Once-daily tacrolimus in liver transplantation: a ‘me-too drug’, or a therapeutic advantage

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Purpose of review

To provide latest information on differences between standard tacrolimus (TAC BID) and slow-released formulation of tacrolimus (Advagraf) in liver transplantation (LTx), and to discuss the latter's therapeutic value as a distinct entity.

Recent findings

Two articles on de-novo studies, several on conversion and one on survival analysis from the European Liver Transplant Registry published recently showed that low-dose Advagraf immediately after transplantation provided same protection to the kidney as standard dose delayed until day 5, and was associated with lower rejection rate; to maintain the same trough level after late conversion to Advagraf, an approximately 1.25-fold higher dose was needed on average; if studied by questionnaire, conversion improved medication adherence; and registry data provided evidence of long-term survival benefit of Advagraf over TAC BID (7 and 8% graft and patient survival rates over a 3-year period; P < 0.002 and P < 0.003, respectively).


Pharmacokinetic differences between TAC BID and Advagraf translate into less interpatient and intrapatient variability and improve adherence. If survival benefit of Advagraf administration de novo after LTx as demonstrated by the European Liver Transplant Registry analysis is confirmed in an independent cohort, Advagraf will leave the area of the ‘me-too’ drugs to become the immunosuppressant of choice.

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