Drug Interaction Report

Dofetilide and Methadone: Interaction Details

A pharmacist-reviewed analysis of the Dofetilide 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
+

Dofetilide

Tikosyn Tikosyn®
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 454 documented Dofetilide interactions, 288 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

An increased risk of QT interval prolongation

Interaction Deep Dive

Cases of QT interval prolongation and serious arrhythmias, including torsade de pointes (TdP), have been reported with methadone use2. Dofetilide use can cause ventricular arrhythmias, including TdP, associated with QT interval prolongation. Although no formal drug interaction studies have been done, the coadministration of dofetilide and other drugs known to prolong the QTc interval, including methadone, is not recommended due to the potential for additive QT interval prolongation and torsade de pointes 1. If coadministered, closely monitor the patient for the cardiac conduction changes and development of prolonged QT interval 345.

Why it happens (mechanism)

Additive QT interval prolongation

Common questions

Can I take Dofetilide and Methadone together?

An increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.

How serious is the Dofetilide 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 Dofetilide 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 (5)

  1. Product Information: TIKOSYN(R) oral capsules, dofetilide oral capsules. Pfizer Labs (per FDA), New York, NY, 2019. DailyMed
  2. Product Information: DOLOPHINE(R) oral tablets, methadone HCl oral tablets. West-Ward Pharmaceuticals Corp (per FDA), Eatontown, NJ, 2019. DailyMed
  3. Product Information: DISKETS dispersible tablets, methadone HCl dispersible tablets. Hikma Pharmaceuticals USA Inc (per FDA), Berkeley, NJ, 2023.
  4. Product Information: METHADOSE oral concentrate, methadone HCl oral concentrate. SpecGx LLC (per FDA), Webster Groves, MO, 2023. DailyMed
  5. 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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Dofetilide

Keep reading about Dofetilide

All Dofetilide interactions (454) Dofetilide drug information
Also serious with: Bictegravir Cimetidine Saquinavir Cisapride
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
Dofetilide + Activated Charcoal American Hellebore Arsenic Cesium Ephedra Grapefruit Sida Cordifolia St. John's Wort + 138 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.