Fluconazole-Cyclosporine Interaction: A Dose-Dependent Effect?

Abstract

OBJECTIVE: To present cases supporting the hypothesis that fluconazole inhibition of cyclosporine metabolism is dose-dependent. DESIGN: Case reports. PATIENTS AND INTERVENTIONS: One renal-pancreatic transplant patient taking fluconazole 100 and 300 mg/d for 37 and 17 days, respectively; four bone marrow transplant recipients taking fluconazole 100 mg/d as antifungal prophylaxis and five other concurrent nonmatched recipients whose antifungal prophylactic agent is nystatin mouthwash. All of these patients underwent transplantation during the same period. RESULTS: There was a sharp rise in cyclosporine trough concentration (ng/mL), concentration: dose ratio (ng·mL−1/mg·kg−1), and serum creatinine concentration (μmol/L) in the renal-pancreatic transplantation patient taking fluconazole 300 mg/d. No such increase occurred at 100 mg/d. No significant alterations in cyclosporine concentration:dose ratio were seen in the patients undergoing bone marrow transplantation and receiving fluconazole 100 mg/d. CONCLUSIONS: The case of the renal-pancreatic transplantation patient shows a characteristic interaction profile, and it supports the hypothesis of a dose-dependent interaction between cyclosporine and fluconazole. Given the nephrotoxic potential of the immunosuppressant drug, dosage reduction and closer monitoring of cyclosporine concentrations and/or renal function in patients receiving fluconazole dosages greater than 200 mg/d must be considered.