Safety and efficacy of once-daily modified-release tacrolimus in liver transplant recipients: a multicenter postmarketing surveillance in Japan.
BACKGROUND
Modified-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.


METHODS
This 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.


RESULTS
Regarding 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.


CONCLUSIONS
This study shows that a TAC-MR-based immunosuppressive regimen is safe and effective as used in Japanese clinical practice.
Division of HBP Surgery and Transplantation, Kyoto University, Kyoto, Japan.
S
S
Uemoto
Medical Affairs, Astellas Pharma Inc., Tokyo, Japan. Electronic address: rika.abe@astellas.com.
R
R
Abe
Medical Affairs, Astellas Pharma Inc., Tokyo, Japan.
H
H
Horike
Medical Affairs, Astellas Pharma Inc., Tokyo, Japan.
M
M
So
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007564:Japan; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
D007166:Immunosuppressive Agents; D016559:Tacrolimus