title: Safety and efficacy of once-daily modified-release tacrolimus in kidney transplant recipients: interim analysis of multicenter postmarketing surveillance in Japan.
abstract: 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 TAC. However, its dosage, trough level, safety, and efficacy in the multicenter clinical experience of Japanese kidney transplant recipients have not been reported.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  Regarding 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.
  
  
  CONCLUSIONS
  This interim analysis shows that a TAC-MR-based immunosuppressive regimen is safe and effective as used in Japanese clinical practice.
authors.affiliation: Department of Regenerative and Transplant Medicine, Niigata University, Nigata, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Medical Affairs, Astellas Pharma Inc., Tokyo, Japan. Electronic address: rika.abe@astellas.com.
authors.forename: R
authors.initials: R
authors.lastname: Abe
authors.affiliation: Medical Affairs, Astellas Pharma Inc., Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Usuki
authors.affiliation: Medical Affairs, Astellas Pharma Inc., Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: So
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007564:Japan; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus