CPMC Proposes Dosing Guide for Widely Prescribed Medication

May 2016

The Coriell Personalized Medicine Collaborative (CPMC) study has informed a publication focused on one the country's most frequently prescribed medications.

Published in the April volume of the "Journal of Thrombosis and Haemostasis," which serves as a platform to advance significant reports and developments on blood clotting and bleeding disorders, the scientific paper examines the drug-gene relationship of the anti-coagulant warfarin.

While widely adopted and highly effective, warfarin is also a source of adverse drug reactions due to its narrow therapeutic index-the small difference between the dose that is helpful for a patient and the dose that would be harmful or toxic to the patient.

Individual differences in the amount of warfarin needed for therapeutic response in populations of European descent can be attributed to several genetic and non-genetic factors, and two-thirds of this variability in dosing is linked to genetic makeup. Dosing guidelines that incorporate both genetic and non-genetic factors for the drug have been acknowledged as a key requirement for physicians.

To address this need, the Food and Drug Administration (FDA) added advisory pharmacogenomic information to warfarin labels for variants in two genes: CYP2C9 and VKORC1. Furthermore, publicly available warfarin dosing calculators have been established to assist physicians with adjusting warfarin dosing based on a patient's demographics, medical history, and genetic variants.

As presented in the recent publication, titled, "An expanded pharmacogenomics warfarin dosing table with utility in generalised dosing guidance," the CPMC research study team builds on this model and developed a genotype-based dose prediction table that evaluates nine genetic variants in three genes, as opposed to the current, consensus FDA table that evaluates three genetic variants in two genes and represents a more narrow demographic.

"Continuing to make inroads in the pharmacogenomics space means physicians will be able to identify and implement more targeted treatment routes," says Tara Schmidlen, MS, LCGC, a genetic counselor with Coriell and one of the contributing authors. "Considering and interpreting genetic data while determining warfarin dosage has the potential to reverse adverse drug reaction trends and deliver better health outcomes."

To access the full findings, click here.