An expanded pharmacogenomics warfarin dosing table with utility in generalised dosing guidance.

Pharmacogenomics (PGx) guided warfarin dosing, using a comprehensive dosing algorithm, is expected to improve dose optimisation and lower the risk of adverse drug reactions. As a complementary tool, a simple genotype-dosing table, such as in the US Food and Drug Administration (FDA) Coumadin drug label, may be utilised for general risk assessment of likely over- or under-anticoagulation on a standard dose of warfarin. This tool may be used as part of the clinical decision support for the interpretation of genetic data, serving as a first step in the anticoagulation therapy decision making process. Here we used a publicly available warfarin dosing calculator (www.warfarindosing.org) to create an expanded gene-based warfarin dosing table, the CPMC-WD table that includes nine genetic variants in CYP2C9, VKORC1, and CYP4F2. Using two datasets, a European American cohort (EUA, n=73) and the Quebec Warfarin Cohort (QWC, n=769), we show that the CPMC-WD table more accurately predicts therapeutic dose than the FDA table (51 % vs 33 %, respectively, in the EUA, McNemar's two-sided p=0.02; 52 % vs 37 % in the QWC, p<1×10(-6)). It also outperforms both the standard of care 5 mg/day dosing (51 % vs 34 % in the EUA, p=0.04; 52 % vs 31 % in the QWC, p<1×10(-6)) as well as a clinical-only algorithm (51 % vs 38 % in the EUA, trend p=0.11; 52 % vs 45 % in the QWC, p=0.003). This table offers a valuable update to the PGx dosing guideline in the drug label.