naltrexone

General Information

Naltrexone is an opioid receptor antagonist used to support treatment of alcohol dependence and to block the effects of exogenous opioids in opioid dependence management (label).

It does not treat acute withdrawal. Its role is typically relapse prevention and craving reduction as part of a broader treatment plan (label/clinical).

An opioid-free period is required before initiation for opioid dependence because naltrexone can trigger precipitated withdrawal in physically dependent individuals (label).

Liver safety is a central consideration; baseline and follow-up liver testing is common, especially when alcohol-related liver disease is present (label/clinical).

The naltrexone compare view, evidence feed, and print page support review of safety and tolerability profiles.

Naltrexone can be an effective option for alcohol use disorder (AUD) and for opioid blockade in opioid use disorder (OUD), but safe use requires planning around opioid exposure, perioperative pain management, and liver monitoring. Adherence is a key practical determinant of effectiveness for oral regimens (label/clinical).

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Naltrexone is a competitive opioid receptor antagonist (μ-opioid receptor antagonism is clinically central), reducing the reinforcing effects of opioids and, in alcohol use disorder (AUD), reducing reward/craving pathways in some patients (label/clinical).

• Opioid receptor antagonism (μ-opioid receptor blockade; primary clinical effect).

Metabolism and Pharmacokinetics

• Naltrexone is well absorbed orally but undergoes significant first-pass metabolism with variable oral bioavailability (label).
• Mean elimination half-life is ~4 hours for naltrexone and ~13 hours for the major metabolite 6-β-naltrexol (label).
• Excretion is primarily renal (unchanged and conjugated metabolites), and the pharmacokinetic profile suggests enterohepatic recycling (label).

Dosing and Administration

• Alcohol dependence: 50 mg once daily was used in placebo-controlled outpatient trials for up to 12 weeks as an adjunct to psychosocial methods (label).
• Opioid dependence relapse prevention: the label describes starting with 25 mg and, if no withdrawal signs occur, continuing with 50 mg daily thereafter (label).
• Alternative supervised dosing schedules (e.g., 50 mg weekdays with 100 mg on Saturday, or 100 mg every other day) are described in labeling; higher single doses may increase hepatotoxicity risk and require careful risk–benefit consideration (label/clinical).
• The label notes no completely reliable method to confirm adequate opioid-free period; naloxone challenge testing is described as one approach when uncertainty exists (label).

Monitoring & Labs

• Liver function testing (baseline and follow-up), especially with alcohol-related liver disease (label/clinical).
• Opioid exposure screening and documentation of opioid-free verification strategy (label/clinical).
• Monitoring for nausea, dizziness, and fatigue that can affect adherence and function (clinical).
• Perioperative/acute pain planning because opioid analgesia may be ineffective while naltrexone is active (clinical).

Adverse Effects

Interactions

• Opioid-containing medications (analgesics, antidiarrheals, cough suppressants) may be ineffective while naltrexone is active and can precipitate withdrawal if opioid dependence is present (label/clinical).
• Perioperative planning is important because standard opioid-based analgesia may be ineffective; coordination across teams is common (clinical).

Other Useful Information

• Evidence syntheses support oral naltrexone (50 mg/day) as one effective option for alcohol use disorder (AUD), with benefit depending on adherence and integration with psychosocial supports (Jonas 2014/clinical).
• For opioid use disorder (OUD), oral adherence barriers are common; extended-release injectable naltrexone exists but is a distinct formulation and implementation pathway (clinical).

References

1. Naltrexone hydrochloride tablets prescribing information — DailyMed (2026)
2. Pharmacotherapy FOR Adults With Alcohol USE Disorders IN Outpatient Settings: A Systematic Review AND Meta Analysis — JAMA (2014)
3. AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)