Impact of once‐daily ER‐Tac on trough concentration variability in a stable AYA renal transplant recipient cohort

Abstract

Background Successful renal transplantation requires complex medication regimens that rely on strict adherence to be effective. Variability in immunosuppression exposure, specifically tacrolimus, is associated with poor allograft outcomes. Wide intra‐patient variability of tacrolimus trough concentrations (Vtac) is likely, in part, attributable to regimen complexity and poor medication adherence. Once‐daily tacrolimus formulations create opportunity to simplify therapeutic regimens, and this study aims to evaluate their impact on Vtac and ultimately transplant outcomes. Methods This retrospective cohort study investigated stable (AYA) renal transplant recipients converted from (IR‐Tac) to (ER‐Tac). Subjects served as their own controls. Vtac was assessed by measuring the (SD) of serial tacrolimus trough concentrations prior to and at four time points post‐conversion to ER‐Tac over 24‐month follow‐up. Secondary outcome measures included graft function, infection rates, and effect on modifiable treatment‐related factors. Results Twenty‐eight AYA subjects were converted from IR‐Tac to ER‐Tac. Vtac significantly improved following conversion and was sustained for 24 months (Vtac0 2.32 vs. Vtac24 1.11, p .017). Renal function remained stable, and (BPAR) rates were modest (14%). Mean pill burden was reduced by 15%, and 42.9% of subjects achieved a once‐daily medication regimen. Conclusions Conversion from IR‐Tac to ER‐Tac in this AYA population significantly improved Vtac with sustained effect over 2 years. This effect is likely attributable in part to simplification of the medication regimen and presumably improved medication adherence. Such conversion does not appear to compromise graft function for at least 2 years post‐conversion.

Pharmacokinetics of Envarsus in pediatric kidney transplant recipients – phase 1 pilot conversion study

“…Switching to once-daily preparations of tacrolimus has potential benefit in improving adherence, as shown in previous studies which assessed adherence through questionnaires and improved intrapatient covariation (IPV). [25][26][27][28] The effects of missed doses for BD-tac have been simulated using population Pk characteristics. 29 Missing a morning dose will result in a significant drop in subsequent AUC with a relatively lower drop in C 0 level.…”

Pathophysiological Implications of Variability in Blood Tacrolimus Levels in Pediatric and Adolescent Kidney Transplant Recipients

“…Interventions aimed at reducing these barriers decrease the risk of acute rejection in this population (10). Conversion to a once daily extended release tacrolimus formulation has been shown to reduce tacrolimus intrapatient variation in adolescents and young adults, but further study is necessary to determine the effects on graft outcomes in this age group (11). Extended release formulations are not yet approved in patients under the age of 18.…”