Magid Mackenzie, Sanoff Scott, Lee Hui-Jie, Yang Zidanyue, Byrns Jennifer
Department of Pharmacy, Duke University Hospital, Durham, NC, USA.
Department of Medicine, Duke University Hospital, Durham, NC, USA.
J Pharm Pract. 2023 Feb;36(1):39-45. doi: 10.1177/08971900211021054. Epub 2021 Jun 8.
Manufacturer recommendations for conversion from immediate-release to extended-release tacrolimus, Envarsus XR®, suggests 80% of the total daily dose of the immediate-release formulation. This conversion has not consistently achieved therapeutic levels in the kidney transplant population.
To determine if a reliable weight-based dosing strategy could be utilized to transition kidney transplant patients from immediate-release to extended-release tacrolimus. This may help establish a safe protocol to guide transition between formulations.
Retrospective, single-center study of adult kidney transplant recipients between July 2015 and December 2018. Excluded patients received dual organs, lacked appropriately drawn tacrolimus levels, or were prescribed interacting medications. Patients were identified by querying prescriptions for extended-release tacrolimus and chart review was performed to exclude any patients without sufficient follow-up after transition.
30 patients who transitioned from immediate-release tacrolimus to tacrolimus XR were included in the final analysis. The median weight-based dose of tacrolimus XR that achieved a therapeutic level among the cohort was 0.158 mg/kg/day (Q1-Q3: 0.0587-0.221), which was about 80% of the original median weight-based immediate-release tacrolimus dose. Therapeutic dosing strategies were widely variable, represented by an R of 0.33 on linear regression. There was a statistically significant difference in median weight-based dosing strategies among patients of various racial backgrounds (p = 0.0148).
A weight-based dose of tacrolimus XR could not reliably predict a therapeutic level among the total cohort due to the wide inter-patient variability. The median weight-based rate of conversion from immediate-release to extended-release tacrolimus was 80%.
对于从速释他克莫司转换为缓释他克莫司（Envarsus XR®），制造商建议采用速释制剂每日总剂量的80%。在肾移植人群中，这种转换并未始终达到治疗水平。
确定是否可以采用基于体重的可靠给药策略，将肾移植患者从速释他克莫司转换为缓释他克莫司。这可能有助于建立一个安全方案，以指导不同制剂之间的转换。
对2015年7月至2018年12月期间的成年肾移植受者进行回顾性单中心研究。排除接受双器官移植、他克莫司血药浓度检测数据不完整或正在服用相互作用药物的患者。通过查询缓释他克莫司处方来确定患者，并进行病历审查，以排除转换后随访不足的患者。
最终分析纳入了30例从速释他克莫司转换为他克莫司XR的患者。在该队列中，达到治疗水平的他克莫司XR基于体重的中位剂量为0.158 mg/kg/天（四分位间距：0.0587 - 0.221），约为原来基于体重的速释他克莫司中位剂量的80%。治疗给药策略差异很大，线性回归显示R值为0.33。不同种族背景患者基于体重的中位给药策略存在统计学显著差异（p = 0.0148）。
由于患者间差异较大，基于体重的他克莫司XR剂量无法可靠地预测整个队列中的治疗水平。从速释他克莫司转换为缓释他克莫司基于体重的中位转换率为80%。
