Abstract: International Journal of Clinical Pharmacy (2021) 43:1116–1122 https://doi.org/10.1007/s11096-021-01311-5 RESEARCH ARTICLE 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 Huilin Tang1 · Liyuan Zhou2 · Xiaotong Li3 · Alan C. Kinlaw4,5 · Jeff Y. Yang6 · Andrew M. Moon7,8 · Edward L. Barnes7,8 · Tiansheng Wang6 Received: 4 May 2021 / Accepted: 21 July 2021 / Published online: 30 July 2021 © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021 Abstract Background Liver injury has been documented independently in novel coronavirus disease 2019 (COVID-19) patients and patients treated with lopinavir-ritonavir. Objective to investigate the drug-induced liver injury associated with lopinavirritonavir among the patients with COVID-19. Methods We conducted a disproportionality analysis of US Food and Drug Administration Adverse Event Reporting System (FAERS) between 2020Q1 and 2021Q1 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). Results A total of 3,425 cases of drug-induced liver injury were reported in 19,782 patients with COVID-19. The ROR for drug-induced liver injury was 2.99 (2.59–3.46), 3.16 (2.68–3.73), and 5.39 (4.63–6.26) 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 (3.98; 3.15–5.05), compared with hydroxychloroquine/chloroquine only (5.33; 4.09–6.94), and compared with remdesivir (3.85; 3.03–4.89). Conclusions In the FAERS, we observed a disproportional signal for druginduced liver injury associated with lopinavir-ritonavir in patients with COVID-19. Keywords FAERS · Liver injury · Lopinavir-ritonavir · Novel coronavirus disease 2019 Impacts on practice • COVID-19 patients treated with lopinavir-ritonavir are at increased risk of liver injury. Huilin Tang and Liyuan Zhou contributed equally to this work * Huilin Tang tang.huilin@ufl.edu 1 Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, FL, USA 2 Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA 3 Institute for Drug Evaluation, Peking University Health Science Center, Beijing, China 4 Division of Pharmaceutical Outcome and Policy, University of North Carolina School of Pharmacy, Chapel Hill, NC, USA 13 Vol:.(1234567890) 5 Cecil G. Sheps Center for Health Services Research, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA 6 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA 7 Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA 8 Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA International Journal of Clinical Pharmacy (2021) 43:1116–1122 • The risk of liver injury reinforces recent..