National Coverage Determination (NCD) for Pharmacogenomic Testing for Warfarin Response (90.1)

Excerpt

General: Warfarin sodium is an orally administered anticoagulant drug that is marketed most commonly as Coumadin®. (The Food and Drug Administration (FDA) approved labeling for Coumadin® includes a Black Box Warning dating back to 2007.) Anticoagulant drugs are sometimes referred to as blood thinners by the lay public. Warfarin affects the vitamin K-dependent clotting factors II, VII, IX, and X. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of the vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K1 epoxide. The elimination of warfarin is almost entirely by metabolic conversion to inactive metabolites by cytochrome P450 (CYP) enzymes in liver cells. CYP2C9 is the principal cytochrome P450 enzyme that modulates the anticoagulant activity of warfarin. From results of clinical studies, genetic variation in the CYP2C9 and/or VKORC1 genes can, in concert with clinical factors, predict how each individual responds to warfarin.

Pharmacogenomics denotes the study of how an individual's genetic makeup, or genotype, affects the body's response to drugs. Pharmacogenomics as a science examines associations among variations in genes with individual responses to a drug or medication. In application, pharmacogenomic results (i.e., information on the patient’s genetic variations) can contribute to predicting a patient’s response to a given drug: good, bad, or none at all. Pharmacogenomic testing of CYP2C9 or VKORC1 alleles to predict a patient’s response to warfarin occurs ideally prior to initiation of the drug. This would be an once-in-a-lifetime test, absent any reason to believe that the patient’s personal genetic characteristics would change over time. Although such pharmacogenomic testing would be used to attempt to better approximate the best starting dose of warfarin, it would not eliminate the need for periodic PT/INR testing, a standard diagnostic test for coagulation activity and for assessing how a patient is reacting to a warfarin dose.