Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 Genotypes and Warfarin Dosing

TLDR

Warfarin is a widely used anticoagulant with a narrow therapeutic index and substantial interpatient dose variability, largely driven by common CYP2C9 and VKORC1 genetic variants that explain about half of the dose differences. The article aims to aid clinicians in interpreting CYP2C9 and VKORC1 genotype data to estimate therapeutic warfarin doses targeting an INR of 2‑3 when genotype results are available. CPIC, part of the NIH Pharmacogenomics Research Network, publishes and periodically updates peer‑reviewed gene‑drug guidelines on http://www.pharmgkb.org, incorporating new evidence.

Abstract

Warfarin is a widely used anticoagulant with a narrow therapeutic index and large interpatient variability in the dose required to achieve target anticoagulation. Common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K-epoxide reductase complex (VKORC1) enzymes, in addition to known nongenetic factors, account for ~50% of warfarin dose variability. The purpose of this article is to assist in the interpretation and use of CYP2C9 and VKORC1 genotype data for estimating therapeutic warfarin dose to achieve an INR of 2-3, should genotype results be available to the clinician. The Clinical Pharmacogenetics Implementation Consortium (CPIC) of the National Institutes of Health Pharmacogenomics Research Network develops peer-reviewed gene-drug guidelines that are published and updated periodically on http://www.pharmgkb.org based on new developments in the field.(1).