When is Naltrexone (Revia) indicated for the treatment of Alcohol Use Disorder (AUD)?

From the Guidelines

Naltrexone (Revia) should be used for treating alcohol use disorder in patients who have stopped drinking and want to maintain abstinence or reduce heavy drinking, but not in patients with acute hepatitis, liver failure, or those taking opioid medications, due to the risk of hepatotoxicity and precipitation of withdrawal in opioid-dependent individuals. The standard oral dose is 50 mg once daily, though some patients may start at 25 mg to minimize side effects, as indicated in the 2013 study 1. Treatment typically continues for at least 3-6 months, but can be maintained longer if beneficial. Naltrexone works best when combined with counseling or behavioral therapy. Before starting treatment, patients should be abstinent from alcohol for at least 3-4 days and should undergo liver function tests, as naltrexone can cause hepatotoxicity in high doses.

According to the 2020 study 1, naltrexone is not recommended for use in patients with alcoholic liver disease (ALD) due to hepatotoxicity concerns. The study also notes that naltrexone has not been studied in patients with ALD, and its use in this population is not well established. However, for patients without ALD, naltrexone can be an effective treatment option for alcohol use disorder. Common side effects include nausea, headache, dizziness, and fatigue, which often improve with time. Naltrexone works by blocking opioid receptors in the brain, reducing the pleasurable effects of alcohol and decreasing cravings. This helps patients maintain motivation for abstinence by diminishing the reward associated with drinking. For patients who struggle with daily pill adherence, a long-acting injectable form (Vivitrol, 380 mg monthly) is available as an alternative.

Some key considerations when using naltrexone for alcohol use disorder include:

• Monitoring liver function tests to minimize the risk of hepatotoxicity
• Avoiding use in patients with acute hepatitis, liver failure, or those taking opioid medications
• Combining naltrexone with counseling or behavioral therapy for optimal results
• Starting treatment with a lower dose (25 mg) to minimize side effects and gradually increasing to 50 mg as needed
• Considering alternative treatment options, such as acamprosate or baclofen, for patients with ALD or other contraindications to naltrexone.

From the FDA Drug Label

Naltrexone hydrochloride tablets USP 50 mg is indicated in the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids. To reduce the risk of precipitated withdrawal in patients dependent on opioids, or exacerbation of a preexisting subclinical withdrawal syndrome, opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free (including tramadol) before starting naltrexone hydrochloride treatment A dose of 50 mg once daily is recommended for most patients The placebo-controlled studies that demonstrated the efficacy of naltrexone hydrochloride as an adjunctive treatment of alcoholism used a dose regimen of naltrexone hydrochloride 50 mg once daily for up to 12 weeks.

When to Use Naltrexone for Treating Alcohol Use Disorder:

• Naltrexone should be used as part of a comprehensive plan of management for alcohol dependence.
• Patients should be opioid-free for at least 7-10 days before starting naltrexone treatment.
• A dose of 50 mg once daily is recommended for most patients.
• Naltrexone should be considered as only one of many factors determining the success of treatment of alcoholism.
• Factors associated with a good outcome include the type, intensity, and duration of treatment; appropriate management of comorbid conditions; use of community-based support groups; and good medication compliance.
• Treatment should be initiated under the guidance of a healthcare provider, with careful monitoring for signs of opioid withdrawal and other potential side effects 2, 2, 2.

From the Research

Naltrexone (Revia) for Treating Alcohol Use Disorder

• Naltrexone is increasingly being prescribed in American patients with mild and severe alcohol-related liver disease, with similar tolerability and efficacy to acamprosate and disulfiram 3.
• The duration of use was longest with naltrexone compared to acamprosate and disulfiram, with a mean duration of 360 days 3.
• A meta-analysis of 16 randomized controlled trials found that naltrexone was 27% better than placebo in supporting continuous abstinence, with a relative risk of 1.27 (95% CI: 1.06-1.52) 4.
• Naltrexone therapy has been shown to be effective in reducing drinking outcomes, including time to first heavy drinking day and average weekly alcohol consumption 5.
• A systematic review of 11 studies found that injectable naltrexone therapy produced positive AUD treatment outcomes, including reduced mean time to first drinking day and/or heavy drinking day, and increased abstinence 6.

Clinical Use of Naltrexone

• Naltrexone is one of three medications approved by the US Food and Drug Administration (FDA) for the treatment of alcohol use disorder, along with disulfiram and acamprosate 7.
• Oral and long-acting injectable naltrexone are available, with the injectable form showing promise for addressing AUD when used in combination with psychosocial therapy 6.
• Current evidence does not support the use of pharmacogenetic testing for treatment individualization, and less than 9% of patients who undergo any form of alcohol use disorder treatment receive pharmacotherapies 7.