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直接作用口服抗凝剂与钙调磷酸酶抑制剂在实体器官移植中的药物相互作用:治疗注意事项。

Drug interactions between direct-acting oral anticoagulants and calcineurin inhibitors during solid organ transplantation: considerations for therapy.

机构信息

a Department of Pharmacology & Experimental Therapeutics, Thomas Jefferson University , Philadelphia , PA , USA.

b Department of Medical Oncology, Thomas Jefferson University Hospital , Philadelphia , PA , USA.

出版信息

Expert Rev Clin Pharmacol. 2019 Aug;12(8):781-790. doi: 10.1080/17512433.2019.1637733. Epub 2019 Jul 4.

Abstract

: There is a high incidence of venous thromboembolism (VTE) in solid organ transplant recipients. The safety and efficacy of direct-acting oral anticoagulants (DOAC) have been well established in clinical practice for the prevention and treatment of VTE in broad populations. However, the management of VTE in the setting of solid organ transplantation remains a challenge to clinicians due to limited evidence of DOAC usage with calcineurin inhibitors. : The current literature available on the pharmacokinetic-pharmacodynamic interaction between DOACs and calcineurin inhibitors is presented. A comprehensive review was undertaken using PubMed, Embase, drug product labeling, and drug product review conducted by the US Food and Drug Administration using Drugs@FDA. The potential for mitigation strategies and clinical management using extant knowledge is explored. : Immunosuppression therapy is necessary to prevent graft rejection by the host. The sparsity of data together with the lack of well-designed prospective studies of DOAC use in solid organ transplant recipients presents a unique challenge to clinicians in determining the clinical relevance of possible drug interactions. Existing evidence suggests that with attention to concomitant drug use and renal function, the co-administration of DOACs and calcineurin inhibitors is safe and effective.

摘要

在实体器官移植受者中,静脉血栓栓塞症(VTE)的发病率很高。直接口服抗凝剂(DOAC)在广泛人群中预防和治疗 VTE 的临床实践中已被证实具有良好的安全性和有效性。然而,由于 DOAC 与钙调神经磷酸酶抑制剂联合使用的证据有限,实体器官移植背景下 VTE 的管理仍然对临床医生构成挑战。

本文介绍了 DOAC 与钙调神经磷酸酶抑制剂之间药代动力学-药效学相互作用的现有文献。使用 PubMed、Embase、药物产品标签以及美国食品和药物管理局使用 Drugs@FDA 进行的药物产品审查,全面回顾了相关文献。利用现有知识探索了缓解策略和临床管理的可能性。

免疫抑制治疗对于防止宿主对移植物的排斥反应是必要的。数据的缺乏以及缺乏关于 DOAC 在实体器官移植受者中使用的精心设计的前瞻性研究,使得临床医生在确定可能的药物相互作用的临床相关性方面面临独特的挑战。现有证据表明,在注意到伴随药物使用和肾功能的情况下,DOAC 和钙调神经磷酸酶抑制剂联合使用是安全有效的。

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