From the Guidelines
Azithromycin can potentially cause cardiac issues, particularly QT interval prolongation, which may lead to dangerous heart rhythm disturbances, and its use should be approached with caution in patients with pre-existing heart conditions or risk factors for QT prolongation. Patients with electrolyte abnormalities (especially low potassium or magnesium), or those taking other QT-prolonging medications, should also use azithromycin with caution 1. The risk is higher in elderly patients and those with congenital long QT syndrome. When prescribing azithromycin, consider obtaining a baseline ECG in high-risk patients and monitor for symptoms like palpitations, dizziness, or fainting during treatment.
The standard adult dose of azithromycin (500mg on day 1 followed by 250mg daily for 4 days) is generally safe for most patients without cardiac risk factors. However, the risk increases with higher doses or when combined with other QT-prolonging medications 1. The cardiac effects occur because azithromycin can block potassium channels in heart cells, delaying cardiac repolarization and extending the QT interval. If a patient develops concerning cardiac symptoms while taking azithromycin, they should seek immediate medical attention and consider discontinuing the medication after consulting with their healthcare provider.
Some key points to consider when prescribing azithromycin include:
- Advanced age and female sex have been implicated as risk factors for QT interval prolongation and cardiac arrhythmias 1
- Azithromycin can provoke non-pause-dependent polymorphic ventricular tachycardia 1
- The US Food and Drug Administration recommends careful review of patient-level risk factors for ventricular arrhythmias when using azithromycin 1
- Macrolides are known to cause ventricular arrhythmias that could be fatal, but the incidence with long-term azithromycin in COPD is unknown 1
From the FDA Drug Label
Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with macrolides, including azithromycin Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving azithromycin Providers should consider the risk of QT prolongation which can be fatal when weighing the risks and benefits of azithromycin for at-risk groups including: patients with known prolongation of the QT interval, a history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias or uncompensated heart failure patients on drugs known to prolong the QT interval patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval.
Azithromycin and Cardiac Issues: Azithromycin may cause QT prolongation, which can lead to cardiac arrhythmia and torsades de pointes, particularly in at-risk groups, such as patients with known QT interval prolongation, congenital long QT syndrome, or uncompensated heart failure. Providers should weigh the risks and benefits of azithromycin in these patients, and consider alternative treatments if necessary 2. Key points to consider include:
- QT prolongation can be fatal
- At-risk groups include patients with certain heart conditions or those taking certain medications
- Elderly patients may be more susceptible to drug-associated effects on the QT interval
- Alternative treatments should be considered in at-risk patients.
From the Research
Azithromycin and Cardiac Issues
- Azithromycin has been associated with an increased risk of cardiac issues, including QTc interval prolongation and torsade de pointes 3, 4, 5, 6, 7
- The US Food and Drug Administration has issued a warning regarding the use of azithromycin and the risk of fatal dysrhythmias 4
- Studies have shown that azithromycin can prolong the QTc interval, particularly in patients with additional risk factors such as female sex, older age, heart disease, and use of concurrent QTc interval prolonging drugs 3, 5, 6
- The risk of QT prolongation is increased in patients aged 60-79 years when exposed to azithromycin 6
- Azithromycin has been compared to other antibiotics, such as amoxicillin, and has been found to have a higher risk of QT prolongation 4, 6, 7
- Clinicians should exercise caution when using azithromycin, particularly in patients with underlying cardiac conditions or other risk factors for QT prolongation 3, 5, 6, 7
- The benefits and risks of azithromycin should be carefully considered when making prescription decisions, and alternative antibiotics may be preferred in certain cases 7