Annotation of CPNDS Guideline for warfarin and CYP2C9, VKORC1
Summary
The Canadian Pharmacogenomics Network for Drug Safety (CPNDS) clinical recommendation group has published guidelines for the use of pharmacogenetic testing for variants in VKORC1 and CYP2C9 in adult and pediatric patients with an indication for warfarin. They recommend testing for the VKORC1 SNP -1639G>A (rs9923231) and the CYP2C9 alleles *2 and *3 in order to better guide warfarin dosage.
Annotation
The Canadian Pharmacogenomics Network for Drug Safety (CPNDS) clinical recommendation group has published guidelines in the journal Therapeutic Drug Monitoring. Excerpts from “Clinical Practice Recommendations on Genetic Testing of CYP2C9 and VKORC1 Variants in Warfarin Therapy” [Article:26186657] follow:
Testing of all warfarin-naive patients for VKORC1 (-1639G>A), CYP2C9*2, and CYP2C9*3 should be considered before initiation of therapy and within the first 2 weeks of therapy (level B - moderate recommendation). Genetic testing for CYP2C9*5, *6, *8 or *11 and CYP4F2 V433M is currently not recommended (level C - optional recommendation). Management of patients with VKORC1 and CYP2C9 variants
Genotyping results should be interpreted using a pharmacogenetic dosing algorithm to estimate the required dose (level A – strong recommendation).
After testing for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639G>A), pharmacogenetic dosing algorithms that incorporate both clinical variables and genetic information should be used to predict a stable warfarin dose.
Of importance, pharmacogenetic-guided dosing should not replace regular INR monitoring. Rather, test results should be used to help physicians estimate an appropriate warfarin dose, while still using regular INR monitoring to ensure that stable anticoagulation is achieved.
See full guideline [Article:26186657] for further details and grading scheme.