Amiodarone with Bosentan Interaction Details
Brand Names Associated with Amiodarone
- Amiodarone
- Cordarone®
- Pacerone®
Brand Names Associated with Bosentan
- Bosentan
- Tracleer®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 27, 2024
Interaction Effect
Reduced amiodarone exposure and/or increased bosentan exposure
Interaction Summary
Bosentan is a substrate and inducer of CYP3A and CYP2C9 and has decreased exposure to coadministered CYP3A and CYP2C9 substrates[1] . Amiodarone is a substrate of CYP3A with a potential to inhibit CYP2C9 and CYP3A. Increased plasma concentrations of coadministered CYP3A substrates has been observed [2]. Coadministration of bosentan with both a CYP2C9 inhibitor and a strong or moderate CYP3A inhibitor is not recommended, as increases in plasma concentration of bosentan are likely [1]. Drug interactions with amiodarone can persist for weeks to months after discontinuation, due to a long half-life [2]. Consider monitoring for decreased effects of amiodarone and/or an increase in exposure-related toxicities of bosentan when coadministration is required.
Severity
Moderate
Onset
Delayed
Evidence
Theoretical
How To Manage Interaction
Bosentan is a substrate and inducer of CYP3A and CYP2C9[1] and amiodarone is a substrate of CYP3A with a potential to inhibit CYP2C9 and CYP3A. Coadministration of amiodarone and a CYP3A inducer can lead to reduced amiodarone serum levels [2].. Coadministration of bosentan with both a CYP2C9 inhibitor and a strong or moderate CYP3A inhibitor is not recommended, as increases in plasma concentration of bosentan are likely [1]. Drug interactions with amiodarone can persist for weeks to months after discontinuation, due to a long half-life [2]. Consider monitoring for decreased effects of amiodarone and/or an increase in exposure-related toxicities of bosentan when coadministration is required.
Mechanism Of Interaction
Increased CYP3A-mediated metabolism of amiodarone; reduced CYP3A- and CYP2C9-mediated metabolism of bosentan
Literature Reports
A) Bosentan 500 mg twice daily for 6 days in healthy subjects decreased the plasma concentrations of both S-warfarin (a CYP2C9 substrate) and R-warfarin (a CYP3A substrate) by 29% and 38%, respectively. Similarly, significant decreases in exposure to the coadministered drug were observed with the CYP3A substrates cyclosporine A, digoxin, glyburide, sildenafil, and ethinyl estradiol; however, Cmax was not significantly affected in all cases [1].
B) Amiodarone increased plasma concentrations of CYP3A substrates quinidine (33% after 2 days) and procainamide and n-acetyl procainamide (55% and 33% within less than 7 days) [2].
References
1 ) Product Information: TRACLEER(R) oral tablets, tablets for oral suspension, bosentan oral tablets, tablets for oral suspension. Actelion Pharmaceuticals US, Inc (per FDA), South San Francisco, CA, 2017.
2 ) Product Information: CORDARONE(R) oral tablets, amiodarone oral tablets. Wyeth Pharmaceuticals Inc (per FDA), Philadephia, PA, 2018.
Amiodarone Overview
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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.
Bosentan Overview
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Bosentan is used to treat pulmonary arterial hypertension (PAH, high blood pressure in the vessels that carry blood to the lungs) in adults and children 3 years of age and older. Bosentan may improve the ability to exercise and slow the worsening of symptoms in patients with PAH. Bosentan is in a class of medications called endothelin receptor antagonists. It works by stopping the action of endothelin, a natural substance that causes blood vessels to narrow and prevents normal blood flow in people who have PAH.
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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:
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.