Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison, WI, USA.
Pharmacy Department, Indiana University Health University Hospital, Indianapolis, IN, USA.
Clin Transplant. 2020 Jul;34(7):e13903. doi: 10.1111/ctr.13903. Epub 2020 May 29.
Given the current climate of drug shortages in the United States, this review summarizes available comparative literature on the use of alternative immunosuppressive agents in adult solid organ transplant recipients including kidney, pancreas, liver, lung, and heart, when immediate-release tacrolimus (IR-TAC) is not available. Alternative options explored include extended-release tacrolimus (ER-TAC) formulations, cyclosporine, belatacept, mammalian target of rapamycin inhibitors, and novel uses of induction therapy for maintenance immunosuppression. Of available alternatives, only ER-TAC formulations are of non-inferior efficacy compared to IR-TAC when used de novo or after conversion in stable kidney transplant recipients (KTRs). All other alternatives were associated with higher rates of biopsy-proven rejection, but improved tolerance from classic adverse effects of IR-TAC including nephrotoxicity and development of diabetes. While most alternative therapies are approved in KTRs, access via third-party payors is an obstacle in non-KTRs. In the setting of IR-TAC shortage, alternate therapeutic options may be plausible depending on the organ population and individual patient situation to ensure appropriate, effective immunosuppression for each patient.
鉴于美国目前药物短缺的情况,本文综述了在即时释放他克莫司(IR-TAC)不可用时,成人实体器官移植受者(包括肾、胰腺、肝、肺和心脏)中可使用的替代免疫抑制剂的相关文献,包括:延长释放他克莫司(ER-TAC)制剂、环孢素、巴利昔单抗、雷帕霉素靶蛋白抑制剂,以及诱导治疗在维持性免疫抑制中的新用途。在现有的替代药物中,只有 ER-TAC 制剂在新开始使用或在稳定的肾移植受者(KTR)中转换使用时与 IR-TAC 相比具有非劣效性。所有其他替代药物与活检证实的排斥反应发生率较高相关,但与 IR-TAC 的经典不良反应(包括肾毒性和糖尿病的发生)相比,具有更好的耐受性。虽然大多数替代疗法已在 KTR 中获得批准,但非 KTR 患者获得这些药物的途径仍存在障碍。在 IR-TAC 短缺的情况下,根据器官人群和个体患者情况,替代治疗方案可能是合理的,以确保每位患者都能获得适当、有效的免疫抑制治疗。