Low-dose fluconazole prophylaxis in kidney transplant recipients receiving tacrolimus

The use of prophylactic antifungal therapy is suggested after kidney transplantation. However, efficacy of low-dose (50 mg) oral fluconazole and its effect on tacrolimus trough levels in patients maintained on tacrolimus and mycophenolic acid, with or without corticosteroids, is unknown.

A retrospective analysis to evaluate efficacy was performed in 305 kidney transplant recipients. An additional analysis to evaluate the fluconazole-tacrolimus drug interaction was performed in 103 patients. Complete tacrolimus area under the curve measurements were also performed in seven patients to further evaluate this drug interaction.

The incidence of fungal infections was very low (0.6%, n = 2). The average tacrolimus trough level at the time of discontinuation and one wk after stopping fluconazole was unchanged (11.69 ± 3.18 and 11.15 ± 3.69 ng/mL, p = 0.145, n = 103). Tacrolimus trough levels on and off of fluconazole in a subgroup of patients continued on corticosteroids, was not significantly different (p = 0.952) but was significantly lower after fluconazole discontinuation if corticosteroids were withdrawn (p = 0.037). However, data from complete tacrolimus pharmacokinetics in the corticosteroid withdrawal group demonstrated no clinically significant differences.

Low-dose, once daily oral fluconazole is effective antifungal prophylaxis after kidney transplantation without significant effects on tacrolimus trough levels or overall exposure.