Drug Interactions and QTc in Exploratory COVID-19 Treatment

Authors:
Roden DM, Harrington RA, Poppas A, Russo AM.
Citation:
Considerations for Drug Interactions on QTc in Exploratory COVID-19 (Coronavirus Disease 2019) Treatment. Circulation 2020;Apr 8:[Epub ahead of print].

The key points about drug interactions impacting QT interval in a postulated treatment algorithm for COVID-19, according to this Consensus Report, are as follows:

  1. Hydroxychloroquine and azithromycin are definite causes of torsade de pointes and are listed as such at crediblemeds.org. They can provoke proarrhythmia via mechanisms beyond block of IKr implicated in usual cases of torsade de pointes. There are very limited data evaluating the safety of combination therapy.
  2. The US Food and Drug Administration Adverse Event Reporting System lists 458 cardiac arrests suspected to be secondary to the administration of chloroquine, hydroxychloroquine, lopinavir/ritonavir, and azithromycin individually.
  3. The following interventions may be considered in order to reduce the risk of torsade de pointes and death:
    • Withholding the drugs in patients with baseline QT prolongation (especially QTc ≥500 msec) or with known congenital long QT syndrome.
    • Monitoring cardiac rhythm and QT interval and drug withdrawal if QTc exceeds 500 msec.
    • Correcting of hypokalemia and hypomagnesemia.
    • Avoiding concomitant QTc prolonging agents.

Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Prevention, Implantable Devices, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, Novel Agents, Statins

Keywords: Arrhythmias, Cardiac, Azithromycin, Chloroquine, COVID-19, Coronavirus, Heart Arrest, Heart Defects, Congenital, Hydroxychloroquine, Hypokalemia, Long QT Syndrome, Lopinavir, Pharmaceutical Preparations, Ritonavir, severe acute respiratory syndrome coronavirus 2, Secondary Prevention, Torsades de Pointes


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