Pharmacokinetic drug evaluation of letermovir prophylaxis for cytomegalovirus in hematopoietic stem cell transplantation

ABSTRACT

Introduction: Letermovir is a new antiviral approved to prevent cytomegalovirus infection in hematopoietic stem cell transplant recipients. It has a distinct mechanism of action as it acts as a terminase complex inhibitor, and shows some advantages compared to the current treatment options for cytomegalovirus infection.

Areas covered: This review focuses on the efficacy, safety, pharmacokinetics, pharmacodynamics, and drug-drug interactions of letermovir.

Expert opinion: Letermovir is a new antiviral to prevent cytomegalovirus infection. Unlike the currently used polymerase inhibitors, it has a distinct mechanism of action with better safety, limited resistance, and no cross-resistance. Although a lot of research on pharmacokinetics and drug-drug interactions has already been performed, it might be useful to clarify the effect of letermovir on voriconazole exposure, the drug–drug interaction between caspofungine and letermovir and the effect of statins on letermovir exposure. Also, the lack of an exposure–response relationship should be confirmed in large real-life post-marketing studies in order to be able to lower the intravenous dose of letermovir.

KEYWORDS:

• Letermovir
• cytomegalovirus
• hematopoietic stem cell transplantation
• pharmacokinetics
• pharmacodynamics
• terminate complex inhibitor
• efficacy
• drug–drug interactions

Box 1. Drug summary box

Table

Acknowledgments

We thank Jonas Dehairs (PhD, Department of Oncology, Laboratory of Lipid Metabolism and Cancer, KULeuven, Leuven, Belgium) for the graphical support in adapting Figure 2 and producing Figure 3.

Declaration of interest

I Spriet has received research grants, speaker’s fees and travel grants from Merck, Sharp & Dhome (MSD). J Maertens has served as a consultant to MSD, has received research funding from MSD and has been on the speaker’s bureau for MSD.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.