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Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon

Lookup NU author(s): Professor Ann DalyORCiD


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Coumarin derivatives, such as warfarin, acenocoumarol and phenprocoumon are frequently prescribed oral anticoagulants to treat and prevent thromboembolism. Because there is a large inter-individual and intra-individual variability in dose-response and a small therapeutic window, treatment with coumarin derivatives is challenging. Certain polymorphisms in CYP2C9 and VKORC1 are associated with lower dose requirements and a higher risk of bleeding. In this review we describe the use of different coumarin derivatives, pharmacokinetic characteristics of these drugs and differences amongst the coumarins. We also describe the current clinical challenges and the role of pharmacogenetic factors. These genetic factors are used to develop dosing algorithms and can be used to predict the right coumarin dose. The effectiveness of this new dosing strategy is currently being investigated in clinical trials.

Publication metadata

Author(s): Verhoef TI, Redekop WK, Daly AK, van Schie RMF, de Boer A, Maitland-van der Zee AH

Publication type: Article

Publication status: Published

Journal: British Journal of Clinical Pharmacology

Year: 2014

Volume: 77

Issue: 4

Pages: 626-641

Print publication date: 01/04/2014

ISSN (print): 0306-5251

ISSN (electronic): 1365-2125

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/bcp.12220


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Funder referenceFunder name
Dutch Health Care Insurance Board (CVZ)
EU InnovativeMedicines Initiative (IMI)
Dutch Ministry of Health and industry
Netherlands Organisation for Health Research and Development (ZonMW)
Royal Dutch Pharmacists Association (KNMP)
HEALTH-F2-2009-223062European Community