Warfarin dosing

Aithal, G.P., Day, C.P., and Kesteven, P.J. et al. (1999). Association of polymorphisms in the cytochrome P450 C YP2C9 with warfarin dose requirement and risk of bleeding comph-cations. Lancet 353, 717-719. 

Hold or adjust warfarin dose as necessary. If the patient is being treated with UFH, measure aPTT daily (or antifactor Xa activity), and adjust dose if necessary. If the patient is being treated with an LMWH or fondaparinux, continue therapy. 

Adjust warfarin dose as necessary. Consider restarting LMWH or fondaparinux if INR drops below 1.5. 

Disulfiram inhibits several of the enzymes responsible for warfarin metabolism increased PT/INR have been noted if disulfiram is added to warfarin therapy, carefully monitor PT/INR the warfarin dose will probably have to be decreased. 

Avoid jejunal administration of ciprofloxacin Monitor clinical response Adjust warfarin dose based on international normalized ratio... 

Obayashi, K., Nakamura, K., Kawana, J., et at. (2006) VKORCl gene variations are the major contributors of variation in warfarin dose in Japanese patients. Clin. Pharmacol. Then 80,169-178. 

Case Study How Long Until My Warfarin Dose Stabilizes ... 

Rieder MJ, Reiner AP, Gage BF et al. Effect of VKORCl haplotypes on transcriptional regulation and warfarin dose. NEngl JMed2005 352 2285-2293. 

Sconce EA, Khan TI, Wynne HA et al. The impact of CYP2C9 and VKORCl genetic polymorphism and patient characteristics upon warfarin dose requirements proposal for a new dosing regimen. Blood 2005 106 2329-2233. 

Wadelius M, Chen LY, Downes K et al. Common VKORCl and GGCX polymorphisms associated with warfarin dose. Pharmacogenomics J2005 5. 262-270. 

Lesko U The critical path of warfarin dosing Finding an optimal dosing strategy using pharmacogenetics. Clin Pharmacol Ther 2008 84 301 http //www.fda.gov/cder/genomics/publications.htm... 

In 12 patients chronically maintained on warfarin, atorvastatin 80 mg/day for 2 weeks reduced mean prothrombin times slightly, but only for the first few days of the 2-week treatment period (35). Thus, atorvastatin had no consistent effect on the anticoagulant activity of warfarin and adjustments in warfarin doses should not be necessary. 

Jackevicius C. 2002. Quality improvement initiative for pharmacist-assisted warfarin dosing Implementation and evaluation of a new protocol. Can J Hosp Pharm 55 105. 

Improved prediction of maintenance warfarin dose is linked to SNPs in the vitamin K epoxide reductase complex subunit... 

Veenstra DL, Ydu JH, Rieder MJ, et al. Association of vit K epoxide reductase complex I (VKORKCI) variants with warfarin dose in a Hong Kong Chinese patient population. Pharmacogenet Genomics 2005 15 687-691. 

Figure 1 The INR values and warfarin doses of a patient with CYP2C9 3 allelic variant requiring over 1 year to maintain a therapeutic INR.

More prospective studies are needed to test the feasibility and cost effectiveness of using algorithms based on these parameters for adjusting initial warfarin dose to meet individual needs, but the data at present make a strong case for the use of CYP2C9 genotyping testing prior to warfarin treatment, especially in the elderly. 

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