Tacrolimus dose reduction needed in renal transplant patients on fluconazole

Renal transplant patients require a 20-percent reduction in tacrolimus (TAC) total daily dose (TDD) when used in tandem with low-dose fluconazole (LDF) to achieve therapeutic levels, suggests a study.

A team of investigators performed a retrospective chart review of renal transplant patients at least 18 years of age who received LDF or nystatin and TAC in a single centre.

The difference in TAC TDD for LDF compared with nystatin groups was the primary outcome. Secondary ones included days with supratherapeutic, therapeutic and subtherapeutic TAC levels, time to therapeutic level, incidence of adverse drug reactions, and graft rejection.

Of the 94 patients identified, 81 met the eligibility criteria. LDF received a higher TAC TDD prior to postoperative day (POD) 10 (10.5 vs 7.1 mg; p<0.001) but a lower TAC TDD during POD 10‒30 (8.6 vs 9.8 mg; p<0.001) and after LDF discontinuation (6.9 vs 9.0 mg; p<0.001).

LDF saw more patient-days with supratherapeutic TAC levels (17.9 vs 13.9; p=0.02) but fewer with subtherapeutic TAC levels (6.7 vs 12.9; p<0.01). No difference in patient-days was observed with therapeutic TAC levels (15.9 vs 14.4; p=0.28), whereas LDF warranted fewer patient-days to therapeutic TAC level (7.1 vs 11.5; p<0.01).

In addition, no between-group difference was seen in adverse drug reactions. There was also no incident of graft rejection noted.

“The interaction between azole antifungal therapy and immunosuppressant TAC is a barrier to use,” according to the investigators.