Amiodarone with Sofosbuvir Interaction Details

Brand Names Associated with Amiodarone

  • Amiodarone
  • Cordarone®
  • Pacerone®

Brand Names Associated with Sofosbuvir

  • Sofosbuvir
  • Sovaldi®

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Last updated Feb 27, 2024

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Interaction Effect

Increased risk of serious bradycardia

Interaction Summary

Coadministration of amiodarone and sofosbuvir-containing hepatitis C virus treatment has resulted in symptomatic bradycardia including at least 1 fatality. Pacemaker insertion was required in some cases. Bradycardia occurred within hours to days of coadministration, but in some cases up to 2 weeks after initiating antiviral treatment. Bradycardia generally resolved after discontinuation of antiviral treatment[1]. Bradycardia recurred after rechallenged with sofosbuvir-containing treatment while on amiodarone, but no bradycardia occurred when amiodarone was discontinued. A proposed mechanism includes displacement of amiodarone (96% to 99.98% protein bound) from its protein-binding sites by sofosbuvir resulting in rapidly increased free amiodarone levels [2]. Concomitant use is not recommended; however, if it is required , cardiac monitoring is recommended. Cardiac monitoring should take place in an inpatient setting for the first 48 hours of coadministration, followed by daily self-monitoring of heart rate for 2 weeks. If a patient has discontinued amiodarone just prior to starting a sofosbuvir-containing regimen, the same monitoring is recommended due to amiodarone's long half-life [3][4].

Severity

Major

Onset

Unspecified

Evidence

Established

How To Manage Interaction

Coadministration of amiodarone and sofosbuvir-containing hepatitis C virus treatment has resulted in symptomatic bradycardia including at least 1 fatality. Pacemaker insertion was required in some cases. Bradycardia occurred within hours to days of coadministration, but in some cases up to 2 weeks after initiating antiviral treatment. Bradycardia generally resolved after discontinuation of antiviral treatment[1]. Concomitant use is not recommended; however, if it is required, cardiac monitoring is recommended. Cardiac monitoring should take place in an inpatient setting for the first 48 hours of coadministration, followed by daily self-monitoring of heart rate for 2 weeks. If a patient has discontinued amiodarone just prior to starting a sofosbuvir-containing regimen, the same monitoring is recommended due to amiodarone's long half-life [3][4].

Mechanism Of Interaction

Increased free-amiodarone concentration by displacement from protein binding sites

Literature Reports

A) In 3 case reports of severe bradycardia occurring in patients receiving amiodarone and sofosbuvir-containing treatment for chronic hepatitis C virus. One patient experienced symptomatic bradycardia 30 minutes after sofosbuvir administration and experienced transient cardiac arrest. Another patient had syncope 2 hours after sofosbuvir administration. In both patients, heart rhythm returned to normal with discontinuation of both amiodarone and sofosbuvir. A third patient developed symptomatic bradyarrhythmia on the day following sofosbuvir administration and again when rechallenged, 6 days later [5].

B) In 9 case reports in patients receiving amiodarone and sofosbuvir-containing hepatitis C treatment, bradycardia was observed and was fatal in 1 patient with 3 others requiring pacemaker insertion. In 6 of the 9 patients, symptoms occurred within 24 hours after the first dose of therapy for hepatitis C virus (HCV) infection. In the other 3 patients, bradycardia occurred between 2 and 12 days. All patients stopped sofosbuvir after bradycardia occurred. However, 3 patients rechallenged with sofosbuvir while on amiodarone resulted in recurrence of symptomatic bradycardia. One patient was asymptomatic when rechallenged with amiodarone while receiving sofosbuvir while amiodarone was discontinued. The Naranjo scale for causal relationship of this drug interaction was rated as probable (total score 7). A proposed mechanism includes displacement of amiodarone (99.6% to 99.98% protein bound) from its protein-binding sites by sofosbuvir resulting in rapidly increased free amiodarone levels [2].

References

    1 ) Product Information: Cordarone(R) oral tablets, amiodarone HCl oral tablets. Wyeth Pharmaceuticals Inc (per FDA), Philadephia, PA, 2017.

    2 ) Back DJ & Burger DM: Interaction between amiodarone and sofosbuvir-based treatment for hepatitis C virus infection: potential mechanisms and lessons to be learned. Gastroenterology 2015; 149(6):1315-1317.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

    3 ) Product Information: VOSEVI(TM) oral tablets, sofosbuvir velpatasvir voxilaprevir oral tablets. Gilead Sciences Inc (per manufacturer), Foster City, CA, 2017.

    4 ) Product Information: EPCLUSA(R) oral tablets , sofosbuvir velpatasvir oral tablets. Gilead Sciences Inc (per FDA), Foster City, CA, 2016.

    5 ) Ghembaza Mel A & Lounici A: Bradyarrhythmia induced by amiodarone-sofosbuvir co-administration. Indian J Gastroenterol 2016; 35(4):319-320.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.

See More information Regarding Amiodarone

Sofosbuvir Overview

  • Sofosbuvir is used along with ribavirin (Copegus, Rebetol, Ribasphere, others) and sometimes another medication (peginterferon alfa [Pegasys]) to treat certain types of chronic hepatitis C (an ongoing viral infection that damages the liver) in adults. Sofosbuvir is also used along with ribavirin to treat certain types of chronic hepatitis C (an ongoing viral infection that damages the liver) in children 3 years of age and older. Sofosbuvir is in a class of antiviral medications called nucleotide polymerase inhibitors. It works by decreasing the amount of hepatitis C virus (HCV) in the body. Sofosbuvir may not prevent the spread of hepatitis C to other people.

See More information Regarding Sofosbuvir

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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.

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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.