Are there any antibiotics, aside from metronidazole, that can cause a disulfiram-like reaction when combined with alcohol?

Antibiotics That Cause Disulfiram-Like Reactions Beyond Metronidazole

Yes, several other antibiotics can cause disulfiram-like reactions with alcohol, most notably certain cephalosporins containing a methylthiotetrazole (MTT) side chain, other nitroimidazoles beyond metronidazole, and azole antifungals like ketoconazole. 1, 2

Cephalosporins with Methylthiotetrazole Side Chains

The most clinically significant non-metronidazole antibiotics causing disulfiram-like reactions are specific cephalosporins:

• Cefotetan is explicitly documented in FDA labeling to cause disulfiram-like reactions characterized by flushing, sweating, headache, and tachycardia when alcohol is consumed within 72 hours of administration 3
• Cefamandole, cefoperazone, cefmetazole, moxalactam, cefonicid, cefmenoxime, cefotiam, and ceforanide all contain the N-methyltetrazolethiol substituent that directly correlates with the ability to induce disulfiram-like reactions 4
• The reaction mechanism involves the MTT side chain at the 3-position of the cephalosporin structure, which inhibits aldehyde dehydrogenase similarly to disulfiram itself 4, 5

Clinical severity ranges from mild flushing to fatal cardiovascular collapse, with a retrospective review documenting 5 deaths among 78 cases (6.41% mortality) of cephalosporin-induced disulfiram-like reactions 6

Nitroimidazole Antibiotics

All nitroimidazole derivatives carry risk:

• Ornidazole has documented case reports of disulfiram-like reactions, despite being less commonly recognized than metronidazole 7
• The entire nitroimidazole class (metronidazole, ornidazole, tinidazole) should be considered capable of this interaction, as acknowledged by multiple medical societies 1

Important caveat: Recent evidence questions the strength of the metronidazole-alcohol interaction, with some studies finding no convincing evidence of clinically relevant reactions 8. However, given documented cases with other nitroimidazoles and the potential severity, caution remains warranted 7

Azole Antifungals

• Ketoconazole and other azole antifungals can cause disulfiram-like reactions, as reported by the CDC and American College of Clinical Pharmacy 1, 2

Critical Timing Considerations

Patients must avoid alcohol during treatment AND for at least 72 hours after the last antibiotic dose 3:

• For cefotetan specifically, the FDA mandates warning patients about alcohol ingestion within 72 hours post-administration 3
• For metronidazole, avoid alcohol during treatment and for at least one day afterward 1
• The timing depends on the drug's half-life and the persistence of aldehyde dehydrogenase inhibition 1

Management Priorities

When disulfiram-like reaction occurs:

• Immediately discontinue alcohol consumption 1
• Provide supportive care based on symptoms: IV fluids for hypotension, antiemetics for nausea/vomiting, oxygen for respiratory distress 1
• Monitor vital signs until complete symptom resolution, as severity can progress to cardiovascular compromise 1
• Document the reaction prominently in the medical record to prevent future occurrences 1

Hidden Alcohol Sources to Avoid

Warn patients about non-beverage alcohol sources 1:

• Alcohol-containing mouthwashes
• Liquid medications with alcohol vehicles (like alcohol-containing acetaminophen elixir, which triggered reactions in documented cases) 5
• Food preparations with cooking alcohol

Clinical Decision-Making

If a patient cannot guarantee alcohol abstinence, choose alternative antibiotics without this interaction 1. For infections requiring cephalosporins, select agents without the MTT side chain (e.g., ceftriaxone, cefazolin, cephalexin) rather than cefotetan, cefamandole, or cefoperazone 9, 4.