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Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon.
Br J Clin Pharmacol. 2014 Apr; 77(4):626-41.BJ

Abstract

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.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

23919835

Citation

Verhoef, Talitha I., et al. "Pharmacogenetic-guided Dosing of Coumarin Anticoagulants: Algorithms for Warfarin, Acenocoumarol and Phenprocoumon." British Journal of Clinical Pharmacology, vol. 77, no. 4, 2014, pp. 626-41.
Verhoef TI, Redekop WK, Daly AK, et al. Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon. Br J Clin Pharmacol. 2014;77(4):626-41.
Verhoef, T. I., Redekop, W. K., Daly, A. K., van Schie, R. M., de Boer, A., & 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), 626-41. https://doi.org/10.1111/bcp.12220
Verhoef TI, et al. Pharmacogenetic-guided Dosing of Coumarin Anticoagulants: Algorithms for Warfarin, Acenocoumarol and Phenprocoumon. Br J Clin Pharmacol. 2014;77(4):626-41. PubMed PMID: 23919835.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon. AU - Verhoef,Talitha I, AU - Redekop,William K, AU - Daly,Ann K, AU - van Schie,Rianne M F, AU - de Boer,Anthonius, AU - Maitland-van der Zee,Anke-Hilse, PY - 2013/03/13/received PY - 2013/07/17/accepted PY - 2013/8/8/entrez PY - 2013/8/8/pubmed PY - 2014/12/15/medline KW - CYP2C9 KW - VKORC1 KW - acenocoumarol KW - pharmacogenetics KW - phenprocoumon KW - warfarin SP - 626 EP - 41 JF - British journal of clinical pharmacology JO - Br J Clin Pharmacol VL - 77 IS - 4 N2 - 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. SN - 1365-2125 UR - https://www.unboundmedicine.com/medline/citation/23919835/Pharmacogenetic_guided_dosing_of_coumarin_anticoagulants:_algorithms_for_warfarin_acenocoumarol_and_phenprocoumon_ L2 - https://doi.org/10.1111/bcp.12220 DB - PRIME DP - Unbound Medicine ER -