Differences in kinetics of tacrolimus concentration after letermovir discontinuation by type of concomitant azole antifungal

Toshihisa Nakashima, Yoshihiro Inamoto, Jun Aoki, Ayumu Ito, Takashi Tanaka, Sung Won Kim, Hironobu Hashimoto, Takahiro Fukuda, Tetsuya Furukawa

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Letermovir is commonly used for CMV prophylaxis after allogeneic hematopoietic cell transplantation (HCT). Pharmacokinetic studies have shown an increase in tacrolimus exposure among healthy volunteers who took letermovir. However, studies in HCT recipients are needed because these patients are typically using concomitant antifungals with different degrees of CYP3A4 inhibition that may further interact with tacrolimus pharmacokinetics. In this study, we retrospectively evaluated the kinetics of tacrolimus concentration after letermovir discontinuation by type of concomitant azole antifungal in 57 HCT recipients. The median fold change in tacrolimus concentration-to-dose (C/D) ratio after discontinuing letermovir was 0.64 (range 0.43–0.99) with fluconazole and 1.10 (range 0.59–1.73) with voriconazole (p < 0.001). The tacrolimus C/D ratio decreased ≥ 30% after discontinuing letermovir (p < 0.001) in 66% of patients on fluconazole and 9% on voriconazole. Among patients whose tacrolimus C/D ratio decreased ≥ 30%, three (9%) patients in the fluconazole group and one (4%) in the voriconazole group experienced worsening of GVHD. Careful monitoring of tacrolimus concentration is important after letermovir discontinuation to avoid worsening of GVHD due to decreased tacrolimus concentration.

Original languageEnglish
Pages (from-to)158-162
Number of pages5
JournalInternational Journal of Hematology
Volume115
Issue number2
DOIs
Publication statusPublished - 02-2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology

Fingerprint

Dive into the research topics of 'Differences in kinetics of tacrolimus concentration after letermovir discontinuation by type of concomitant azole antifungal'. Together they form a unique fingerprint.

Cite this