Summary

The combination of dasatinib and azithromycin poses a significant risk for QT interval prolongation and potentially life-threatening cardiac arrhythmias. Both medications independently prolong the QT interval, and their concurrent use creates an additive effect that increases the risk of torsades de pointes and sudden cardiac death.

Introduction

Dasatinib is a second-generation tyrosine kinase inhibitor primarily used to treat chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). It works by blocking multiple tyrosine kinases including BCR-ABL, SRC family kinases, and others. Azithromycin is a macrolide antibiotic commonly prescribed for respiratory tract infections, skin infections, and sexually transmitted diseases. It inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit.

Mechanism of Interaction

Both dasatinib and azithromycin can prolong the QT interval through different mechanisms. Dasatinib blocks cardiac potassium channels (particularly hERG channels), delaying ventricular repolarization and extending the QT interval. Azithromycin also affects cardiac ion channels, specifically blocking potassium currents and potentially calcium channels, leading to QT prolongation. When used together, these effects are additive, significantly increasing the risk of developing a prolonged QT interval and predisposing patients to dangerous ventricular arrhythmias such as torsades de pointes.

Risks and Symptoms

The primary clinical risk of combining dasatinib and azithromycin is the development of serious cardiac arrhythmias, including torsades de pointes, which can be fatal. Patients may experience symptoms such as dizziness, fainting, palpitations, or sudden cardiac arrest. The risk is particularly elevated in patients with pre-existing cardiac conditions, electrolyte imbalances (especially hypokalemia or hypomagnesemia), bradycardia, or those taking other QT-prolonging medications. Elderly patients and those with hepatic or renal impairment may also be at increased risk due to altered drug metabolism and clearance.

Management and Precautions

If concurrent use of dasatinib and azithromycin is necessary, close cardiac monitoring is essential. Obtain a baseline ECG and monitor QT intervals regularly during treatment. Correct any electrolyte abnormalities, particularly potassium and magnesium levels, before and during therapy. Consider alternative antibiotics with lower QT prolongation risk when possible. If the QT interval becomes significantly prolonged (>500 ms or >60 ms increase from baseline), consider discontinuing one or both medications. Patients should be counseled about symptoms of arrhythmias and advised to seek immediate medical attention if they experience dizziness, fainting, or palpitations.

Azithromycin interactions with food and lifestyle

Azithromycin can be taken with or without food. However, taking azithromycin with food may help reduce stomach upset in some patients. Antacids containing aluminum or magnesium should be avoided within 2 hours before or after taking azithromycin, as they may decrease the absorption of the medication. No significant interactions with alcohol have been established, but patients should use alcohol cautiously while taking any antibiotic due to potential effects on immune function and healing.