Clinical Impact of Conversion from Prograf to Advagraf in Simultaneous Kidney-Pancreas Transplant Recipients

Abstract

Introduction: Advagraf is a modified release preparation of Tacrolimus absorbed throughout the intestinal tract. Due to the GI tract disturbances in simultaneous pancreas-kidney (SPK) recipients, there are concerns about the efficacy of Advagraf in these patients. Given the lack of data in this area, we set to investigate what is the clinical impact of conversion from twice-daily to once-daily Tacrolimus in SPK recipients. Methods: Between November 2008 and December 2011, 27 SPK recipients have been converted from Prograf to Advagraf. Demographic data, drug doses and levels, serum creatinine, serum glucose and HbA1C, the incidence of rejection episodes as well as patient and graft outcome data were prospectively collected at the time of conversion and at 1, 2, 3, 6, 18 and 24 months following conversion. Results: The mean time to conversion following transplantation was 35.8 ± 5.26 months. 11 SPK recipients (40.7%) were converted on a 1:1 mg basis, whilst another 11 patients required conversion on a +/- 1 mg basis compared to the Prograf dose. Only 4 patients were switched with a dose change > 1 mg. During follow-up, 13 (48%) patients had no dose change following conversion, whilst 11 (40.7%) patients required only 1 or 2 dose adjustments. The mean Advagraf dose at conversion (0.10±0.01 mg/kg) was comparable with the Prograf dose immediately pre-conversion (0.096±0.01 mg/kg) (p=0.98, paired T-test). There were no significant variations in subsequent Advagraf doses at all timepoints during the follow-up (p=0.99, Kruskal-Wallis test). The C0 tacrolimus level pre-switch (8.85±0.87 μg/L) was comparable with the levels postconversion at all time points during the study (p=0.72, Kruskal-Wallis) (fig. 1) with no need for increased monitoring frequency. Serum creatinine levels, the glucose and HbA1c levels remained stable over time with no clinical change following conversion. Only one patient experienced one episode of acute rejection following conversion. 5 patients were converted back to Prograf (1 - acute rejection, 1 - diarrhoea and 1 -CNI toxicity, 2 unspecified). One patient was switched to Sirolimus due to high CNI levels. There was no allograft loss and no patient deaths in this series.Figure: [Tacrolimus C0 levels in SPK patients on Advagraf]Conclusion: Stable SPK recipients can safely be converted from Prograf to Advagraf, with no clinical impact on the transplant function and survival and no changes in drug dosing or levels. Further studies are needed to determine the optimum time for conversion in these patients.