Department of Pharmacy Practice, Midwestern University College of Pharmacy, Glendale, Arizona, USA.
Department of Pharmacy Services, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Transpl Infect Dis. 2024 Apr;26(2):e14267. doi: 10.1111/tid.14267. Epub 2024 Mar 15.
The antiviral letermovir has been increasingly used as off-label cytomegalovirus prophylaxis in solid organ transplant recipients. Observational studies have reported notable increases in tacrolimus (FK) exposure following letermovir; however, whether a significant interaction occurs in the setting of existing moderate-to-strong CYP3A4 inhibition is unknown. Therefore, the purpose of this study was to evaluate FK trough changes before and after letermovir among lung transplant recipients receiving azole antifungal prophylaxis.
This retrospective cohort study included lung transplant recipients newly initiated on letermovir between 2019-2022 following valganciclovir intolerance. Tacrolimus doses and concentrations were collected up to 30 days before and after the letermovir start date. No pre-emptive FK dose adjustments occurred prior to letermovir initiation. Patients admitted to the hospital or lacking an appropriately timed trough in the pre- or post-period were excluded.
A total of 78 lung transplant recipients receiving FK (1.5 mg median total daily dose) and itraconazole (56.4%), isavuconazole (25.6%) or posaconazole (17.9%) prophylaxis were included. Letermovir was started at a median of 8.4 months post-transplant. The pre-/post-letermovir median FK trough was 9.6/9.0 ng/mL (p = .151), median dose-corrected trough was 4.2/4.7 ng/mL/mg (+11.9%, p = .032), and median weight-based dose-corrected trough was 362/326 [ng/mL]/[mg/kg/day] (-9.9%, p = .036). There was no significant difference in the proportion of patients within their goal trough range before and after letermovir initiation (62% vs. 72%, p = .229).
Empiric FK dose adjustments do not appear warranted before letermovir initiation in lung transplant recipients receiving antifungal prophylaxis with moderate-to-strong CYP3A4 inhibitors.
抗病毒药物乐特韦已被越来越多地用于实体器官移植受者的非适应证巨细胞病毒预防。观察性研究报告称，在使用乐特韦后，他克莫司（FK）的暴露量显著增加；然而，在现有的中效至强效 CYP3A4 抑制的情况下是否存在显著相互作用尚不清楚。因此，本研究的目的是评估在接受唑类抗真菌预防治疗的肺移植受者中，在开始使用乐特韦前后 FK 的谷值变化。
本回顾性队列研究纳入了 2019 年至 2022 年间因更昔洛韦不耐受而开始使用乐特韦的肺移植受者。收集乐特韦开始日期前 30 天和后 30 天的他克莫司剂量和浓度。在开始使用乐特韦之前，没有进行预防性 FK 剂量调整。排除住院或在预治疗或后治疗期间没有适当时间采集谷值的患者。
共纳入 78 例接受 FK（中位数总日剂量为 1.5mg）和伊曲康唑（56.4%）、伏立康唑（25.6%）或泊沙康唑（17.9%）预防的肺移植受者。乐特韦开始使用的中位时间为移植后 8.4 个月。在开始使用乐特韦前后，FK 的谷值中位数分别为 9.6ng/mL 和 9.0ng/mL（p =.151），剂量校正后的谷值中位数分别为 4.2ng/mL/mg 和 4.7ng/mL/mg（增加 11.9%，p =.032），体重校正后的剂量校正后的谷值中位数分别为 362ng/mL/mg/kg/day 和 326ng/mL/mg/kg/day（减少 9.9%，p =.036）。在开始使用乐特韦前后，有目标谷值范围的患者比例无显著差异（62% vs. 72%，p =.229）。
在接受中效至强效 CYP3A4 抑制剂抗真菌预防治疗的肺移植受者中，在开始使用乐特韦之前，似乎不需要经验性调整 FK 剂量。
