Letermovir and tacrolimus interaction effects in hematopoietic cell transplantation recipients receiving moderate cytochrome P450 3A4 inhibitors for antifungal prophylaxis

被引:3
作者
Malespini, Jack [1 ]
Lei, Matthew [1 ]
Tavares, Erica [1 ]
Hammond, Sarah P. [2 ]
Chen, Yi-Bin [3 ]
Luk, Samantha O. [1 ]
DeFilipp, Zachariah [3 ]
机构
[1] Massachusetts Gen Hosp, Dept Pharm, 55 Fruit St, GRB 005, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA
[3] Massachusetts Gen Hosp, Hematopoiet Cell Transplant & Cellular Therapy Pr, Boston, MA USA
基金
美国国家卫生研究院;
关键词
Cytomegalovirus; letermovir; tacrolimus; drug interactions; hematopoietic stem cell transplant; PHARMACOKINETICS; CYTOMEGALOVIRUS;
D O I
10.1177/10781552221139772
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Introduction Letermovir inhibits cytomegalovirus replication and is approved for the prevention of cytomegalovirus infection in cytomegalovirus seropositive hematopoietic cell transplantation recipients. Studies have found that letermovir coadministration has minimal effect on tacrolimus levels prior to the start of voriconazole, a strong cytochrome P450 (CYP) 3A4 inhibitor. However, data are lacking for hematopoietic cell transplantation recipients receiving letermovir and tacrolimus with moderate CYP 3A4 inhibitors as antifungal prophylaxis. Methods In this retrospective single-center analysis, we reviewed the charts of 92 consecutive adult allogeneic hematopoietic cell transplantation recipients receiving letermovir, tacrolimus, and moderate CYP3A4 inhibitors for antifungal prophylaxis. Results Tacrolimus concentration/dose (C/D) ratios were evaluated for the first 7 days pre-letermovir and for the first and second 7-day periods after letermovir. The tacrolimus mean C/D ratios [(ng/mL)/(mg/kg/day)] increased significantly with the addition of letermovir: 172.99 (95% confidence interval (CI): 158.2-187.78) pre-letermovir, 268.66 (95% CI: 244.34-292.98) first-week letermovir, and 312.19 (95% CI: 279.39-344.99) second-week letermovir (P < 0.001). The average dosages (mg/kg) of tacrolimus also decreased significantly across the three-time intervals (P < 0.001). Only four patients experienced clinically significant cytomegalovirus reactivation which required systemic treatment. Conclusion These results demonstrate a reduction in tacrolimus dosing requirements for patients receiving tacrolimus and letermovir with concomitant moderate CYP3A4 inhibitors. The results of this interaction suggest that frequent monitoring of tacrolimus trough levels is warranted when starting letermovir and that empiric reduction of tacrolimus dosing upon letermovir initiation should be considered.
引用
收藏
页码:1574 / 1579
页数:6
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