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.

Additional Metadata
Keywords acenocoumarol, CYP2C9, pharmacogenetics, phenprocoumon, VKORC1, warfarin
Persistent URL dx.doi.org/10.1111/bcp.12220, hdl.handle.net/1765/71953
Journal British Journal of Clinical Pharmacology
Grant This work was funded by the European Commission 7th Framework Programme; grant id fp7/223062 - A pharmacogenomic approach to coumarin anticoagulant therapy (EU-PACT)
Citation
Verhoef, T.I, Redekop, W.K, Daly, A.K, van Schie, R.F.M, de Boer, A.C, & Maitland-van der Zee, A-H. (2014). Pharmacogenetic-guided dosing of coumarin anticoagulants: Algorithms for warfarin, acenocoumarol and phenprocoumon. British Journal of Clinical Pharmacology, 77(4), 626–641. doi:10.1111/bcp.12220