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UNLABELLED: Prolonged-release tacrolimus (PRT) may offer improved outcomes after kidney transplantation compared with immediate-release tacrolimus (IRT). However, data on outcomes beyond 5-y posttransplantation are lacking. METHODS: A retrospective, noninterventional chart review study examined long-term graft survival in adult kidney transplant participants in the Adherence Measurement in Stable Renal Transplant Patients Following Conversion From Prograf to Advagraf (ADMIRAD) clinical trial at 4 Belgian sites. Patients were randomized to receive once-daily PRT or twice-daily IRT for 6 mo, followed by treatment as per real-world clinical practice. Data were collected retrospectively from randomization day until December 31, 2018. Primary endpoints included efficacy failure, defined as a composite endpoint of graft loss, biopsy-confirmed acute rejection, and graft dysfunction. Secondary endpoints included overall patient survival and course of kidney function. RESULTS: This analysis included 78.5% of patients from ADMIRAD (n = 108 PRT; n = 64 IRT). The Kaplan-Meier survival rate without efficacy failure from randomization to year 5 was 0.741 (95% confidence interval [CI]: 0.647, 0.813) for the PRT group (n = 80), and 0.667 (95% CI: 0.536, 0.768) for the IRT group (n = 42) and remained higher for PRT throughout 10 y follow-up (P = 0.041). The Kaplan-Meier estimate of overall survival from the time of last transplant was 0.981 (95% CI: 0.928, 0.995) and 0.880 (95% CI: 0.802, 0.928) at 5 and 10 y in the PRT group. Kidney function parameters and tacrolimus trough levels remained stable over the follow-up period. CONCLUSIONS: Patients in the ADMIRAD study who received PRT for up to 10 y had improved long-term outcomes compared with patients receiving IRT, with a consistent effect on both graft and patient survival. ispartof: TRANSPLANTATION DIRECT vol:9 issue:4 ispartof: location:United States status: published

Introduction We assessed our clinical experience with de novo kidney transplant recipients from living donors who received once–daily tacrolimus (OD TAC). In addition, we investigated tacrolimus pharmacokinetics and compared the dose of tacrolimus in de novo kidney transplant patients treated with OD TAC or twice–daily tacrolimus (BD TAC). Material and methods Ten patients (3 ABO incompatible, 2 preemptive), who had received a living donor kidney transplant at our hospital since February, 2009, received OD TAC with mycophenolate mofetil, methylprednisolone, and basiliximab. OD TAC doses were adjusted to maintain tacrolimus trough levels in the range of 9–12 ng/mL. We assessed clinical and pharmacokinetic profiles. We compared average total daily dose of tacrolimus between the OD TAC and BD TAC groups. Results Patient survival and graft survival rates were 100% at 15.7 months. Acute rejection was not found clinically. The protocol biopsies (week 3 and month 3) did not reveal biopsy–proven acute rejection, either. No calcineurin inhibitor toxicity occurred. Doses in the OD TAC and BD TAC groups at week 3 posttransplant were 0.308 mg/kg/day and 0.149 mg/kg/day, respectively. Conclusions OD TAC appears to have efficacy and safety equivalent to that of BD TAC. However, a larger dose of OD TAC compared to that of BD TAC may be required during the early period after kidney transplantation.

Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC(0-24) of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC(0-24) and C(min) for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID.