Follow-up study finds generic tacrolimus safe for kidney transplant patients

Generics/Research | Posted 14/07/2017 post-comment0 Post your comment

Researchers from Portugal, who carried out a long-term follow-up study, have found that switching stable kidney transplant patients to generic tacrolimus is safe [1].

Health and Safety V15C26

Following organ transplantation, patients require lifelong treatment with immunosuppressants. Many transplant patients are faced with complicated post-transplant medication regimens and significant financial burden. There is therefore a need for safe and effective generic immunosuppressants.

Tacrolimus is a key immunosuppression drug in solid organ transplantation with a narrow therapeutic index. Drugs with a narrow therapeutic index are defined by a narrow distance between the dosage that induces a desired effect and that dosage which already has a toxic effect [2]. For this reason, in the case of generic immunosuppressants, the acceptance range is narrowed in order to further reduce the chances of obtaining clinically relevant differences in exposure when switching to and from generics [3]. However, despite such measures, doubts remain over generic immunosuppressants.

In this study, the authors aimed to find out if the conversion from brand-name tacrolimus Advagraft to twice-daily generic tacrolimus from Sandoz was still considered safe at 36 months. In a previously published study comparing the clinical outcomes of renal transplant patients switched from Advagraf to generic tacrolimus good results were observed at the 9-month follow-up.

The study included patients with stable renal function, serum creatinine less than 2.0 mg/dL, transplanted for six months or longer. Tacrolimus conversion was performed on a 1 mg:1 mg basis. Thereafter, doses were adjusted to maintain target trough levels between 5 and 10 ng/mL.

From the 109 included patients, there were 99 active on tacrolimus at 36 months. Graft and patient survival was 100% at 12- and 24-month follow-up. At 36 months, death-censored graft survival was 93% and patient survival was 97%. Serum creatinine levels were not statistically different at conversion and 36 months follow-up (p = 0.737). There were no episodes of acute rejection. Doses were statistically different between conversion and 3 months (p < 0.001) and between 3 and 36 months (p < 0.001). Trough levels were not statistically different at conversion and 3 months (p = 0.595) but were between 3 and 36 months (p < 0.001).

The results, according to the authors, showed that ‘the twice-daily generic formulation proved to be safe, with serum creatinine levels stable at conversion and at 36 months follow-up’. They concluded that ‘the twice-daily generic tacrolimus seems to provide similar efficacy and safety to Advagraf at 36-month follow-up’.

Conflict of interest
The authors of the research paper [1] declared that there were no conflicts of interest.

Related article
Novartis introduces branded generic tacrolimus

1. Melo MJ, Gonçalves J, Guerra JO, Santana A, Nascimento C. Impact of conversion from Advagraf to twice-daily generic tacrolimus in kidney transplant recipients: a single-center study. Transplant Proc. 2015;47(4):911-3.
2. Godman B, Baumgärtel C. Bioequivalence of narrow therapeutic index drugs and immunosuppressives. Generics and Biosimilars Initiative Journal (GaBI Journal). 2015;4(4):159-60. doi:10.5639/gabij.2015.0404.035
3. GaBI Online - Generics and Biosimilars Initiative. Equivalence of generic immunosuppressants []. Mol, Belgium: Pro Pharma Communications International; [cited 2017 Jul 14]. Available from:

Permission granted to reproduce for personal and non-commercial use only. All other reproduction, copy or reprinting of all or part of any ‘Content’ found on this website is strictly prohibited without the prior consent of the publisher. Contact the publisher to obtain permission before redistributing.

Copyright – Unless otherwise stated all contents of this website are © 2017 Pro Pharma Communications International. All Rights Reserved.

comment icon Comments (0)
Post your comment
Most viewed articles
About GaBI
Home/About GaBI Posted 06/08/2009
EU guidelines for biosimilars
EMA logo 1 V13C15
Home/Guidelines Posted 08/10/2010