Application of a genomics‐guided warfarin dosing nomogram for hospitalized patients

Abstract

Adverse drug reactions (ADRs) due to warfarin are an important cause of emergency department visits, and also occur frequently among hospitalized patients. We now know common genetic variations in CYP2C9‐mediated metabolism of warfarin, as well as its target VKORC1, account for much of the dosing variation. Accordingly, we hypothesized that application of a pharmacogenomics‐guided warfarin dosing algorithm that our group developed, known as WRAPID, may be clinically useful in guiding warfarin initiation and dosing for hospitalized patients. We initiated a personalized medicine‐based inpatient consult service with a goal of providing WRAPID‐based warfarin dosing recommendations. We now have data on a series of patients who were initiated on warfarin as inpatients who subsequently developed a supratherapeutic international normalized ratio (INR). When assessed by our service, most were shown to possess genotypes associated with marked sensitivity to warfarin, including one patient with the rare CYP2C9 *3/*3 genotype, as well as several with CYP2C9 *2/*2 and/or VKORC1‐1639 A/A genotype. Based on our WRAPID‐guided dosing, warfarin dose was accurately predicted to be as low as 0.5 mg. Accordingly, we believe genomics‐guided warfarin dosing is useful for identifying hospitalized patients at risk for ADRs, thereby reducing length of stay and preventing readmissions. Funding: AMOSO Drug Innovation Fund.