Amiodarone with Docetaxel Interaction Details
Brand Names Associated with Amiodarone
- Amiodarone
- Cordarone®
- Pacerone®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 27, 2024
Interaction Effect
Increase in docetaxel exposure and risk of toxicity
Interaction Summary
Concomitant use of amiodarone (a CYP3A4 and P-gp inhibitor) and docetaxel (a CYP3A4 and P-gp substrate) may increase docetaxel exposure and increase the risk of toxicity. In a case report, a patient experienced severe skin and mucosal toxicity within 3 days of docetaxel initiation with confirmed significant increase in docetaxel exposure via pharmacokinetic analysis. Amiodarone has a half-life of 20 to 100 days, so effects on docetaxel metabolism may be expected to persist well after discontinuation of amiodarone. Consider alternative chemotherapeutic agents for patients receiving or who have recently received amiodarone[1].
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Concomitant use of amiodarone (a CYP3A4 and P-gp inhibitor) and docetaxel (a CYP3A4 and P-gp substrate) may increase docetaxel exposure and increase the risk of toxicity. Amiodarone has a half-life of 20 to 100 days, so effects on docetaxel metabolism may be expected to persist well after discontinuation of amiodarone. Consider alternative chemotherapeutic agents for patients receiving or who have recently received amiodarone[1].
Mechanism Of Interaction
Inhibition of CYP3A4- and P-gp-mediated docetaxel metabolism by amiodarone
Literature Reports
A) In a case report, a 77-year-old woman on stable amiodarone therapy was initiated on paclitaxel and subsequently on docetaxel and developed severe skin and mucosal toxicity with confirmed significant increase in docetaxel exposure via pharmacokinetic analysis. The patient had a history of hypertension, hyperlipidemia, and palpitations receiving long-term amiodarone and was initiated on paclitaxel 80 mg/m(2) once a week and trastuzumab for HER2-positive breast cancer. During the first 4 cycles, she developed increasing abdominal pain and facial rash that progressed to overt peeling of the palms, soles, and back of the arms and hands. Therapy was changed to docetaxel 100 or 75 mg/m(2) weekly but within 3 days she developed pain on swallowing, diarrhea, and vomiting. Upon admission, mucositis was diagnosed which required nasogastric tube insertion for enteral feeding. She was treated with predniSONE, topical ointments and cooling. Worsening of her status necessitated discontinuation of chemotherapy. A pharmacokinetic analysis revealed a 79% decrease in docetaxel clearance (9.15 vs 44.1 L/hr) and a 5-fold increase in AUC(0 to infinity; 10.9 vs 2.27 mg x L/hr). Amiodarone has a half-life of 20 to 100 days, so effects on docetaxel metabolism may be expected to persist well after discontinuation of amiodarone [1].
References
1 ) Hammann F , Gotta V , Conen K , et al: Pharmacokinetic interaction between taxanes and amiodarone leading to severe toxicity. Br J Clin Pharmacol 2017; 83(4):927-930.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...
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.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
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:
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.