A Study on the Pharmacokinetic Profile and Clinical Outcome of Generic Tacrolimus (Cidimus®) Versus Reference Tacrolimus (Prograf®) in De Novo Kidney Transplant Recipients

Abstract

Objectives: Tacrolimus is the cornerstone immunosuppressive medication of kidney transplantation.  This study sought to demonstrate bioequivalence and non-inferiority in the clinical outcomes of renal transplant recipients administered either reference tacrolimus (Prograf®) or generic tacrolimus (Cidimus®).  Methodology: A randomized controlled study on standard immunologic risk primary kidney transplant patients were given either reference or generic Tacrolimus and standard doses of mycophenolate mofetil and prednisone and followed up to 6 months post- transplant. An abbreviated area under the curve (AUC) profile on Day 3 post-transplant using C0, C2 and C4 and Cmax and Tmax were determined.  Adverse events including new onset diabetes after transplant (NODAT) were noted. Graft biopsy was performed for suspected acute rejection (BPAR).  Graft and patient survival were reported. Results: There were 44 patients randomized and 22 were assigned to each arm.  Baseline characteristics were similar in both groups. There was 100% patient and graft survival between the two groups after 6 months (p<0.05).  The most common adverse event was urinary tract infection (UTI) in 6.82% of the study population. Incidences of biopsy proven acute rejection (BPAR) (p 0.55) and new onset diabetes after transplant (NODAT) (p 0.32) were not statistically significant between the two groups. There were 1 (4.55%) and 2 (9.09%) patients who developed BPAR in the Prograf and Cidimus group respectively.  One patient (4.55%) in the Cidimus group developed NODAT.   Both CMAX and AUC of Cidimus® and Prograf® had a 90% CI of differences of -0.1662 to 0.0695 and -0.1594 to 0.0356 respectively, which is within the bioequivalence confidence interval of -0.2231 to 0.223. Conclusion: Generic Tacrolimus Cidimus® was bioequivalent to reference Tacrolimus (Prograf®) and was non- inferior based on pharmacokinetic parameters and clinical outcomes up to 6 months post-transplant.