Warfarin response

This section contains excerpted¹information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.

2015 Statement from the US Food and Drug Administration (FDA):

Dosing Recommendations without Consideration of Genotype

If the patient’s CYP2C9 and VKORC1 genotypes are not known, the initial dose of warfarin is usually 2 to 5 mg once daily. Determine each patient’s dosing needs by close monitoring of the INR response and consideration of the indication being treated. Typical maintenance doses are 2 to 10 mg once daily.

Dosing Recommendations with Consideration of Genotype

Table 1 displays three ranges of expected maintenance COUMADIN doses observed in subgroups of patients having different combinations of CYP2C9 and VKORC1 gene variants […]. If the patient’s CYP2C9 and/or VKORC1 genotype are known, consider these ranges in choosing the initial dose. Patients with CYP2C9 *1/*3, *2/*2, *2/*3, and *3/*3 may require more prolonged time (>2 to 4 weeks) to achieve maximum INR effect for a given dosage regimen than patients without these CYP variants.

Please review the complete therapeutic recommendations that are located here: (1)

2014 Statement from the Clinical Pharmacogenetics Implementation Consortium (CPIC): The pharmacogenetic algorithms available on http://www.warfarindosing.org should be used whenever possible to determine the dose of warfarin required. Such algorithms have been derived from large studies across different ethnic populations, and they take into account both the genetic and non-genetic factors that influence the variability in warfarin response. The existence of rare genetic variants may be responsible for individuals whose warfarin dosing is not well predicted. However, overall the dosing equations are well validated and fairly precise. Only if electronic access to a pharmacogenetic algorithm is not possible should the table-based dosing approach be used, which is preferable to a fixed-dose approach.

Please review the complete therapeutic recommendations that are located here: (2, 30).

¹ The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labelled all formulations containing the generic drug.

1. COUMADIN- warfarin sodium tablet) [package insert]. Princeton, NJ: Bristol-Myers Squibb Pharma Company; 2015. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d91934a0-902e-c26c-23ca-d5accc4151b6

4. Furie B. Do pharmacogenetics have a role in the dosing of vitamin K antagonists? N Engl J Med. 2013;369(24):2345–6.

2. Johnson J.A., Gong L., Whirl-Carrillo M., Gage B.F., et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clinical pharmacology and therapeutics. 2011;90(4):625–9.