Effects of Isavuconazole on the Plasma Concentrations of Tacrolimus among Solid-Organ Transplant Patients

Antimicrob Agents Chemother. 2017 Aug 24;61(9):e00970-17. doi: 10.1128/AAC.00970-17. Print 2017 Sep.

Abstract

We evaluated the interaction between isavuconazole and tacrolimus among 55 organ transplant recipients. After isavuconazole discontinuation, the tacrolimus concentration/dose ratio normalized by weight (C/D) was reduced by 16%. Liver transplant recipients experienced the largest C/D reduction. A 1.3-fold decrease in tacrolimus daily dose was required to maintain desired tacrolimus levels. There was considerable interpatient variability in the magnitude of the drug interaction. Tacrolimus doses should not be adjusted uniformly but, rather, be guided by therapeutic drug monitoring.

Keywords: drug interactions; isavuconazole; pharmacokinetics; tacrolimus; zygomycetes.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antifungal Agents / therapeutic use*
  • Cytochrome P-450 CYP3A / metabolism
  • Cytochrome P-450 CYP3A Inhibitors / therapeutic use
  • Drug Interactions / physiology*
  • Drug Monitoring
  • Female
  • Heart Transplantation
  • Humans
  • Immunosuppressive Agents / blood*
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation
  • Liver Transplantation
  • Lung Transplantation
  • Male
  • Middle Aged
  • Nitriles / therapeutic use*
  • Pyridines / therapeutic use*
  • Retrospective Studies
  • Tacrolimus / blood*
  • Tacrolimus / therapeutic use*
  • Transplant Recipients
  • Triazoles / therapeutic use*
  • Young Adult

Substances

  • Antifungal Agents
  • Cytochrome P-450 CYP3A Inhibitors
  • Immunosuppressive Agents
  • Nitriles
  • Pyridines
  • Triazoles
  • isavuconazole
  • Cytochrome P-450 CYP3A
  • Tacrolimus