TY - CHAP M1 - Book, Section TI - Pharmacogenetics of Warfarin A1 - Scott, Stuart A. A1 - Desnick, Robert J. A2 - Murray, Michael F. A2 - Babyatsky, Mark W. A2 - Giovanni, Monica A. A2 - Alkuraya, Fowzan S. A2 - Stewart, Douglas R. PY - 2014 T2 - Clinical Genomics: Practical Applications in Adult Patient Care AB - Drug summary:Warfarin (Coumadin) is a commonly prescribed vitamin K antagonist for the prevention of thromboembolism. However, the drug has a very narrow therapeutic index and a large interindividual variability in response, in part due to inherited genetic variability within genes involved in warfarin pharmacokinetics and pharmacodynamics.Clinical indications for anticoagulation therapy include atrial fibrillation, mechanical heart valves, deep venous thrombosis, and dilated cardiomyopathies.Interindividual and interethnic variability in therapeutic warfarin dose requirements is responsible for frequent adverse drug reactions and underutilization due to its toxicity.Several factors affect warfarin dosage, including age, body weight, concomitant medications, and DNA sequence variants in cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase subunit 1 (VKORC1).Common variant CYP2C9 and VKORC1 alleles are associated with impaired warfarin metabolism and sensitivity to warfarin, respectively, both resulting in lower therapeutic dose requirements.Individuals with impaired warfarin metabolism and/or increased sensitivity require decreased dosage to avoid their international normalized ratio (INR) increasing beyond the target range (typically 2-3). Increased INR values can be associated with morbidity and mortality due to major bleeding episodes.Although many variant CYP2C9 and VKORC1 alleles are found in several major racial and ethnic groups, some are specific to various subpopulations.Pharmacogenetic dosing algorithms including both clinical and genetic variables have been developed that predict the therapeutic warfarin dose.Clinical testing for variant CYP2C9 and VKORC1 alleles is available and generalized FDA-approved dosing recommendations are now noted on the warfarin package insert. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/10/09 UR - accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102698531 ER -