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Evidence for a pharmacogenetic adapted dose of oral anticoagulant in routine medical practice.
Eur J Clin Pharmacol. 2008 Oct; 64(10):953-60.EJ

Abstract

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.

Authors+Show Affiliations

Pharmacology Department, Faculté de médecine Paris Sud, Université Paris-Sud, Le Kremlin Bicêtre, France. laurent.becquemont@bct.ap-hop-paris.fr

Pub Type(s)

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

Language

eng

PubMed ID

18758764

Citation

Becquemont, Laurent. "Evidence for a Pharmacogenetic Adapted Dose of Oral Anticoagulant in Routine Medical Practice." European Journal of Clinical Pharmacology, vol. 64, no. 10, 2008, pp. 953-60.
Becquemont L. Evidence for a pharmacogenetic adapted dose of oral anticoagulant in routine medical practice. Eur J Clin Pharmacol. 2008;64(10):953-60.
Becquemont, L. (2008). Evidence for a pharmacogenetic adapted dose of oral anticoagulant in routine medical practice. European Journal of Clinical Pharmacology, 64(10), 953-60. https://doi.org/10.1007/s00228-008-0542-2
Becquemont L. Evidence for a Pharmacogenetic Adapted Dose of Oral Anticoagulant in Routine Medical Practice. Eur J Clin Pharmacol. 2008;64(10):953-60. PubMed PMID: 18758764.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for a pharmacogenetic adapted dose of oral anticoagulant in routine medical practice. A1 - Becquemont,Laurent, Y1 - 2008/08/30/ PY - 2008/03/20/received PY - 2008/07/08/accepted PY - 2008/9/2/pubmed PY - 2008/12/17/medline PY - 2008/9/2/entrez SP - 953 EP - 60 JF - European journal of clinical pharmacology JO - Eur. J. Clin. Pharmacol. VL - 64 IS - 10 N2 - 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. SN - 1432-1041 UR - https://www.unboundmedicine.com/medline/citation/18758764/Evidence_for_a_pharmacogenetic_adapted_dose_of_oral_anticoagulant_in_routine_medical_practice_ L2 - https://dx.doi.org/10.1007/s00228-008-0542-2 DB - PRIME DP - Unbound Medicine ER -