内容紹介
Summary
Several studies have reported increased anticoagulation effect of warfarin(WF)when combined with tyrosine kinase inhibitors(TKIs), such as gefitinib and erlotinib. However, effects of TKIs other than gefitinib and erlotinib on the anticoagulation effect of WF have not been clarified. To assess the degree and onset of prothrombin time-international normalized ratio(PT-INR)elevation and changes in WF daily doses in patients additionally receiving TKIs, this retrospective, single-center observational study compared PT-INR values and WF daily doses during WF treatment in the absence and presence of TKIs. Seven different TKIs(afatinib, alectinib, axitinib, crizotinib, pazopanib, regorafenib, and vandetanib)were prescribed during treatment with WF of venous thromboembolism in 10 cancer patients. Compared to baseline PT-INR, significant PT-INR elevations were observed in all patients during the combination therapy. The median PT-INR increased 1.6-fold from the baseline in the presence of TKIs(p<0.01), and the onset of PT-INR elevation was observed at a median of 18 days. As all patients receiving WF with the 7 TKIs showed PT-INR elevation, enhancement of the anticoagulation effect of WF in the presence of TKIs appears to be highly frequent. PT-INR should be carefully monitored, and adjusting the WF dosage may become necessary during the WF and TKI combination therapy.
要旨
gefitinibやerlotinibなどのチロシンキナーゼ阻害薬(tyrosine kinase inhibitors: TKIs)はwarfarin(WF)の抗凝固効果を増強させることが報告されている。しかしgefitinibやerlotinib以外のTKIsがWFの抗凝固効果に及ぼす影響は明らかになっていない。本研究ではWFの抗凝固効果に影響を及ぼすTKIsの抽出を目的とし,7種のTKIsがWFの抗凝固効果へ及ぼす影響について調査を行った。対象患者は静脈血栓塞栓症の治療に対してWF投与中に7種のTKIs(afatinib,alectinib,axitinib,crizotinib,pazopanib,regorafenib,vandetanib)が併用開始となった10例とし,TKIs併用前後のPT-INRの変動を評価した。TKIsとWFの併用によるPT-INRの上昇は10例中10例(100.0%)に認められ,PT-INR上昇率の中央値は1.6倍であった(p<0.01)。また,PT-INR上昇の発現時期の中央値は18日であった。本研究では,WFの添付文書に相互作用に関する記載のない7種のTKIsにおいてもWFとの併用でPT-INRの上昇を認めた。以上の結果から,TKIsとWFの相互作用はまれではなく,併用時には注意深いPT-INRや出血のモニタリングとWF投与量の調整が必要となる可能性が示唆された。
目次
Several studies have reported increased anticoagulation effect of warfarin(WF)when combined with tyrosine kinase inhibitors(TKIs), such as gefitinib and erlotinib. However, effects of TKIs other than gefitinib and erlotinib on the anticoagulation effect of WF have not been clarified. To assess the degree and onset of prothrombin time-international normalized ratio(PT-INR)elevation and changes in WF daily doses in patients additionally receiving TKIs, this retrospective, single-center observational study compared PT-INR values and WF daily doses during WF treatment in the absence and presence of TKIs. Seven different TKIs(afatinib, alectinib, axitinib, crizotinib, pazopanib, regorafenib, and vandetanib)were prescribed during treatment with WF of venous thromboembolism in 10 cancer patients. Compared to baseline PT-INR, significant PT-INR elevations were observed in all patients during the combination therapy. The median PT-INR increased 1.6-fold from the baseline in the presence of TKIs(p<0.01), and the onset of PT-INR elevation was observed at a median of 18 days. As all patients receiving WF with the 7 TKIs showed PT-INR elevation, enhancement of the anticoagulation effect of WF in the presence of TKIs appears to be highly frequent. PT-INR should be carefully monitored, and adjusting the WF dosage may become necessary during the WF and TKI combination therapy.
要旨
gefitinibやerlotinibなどのチロシンキナーゼ阻害薬(tyrosine kinase inhibitors: TKIs)はwarfarin(WF)の抗凝固効果を増強させることが報告されている。しかしgefitinibやerlotinib以外のTKIsがWFの抗凝固効果に及ぼす影響は明らかになっていない。本研究ではWFの抗凝固効果に影響を及ぼすTKIsの抽出を目的とし,7種のTKIsがWFの抗凝固効果へ及ぼす影響について調査を行った。対象患者は静脈血栓塞栓症の治療に対してWF投与中に7種のTKIs(afatinib,alectinib,axitinib,crizotinib,pazopanib,regorafenib,vandetanib)が併用開始となった10例とし,TKIs併用前後のPT-INRの変動を評価した。TKIsとWFの併用によるPT-INRの上昇は10例中10例(100.0%)に認められ,PT-INR上昇率の中央値は1.6倍であった(p<0.01)。また,PT-INR上昇の発現時期の中央値は18日であった。本研究では,WFの添付文書に相互作用に関する記載のない7種のTKIsにおいてもWFとの併用でPT-INRの上昇を認めた。以上の結果から,TKIsとWFの相互作用はまれではなく,併用時には注意深いPT-INRや出血のモニタリングとWF投与量の調整が必要となる可能性が示唆された。