Warfarin (Coumadin) and DNA
Do not alter the dosage amount or schedule of any drug you are
taking without first consulting your physician.
Information for Anticoagulation Patients
Click
here to see the Web Seminar - Coumadin
(warfarin) Genetics
News - FDA Approves Updated Warfarin (Coumadin)
Prescribing Information
NPR story "Genetic
Testing Can Help with Drug Dosages"
Every day millions of people take warfarin or Coumadin, powerful
drugs used to control life threatening conditions. How much of
these medicines people need is difficult to determine and often
it takes several months of weekly clinic visits and blood tests.
According to the FDA, hemorrhage during warfarin therapy
is a leading cause of death in Western countries and related
adverse
events account for 1 in 10 hospital admissions. Click here to
see the FDA slides.
Thankfully, recent discoveries in DNA research make predicting
the dose of warfarin a person needs much more accurate, and of
equal importance, how long it takes them to eliminate the drug.
More than half the population have variations in at least one
of the two genes that are tested. These genetic variations are
responsible for almost half of the individual variation seen
in warfarin dose.
Order this pair of DNA tests, now available from Genelex, and
help your doctor help you to reach your target dosage and INR
(a measurement of your blood clotting levels) faster and safer.
Here's what a blue ribbon FDA advisory panel has to say about
the genetics of warfarin/Coumadin:
The FDA and others are sponsoring clinical trials to prove the
extent to which using DNA testing will reduce adverse bleeding
events and save money. Many scientists believe that the use of
this testing will dramatically improve Warfarin efficacy and
safety. In the meantime you can order these tests now, share
the results with your doctor and know that you're taking advantage
of the most recent scientific discoveries.
Genelex has available computer programs to help interpret the
test results taking into account your size, age and other medicines
that you may be taking.
The Testing Process
The process is simple. You can order testing directly if you have a physician prescription or your healthcare provider can request testing for you. We send a cheek swab collection kit with directions by mail. Use the return mailer to submit samples and receive results in ten days or less. Faster testing is available for an additional charge. Call a DNA testing consultant at (800) 523-3080 for details and to order.
Frequently Asked Questions
Q: Do I need a prescription to order this testing?
A: Yes, a prescription is needed, or testing needs to be requested by your physician.
(The following information is provided
by Dr. Mark Linder and Dr. Kristen Reynolds.)
How are patients currently managed on warfarin therapy?
Coumadin (warfarin) is the most commonly
prescribed anticoagulant for the treatment and prevention of
thromboembolic events. The
dose of warfarin required to maintain a safe degree of anticoagulation
ranges from 2 mg/day or lower for some individuals to 10 mg
per day or higher for others. Patients who are not taking the
dose
that is right for them are at an increased risk for severe
toxicity or an inadequate response.
Currently, clinicians anticipate maintenance dose requirements
based on the patients physical characteristics such as age, gender
and weight and monitor the therapeutic effects closely by measuring
the INR. However these physical characteristics do not account
for the major sources of variation in dose requirement. Therefore
the clinician must adjust the warfarin dosage when the INR is
not within the safe range for anticoagulation. This can be a
lengthy trial and error process where the patient is at increased
risk until the most appropriate dosage for that patient is determined.
How does an individual’s genetic make-up effect
how much warfarin should be administered?
In addition to the physical characteristics mentioned above,
functional characteristics also influence the most appropriate
dose of warfarin. The major functional characteristics which
influence the warfarin dose are how rapidly the individual metabolizes
warfarin and how much warfarin is required in the body to inhibit
to formation of clotting factors. These characteristics can not
be assessed without specific diagnostic testing.
The active component of warfarin is metabolized by cytochrome
P450 2C9 (CYP2C9). Up to 35% of the population inherits a form
of the CYP2C9 gene which results in a CYP2C9 enzyme deficiency.
A deficiency in CYP2C9 causes slow metabolism and higher than
expected concentrations of the active drug to accumulate. This
increased warfarin concentration in the body increases the risk
of bleeding.
Warfarin inhibits the formation of active clotting factors by
inhibition of vitamin K epoxide reductase complex subunit 1 (VKORC1).
Inherited differences in VKORC1 increase or decrease the amount
of warfarin needed to inhibit the formation of the clotting factors.
When the amount of warfarin exceeds what is needed, the risk
of bleeding is increased.
How can this information be applied?
The difference in warfarin dose that is affected by the patient’s
metabolism or the amount of drug needed for effect do not become
apparent until the four to fifth day of therapy (Peyvandi F et
al. Clin Pharm Ther 2004;75:198-203). Therefore, standard approaches
to initiating treatment do not need to be postponed. A sample
of blood can be collected for determination of CYP2C9 and VKORC1
status on the first day of therapy. Preferably the results of
testing should be applied to dose selection on or shortly after
the fifth day of therapy.
What is the scientific community saying about these services?
In November of 2005, the clinical pharmacology advisory committee
reporting to the FDA reviewed the current literature surrounding
the application of CYP2C9 and VKORC1 testing to treatment
of patients with warfarin. At that meeting, the committee unanimously
agreed that “…sufficient mechanistic and clinical
evidence exists to support the recommendation: to use lower
doses of warfarin for patients with genetic variations in CYP2C9
and or VKORC1 that lead to reduced activities”. And genotyping
patients in the induction phase of warfarin therapy would reduce
adverse events and improve achievement of stable INR? Eight
out of ten committee members agreed “…that existing
evidence of the influence of CYP2C9 and VKORC1 genotypes
warrants re-labeling of warfarin to include genomic and test
information."
Based on official meeting transcripts which can be found at:
http://www.fda.gov/ohrms/dockets/ac/cder05.html#PharmScience
Is this testing likely to be cost effective?
There is a high likelihood that this testing will improve patient
safety while providing significant savings to the healthcare
system. Recent reports indicate that 70 to 100 severe bleeding
events occur each year for every 1000 patients treated with
warfarin (Higashi et al. JAMA 2002;287:1690-98; Margaglione
M et al. Thromb Haemost 2000;84:775-8). Each of these events
can result in an average hospital stay of 6 days and average
healthcare costs of $16,000.00 for each event (Fanikos J et
al Am J Cardiology 2005;96:595-8). PGXL charges $35.00 to process
the sample, $ 266.00 for each CYP2C9 and VKORC1 test thus the
total cost of testing is $ 567.00. If we apply this to a patient
population of 1000 patients treated for a year, cost effectiveness
will be achieved if 33 to 47% of the anticipated number of
bleeding events are avoided. Any events avoided beyond this
will have obvious positive benefits for the patient and directly
reduce the financial burden on the healthcare system.
Are these laboratory services covered by health insurance?
This year, the American Medical Association (AMA) recommended
to the Centers for Medicare & Medicaid Services (CMS) to
establish CPT codes and reimbursement schedules which can be
applied to pharmacogenetic diagnostics. The appropriate coding
is dependent upon the technology used by the laboratory. The
anticipated reimbursement is 70% of the total charge. Private
insurance companies such as Anthem, Humana and others (By Lisa
Barrett Mann, Special to The Washington Post, Tuesday, April
18, 2006; Page HE01) have covered costs for testing for the
majority of our clients who submitted for coverage.
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health information and as an educational tool. It is not intended
as medical advice. Only a physician, pharmacist, or other healthcare
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and documented as part of the health professional/patient relationship.
