What is the maximum recommended dose of naltrexone (oral and extended‑release injectable) for an adult with normal hepatic function?

Maximum Dose of Naltrexone

For oral naltrexone in adults with normal hepatic function, the standard maximum dose is 50 mg daily, though doses up to 300 mg daily have been studied and used safely in specialized settings for extended periods without significant hepatotoxicity. 1, 2, 3

Oral Naltrexone Dosing

Standard Maximum Dose

• The typical maximum dose is 50 mg once daily for alcohol dependence and opioid use disorder 1, 4, 5
• This represents the FDA-approved dose for most indications 4, 6

Higher Doses in Specialized Settings

• Doses up to 300 mg daily have been safely administered for periods of 10-36 months in clinical studies without significant changes in liver function as measured by transaminase levels 2
• High-dose regimens of 100-200 mg twice daily (200-400 mg total daily) have been studied in eating disorders without adverse liver function changes 3
• These higher doses should only be used in specialized clinic settings with appropriate monitoring 1

Dose Adjustments for Hepatic Impairment

• In patients with moderate to severe hepatic impairment, the total daily dose should not exceed 1 tablet (8 mg naltrexone) when used in combination formulations 1
• Naltrexone is contraindicated in patients with alcoholic liver disease due to hepatotoxicity risk 4, 7

Extended-Release Injectable Naltrexone

Standard Dose

• The maximum dose is 380 mg intramuscularly once monthly 4, 8
• This formulation has demonstrated no hepatotoxicity in actively drinking alcohol-dependent patients over 6 months 8

Safety Profile

• Extended-release naltrexone at 380 mg monthly showed no significant differences in liver chemistry tests compared to placebo, even in patients drinking heavily throughout treatment 8
• Gamma-glutamyltransferase levels were actually lower in the 380 mg group compared to placebo at multiple time points 8

Critical Dosing Considerations

Titration for Oral Naltrexone

• Start at 12.5 mg daily and titrate slowly to avoid opiate withdrawal-like symptoms 1
• Some patients require an intravenous induction stage before transitioning to oral therapy 1
• The slow titration is essential as many patients experience ongoing opiate withdrawal-like reactions or reduced pain threshold 1

Monitoring Requirements

• Follow-up liver chemistry tests should be performed every 3-6 months during naltrexone treatment 4
• This is particularly important given that hepatotoxicity has been reported with oral naltrexone, though it has not emerged as a clinical problem at the standard 50 mg dose 6

Common Pitfalls to Avoid

• Never use naltrexone in patients with alcoholic liver disease or significant hepatic impairment - this is an absolute contraindication 4, 7
• Do not initiate naltrexone during active alcohol withdrawal 4
• Avoid in patients requiring short-term or long-term opioid therapy, as naltrexone will reduce analgesic efficacy or precipitate withdrawal 1
• Discontinue before procedures requiring opioid analgesia (e.g., endoscopies using fentanyl) 1
• Do not exceed 50 mg daily in routine clinical practice without specialized monitoring and clear clinical justification 1, 2, 3