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CPIC Issues 2017 Guidelines for Optimal Warfarin Dosing

warfarin side effects

Warfarin (brand name Coumadin) is the most commonly used anticoagulant medication worldwide. It achieves its desired results with great efficacy, but is also a reason why patients are frequently hospitalized for adverse drug reactions. This is due to drug-gene interactions, complicated by warfarin’s narrow therapeutic window.
To address the need for greater the CPIC (Clinical Pharmacogenetics Implementation Consortium) has updated its guidelines to determine optimal warfarin dosing a more effective manner through pharmacogenetic testing, as reported by PharmGKB (02/08/2017).
Specifically, the CPIC’s revised 2017 recommendations are specific to continental ancestry, and are based on genotypes from CYP2C9, VKORC1, CYP4F2, and rs12777823. The CYP2C9 hepatic enzyme is one of the primary metabolizer of warfarin. Additional or lack of the sixty CYP2C9 alleles are associated with adverse drug reactions. Another factor of warfarin-gene interaction is VKORC1, which encodes the vitamin K epoxide reductase protein, the target enzyme of warfarin. Variants of this protein determine warfarin sensitivity. Genes CYP4F2 and CYP2C rs12777823, also greatly affect the patient’s response to the medication and susceptibility to adverse reactions to anticoagulants.
Warfarin dosing algorithms grounded in pharmacogenetics have been effective at determining appropriate treatment. According to the CPIC, “[i]ncorporation of genetic information has the potential to shorten the time to attain stable INR [international normalized ratio], increase the time within the therapeutic INR range, and reduce underdosing or overdosing during the initial treatment period.”

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