Fluconazole-cyclosporine interaction: a dose-dependent effect?
OBJECTIVE
To present cases supporting the hypothesis that fluconazole inhibition of cyclosporine metabolism is dose-dependent.


METHODS
Case reports.


METHODS
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 (mumol/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.
López-Gil
J A
JA
Clinical Pharmacology Service, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
D000328:Adult; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D015725:Fluconazole / Q000009:adverse effects*; D006801:Humans; D016030:Kidney Transplantation; D009181:Mycoses / Q000517:prevention & control; D016035:Pancreas Transplantation
D016572:Cyclosporine; D015725:Fluconazole