Capecitabine (Xeloda®, Roche) is a cytostatic agent indicated for metastatic breast cancer when used as an adjunct to docetaxel, and for metastatic colorectal cancer.

The co-administration of capecitabine and warfarin may predispose a patient to an increased risk of bleeding. The probable mechanism for the interaction is the down-regulation of CYP 2C9 isoenzyme by which warfarin is principally metabolised.

Post-marketing reports have revealed clinically significant increases in prothrombin time (PT) and the international normalised ratio (INR) in patients who were stabilised on anticoagulants when capecitabine therapy was initiated. These events occurred within several days to several months after concurrent therapy.

In 4 patients with cancer, chronic administration of capecitabine (1250 mg/m² 2 times daily) with a single 20 mg dose of warfarin increased the mean AUC of S-warfarin by 57% and decreased its clearance by 37%. Baseline corrected AUC of INR in these 4 patients increased by 2.8-fold, and the maximum observed mean INR value was increased by 91%.

A 91-year-old woman was prescribed a 2.5 mg/day dose of warfarin with target INR of 2-2.5 while concurrently receiving capecitabine for rectal adenocarcinoma. After 2 cycles of capecitabine, she was admitted to the hospital with a PT of 72.9 and INR>10.

Another 72-year-old woman received 2.5 mg/day of warfarin with target INR 2-3 for pulmonary embolism. She subsequently received capecitabine eight months later, and was admitted to the hospital with a PT >100 and INR >10 after 2 cycles of capecitabine.

Patients being prescribed warfarin and capecitabine concurrently should be closely and regularly monitored for alterations in the PT or INR; the dose of warfarin should be reiterated if necessary.

1. Klasco RK (Ed): DRUGDEX® System (electronic version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at: http://www.thomsonhc.com (cited: 09/06/2005).
   
   
2. Product Info Xeloda®, 15/06/2005.