoholic liver disease or cirrhosis, prescribe baclofen 10 mg three times daily or acamprosate 666 mg three times daily instead of naltrexone. 4, 5

Baclofen

• Only alcohol pharmacotherapy proven safe in cirrhotic patients in randomized trials 4, 5
• Dose: 10 mg three times daily 4
• Avoid in hepatic encephalopathy 5

Acamprosate

• Renally eliminated with no hepatotoxicity risk 4, 5
• Dose: 666 mg three times daily 4
• Initiate 3-7 days after last alcohol consumption after withdrawal resolves 4
• Reduces withdrawal effects and alcohol craving 4

Clinical Efficacy and Evidence

Naltrexone reduces relapse to heavy drinking by approximately 50% when combined with behavioral therapy, with a modest effect size of 0.15-0.2 and number needed to treat of approximately 20. 1, 6

Mechanism of Action

• Competitive antagonist at mu opioid receptors blocking euphoric effects of opioids and reducing alcohol cravings 1
• Blocks opioid receptors that mediate alcohol-induced reward, diminishing the "high" while drinking 1, 7
• Prevents impulsive opioid use by providing time to consider consequences and seek support 1

Evidence Quality

• Placebo-controlled trials demonstrated 50% reduction in relapse rates with 50 mg daily for up to 12 weeks 1
• Meta-analyses of ~4,000 patients show naltrexone effective in reducing heavy drinking but less effective for enhancing abstinence 6
• Injectable formulation shows substantial reductions in heavy drinking days 1

Mandatory Psychosocial Treatment Integration

Naltrexone must be combined with comprehensive psychosocial interventions including counseling, group therapy, and support programs—medication alone is insufficient. 1, 4, 3

Required Components

• Behavioral therapy (cognitive behavioral therapy or motivational enhancement therapy) 5
• Individual and group therapy 1
• Community-based support groups (e.g., Alcoholics Anonymous) 4, 3
• Compliance-enhancing techniques for all treatment components 3

Factors Associated with Good Outcomes

• Type, intensity, and duration of psychosocial treatment 3
• Appropriate management of comorbid conditions 3
• Good medication compliance 3

Critical Safety Warnings

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

Overdose Risk Education

• Provide opioid overdose education to all patients 1
• Consider offering naloxone to patients on naltrexone 1
• Warn about increased sensitivity to opioids after discontinuation 1

Depression and Mental Health Monitoring

• Screen for depression, anxiety, and insomnia before initiation 1, 5
• Naltrexone may cause or worsen depression 1
• Monitor closely during treatment for mental health changes 1

Renal Impairment

• Reduce dose to 25 mg daily in moderate-to-severe renal impairment 1

Common Clinical Pitfalls to Avoid

• Never start naltrexone during active alcohol withdrawal—use benzodiazepines first 4
• Never prescribe to patients currently using opioids—precipitates severe withdrawal 2, 3
• Never use in patients requiring opioid pain management—blocks analgesic effects 1
• Never skip baseline liver function testing or ongoing monitoring 1, 4
• Never prescribe naltrexone alone without psychosocial treatment—medication is only one component 1, 4, 3
• Never use in acute hepatitis or decompensated cirrhosis—absolute contraindication 4, 5
• Never fail to educate about overdose risk after discontinuation 1