Comparison of the long-term efficacy and safety of generic Tacrobell with original tacrolimus (Prograf) in kidney transplant recipients

Abstract

This study aimed to evaluate the long-term efficacy and safety of a generic tacrolimus (Tacrobell [TCB]) compared to the original tacrolimus (Prograf [PGF]) in kidney transplant recipients. In this retrospective observational study, we analyzed the data from 444 patients who took TCB as a first-line immunosuppressive drug and 245 patients who took PGF. The 5-year graft survival rate was 92% for patients in the PGF group and 97% for patients in the TCB group, respectively. Cox proportional hazards for a one-sided, noninferiority model showed noninferiority (upper confidence interval [CI] limit of the hazard ratio [HR]<1.2) for TCB compared to PGF (HR: 0.58; 95% CI: 0–1.14). The 5-year patient survival rate was 96% for patients in the PGF group and 97% for patients in the TCB group. Cox proportional hazards for a one-sided, noninferiority model showed noninferiority (upper confidence interval limit of the HR<2.0) for TCB compared to PGF (HR: 0.83; 95% CI: 0–1.95). The 5-year acute rejection-free graft survival rate was not significantly different between the groups (TCB 67%, PGF 68.8%; P=0.6286). The incidence of adverse events including adverse cardiovascular or cerebrovascular events, malignancies, new-onset diabetes after transplantation, and infection events did not differ significantly between the two groups. We conclude that TCB is a comparable alternative to the original tacrolimus as a first-line immunosuppressive drug. Producers of generics should support further study of their products after approval to assure physicians of their efficacy and safety.

Immunosuppression with generic tacrolimus in liver and kidney transplantation—systematic review and meta‐analysis on biopsy‐proven acute rejection and bioequivalence

“…). Only one study after KT conversion found a significant difference between generic and innovator Tac favoring innovator Tac , while one in KT de novo found a significant benefit of generic Tac . Two further crossover studies including 103 patients after KT and 36 patients after LT conversion did not report any BPAR event.…”

“…A total of 390 publications were excluded during abstract screening. After the elimination of preliminary reports (2), case reports (3), reviews (25), and studies without a control group (16), 17 studies met the inclusion criteria (Fig. ).…”

“…A few studies on generic Tac have been performed on BPAR rates , whereas five studies found risk ratios favoring innovator Tac and eight studies favoring generic Tac, CIs were often wide due to the low sample sizes. Only one study each found a significant benefit of innovator and generic Tac.…”

“…Only few of the studies reported the 90% confidence intervals for AUC 0–12 and C max geometric mean ratios as standard criteria for bioequivalence, and those were partially underpowered for the demonstration of bioequivalence. Only one study included in the systematic review investigated the null‐hypothesis that the generic was inferior to the innovator tacrolimus , the other studies did not.…”

Comparison of the long-term efficacy and safety of generic tacrolimus, Tacrobell, with Prograf in liver transplant recipients

“…A previous study of kidney transplant patients also found no difference in adverse events (cardiovascular events, cerebrovascular events, malignancies, newly diagnosed onset of diabetes, and infectious events). 14 These results indicate that TCB is as safe as PGF.…”