内容紹介
A Study on Drug Interaction between Warfarin and Capecitabine with Special Reference to the Co-Administered Term or the Discontinuation Term of Capecitabine
Summary
We used the prothrombin time international normalized ratio(PT-INR)to investigate the change in degree and term of warfarin following co-administration and after discontinuation of capecitabine. In this study, approximately 3 years of medical records of 7 patients receiving co-administration therapy of warfarin and capecitabine were obtained from 4 hospitals. We observed daily increases in PT-INR values up to peak PT-INR levels following co-administration of warfarin and capecitabine. Interestingly, the peak PT-INR values of 4 of the patients remained remarkably high despite discontinuation of capecitabine. The peak PT-INR values for concomitant warfarin and capecitabine were attained after an average of 31.3 days of usage. When compared with the average PT-INR values attained before co-administration, the PT-INR values following co-administration significantly increased by 3 times(p<0.05). After discontinuation of capecitabine for an average of 15.1 days, i. e., for approximately 14 days, the PT-INR values returned to the PT-INR values attained prior to co-administration. These results suggest that capecitabine has influence on the anticoagulant effect of warfarin during not only the co-administered term but also the discontinuation term, and that this influence occasionally continues after discontinuation of capecitabine. These findings also suggest that a period of approximately 14 days after discontinuation is necessary for the interaction of capecitabine to dissipate and the PT-INR values to return the levels attained before receiving concomitant warfarin and capecitabine.
要旨
カペシタビン併用および中止後(休薬期間中)におけるワルファリンの抗血液凝固作用の変化,すなわち作用期間および程度を評価するためにprothrombin time international normalized ratio(PT-INR)を用い,併用投与した症例を回顧的に調査した。対象は7症例(4施設)であり,カペシタビン併用後,全例でPT-INRは上昇した。また,PT-INR最高値に達するまでに平均31.3日を要し,併用前と比べ,PT-INR値は平均して約3倍に増加(p<0.05)した。一方,カペシタビン中止後,カペシタビン開始前に得られていたPT-INR値へ改善するには,平均15.1日すなわち約14日(約2週間)要した。以上,カペシタビンは併用期間のみならず,中止後においてもワルファリンの抗血液凝固作用へ影響が持続する可能性が示唆された。さらにカペシタビン中止後,その開始前に得られていたPT-INR値へ改善するには,少なくとも約14日間持続することが示されたことから,特にこの期間中は相互作用を十分考慮して注意深く血液凝固能をモニターする必要が示唆された。
目次
癌と化学療法 TOPへ
癌と化学療法 42巻7号 2015年7月号トップへ
【薬事】
▶A Study on Drug Interaction between Warfarin and Capecitabine with Special Reference to the Co-Administered Term or the Discontinuation Term of Capecitabine…池西 政幸ほか
Summary
We used the prothrombin time international normalized ratio(PT-INR)to investigate the change in degree and term of warfarin following co-administration and after discontinuation of capecitabine. In this study, approximately 3 years of medical records of 7 patients receiving co-administration therapy of warfarin and capecitabine were obtained from 4 hospitals. We observed daily increases in PT-INR values up to peak PT-INR levels following co-administration of warfarin and capecitabine. Interestingly, the peak PT-INR values of 4 of the patients remained remarkably high despite discontinuation of capecitabine. The peak PT-INR values for concomitant warfarin and capecitabine were attained after an average of 31.3 days of usage. When compared with the average PT-INR values attained before co-administration, the PT-INR values following co-administration significantly increased by 3 times(p<0.05). After discontinuation of capecitabine for an average of 15.1 days, i. e., for approximately 14 days, the PT-INR values returned to the PT-INR values attained prior to co-administration. These results suggest that capecitabine has influence on the anticoagulant effect of warfarin during not only the co-administered term but also the discontinuation term, and that this influence occasionally continues after discontinuation of capecitabine. These findings also suggest that a period of approximately 14 days after discontinuation is necessary for the interaction of capecitabine to dissipate and the PT-INR values to return the levels attained before receiving concomitant warfarin and capecitabine.
要旨
カペシタビン併用および中止後(休薬期間中)におけるワルファリンの抗血液凝固作用の変化,すなわち作用期間および程度を評価するためにprothrombin time international normalized ratio(PT-INR)を用い,併用投与した症例を回顧的に調査した。対象は7症例(4施設)であり,カペシタビン併用後,全例でPT-INRは上昇した。また,PT-INR最高値に達するまでに平均31.3日を要し,併用前と比べ,PT-INR値は平均して約3倍に増加(p<0.05)した。一方,カペシタビン中止後,カペシタビン開始前に得られていたPT-INR値へ改善するには,平均15.1日すなわち約14日(約2週間)要した。以上,カペシタビンは併用期間のみならず,中止後においてもワルファリンの抗血液凝固作用へ影響が持続する可能性が示唆された。さらにカペシタビン中止後,その開始前に得られていたPT-INR値へ改善するには,少なくとも約14日間持続することが示されたことから,特にこの期間中は相互作用を十分考慮して注意深く血液凝固能をモニターする必要が示唆された。