Analysis of chloroquine fatal cardiotoxic adverse events based on VigiBase database

Abstract

Objective To analyze the clinical characteristics of lethal cardiac adverse events associated with chloroquine, the antiviral drug recommended for the treatment of novel coronavirus pneumonia, and provide reference for clinical safe drug use. Methods Search the WHO global database of individual case safety reports (VigiBase) for chloroquine fatal adverse events of cardiac disorders. All variables contained in the lethal quinidine associated cardiac disorders were reviewed. Well-documented reports (VigiGrade completeness score ≥ 0.80 or with informative narrative) were fully analyzed and described with focus on clinical features of the cases. The adverse events were coded using the systematic organ classification (SOC) and preferred term (PT) of ICH MedDRA 22.1. Results Up to 23 February 2020, there were 45 unique cases of fatal heart injuries reported in VigiBase from 16 countries. Thirty of these cases were reported with sufficient information and were analyzed fully. Among them, 20 cases with fatal cardiac adverse events occurred after a SINGLE large dose of chloroquine: 17 cases were related to overdose (15 suicide or suspected suicide, 2 cases of children taking the medication by mistake); and three cases were under clinical use; 18 cases (90%) died of arrhythmia and cardiac arrest. Electrocardiogram (ECG) showed QRS or QT interval prolongation in 6 cases where ECG results were mentioned and 4 of them with severe hypokalemia; Ten cases with fatal cardiac adverse events occurred following clinical treatment with MULTIPLE administration of chloroquine: 4 cases were treated for 23 days to 2 months, and died of heart failure / cardiac arrest or myocardial infarction. Chloroquine was used in 6 patients for 20 months to 29 years. Cardiomyopathy occurred in all the 6 cases (confirmed by biopsy in 3 of them). Conclusion Cardiac toxicity was the primary cause of chloroquine fatal adverse events. Single large dose of chloroquine related mainly to arrhythmia; and cardiomyopathy was the main manifestation of multiple administration. Intravenous administration, combination with other drugs or diseases that increase the risk of chloroquine's cardiac adverse events, can increase the risk of cardiac toxicity. Key words: chloroquine; arrhythmia, cardiac; electrocardiography, long-QT syndrome(LQTS); cardiomyopathy; drug toxicity; adverse drug reaction reporting system