Alicia Lichvar1, Simon Tremblay2,3, Devanshi Naik4, Jessi Lipscomb5, Eileen King5, Alexander A Vinks6, Uwe Christians7, Rita R Alloway2. 1. Division of Transplantation, Department of Surgery, University of Cincinnati, Cincinnati, Ohio. 2. Department of Surgery, Division of Transplantation, University of Cincinnati, Cincinnati, OH. 3. Department of Environmental Health, Division of Epidemiology, University of Cincinnati, Cincinnati, OH. 4. University of Cincinnati, James L. Winkle College of Pharmacy, Cincinnati, Ohio. 5. Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 6. Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 7. Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Denver, Colorado.
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 post-transplant 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.
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 post-transplant 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.