Increased anticoagulant activity of warfarin used in combination with doxifluridine

Purpose: The purpose of this article is to report the first case of markedly increased anticoagulant activity of warfarin when used in combination with doxifluridine, given as a replacement for capecitabine. Methods: International normalized ratio (INR) of a 73-year-old female patient receiving warfarin was increased after starting chemotherapy using oral fluoropyrimidines (capecitabine or doxifluridine). Since the concomitant use of warfarin and the oral fluoropyrimidines was unavoidable in this case, the warfarin dosage was adjusted to keep INR within goal range (1.7-2.7). To evaluate the effects of the oral fluoropyrimidines on the anticoagulant activity of warfarin, the INR/Dose (warfarin dose in mg/day) was used. Results: To keep INR within goal range, the maintenance dosage of warfarin was reduced during the treatment with doxifluridine as well as capecitabine. It was finally reduced from 5 mg daily in the absence of oral fluoropyrimidines to 1.5 mg daily during the concomitant use of doxifluridine (600 mg daily). In contrast, the higher INR/Dose (1.03-1.66) was continued during the concomitant use of warfarin and doxifluridine compared with the INR/Dose before the start of chemotherapy (about 0.5). These results clearly indicate that the anticoagulant activity of warfarin was markedly increased by the concomitant use of doxifluridine as well as capecitabine. Conclusions: It is important that physicians closely monitor anticoagulant activity in patients concomitantly receiving doxifluridine and warfarin, and appropriately adjust the dose of warfarin.