Major
Established
Description
Both azithromycin and hydroxychloroquine independently prolong the cardiac QT interval; concurrent use substantially raises the risk of torsades de pointes and sudden cardiac death.
Mechanism
Both drugs block cardiac hERG (IKr) potassium channels, prolonging ventricular repolarization in an additive or supra-additive manner.
Clinical Significance
This combination received global attention during the COVID-19 pandemic when pharmacovigilance data showed excess arrhythmia-related deaths.
Management
Avoid concurrent use; obtain baseline and follow-up ECG if co-prescription is unavoidable, correct electrolytes, and avoid other QT-prolonging drugs.