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

Abstract

PURPOSE To compare clinical and safety outcomes of transplant recipients converted between different tacrolimus formulations to those patients who remained on a single formulation in an outpatient environment. METHODOLOGY This was a single-center, retrospective cohort study at a large tertiary care medical center with an associated institutional outpatient pharmacy system. Adult transplant recipients with institutional pharmacy refill from August 1, 2009, to May 31, 2016, were assessed. Patients were allocated into four separate groups: Group (A) innovator tacrolimus (no conversion), Group (B) generic tacrolimus (no conversion), Group (C) single conversion (from innovator to single generic or from generic to innovator tacrolimus), and Group (D) multiple conversions. Index date was either the date of first tacrolimus product conversion (Groups C and D) or a pre-specified posttransplant time (Groups A and B). RESULTS Overall, 100 patients were included in the analysis, 63% were male, 62% were Caucasian, and 59% were renal transplant recipients. When compared between groups, linear trends in dose-normalized tacrolimus levels were similar in the pre-index date period (p=0.52) and in the post-index date period (p=0.08). When groups were compared individually, linear trends in dose-normalized tacrolimus levels were significantly different pre-versus post-index date for Group B (p=0.008). There were no differences in the linear trends of dose-normalized tacrolimus levels across the other groups (p>0.05 for all). After the index date, 43% of patients across all groups required tacrolimus dose modification with no differences by group (p=0.32). Allograft function and hospitalizations were similar across all groups.CONCLUSIONS Conversion between tacrolimus generic formulations has been suggested to be unsafe. This study demonstrates that switching tacrolimus products in post-transplant recipients does not alter dose-normalized tacrolimus trough concentrations, renal or hepatic function, pathology, or hospitalizations.

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

“…Therefore, drug homogeneity in the generic group may be suspicious. In Lichvar's study (21), there were no differences in renal functions, acute rejection and hospitalization episodes between the groups of original tacrolimus (Prograf®, group 1), generic tacrolimus (Tacrolimus-Sandoz®, group 2), change from original to generic (group 3), change from generic to generic (group 4). In Liu's study (22), it was reported that generic tacrolimus was widely accepted in the USA, with a % 90 market share in some states.…”