Spontaneous reported cardiotoxicity induced by lopinavir/ritonavir in COVID-19. An alleged past-resolved problem

INTERNATIONAL JOURNAL OF CARDIOLOGY

卷:324

Article

Fresse, Audrey¹  Viard, Delphine¹  Romani, Serena¹  Gerard, Alexandre¹  Lepelley, Marion²  Rocher, Fanny¹  Salem, Joe-Elie^3,4,5  Drici, Milou-Daniel¹ 

[1] Univ Cote dAzur, Dept Clin Pharmacol, Med Ctr, Pasteur Hosp, Bat J4,30,Ave Voie Romaine,CS51069, F-06001 Nice 01, France

[2] Univ Grenoble, Med Ctr, RCPV Grenoble, F-38043 Grenoble, France

[3] Sorbonne Univ, Pitie Salpetriere Hosp, AP HP, INSERM,Clin Invest Ctr,Dept Pharmacol, CIC 1901, F-75013 Paris, France

[4] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA

[5] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA

关键词: Lopinavir-ritonavir drug combination;    Cardiotoxicity;    COVID-19;    Drug-related side effects and adverse reactions;    Long QT syndrome;    Cardiac arrhythmia;    Conduction disorder;   

DOI  :  10.1016/j.ijcard.2020.10.028

来源: Elsevier

【 摘 要 】

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. (C) 2020 Elsevier B.V. All rights reserved.

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