Use of Generic Tacrolimus in Elderly Renal Transplant Recipients

Robertsen, Ida; Åsberg, Anders; Ingerø, Aleksander Olsen; Vethe, Nils Tore; Bremer, Sara; Bergan, Stein; Midtvedt, Karsten

doi:10.1097/tp.0000000000000384

Cited by 49 publications

(38 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There were three crossover (25 patients de novo KT, 139 patients conversion LT and KT) and two parallel design studies (79 patients de novo KT), all RCTs, reporting the primary pharmacokinetic outcome of C max and AUC 0–12 (Fig. ) . Three prospective randomized pharmacokinetic studies in KT were conducted with de novo generic Tac (one study including a crossover substudy), and one after conversion .…”

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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…In 2015, the only generic tacrolimus study specifically evaluating generic tacrolimus in the elderly was published. 59 This prospective, single-center, randomized, crossover trial evaluated the pharmacokinetic parameters of a generic tacrolimus (Tacni; Teva Pharmaceutical Industries, Petah Tikva, Israel) in 25 renal transplant recipients older than 60 years. Patients were randomized to receive either brand or generic tacrolimus at the time of transplantation.…”

Section: Introductionmentioning

confidence: 99%

A Rationale for Age-Adapted Immunosuppression in Organ Transplantation

et al. 2015

View full text Add to dashboard Cite

Demographic changes are associated with a steady increase of older patients with end-stage organ failure in need for transplantation. As a result, the majority of transplant recipients are currently older >50 years and organs from elderly donors are more frequently utilized. Nevertheless, the benefit of transplantation in older patients is well recognized whereas the most frequent causes of death among older recipients are potentially linked to side effects of their immunosuppressants. Immunosenescence is a physiological part of aging linked to higher rates of diabetes, bacterial infections and malignancies representing the major causes of death in older patients. These age-related changes impact older transplant candidates and may have significant implications for an age-adapted immunosuppression. For instance, immunosenescence is linked to lower rates of acute rejections in older recipients while the engraftment of older organs has been associated with higher rejection rates. Moreover, new-onset diabetes mellitus following transplantation is more frequent in the elderly, potentially related to corticosteroids, calcineurin inhibitors and mTOR inhibitors. This review presents current knowledge for an age-adapted immunosuppression based on both, experimental and clinical studies in and beyond transplantation. Recommendations of maintenance and induction therapy may help to improve graft function and to design future clinical trials in the elderly.

show abstract

“…Some excipients can alter the activity of efflux pumps that remove lipophilic molecules from the intracellular space. Sandimmune capsules (where the active component is dissolved in olive oil) were not bioequivalent to Sandimmune solution (where the active compo- Retrospective study in de novo renal transplant recipients (n = 188) [16] Pharmacokinetics not reported Acute rejections increased with Gengraf vs. Neoral (39 vs. 25%) [16] Gengraf patients more likely to receive antibody preparations to treat acute rejections (19 vs. 8%) [16] No difference in 12 h cyclosporin levels between Gengraf vs. Neoral groups [16] Graft and patient survival similar in both groups [16] Robertsen et al [19], 2015…”

Section: Discussionmentioning

confidence: 99%

New Onset Hypertension Linked to Generic Cyclosporine Substitution in Post-Renal Transplant Patient

Dhaybi

Bakris²

2016

Am J Nephrol

View full text Add to dashboard Cite

This is case report and review of the literature focused on generic substitutions of cyclosporine and its consequences. The pharmacokinetics and pharmacodynamics of the generic substitutions are clear different than the parent compound Sandimmune and can lead to different outcomes, as was the case in this report. A detailed accounting of the patients history led to the discovery of the problem and sorting back to a the branded drug supported the hypothesis.

show abstract

Use of Generic Tacrolimus in Elderly Renal Transplant Recipients

Abstract: Generic tacrolimus (Tacni) was not found to be bioequivalent to the original formulation in elderly renal transplant recipients. The significantly higher systemic exposure of tacrolimus, despite similar trough concentrations, may in the long run increase the risk of adverse effects.

Cited by 49 publications

References 33 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

A Rationale for Age-Adapted Immunosuppression in Organ Transplantation

New Onset Hypertension Linked to Generic Cyclosporine Substitution in Post-Renal Transplant Patient

Contact Info

Product

Resources

About