Amiodarone with Phenobarbital Interaction Details
Brand Names Associated with Amiodarone
- Amiodarone
- Cordarone®
- Pacerone®
Brand Names Associated with Phenobarbital
- Phenobarbital
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 27, 2024
Interaction Effect
An increased risk of QT interval prolongation, reduced amiodarone exposure, reduced efficacy of amiodarone, increased PHENobarbital exposure and an increased risk of PHENobarbital-related adverse effects
Interaction Summary
Concomitant use of PHENobarbital (a QTc interval prolongation agent) with other QTc interval prolongation agents like amiodarone may result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation. Also, concomitant use of PHENobarbital (a CYP2C8/CYP3A inducer) with amiodarone (a CYP2C8/CYP3A substrate) may decrease amiodarone exposure, which may reduce the efficacy of amiodarone. Also, the concomitant use of PHENobarbital (a CYP2C9 substrate) with amiodarone (a CYP2C9 inhibitor) may increase PHENobarbital exposure, which may increase the risk of PHENobarbital-related adverse reactions. If concomitant use cannot be avoided, monitor patients for increased risk of QTc interval prolongation, closely monitor for PHENobarbital-related adverse reactions and consider titration of the PHENobarbital maintenance dosage accordingly, closely monitor neonates for decreased amiodarone exposure and consider increasing the amiodarone dosage accordingly[1]. 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 [2][3][4].
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Concomitant use of PHENobarbital (a QTc interval prolongation agent) with other QTc interval prolongation agents like amiodarone may result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation. Also, concomitant use of PHENobarbital (a CYP2C8/CYP3A inducer) with amiodarone (a CYP2C8/CYP3A substrate) may decrease amiodarone exposure, which may reduce the efficacy of amiodarone. Also, the concomitant use of PHENobarbital (a CYP2C9 substrate) with amiodarone (a CYP2C9 inhibitor) may increase PHENobarbital exposure, which may increase the risk of PHENobarbital-related adverse reactions. If concomitant use cannot be avoided, monitor patients for increased risk of QTc interval prolongation, closely monitor for PHENobarbital-related adverse reactions and consider titration of the PHENobarbital maintenance dosage accordingly, closely monitor neonates for decreased amiodarone exposure and consider increasing the amiodarone dosage accordingly[1]. 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 [2][3][4].
Mechanism Of Interaction
Additive QT interval prolongation; induction of CYP2C8-mediated metabolism of amiodarone; induction of CYP3A-mediated metabolism of amiodarone; inhibition of CYP2C9-mediated metabolism of PHENobarbital
References
1 ) Product Information: SEZABY(TM) intravenous injection, phenobarbital sodium intravenous injection. Sun Pharmaceutical Industries Inc (per manufacturer), Cranbury, NJ, 2022.
2 ) Product Information: CORDARONE(R) oral tablets, amiodarone oral tablets. Wyeth Pharmaceuticals Inc (per FDA), Philadephia, PA, 2018.
3 ) Product Information: Amiodarone HCl intravenous injection, amiodarone HCl intravenous injection. Wockhardt USA LLC (per DailyMed), Parsippany, NJ, 2017.
4 ) Product Information: Amiodarone HCl oral tablets, amiodarone HCl oral tablets. Cameron Pharmaceuticals LLC (per DailyMed), Louisville, KY, 2017.
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.
Phenobarbital Overview
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Phenobarbital is used to control seizures. Phenobarbital is also used to relieve anxiety. It is also used to prevent withdrawal symptoms in people who are dependent ('addicted'; feel a need to continue taking the medication) on another barbiturate medication and are going to stop taking the medication. Phenobarbital is in a class of medications called barbiturates. It works by slowing activity in the brain.
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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.