Therapeutic equivalence and pharmacokinetics of generic tacrolimus formulation in de novo kidney transplant patients

Ha, Jong‐Won; Kim, Yon Su; Ahn, Sang Hyun; Park, Taejin; Park, Dae Do; Kim, Suh Min; Min, Sang Il; Hong, Hyun-Ki; Ahn, Curie; Kim, Sang Joon

doi:10.1093/ndt/gft300

Cited by 25 publications

(32 citation statements)

References 25 publications

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“…Five studies including 365 patients after LT (191 de novo, 174 conversion) and nine studies including 883 patients after KT (735 de novo, and 148 conversion) compared BPAR of patients on generic Tac with those on innovator Tac after LT or KT, all of them in a parallel design (Table ). However, only two of those studies were randomized controlled trials and a further two were non‐randomized prospective studies . Risk ratios for BPAR rates of patients on generic Tac versus innovator Tac were compared in a forest plot stratified visually by organ and study design (Fig.…”

Section: Resultsmentioning

confidence: 99%

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

2020

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Summary While rejection prevention with innovator tacrolimus (Tac) is one of the key factors for long‐lasting graft function, the use of generic Tac is still under debate. Thus, we performed a systematic review and meta‐analysis to provide an overview on the current body of evidence for the effect of generic Tac in adult liver (LT) and kidney transplantation (KT) with focus on both biopsy‐proven acute rejection (BPAR) and bioequivalence. A systematic literature search for trials comparing generic versus innovator Tac was conducted accordingly. Seventeen studies (5 LT, 11 KT, 1 LT/KT) including 1412 patients were identified. About 92.9% (13/14; 5/5 LT, 8/9 KT) of studies reported the same or lower BPAR with generics (pooled RR: 0.84, 95% CI: 0.65–1.09); however, de novo studies showed a significantly lower risk with generic Tac (RR: 0.75, 95% CI: 0.63–0.90), whereas conversion studies showed increased risk (RR: 1.93, 95% CI: 1.00–3.70). Bioequivalence was demonstrated primarily in studies on conversion. The current evidence is mostly based on observational data and studies showing some risk of bias. In conclusion, whereas overall there was no significant difference in terms of BPAR, there is some evidence suggesting lower BPAR risk with generic Tac for de novo use.

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Section: Resultsmentioning

confidence: 99%

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

2020

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“…Data are presented as mean±SD. 17 This may indicate that aging is not the main parameter responsible for the nonbioequivalence observed in our study. of the intended patient population.…”

Section: Discussionmentioning

confidence: 68%

“…T max was analyzed using Wilcoxon signed rank test. 16,17,[20][21][22][23] Alloway et al 16 conducted the first prospective study specifically designed to compare the steady-state PK of a generic Tac formulation to the original drug in renal transplant recipients. AUC 0-12 , area under the plasma concentration versus time curve from zero to 12 hr; CI, confidence interval; C max , maximum whole blood concentration; T max , time to C max ; C 0 , concentration before the dose; Tac, tacrolimus.…”

Section: Discussionmentioning

confidence: 99%

“…8,9 Concern has however been raised that the current bioequivalent requirements with "one size fits all" approach may be insufficient to ensure the safety and efficacy of generic immunosuppressive drugs in transplant patients. 16,17 Consequently, we aimed to investigate the bioequivalence of an approved generic Tac formulation (Tacni; Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel) in elderly renal transplant recipients at steady state, using the original drug (Prograf; Astellas Pharma Inc., Tokyo, Japan) as reference. 10 In an attempt to assure that only truly bioequivalent NTI drugs are allowed on the market, the European Medicines Agency (EMA) has adopted somewhat stricter bioequivalence criteria for these drugs.…”

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confidence: 99%

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Use of Generic Tacrolimus in Elderly Renal Transplant Recipients

et al. 2015

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“…There were no unexpected serious adverse events. The other trial was a pharmacokinetic study in KT recipients to compare the pharmacokinetic parameters of the original and the generic tacrolimus 18. This study showed that the generic tacrolimus had an earlier and higher C max than the original tacrolimus.…”

Section: Discussionmentioning

confidence: 99%

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

Son¹,

Jang²,

Lee³

et al. 2017

DDDT

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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.

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Therapeutic equivalence and pharmacokinetics of generic tacrolimus formulation in de novo kidney transplant patients

Abstract: Therapeutic equivalence and the PK of GEN tacrolimus should be evaluated in patients undergoing de novo renal transplantation.

Cited by 25 publications

References 25 publications

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

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

Use of Generic Tacrolimus in Elderly Renal Transplant Recipients

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

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