Which medications can cause a disulfiram reaction?

Medications That Can Cause Disulfiram-Like Reactions

Multiple medication classes can cause disulfiram-like reactions when combined with alcohol, most notably certain cephalosporins with methylthiotetrazole side chains, nitroimidazole antibiotics (metronidazole and ornidazole), and azole antifungals (ketoconazole). 1, 2, 3

Cephalosporin Antibiotics

Cephalosporins containing a methylthiotetrazole (MTT) side chain are the primary culprits:

• Cefotetan is explicitly documented to cause disulfiram-like reactions characterized by flushing, sweating, headache, and tachycardia when alcohol is consumed within 72 hours of administration 2
• Cefoperazone is well-established as causing disulfiram-like reactions 4
• Cefmetazole has been reported to cause disulfiram-like reactions, with documented cases of skin flushing and chest discomfort occurring 30 minutes after alcohol consumption 5
• Cefmenoxime has been reported to cause disulfiram-like reactions in patients receiving alcohol-containing medications 6

Clinical Significance of Cephalosporin Reactions

• Fatal outcomes have been documented, with 5 of 78 patients (6.41%) in one retrospective review developing severe reactions that could not be successfully rescued 4
• Patients should avoid alcohol for at least 72 hours after cefotetan administration 2
• The reaction severity does not differ significantly whether alcohol is consumed before or after antibiotic administration 4

Nitroimidazole Antibiotics

Metronidazole and related compounds are well-documented causes:

• Metronidazole causes abdominal cramps, nausea, vomiting, headaches, and flushing when combined with alcohol 3
• Patients must avoid alcoholic beverages during metronidazole therapy and for at least one day afterward 3
• Ornidazole has been reported to cause disulfiram-like reactions, and caution is advised with all imidazole derivatives 7

Critical Drug Interactions

• Psychotic reactions have been reported in alcoholic patients using metronidazole and disulfiram concurrently 3
• Metronidazole should not be given to patients who have taken disulfiram within the last two weeks 3

Azole Antifungals

• Ketoconazole and other azole antifungals can cause disulfiram-like reactions 1

Other Medications

Additional drug classes with documented disulfiram-like potential:

• Isoniazid may increase toxicity when combined with disulfiram, though this interaction has not been well studied 8
• Sulfonylureas (oral hypoglycemic agents) have been implicated in causing disulfiram-like reactions 6
• 5-nitroimidazoles as a class can cause these reactions 6
• Nitrofurans have been associated with disulfiram-like reactions 6

Mechanism and Clinical Presentation

The reaction results from inhibition of aldehyde dehydrogenase, leading to acetaldehyde accumulation 7. Symptoms typically include:

• Flushing and skin redness
• Sweating
• Headache
• Tachycardia
• Nausea and vomiting
• Chest discomfort
• In severe cases: cardiovascular compromise 1, 2

Critical Clinical Pitfalls

Avoid these common errors:

• Failing to warn patients about hidden alcohol sources including mouthwashes and food preparations with cooking alcohol 1
• Not documenting the reaction in the medical record to prevent future occurrences 1
• Prescribing cephalosporins with MTT side chains to known alcoholics without explicit warnings 4
• Underestimating reaction severity—fatal outcomes are possible and require monitoring vital signs until symptoms resolve 1, 4

Special Population: Pregnancy

• Disulfiram should be avoided in pregnancy for women with alcohol use disorder 8
• Alternative medications such as naltrexone or acamprosate should be considered with careful risk-benefit assessment 8