Evaluation of clotrimazole prophylaxis on tacrolimus trough concentrations in kidney transplant recipients

Abstract

Background: Clotrimazole troches are used as prophylaxis against oropharyngeal candidiasis post-transplant and have limited systemic absorption. Following several occurrences of tacrolimus concentration fluctuations after clotrimazole discontinuation, its use as prophylaxis was discontinued post-kidney transplant.

Methods: We conducted a retrospective cohort study to evaluate the effect of clotrimazole prophylaxis on tacrolimus trough concentrations post-kidney transplant. The study included adult patients who received a kidney transplant at Cleveland Clinic Main Campus from August 1, 2019 to July 1, 2020 and were maintained on per-protocol, standard-dose tacrolimus through 90 days post-transplant. Patients were excluded if they received cyclosporine, systemic antifungals, strong CYP3A4 inhibitors or inducers, or a simultaneous multiorgan transplant. The primary objective was to compare tacrolimus trough concentrations before and after completion of clotrimazole prophylaxis. Secondary objectives were to compare the time to first post-transplant goal tacrolimus trough concentration, the rate of for-cause allograft biopsies within 90 days after transplant, and the incidence and type of candidiasis within 30 days after transplant, pre- and post-protocol change.

Results: Following clotrimazole discontinuation, the median tacrolimus trough concentration decreased from 10.5 ng/ml (IQR 8.4-12.2) to 6.6 ng/ml (IQR 5-8.7, p < 0.0001). No statistically significant differences in the rate of for-cause allograft biopsies (4.9% vs. 9.7%, p = 0.264) or incidence of candidiasis (1.2% vs. 5.4%, p = 0.217) were observed between those who received clotrimazole and those who did not receive clotrimazole.

Conclusions: Our study provides further evidence of a significant drug-drug interaction between tacrolimus and clotrimazole among kidney transplant recipients that can potentially lead to negative allograft outcomes.

Keywords: clotrimazole; drug-drug interaction; tacrolimus; transplant.

FIGURE 1

Tacrolimus trough concentrations before and after clotrimazole discontinuation. Median tacrolimus trough concentrations before and after clotrimazole discontinuation were 10.5 ng/ml (IQR 8.4–12.2) and 6.6 ng/ml (IQR 5–8.7), respectively. The goal tacrolimus trough concentration of 8–12 ng/ml is highlighted in gray