Immunosuppression with prolonged-release tacrolimus in kidney or liver transplantation in India

Aim: Tacrolimus has proven efficacy as an immunosuppressive therapy to prevent transplant rejection and is widely used as an immediate-release formulation in a twice-daily regimen. Once-daily prolonged-release tacrolimus aims to improve the outcomes by reducing variability in exposure and improving adherence. However, there are limited published data available on prolonged-release tacrolimus in routine clinical practice in India. Methods: This was a Phase IV, multicenter, prospective study of prolonged-release tacrolimus conducted over 12 weeks in adult patients eligible for de novo kidney or liver transplantation in India. Primary efficacy end-point was the event rate of biopsy-confirmed acute rejections (BCARs). Secondary end-points included corticosteroid-resistant rejection incidence, time to first BCAR, graft loss, and death. Safety end-points included renal function, lipid profile, incidence of new-onset diabetes mellitus after transplantation (NODAT), and infection. Results: The study enrolled 92 patients undergoing kidney (81 [88.0%]) or liver transplantation (11 [12.0%]); a total of 76 patients (82.6%) completed the study. Ten kidney transplant patients (overall 10.9%) experienced BCAR. There were seven corticosteroid-sensitive and three corticosteroid-resistant rejections. Median (range) time to kidney transplant rejection was 6.5 (1.0–76.0) days. Renal function was stable or improved. Lipid levels showed a significant increase. Eleven instances of NODAT and seven infections occurred and there were eight deaths (8.7%; six kidney and two liver transplant patients). Conclusions: In de novo kidney and liver transplant recipients in India, prolonged-release tacrolimus was well-tolerated and efficacious with a low incidence of acute rejection. Safety profile was similar to immediate-release tacrolimus from published data