Azithromycin with Disopyramide Interaction Details

Brand Names Associated with Azithromycin

Brand Names Associated with Disopyramide

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

Interaction Effect

An increased risk of QT interval prolongation and serious cardiac arrhythmias

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[1]. Disopyramide has also been associated with prolongation of the QT interval and may cause exacerbation of arrhythmia, including ventricular tachycardia (VT) and ventricular fibrillation [2]. Although risk appears to be low, concomitant use of azithromycin and a class IA antiarrhythmic, such as disopyramide, should be avoided due to the potential for additive effects on the QT interval and an increased risk of serious cardiac events [1]. A patient stabilized on disopyramide and metoprolol for 5 years developed VT associated with an elevated disopyramide level 11 days after initiation of azithromycin [3]. If concomitant therapy is warranted, closely monitor ECG for QT interval prolongation. If a QRS interval prolongation of greater than 25% occurs, discontinue disopyramide. If a QT interval prolongation of greater than 25% with persistent ectopy occurs, monitor the patient closely and consider discontinuation of disopyramide therapy [2].

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Concomitant use of azithromycin and disopyramide should be avoided[3] due to an increased risk of additive effects on QT interval prolongation and cardiac arrhythmias. Although risk appears to be low, concomitant use of azithromycin and a class IA antiarrhythmic, such as disopyramide, may result in additive effects on the QT interval and an increased risk of serious cardiac events [1]. If concomitant therapy is warranted, closely monitor ECG for QT interval prolongation. If a QRS interval prolongation of greater than 25% occurs, discontinue disopyramide. If a QT interval prolongation of greater than 25% with persistent ectopy occurs, monitor the patient closely and consider discontinuation of disopyramide therapy [2].

Mechanism Of Interaction

Additive effects on QT interval prolongation

Literature Reports

A) A case report describes a 35-year-old female who experienced a potentially fatal interaction with azithromycin and disopyramide. The patient began taking disopyramide and metoprolol for vasopressor syncope and was stabilized on this regimen for five years. Azithromycin was initiated when the patient developed a fever and lower abdominal pain. Eleven days after initiation of azithromycin she presented to the emergency room with malaise, lightheadedness, and urinary retention. Ventricular tachycardia (123 beats/min) with left bundle branch morphology was evident on an electrocardiogram. The patient subsequently experienced hypotension and loss of consciousness. Dopamine was initiated and disopyramide levels were 11.1 mg/L. Another electrocardiogram demonstrated junctional rhythm at 87 beats/min, a markedly prolonged QT interval of 560 ms, and anterolateral T wave inversions. An echocardiogram demonstrated diffuse left ventricular dysfunction and was remarkable for an ejection fraction of approximately 0.20. The patient subsequently regained consciousness and required a continuous infusion of dopamine for some time. Despite recovery from arrhythmias, fevers continue to recur in this patient [3].

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: NORPACE(R), NORPACE(R) CR oral capsules, extended-release capsules, disopyramide phosphate oral capsules, extended-release capsules. G.D. Searle LLC, Chicago, IL, 2006.

3 ) Granowitz E, Tabor K, & Kirchhoffer J: Potentially fatal interaction between azithromycin and disopyramide. PACE 2000; 23:1433-1435.

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.

Disopyramide Overview

• Disopyramide is used to treat certain types of irregular heartbeats). Disopyramide is in a class of medications called antiarrhythmic medications. It works by making your heart more resistant to abnormal activity.

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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.