Drug interactions and safety profiles with concomitant use of caspofungin and calcineurin inhibitors in allogeneic haematopoietic cell transplantation

Br J Clin Pharmacol. 2017 Sep;83(9):2000-2007. doi: 10.1111/bcp.13303. Epub 2017 May 24.

Abstract

Aim: Small-scale clinical studies have reported on drug interactions between caspofungin (CPFG) and calcineurin inhibitors in healthy subjects; however, little is known about these interactions in allogeneic haematopoietic cell transplantation (allo-HCT) patients.

Methods: We retrospectively assessed the drug interactions and safety profiles in allo-HCT recipients treated concomitantly with CPFG and calcineurin inhibitors.

Results: Ninety-one consecutive cases were evaluated. There were no statistically significant differences in the plasma concentration/dose (C/D) ratios of tacrolimus (TAC) in 34 patients before and after co-administration with CPFG (median: 575.6-672.4, P = 0.200). In contrast, the median C/D ratio of cyclosporin A (CsA) in 16 patients was significantly elevated after co-administration with CPFG (median: 62.8-74.9, P = 0.016). There were no serious adverse effects on liver or renal function associated with the therapy.

Conclusions: Our data show that CPFG did not affect the pharmacokinetics of TAC and that it could mildly increase CsA blood concentrations in allo-HCT patients.

Keywords: allogeneic haematopoietic cell transplantation; caspofungin; drug interaction.

MeSH terms

  • Adult
  • Aged
  • Antifungal Agents / pharmacology
  • Calcineurin Inhibitors / adverse effects
  • Calcineurin Inhibitors / blood
  • Calcineurin Inhibitors / pharmacokinetics
  • Caspofungin
  • Cyclosporine / adverse effects
  • Cyclosporine / blood
  • Cyclosporine / pharmacokinetics*
  • Drug Interactions*
  • Drug Therapy, Combination / adverse effects*
  • Echinocandins / pharmacology*
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents
  • Lipopeptides / pharmacology*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Tacrolimus / adverse effects
  • Tacrolimus / blood
  • Tacrolimus / pharmacokinetics*
  • Young Adult

Substances

  • Antifungal Agents
  • Calcineurin Inhibitors
  • Echinocandins
  • Immunosuppressive Agents
  • Lipopeptides
  • Cyclosporine
  • Caspofungin
  • Tacrolimus