Copur M S, Ledakis P, Bolton M, Morse A K, Werner T, Norvell M, Muhvic J, Chu E
Saint Francis Cancer Center, Medical and Radiation Oncology Department, 2116 W. Faidley Avenue, Grand Island, Nebraska, USA.
Clin Colorectal Cancer. 2001 Nov;1(3):182-4. doi: 10.3816/CCC.2001.n.019.
Warfarin is one of the most commonly used oral anticoagulants in the clinic. It is well established that a wide range of antineoplastic drugs interact with warfarin, resulting in altered coagulation parameters and/or bleeding sequelae. While altered coagulation parameters have been observed in patients taking the oral 5-fluorouracil prodrug, capecitabine, in combination with warfarin, no report to date has described clinically overt evidence of bleeding. Herein, we report 2 cancer patients who presented with bleeding episodes that most likely resulted from an adverse interaction between capecitabine and warfarin after 6 weeks of concomitant therapy. In each case, there was a marked elevation in both the prothrombin time and international normalized ratio (> 10), with subsequent gastrointestinal bleeding. The exact mechanism of this interaction is yet unknown, but it is possible that capecitabine might, in some manner, reduce the hepatic metabolism of warfarin. Close monitoring of coagulation parameters is recommended for all patients receiving concomitant warfarin and capecitabine, with appropriate adjustment of warfarin dosage. The nature and extent of this interaction requires further investigation.
华法林是临床上最常用的口服抗凝剂之一。众所周知，多种抗肿瘤药物会与华法林相互作用，导致凝血参数改变和/或出血后遗症。虽然在服用口服5-氟尿嘧啶前体药物卡培他滨并联合使用华法林的患者中观察到了凝血参数的改变，但迄今为止尚无报告描述临床上明显的出血证据。在此，我们报告2例癌症患者，在联合治疗6周后出现了出血事件，极有可能是卡培他滨与华法林之间的不良相互作用所致。在每例病例中，凝血酶原时间和国际标准化比值均显著升高（>10），随后出现胃肠道出血。这种相互作用的确切机制尚不清楚，但卡培他滨可能以某种方式降低了华法林的肝脏代谢。建议对所有同时接受华法林和卡培他滨治疗的患者密切监测凝血参数，并适当调整华法林剂量。这种相互作用的性质和程度需要进一步研究。
