Recommended Starting Dose for Naltrexone in Alcohol Use Disorder
The recommended starting dose of naltrexone for alcohol use disorder is 50 mg once daily orally, as established by FDA labeling and major clinical guidelines. 1, 2, 3
Standard Dosing Regimen
- Oral naltrexone should be initiated at 50 mg once daily for most patients with alcohol use disorder 1, 2
- This dosing was validated in placebo-controlled efficacy trials demonstrating reduction in return to drinking 1
- An alternative formulation is extended-release injectable naltrexone at 380 mg intramuscularly once monthly, which may improve adherence compared to daily oral dosing 2, 3
Alternative Initial Dosing for Opioid-Dependent Patients
- For patients with recent opioid use or concern for occult opioid dependence, start with 25 mg on day 1 1
- If no withdrawal signs occur after the 25 mg test dose, advance to 50 mg daily thereafter 1
- This lower initial dose reduces risk of precipitating severe opioid withdrawal 1
Critical Pre-Treatment Requirements
Patients must be opioid-free for a minimum of 7-10 days before starting naltrexone to avoid precipitated withdrawal 1:
- Short-acting opioids require 7-10 day washout period 1
- Patients transitioning from buprenorphine or methadone may be vulnerable to precipitated withdrawal for up to 2 weeks 1
- Consider naloxone challenge testing if occult opioid dependence is suspected 1
Hepatotoxicity Monitoring Considerations
- Naltrexone undergoes hepatic metabolism and carries theoretical hepatotoxicity concerns 2
- However, hepatotoxicity is uncommon at the standard 50 mg daily dose and occurs only at supratherapeutic doses 3, 4
- Baseline liver function tests should be obtained, with repeat testing every 3-6 months during treatment 3
- Naltrexone has not been studied in patients with alcoholic hepatitis or cirrhosis; acamprosate may be safer for patients with significant liver disease 2, 3
Efficacy and Treatment Context
- The number needed to treat to prevent return to any drinking is approximately 20 for naltrexone 2, 3
- Naltrexone must be combined with psychosocial interventions (cognitive-behavioral therapy, motivational enhancement therapy, or mutual aid societies) as monotherapy is insufficient 2, 1, 4
- Treatment compliance is critical—naltrexone shows robust effects only in compliant patients who attend treatment sessions regularly 5
Common Pitfalls to Avoid
- Do not initiate naltrexone without confirming adequate opioid-free period, as precipitated withdrawal can be severe 1
- Do not use naltrexone in patients requiring opioid analgesics; oral formulations should be held 2-3 days before elective procedures if opioids are anticipated 3
- Do not rely on naltrexone alone without implementing compliance-enhancing techniques and psychosocial support 1, 5
- The most common adverse effects at 50 mg daily are nausea and vomiting, which are generally manageable 6