From the Guidelines
Azithromycin is contraindicated in patients with prolonged QT interval due to its potential to cause serious arrhythmias and increased risk for sudden death. According to a recent study published in the Journal of the American College of Cardiology in 2020 1, azithromycin is recognized as a rare cause of QT interval prolongation, serious arrhythmias, and increased risk for sudden death. The study highlights that advanced age and female sex are risk factors for azithromycin-induced QT prolongation. Key considerations for patients with prolonged QT interval include:
- Advanced age as a risk factor for azithromycin-induced QT prolongation
- Female sex as a risk factor for azithromycin-induced QT prolongation
- History of serious arrhythmias or sudden death
- Concomitant use of other QT-prolonging medications
- Presence of electrolyte abnormalities, such as hypokalemia or hypomagnesemia
- Bradycardia or heart failure
In patients with prolonged QT interval, alternative antibiotics that do not affect the QT interval may be preferable when appropriate for the infection being treated. If azithromycin is necessary, careful evaluation and monitoring are crucial to minimize the risk of QT prolongation and torsades de pointes. The mechanism behind azithromycin's QT-prolonging effect involves blocking potassium channels in cardiac cells, which can delay ventricular repolarization and potentially lead to torsades de pointes in susceptible individuals 1.
From the FDA Drug Label
QT Prolongation 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.
Co-administration of azithromycin increased the QTc interval in a dose-and concentration-dependent manner.
Azithromycin is not contraindicated in patients with prolonged QT interval, but the risk of QT prolongation should be considered when weighing the risks and benefits of azithromycin for at-risk groups, including patients with known prolongation of the QT interval. Providers should be aware of the potential risk of QT prolongation and take necessary precautions. 2 2
From the Research
Azithromycin and QT Interval Prolongation
- Azithromycin has been associated with an increased risk of QT interval prolongation, which can lead to life-threatening arrhythmias such as torsades de pointes 3, 4, 5, 6.
- Studies have shown that the risk of QT interval prolongation is higher in certain populations, such as elderly women with heart disease 3, patients aged 60-79 years 4, and those with underlying heart conditions or taking other QT-prolonging medications 5, 6.
- The FDA has warned healthcare providers to consider the risk of azithromycin-induced fatal cardiac arrhythmias in patients already at risk for cardiac death and other potentially arrhythmogenic cardiovascular conditions 3.
Contraindications and Precautions
- Azithromycin is not strictly contraindicated in patients with prolonged QT intervals, but caution is advised when prescribing the medication to these patients 4, 6.
- Patients with a history of QT interval prolongation, torsades de pointes, or other arrhythmias should be monitored closely while taking azithromycin 5, 6.
- Alternative antibiotics, such as amoxicillin, may be considered in patients at high risk for QT interval prolongation or other cardiac complications 4, 6.
Risk Factors and Monitoring
- Risk factors for azithromycin-induced QT interval prolongation include female sex, older age, heart disease, QTc interval prolonging drugs and metabolic inhibitors, hypokalemia, and bradycardia 3, 4, 5, 6.
- Patients taking azithromycin should be monitored for signs of QT interval prolongation, including electrocardiogram (ECG) changes and symptoms such as dizziness, syncope, or palpitations 4, 5, 6.
- Regular monitoring of QTc intervals and cardiac function is recommended in patients at high risk for azithromycin-induced QT interval prolongation 5, 6.