Naltrexone (ReVia) 50 mg Tablets / Vivitrol 380 mg Extended-Release Injectable: Prescription Mu-Opioid Receptor Antagonist for Alcohol Use Disorder and Opioid Use Disorder

Reviewed by the Lucas Clinic Medical Team | Updated May 2026

Naltrexone is a potent, selective mu-opioid receptor antagonist with additional antagonist activity at kappa and delta opioid receptors. Unlike naloxone (which is used for acute opioid overdose reversal and has a very short duration of action), naltrexone is orally bioavailable, has an active metabolite (6-beta-naltrexol), and has a duration of action of approximately 24–72 hours per dose — making it suitable for daily oral administration or monthly injectable administration (Vivitrol). Naltrexone is not a scheduled controlled substance in the US — it has no abuse potential or intrinsic opioid agonist activity. No DEA waiver is required to prescribe naltrexone, distinguishing it from buprenorphine-based treatments (which were historically waiver-restricted).

Naltrexone has two distinct FDA-approved indications: alcohol use disorder (AUD) and opioid use disorder (OUD). For AUD, naltrexone reduces the euphoric and reinforcing effects of alcohol by blocking opioid pathways involved in alcohol reward, and reduces alcohol craving — leading to reduced drinking frequency, reduced drinks per drinking occasion, and higher rates of abstinence compared to placebo. For OUD, naltrexone blocks the euphoric and analgesic effects of exogenous opioids, eliminating the reinforcing value of opioid use. It does not prevent overdose if a patient takes sufficiently large doses of opioids to overwhelm receptor blockade — opioid tolerance may be greatly reduced during the opioid-free period before and during naltrexone treatment, significantly increasing overdose risk if relapse occurs at previously used doses.

What Is Naltrexone (ReVia / Vivitrol)?

For alcohol use disorder, naltrexone is one of only three FDA-approved pharmacotherapies and has the strongest evidence base. The COMBINE study (one of the largest AUD pharmacotherapy trials) found naltrexone reduces heavy drinking days and increases abstinence rates compared to placebo when combined with medical management. The Sinclair Method (TSM) — a protocol in which naltrexone is taken specifically before (not after) every drinking occasion — has been shown in European long-term studies (including COMBINE) to produce extinction of conditioned alcohol reward; advocates argue this approach has superior evidence for long-term remission compared to abstinence-only models. TSM is gaining increasing clinical recognition though it is not universally adopted in US addiction medicine practice.

A critical safety requirement: naltrexone must only be started after confirming the patient has been opioid-free for at least 7–10 days (for short-acting opioids such as heroin, oxycodone, hydrocodone) or at least 14 days (for long-acting opioids or buprenorphine/methadone). Administration of naltrexone to a patient with opioid physical dependence will precipitate acute, severe, rapid-onset opioid withdrawal — far more intense than naturally occurring withdrawal. This is not a minor adverse effect: precipitated withdrawal is an emergency and causes tremendous suffering. A naloxone challenge test can be used to confirm opioid-free status before initiating naltrexone. Liver toxicity is a risk — baseline liver function tests (LFTs) are required; naltrexone is contraindicated in acute hepatitis or hepatic failure. It should be used with caution in patients with chronic active hepatitis or significant LFT elevation.

Prescription vs. Over-the-Counter Status

Naltrexone (oral tablets and injectable) is a prescription-only medication, though it is not a controlled substance. It is not available over the counter. The requirement for opioid-free confirmation before initiation, the need for baseline liver function testing, and the monitoring requirements during treatment necessitate physician prescribing. For primary care physicians and addiction specialists, naltrexone is straightforward to prescribe for either indication without the regulatory complexity associated with buprenorphine or methadone for OUD. This accessibility makes it a preferred first-line option in primary care settings for both AUD and OUD management.

Available Strengths and Forms

ReVia (naltrexone oral tablets): 50 mg scored tablets. Standard daily dose for both AUD and OUD is 50 mg once daily. Some protocols use 3×/week dosing (100 mg Monday/Wednesday; 150 mg Friday) for OUD where daily adherence is uncertain. For AUD using the Sinclair Method, 50 mg is taken 1–2 hours before drinking — not every day.

Vivitrol (naltrexone extended-release injectable suspension): 380 mg IM injection administered once monthly by a healthcare provider into the gluteal muscle. Provides sustained naltrexone plasma levels for approximately 30 days; particularly useful for patients with adherence difficulties or those who prefer monthly appointments over daily medication management. Vivitrol is FDA-approved for both AUD and OUD. Injection site reactions (induration, pain, pruritus) are common but generally self-limiting; serious injection site reactions requiring surgical intervention are rare but reported.

Price of Naltrexone / Vivitrol

Generic naltrexone 50 mg tablets are inexpensive: approximately $30–$60 per month without insurance, and often under $20 with GoodRx at many pharmacies. Branded ReVia is rarely prescribed given generic equivalence. Vivitrol 380 mg monthly injection is significantly more expensive — the wholesale acquisition cost is approximately $1,500–$1,800 per injection (approximately $18,000–$22,000 per year). Manufacturer (Alkermes) patient assistance programmes and insurance coverage can substantially reduce out-of-pocket costs for Vivitrol. Many state Medicaid programmes cover Vivitrol for OUD. The cost-effectiveness calculation must include the substantial healthcare and societal costs avoided by successful treatment relative to the ongoing costs of untreated AUD or OUD.

Frequently Asked Questions

Will I experience withdrawal when I start naltrexone?

If you are opioid-dependent and start naltrexone before being fully opioid-free, you will experience precipitated opioid withdrawal — abrupt, severe, rapid-onset withdrawal within 30–60 minutes of taking naltrexone. This is distinct from and much more intense than naturally occurring withdrawal. To prevent this, your prescriber must confirm (through history, urine drug screen, and optionally a naloxone challenge test) that you have been opioid-free for the required period: at least 7–10 days for short-acting opioids and at least 14 days for methadone or buprenorphine. If you are starting naltrexone for alcohol use disorder only (with no opioid use), there is no withdrawal risk from naltrexone itself — common initial side effects include nausea, headache, fatigue, and insomnia, typically mild and improving within the first 1–2 weeks.

Can I still be treated for pain if I am taking naltrexone?

Naltrexone blocks opioid receptors, making standard opioid analgesics (morphine, oxycodone, hydromorphone) ineffective — opioid pain relief requires mu-opioid receptor activation, which naltrexone prevents. For elective surgery, naltrexone should be stopped at least 72 hours (3 days) before the procedure to allow sufficient opioid receptor availability for post-operative pain management. For emergency situations where opioid pain relief is unavoidable, much higher-than-standard opioid doses may be needed to overcome receptor blockade — this carries significant respiratory depression risk and should only be managed by anesthesiology specialists with careful monitoring. Non-opioid analgesia (NSAIDs, ketamine, regional anaesthesia) should be maximised for all planned procedures in naltrexone-treated patients. Patients must carry a medical alert card or equivalent disclosure documenting their naltrexone use.

What is the Sinclair Method for alcohol use disorder?

The Sinclair Method (TSM), developed by Dr. John David Sinclair, involves taking 50 mg naltrexone specifically 1–2 hours before drinking any alcohol — not as a fixed daily dose. The theoretical basis is pharmacological extinction: naltrexone blocks the opioid-mediated reward signal that reinforces alcohol consumption, and by specifically pairing naltrexone with drinking occasions, the conditioned reinforcement of alcohol is progressively extinguished over months. Finnish clinical data and reanalysis of controlled trial data suggest 78% of TSM patients achieve controlled drinking or abstinence, with ongoing benefit over years. TSM allows continued drinking during treatment (which improves adherence relative to requiring abstinence before treatment), but the overall direction of therapy is progressive reduction in drinking through extinction. TSM is an alternative to abstinence-focused naltrexone prescribing; it has a growing patient community and increasing clinician interest, though adoption is uneven across US addiction medicine practices.

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