Micafungin does not influence the concentration of tacrolimus in patients after allogeneic hematopoietic stem cell transplantation

Transplant Proc. 2010 Sep;42(7):2725-30. doi: 10.1016/j.transproceed.2010.04.030.

Abstract

Background: Tacrolimus is commonly used in stem cell transplant recipients for prophylaxis of graft-vs-host disease. Micafungin is widely used as a strong antifungal agent in empirical therapy in patients with febrile neutropenia. Both tacrolimus and micafungin are substrates of cytochrome P450 3A4 in vitro. Therefore, there is risk of drug interaction with concomitant administration of these drugs.

Objective: To estimate the drug interaction of tacrolimus and micafungin by evaluating the pharmacokinetics in 6 patients who had undergone allogeneic stem cell transplantation.

Results: The mean (SD) concentration-dose ratio of tacrolimus in all patients at 1, 4, 8, and 24 hours after concomitant administration of micafungin was 607 ± 306, 653 ± 328, 699 ± 340 and 671 ± 403 (ng/mL)/(mg/kg/d), respectively, and without micafungin was 756 ± 314 (ng/mL)/(mg/kg/d). The percentage of the concentration-dose ratio in patients treated with tacrolimus and micafungin vs patients treated with tacrolimus alone was 98%, 105%, 112%, and 108% at 1, 4, 8, and 24 hours, respectively. For both tacrolimus and micafungin, the 90% confidence intervals for the primary pharmacokinetic parameters (ie, the concentration-dose ratio at each point) ranged from 80% to 125%.

Conclusion: We conclude that there is no drug interaction between tacrolimus and concomitantly administered micafungin in stem cell transplantation recipients.

MeSH terms

  • Adult
  • Aged
  • Antifungal Agents / therapeutic use*
  • Area Under Curve
  • Cord Blood Stem Cell Transplantation / methods
  • Drug Therapy, Combination
  • Echinocandins / blood
  • Echinocandins / therapeutic use*
  • Female
  • Hematologic Neoplasms / surgery*
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Lipopeptides / blood
  • Lipopeptides / therapeutic use*
  • Male
  • Micafungin
  • Middle Aged
  • Recurrence
  • Tacrolimus / therapeutic use*
  • Transplantation, Homologous

Substances

  • Antifungal Agents
  • Echinocandins
  • Immunosuppressive Agents
  • Lipopeptides
  • Micafungin
  • Tacrolimus