Fentanyl with Amiodarone Interaction Details

Brand Names Associated with Fentanyl

Brand Names Associated with Amiodarone

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Feb 27, 2024

Interaction Effect

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

Interaction Summary

Concomitant use of amiodarone and fentanyl, a CYP3A substrate, can cause hypotension, bradycardia, and decreased cardiac output[1]. 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 [2][3][4]. 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 [5]. Drug interactions may persist for weeks to months after discontinuation of amiodarone [1].

Severity

Major

Onset

Rapid

Evidence

Probable

How To Manage Interaction

Concomitant use of amiodarone and fentanyl, a CYP3A substrate, can cause hypotension, bradycardia, and decreased cardiac output[1] associated with elevated fentanyl plasma concentrations. Monitor patients for signs of excessive respiratory and central nervous system depression [5]. Drug interactions may persist for weeks to months after discontinuation of amiodarone [1].

Mechanism Of Interaction

Inhibition of CYP3A4-mediated fentanyl metabolism by amiodarone

References

1 ) Product Information: CORDARONE(R) oral tablets, amiodarone oral tablets. Wyeth Pharmaceuticals Inc (per FDA), Philadephia, PA, 2018.

2 ) Gallagher JD, Lieberman RW, Meranze J, et al: Amiodarone-induced complications during coronary artery surgery. Anesthesiology 1981; 55:186-188.

3 ) Liberman BA & Teasdale SJ: Anaesthesia and amiodarone. Can Anaesth Soc J 1985; 32:629-638.

4 ) 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.

5 ) Product Information: DURAGESIC(R) transdermal patches, fentanyl transdermal system transdermal patches. Janssen,division of Ortho-McNeil-Janssen Pharmaceuticals,Inc, Titusville, NJ, 2008.

Fentanyl Overview

• Fentanyl is used to treat breakthrough pain (sudden episodes of pain that occur despite round the clock treatment with pain medication) in cancer patients at least 18 years of age (or at least 16 years of age if using Actiq brand lozenges) who are taking regularly scheduled doses of another narcotic (opiate) pain medication, and who are tolerant (used to the effects of the medication) to narcotic pain medications. Fentanyl is in a class of medications called narcotic (opiate) analgesics. It works by changing the way the brain and nervous system respond to pain.

Amiodarone Overview

• Amiodarone is used to treat and prevent certain types of serious, life-threatening ventricular arrhythmias (a certain type of abnormal heart rhythm when other medications did not help or could not be tolerated. Amiodarone is in a class of medications called antiarrhythmics. It works by relaxing overactive heart muscles.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.