From the FDA Drug Label
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.
Naltrexone and Antabuse (disulfiram) should not be used together unless the probable benefits outweigh the known risks, due to the potential for increased risk of liver injury. 1
From the Research
Naltrexone and disulfiram (Antabuse) can be used together in the treatment of alcohol use disorder, but with caution due to potential liver toxicity, as evidenced by a recent study 2 that highlighted the risk of drug-induced liver injury associated with disulfiram. This combination therapy approach targets alcohol dependence through different mechanisms. Naltrexone works by blocking opioid receptors, reducing the pleasurable effects of alcohol and decreasing cravings, while disulfiram creates an unpleasant reaction when alcohol is consumed by inhibiting the enzyme aldehyde dehydrogenase. The standard dosing for naltrexone is typically 50 mg once daily, while disulfiram is usually prescribed at 250-500 mg daily. When using these medications together, patients should be monitored closely for side effects, particularly liver function, as both medications can potentially cause hepatotoxicity. It's essential to note that disulfiram requires complete abstinence from alcohol, as even small amounts can trigger severe reactions, including flushing, nausea, vomiting, and headaches. Before starting this combination, patients should have baseline liver function tests and be informed about potential side effects. This dual approach may be particularly beneficial for patients who have not responded adequately to single-medication therapy, as it addresses both the reward pathway and creates a deterrent to drinking, with recent evidence supporting the efficacy of naltrexone in reducing alcohol consumption 3. Key considerations for this combination include:
- Monitoring liver function closely due to the potential for hepatotoxicity
- Ensuring patients understand the importance of complete abstinence from alcohol while on disulfiram
- Baseline liver function tests before initiating therapy
- Informing patients about potential side effects, including severe reactions to alcohol consumption while on disulfiram.