Safety and Efficacy of Once-Daily Modified-Release Tacrolimus in Kidney Transplant Recipients: Interim Analysis of Multicenter Postmarketing Surveillance in Japan

IntroductionModified-release formulation of tacrolimus (TAC-MR) has been developed with the intent of improving patient adherence and quality of life. A number of studies have indicated that the efficacy and safety of once-daily TAC-MR were comparable with those of the original formulation, twice-daily TAC. However, its dosage, trough level, safety, and efficacy in the multicenter clinical experience of Japanese kidney transplant recipients have not been reported.MethodsThis post-marketing surveillance designed as an open-label, prospective, noncomparative, noninterventional observational study was performed. The 256 patients were enrolled for de novo transplantation, and the 106 patients were enrolled for conversion to TAC-MR from 52 medical institutions in Japan. The follow-up period in de novo transplantation was 5 years, but here we report the results of the 24-week interim analysis. The observation period in conversion was 24 weeks.ResultsRegarding de novo transplantation, the median daily TAC-MR dose was 0.150 mg/kg/d at the initial administration and the median TAC trough level was 12.1 ng/mL at 3 days. The common adverse drug reactions were infections, renal disorders, and glucose tolerance disorders at incidence rates of 23.6%, 6.8%, and 5.6%, respectively. Both patient and graft survival rates at 24 weeks were 98.2% and the rejection rate was 16.1%. Regarding conversion to TAC-MR, the median conventional TAC dose before conversion was 3.2 mg/d, and the median TAC-MR dose at the converted day was 3.2 mg/d. The median TAC trough level was 5.4 ng/mL before conversion, and it was 5.2 ng/mL after conversion. The most common adverse drug reactions were infections at an incidence rate of 4.9%. There was 1 graft loss and death, and there was 1 episode of rejection.ConclusionThis interim analysis shows that a TAC-MR–based immunosuppressive regimen is safe and effective as used in Japanese clinical practice.