The U.S. Food and Drug Administration has announced the approval of updated labeling for the widely used blood-thinning drug, Coumadin, to explain that people's genetic makeup may influence how they respond to the drug.
Manufacturers of warfarin, the generic version of Coumadin, are to add similar information to their products' labeling, FDA said.
The labeling change highlights the opportunity for healthcare providers to use genetic tests to improve their initial estimate of what is a reasonable warfarin dose for individual patients. Testing may help optimize the use of warfarin and lower the risk of bleeding complications from the drug.
These labeling updates are based on an analysis of recent studies that found people respond to the drug differently based, in part, on whether they have variations of certain genes.
FDA estimates that 2 million persons start taking warfarin in the United States every year to prevent blood clots, heart attacks and stroke. 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.
Warfarin is the second most common drug – after insulin –implicated in emergency room visits for adverse drug events.
Physicians and other health care professionals who prescribe warfarin regularly check to see if the drug is working properly by ordering a test called the PT or prothrombin time that evaluates the blood's ability to clot properly. The results are measured in seconds and compared with the expected value in healthy people, known as the International Normalized Ratio or INR.
"Today's approved labeling change is one step in our commitment to personalized medicine. By using modern science to get the right drug in the right dose for the right patient, FDA will further enhance the safety and effectiveness of the medicines Americans depend on," said Commissioner of Food and Drugs Andrew C. von Eschenbach, M.D.
The FDA's "personalized medicine" initiative makes use of pharmacogenomics—the science that predicts a response to drugs based upon a person's genetic makeup. This effort supports the personalized health program spearheaded by Health and Human Services Secretary Mike Leavitt.
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.
One-third of patients receiving warfarin metabolize it quite differently than expected. Research has shown that some of the unexpected response to warfarin depends on a patient's variants of the genes CYP2C9 and VKORC1.