Department of Pharmacy, Vanderbilt University Medical Center, Nashville, USA.
Department of Pharmacy, Yale New Haven Hospital, Nashville, USA.
Clin Transplant. 2023 Nov;37(11):e15102. doi: 10.1111/ctr.15102. Epub 2023 Aug 17.
Sirolimus and everolimus are mechanistic target of rapamycin inhibitors (mTORi) that may be included in immunosuppression regimens for orthotopic heart transplant (OHT) recipients. mTORi play a role in slowing progression of cardiac allograft vasculopathy; however, they have poor tolerability, sometimes necessitating a change between agents or therapies. The literature surrounding a conversion between mTORi are incongruent, thus this study was designed to assess the concentration/dose ratio for each medication around the time of conversion to provide guidance for a conversion strategy between mTORi.
We conducted a retrospective study of adult OHT recipients who were maintained on both sirolimus- and everolimus-based immunosuppression regimens. The primary outcome was the concentration/dose (C/d) ratio of sirolimus to everolimus. Secondary outcomes included changes in hematologic and lipid labs and patient-reported intolerances.
The C/d ratio of sirolimus was 4.42, whereas the everolimus ratio was 2.23, resulting in a sirolimus: everolimus ratio of 1.98. Secondarily, after converting between mTORi, 93% of patients who reported intolerance(s) to one agent had a resolution of that intolerance. In our patient population, everolimus appeared better tolerated than sirolimus, with significantly more patients having no reported intolerances and significantly fewer patients experiencing edema. Other lab values were similar between patients receiving sirolimus and everolimus, except for an increased hemoglobin level in those receiving everolimus.
The conversion ratio of 1:2 observed in our population suggests OHT recipients may require an increased dose of EVL compared with SRL to maintain the same goal trough levels. A conversion between mTORi appeared to improve tolerability and did not lead to clinically significant worsening of any measured lab value.
西罗莫司和依维莫司是雷帕霉素靶蛋白抑制剂（mTORi），可能被纳入原位心脏移植（OHT）受者的免疫抑制方案中。mTORi 在减缓心脏移植物血管病的进展中发挥作用；然而，它们的耐受性较差，有时需要在药物或治疗之间进行转换。关于 mTORi 之间转换的文献不一致，因此本研究旨在评估转换时每种药物的浓度/剂量比，为 mTORi 之间的转换策略提供指导。
我们对同时接受西罗莫司和依维莫司免疫抑制方案的成年 OHT 受者进行了回顾性研究。主要结局是西罗莫司与依维莫司的浓度/剂量（C/d）比。次要结局包括血液学和脂质实验室检查的变化以及患者报告的不耐受情况。
西罗莫司的 C/d 比为 4.42，而依维莫司的比为 2.23，导致西罗莫司：依维莫司比为 1.98。其次，在 mTORi 之间转换后，93%报告对一种药物不耐受的患者的不耐受得到缓解。在我们的患者人群中，依维莫司的耐受性似乎优于西罗莫司，报告无不耐受的患者明显更多，且发生水肿的患者明显更少。接受西罗莫司和依维莫司的患者的其他实验室值相似，除了接受依维莫司的患者的血红蛋白水平升高。
我们人群中观察到的转换比 1:2 表明，与 SRL 相比，OHT 受者可能需要增加 EVL 的剂量以维持相同的目标谷浓度。mTORi 之间的转换似乎提高了耐受性，并且不会导致任何测量的实验室值出现临床显著恶化。
