Changes in Tacrolimus and Everolimus Trough Concentrations and Dose Requirements After Initiation and Discontinuation of Letermovir Prophylaxis in Kidney Transplant Recipients: A Single-Center Retrospective Study

Background/Objectives: Letermovir is effective for cytomegalovirus (CMV) prophylaxis after kidney transplantation, but cytochrome P450 3A inhibition may alter tacrolimus and everolimus exposure. We evaluated changes in trough concentrations and dose requirements during letermovir initiation and discontinuation in de novo kidney transplant recipients. Methods: This single-center retrospective observational study included 20 living-donor kidney transplant recipients with D+/R− or R+ CMV serostatus receiving everolimus-based reduced-tacrolimus immunosuppression and letermovir prophylaxis. Trough concentrations, daily doses, kidney allograft function, CMV outcomes, and safety were assessed descriptively. Results: After letermovir initiation, mean tacrolimus trough concentrations increased by approximately 40–60% and everolimus trough concentrations by approximately 35–50%, requiring dose reductions of approximately 45% and 30–40%, respectively. By day 7 after discontinuation, mean tacrolimus and everolimus trough concentrations decreased to 57.4% and 65.9% of baseline, respectively, while daily doses increased to 136.6% and 132.5%, respectively. Group mean serum creatinine and eGFR remained within approximately 10% of baseline. No CMV DNAemia or disease, leukopenia, neutropenia, acute T cell-mediated rejection, or antibody-mediated rejection occurred during letermovir prophylaxis; gastrointestinal symptoms occurred in three recipients. Conclusions: Letermovir was associated with rapid, reversible changes in tacrolimus and everolimus trough concentrations and dose requirements. Intensive therapeutic drug monitoring is warranted at both initiation and discontinuation.