Drug Interaction Report

Belzutifan and Dofetilide: Interaction Details

A pharmacist-reviewed analysis of the Belzutifan and Dofetilide 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

Belzutifan

Welireg
+

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 49 documented Belzutifan interactions, 47 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

Reduced CYP3A4 substrates with NTI exposure and reduced efficacy of CYP3A4 substrates with NTI

Interaction Deep Dive

Avoid coadministration of belzutifan with sensitive CYP3A4 substrates for which minimal decrease in concentration may lead to therapeutic failures of the substrate. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage as needed. Coadministration of belzutifan with CYP3A4 substrates may reduce CYP3A4 substrates wit NTI exposure, which may reduce the efficacy of these substrates. The magnitude of this effect may be more pronounced in patients who are dual UGT2B17 and CYP2C19 poor metabolizers. Coadministration of belzutifan with midazolam (a sensitive CYP3A4 substrate) decreased the midazolam AUC by 40% and the Cmax by 34%. Midazolam AUC is predicted to decrease up to 70% in patients with higher belzutifan concentrations (eg, dual poor metabolizers)1.

Why it happens (mechanism)

Induction of CYP3A4-mediated metabolism by belzutifan

Literature reports

1 report — tap to read

a) Coadministration of belzutifan 120 mg once daily with midazolam (a sensitive CYP3A4 substrate) decreased the midazolam AUC by 40% and the Cmax by 34%. Midazolam AUC is predicted to decrease up to 70% in patients with higher belzutifan concentrations (eg, dual poor metabolizers) 1.

Common questions

Can I take Belzutifan and Dofetilide together?

Reduced CYP3A4 substrates with NTI exposure and reduced efficacy of CYP3A4 substrates with NTI Always confirm with your pharmacist or prescriber before making any change.

How serious is the Belzutifan and Dofetilide 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 Belzutifan or Dofetilide 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 (1)

  1. Product Information: WELIREG(R) oral tablets, belzutifan oral tablets. Merck Sharp & Dohme LLC (per manufacturer), Rahway, NJ, 2025. DailyMed
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Belzutifan

Keep reading about Belzutifan

All Belzutifan interactions (49)
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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:

Belzutifan + Activated Charcoal Adrafinil Artichoke Bacopa Baikal Skullcap Boswellia Serrata Breadfruit Brussels Sprout + 52 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.