1.Fluoropyrimidines S-1 and Capecitabine may Prolong International Normalized Ratios of Prothrombin Time by 3-Fold in Cancer Patients Receiving Warfarin
Masayuki Ikenishi ; Akiko Kuroda ; Haruhiko Tsukazaki ; Masahiko Nakao ; Masashi Takeuchi ; Yuji Konishi ; Toshiyuki Matsuda ; Tohru Ohtori ; Kenji Matsuyama ; Mitsutaka Takada ; Hiroki Satoh ; Yasufumi Sawada ; Mutsuaki Ueda
Japanese Journal of Drug Informatics 2016;18(3):172-178
Objective: To compare effects of the fluoropyrimidines S-1 and capecitabine on prothrombin time international normalized ratios (PT-INR) of warfarin following coadministration and after discontinuation of each fluoropyrimidine treatment.
Methods: Medical records of patients receiving warfarin with either S-1 (6 patients) or capecitabine (7 patients) were obtained from four hospitals.
Results: Increased PT-INR was observed until peak levels of warfarin were achieved in all patients in S-1 and capecitabine treatment groups. Moreover, PT-INR significantly changed after coadministration within each group (p＜0.05). Specifically, ratios of peak PT-INR after coadministration of each fluoropyrimidine and those following administration of warfarin alone (PT-INR elevation ratio) were 3.31 and 3.29 in S-1 and capecitabine coadministration groups, respectively. Moreover, numbers of days to peak PT-INR were 38.3 and 31.3 days, respectively, and did not significantly differ between the treatment groups. Furthermore, PT-INR returned to pretreatment levels by 17.5 and 15.1 days after discontinuation of S-1 and capecitabine, respectively, and did not significantly differ between the treatment groups.
Conclusion: Coadministration of S-1 and capecitabine similarly prolongs PT-INR by approximately 3-fold compared with administration of warfarin alone; therefore, these drug-drug interactions were clinically suggested to be of high risk for episodes of bleeding and remarkable alterations in coagulation parameters. Therefore, blood coagulation ability should be more carefully monitored with regard to PT-INRs in patients receiving warfarin with S-1 or capecitabine not only during coadministration but also after discontinuation of fluoropyrimidine treatments.
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