FDA revised the Coumadin® (Warfarin) label in August, 2007 including
DNA variants to personalize initial dose and subsequent management
Coumadin® management presents a clinical conundrum. There is a broad range of
Coumadin® maintenance doses within the population with patients requiring from 1
mg/day to 10 mg/day to obtain therapeutic anticoagulation. Despite early dose titration
and subsequent periodic monitoring by Prothrombin Time (PT) and International
Normalized Ratio (INR), hemorrhagic complications are frequent and can be fatal. The
Warfarin DNA Typing system is revolutionary for clinical practice. By means of DNA
Typing, the innate Coumadin® metabolic capacity and sensitivity of the patient can be
predicted and diagnosed simply from a blood sample.
Coumadin® exerts its anticoagulant effect through its inhibition of Vitamin K Epoxide Reductase (VKOR). VKOR reduces oxidized Vitamin K, which is necessary for activation of Clotting Factors II, VII, IX
and X. Coumadin® is metabolized to inactive metabolites by the hepatic cytochrome P450 CYP2C9 isoenzyme.
VKOR and CYP2C9 are coded by independently segregating genes. Their individual contributions when added yield at least ~50% prediction of Coumadin® variability by DNA Typing. DNA thus adds significant predictive power to Coumadin® therapeutic algorithms. The combined predictive power of clinical factors and DNA is ~70%.
The Warfarin DNA Typing System determines an individual’s Coumadin® metabolic capacity and sensitivity by DNA Typing simultaneously the CYP2C9 and VKORC genes, at 12 variable sites. The report to the physician includes DNA Typing results and derived dosage guidelines.
HILOmet Warfarin Test: DNA Typing for Warfarin (Coumadin®) Management
FDA Approves Updated Warfarin (Coumadin) Prescribing Information
Warfarin Label, August 2007 (Bristol-Myers Squibb Company)
Integrating Genomic Based Information into Clinical Warfarin (Coumadin®) Management
Warfarin Combinatorial Genotypes (Personalized Medicine)
The Pharmacogenomics of Warfarin (Coumadin®) Administration
Warfarin DNA Typing System Trifold