Tacrolimus Trough Level Variation and Its Correlation to Clinical Outcomes and Consequences in Solid Organ Transplantation

Abstract

Purpose: Tacrolimus is a calcineurin inhibitor that suppresses immunity by inhibiting T-lymphocyte activation. It has a high intra-and inter-patient variability in its pharmacokinetics. Therefore, therapeutic drug monitoring is required to individualize the dose. High tacrolimus trough level variability is associated with a higher risk of adverse effects. In practice, the initial dosing and sampling time of tacrolimus levels is not standardized, which may result in resource wastage, frequent blood sampling, and a longer time to achieve therapeutic levels. The aim of this study was to evaluate tacrolimus trough level variation and its correlation to clinical outcomes and consequences. Patients and Methods: A retrospective cohort study At King Abdulaziz Medical City in Riyadh, Saudi Arabia, 01/01/2018 to 31/12/ 2021. Inclusion Criteria: >18 years old solid organ transplant patients who received tacrolimus as part of their initial immunosuppres-sion regimen. Tacrolimus initial dosing, trough levels, and dose adjustments were recorded during the early post-transplantation period (first 10 days). The coefficients of variation (CV%) in tacrolimus doses and trough concentrations were calculated and compared for different demographics and clinical characteristics. Results: The higher coefficient of variation in dose and trough level is associated with different demographic and clinical factors that will predict the incidence of adverse events. In our study, there was a significant increase in adverse effect reporting in the high variability group but was not clear for the risk of graft function, acute rejection, or infections. Conclusion: The variation in trough levels is associated with clinical consequences. Therefore, better dosing strategies can be modified to reduce the variation (fluctuation) which is associated with poor outcomes.