Abstract
The antiretroviral drug lopinavir/ritonavir has been recently repurposed for the treatment of COVID-19. Its empirical use has been associated with multiple cardiac adverse reactions pertaining to its ancillary multi-channel blocking properties, vaguely characterized until now. We aimed to characterize qualitatively the cardiotoxicity associated with lopinavir/ritonavir in the setting of COVID-19. Spontaneous notifications of cardiac adverse drug reactions reported to the national Pharmacovigilance Network were collected for 8 weeks since March 1st 2020. The Nice Regional Center of Pharmacovigilance, whose scope of expertise is drug-induced long QT syndrome, analyzed the cases, including the reassessment of all available ECGs. QTc ≥ 500 ms and delta QTc > 60 ms from baseline were deemed serious. Twenty-two cases presented with 28 cardiac adverse reactions associated with the empirical use of lopinavir/ritonavir in a hospital setting. Most adverse reactions reflected lopinavir/ritonavir potency to block voltage-gated potassium channels with 5 ventricular arrhythmias and 17 QTc prolongations. An average QTc augmentation of 97 ± 69 ms was reported. Twelve QTc prolongations were deemed serious. Other cases were likely related to lopinavir/ritonavir potency to block sodium channels: 1 case of bundle branch block and 5 recurrent bradycardias. The incidence of cardiac adverse reactions of lopinavir/ritonavir was estimated between 0.3% and 0.4%. These cardiac adverse drug reactions offer a new insight in its ancillary multi-channel blocking functions. Lopinavir/ritonavir cardiotoxicity may be of concern for its empirical use during the COVID-19 pandemic. Caution should be exerted relative to this risk where lopinavir/ritonavir summary of product characteristics should be implemented accordingly.
Keywords: COVID-19; Cardiac arrhythmia; Cardiotoxicity; Conduction disorder; Drug-related side effects and adverse reactions; Long QT syndrome; Lopinavir-ritonavir drug combination.
【저자키워드】 COVID-19, Cardiac arrhythmia, drug-related side effects and adverse reactions, Long QT syndrome, Cardiotoxicity, Conduction disorder, Lopinavir-ritonavir drug combination., 【초록키워드】 Treatment, Lopinavir/ritonavir, sodium, COVID-19 pandemic, hospital, Lopinavir, Ritonavir, risk, pharmacovigilance, arrhythmia, Cardiac arrhythmia, Adverse reactions, Characteristics, network, Potassium, incidence, Other, QTc, Adverse drug reaction, Adverse drug reactions, Lopinavir-ritonavir, QTC prolongation, Long QT syndrome, cardiac, Adverse reaction, Cardiotoxicity, ventricular arrhythmias, Side effect, bundle branch block, treatment of COVID-19, caution, average, drug combination, syndrome, center, functions, National, ECGs, antiretroviral drug, offer, MOST, Regional, conduction, Long, Bundle branch, analyzed, collected, reported, characterized, reflected, Spontaneous, baseline, potassium channel, ventricular, 【제목키워드】 reported, Spontaneous,