On October 30, 2007, under the title, “Anticoagulant Forum and CYP2C9,” Kim Kinney and I briefly addressed the polymorphisms that affect warfarin dosage. In August, 2007 the FDA had begun requiring a box on the warfarin label recommending genetic screening prior to dosing as a patient safety measure. Here is a little more detail…
Three polymorphisms render us sensitive to warfarin, requiring initial dosage reductions. These are CYP2C9*2 and CYP2C9*3, two modifications that reduce the activity of a warfarin-metabolizing cytochrome enzyme pathway, and VKORC1, which reduces vitamin K epoxide reductase activity, part of the prothrombin carboxylation mechanism. If a warfarin patient possesses one or more, they require warfarin dosages closer to 2 mg/day instead of the standard 5 mg/day, and risk bleeding at standard doses. Subsequent to the FDA requirement, US laboratories have begun routine screening for these three polymorphisms in response to physician orders, and the molecular diagnostics industry has responded with novel, quick turnaround techniques.
The latest molecular offering is an interesting instrument that approaches “near-patient” test capability, the Osmetech eSensor XT-8 system. This instrument, equipped to assay the three polymorphisms, was released for distribution by the FDA on July 21. It will be interesting to track the success of this instrument and to see where we go in quick turnaround genetic assays and in warfarin dosing. We are moving rapidly into the world of pharmacogenomics. Geo
No comments here.