Greater impact of oral fluconazole on drug interaction with intravenous calcineurin inhibitors as compared with intravenous fluconazole

Objective: Although the drug interaction between fluconazole and calcineurin inhibitors has been established, the influence of the route of fluconazole administration on its drug interaction with calcineurin inhibitors has yet to be fully examined. The aim of the present study is to examine whether different routes of fluconazole administration alter its drug interactions with intravenous calcineurin inhibitors. Methods: In 53 recipients of allogeneic hematopoietic cell transplantation receiving calcineurin inhibitors intravenously, steady-state whole-blood levels of cyclosporine A (CsA) or tacrolimus were measured after the route of fluconazole (200 mg/day) administration was switched from intravenous to oral. Results: The mean steady-state whole-blood level of CsA or tacrolimus significantly increased after the route of fluconazole administration was switched from intravenous to oral (CsA: to 394±28.4 from 362±17.8 ng/mL; tacrolimus: to 18.8±0.64 from 17.4±0.39 ng/mL, P<0.05). Conclusion: This finding strongly suggests that oral fluconazole has a greater impact on its drug interactions with intravenous calcineurin inhibitors than intravenous fluconazole. Monitoring of blood levels of intravenous calcineurin inhibitors is recommended when the route of fluconazole administration is switched from intravenous to oral.