Drug Interaction Report

Disulfiram and Methadone: Interaction Details

A pharmacist-reviewed analysis of the Disulfiram and Methadone interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Methadone

Diskets Dolophine Methadose
+

Disulfiram

Antabuse Antabuse®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
How we grade severity & evidence

Severity levels

  • Contraindicated: These should generally not be used together.
  • Major: Potentially serious — often needs a change or close monitoring.
  • Moderate: Can be significant — usually manageable with monitoring.
  • Minor: Usually limited clinical impact.

Evidence grades

  • Established: Well documented — supported by controlled studies or strong clinical data.
  • Probable: Good supporting evidence, though not definitively proven.
  • Suspected: Some evidence suggests this interaction, but it is not well established.
  • Possible: Limited or conflicting evidence; the interaction may occur.
  • Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 45 documented Disulfiram interactions, 25 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

Increased methadone exposure and an increased risk of opioid adverse effects

Interaction Deep Dive

Concomitant use of methadone (a CYP2B6 substrate) and a CYP2B6 inhibitor may increase the plasma concentrations of methadone, prolong opioid adverse reactions, and may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dosage of methadone is achieved. Consider dosage reduction of methadone when using concomitant CYP2B6 inhibitor in methadone-treated patients, and monitor patients closely at frequent intervals for signs and symptoms of respiratory depression and sedation. When discontinuing a CYP2B6 inhibitor, monitor patients for signs or symptoms of opioid withdrawal and consider increasing the methadone dosage as needed1234.

Why it happens (mechanism)

Inhibition of CYP2B6-mediated metabolism of methadone

Common questions

Can I take Disulfiram and Methadone together?

Increased methadone exposure and an increased risk of opioid adverse effects Always confirm with your pharmacist or prescriber before making any change.

How serious is the Disulfiram and Methadone interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

From our Q&A

Real reader questions about these medications, each personally answered by our pharmacist:

Questions for your pharmacist

  • Does my dose of Disulfiram or Methadone need adjusting while I take them together?
  • What symptoms should prompt me to call you or my prescriber right away?
  • Does the timing of my doses matter for this combination?
  • Is there a safer alternative to one of these medications for me?

References (4)

  1. Product Information: DOLOPHINE(R) oral tablets, methadone HCl oral tablets. West-Ward Pharmaceuticals Corp (per FDA), Eatontown, NJ, 2019. DailyMed
  2. Product Information: DISKETS dispersible tablets, methadone HCl dispersible tablets. Hikma Pharmaceuticals USA Inc (per FDA), Berkeley, NJ, 2023.
  3. Product Information: METHADOSE oral concentrate, methadone HCl oral concentrate. SpecGx LLC (per FDA), Webster Groves, MO, 2023. DailyMed
  4. Product Information: Methadone HCl injection, methadone HCl injection. Mylan Institutional LLC (per FDA), Morgantown, WV, 2023. DailyMed
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Methadone

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All Methadone interactions (129)
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Disulfiram

Keep reading about Disulfiram

All Disulfiram interactions (45) Disulfiram drug information
Also serious with: Metronidazole Vaginal Metronidazole Injection Metronidazole Topical Amprenavir
Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Methadone + 1,4-butanediol Activated Charcoal Beer Gamma-hydroxybutyrate (ghb) Grapefruit Kava L-tryptophan Lithium + 215 more
Disulfiram + Activated Charcoal Bach Flower Remedies Beer Wine Biofeedback Black Tea Caffeine Cannabinol (cbn) + 37 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.