Naltrexone

• Alcohol Use Disorder
• Opioid Use Disorder
• Addiction Treatment

Naltrexone is a long-acting opioid receptor antagonist used to treat alcohol use disorder and to prevent relapse to opioid use disorder after medically supervised withdrawal. Sold as oral tablets (ReVia, generic) and as a once-monthly intramuscular extended-release suspension (Vivitrol), it works by blocking the rewarding effects of alcohol and opioids without producing euphoria, dependence, or tolerance itself. Within addiction medicine, naltrexone is a foundational medication-assisted treatment option for patients who want to remain abstinent and are not actively using opioids. Used alongside counseling, mutual-help groups, and a structured recovery plan, it improves abstinence rates, reduces heavy drinking days, and lowers the risk of returning to opioid use. Understanding the strict requirement for opioid-free status before initiation, the boxed warning about hepatotoxicity, and how the medication interacts with pain management is essential for safe, effective use.

Mechanism of Action

Naltrexone competitively binds opioid receptors with greatest affinity at the mu receptor, where it produces no agonist activity. This pure antagonist action displaces or prevents the binding of exogenous opioids such as oxycodone, heroin, fentanyl, hydrocodone, or methadone, blocking their analgesic and euphoric effects. It also blocks endogenous opioids (beta-endorphin, enkephalin, dynorphin) that are released in response to alcohol consumption, drug-related cues, and stress.

In alcohol use disorder, the clinical effect is primarily a reduction in the rewarding sensation of drinking and a decrease in craving. Acute alcohol intake stimulates release of endogenous opioids in the ventral tegmental area and nucleus accumbens, which mediates much of the pleasurable response. By dampening this response, naltrexone lowers the reinforcing value of alcohol so patients can drink less, drink less heavily, and progress toward abstinence. In opioid use disorder, the effect is more direct: as long as therapeutic naltrexone levels are present, opioids cannot produce a high. This both protects against impulsive use and removes the positive reinforcement that perpetuates the disorder. Unlike methadone or buprenorphine, naltrexone has no opioid agonist activity, so it does not relieve withdrawal symptoms, does not produce physical dependence, and cannot be diverted for misuse. Because it has no agonist effect, however, patients who relapse to opioids while compliant face risk of overdose if they attempt to override the blockade with high doses; after discontinuation, opioid tolerance is reduced and overdose risk is elevated.

Clinical Use

For alcohol use disorder, the American Psychiatric Association and SAMHSA recognize naltrexone as a first-line pharmacotherapy along with acamprosate and disulfiram. Naltrexone is particularly useful for patients with strong cravings, family history of alcohol problems, those who want to reduce heavy drinking before achieving abstinence, and those whose drinking is triggered by stress and reward seeking. Acamprosate is often preferred for patients who have already achieved abstinence and want to maintain it; disulfiram requires high motivation and intact judgment because it relies on aversive effects. Patients can begin naltrexone whether or not they have stopped drinking; abstinence at the start is not required.

For opioid use disorder, the picture is different. Naltrexone is appropriate only after a patient has been opioid-free for 7 to 10 days for short-acting opioids and 10 to 14 days for long-acting opioids such as methadone or extended-release formulations. Starting naltrexone too early triggers immediate, severe precipitated withdrawal that is markedly worse than spontaneous withdrawal. For this reason, many patients with opioid use disorder choose buprenorphine or methadone instead, since these can be initiated during withdrawal rather than after it. The extended-release intramuscular formulation generally outperforms oral naltrexone for opioid use disorder because adherence is the major limitation of the oral form. Excellent SAMHSA guidance is available at samhsa.gov. Naltrexone is also used off-label in low doses for fibromyalgia and certain chronic pain conditions, although that practice falls outside its FDA-approved indications. Our internal medicine team coordinates with psychiatric and addiction medicine colleagues for patients managing co-occurring conditions such as depression or anxiety.

How to Take It

Oral naltrexone is taken as a 50 mg tablet once daily, with or without food. Some clinicians use alternative regimens (100 mg Monday, 100 mg Wednesday, 150 mg Friday) to support adherence with three weekly doses instead of seven. The extended-release intramuscular formulation, Vivitrol, is given as a 380 mg gluteal injection every four weeks, alternating sides. The injection must be administered by a health professional using the supplied diluent and needle, with proper site selection and a deep intramuscular technique to avoid soft-tissue injury.

Before the first dose of either formulation, opioid-free status must be confirmed, typically through patient history, urine drug screen, and sometimes a naloxone challenge in higher-risk situations. Patients should carry a wallet card and inform every health care provider, including dentists and emergency personnel, that they are on naltrexone. If a tablet dose is missed and remembered the same day, take it as soon as possible; if it is the next day, simply resume the schedule. For the injectable, missed appointments should be rescheduled as soon as possible. Storage for tablets is at room temperature; the injection vial requires refrigeration. The first week often produces nausea, headache, decreased appetite, and mild dysphoria. These usually subside; staying hydrated, taking the dose with food, and ensuring adequate sleep help. Injection-site reactions are common in the first few days after Vivitrol administration; severe pain, fluctuance, or signs of abscess require evaluation.

Monitoring and Follow-Up

Liver function tests are checked at baseline and periodically during therapy because dose-related hepatotoxicity has been reported, particularly at doses above the recommended range. Most clinicians repeat AST and ALT one month after starting and then every three to six months. A persistent rise of ALT or AST greater than three to five times the upper limit of normal warrants discontinuation. Baseline assessment for chronic hepatitis and other liver disease is helpful, although stable, well-compensated liver disease is not an absolute contraindication.

Psychiatric monitoring is equally important. Naltrexone has been associated with depressed mood, anhedonia, and rare suicidal ideation; patients with prior depression should be observed and have brief mood screening (PHQ-9 or similar) at follow-up visits. Adherence to oral naltrexone is the biggest predictor of effectiveness; pharmacy refill data and patient self-report help track this. For alcohol use disorder, follow drinking days per month, heavy drinking days, craving scores, and biomarkers such as gamma-glutamyl transferase, mean corpuscular volume, and carbohydrate-deficient transferrin if available. For opioid use disorder, urine toxicology screening at intervals tailored to clinical judgment helps confirm continued abstinence. Red numbers include AST or ALT above three times baseline, total bilirubin above 2 mg/dL, new jaundice, or pulmonary symptoms suggesting eosinophilic pneumonia, which has been reported rarely.

Special Populations

Elderly patients have not been extensively studied; standard doses are typically used, but baseline liver and renal function should guide monitoring. Mild to moderate hepatic impairment does not require dose adjustment, but severe hepatic impairment or acute hepatitis is a contraindication for the injectable formulation and a relative contraindication for oral therapy. In renal impairment, no formal adjustment is recommended, but caution is warranted given limited data. Pregnancy data are limited; the medication should be used during pregnancy only if benefits clearly outweigh risks, and shared decision-making is essential, particularly for women already stable on therapy. Breastfeeding is similarly individualized; small amounts pass into milk.

Pediatric safety and efficacy have not been established. A particularly important population includes patients on naltrexone who require emergency surgery or pain control. Standard opioid analgesics are blocked, sometimes for several weeks after the last injectable dose. Anesthesia teams should plan multimodal analgesia using regional blocks, NSAIDs such as ibuprofen where appropriate, acetaminophen, and adjuncts such as gabapentin or ketamine. If high-dose opioid is required despite blockade, intensive respiratory monitoring is necessary because doses needed to overcome blockade can cause life-threatening respiratory depression once the antagonist wears off.

When to Contact Your Doctor

Call the office promptly for new yellowing of the skin or eyes, dark urine, persistent right upper abdominal pain, severe fatigue, or other signs of liver problems. Severe injection-site pain, fever, drainage, or a hard lump that worsens may indicate infection or sterile abscess and warrants evaluation. New depression, suicidal thoughts, severe anhedonia, or significant mood changes should be reported. Symptoms of allergic reaction such as rash, itching, swelling of the face or throat, or breathing difficulty require emergency care. New cough, shortness of breath, or wheezing might suggest rare eosinophilic pneumonia.

Any patient who relapses to opioid use while taking naltrexone or shortly after stopping it should be considered at high risk of overdose; family members should be trained on naloxone rescue. Plans for elective surgery, dental procedures, or any need for opioid analgesics should be discussed in advance so a safe pain management plan can be coordinated. For evaluation of alcohol or opioid use disorder and consideration of naltrexone or other medication-assisted treatment, contact us or schedule a visit. Detailed dosing tables, drug interactions, and frequently asked questions are provided on this page below.