"Off-label" use of hydroxychloroquine, azithromycin, lopinavir-ritonavir and chloroquine in COVID-19: A survey of cardiac adverse drug reactions by the French Network of Pharmacovigilance Centers

COVID-19 is an unprecedented challenge for physicians and scientists. Several publicized drugs are being used with not much evidence of their efficacy such as hydroxychloroquine, azithromycin or lopinavir-ritonavir. Yet, the cardiac safety of these drugs in COVID-19 deserves scrutiny as they are kno...

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Bibliographic Details
Published in:	Therapie Vol. 75; no. 4; p. 371
Main Authors:	Gérard, Alexandre, Romani, Serena, Fresse, Audrey, Viard, Delphine, Parassol, Nadège, Granvuillemin, Aurélie, Chouchana, Laurent, Rocher, Fanny, Drici, Milou-Daniel
Format:	Journal Article
Language:	English
Published:	France 01-07-2020
Subjects:	Adverse Drug Reaction Reporting Systems - statistics & numerical data Aged Azithromycin - administration & dosage Azithromycin - adverse effects Chloroquine - administration & dosage Chloroquine - adverse effects Coronavirus Infections - drug therapy COVID-19 Drug Combinations Electrocardiography Female France - epidemiology Heart Diseases - chemically induced Heart Diseases - epidemiology Humans Hydroxychloroquine - administration & dosage Hydroxychloroquine - adverse effects Long QT Syndrome - chemically induced Long QT Syndrome - epidemiology Lopinavir - administration & dosage Lopinavir - adverse effects Male Middle Aged Off-Label Use Pandemics Pharmacovigilance Pneumonia, Viral - drug therapy Risk Factors Ritonavir - administration & dosage Ritonavir - adverse effects France COVID-19 Cardiac adverse effects Hydroxychloroquine Arrhythmia Lopinavir Azithromycin QTc prolongation
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Summary:	COVID-19 is an unprecedented challenge for physicians and scientists. Several publicized drugs are being used with not much evidence of their efficacy such as hydroxychloroquine, azithromycin or lopinavir-ritonavir. Yet, the cardiac safety of these drugs in COVID-19 deserves scrutiny as they are known to foster cardiac adverse ADRs, notably QTc interval prolongation on the electrocardiogram and its arrhythmogenic consequences. Since March 27th, 2020, the French Pharmacovigilance Network directed all cardiac adverse drug reactions associated with "off-label" use of hydroxychloroquine, azithromycin and lopinavir-ritonavir in COVID-19 to the Nice Regional Center of Pharmacovigilance. Each Regional Center of Pharmacovigilance first assessed causality of drugs. We performed a specific analysis of these cardiac adverse drug reactions amidst an array of risk factors, reassessed the electrocardiograms and estimated their incidence in coronavirus disease 2019. In one month, 120 reports of cardiac adverse drug reactions have been notified, 103 of which associated with hydroxychloroquine alone (86%), or associated with azithromycin (60%). Their estimated incidence is 0.77% to 1.54% of all patients, notwithstanding strong underreporting. Lopinavir-ritonavir came third with 17 reports (14%) and chloroquine fourth with 3 reports (2.5%). There were 8 sudden, unexplained or aborted deaths (7%), 8 ventricular arrhythmias (7%), 90 reports of prolonged QTc (75%) most of them "serious" (64%), 48 of which proved ≥ 500ms, 20 reports of severe conduction disorders (17%) and 5 reports of other cardiac causes (4%). Six reports derived from automedication. "Off-label" use of treatments in COVID-19 increases the risk of cardiac ADRs, some of them avoidable. Even if these drugs are perceived as familiar, they are used in patients with added risk factors caused by infection. Precautions should be taken to mitigate the risk, even if they will be proven efficacious.
ISSN:	1958-5578
DOI:	10.1016/j.therap.2020.05.002