Capecitabine–Warfarin Interaction

OBJECTIVE: To report a case of concomitant warfarin therapy with consecutive cycles of capecitabine therapy, providing time of onset, magnitude, and assessment of the interaction. CASE SUMMARY: A 59-year-old man receiving chronic warfarin therapy for a mechanical mitral valve replacement was diagnosed with stage IV metastatic colon cancer. He was started on capecitabine/irinotecan after his cancer progressed with fluorouracil/leucovorin and the FOLFOX 6 regimen (oxaliplatin, leucovorin, and continuous fluorouracil infusion). He received 3 consecutive cycles of capecitabine/irinotecan with concomitant oral anticoagulation and, with each cycle, the warfarin dose was reduced. Over the course of these 3 cycles, the total weekly dose of warfarin was reduced by >85%. DISCUSSION: The capecitabine-warfarin interaction is clinically significant, requiring a black box warning in the package insert. The mechanism of action for the interaction is not clear, but may be related to down-regulation of CYP2C9 by capecitabine or its metabolites or a pharmacodynamic interaction with warfarin. A common response to this interaction, as discussed in previously published case reports, is the discontinuation of warfarin, capecitabine, or both. In this case, the Naranjo probability scale indicates a highly probable drug interaction between warfarin and capecitabine. CONCLUSIONS: As more patients require anticoagulation, and as chemotherapy agents such as capecitabine become available, the likelihood for these drug interactions increases. In our patient, close monitoring of therapy allowed successful use of warfarin and capecitabine.