17 to 20 Years Longitudinal Follow-Up of 1000 Consecutive Primary Liver Transplant Under Tacrolimus

Abstract

Introduction: Tacrolimus is the immunosuppressive drug of choice in solid organ transplant patients. Recently tacrolimus has become available as a generic product. The aim of this study was to evaluate the safety and equivalence of switching to generic tacrolimus in solid organ transplant patients. Methods: Patients who were switched to the generic formulation of tacrolimus by insurance providers were enrolled in this analysis. We compared the steady state blood concentrations of tacrolimus, measured by a sensitive and specific high performance liquid chromatography mass spectrometric technique, before (2-5 data points) and after (2-4 data points) the switch to the generic product. Biochemical parameters indicative of liver and kidney status were also collected in these patients. Results: Twenty five liver transplant patients and 29 kidney transplant patients (total n=54) were included in this analysis. The subjects were followed for a period of 4 days to 2.6 months after the switch to the generic product. Tacrolimus blood levels ranged from 1 ng/ml to 19.4 ng/ml before and 1.1 to 18.2 ng/ml after the switch. In kidney transplant recipients, the overall mean change in dose normalized tacrolimus blood concentrations was less than 5% (n=29). Ten of these subjects had an increase (2/10 (20%) were > 20% increase) and 19 subjects had a decrease (5/19 (26%) were > 20% decrease). In liver transplant recipients, the overall mean change in dose normalized tacrolimus blood concentrations was -12% (n=25). Ten of these subjects had an increase (3/10 (30%) were > 20% increase) and 15 subjects had a decrease (8/15 (53%) were > 20% decrease). For both brand and generic tacrolimus, the liver transplant group exhibited higher dose normalized tacrolimus concentrations compared to the kidney transplant group (p<0.05). Total bilirubin, SGOT, SGPO, alkaline phosphatase, and serum creatinine levels were not significantly altered during the observational period. There were no acute rejection episodes during the observed time. Conclusion: Overall there was no significant change in the mean dose normalized blood concentrations of tacrolimus before and after switch to the generic product. The switch to generic appears to be safe in the short term. However, given that 33% of the patients had greater than 20% change in blood concentrations, it is prudent to measure tacrolimus levels when patients are switched to the generic product.