Posted 08/16/2007 FDA approved updated labeling to include pharmacogenomics information to the CLINICAL PHARMACOLOGY, PRECAUTIONS, and DOSAGE AND ADMINISTRATION sections of the prescribing information for the widely used blood-thinning drug, warfarin (Coumadin). This new information explains that people's genetic makeup may influence how they respond to the drug. Specifically, people with variations in two genes may need lower warfarin doses than people without these genetic variations. The two genes are called CYP2C9 and VKORC1. The CYP2C9 gene is involved in the breakdown (metabolism) of warfarin and the VKORC1 gene helps regulate the ability of warfarin to prevent blood from clotting.

The dosage and administration of warfarin must be individualized for each patient according to the particular patient's prothrombin time (PT) / International Normalized Ratio (INR) response to the drug. The specific dose recommendations are described in the warfarin product labeling, along with the new information regarding the impact of genetic information upon the initial dose and the response to warfarin. Ongoing warfarin therapy should be guided by continued INR monitoring. For more information visit the FDA website at: http://www.fda.gov/medwatch/safety/2007/safety07.htm#Warfarin and http://www.fda.gov/cder/drug/infopage/warfarin/default.htm.

Warfarin may cause severe bleeding that can be life-threatening and even cause death. Tell your doctor if you have or have ever had a blood or bleeding disorder; bleeding problems, especially in your stomach or your esophagus (tube from the throat to the stomach), intestines, urinary tract or bladder, or lungs; high blood pressure; heart attack; angina (chest pain or pressure); heart disease; pericarditis (swelling of the lining (sac) around the heart); endocarditis (infection of one or more heart valves); a stroke or ministroke; aneurysm (weakening or tearing of an artery or vein); anemia (low number of red blood cells in the blood); cancer; chronic diarrhea; or kidney, or liver disease. Also tell your doctor if you fall often or have had a recent serious injury or surgery. Bleeding is more likely during warfarin treatment for people over 65 years of age, and it is also more likely during the first few weeks of warfarin treatment. It is also more likely for people who take high doses of warfarin, or take this medication for a long time. The risk for bleeding while taking warfarin is also higher for people participating in an activity or sport that may result in serious injury. Tell your doctor and pharmacist if you are taking or plan to take any prescription or nonprescription medications, vitamins, nutritional supplements, and herbal or botanical products (See SPECIAL PRECAUTIONS), as some of these products may increase the risk for bleeding while you are taking warfarin. If you experience any of the following symptoms, call your doctor immediately: pain, swelling, or discomfort, bleeding from a cut that does not stop in the usual amount of time, nosebleeds or bleeding from your gums, coughing up or vomiting blood or material that looks like coffee grounds, unusual bleeding or bruising, increased menstrual flow or vaginal bleeding, pink, red, or dark brown urine, red or tarry black bowel movements, headache, dizziness, or weakness.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests to check your body's response to warfarin.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with warfarin and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/cder) or the manufacturer's website to obtain the Medication Guide.

Talk to your doctor about the risk(s) of taking warfarin.

• Coumadin®