Azithromycin is a widely prescribed antibiotic, effective against various bacterial infections. It belongs to the macrolide class and inhibits bacterial protein synthesis. The QTc interval, measured by an electrocardiogram (ECG), reflects the heart’s electrical activity, specifically the time it takes for the ventricles to recharge after each beat.
Understanding QTc Prolongation
The QTc interval on an ECG represents the duration from the beginning of the Q wave to the end of the T wave, indicating the time required for ventricular depolarization and repolarization. This measurement is adjusted for heart rate (QTc) to allow consistent comparison, as the QT interval naturally changes with heart rate. A normal QTc interval is less than 450 milliseconds for men and less than 470 milliseconds for women.
When the QTc interval extends beyond these ranges, it is referred to as QTc prolongation. This signifies that the heart’s ventricles are taking longer than usual to reset for the next beat, which can disrupt the heart’s normal electrical stability. An abnormally long QTc interval can increase the susceptibility to irregular heart rhythms, particularly Torsades de Pointes (TdP). TdP is a rapid, irregular heartbeat that can progress to ventricular fibrillation, a chaotic electrical activity that prevents the heart from pumping blood effectively, potentially leading to sudden cardiac death.
Azithromycin’s Specific Effect on QTc
Azithromycin has the potential to influence the QTc interval, leading to its prolongation in some individuals. This effect is rare but a recognized concern due to the risk of Torsades de Pointes. The mechanism involves azithromycin’s interaction with the heart’s electrical system, specifically by affecting ion channels responsible for cardiac repolarization.
While other macrolides like erythromycin are known to block the hERG potassium channel, which directly delays cardiac repolarization, azithromycin’s effect is different. Azithromycin has a much lower affinity for the hERG channel compared to erythromycin, approximately 27 times lower. Research suggests azithromycin may prolong the QTc interval by increasing the late sodium current in heart cells, which can contribute to abnormal electrical activity. Although azithromycin can cause a small average QTc prolongation, some studies indicate it may prolong the action potential itself rather than solely delaying repolarization, which could differentiate its proarrhythmic potential from other macrolides.
Individuals at Higher Risk
Certain individuals face increased susceptibility to azithromycin-induced QTc prolongation and the associated risks of cardiac arrhythmias. Pre-existing heart conditions are a significant factor, including a known prolonged QTc interval, congenital long QT syndrome, slow heart rate (bradycardia), and uncompensated heart failure. Individuals with a history of serious arrhythmias or sudden cardiac death are also at elevated risk.
Electrolyte imbalances, specifically low levels of potassium (hypokalemia) or magnesium (hypomagnesemia), can further predispose individuals to QTc prolongation. These imbalances disrupt the electrical balance within heart cells, making them more vulnerable to arrhythmogenic effects. Concurrent use of other medications known to prolong the QTc interval significantly elevates the risk. These include certain antiarrhythmic drugs, some antipsychotics, or fluoroquinolone antibiotics. Advanced age and female sex have also been identified as independent risk factors for azithromycin-induced QTc prolongation. Elderly women with underlying heart conditions appear particularly vulnerable to this adverse effect.
Clinical Management and Safety Measures
Healthcare providers employ various strategies to manage and reduce the risk of QTc prolongation when prescribing azithromycin. A thorough review of a patient’s medical history is performed, including any pre-existing cardiac conditions, previous episodes of QTc prolongation, or family history of sudden cardiac death. This also involves detailed medication reconciliation to identify any other drugs the patient is taking that could interact with azithromycin or independently prolong the QTc interval.
For patients identified as high-risk, such as those with known QTc prolongation, electrolyte imbalances, or concurrent use of other QTc-prolonging medications, electrocardiogram (ECG) monitoring may be considered at baseline and during treatment. If azithromycin is deemed necessary, the benefits of treatment are carefully weighed against the potential cardiac risks, and alternative antibiotics that do not affect the QTc interval may be considered when appropriate for the infection. Patients are advised to inform their doctor about all medications they are currently taking, including over-the-counter drugs and supplements, and to report any symptoms such as palpitations, dizziness, or fainting during treatment.