Document Type
Article
Publication Date
2-28-2024
Abstract
OBJECTIVE: To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database.
METHODS: Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020.
RESULTS: Among DILIN's 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0.50) and the median ALT at DILI onset was significantly lower with amiodarone (118 vs 1191 U/L, p = 0.05). Liver biopsies in five amiodarone cases showed fibrosis, steatosis, and numerous Mallory-Denk bodies. Five patients died although only one from liver failure. One patient with dronedarone induced liver injury died of a non-liver related cause. Nine additional cases of DILI due to dronedarone requiring hospitalization were identified in the FAERS database. Three patients developed liver injury within a month of starting the medication. Two developed acute liver failure and underwent urgent liver transplant, one was evaluated for liver transplant but then recovered spontaneously, while one patient with cirrhosis died of liver related causes.
CONCLUSION: Amiodarone hepatotoxicity resembles that seen in alcohol related liver injury, with fatty infiltration and inflammation. Dronedarone is less predictable, typically without fat and with a shorter latency of use before presentation. These differences may be explained, in part, by the differing pharmacokinetics of the two drugs leading to different mechanisms of hepatotoxicity.
Recommended Citation
Pop, Alexander; Halegoua-De Marzio, Dina; Barnhart, Huiman; Kleiner, David; Avigan, Mark; Gu, Jiezhun; Chalasani, Naga; Ahmad, Jawad; Fontana, Robert J.; Lee, William; Barritt, A. Sidney; Durazo, Francisco; Hayashi, Paul H.; and Navarro, Victor J., "Amiodarone and Dronedarone Causes Liver Injury with Distinctly Different Clinical Presentations" (2024). Einstein Health Papers. Paper 42.
https://jdc.jefferson.edu/einsteinfp/42
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Language
English
Comments
This article is the author’s final published version in Digestive Diseases and Sciences, Volume 69, 2024, Pages 1479-1487.
The published version is available at https://doi.org/10.1007/s10620-023-08251-2. Copyright © The Author(s) 2024.
Publication made possible in part by support through a transformative agreement between Thomas Jefferson University and the publisher.