Amiodarone with Azithromycin Interaction Details

Brand Names Associated with Amiodarone

Brand Names Associated with Azithromycin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

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

Interaction Summary

Use of macrolides, including azithromycin, has been associated with prolonged cardiac repolarization and QT interval. Rare reports of torsades de pointes during azithromycin therapy have occurred during postmarketing surveillance. Although risk appears to be low, concomitant therapy with azithromycin and Class III antiarrhythmic agents should be avoided due to the potential for additive effects on QT prolongation and increased risk for serious cardiac events[1]. If concomitant use is clinically warranted, carefully assess potential risks and benefits before using azithromycin and Class III antiarrhythmic agents together [2][3][4], and closely monitor for QT interval prolongation.

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Concomitant use of azithromycin and a class III antiarrhythmic should be avoided due to the potential for additive effects on the QT interval and an increased risk of serious cardiac events (eg, torsades de pointes)[1]. If coadministration is clinically warranted, carefully assess potential risks and benefits before using azithromycin and Class III antiarrhythmic agents together [1][2][3][4], and closely monitor cardiac function.

Mechanism Of Interaction

Additive effects on QT prolongation

Literature Reports

A) One case report describes a female patient maintained on amiodarone 200 mg/day, furosemide 40 mg/day, enalapril 7.5 mg twice a day and aspirin 325 mg/day, who experienced a marked prolongation of the QT interval and increased QT dispersion on day 3 of azithromycin treatment for pneumonia. The patient's admission EKG showed a regular sinus rhythm with a heart rate of 60 beats/min, normal PR, QRST, and QTc (510 msec), and QT dispersion of 58 msec. Serum electrolytes were within normal limits. On day 3 of azithromycin therapy (500 mg on day one, followed by 250 mg/day) the patient was seen again for not feeling well and intermittent dizziness. Clinical examination was significant for improved lung symptoms and an electrocardiogram showing bradycardia (53 beats/min), increased QT interval (676 msec), QTc (660 msec), and QT dispersion (140 msec). Azithromycin was discontinued, and EKG values returned to baseline 4 days later. Prior to the azithromycin, the patient had tolerated the amiodarone without incident [5].

B) Cases of QTc prolongation and/or torsades de pointes have been reported with all class III antiarrhythmic agents, including acecainide [6], amiodarone [7], azimilide [8], bretylium [9], ibutilide [10], sematilide [11], dofetilide [12], sotalol [13], and tedisamil [14]

References

1 ) Product Information: Zmax(R) oral extended release powder for suspension, azithromycin oral extended release powder for suspension. Pfizer Labs (Per FDA), New York, NY, 2012.

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

3 ) Product Information: BETAPACE AF(R) oral tablets, sotalol hcl oral tablets. Bayer Healthcare Pharmaceuticals,Inc, Wayne, NJ, 2007.

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

5 ) Samarendra P, Kumari S, Evans S, et al: QT prolongation associated with azithromycin/amiodarone combination. PACE 2001; 24:1572-1574.

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

7 ) 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.

8 ) 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.

9 ) 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.

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

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

12 ) 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.

13 ) 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.

14 ) 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.

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.

Azithromycin Overview

• Azithromycin is used to treat certain bacterial infections, such as bronchitis; pneumonia; sexually transmitted diseases (STD); and infections of the ears, lungs, sinuses, skin, throat, and reproductive organs. Azithromycin also is used to treat or prevent disseminated Mycobacterium avium complex (MAC) infection [a type of lung infection that often affects people with human immunodeficiency virus (HIV)]. Azithromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as azithromycin 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.

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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.