Impact of Low-Dose Fluconazole on Tacrolimus Dosing in Renal Transplant

Background: The interaction between azole antifungal therapy and immunosuppressant tacrolimus (TAC) is a barrier to use. Objective: This study quantified the drug interaction between low-dose fluconazole (LDF) and TAC to determine the appropriate TAC dose adjustment when used concurrently in renal transplant recipients. Methods: We conducted a single-center retrospective chart review of renal transplant patients >18 years who received LDF or nystatin (NYS), and TAC. The primary outcome was the difference in tacrolimus total daily dose (TAC TDD) for LDF versus NYS groups. Secondary outcomes included days with supratherapeutic, therapeutic and subtherapeutic tacrolimus levels, time to therapeutic level, incidence of adverse drug reactions and graft rejection. Results: We evaluated 94 patients and included 81. Low-dose fluconazole received a greater TAC TDD prior to post-operative day (POD) 10 (10.5 +/- 4.7 mg vs. 7.1 +/- 4.5 mg, p < 0.001), but a decreased TAC TDD POD 10 - 30 (8.6 +/- 2.2 mg vs. 9.8 +/- 0.8 mg, p < 0.001) and following LDF discontinuation (6.9 +/- 0.1 mg vs. 9.0 +/- 0.4 mg, p < 0.001). Low-dose fluconazole had more patient-days with supratherapeutic (17.9 +/- 7.0 vs. 13.9 +/- 8.5; p = 0.02) but fewer with subtherapeutic (6.7 +/- 5.7 vs. 12.9 +/- 7.2; p < 0.01) TAC levels. There was no difference in patient-days with therapeutic TAC levels (15.9 +/- 5.8 vs. 14.4 +/- 6.6, p = 0.28), meanwhile LDF required less patient-days to therapeutic TAC level (7.1 +/- 2.7 vs. 11.5 +/- 7.7; p < 0.01). There was no difference in adverse drug reactions between groups and no incidence of graft rejection. Conclusion: A 20% reduction in TAC TDD is warranted in renal transplant patients when used concomitantly with LDF to achieve therapeutic levels.