Guidelines for Prescribing Naltrexone for Alcohol and Opioid Dependence
Naltrexone should be prescribed as an opioid antagonist at 50 mg once daily for alcohol dependence and opioid dependence, with the critical requirement that patients must be completely opioid-free for 7-10 days before initiation to prevent potentially severe precipitated withdrawal. 1
Mechanism of Action and Formulations
Naltrexone is a competitive opioid receptor antagonist that:
- Blocks mu (highest affinity), kappa, and delta opioid receptors 2
- Prevents the euphoric effects of narcotics and alcohol 2
- May reset the reward pathway through an opponent process mechanism 2
Available formulations:
- Oral tablets (50 mg daily)
- Alternative oral dosing: 100 mg on Mondays/Wednesdays, 150 mg on Fridays 2
- Injectable extended-release (Vivitrol): 380 mg monthly injection 2
Prescribing for Alcohol Dependence
Dosing and Administration
- Standard dose: 50 mg once daily 1
- Duration: FDA-approved for up to 12 weeks, though longer treatment may be appropriate 1
- Efficacy demonstrated only as part of a comprehensive treatment program 1
Patient Selection
- Ideal candidates: Patients with alcohol dependence who:
Monitoring
- Baseline liver function tests
- Follow-up liver function tests every 3-6 months 2
- Monitor for depression or suicidal ideation 1
Prescribing for Opioid Dependence
Critical Pre-Treatment Requirements
- Patients MUST be completely opioid-free before starting naltrexone 1
- Required opioid-free period:
- Minimum 7-10 days for short-acting opioids
- Up to 2 weeks when transitioning from buprenorphine or methadone 1
Naloxone Challenge Test
- Consider performing if uncertain about opioid-free status
- Do NOT perform if patient shows signs of opioid withdrawal or has opioids in urine
- Administration options:
- Intravenous: 0.2 mg naloxone, observe 30 seconds; if no withdrawal, give 0.6 mg and observe 20 minutes
- Subcutaneous: 0.8 mg naloxone, observe 20 minutes 1
Dosing for Opioid Dependence
- Initial dose: 25 mg
- Maintenance dose: 50 mg once daily if no withdrawal occurs 1
- For extended-release injectable: 380 mg monthly 2
Perioperative Management
Oral Naltrexone
- Hold for 2-3 days prior to elective procedures if opioids are expected to be used perioperatively 2
Extended-Release Naltrexone
- Hold for 24-30 days after the last injection before elective procedures if opioids are expected 2
Contraindications and Precautions
Absolute Contraindications
- Current opioid use or dependence without adequate opioid-free period
- Acute opioid withdrawal
- Positive naloxone challenge test
- Need for opioid analgesia 2, 1
Relative Contraindications
- Severe hepatic impairment
- Concurrent use with other opioid antagonists 1
Major Risks
Precipitated opioid withdrawal:
- Can be severe enough to require hospitalization
- Symptoms appear within 5 minutes of ingestion and last up to 48 hours
- Can include mental status changes, severe fluid losses requiring IV fluids 1
Hepatotoxicity:
- Rare at recommended doses
- Monitor liver function tests at baseline and periodically 1
Depression and suicidality:
- Monitor for development of depression or suicidal thinking 1
Reduced opioid efficacy:
- Blocks effects of opioid analgesics
- Risk of overdose if patients attempt to overcome blockade 1
Special Considerations
Naltrexone-bupropion combination for obesity: Contains 8 mg naltrexone and should be discontinued before procedures requiring opiates 2
Patient education: Warn patients about:
- Risk of opioid overdose if attempting to overcome blockade
- Need to inform all healthcare providers about naltrexone use
- Risk of hepatic injury and when to seek medical attention 1
Efficacy expectations: Most effective in motivated populations (e.g., healthcare professionals) for opioid dependence 2
Treatment success factors: Compliance-enhancing techniques, intensity of treatment, management of comorbidities, and community-based support groups 1