Impact of capecitabine and S-1 on anticoagulant activity of warfarin in patients with gastrointestinal cancer

Purpose: Capecitabine and S-1 are orally administered fluoropyrimidine anticancer drugs widely used to treat gastrointestinal cancer. While anticoagulant therapy for cancer patients is recommended, many studies have shown that the effects of warfarin are enhanced by its interaction with fluoropyrimidine. We investigated the effects of capecitabine or S-1 on the anticoagulant activity of warfarin in patients coadministered both drugs. Methods: We retrospectively investigated the clinical features of and anticoagulant activity in nine consecutive patients who received capecitabine or S-1 in combination with warfarin from January 2008 to December 2014 at our institution. The prothrombin time international normalized ratio divided by current warfarin dosage (PT-INR/dose) was measured over time to evaluate warfarin titer in each patient. Results: Reductions in warfarin dosage were required, from 2.6 mg/day before chemotherapy to a minimum of 1.7 mg/day after chemotherapy initiation, on average. The median time until the first dosage reduction after initiation was 22 days for the capecitabine group and 43 days for the S-1 group. The median time until minimal dosage of warfarin was reached was 43 days in both groups. PT-INR/dose was elevated from 0.85 before chemotherapy to a maximum of 1.41 after its initiation. The median time until the maximal PT-INR/dose was reached was 46 days for the capecitabine group and 46.5 days for the S-1 group. Conclusions: The anticoagulant activity of warfarin may be enhanced by coadministration with capecitabine or S-1. Close monitoring of anticoagulant activity is required to avoid a hyperfibrinolytic state due to a severe adverse interaction.