Safety and Efficacy of Conversion from Twice-Daily Tacrolimus to Once-Daily Tacrolimus One Month after Transplantation: Randomized Controlled Trial in Adult Renal Transplantation

Abstract

PurposeThe purpose of this study was to compare once-daily tacrolimus with twice-daily tacrolimus in terms of safety, efficacy, and patient satisfaction.Materials and MethodsThis prospective, randomized, open-label, multicenter study was conducted at three institutes. Patients in the investigational group were converted from tacrolimus twice daily to the same dose of extended-release tacrolimus once daily at 1 month post-transplantation, while patients in the control group were maintained on tacrolimus twice daily. The efficacies, safeties, and patient satisfaction for the two drugs at 6 months post-transplantation were compared.ResultsSixty patients were enrolled and randomized to the investigational group (28 of 29 patients completed the study) or the control group (26 of 31 patients completed the study). At 6 months post-transplantation, composite efficacy failure rates including the incidences of biopsy-confirmed acute rejection in the investigational and control groups were 0% and 10.7%, respectively; patient survival was 100% in each group. No difference in estimated glomerular filtration rate values were observed at 6 months post-transplantation (p=0.97). The safety and satisfaction profile (immunosuppressant therapy barrier scale) of once-daily tacrolimus was comparable with that of twice-daily tacrolimus (p=0.35).ConclusionConversion from twice-daily tacrolimus to once-daily tacrolimus one month after transplantation is safe and effective.

Cyclosporine Sparing Effect of Enteric-Coated Mycophenolate Sodium inDe NovoKidney Transplantation

“…Second, we only showed the non-inferiority of the study group (low-dose CsA with standard dose EC-MPS). Although, previous studies have outlined the efficacy and safety of low-dose CsA,1217 recently, tacrolimus has been primarily used for CNI in KT 11. Therefore, we believe further studies focusing on optimal CNI-sparing regimes with MMF in de novo KT are needed.…”

“…CsA was given orally at a starting dose of 10 mg/kg/day from one day before transplantation. According to a previous study,11 methyl-prednisolone was injected intravenously at the following doses: 500 mg on the day of operation, 250 mg on the day after, and corticosteroids were tapered to a maintenance dose of more than 5 mg a day (prednisolone or equivalent).…”

“…Safety assessments included incidences of AEs and SAEs. According to a previous study,11 AE was defined as any untoward medical occurrence, including exacerbation of a pre-existing condition, in a patient in a clinical investigation who has received a pharmaceutical product. The event did not necessarily have a causal relationship with this treatment.…”

Population pharmacokinetics of immediate‐ and prolonged‐release tacrolimus formulations in liver, kidney and heart transplant recipients

“…Data were obtained for liver, kidney and heart transplant recipients from 8 Phase II studies with immediate‐release tacrolimus (Prograf, Astellas Pharma Ltd, Chertsey, UK) and prolonged‐release tacrolimus (Advagraf or Astagraf XL, Astellas Pharma Europe BV, The Netherlands) (Table ). The data presented here were derived from the internal databases of each Phase II study; 6 studies assessed tacrolimus PK in stable transplant recipients converted from immediate‐ to prolonged‐release tacrolimus .…”

“…Data were obtained for liver, kidney and heart transplant recipients from 8 Phase II studies with immediate‐release tacrolimus (Prograf, Astellas Pharma Ltd, Chertsey, UK) and prolonged‐release tacrolimus (Advagraf or Astagraf XL, Astellas Pharma Europe BV, The Netherlands) (Table ). The data presented here were derived from the internal databases of each Phase II study; 6 studies assessed tacrolimus PK in stable transplant recipients converted from immediate‐ to prolonged‐release tacrolimus . Of these, 3 studies assessed adult kidney transplant recipients (02–0‐131, FG‐506E‐12‐02, and FJ‐506E‐KT01), 1 assessed adult liver recipients (02–0‐152), 1 assessed paediatric (mean age 9 years) liver recipients (03–0‐160) and 1 assessed adult heart recipients (FG‐506‐15‐02) .…”