Cardiac Events Potentially Associated to Remdesivir: An Analysis from the European Spontaneous Adverse Event Reporting System

Abstract

Remdesivir was recommended for hospitalized patients with COVID-19. As already reported in the Summary of Product Characteristics, most of remdesivir’s safety concerns are hepatoxicity and nephrotoxicity related. However, some cases have raised concerns regarding the potential cardiac events associated with remdesivir; therefore, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency requested to investigate all available data. Therefore, we analyzed all Individual Case Safety Reports (ICSRs) collected in the EudraVigilance database focusing on cardiac adverse events. From April to December 2020, 1375 ICSRs related to remdesivir were retrieved from EudraVigilance, of which 863 (62.8%) were related to male and (43.3%) adult patients. A total of 82.2% of all AEs (N = 2604) was serious and one third of the total ICSRs (N = 416, 30.3%) had a fatal outcome. The most frequently reported events referred to hepatic/hepatobiliary disorders (19.4%,), renal and urinary disorders (11.1%) and cardiac events (8.4%). Among 221 cardiac ICSRs, 69 reported fatal outcomes. Other drugs for cardiovascular disorders were reported as suspected/concomitant together with remdesivir in 166 ICSRs (75.1%), 62 of which were fatal. Moreover, the mean time to overall cardiac event was 3.3 days (±2.2). Finally, disproportionality analysis showed a two-fold increased risk of reporting a cardiac adverse event associated with remdesivir compared to both hydroxychloroquine and azithromycin. This study showed that remdesivir could be associated to risk of cardiac events, suggesting a potential safety signal which has not been completely evaluated yet. Further studies are needed to confirm these findings.

The Reporting Frequency of Ketoacidosis Events with Dapagliflozin from the European Spontaneous Reporting System: The DAPA-KETO Study

“…The 94.31% of ICSRs were reported by HCPs in accordance with other studies [ 27 , 28 , 29 , 30 , 31 ]. In most ICSRs was reported one suspected drug and no concomitant drugs.…”

Efficacy of the early treatment with tocilizumab-hydroxychloroquine and tocilizumab-remdesivir in severe COVID-19 Patients

“…Wang et al showed that the use of remdesivir therapy was related to hyponatremia and hypokalemia which was the leading cause of discontinuing remdesivir in some patients [ 53 ]. In addition, as in our study, Rafaniello et al showed that remdesivir was associated with a two-fold increased risk in cardiac adverse reactions compared to both hydroxychloroquine and azithromycin [ 54 ]. Again, the elevated number of mechanically ventilated patients in the TCZ-RMV group, compared to the TCZ-HCQ group, might contribute to the detection of myocarditis either due to mechanical ventilation or the use of RMV.…”

Potential Cardiotoxic Effects of Remdesivir on Cardiovascular System: A Literature Review

“…Data analysis revealed a twofold increased risk of an adverse cardiac event associated with remdesivir in comparison with hydroxychloroquine and azithromycin. The result of this study showed that remdesivir might increase the risk of adverse cardiac events [ 15 ]. Sanchez-Codez et al reported a 13-year-old boy with a history of bronchial asthma who was admitted with severe bilateral pneumonia and hypoxemia by COVID-19 with a baseline heart rate of 80–90 bpm.…”