D321 - Evaluation of the Drug Drug Interaction Between Letermovir and Tacrolimus in Abdominal Transplant Recipients

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Author Block: H. Devall¹, B. Fischbach², S. Elwir², E. Martinez², A. D. Kataria², ¹Baylor University Medical Center, Texas, TX, ²Baylor University Medical Center, Dallas, TX
*Purpose: Current consensus guidelines for management of cytomegalovirus (CMV) in solid organ transplantation (SOT) recommended letermovir as an additional prophylaxis strategy but highlighted the need for more data in non-kidney organ groups and R+ recipients. Additionally, letermovir may alter tacrolimus (FK) levels, but the interaction is not well-described in SOT. This study aimed to evaluate the magnitude of the letermovir-FK interaction in kidney, pancreas, and liver transplants, including R+ recipients.
*Methods: This single-center, retrospective cohort study included adult abdominal SOT who received letermovir prophylaxis during the study period. Eligible patients were those transitioned to letermovir while receiving immediate-release (IR) or extended-release (ER) tacrolimus (FK). Recipients who were on a non-tacrolimus maintenance immunosuppression regimen, or received a concomitant interacting medication with FK were excluded. Baseline characteristics, allograft function, and safety parameters were collected. Three FK trough concentrations and corresponding dose (C/D) were collected before and after letermovir initiation. The primary outcome was the percentage change between the mean C/D ratio pre and post letermovir initiation.
*Results: Thirty-four kidney (53%), liver (32%), and kidney/pancreas (15%) transplants were included. The median age was 50.5 years (IQR 40-60); 56% were Caucasian, and 53% were male, with 21% CMV R+. Letermovir was initiated at a dose of 480 mg once daily, at a median of 83 days (IQR 48-156) post-transplant, primarily due to leukopenia with valganciclovir therapy (91%). The majority of patients (68%) received IR FK. At the time of letermovir initiation, 56% received preemptive FK dose reduction. Among patients receiving IR FK, the mean C/D ratio increased from 1.9 (95% CI, 1.65-2.14) to 3.14 (95% CI, 2.37-3.91) following letermovir initiation (P < 0.01). For those on ER FK, the mean C/D ratio increased from 2.48 (95% CI, 1.67-3.29) to 4.20 (95% CI, 3.07-5.33) (P = 0.02). Overall, the percentage change in mean FK C/D ratio was 40% in this study cohort. Allograft function remained stable following addition of letermovir. Additionally, there was no CMV breakthrough observed during letermovir prophylaxis therapy.
*Conclusions: Letermovir appears to be an effective prophylaxis option in non-kidney and R+ recipients. Based on these findings, a preemptive dose reduction of FK by 40% appears to be warranted when initiating letermovir in abdominal SOT recipients to mitigate drug interactions.