Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Coumarin-induced Hepatotoxicity: A Narrative Review

Version 1 : Received: 21 September 2022 / Approved: 22 September 2022 / Online: 22 September 2022 (03:20:25 CEST)

How to cite: Pitaro, M.; Croce, N.; Gallo, V.; Arienzo, A.; Salvatore, G.; Antonini, G. Coumarin-induced Hepatotoxicity: A Narrative Review. Preprints 2022, 2022090330 (doi: 10.20944/preprints202209.0330.v1). Pitaro, M.; Croce, N.; Gallo, V.; Arienzo, A.; Salvatore, G.; Antonini, G. Coumarin-induced Hepatotoxicity: A Narrative Review. Preprints 2022, 2022090330 (doi: 10.20944/preprints202209.0330.v1).

Abstract

Coumarin is an effective treatment for primary lymphoedema, as well as lymphoedema related to breast cancer radiotherapy or surgery. However, its clinical use is limited in several countries due to the possible occurrence of hepatotoxicity, mainly in the form of mild to moderate transaminase elevation. Noteworthy, only few cases of severe hepatotoxicity have been described in literature, with no reported cases of liver failure. Data available on coumarin absorption, distribution, metabolism and excretion have been reviewed, focusing on hepatotoxicity studies carried out in vitro and in vivo. Finally, safety and tolerability data from clinical trials have been thoroughly discussed. On the basis of these data, coumarin-induced hepatotoxicity seems to be restricted to a small subset of patients, probably due to the expression of specific alleles of CYP450 isoform not yet well characterized. In summary, more research is needed in order to identify patients at risk of developing hepatotoxicity following coumarin treatment, in order to improve the risk/benefit ratio of the product and allow more patients to benefit from its therapeutic properties.

Keywords

coumarin; 1,2-benzopyrone; Melilotus officinalis; narrative review; primary lymphoedema; secondary lymphoedema; hepatotoxicity

Subject

LIFE SCIENCES, Other

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