European Journal of Clinical Pharmacology

, 64:953

Evidence for a pharmacogenetic adapted dose of oral anticoagulant in routine medical practice

Review Article

DOI: 10.1007/s00228-008-0542-2

Cite this article as:
Becquemont, L. Eur J Clin Pharmacol (2008) 64: 953. doi:10.1007/s00228-008-0542-2


Oral anticoagulants (OA) are a leading cause of fatal haemorrhagic adverse events in relation with an important interindividual variability of response to these drugs. Besides several clinical factors, this interindividual variability of response to OA has a pharmacogenetic basis. Carriers of cytochrome P450 2C9 (CYP2C9)-deficient alleles have a reduced clearance of warfarin and are exposed to dramatic overdoses in the first weeks of treatment. Genetic polymorphisms of vitamin K epoxide reductase (VKORC1), the target of OA, identify patients with a high sensitivity to OA who are at risk of early overdose. Most pharmacogenetic evidence is presently restricted to warfarin. Several warfarin dosing algorithms have been constructed, adapted on CYP2C9 and VKORC1 genotypes and clinical factors, to predict the best dose for each patient. Carriers of one of allelic variant need a 20–30% reduction of warfarin dose. However, definite evidence concerning the usefulness of these algorithms in terms of reducing the frequency of major bleeding episodes is still lacking. Ongoing prospective randomised trials will ascertain definitive answer over the coming years.


Cytochrome P450 2C9VKORC1Oral anticoagulantsVitamin K antagonistsPharmacogeneticsDosing algorithmWarfarinAcenocoumarolPhenprocoumonFluindione

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Pharmacology Department, Faculté de médecine Paris SudUniversité Paris-SudLe Kremlin BicêtreFrance
  2. 2.Unité de recherche clinique Paris Sud, Assistance Publique Hôpitaux de Paris, Hôpital BicêtreLe Kremlin Bicêtre CedexFrance