Open AccessEfficacy and safety of prolonged‐release tacrolimus in stable pediatric allograft recipients converted from immediate‐release tacrolimus – a Phase 2, open‐label, single‐arm, one‐way crossover study
Author(s) -
Rubik Jacek,
Debray Dominique,
Kelly Deirdre,
Iserin Franck,
Webb Nicholas J. A.,
Czubkowski Piotr,
Vondrak Karel,
SellierLeclerc AnneLaure,
Rivet Christine,
Riva Silvia,
Tönshoff Burkhard,
D'Antiga Lorenzo,
Marks Stephen D.,
Reding Raymond,
Kazeem Gbenga,
Undre Nasrullah
Publication year - 2019
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.13479
Subject(s) - tacrolimus , medicine , trough level , adverse effect , liver transplantation , calcineurin , clinical endpoint , gastroenterology , kidney transplantation , urology , kidney , surgery , transplantation , clinical trial
Summary There are limited clinical data regarding prolonged‐release tacrolimus ( PR ‐T) use in pediatric transplant recipients. This Phase 2 study assessed the efficacy and safety of PR ‐T in stable pediatric kidney, liver, and heart transplant recipients (aged ≥5 to ≤16 years) over 1 year following conversion from immediate‐release tacrolimus ( IR ‐T), on a 1:1 mg total‐daily‐dose basis. Endpoints included the incidence of acute rejection ( AR ), a composite endpoint of efficacy failure (death, graft loss, biopsy‐confirmed AR , and unknown outcome), and safety. Tacrolimus dose and whole‐blood trough levels (target 3.5–15 ng/ ml ) were also evaluated. Overall, 79 patients (kidney, n = 48; liver, n = 29; heart, n = 2) were assessed. Following conversion, tacrolimus dose and trough levels remained stable; however, 7.6–17.7% of patients across follow‐up visits had trough levels below the target range. Two (2.5%) patients had AR , and 3 (3.8%) had efficacy failure. No graft loss or deaths were reported. No new safety signals were identified. Drug‐related treatment‐emergent adverse events occurred in 28 patients (35.4%); most were mild, and all resolved. This study suggests that IR ‐T to PR ‐T conversion is effective and well tolerated over 1 year in pediatric transplant recipients and highlights the importance of therapeutic drug monitoring to maintain target tacrolimus trough levels.