Can a patient with alcohol use disorder take Antabuse (disulfiram) and naltrexone simultaneously?

Can Disulfiram and Naltrexone Be Used Together?

Yes, a patient can technically take both disulfiram (Antabuse) and naltrexone simultaneously, but this combination is not ordinarily recommended due to the risk of additive hepatotoxicity, and there is no evidence that combining them provides additional benefit over either medication alone. 1

Key Safety Concerns

Hepatotoxicity Risk

• Both disulfiram and naltrexone undergo hepatic metabolism and can cause liver damage, making their concomitant use potentially problematic 2
• The FDA drug label explicitly states: "The safety and efficacy of concomitant use of naltrexone hydrochloride and disulfiram is unknown, and the concomitant use of two potentially hepatotoxic medications is not ordinarily recommended unless the probable benefits outweigh the known risks" 1
• Disulfiram is contraindicated in patients with alcoholic liver disease according to the American Association for the Study of Liver Diseases 2, 3

Clinical Evidence Shows No Advantage

• A randomized controlled trial in 254 patients with alcohol dependence and comorbid psychiatric disorders found no advantage of combining disulfiram and naltrexone over either medication alone 4
• Both medications reduced craving and alcohol consumption when used individually, but the combination did not improve outcomes 4

Clinical Decision Algorithm

For Patients WITHOUT Liver Disease:

• Choose ONE first-line medication, not both:
  • Naltrexone 50 mg daily (number needed to treat = 20) 2, 5
  • OR Acamprosate 666 mg three times daily (number needed to treat = 12) 2, 5
  • Disulfiram can be considered as an alternative if patient preference or clinical factors favor it 6

For Patients WITH Advanced Liver Disease or Cirrhosis:

• Baclofen 30-60 mg/day (10 mg three times daily) is the only proven safe and effective option 2, 5, 7
• Naltrexone is contraindicated in severe liver disease 8
• Disulfiram is contraindicated in alcoholic liver disease 2, 3
• Acamprosate is safe (no hepatic metabolism) but has not been studied in this population 2, 8

Critical Pitfalls to Avoid

• Never combine disulfiram and naltrexone routinely - the hepatotoxicity risk outweighs any theoretical benefit, and clinical trials show no advantage 1, 4
• Always assess liver function before prescribing either medication - check AST, bilirubin, and consider transient elastography 8
• If combination therapy is considered in exceptional circumstances, intensive liver function monitoring is mandatory, though this approach lacks evidence support 1
• Both medications require combination with psychosocial interventions for optimal efficacy 5, 6

When Combination Might Be Considered (Rare)

If a clinician determines that probable benefits outweigh known risks in a specific patient without liver disease, the combination would require:

• Baseline and frequent liver function test monitoring 1
• Clear documentation of why monotherapy is insufficient 1
• Patient education about hepatotoxicity warning signs 1
• However, evidence does not support this approach as standard practice 4