Predict the maintenance dose of warfarin to within 1.5 mg per day, or less, by ordering a set of two DNA tests and using simple algorithms that take also take into account clinical and demographic factors.

Genetic variants detected by the tests are found in approximately half of patients and are the major contributor to variation in warfarin dose requirement.

The two genes CYP2C9 and VKORC1 are a model for the application of pharmacogenetic data because one controls the metabolism of the drug and the other controls the effective concentration requirement at the site of action.

• Cytochrome P450 2C9 is the most important enzyme in the metabolism of warfarin and greatly affects the half life and time to a stable dose. Without genetic testing it is not known if INR test results represent a steady state or one that is climbing.

  CYP2C9 genotype	Time to stable dose
  *1/*1 extensive(normal) metabolizer	4 - 5 days
  *1/*2 intermediate metabolizer	8 -10 days
  *1/*3, *2/*2, *3/*3 intermediate or poor metabolizer	12-15 days

  
  
• Vitamin K receptor, VKORC1, is the site of action of warfarin. The level of the enzyme is under genetic control according to the DNA sequence present in the control region of the gene. The more receptor present the more warfarin required.
  
  
• This graph illustrates the genotype based maintenance dose for a 160 cm tall, 66 year old female without significant drug interactions or other impairments. GG, GA and AA are the VKORC1 genotypes *1/*1 etc. are the CYP2C9 genotypes.

Here's what a blue ribbon FDA advisory panel has to say about the genetics of warfarin (Click here to view the meeting notes):

• Use lower doses of warfarin for patients with genetic variations in CYP2C9 and or VKORC1 that lead to reduced activities.
  
  
• Genotyping patients in the induction phase of warfarin therapy would reduce adverse events and improve achievement of stable INR.
  
  
• Existing evidence of the influence of CYP2C9 and VKORC1 genotypes warrants re-labeling of warfarin to include genetic test information.

The FDA and others are sponsoring clinical trials to prove the extent to which using DNA testing will reduce the morbidity and mortality associated with warfarin induced adverse bleeding events. Many scientists believe that the use of this testing will dramatically improve warfarin efficacy and safety. In fact, the FDA just updated the label to include genetic testing infotmation. ( Click here to view the release.) In the meantime you can order these tests now, and let your patients know that you're taking advantage of the most recent scientific discoveries.

Ordering Tests
Now you can add another dimension to providing safer and more efficacious care to your patients by ordering warfarin pharmacogenetic testing for them. Call Genelex today at 800-523-3080 to set up a medical account, order on-line, or download the order form and fax or mail in your order. Cost for the two genes with 4-day turnaround is only $550 and is typically reimbursed by insurance.

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