Which antibiotics cause a disulfiram (antabuse) reaction?

Antibiotics That Cause Disulfiram Reactions

Metronidazole is the primary antibiotic that causes disulfiram-like reactions when combined with alcohol, while other nitroimidazoles like ornidazole and certain sulfonamides like trimethoprim-sulfamethoxazole can also trigger this reaction.

Primary Culprits

Metronidazole

• Clearly identified in the FDA drug label as causing disulfiram-like reactions 1
• The FDA explicitly warns: "Alcoholic beverages should not be consumed during metronidazole therapy and for at least one day afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur" 1
• The mechanism involves inhibition of aldehyde dehydrogenase, leading to acetaldehyde accumulation when alcohol is consumed

Other Nitroimidazoles

• Ornidazole has been reported to cause disulfiram-like reactions 2
• All imidazole derivatives should be considered potential triggers for this reaction

Sulfonamides

• Trimethoprim-sulfamethoxazole (cotrimoxazole) has been documented to cause disulfiram-like reactions 3

Clinical Manifestations of Disulfiram-Like Reactions

The reaction typically presents with:

• Flushing
• Sweating
• Palpitations
• Dyspnea
• Hyperventilation
• Tachycardia
• Hypotension
• Nausea and vomiting
• Abdominal discomfort
• Headache
• Drowsiness

Recent Evidence and Controversy

It's worth noting that a recent 2023 case-control study has challenged the existence of metronidazole-induced disulfiram-like reactions in acute care settings 4. This study found no significant difference in disulfiram-like effects between patients who received metronidazole with detectable ethanol levels compared to matched controls. However, this single study contradicts established clinical warnings and the FDA label.

Clinical Implications

1. Patient Education: Always warn patients taking metronidazole or other nitroimidazoles to avoid all forms of alcohol during treatment and for at least 24-48 hours afterward

2. Medication Awareness: Be alert to hidden sources of alcohol in medications:

   • A case report documents a disulfiram-like reaction in a 14-year-old patient receiving metronidazole who was also given Prednisone Intensol solution, which contains alcohol 5
   • Liquid medications, elixirs, and some oral solutions may contain alcohol as a vehicle

3. Duration of Precaution: Advise patients to avoid alcohol:

   • During the entire course of metronidazole therapy
   • For at least 24 hours (and preferably 48-72 hours) after completing therapy

4. Alternative Antibiotics: For patients with alcohol use disorder or those who cannot abstain from alcohol:

   • Consider alternative antibiotics when clinically appropriate
   • For anaerobic infections, consider clindamycin as an alternative when appropriate

High-Risk Scenarios

• Patients with alcohol use disorder
• Patients taking disulfiram (Antabuse) - metronidazole should not be given to patients who have taken disulfiram within the last two weeks 1
• Patients receiving medications with alcohol content (liquid formulations)
• Patients with impaired liver function who may have reduced ability to metabolize both the antibiotic and alcohol

Remember that disulfiram-like reactions can range from mild discomfort to potentially severe reactions with significant hemodynamic effects. The safest approach is complete alcohol avoidance when prescribing antibiotics known to cause this interaction.