Shah Heather R, Ledbetter Leslie, Diasio Robert, Saif M Wasif
University of Alabama at Birmingham, AL, USA.
Clin Colorectal Cancer. 2006 Jan;5(5):354-8. doi: 10.3816/CCC.2006.n.006.
The extent and complications of the interaction between capecitabine and warfarin are not fully known.
A retrospective study of 77 patients who received capecitabine was performed to analyze coagulation abnormalities with or without warfarin.
Twenty-one patients received warfarin with capecitabine. Twelve were on an average warfarin dosage of 19.4 mg per week (range, 7-35 mg) before capecitabine treatment, with a stable international normalized ratio (INR; range, 0.9-3.3). The dose of capecitabine ranged from 1.6 g/m2 to 2 g/m2 per day. Thirteen patients (11 on warfarin) had an INR > 3 (range, 3.23-11.5), resulting in a probability of an INR > 3 of 32% in the warfarin group versus 4% for those not on warfarin (P = 5.1 x 10(-14)) at 130 days. Six patients required a warfarin dose reduction (1-2.5 mg decrease). There were 7 episodes of bleeding (all gastrointestinal; 5 with warfarin). Seven patients who experienced bleeding had INRs ranging from 1.06 to 8 (average, 3.31) at the time bleeding occurred. Of the 7 bleeding episodes, 5 patients required transfusions, averaging 3.25 units of red blood cells and 2.4 units of fresh frozen plasma. The incidence of bleeding at 130 days of treatment with capecitabine was 18% with warfarin versus 2% without (P = 4 x 10(-13)). Bleeding episodes were not significantly different between patients with or without liver involvement (4 of 40 episodes vs. 3 of 37 episodes, respectively; P = 0.12). Patients with an INR > 3 were evenly distributed between those with or without liver involvement (6 of 40 patients vs. 7 of 37 patients, respectively). No INR increases persisted after discontinuation of capecitabine.
This study confirms a clinically significant interaction between warfarin and capecitabine-based chemotherapy akin to that already known for 5-fluorouracil. In addition to altered coagulation parameters, bleeding can be a complication. These events occurred in patients with and without liver metastases. We recommend weekly monitoring of coagulation parameters for all patients receiving concomitant warfarin and capecitabine, with an appropriate adjustment of warfarin dose. The nature and extent of this interaction requires further investigation.
卡培他滨与华法林之间相互作用的程度及并发症尚未完全明确。
对77例接受卡培他滨治疗的患者进行回顾性研究，以分析使用或未使用华法林时的凝血异常情况。
21例患者在接受卡培他滨治疗时使用了华法林。其中12例患者在卡培他滨治疗前华法林的平均剂量为每周19.4毫克（范围为7 - 35毫克），国际标准化比值（INR）稳定（范围为0.9 - 3.3）。卡培他滨的剂量为每天1.6克/平方米至2克/平方米。13例患者（其中11例使用华法林）的INR > 3（范围为3.23 - 11.5），在130天时，使用华法林组INR > 3的概率为32%，未使用华法林组为4%（P = 5.1 x 10⁻¹⁴）。6例患者需要减少华法林剂量（减少1 - 2.5毫克）。发生了7次出血事件（均为胃肠道出血；5次与使用华法林有关）。7例出血患者在出血发生时INR范围为1.06至8（平均为3.31）。在这7次出血事件中，5例患者需要输血，平均输注3.25单位红细胞和2.4单位新鲜冰冻血浆。在接受卡培他滨治疗130天时，使用华法林患者的出血发生率为18%，未使用华法林患者为2%（P = 4 x 10⁻¹³）。有或无肝脏受累患者的出血事件无显著差异（分别为40次事件中的4次与37次事件中的3次；P = 0.12）。INR > 3的患者在有或无肝脏受累患者中分布均匀（分别为40例患者中的6例与37例患者中的7例）。停用卡培他滨后，INR升高情况未持续存在。
本研究证实华法林与基于卡培他滨的化疗之间存在具有临床意义的相互作用，类似于已知的5 - 氟尿嘧啶的情况。除凝血参数改变外，出血可能是一种并发症。这些事件在有或无肝转移的患者中均有发生。我们建议对所有同时接受华法林和卡培他滨治疗的患者每周监测凝血参数，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。
