Amiodarone with Rifampin Interaction Details

Brand Names Associated with Amiodarone

  • Amiodarone
  • Cordarone®
  • Pacerone®

Brand Names Associated with Rifampin

  • Rifadin®
  • Rifamate® (as a combination product containing Isoniazid, Rifampin)
  • Rifampin
  • Rifater® (as a combination product containing Isoniazid, Pyrazinamide, Rifampin)
  • Rimactane®

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Last updated Feb 27, 2024

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Interaction Effect

Decreased amiodarone exposure and reduced efficacy

Interaction Summary

Amiodarone is primarily metabolized by CYP3A and CYP2C8[1]. Addition of rifampin, a strong CYP inducer, to stable amiodarone therapy decreased exposure to amiodarone [2] and decreased efficacy [3]. Consider dosage adjustment of amiodarone [2][3] based on serial measurement of serum concentration during concomitant use of drugs affecting CYP3A activity. The potential for drug interactions persists after discontinuation of amiodarone due to its long half-life [4].

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Concomitant use of amiodarone with rifampin, a CYP3A and CYP2C8 inducer, may lead to reduced amiodarone serum levels and loss of efficacy. Consider serial measurement of amiodarone serum concentration during concomitant use of drugs affecting CYP3A activity. The potential for drug interactions persists after discontinuation of amiodarone due to its long half-life[4][1][5]. Dosage adjustment may be necessary [2][3].

Mechanism Of Interaction

Induction of CYP3A-mediated metabolism of amiodarone; induction of CYP2C8-mediated metabolism of amiodarone

Literature Reports

A) Following 10 days of concomitant rifampicin , a strong CYP3A inducer, 900 mg/day plus amiodarone 200 mg/day in a 69-year-old man, cumulative amiodarone and desethylamiodarone (DEA; major, active metabolite) concentration was reduced by 52% from a baseline of 1.72 mg/L to 0.83 mg/L. The patient had been stable on amiodarone therapy for arrhythmogenic right ventricular cardiomyopathy and had a history of left knee arthritis. Rifampin was initiated to treat a prothesis infection pursuant to a total knee replacement. Amiodarone dose was increased to 600 mg/day but 1 week later, the cumulative amiodarone/DEA concentration was further decreased to 0.65 mg/L. With an increase of amiodarone dose to 900 mg/day (a 450% increase from baseline), the cumulative amiodarone/DEA concentration returned to 1.52 mg/L, within the reference range of 1 to 4 mg/L. Two weeks after finishing the rifampin course, the amiodarone dose was readjusted to 200 mg/day and levels remained in therapeutic range [2].

B) A 33-year-old woman on stable amiodarone 400 mg/day therapy (baseline amiodarone and desethylamiodarone (DEA) levels of 0.5 and 0.7 mg/L) was hospitalized with palpitations, implantable cardioverter defibrillator shock, and atrial fibrillation-flutter paroxysms 1 month after starting rifampin, a strong CYP3A inducer, 600 mg/day for a methicillin-resistant staphylococcal infection of her pacing system. On admission, serum amiodarone levels were 0.3 mg/L and DEA was undetectable. Amiodarone dose was increased to 400 mg twice daily, but 2 months later, palpitations continued and the amiodarone and DEA levels were 0.4 and 0.6 mg/L. Rifampin was discontinued and 2 weeks later the repeat serum amiodarone and DEA levels were 1.2 and 1 mg/L. Amiodarone 400 mg twice daily was continued for several months then decreased to 600 mg/day. One month later, serum amiodarone and DEA levels were 1.6 and 1.3 mg/L [3].

References

    1 ) Product Information: Amiodarone HCl intravenous injection, amiodarone HCl intravenous injection. Wockhardt USA LLC (per DailyMed), Parsippany, NJ, 2017.

    2 ) Oude Munnink TH, Demmer A, Slenter RHJ, et al: Amiodarone rifampicin drug-drug interaction management with therapeutic drug monitoring. Ther Drug Monit 2018; 40(2):159-161.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

    3 ) Zarembski DG, Fischer SA, Santucci PA, et al: Impact of rifampin on serum amiodarone concentrations in a patient with congenital heart disease. Pharmacotherapy 1999; 19(2):249-251.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

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

    5 ) Product Information: Amiodarone HCl oral tablets, amiodarone HCl oral tablets. Cameron Pharmaceuticals LLC (per DailyMed), Louisville, KY, 2017.

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

Rifampin Overview

  • Rifampin is used with other medications to treat tuberculosis (TB; a serious infection that affects the lungs and sometimes other parts of the body). Rifampin is also used to treat some people who have Neisseria meningitidis (a type of bacteria that can cause a serious infection called meningitis) infections in their noses or throats. These people have not developed symptoms of the disease, and this treatment is used to prevent them from infecting other people. Rifampin should not be used to treat people who have developed symptoms of meningitis. Rifampin is in a class of medications called antimycobacterials. It works by killing the bacteria that cause infection.

  • Antibiotics such as rifampin will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

See More information Regarding Rifampin

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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.