Study on signal mining of adverse reactions induced by lopinavir/ritonavir based on FDA Adverse Event Reporting System (FAERS) database

Abstract

Objective To detect the adverse drug reaction (ADR) signals of lopinavir / ritonavir(LPV/r) , which is the major recommended drugs for the treatment of Novel Coronavirus Pneumonia(NCP) due to SARS-CoV-2, using the U.S. FDA Adverse Event Reporting System (FAERS) database, and provide reference for the safe and rational medication. Methods Reporting Odds Ratio (ROR) was used to mine the FAERS database report data from the first quarter of 2010 to the third quarter of 2019. A positive ADR signal is determined if the number of reports is greater than 3 and the 95% CI lower limit of ROR is greater than 1. We use the system organ classification (SOC) of the WHO ADR terminology and preferred terms (PT) to classify and coding ADR. Results We identified 13 335 cases of LPV/r ADR reports, accounting for 0.04% of the total ADR reports (32 788 098 cases), and 455 positive ADR signals in 1968 involved ADRs in the FEARS database over the past decade. 95 types of ADRs were identified after deduplication among the top 50 of the reported number and the signal strength (95% CI lower limit of the ROR value) . There are 36 types of ADRs mentioned in the package insert which accounting for 37.9%. There are 43 types of ADR (45.3%) related with the perinatal and neonatal. There 144 cases of ADR due to drug interactions, and the number of reported cases ranked 9th. Conclusions There are strong signals in Gastrointestinal system damage, body as a whole-general disorders、hepatobiliary system damage, metabolic and nutritional disorders, which verifies the ADRs in the package insert. This study suggests potential new serious ADRs that are not included in the package insert ,including fetal abnormalities, neonatal and infant abnormalities, and tumors. There may be risks associated with lopinavir/ritonavir use in pregnant women and infants, as well as an increased risk when combined other drugs. Pre-medication evaluation and medication monitoring should be done to reduce the risk of ADR. Key words: Lopinavir/ritonavir; New coronavirus; Novel coronavirus pneumonia; FAERS database; Adverse reaction signals; Real-world data