目的阐明艾多沙班药代动力学相互作用(PK-DDI)的机制和剂量调整意见,为临床合理联合用药提供参考。方法检索PubMed、Web of Science、中国知网、万方数据、维普网中艾多沙班的药物相互作用(DDIs)文献,结合2021年欧洲心律协会指南、美国...目的阐明艾多沙班药代动力学相互作用(PK-DDI)的机制和剂量调整意见,为临床合理联合用药提供参考。方法检索PubMed、Web of Science、中国知网、万方数据、维普网中艾多沙班的药物相互作用(DDIs)文献,结合2021年欧洲心律协会指南、美国食品药品监督管理局(FDA)说明书、欧盟产品特性概要(SmPC)和Lexicomp数据库,总结不同种类药物与艾多沙班的PK-DDI机制、临床证据以及推荐剂量调整方法。结果共涉及17类69种药品,其中无需调整剂量药品24种和需要禁用、慎用或者需要调整剂量药品45种。结论艾多沙班PK-DDI涉及多种药品,机制主要与CYP3A4和P-糖蛋白抑制剂/诱导剂相关,但是目前PK数据缺乏。此外患者的个体特征和疾病状态也会对艾多沙班的体内过程产生影响,目前对于多因素的研究较欠缺,需进一步研究为临床合理用药提供证据。展开更多
Novel oral anticoagulants(NOACs), which include direct thrombin inhibitor(dabigatran) and direct factor Xa inhibitors(rivaroxaban, apixaban and edoxaban), are gaining popularity in the prevention of embolic stroke in ...Novel oral anticoagulants(NOACs), which include direct thrombin inhibitor(dabigatran) and direct factor Xa inhibitors(rivaroxaban, apixaban and edoxaban), are gaining popularity in the prevention of embolic stroke in non-valvular atrial fibrillation as well as in the prevention and treatment of venous thromboembolism. However, similar to traditional anticoagulants, NOACs have the side effects of bleeding, including gastrointestinal bleeding(GIB). Results from both randomized clinical trials and observations studies suggest that high-dose dabigatran(150 mg b.i.d), rivaroxaban and high-dose edoxaban(60 mg daily) are associated with a higher risk of GIB compared with warfarin. Other risk factors of NOAC-related GIB include concomitant use of ulcerogenic agents, older age, renal impairment, Helicobacter pylori infection and a past history of GIB. Prevention of NOAC-related GIB includes proper patient selection, using a lower dose of certain NOACs and in patients with renal impairment, correction of modifiable risk factors, and prescription of gastroprotective agents. Overt GIB can be managed by withholding NOACs followed by delayed endoscopic treatment. In severe bleeding, additional measures include administration of activated charcoal, use of specific reversal agents such as idarucizumab for dabigatran and andexanent alfa for factor Xa inhibitors, and urgent endoscopic management.展开更多
In recent years,the traditional concept that cirrhosis-related coagulopathy is an acquired bleeding disorder has evolved.Currently,it is known that in cirrhotic patients,the hemostatic system is rebalanced,which invol...In recent years,the traditional concept that cirrhosis-related coagulopathy is an acquired bleeding disorder has evolved.Currently,it is known that in cirrhotic patients,the hemostatic system is rebalanced,which involves coagulation factors,fibrinolysis and platelets.These alterations disrupt homeostasis,skewing it toward a procoagulant state,which can lead to thromboembolic manifestations,especially when hemodynamic and endothelial factors co-occur,such as in the portal vein system in cirrhosis.Portal vein thrombosis is a common complication of advanced liver cirrhosis that negatively affects the course of liver disease,prognosis of cirrhotic patients and success of liver transplantation.It is still debated whether portal vein thrombosis is the cause or the consequence of worsening liver function.Anticoagulant therapy is the mainstay treatment for acute symptomatic portal vein thrombosis.In chronic portal vein thrombosis,the role of anticoagulant therapy is still unclear.Traditional anticoagulants,vitamin K antagonists and low-molecular-weight heparin are standard-of-care treatments for portal vein thrombosis.In the last ten years,direct oral anticoagulants have been approved for the prophylaxis and treatment of many thromboembolicrelated diseases,but evidence on their use in cirrhotic patients is very limited.The aim of this review was to summarize the evidence about the safety and effectiveness of direct oral anticoagulants for treating portal vein thrombosis in cirrhotic patients.展开更多
文摘目的阐明艾多沙班药代动力学相互作用(PK-DDI)的机制和剂量调整意见,为临床合理联合用药提供参考。方法检索PubMed、Web of Science、中国知网、万方数据、维普网中艾多沙班的药物相互作用(DDIs)文献,结合2021年欧洲心律协会指南、美国食品药品监督管理局(FDA)说明书、欧盟产品特性概要(SmPC)和Lexicomp数据库,总结不同种类药物与艾多沙班的PK-DDI机制、临床证据以及推荐剂量调整方法。结果共涉及17类69种药品,其中无需调整剂量药品24种和需要禁用、慎用或者需要调整剂量药品45种。结论艾多沙班PK-DDI涉及多种药品,机制主要与CYP3A4和P-糖蛋白抑制剂/诱导剂相关,但是目前PK数据缺乏。此外患者的个体特征和疾病状态也会对艾多沙班的体内过程产生影响,目前对于多因素的研究较欠缺,需进一步研究为临床合理用药提供证据。
基金Supported by the Li Shu Fan Medical Foundation Professorship(to Leung WK)
文摘Novel oral anticoagulants(NOACs), which include direct thrombin inhibitor(dabigatran) and direct factor Xa inhibitors(rivaroxaban, apixaban and edoxaban), are gaining popularity in the prevention of embolic stroke in non-valvular atrial fibrillation as well as in the prevention and treatment of venous thromboembolism. However, similar to traditional anticoagulants, NOACs have the side effects of bleeding, including gastrointestinal bleeding(GIB). Results from both randomized clinical trials and observations studies suggest that high-dose dabigatran(150 mg b.i.d), rivaroxaban and high-dose edoxaban(60 mg daily) are associated with a higher risk of GIB compared with warfarin. Other risk factors of NOAC-related GIB include concomitant use of ulcerogenic agents, older age, renal impairment, Helicobacter pylori infection and a past history of GIB. Prevention of NOAC-related GIB includes proper patient selection, using a lower dose of certain NOACs and in patients with renal impairment, correction of modifiable risk factors, and prescription of gastroprotective agents. Overt GIB can be managed by withholding NOACs followed by delayed endoscopic treatment. In severe bleeding, additional measures include administration of activated charcoal, use of specific reversal agents such as idarucizumab for dabigatran and andexanent alfa for factor Xa inhibitors, and urgent endoscopic management.
文摘In recent years,the traditional concept that cirrhosis-related coagulopathy is an acquired bleeding disorder has evolved.Currently,it is known that in cirrhotic patients,the hemostatic system is rebalanced,which involves coagulation factors,fibrinolysis and platelets.These alterations disrupt homeostasis,skewing it toward a procoagulant state,which can lead to thromboembolic manifestations,especially when hemodynamic and endothelial factors co-occur,such as in the portal vein system in cirrhosis.Portal vein thrombosis is a common complication of advanced liver cirrhosis that negatively affects the course of liver disease,prognosis of cirrhotic patients and success of liver transplantation.It is still debated whether portal vein thrombosis is the cause or the consequence of worsening liver function.Anticoagulant therapy is the mainstay treatment for acute symptomatic portal vein thrombosis.In chronic portal vein thrombosis,the role of anticoagulant therapy is still unclear.Traditional anticoagulants,vitamin K antagonists and low-molecular-weight heparin are standard-of-care treatments for portal vein thrombosis.In the last ten years,direct oral anticoagulants have been approved for the prophylaxis and treatment of many thromboembolicrelated diseases,but evidence on their use in cirrhotic patients is very limited.The aim of this review was to summarize the evidence about the safety and effectiveness of direct oral anticoagulants for treating portal vein thrombosis in cirrhotic patients.
