A prospective cohort conversion study of twice-daily to once-daily extended-release tacrolimus: role of ethnicity

BACKGROUND: Tacrolimus is a widely used calcineurin inhibitor in kidney transplantation. It is available as twice-daily Prograf® (Tac-BID) and once-daily Advagraf® (Tac-OD). Although therapeutically equivalent, some patients require dose adjustments to achieve similar trough concentrations [C(0)] after conversion. Tacrolimus exposure is affected by ethnicity in the de novo setting but the role of ethnicity in determining dose requirements and adjustments after conversion is unknown. METHODS: In this study, 496 renal transplant recipients (RTRs) were prospectively converted from Tac-BID to Tac-OD, with dose adjustments targeted to achieve similar [C(0)] at 12 months post-conversion. Renal function, acute rejection and Tac dose adjustments by ethnicity were analyzed. RESULTS: There were similar numbers of recipients from living and deceased donors. The mean transplant duration was 7 years. Of the RTRs, 60% were Caucasian and 40% were identified as belonging to an ethnic minority. There was no change in estimated renal function (eGFR) post-conversion to Tac-OD. At 12 months, 35/488 (7%) RTRs were receiving a reduced dose, 101/488 (21%) required a dose increase of which 77 (16%) were receiving at least a 30% increase in dose over baseline. The percentage of those in ethnic groups requiring a dose increase of >30% varied from 8.0% for South Asians to 27.5% for East Asians (P = 0.03), despite East Asians having a similar baseline dose of Tac-BID (3.59 mg/day) compared to the entire cohort (3.53 mg/day). CONCLUSIONS: Ethnicity may play an important role in dosing requirements when converting from Tac-BID to Tac-OD, unrelated to baseline dose. Further investigation is required to determine the reasons for ethnic variability when patients are converted between tacrolimus preparations.