Risk of QT Prolongation related to Drug used in COVID-19: Use of a database mining strategy to detect risk and predict adverse reactions.

FERREIRÓS GAGO MARÍA LAURA; DI GIROLAMO GUILLERMO; KELLER GA; DIEZ, ROBERTO A; DI SALVO HE1

Ciudad Autónoma de Buenos Aires - VIRTUAL

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2020 SAIC-SAI-SAFIS; 2020

Sociedad Argentina de Investigación Clínica (SAIC)

Introduction: The search for effective drugs in COVID led to an insufficient assessment of adverse reactions. Hydroxychloroquine was has a known risk of arrhytmia and was used without proven efficacy. This situation may have been partially repeated for other drugs. We analyzed the FAERS database in search of signals of new associations. Methods: FAERS reports (2004 to 2020) were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify TdP/QTP cases. We calculated the Reporting Odds Ratios (RORs), Proportional Reporting Ratio (PPR), Yule?s Q, and Chi Square with Yate?s correction for the association between each Drug used in CoViD treatment, moxifloxacine (positive control) and ceftriaxone (negative control) using MedDRA Standarized Medical Querry for QT Prolongation. Signals were defined as lower limit of the 95%CI greater than 1.0 (for ROR or PPR), greater than 0 (Yule?s Q) or a P value less than 0,05 (Chi Square). Results: 17.734.379 reports (including 48.364 arrhytmias) were analyzed. No significant signals were found for Dexamethasone, Remdesivir, ritonavir / lopinavir, and Ceftriaxone. A significant signal was found for prolonged qt prolongation and arrhythmias for: hydroxychlorocine 1.23 (1.10 to 1.56); ivermectin 1.63 (1.09 to 4.51); tocilizumab 1.07 (1.02 to 0.28); ticarcilina clavulanico 3.57 (2.60 to 4.91); piperacillin + tazobactam 2.32 (2.17 to 2.48); ampicillin + sulbactam 1.91 (1.68 to 2.17); clarithromycin 1.46 (1.37 to 1.55); azithromycin 1.54 (1.44 to 1.64); and moxifloxacin 1.84 (1.76 to 1.93). Discussion: There is not only a risk of arrhythmias with drugs such as hydroxychloroquine, but also with antibiotics used in the management of COVID (ampicillin + sulbactam, clarithromycin), and other drugs under study for potential efficacy in COVID (azithromycin, toxilizumab, ivermectin). This information must be taken into account to monitor the ECG and prevent pharmacodynamic interactions that enhance the effect.