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.

INTRODUCTION:Valproic acid (VPA) is an anticonvulsant and mood stabilizer that is extensively protein bound and susceptible to variable binding. VPA's pharmacologically active free fraction is typically 5-10%; however, four case reports and one small observational study have described variations in the free fraction in critically ill patients. The purpose of this analysis was to characterize concordance between free and total serum VPA concentrations in critically ill patients at a quaternary care, academic medical center.METHODS: This single-center, retrospective analysis included patients admitted to an adult ICU, between July 1, 2013 and July 1, 2019, with at least one free and total serum VPA trough level. Reference ranges for the free and total serum VPA concentrations were 5 to 17 µg/mL and 50 to 125 µg/mL, respectively. Serum concentrations were classified as "in range", "low", or "high" with free and total concentrations considered therapeutically concordant with the same classifications.