Can Vivitrol (naltrexone) and Antabuse (disulfiram) be used together to treat patients with alcohol use disorder, particularly those with a history of severe or chronic alcohol use?

Combining Vivitrol and Antabuse for Alcohol Use Disorder

While there is no pharmacological contraindication to combining naltrexone (Vivitrol) and disulfiram (Antabuse), this combination should generally be avoided in patients with severe or chronic alcohol use disorder who likely have underlying liver disease, as both medications carry hepatotoxicity concerns. 1

Critical Hepatotoxicity Considerations

Both naltrexone and disulfiram are contraindicated or not recommended in patients with alcoholic liver disease (ALD):

• Disulfiram should be avoided in patients with severe ALD due to documented hepatotoxicity risk and is explicitly excluded from treatment recommendations for patients with liver disease 1, 2
• Naltrexone (including Vivitrol) has not been tested in patients with cirrhosis and carries hepatotoxicity concerns, particularly at higher doses, making its use in ALD patients not recommended 1
• Naltrexone requires baseline liver function tests and monitoring every 3-6 months due to potential hepatic injury 1

Evidence for Combination Therapy

The limited research on combining these medications does not demonstrate superiority over monotherapy:

• A 2005 study in dually-diagnosed patients (psychiatric disorders plus alcohol dependence) found that combining disulfiram and naltrexone provided no advantage over either medication alone 3
• Both active medications showed modest benefits over placebo in consecutive weeks of abstinence and reduced craving, but the combination did not enhance these effects 3
• The study population did not include patients with severe liver disease, limiting generalizability to chronic alcohol users 3

Recommended Approach Based on Liver Function

For patients WITHOUT significant liver disease:

• Either naltrexone (Vivitrol 380 mg monthly IM) or disulfiram (250 mg daily) can be used as monotherapy 1
• Combination therapy offers no proven additional benefit and doubles hepatotoxicity monitoring requirements 3
• Acamprosate (666 mg three times daily) is the safest alternative as it has no hepatic metabolism and no reported hepatotoxicity 1

For patients WITH alcoholic liver disease or cirrhosis:

• Baclofen (30-60 mg daily) is the only medication specifically studied and proven safe/effective in patients with cirrhosis, including decompensated disease 1, 2
• Neither disulfiram nor naltrexone should be used 1, 2
• Acamprosate is a reasonable alternative given its renal excretion, though not studied in cirrhotic patients 1

Critical Pitfalls to Avoid

• Do not assume chronic/severe alcohol users have normal liver function - patients with a history of severe alcohol use disorder should be screened for liver disease before initiating either medication 1
• Do not combine medications without clear evidence of superiority - polypharmacy increases adverse effects without proven benefit 3
• Monitor liver enzymes closely if naltrexone is used in patients without known liver disease, as hepatotoxicity can develop 1

Practical Algorithm

1. Assess liver function (AST, ALT, bilirubin, INR, clinical signs of cirrhosis) in all patients with severe/chronic alcohol use 1
2. If cirrhosis or severe ALD present: Use baclofen as first-line pharmacotherapy 1, 2
3. If normal liver function: Choose naltrexone OR disulfiram as monotherapy based on patient preference and adherence likelihood 1, 3
4. If neither medication effective alone: Consider switching to acamprosate or adding behavioral interventions rather than combining hepatotoxic agents 1, 3

1, 2, 3