Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
Department of Pharmacy, University Health Network, Toronto, Canada.
J Oncol Pharm Pract. 2021 Jan;27(1):33-39. doi: 10.1177/1078155220908948. Epub 2020 Mar 17.
At our institution, tacrolimus is used as a second-line agent for the prevention and treatment of graft-versus-host-disease in the allogeneic hematopoietic stem cell transplantation (HSCT) unit after patients have experienced a serious or intolerable adverse event to cyclosporine. As per our standard practice, tacrolimus is administered via 2-h intermittent IV infusions (IIVs) every 12 h rather than continuous IV infusion. Shorter infusion times are cautioned due to concerns of higher rates of nephrotoxicity, neurotoxicity and infusion-related reactions, although there is a paucity of data to support this claim. Our primary objective was to evaluate the safety of a 2-h IIV of tacrolimus in an adult HSCT population. We retrospectively reviewed the charts of 104 patients who received tacrolimus by IIV (3574 doses; median = 22, range 1-158, IQR = 28) from 2002 to 2016. Primary outcomes collected include rates of nephrotoxicity, neurotoxicity and infusion-related reactions. One (0.9%) grade 2 infusion-related reaction occurred and resolved without discontinuation of tacrolimus. Of 16 incidences (13.6%) of nephrotoxicity, all but 10 (8.5%) cases resolved. Precipitating factors for nephrotoxicity unrelated to tacrolimus were identified in all 10 cases. There were 41 incidences (35%) of neurotoxicity, of which, 8 (6.8%) were considered serious. All neurotoxicity reverted to baseline or resolved completely. We propose that a 2-h IIV of tacrolimus is a safe method of administration in the adult HSCT setting.
在我们的机构中，在异体造血干细胞移植（HSCT）单元中，当患者经历环孢素严重或不能耐受的不良反应后，他克莫司被用作预防和治疗移植物抗宿主病的二线药物。根据我们的标准做法，他克莫司通过每 12 小时两次 2 小时间歇性静脉输注（IIV）给药，而不是连续静脉输注。由于担心更高的肾毒性、神经毒性和输注相关反应的发生率，较短的输注时间受到警告，尽管缺乏数据支持这一说法。我们的主要目标是评估成人 HSCT 人群中他克莫司 2 小时 IIV 的安全性。我们回顾性分析了 104 例接受他克莫司 IIV（3574 剂；中位数=22，范围 1-158，IQR=28）的患者的图表，时间范围为 2002 年至 2016 年。收集的主要结果包括肾毒性、神经毒性和输注相关反应的发生率。发生 1 例（0.9%）2 级输注相关反应，未停药自行缓解。16 例（13.6%）肾毒性中，除 10 例（8.5%）外均缓解。所有 10 例与他克莫司无关的肾毒性均确定了诱发因素。神经毒性发生 41 例（35%），其中 8 例（6.8%）认为严重。所有神经毒性均恢复至基线或完全缓解。我们提出，他克莫司 2 小时 IIV 是成人 HSCT 环境中安全的给药方法。
