*Purpose: The purpose of this study was to characterize the effects of fluconazole (fluc) discontinuation on tacrolimus (tac) levels and the role of prophylactic dose adjustments of tac.

*Methods: Thrush prophylaxis in liver transplant recipients during the early post-transplant period is common practice. Due to shortages of nystatin and clotrimazole in 2018, systemic thrush prophylaxis with fluc was initiated for 30 days post-transplant. This is a retrospective single center study from March 2019 to September 2019. Liver transplant recipients were included for chart review if they were simultaneously on tac and fluc prophylaxis after transplant, and recipients were excluded if tac was discontinued or switched to another agent, patients were prescribed another known CYP3A4/5 inhibitor, or multi-organ transplant.

*Results: Thirty patients were included in the final data analysis. The mean duration of fluc therapy was 28.7 days, 67% of patients received < 30 days of fluc (20/30); 8 patients received fluc for 31-32 days and 2 for more than 35 days. The majority of patients had a tac goal of 8-10; 33% (10/30) of patients had a documented reduced tac goal, mostly associated with elevated serum creatinine. Prior to discontinuation of fluc, 30% of patients (9/30) had supratherapeutic tac levels, 30% (9/30) had subtherapeutic levels, and 40% (12/30) were therapeutic. For the supratherapeutic group, tac total daily dose (TDD) was not adjusted prophylactically; ≥4 days after fluc was completed 2/9 remained supratherapeutic, 4/9 became therapeutic, and 3/9 became subtherapeutic. In the subtherapeutic group, 5/9 had their TDD prophylactically increased before fluc cessation, and 2/9, 4/9, and 3/9 became supratherapeutic, therapeutic, or remained subtherapeutic. Of the therapeutic patients, 11/12 (92%) did not have their tac dose increased prophylactically, and 9/12 (75%) became subtherapeutic > 4 days after fluc cessation. Mean time to a therapeutic level after fluc discontinuation was 15.3 days in this group. Also among the supratherapeutic patients, 8/9 had an increase in serum creatinine associated with the supratherapeutic level (6/9 had an increase in serum creatinine of > 0.4 from time of discharge). In the supratherapeutic group 6/9 experienced hyperkalemia versus 2/9 in the subtherapeutic group, though this difference was not statistically significant (p=0.058).

*Conclusions: These results highlight the importance of adjusting tac upon discontinuation of an interacting medication such as fluconazole, and the potential for pharmacist intervention in ambulatory transplant clinics. It also identifies the potential benefit of standardizing timing of dose adjustment by pharmacists or nurse coordinators.

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