Goto Sotaro, Sadato Daichi, Toya Takashi, Shimizu Akihiro, Narita Koki, Shimizu Hiroaki, Najima Yuho, Yamamura Yasuhiko, Doki Noriko
Department of Pharmacy, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
Clinical Research and Trials Center, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
Int J Hematol. 2025 Aug;122(2):199-205. doi: 10.1007/s12185-025-04017-w. Epub 2025 Jun 16.
Letermovir can effectively prevent clinically significant cytomegalovirus infections following allogeneic hematopoietic stem cell transplantation (HCT). Although some antifungal agents influence the pharmacokinetics of tacrolimus after the discontinuation of letermovir, the effect of posaconazole (PSCZ) has not been previously described. This study retrospectively evaluated the association between azole type and tacrolimus pharmacokinetics before and after discontinuation of letermovir prophylaxis. The analysis included 89 patients who underwent HCT at our hospital. In the PSCZ group, the tacrolimus concentration-to-dose (C/D) ratio after letermovir discontinuation was significantly higher than that observed before discontinuation (median 7.91 vs 6.50, P = 0.004). The fold-change in the C/D ratio (post-/pre-discontinuation) was significantly higher in the PSCZ group compared with the fluconazole group (median 1.23 vs 0.83, P = 0.003). These findings suggest that tacrolimus pharmacokinetics after letermovir discontinuation in HCT recipients vary depending on which concomitant azole antifungal agent is used. Furthermore, the tacrolimus C/D ratio could increase following letermovir discontinuation in patients receiving PSCZ. Careful monitoring of tacrolimus concentrations at letermovir discontinuation is crucial to avoid an unexpected reversal of tacrolimus concentrations and prevent adverse events.
来特莫韦可有效预防异基因造血干细胞移植（HCT）后具有临床意义的巨细胞病毒感染。尽管一些抗真菌药物在来特莫韦停药后会影响他克莫司的药代动力学，但泊沙康唑（PSCZ）的影响此前尚未见报道。本研究回顾性评估了在停用预防剂量的来特莫韦前后，唑类药物类型与他克莫司药代动力学之间的关联。分析纳入了我院89例行HCT的患者。在PSCZ组中，来特莫韦停药后的他克莫司浓度-剂量（C/D）比值显著高于停药前（中位数7.91对6.50，P = 0.004）。与氟康唑组相比，PSCZ组的C/D比值变化倍数（停药后/停药前）显著更高（中位数1.23对0.83，P = 0.003）。这些发现表明，HCT受者在停用来特莫韦后他克莫司的药代动力学因所使用的唑类抗真菌药物不同而有所差异。此外，接受PSCZ治疗的患者在停用来特莫韦后他克莫司的C/D比值可能会升高。在停用来特莫韦时仔细监测他克莫司浓度对于避免他克莫司浓度意外逆转及预防不良事件至关重要。
