The Cardiac Risk of Chloroquine in Unapproved Indications

NEW ORLEANS, March 26, 2020 /PRNewswire/ -- The current COVID-19 pandemic has impacted economic and social aspects of society around the globe.  Recently, the unapproved use of the antimalarial drug, chloroquine, has been touted as a treatment for COVID-19 with some reported deaths with its use in afflicted patients.  Chloroquine has been used clinically for over 60 years and the side effect profile is well established.  A common and potentially life-threatening side effect is a change in the ECG and in particular to the QT interval.  The QT interval corresponds to the time period during which the heart relaxes and prolongation of the QT interval can be associated with life-threatening arrhythmias and sudden cardiac death.  Because the QT interval is influenced by heart rate, it is most often given as the corrected QT interval or QTc. 

Even therapeutic doses of chloroquine in healthy patients are associated with prolongation of QTc¹, although this is generally well tolerated.  The concern with the current off-label use of chloroquine is that people with COVID-19 will self-medicate and take much more than the approved therapeutic dose used for treatment of malaria.  In fact, the WHO reported that most of the cases of life-threatening arrhythmias associated with chloroquine use occur when used to treat other indications². 

In order to provide insight into the effects of various doses of chloroquine on QTc, we used our proprietary QT Fingerprinting™ model to predict the change in QTc at therapeutic doses and doses 2 to 22 times higher than therapeutic.  As seen in the plot, the predicted increase in QTc (8.8ms) was very close to the observed increase in QTc (6.1ms) at a therapeutic dose.  Doses 2-22 times higher were associated with predicted increases in QTc up to approximately 35ms.  While these increases in QTc may be well tolerated in healthy patients, the concern is for patients who have underlying cardiac disease, risk factors for QT prolongation, or are taking other drugs which prolong the QT interval.  This is why chloroquine has specific warnings in its labeling to inform of the potential danger in patients with underlying risk factors (cardiac disease, hypokalemia, hypomagnesemia, bradycardia)³. The QTc prolonging effects of chloroquine will very likely be much greater and life-threatening in patients who take more than the prescribed dose and have existing risk factors.  Caution should be exercised by government leaders and the public in assuming chloroquine is either effective in treating COVID-19 or without significant side-effects.

By: Willam J. Crumb Jr., Ph,D. Director of Scientific Operations, Nova Research Laboratories
New Orleans, LA   [email protected]

1  Pukrittayakamee S et al. Pharmacokinetic Interactions between Primaquine and Chlroquine. Antimicrobial Agents and Chemotherap. 2014. 58:3354-3359.
2  WHO Evidence Review Group. The cardiotoxicity of antimalarials. 2017. http://www.who.int/malaria/mpac/mpac-mar2017-erg-cardiotoxicity-report-session2.pdf.
3  ARALEN CHLOROQUINE PHOSPHATE, USP Label – FDA, www.accessdata.fda.gov › drugsatfda_docs › label

SOURCE Nova Research Laboratories