Introduction: Bioequivalence of the recently available generic Tacrolimus formulation(Adoport;Sandoz),to the reference product (Prograf; Astellas Pharma) has been demonstrated in healthy subjects. However, the safety and efficacy of substitution with generic tacrolimus in liver transplant patients have not been evaluated.
Methods: Tacrolimus trough concentrations and indicesof liver function were recorded before and after generic substitution in 50 liver transplant recipients and compared with case matched 50 liver transplant recipients with the reference product. Inclusion criteria included age > 18 years, liver transplant recipient at least 6 months posttransplant, switched from the reference tacrolimus product to the generic formulation (Adoport;Sandoz) from January 2016 to September 2016, and on a stable dose of tacrolimus for at least 14 days prior to the switch. All subjects received care in the outpatient transplant clinic where tacrolimus trough concentrations, weight, total bilirubin, albumin, serum creatinine, alkaline phosphatase, ALT, AST, GGTP and graft rejection status was routinely monitored. Patients were followed for a minimum of 14 days and a maximum of 90 days before and after the generic conversion. At the time of the switch from the reference to generic product, a 1:1 dose conversion was employed and the dose of generic tacrolimus was then adjusted at the discretion of the treating physician to maintain trough concentrations within the therapeutic range.
Results: The tacrolimus concentration to dose (C/D) ratio, expressed as the concentration divided by daily weight-adjusted dose ([ng/mL]/[mg/kg/day]), was calculated for each trough concentration. In liver transplant patients, the mean tacrolimus concentration/dose (C/D) ratio (±SD) was 178.1 (±123.2) ([ng/mL]/[mg/kg/day]) for the reference product and 150.7 (±87.8) ([ng/mL]/[mg/kg/day]) for the generic product (p < 0.05). No change was observed in biochemical indices of liver or kidney function and no cases of acute rejection occurred following the substitution.
Conclusions: These results suggest that liver transplant patients currently taking the reference tacrolimus formulation may be safely switched to the Sandoz-generic product (Adoport) provided through concentrations are closely monitored following the substitution.