Reduced tacrolimus dose needed when used with fluconazole in renal transplant patients

Renal transplant patients need 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 recent study.

A team of investigators performed a single-centre retrospective chart review of renal transplant patients aged >18 years who received LDF or nystatin and TAC to determine the appropriate TAC dose adjustment when used concurrently in renal transplant recipients.

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

Eighty-one patients met the eligibility criteria. LDF received a higher TAC TDD before postoperative day (POD) 10 (10.5 vs 7.1 mg; p<0.001), but a reduced TAC TDD on POD 10‒30 (8.6 vs 9.8 mg; p<0.001) and following LDF cessation (6.8 vs 9.0 mg; p<0.001).

LDF also had more patient-days with supratherapeutic (17.9 vs 13.9; p=0.02) but fewer subtherapeutic (6.7 vs 12.9; p<0.01) TAC levels. No difference was observed in patient-days with therapeutic TAC levels (15.9 vs 14.4; p=0.28), while 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 incidence of graft rejection.

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