Drug interaction between letermovir and voriconazole after allogeneic hematopoietic cell transplantation

Toshihisa Nakashima, Yoshihiro Inamoto, Yayoi Fukushi, Yoshiyuki Doke, Hironobu Hashimoto, Takahiro Fukuda, Masakazu Yamaguchi

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Letermovir has been approved for the prevention of cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HCT). Letermovir is a cytochrome P450 (CYP) 2C19 inducer. Voriconazole, which is a broad-spectrum triazole antifungal agent, is mainly metabolized by CYP2C19. Thus, voriconazole trough concentration may decrease due to the drug interaction between voriconazole and letermovir. This study aimed to clarify the effects of letermovir on voriconazole trough concentration in allogeneic HCT recipients. We retrospectively examined voriconazole trough concentration in 24 allogeneic HCT recipients who had letermovir for prevention of CMV infection. The median voriconazole C/D ratios significantly decreased after starting letermovir from 0.25 L/kg to 0.11 L/kg (p < 0.01), and increased after discontinuing letermovir from 0.15 L/kg to 0.24 L/kg (p = 0.02). The median fold change of voriconazole trough concentration during letermovir administration was 0.40. Our results suggest that voriconazole trough concentration decreases when voriconazole is combined with letermovir in allogeneic HCT recipients. Therefore, close therapeutic drug monitoring of voriconazole trough concentration is warranted in allogeneic HCT recipients after starting or discontinuing letermovir.

Original languageEnglish
Pages (from-to)872-876
Number of pages5
JournalInternational Journal of Hematology
Volume113
Issue number6
DOIs
Publication statusPublished - 06-2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology

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