Safety and Efficacy of Once-Daily Modified-Release Tacrolimus in Liver Transplant Recipients: A 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 tacrolimus. However, its dosage, trough level, safety, and efficacy in the multicenter clinical experience of Japanese liver transplant recipients have not been reported.MethodsThis postmarketing surveillance designed as an open-label, prospective, noninterventional observational study was performed. The 24 patients were enrolled for de novo transplantation, and the 122 patients were enrolled for conversion to TAC-MR from 22 medical institutions in Japan. The observation period is 1 year in de novo transplantation, and 24 weeks in conversion.ResultsRegarding de novo transplant, the median daily TAC-MR dose was 0.041 mg/kg/d at 1 day after transplantation, and the median tacrolimus trough level was 5.5 ng/mL at 3 days after transplantation. The most common adverse drug reactions were infections, at an incidence rate of 25.0%. The most common infections were cytomegalovirus viremia, at an incidence rate of 12.5%. Both patient and graft survival rates at 1 year were 94.1% and the rejection rate was 20.8%. Regarding conversion to TAC-MR, the median daily conventional TAC dose before conversion was 1.8 mg/d, and the daily TAC-MR dose was 1.5 mg/d. The median TAC trough level was 3.6 ng/mL before conversion and 3.5 ng/mL 1 week after conversion. The most common adverse drug reactions were infections, at an incidence rate of 5.1%. Episodes of death or graft loss did not occur, and there were 3 episodes of rejection. After conversion to once-daily TAC-MR, the patients' adherence was improved.ConclusionThis study shows that a TAC-MR–based immunosuppressive regimen is safe and effective as used in Japanese clinical practice.