Pharmacotherapy Management for COVID-19 and Cardiac Safety: A Data Mining Approach for Pharmacovigilance Evidence from the FDA Adverse Event Reporting System (FAERS)

Jing Yuan; Minghui Li; Yiqun Yu; Tai-Ying Lee; Gang Lv; Bing Han; Xiaoqiang Xiang; Z Kevin Lu

doi:10.1007/s40801-021-00229-8

Pharmacotherapy Management for COVID-19 and Cardiac Safety: A Data Mining Approach for Pharmacovigilance Evidence from the FDA Adverse Event Reporting System (FAERS)

Drugs Real World Outcomes. 2021 Jun;8(2):131-140. doi: 10.1007/s40801-021-00229-8. Epub 2021 Feb 10.

Authors

Jing Yuan^#¹, Minghui Li^#², Yiqun Yu^#³, Tai-Ying Lee⁴, Gang Lv⁵, Bing Han^#³, Xiaoqiang Xiang⁶, Z Kevin Lu⁷

Affiliations

¹ Department of Clinical Pharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Pudong, Shanghai, 201203, People's Republic of China.
² University of Tennessee Health Science Center, Memphis, TN, USA.
³ Department of Pharmacy, Minhang Hospital, Fudan University, Shanghai, People's Republic of China.
⁴ University of South Carolina, 715 Sumter Street, CLS Building 311, Columbia, SC, 29208, USA.
⁵ General Surgery Department, 1st Medical Center of PLA General Hospital, Beijing, China.
⁶ Department of Clinical Pharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Pudong, Shanghai, 201203, People's Republic of China. xiangxq@fudan.edu.cn.
⁷ University of South Carolina, 715 Sumter Street, CLS Building 311, Columbia, SC, 29208, USA. lu32@email.sc.edu.

^# Contributed equally.

Abstract

Background: Several pharmacological agents, such as chloroquine/hydroxychloroquine, have been promoted for COVID-19 treatment or pre-exposure prophylaxis. However, no comprehensive evaluation of the safety of these possible agents is available, and is urgently needed.

Objective: The purpose of this study was to investigate the risks of cardiac adverse events associated with the possible pharmacotherapies for COVID-19, including certain antimalarial, antiviral, and antibiotic drugs.

Patients and methods: We conduced retrospective pharmacovigilance analyses of the US Food and Drug Administration Adverse Event Reporting System database. The reporting odds ratio (ROR), a data mining algorithm commonly used in pharmacovigilance assessment, was generated to quantify the detection signal of adverse events.

Results: Among individuals without coronavirus infection from 2015 Q1 to 2020 Q1, increased risks for cardiac disorders were found for antiviral agents such as chloroquine/hydroxychloroquine (ROR: 1.68; 95% confidence interval [CI] 1.66-1.70), lopinavir/ritonavir (ROR: 1.52; 95% CI 1.39-1.66), and antibiotics such as azithromycin (ROR: 1.37; 95% CI 1.30-1.44) and ceftriaxone (ROR: 1.92; 95% CI 1.80-2.05). Increased serious cardiac adverse events, including myocardial infarction, arrhythmia, and cardiac arrest, were also reported for these drugs. Further analyses of individuals with coronavirus infections revealed that 40% of individuals receiving chloroquine/hydroxychloroquine reported serious cardiac adverse events. Two cases resulted in QT prolongations and one case resulted in cardiac arrest. Chloroquine/hydroxychloroquine and azithromycin contributed to all the QT prolongation and cardiac arrest cases.

Conclusions: The current pharmacotherapies for COVID-19 are associated with increased risks of cardiac adverse events. Variations in the cardiac safety profiles of these pharmacotherapies were also observed. Clinicians should closely monitor patients with COVID-19, especially those at high risk, using chloroquine/hydroxychloroquine and azithromycin.