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Medical Science Monitor Basic Research


eISSN: 2329-0358

Delayed Bottom-Up and Amended Simple Method of Dosing with Once-Daily Tacrolimus Application to Achieve Stable Trough Levels in Liver Transplantation

Andreas A. Schnitzbauer, Ceylan Ayik, Frank Ulrich, Wolf O. Bechstein, Christian Mönch

Department of General and Visceral Surgery, Frankfurt University Hospitals, Goethe University Frankfurt/Main, Frankfurt/Main, Germany

Ann Transplant 2015; 20:1-6

DOI: 10.12659/AOT.891411

Available online: 2015-01-02

Published: 2015-01-02


Background: Tacrolimus once-daily formulation (TacOD) was introduced as an alternative to twice-daily formulations de novo. Dosing recommendations range between 0.1 to 0.2 mg/kg BW/d.
Material and Methods: Amended dosing with a simple bottom-up de novo algorithm is presented. Primary outcome measure was feasibility of establishing adequate target trough levels and avoidance of over-immunosuppression, with adequate safety and efficacy after liver transplantation (LT).
Results: TacOD was given to 101 patients. Standard steroid-free immunosuppression consisted of MMF 2 g/d, basiliximab 20 mg on day 0 and 4, and delayed bottom-up IS with TacOD starting with 1 mg/d and doubling the dosage every day until target trough levels of 5 to 8 ng/ml were reached. By day 7 after LT, all except 3 patients had received TacOD. The earliest time point of introduction was day 2. A median of 9 mg/d (range: 0 to 25 mg/d) of TacOD were necessary to establish the trough levels by day 10, which was then 5.4 ng/ml (range: 1.5 to 20 ng/ml). Incidence of adverse events (AE), in particular neurological AEs (n=3), were low. Efficacy failure (acute rejection) was low (4.9%). Renal function was stable and did not deteriorate under CNI treatment.
Conclusions: This is the first report of bottom-up, amended, and simple dosing of TacOD in LT. The algorithm is feasible, safe, and efficient, avoiding trough level peaks and top-down strategies.

Keywords: Immunosuppression, Liver Transplantation, Tacrolimus