A systematic comparison of hepatobiliary adverse drug reactions in FDA and EMA drug labeling reveals discrepancies

Yue Wu; Wenzhong Xiao; Weida Tong; Jürgen Borlak; Minjun Chen

doi:10.1016/j.drudis.2021.09.009

A systematic comparison of hepatobiliary adverse drug reactions in FDA and EMA drug labeling reveals discrepancies

Drug Discov Today. 2022 Jan;27(1):337-346. doi: 10.1016/j.drudis.2021.09.009. Epub 2021 Oct 1.

Authors

Yue Wu¹, Wenzhong Xiao², Weida Tong¹, Jürgen Borlak³, Minjun Chen⁴

Affiliations

¹ Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA.
² Harvard Medical School, Boston, MA, USA; Massachusetts General Hospital, Boston, MA, USA.
³ Center of Pharmacology and Toxicology, Hannover Medical School, 30625 Hannover, Germany. Electronic address: borlak.juergen@mh-hannover.de.
⁴ Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA. Electronic address: minjun.chen@fda.hhs.gov.

PMID: 34607018
DOI: 10.1016/j.drudis.2021.09.009

Abstract

Drug labeling informs physicians and patients on the safe and effective use of medication. However, recent studies suggested discrepancies in labeling of the same drug between different regulatory agencies. Here, we evaluated the hepatic safety information in labeling for 549 medications approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Limited discrepancies were found regarding risk for hepatic adverse drug reactions (ADRs) (8.7% in hepatic ADR warnings and 21.3% in contraindication for liver disease), while caution should be exercised over drugs with inconsistencies in contraindications for liver disease and evidence for hepatotoxicity (4.9%). Most discrepancies were attributable to less-severe hepatic events and low-frequency hepatic ADR reports and had limited implication on clinical outcomes.

Keywords: Adverse drug reactions; Contraindication; Drug labeling; Drug-induced liver injury; EMA; FDA; LiverTox; Warnings and precautions.

Published by Elsevier Ltd.

Publication types

Research Support, U.S. Gov't, P.H.S.
Review

MeSH terms

Chemical and Drug Induced Liver Injury* / etiology
Chemical and Drug Induced Liver Injury* / prevention & control
Drug Approval / statistics & numerical data
Drug Labeling* / methods
Drug Labeling* / standards
European Union / statistics & numerical data
Humans
Safety Management* / methods
Safety Management* / organization & administration
Safety Management* / statistics & numerical data
United States