(P-289) Drug-induced Liver Injury Associated with Lopinavir-ritonavir in Patients with COVID-19: A Disproportionality Analysis of U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) Data

Location: Poster Gallery-Pharmacovigilance

Presenting Author(s)

HT

Huilin Tang

University of Florida Department of Pharmaceutical Outcomes and Policy
Gainesville, Florida, United States

Co-Author(s)

Lz

Liyuan zhou

Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA, North Carolina, United States
XL

Xiaotong Li

Institute for Drug Evaluation, Peking University Health Science Center, Beijing, China, China (People's Republic)
AK

Alan Kinlaw

Assistant Professor
UNC Eshelman School of Pharmacy, United States
Jeff Y. Yang

PhD Student
UNC Gillings School of Global Public Health
Chapel Hill, North Carolina, United States
AM

Andrew Moon

Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA, United States
EB

Edward Barnes

Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA, United States
Tiansheng Wang

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA, United States

Background: Liver injury has been documented independently in novel coronavirus disease 2019 (COVID-19) patients and patients treated with lopinavir-ritonavir; however, liver injury associated with lopinavir-ritonavir in patients with COVID-19 has not been well described.

Objectives: This study aimed to investigate the drug-induced liver injury associated with lopinavir-ritonavir among the patients with COVID-19 using the US Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods: We searched FAERS between 2020Q1 and 2020Q3 to include all reports of COVID-19. We conducted a disproportionality analysis to evaluate the association between lopinavir-ritonavir and risk of drug-induced liver injury (or severe drug-induced liver injury) and calculated their reporting odds ratios (RORs) with 95% confidence intervals (CIs) in the following 3 comparisons:1) lopinavir-ritonavir vs all other drugs;2) lopinavir-ritonavir vs hydroxychloroquine/chloroquine;3) lopinavir-ritonavir vs remdesivir.

Results: A total of 1,754 reports of drug-induced liver injury in patients with COVID-19. The ROR for drug-induced liver injury was 1.4 (95% CI, 1.1-1.7), 3.6 (95% CI, 2.7-4.7), and 0.8 (95% CI, 0.7-1.0) when comparing lopinavir-ritonavir with all other drugs, hydroxychloroquine/chloroquine only, and remdesivir, respectively. For severe drug-induced liver injury, RORs for lopinavir-ritonavir provided evidence of an association compared with all other drugs (ROR, 4.9; 95% CI, 3.7-6.5), compared with hydroxychloroquine/chloroquine only (ROR, 4.3; 95% CI, 3.0-6.2), and compared with remdesivir (ROR, 10.4; 95% CI, 7.2-15.0).

Conclusions: In the FAERS, we observed a disproportional signal for severe drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19. Given little evidence of the benefit for the use of lopinavir-ritonavir in patients with COVID-19 as well as the possible increase in risk for liver injury, other medications might be recommended for routine treatment of COVID-19 instead of lopinavir-ritonavir.