Warfarin Institute of America
DEDICATED TO YOUR HEALTH SINCE 2000
CAPECITABINE INTERACTIONS WITH WARFARIN (Coumadin, Jantoven)
IT WOULD BE DIFFICULT TO OVERESTIMATE THE POTENTIAL FOR HARM THAT THIS COMBINATION OF DRUGS CAN CAUSE. CLOSE MONITORING IS ESSENTIAL IF THESE MUST BE USED.
Capecitabine is what is known as a prodrug. That is, it is not an active drug itself, but after it is taken, the body changes it into an active drug. The drug that it changed to is the anti-cancer agent 5-fluorouracil (5-FU). The reason for doing this is to avoid the effect of 5-FU on the stomach. The change does not occur until the prodrug is in the liver.
For about a year, I had information posted on this website about this interaction occurring. Then the United States Food and Drug Administration came out with this new box warning - the highest level of warning about this drug:.
XELODA warfarin (Coumadin, Jantoven) Interaction: Patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored frequently in order to adjust the anticoagulant dose accordingly. A clinically important XELODA-warfarin (Coumadin, Jantoven) drug interaction was demonstrated in a clinical pharmacology trial (see CLINICAL PHARMACOLOGY and PRECAUTIONS). Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking XELODA concomitantly with coumarin-derivative anticoagulants such as warfarin (Coumadin, Jantoven) and phenprocoumon. Postmarketing reports have shown clinically significant increases in prothrombin time (PT) and INR in patients who were stabilized on anticoagulants at the time XELODA was introduced. These events occurred within several days and up to several months after initiating XELODA therapy and, in a few cases, within one month after stopping XELODA. These events occurred in patients with and without liver metastases. Age greater than 60 and a diagnosis of cancer independently predispose patients to an increased risk of coagulopathy.
I had a communication with a reader of this website whose mother was experiencing frequent bloody noses on this combination of medications. She noticed on the website that I had seen this interaction once. She copied this page and e-mailed it to her mother's doctor. She later wrote, " Today my mum was told that her warfarin (Coumadin, Jantoven) levels were so high that she needed to be given the antidote of vitamin K immediately! If I hadn't found your website, my mum could quite possibly be dead now!"
Later this person also wrote, "My mums general health is very good. She is up, dressed, makeup on etc.. She is eating good meals regularly. Also with her not being on the chemo at the moment and taking 20mg of mophine twice a day, she actually looks an feels better now than she has done since she first became ill back in July this year. I find it hard to belive that she is so seriously ill! I don't know the names of all of the drugs that she is taking, there seems to be so many: Laxatives, something for nausia (she feels ill after she has been given the warfarin (Coumadin, Jantoven)), Morphine, Iron tablets, Sterroids, Xeloda. She was supposed to start the chemo again last Friday but was told to wait another week until they stabalised the INR levels. They have said that regardless of wheather they can stabalise it this week, she will definately start the chemo again this Friday
Please click on this link and follow the rest of the discussion under fluorouracil.
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Last modified May 6, 2006