De novouse of a generic formulation of tacrolimus versus reference tacrolimus in kidney transplantation: evaluation of the clinical results, histology in protocol biopsies, and immunological monitoring

Abstract

Summary The use of generic formulations of immunosuppressive drugs in renal transplantation has been and still is a controversial subject. The lack of clinical studies about safety and efficacy in transplant patients is one of the factors restricting the diffusion of generic drugs in the renal transplant field. Since March 2013, our transplant unit has incorporated generic tacrolimus (Adoport®; Sandoz), replacing the one we were currently using (Prograf®; Astellas). When carrying out our retrospective analysis comparing the two different formulations, we evaluated several clinical results: tacrolimus trough concentrations (C0) at 5–7 days; 1, 3, and 6 months post‐transplantation; concentration/dose ratio at 6 months; acute rejection incidence; delayed graft function (DGF); renal function (as CKD‐EPI); and proteinuria at 6 months in 120 patients (1:1 ratio of Prograf® versus Adoport®), noticing no important differences. We also evaluated the results of protocol biopsies at 6 months in a subgroup of patients, thus verifying the safety and efficacy of this particular generic drug versus the reference product on a histological basis as well. No difference in the development of dnDSA (de novo donor‐specific antibody) was found between the two groups.

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

“…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. ).…”

Clinical and Safety Outcomes of Conversion Original Tacrolimus to Generic Tacrolimus in Turkish Kidney Transplant Recipients

“…In a study of 28 patients in the geriatric age group (18), generic tacrolimus (Tacni®) was not found to be bioequivalent with the reference product (Prograf®). In the study of Melilli (19), 60 patients using reference tacrolimus (Prograf®; Astellas) and 60 patients using the generic product (Adoport®; Sandoz) compared. At the six-month follow-up, there was no difference between the groups in drug concentration (post-transplant on the 7th day, 1st, 3rd and 6th months), concentration/dose ratio (6th month), e-GFR (6th month), proteinuria (6th month), de novo donor-specific antibody development (6th month) and protocol biopsy results (6th month).…”

Evaluation of Clinical and Safety Outcomes Following Uncontrolled Tacrolimus Conversion in Adult Transplant Recipients

“…Generic tacrolimus use continues to be highly debated, despite studies showing bioequivalence in transplant recipients and significant market penetration. Studies have examined conversion to generic tacrolimus in a variety of settings, both conversion and de novo . While de novo studies provide important efficacy data, a variety of factors may impact tacrolimus dosing and exposure.…”

“…In the community, the dispensed tacrolimus formulation often depends on insurance coverage and availability, creating the possibility of repeated tacrolimus formulation substitution unbeknownst to clinicians. Several studies have compared the clinical and safety outcomes between innovator and generic tacrolimus in both conversion and de novo settings . Conversion from innovator to generic was often conducted in a controlled environment, including stringent protocolized, prospective monitoring.…”