TalkFDA Gives Nod to Gene Test for Warfarin
Yesterday the FDA announced a new label for the blood thinner, Coumadin (generic: warfarin). The new label explains that people’s genetic makeup may influence how they respond to the drug, and that a $300-500 genetic test can help physicians tailor the drug dose to increase effectiveness and reduce the serious risk of bleeding.
Warfarin is a difficult drug to use because the optimal dose varies and depends on many risk factors including a patient’s diet, age, and the use of other medications.
Patients who take a dose larger than they can tolerate are at risk of life-threatening bleeding. Those who receive too low a dose are at risk of equally dangerous blood clots. Dosing is particularly important at the beginning of therapy, when problems in adjusting the dose can lead to complications such as bleeding. …
A person’s genes “encode” enzymes and differences in the sequence of a gene can cause differences in enzyme activity or sensitivity. That is why different people process the same drug differently.
Good news, right? Another example of personalized medicine and how it can revolutionize patient care. Unfortunately the wheels of the machine grind slowly, and defensively. So it will be interesting to see how quickly this testing becomes routine: Will it become routine in top medical centers first, as new technology often is? Or, will Medicare bite at the potential for significant emergency room savings by making the gene test mandatory before prescribing warfarin, a drug so common in their population.
Says the Wall Street Journal, “[W]arfarin is the largest case to date of what happens when the new science of genetics runs up against the practice of medicine.” This article highlights how legalities and issues such as liability muddy the waters of “standard medical practice” and can get in the way of what’s truly best for patients.
Here are two stories, that illustrate in a nutshell the use of genetic testing for warfarin:
Ms. Schmale in St. Louis says she had a rare combination of both genes that made her highly sensitive to warfarin. Doctors had started her on a daily dose of 10 milligrams of the drug, but after the tests she ended up on a dose averaging less than one milligram a day.
For another patient, 60-year-old John D. Marlin, genetics pointed in the opposite direction. When he developed a clot in his lung this May, the retired biology teacher from Evansville, Ill., was told he would start with four milligrams of warfarin each day. But after the genetic test, doctors switched the dose to eight to nine milligrams daily. “I just don’t absorb it very well, so it takes more of it to work,” Mr. Marlin says.
For more info, the FDA website has posted Q&A on the new Warfarin label, including the following:
What is personalized medicine?
Personalized medicine is a term that has been applied to clinical practice when a doctor uses information about a patient’s genotype or gene expression along with other information such as the physical exam, medical history, age, race, gender, co-administered drugs to select a medicine or a dose of a medical product that is thought to be best suited for that patient. The promise of personalized medicine is to improve the safety and effectiveness of drug therapy in an individual patient. …
How does the coumadin labeling change fit into this strategy?
The label change highlights the opportunity for healthcare providers to use genetic tests to improve their initial estimate of a reasonable warfarin dose for a specific patient; this process may optimize the use of warfarin and lower the risk for bleeding.
Has FDA asked other companies to include information in the labeling about genetic variations?
Yes. Specifically, genetic variation information has been approved in the product labeling for the following drugs: 6-mercaptopurine, azathioprine, irinotecan, and atomoxetine.
Can we expect more labeling changes like this in the future? What about other initiatives?
Yes, as new pharmacogenetic data provides evidence that genetic variations importantly affect a drug’s benefit, risk or dosing, the FDA expects the drug label to be revised to include the new information. In the area of new drug development, the FDA is encouraging industry to include the collection of genetic data in clinical trials with the intent that this information would help identify patients most likely to benefit from the new drug as well as to help identify any patients at high risk for adverse reactions to the drug.
WarfarinDosing.org, is a site for physicians to help determine the therapeutic dose in patients beginning warfarin therapy. The calculator takes into account clinical factors and the genotypes of two genes, CYP2C9 and VKORC1.
Update 3/13/07: DNA Direct now offers warfarin response testing services to consumers as well as to physicians.
Technorati Tags: warfarin, coumadin, fda, genes, genetic test, warning, blood thinner, CYP2C19, VKORC1
August 18th, 2007 at 7:39 am
I was prescribed arixtra (expensive) took for two days and had an allergic reaction, then Lovenox (not quite as expensive, but still alot more than coumadin)- also after 2 days allergic reaction, now on coumadin and they did not request this test, this has just happened in the last week, so thank you I will ask about getting this test and anything related to this.