What are the interactions and clinical considerations between Disulfiram (Antabuse) and Metronidazole?

From the Guidelines

Antabuse (disulfiram) and metronidazole should not be used together due to the risk of serious adverse reactions, and patients taking disulfiram should avoid metronidazole completely, with a recommended waiting period of at least 14 days after stopping disulfiram before starting metronidazole. This combination can cause a disulfiram-like reaction characterized by flushing, headache, nausea, vomiting, chest pain, and hypotension, which can be severe and potentially dangerous, as metronidazole can cause gastrointestinal and other side effects, and patients should be advised to consume it in divided doses with food and to avoid alcohol for the therapeutic duration due to a disulfuram-like reaction 1. Both medications inhibit aldehyde dehydrogenase, the enzyme that metabolizes alcohol, and when used together, they can have additive effects that intensify these reactions.

Key Considerations

• The risk of disulfiram-like reactions with metronidazole is significant, and alternative antibiotics should be considered when possible 1.
• If metronidazole must be used, the disulfiram should be discontinued with adequate washout time, and healthcare providers should always check a patient's medication list for disulfiram before prescribing metronidazole to avoid this potentially dangerous interaction.
• Higher doses of metronidazole, at least in the 1.5–2 g/day range, are also associated with significantly improved eradication rates, but might be poorly tolerated due to gastrointestinal and other side effects 1.

Clinical Implications

• Patients requiring treatment with metronidazole who are currently on disulfiram should be closely monitored for signs of disulfiram-like reactions, and alternative treatment options should be considered.
• The use of metronidazole in patients taking disulfiram should be avoided whenever possible, and healthcare providers should be aware of the potential risks and take steps to minimize them.
• The study by 1 provides the most recent and highest quality evidence on the use of metronidazole and its potential interactions with disulfiram, and its findings should be taken into consideration when making clinical decisions.

From the FDA Drug Label

Patients who are receiving or have recently received metronidazole, paraldehyde, alcohol, or alcohol-containing preparations, e.g., cough syrups, tonics and the like, should not be given disulfiram. Metronidazole should not be given to patients who have taken disulfiram within the last two weeks Psychotic reactions have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently.

The interaction between Antabuse (disulfiram) and metronidazole is a significant concern.

• Contraindication: Disulfiram is contraindicated in patients who are receiving or have recently received metronidazole.
• Clinical Considerations: Metronidazole should not be given to patients who have taken disulfiram within the last two weeks.
• Adverse Reactions: Psychotic reactions have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently 2 3.

From the Research

Antabuse and Metronidazole Interactions

• The interaction between Antabuse (disulfiram) and metronidazole has been reported in several studies, with some cases suggesting a disulfiram-like reaction 4, 5.
• However, other studies have found no significant evidence of a disulfiram-like reaction when metronidazole is used in patients with recent ethanol use 6.
• A case-control study found no significant difference in disulfiram-like effects between patients who received metronidazole and a control group matched for age, sex, and ethanol concentration 6.

Clinical Considerations

• Disulfiram-induced encephalopathy is a rare complication that can occur in adults, and its exact mechanism remains unclear 7.
• Symptoms of disulfiram-induced encephalopathy include symmetric sensory and motor neuropathy, confusion, catatonia, parkinsonism, ataxia, choreoathetosis, seizures, and encephalopathy 7.
• A brain imaging test should be performed in patients suspected of disulfiram-induced encephalopathy, as a characteristic involvement of both nuclei pallidus has been described 7.
• Healthcare professionals should be aware of the potential interaction between metronidazole and alcohol-containing medications, which can cause a disulfiram-like reaction 5.

Mechanism of Action

• The underlying mechanism of a disulfiram-like reaction is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the hepatic aldehyde dehydrogenases 8.
• However, metronidazole does not inhibit hepatic aldehyde dehydrogenase nor increase blood acetaldehyde, suggesting that it does not produce a typical disulfiram-like reaction 8.
• All tested agents, including metronidazole, have been found to enhance brain serotonin, which could contribute to ethanol intolerance 8.