Drug Interaction Report

Fentanyl Transdermal Patch and Amiodarone: Interaction Details

A pharmacist-reviewed analysis of the Fentanyl Transdermal Patch and Amiodarone 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
+

Fentanyl Transdermal Patch

Duragesic®
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 493 documented Fentanyl Transdermal Patch interactions, 469 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
rapid
Evidence
probable
Severity
Major

What happens

Cardiac toxicity (low cardiac output) and an increased risk of fentanyl toxicity (CNS depression, respiratory depression)

Interaction Deep Dive

Concomitant use of amiodarone and fentanyl, a CYP3A substrate, can cause hypotension, bradycardia, and decreased cardiac output1. Perioperative complications such as cardiac conduction defects, low cardiac output, and reduced systemic vascular resistance were more frequently encountered in a group of surgical patients maintained on amiodarone 345. Fentanyl is primarily metabolized by CYP3A4. Coadministration of all CYP3A4 inhibitors (eg, amiodarone) may result in an increase of fentanyl plasma concentration and subsequent increased, prolonged, and possibly fatal fentanyl adverse effects 2. Drug interactions may persist for weeks to months after discontinuation of amiodarone 1.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated fentanyl metabolism by amiodarone

Common questions

Can I take Fentanyl Transdermal Patch and Amiodarone together?

Cardiac toxicity (low cardiac output) and an increased risk of fentanyl toxicity (CNS depression, respiratory depression) Always confirm with your pharmacist or prescriber before making any change.

How serious is the Fentanyl Transdermal Patch and Amiodarone interaction?

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

How quickly could this interaction happen?

The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.

How strong is the evidence for this interaction?

The evidence is graded "probable". Good supporting evidence, though not definitively proven.

From our Q&A

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

Questions for your pharmacist

  • Does my dose of Fentanyl Transdermal Patch or Amiodarone 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: CORDARONE(R) oral tablets, amiodarone oral tablets. Wyeth Pharmaceuticals Inc (per FDA), Philadephia, PA, 2018. DailyMed
  2. Product Information: DURAGESIC(R) transdermal patches, fentanyl transdermal system transdermal patches. Janssen,division of Ortho-McNeil-Janssen Pharmaceuticals,Inc, Titusville, NJ, 2008. DailyMed
  3. Gallagher JD, Lieberman RW, Meranze J, et al: Amiodarone-induced complications during coronary artery surgery. Anesthesiology 1981; 55:186-188. PubMed
  4. Liberman BA & Teasdale SJ: Anaesthesia and amiodarone. Can Anaesth Soc J 1985; 32:629-638. PubMed
  5. MacKinnon G, Landymore R, & Marble A: Should oral amiodarone be used for sustained ventricular tachycardia in patients requiring open heart surgery?. Can J Surg 1983; 26:355-357.
Was this write-up helpful?
Amiodarone

Keep reading about Amiodarone

All Amiodarone interactions (141)
Also serious with: Deuruxolitinib Colchicine Ketoconazole Topical Galantamine
Fentanyl Transdermal Patch

Keep reading about Fentanyl Transdermal Patch

All Fentanyl Transdermal Patch interactions (493) Fentanyl Transdermal Patch drug information
Also serious with: Ensitrelvir Samidorphan Safinamide Phenelzine
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

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.