Drug Interaction Report

Amiodarone and Macitentan: Interaction Details

A pharmacist-reviewed analysis of the Amiodarone and Macitentan 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

Amiodarone

Nexterone Pacerone
+

Macitentan

Opsumit Opsumit®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
LinkedIn
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 141 documented Amiodarone interactions, 111 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 macitentan exposure

Interaction Deep Dive

Avoid concomitant use of amiodarone (moderate dual CYP3A4 and CYP2C9 inhibitor) with macitentan, as coadministration may significantly increase macitentan exposure12.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated metabolism of macitentan; inhibition of CYP2C9-mediated metabolism of macitentan

Literature reports

1 report — tap to read

a) Coadministration of macitentan with a moderate dual inhibitor of CYP3A4 and CYP2C9 such as fluconazole (400 mg once daily) is predicted to increase macitentan exposure approximately 4-fold without relevant effect on the exposure to its active metabolite in a physiologically based pharmacokinetic (PBPK) modeling and simulations based analysis 32.

Common questions

Can I take Amiodarone and Macitentan together?

Increased macitentan exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Amiodarone and Macitentan 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 Amiodarone or Macitentan 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 (3)

  1. Product Information: OPSUMIT(R) oral tablets, macitentan oral tablets. Actelion Pharmaceuticals US Inc (per FDA), Titusville, NJ, 2023. DailyMed
  2. Product Information: OPSYNVI(R) oral tablets, macitentan tadalafil oral tablets. Actelion Pharmaceuticals US, Inc. (Per FDA), Titusville, NJ, 2024. DailyMed
  3. Product Information: OPSUMIT(R) oral tablets, macitentan oral tablets. Actelion Pharmaceuticals US Inc (per FDA), South San Francisco, CA, 2021. DailyMed
Was this write-up helpful?
Amiodarone

Keep reading about Amiodarone

All Amiodarone interactions (141)
Also serious with: Deuruxolitinib Colchicine Ketoconazole Topical Galantamine
Macitentan

Keep reading about Macitentan

All Macitentan interactions (58) Macitentan drug information
Also serious with: Ensitrelvir Sparsentan Voriconazole Avacopan
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:

Amiodarone + Activated Charcoal American Hellebore Arsenic Beer Cesium Ephedra Grapefruit Siberian Cocklebur + 202 more
Macitentan + Activated Charcoal American Hellebore American Mistletoe Beer Grapefruit Siberian Cocklebur St. John's Wort Tyramine + 245 more

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

Check another combination

Our instant two-drug interaction checker is almost here.

Coming soon

The instant two-drug checker is on its way.

In the meantime, browse the directory below to look up any drug and see its documented interactions.

Still have questions about this combination?

Every question gets a real answer from a licensed pharmacist — free, and usually within a day.

Ask the pharmacist
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.