Amiodarone with Erythromycin Interaction Details

Brand Names Associated with Amiodarone

Brand Names Associated with Erythromycin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Feb 27, 2024

Interaction Effect

An increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest)

Interaction Summary

Concomitant therapy with erythromycin and class III antiarrhythmic agents is not recommended as the combination can cause prolongation of the QTc interval[1]. Erythromycin has demonstrated QTc prolongation in combination with other drugs that prolong the QT interval [2]. Cases of QTc prolongation and/or torsades de pointes have been reported with all class III antiarrhythmic agents, including acecainide [3], amiodarone [4], azimilide [5], bretylium [6], ibutilide [7], sematilide [8], dofetilide [9], sotalol [10], and tedisamil [11]. CYP3A4 enzymes play a small role in the metabolism of dofetilide. Inhibitors of CYP3A4 such as erythromycin could potentially increase the systemic exposure of dofetilide, which may lead to increased dofetilide levels [12]. Amiodarone is also a substrate of CYP3A4 [13].

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

The concurrent administration of erythromycin and class III antiarrhythmics is not recommended[1].

Mechanism Of Interaction

Additive effects on QT prolongation

Literature Reports

A) Concurrent use of class III antiarrhythmic agents, and other drugs that can prolong the QT interval, such as erythromycin, is not recommended. Dofetilide should be stopped for at least 2 days before any interacting drug is initiated. If concurrent use cannot be avoided, cautious dosing and telemetric monitoring is advised [1].

B) Erythromycin significantly increased the QTc interval compared with baseline in a retrospective study of 49 patients. The erythromycin dose was 500 milligrams or 1 gram four times daily, with a mean of 15 doses received. Patients (n equal to 9) who received 60 mg/kg/day or more all developed increases in QT interval of 15% or greater. For all patients, the mean QTc interval increased from 432 milliseconds (msec) at baseline to 483 msec (p less than 0.01). In patients with delayed repolarization at baseline (n equal to 9), the QTc interval increased from 473 msec to 525 msec (p less than 0.01). In patients with heart disease (n equal to 30), all experienced an increase in QTc interval (mean of 15%), compared with an increase of 8% in patients without heart disease (p less than 0.05). In 5 patients (10%), the QTc interval was severely prolonged. One patient developed torsades de pointes attributed to erythromycin. Of 16 patients receiving cotrimoxazole concomitantly, 8 developed QT prolongation of 15% or greater [14].

References

1 ) Yamreudeewong W, DeBisschop M, Martin LG, et al: Potentially significant drug interactions of class III antiarrhythmic drugs. Drug Safety 2003; 26(6):421-438.

2 ) Product Information: PCE(R), erythromycin particles in tablets. Abbott Laboratories, North Chicago, IL, 1997.

3 ) Chow MJ, Piergies AA, Bowsher DJ, et al: Torsade de pointes induced by N-acetylprocainamide. J Am Coll Cardiol 1984; 4:621-624.

4 ) Faggiano P, Gardini A, D'Aloia A, et al: Torsade de pointes occurring early during oral amiodarone treatment. Int J Cardiol 1996; 55(2):205-208.

5 ) Corey AE, Agnew JR, Valentine SN, et al: Azimilide pharmacokinetics following intravenous and oral administration of a solution and capsule formulation. J Clin Pharmacol 1999; 39(12):1272-1276.

6 ) Gilman AG, Goodman LS, Rall TW, et alGilman AG, Goodman LS, Rall TW, et al (Eds): The Pharmacological Basis of Therapeutics, 7th. Macmillan Publishing Co, New York, NY, 1985.

7 ) Rodriguez I, Kilborn MJ, Liu XK, et al: Drug-induced QT prolongation in women during the menstrual cycle. JAMA 2001; 285(10):1322-1326.

8 ) Singh BN: The coming of age of the class III antiarrhythmic principle: retrospective and future trends. Am J Cardiol 1996; 78(suppl):17-27.

9 ) Allen MJ, Oliver SD, Newgreen MW, et al: Pharmacodynamic effect of continuous vs intermittent dosing of dofetilide on QT interval. Br J Clin Pharmacol 2002; 53:59-65.

10 ) Marill KA & Runge T: Meta-analysis of the risk of torsades de pointes in patients treated with intravenous racemic sotalol. Acad Emerg Med 2001; 8(2):117-124.

11 ) Bargheer K, Bode F, Klein HU, et al: Prolongation of monophasic action potential duration and the refractory period in the human heart by tedisamil, a new potassium-blocking agent. Eur Heart J 1994; 15:1409-1414.

12 ) Product Information: TIKOSYN(R) oral capsules, dofetilide oral capsules. Pfizer,Inc, New York, NY, 2004.

13 ) Product Information: CORDARONE(R) oral tablets, amiodarone hcl oral tablets. Wyeth Pharmaceuticals Inc, Philadelphia, PA, 2008.

14 ) Oberg KC & Bauman JL: QT interval prolongation and torsades de pointes due to erythromycin lactobionate. Pharmacotherapy 1995; 15(6):687-692.

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.

Erythromycin Overview

• Erythromycin is used to treat certain infections caused by bacteria, such as infections of the respiratory tract, including bronchitis, pneumonia, Legionnaires' disease (a type of lung infection), and pertussis (whooping cough; a serious infection that can cause severe coughing); diphtheria (a serious infection in the throat); sexually transmitted diseases (STD), including syphilis; and ear, intestine, gynecological, urinary tract, and skin infections. It also is used to prevent recurrent rheumatic fever. Erythromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

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

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.