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

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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

References

  1. 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. 2.

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

    CAS  Article  Google Scholar 

  3. 3.

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

  4. 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.

    CAS  Article  Google Scholar 

  5. 5.

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

  6. 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.

    CAS  Article  Google Scholar 

  7. 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  Google Scholar 

  8. 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  Google Scholar 

  9. 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.

    CAS  Article  Google Scholar 

  10. 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

Affiliations

Authors

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

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 (2020). https://doi.org/10.1038/s41409-020-01093-w

Download citation

Search