Disulfiram Drug Interactions: What to Avoid and What to Tell Your Doctor

Disulfiram is a powerful medication with a complex interaction profile. It affects multiple liver enzyme pathways — particularly CYP2C9, CYP2E1, and CYP3A4 — that metabolize a wide range of prescription drugs. Before starting disulfiram, you and your prescriber need to review every medication you take to avoid serious or even life-threatening interactions.

Here is a complete guide to disulfiram's most important drug interactions, organized by severity.

The Most Important Interaction: Alcohol

The primary interaction of disulfiram is with alcohol — this is the entire basis of how the drug works. When alcohol is consumed while taking disulfiram, the disulfiram-alcohol reaction occurs: flushing, nausea, vomiting, chest pain, difficulty breathing, and in severe cases, cardiac collapse and death.

Critically, "alcohol" includes hidden sources:

• Mouthwash and some toothpastes
• Liquid cough and cold medicines (check labels)
• Ritonavir oral solution (contains 42% alcohol — contraindicated)
• Vinegar, fermented foods, kombucha
• Cologne, aftershave, and alcohol-based skin products (can absorb transdermally)

Major Interactions (Contraindicated or Require Extreme Caution)

These drug combinations should be avoided or require immediate prescriber review:

• Metronidazole (Flagyl): Contraindicated. Combining disulfiram with metronidazole can cause acute psychosis and confusion. Do not take these two medications together under any circumstances.
• Warfarin (Coumadin, Jantoven): Major interaction. Disulfiram inhibits CYP2C9, the enzyme that metabolizes warfarin. This significantly increases warfarin levels, raising the risk of dangerous bleeding. If both must be used, your prescriber will need to reduce your warfarin dose and monitor your INR very closely.
• Phenytoin (Dilantin, Phenytek): Major interaction. Disulfiram inhibits phenytoin metabolism, causing phenytoin levels to rise. Toxicity symptoms include excessive tiredness, sudden confusion, seizures, or coma. Phenytoin levels must be monitored closely if the combination is unavoidable.
• Carbamazepine (Tegretol): Both drugs increase each other's toxicity. Avoid combination or use with extreme caution under close monitoring.
• Ritonavir oral solution: Contains 42% alcohol — contraindicated with disulfiram. Use ritonavir tablets or capsules instead.

Moderate Interactions (Monitor Closely)

These interactions require monitoring but may not require stopping one of the medications:

• Isoniazid (INH — tuberculosis treatment): Can cause CNS effects including coordination problems (ataxia) and behavioral or mental status changes. Disulfiram may need to be discontinued.
• Benzodiazepines (chlordiazepoxide, diazepam, others): Disulfiram inhibits the liver enzymes that metabolize these drugs, increasing sedation and CNS depression. Dose adjustments may be needed.
• Theophylline (asthma/COPD medication): Disulfiram inhibits theophylline metabolism, potentially causing theophylline toxicity (nausea, tremors, rapid heart rate). Monitor theophylline levels.
• Tricyclic antidepressants (amitriptyline, imipramine): Elevated TCA levels due to inhibited metabolism. Increased risk of TCA side effects including cardiac arrhythmias.
• Acetaminophen (Tylenol): Disulfiram affects CYP2E1, involved in acetaminophen metabolism. Increased risk of hepatotoxicity, especially at high acetaminophen doses. Use with caution and at minimum effective doses.
• Omeprazole (Prilosec) and other PPIs: Disulfiram can inhibit omeprazole metabolism, increasing omeprazole levels. Monitor for increased PPI effects.

What to Tell Your Doctor Before Starting Disulfiram

Before your prescriber writes a disulfiram prescription, provide a complete medication list including:

• All prescription medications (especially warfarin, phenytoin, metronidazole, antibiotics)
• All over-the-counter medications (especially liquid forms that may contain alcohol)
• All supplements and herbal products
• Your history of liver disease or cardiac conditions

For information on the general side effects of disulfiram (not just from interactions), see our companion guide on disulfiram side effects: what to expect and when to call your doctor.

If you have your prescription and are searching for a pharmacy that has disulfiram in stock, medfinder contacts nearby pharmacies to find availability and texts you the results.