Amiodarone and Dronedarone Causes Liver Injury with Distinctly Different Clinical Presentations

Area of Science:

• Hepatology
• Pharmacology
• Toxicology

Background:

• Amiodarone and dronedarone are antiarrhythmic drugs with known risks of drug-induced liver injury (DILI).
• Understanding the distinct patterns of hepatotoxicity for these related drugs is crucial for patient management.

Purpose of the Study:

• To characterize and compare hepatotoxicity profiles of amiodarone and dronedarone.
• To analyze data from the Drug-Induced Liver Injury Network (DILIN) and the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Main Methods:

• Retrospective analysis of DILIN cases (2004-2020) and FAERS data (2009-2020) for amiodarone and dronedarone-induced liver injury.
• Review of clinical presentation, laboratory values, liver biopsy findings, and outcomes.

Main Results:

• Amiodarone DILI showed longer latency (388 days) and lower ALT at onset (118 U/L) compared to dronedarone (119 days, 1191 U/L).
• Amiodarone liver biopsies revealed fibrosis, steatosis, and Mallory-Denk bodies. Dronedarone DILI cases included acute liver failure and cases requiring liver transplant.
• Five deaths occurred in amiodarone cases (one from liver failure), and one death in a dronedarone case (non-liver related).

Conclusions:

• Amiodarone hepatotoxicity resembles alcoholic liver injury with steatosis and inflammation.
• Dronedarone-induced liver injury is less predictable, with shorter latency and often without steatosis.
• Pharmacokinetic differences likely contribute to the distinct mechanisms of hepatotoxicity for amiodarone and dronedarone.