Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Decrease in voriconazole concentration-to-dose ratio after letermovir initiation: a retrospective, observational study

Bone Marrow Transplantation volume 56, pages 949–951 (2021)Cite this article

Subjects

Abstract

Letermovir is used to prevent cytomegalovirus infection in hematopoietic stem cell transplantation (HSCT) recipients. Although this agent decreases voriconazole exposure in healthy individuals, the effect of coadministration of letermovir and voriconazole in HSCT recipients is unknown. This retrospective, observational, single-center study was conducted between January 2016 and July 2019 to examine the voriconazole concentration-to-dose ratio over three periods: (A) (days −7 to −1 [day 0: day of HCST]), (B) (days 4–10), and (C) (days 11–17). Forty-two HSCT recipients administered voriconazole were divided into the following two groups based on letermovir coadministration: letermovir (n = 15) and control (n = 27). The percent change (−33.2%, p < 0.05) in the voriconazole concentration-to-dose ratio from periods A to C in the letermovir group was significantly lower than that in the control group. Therefore, frequent therapeutic drug monitoring of voriconazole concentrations and subsequent dose adjustments should be performed regularly in HSCT recipients.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Percent change in voriconazole concentration-to-dose ratio from period A.

References

  1. Mellinghoff SC, Panse J, Alakel N, Behre G, Buchheidt D, Christopeit M, et al. Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO). Ann Hematol. 2018;97:197–207.

    Article  Google Scholar 

  2. Theuretzbacher U, Ihle F, Derendorf H. Pharmacokinetic/pharmacodynamic profile of voriconazole. Clin Pharmacokinet. 2006;45:649–63.

    Article  CAS  Google Scholar 

  3. Prevymis: EPAR—Product Information. 2020. https://www.ema.europa.eu/en/documents/product-information/prevymis-epar-product-information_en.pdf.

  4. Marshall WL, McCrea JB, Macha S, Menzel K, Liu F, van Schanke A, et al. Pharmacokinetics and tolerability of letermovir coadministered with azole antifungals (posaconazole or voriconazole) in healthy subjects. J Clin Pharm. 2018;58:897–904.

    Article  CAS  Google Scholar 

  5. Letermovir: DrugBank. 2020. https://www.drugbank.ca/drugs/DB12070.

  6. Yamashita F, Sasa Y, Yoshida S, Hisaka A, Asai Y, Kitano H, et al. Modeling of rifampicin-induced CYP3A4 activation dynamics for the prediction of clinical drug-drug interactions from in vitro data. PLoS ONE. 2013;8:e70330.

    Article  CAS  Google Scholar 

  7. Hikasa S, Shimabukuro S, Osugi Y, Ikegame K, Kaida K, Fukunaga K, et al. Tacrolimus concentration after letermovir initiation in hematopoietic stem cell transplantation recipients receiving voriconazole: a retrospective, observational study. Int J Med Sci. 2020;17:859–64.

    Article  CAS  Google Scholar 

  8. Duong A, Sweet A, Jain R, Hill JA, Pergam SA, Boeckh M, et al. Clinically significant drug interaction: letermovir and voriconazole. J Antimicrob Chemother. 2020;75:775–7.

    Article  CAS  Google Scholar 

  9. Trifilio S, Pennick G, Pi J, Zook J, Golf M, Kaniecki K, et al. Monitoring plasma voriconazole levels may be necessary to avoid subtherapeutic levels in hematopoietic stem cell transplant recipients. Cancer 2007;109:1532–5.

    Article  CAS  Google Scholar 

  10. PREVYMIS™ (letermovir) tablets, for oral use: U.S. Full prescribing information. 2020. https://www.merck.com/product/usa/pi_circulars/p/prevymis/prevymis_pi.pdf.

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacy, Hyogo College of Medicine College Hospital, Hyogo, 663-8501, Japan

    Shinichi Hikasa, Shota Shimabukuro, Tomoko Higami, Masami Tada, Kuniyoshi Tanaka, Mina Yanai & Takeshi Kimura

  2. Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, 663-8501, Japan

    Yuko Osugi, Kazuhiro Ikegame, Katsuji Kaida & Keiko Fukunaga

Authors
  1. Shinichi Hikasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shota Shimabukuro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuko Osugi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kazuhiro Ikegame
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Katsuji Kaida
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Keiko Fukunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tomoko Higami
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Masami Tada
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kuniyoshi Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mina Yanai
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Takeshi Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shinichi Hikasa.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hikasa, S., Shimabukuro, S., Osugi, Y. et al. Decrease in voriconazole concentration-to-dose ratio after letermovir initiation: a retrospective, observational study. Bone Marrow Transplant 56, 949–951 (2021). https://doi.org/10.1038/s41409-020-01093-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-020-01093-w

This article is cited by

Search

Advanced search

Quick links