Abstract
Background: Warfarin is a commonly used oral anticoagulant. It has a narrow therapeutic window and wide variation in individualized dosing, and is used clinically for the treatment of thromboembolic diseases. Due to the widespread use of traditional Chinese medicine (TCM) in China and the complex composition and diverse mechanisms of action of TCM, the combination of TCM and warfarin in patients has led to fluctuations in the international normalized ratio of warfarin or bleeding. To ensure rational clinical use, we summarize the TCMs with which warfarin interacts and the possible mechanisms, with a view to providing a clinical reference.Aim of the study: To summarize the mechanisms by which Chinese herbal medicines affect the enhancement or weakening of the anticoagulant effect of warfarin, to provide theoretical references for clinicians and pharmacists to use warfarin safely and rationally, and to avoid the adverse effects associated with the combination of Chinese herbal medicines and warfarin.Methods: A computerized literature search of electronic databases, including PubMed, MEDLINE, Cochrane Library, Web of Science (WOS), China National Knowledge Infrastructure (CNKI) and WANFANG Data was performed. Key words used in the literature search were “warfarin”, “Chinese medicine”, “traditional Chinese medicine”, “Chinese patent medicine” etc. and their combinations in a time limit from January 1, 1990 to May 1, 2021. A total of 64 articles were obtained following the selection process, including clinical reports, pharmacological experiments and in vitro experiments which were reviewed to determine the mechanism of the anticoagulant effect of herbal medicine on warfarin.Results: The mechanisms affecting the anticoagulant effect of warfarin are complex, and herbal medicines may enhance and diminish the anticoagulant effect of warfarin through a variety of mechanisms; thus, clinical use needs to be cautious. Some herbal medicines have shown inconsistent results in both in vivo and ex vivo experiments, pharmacology and clinical studies, and should be the focus of future research.Conclusion: With the widespread use of TCM, the combination of warfarin and TCM is more common. This article will promote clinicians’ knowledge and understanding of the TCMs which interact with warfarin, in order to avoid the occurrence of adverse clinical treatment processes, and improve the efficacy and safety.
Highlights
Warfarin, known as benzylacetone coumarin sodium, warfarin sodium, etc., is a bicoumarin-like ingredient and was first extracted from wild clover by Wisconsin Alumni Foundation-funded chemist Karl Paul Link in 1940, and was officially approved by the Food and Drug Administration (FDA) in 1954 for use as an oral anticoagulant, and is still used (Wong et al, 2010)
Key words used in the literature search were “warfarin”, “Chinese medicine”, “traditional Chinese medicine”, “Chinese patent medicine” etc. and their combinations in a time limit from January 1, 1990 to May 1, 2021
Warfarin sodium is cleared by hepatic metabolism to inactive metabolites excreted in the urine by the hepatic microsomal enzymes CYP2C9 (S-warfarin) and by CYP1A2 and CYP3A (R-warfarin)
Summary
Known as benzylacetone coumarin sodium, warfarin sodium, etc., is a bicoumarin-like ingredient and was first extracted from wild clover by Wisconsin Alumni Foundation-funded chemist Karl Paul Link in 1940, and was officially approved by the Food and Drug Administration (FDA) in 1954 for use as an oral anticoagulant, and is still used (Wong et al, 2010). Warfarin is often used in combination with Chinese medicinal herbs and proprietary Chinese medicines for the treatment of thromboembolic diseases. Due to the complex composition and various mechanisms of action of Chinese medicines, coupled with the narrow therapeutic window of warfarin and large differences in individual doses, the prothrombin time (PT) and international normalized ratio (INR) are often used as its anticoagulation monitoring indices. Warfarin is a commonly used oral anticoagulant It has a narrow therapeutic window and wide variation in individualized dosing, and is used clinically for the treatment of thromboembolic diseases. Due to the widespread use of traditional Chinese medicine (TCM) in China and the complex composition and diverse mechanisms of action of TCM, the combination of TCM and warfarin in patients has led to fluctuations in the international normalized ratio of warfarin or bleeding. To ensure rational clinical use, we summarize the TCMs with which warfarin interacts and the possible mechanisms, with a view to providing a clinical reference
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