Concurrent Apixaban With Itraconazole or Posaconazole Pharmacokinetic and Clinical Outcome Evaluation in Cardiothoracic Transplant Recipients

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation Pub Date : 2025-04-28 DOI:10.1111/ctr.70165

Kennedy Concannon, Rachel Huntsman, Kristin Cole, Cassie Kennedy, Andrew Rosenbaum, Adley Lemke

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引用次数: 0

Abstract

Itraconazole and posaconazole are frequently prescribed following transplantation to prevent and treat fungal infections. Navigating drug interactions is challenging due to these agents’ potent CYP3A4 inhibition, and literature describing concurrent apixaban, a CYP3A4 substrate, is limited. This retrospective study of cardiothoracic transplant recipients evaluates the impact of itraconazole and posaconazole on apixaban exposure and reports clinical outcomes from routine apixaban dose reduction. Institutional practice reduces apixaban to 2.5 mg twice daily with itraconazole or posaconazole and obtains apixaban therapeutic drug monitoring (TDM), expected range 34–230 ng/mL. Eighteen levels collected in 15 patients on itraconazole displayed a median [IQR] apixaban trough of 143 ng/mL [95–195]. Fifteen levels collected in 13 patients on posaconazole displayed a median [IQR] apixaban trough of 124 ng/mL [93–174]. Two major bleed events, three VTE, two stroke, and eight instances of clot resolution were identified. Reduced-dose apixaban resulted in apixaban exposure similar to normal dosing in the general population. Apixaban TDM is encouraged for individualized dosing when administered with itraconazole and posaconazole.

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阿哌沙班与伊曲康唑或泊沙康唑在胸腔移植受者中的并发药代动力学和临床结果评价

伊曲康唑和泊沙康唑常用于移植后预防和治疗真菌感染。由于这些药物具有强效的CYP3A4抑制作用，导航药物相互作用是具有挑战性的，并且描述CYP3A4底物阿哌沙班并发的文献有限。这项对心胸移植受者的回顾性研究评估了伊曲康唑和泊沙康唑对阿哌沙班暴露的影响，并报告了常规阿哌沙班剂量减少的临床结果。机构实践将阿哌沙班减少至2.5 mg，每日两次，与伊曲康唑或泊沙康唑联合使用，并获得阿哌沙班治疗药物监测（TDM），预期范围34-230 ng/mL。15例伊曲康唑患者的18个水平显示阿哌沙班的中位[IQR]波谷为143 ng/mL[95-195]。13例泊沙康唑患者的15个水平显示阿哌沙班的中位[IQR]波谷为124 ng/mL[93-174]。2例主要出血事件，3例静脉血栓栓塞，2例中风，8例血栓溶解。减少阿哌沙班剂量导致阿哌沙班暴露与普通人群中正常剂量相似。当阿哌沙班TDM与伊曲康唑和泊沙康唑联合使用时，鼓励个体化给药。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Transplantation 医学-外科

CiteScore

3.70

自引率

4.80%

发文量

286

审稿时长

2 months

期刊介绍： Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored. Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include: Immunology and immunosuppression; Patient preparation; Social, ethical, and psychological issues; Complications, short- and long-term results; Artificial organs; Donation and preservation of organ and tissue; Translational studies; Advances in tissue typing; Updates on transplant pathology;. Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries. Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.