Coumarin-Induced Hepatotoxicity: A Narrative Review

Area of Science:

• Pharmacology
• Hepatology
• Clinical Therapeutics

Background:

• Coumarin is an effective treatment for primary and secondary lymphoedema.
• Clinical use is limited by potential hepatotoxicity, primarily mild to moderate transaminase elevation.
• Severe hepatotoxicity and liver failure are rare.

Purpose of the Study:

• To review coumarin's absorption, distribution, metabolism, and excretion (ADME) data.
• To analyze in vitro and in vivo hepatotoxicity studies.
• To discuss safety and tolerability data from clinical trials.

Main Methods:

• Literature review of coumarin ADME and hepatotoxicity studies.
• Analysis of in vitro and in vivo experimental data.
• Review of clinical trial safety and tolerability data.

Main Results:

• Coumarin-induced hepatotoxicity affects a small patient subset.
• Hepatotoxicity is likely due to alternative metabolic pathways involving specific CYP450 isoforms.
• Clinical data indicate mild to moderate transaminase elevation as the main adverse effect.

Conclusions:

• Coumarin's hepatotoxicity is idiosyncratic, linked to specific metabolic profiles.
• Identifying patients at risk is crucial for safe coumarin utilization.
• Further research can enable wider therapeutic application for lymphoedema patients.