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

Expert Opin Drug Metab Toxicol. 2018 Dec;14(12):1197-1207. doi: 10.1080/17425255.2018.1550485. Epub 2018 Dec 4.

Abstract

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; drug–drug interactions; efficacy; hematopoietic stem cell transplantation; pharmacodynamics; pharmacokinetics; terminate complex inhibitor.

Publication types

  • Review

MeSH terms

  • Acetates / administration & dosage*
  • Acetates / pharmacokinetics
  • Acetates / pharmacology
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / pharmacology
  • Cytomegalovirus
  • Cytomegalovirus Infections / etiology
  • Cytomegalovirus Infections / prevention & control*
  • Drug Interactions
  • Drug Resistance, Viral
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Quinazolines / administration & dosage*
  • Quinazolines / pharmacokinetics
  • Quinazolines / pharmacology

Substances

  • Acetates
  • Antiviral Agents
  • Quinazolines
  • letermovir