Use of genetic and nongenetic factors in warfarin dosing algorithms.
Despite the fact that warfarin has been used as an anticoagulant for many years, the safety profile for this drug has been poor. Inappropriate dosing continues to contribute to significant morbidity and mortality due to thrombotic disease and bleeding. Therefore, there is a need for the development, characterization and implementation of dosing algorithms using a patient's demographic information and genotype. Recently, polymorphisms in two genes, cytochrome P450 2C9 and vitamin K epoxide reductase complex 1, have been shown to affect warfarin's pharmacogenomics and pharmacodynamics, respectively. Adding genotypes to a dosing algorithm may enable better prediction of initial warfarin dosing than use of demographic data alone. An advisory committee of the US FDA voted on November 14, 2005, to require manufacturers of warfarin to relabel their product, indicating that genotyping is recommended prior to drug administration. The exact date when this recommendation will be enacted remains to be determined. Successful implementation of pharmacogenomics into clinical practice requires genotyping results that can be translated directly into clinical decisions. The development of a warfarin dosing algorithm that includes genotyping may be the means to achieve this goal.
Wu
Alan H B
AH
University of California, San Francisco, Department of Laboratory Medicine, Clinical Chemistry Laboratory, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110, USA. wualan@labmed2.ucsf.edu
D000465:Algorithms; D000925:Anticoagulants / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000592:standards; D014644:Genetic Variation; D006801:Humans; D019934:International Normalized Ratio; D012449:Safety; D014859:Warfarin / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases