Reducing the Pill Burden: Immunosuppressant Adherence and Safety after Conversion from a Twice-Daily (IR-Tac) to a Novel Once-Daily (LCP-Tac) Tacrolimus Formulation in 161 Liver Transplant Patients.

Max M Maurer,Paul Ritschl,Robert Öllinger,Johann Pratschke,Brigitta Globke,Wenzel Schöning,Georg Lurje,Julius Plewe,Marius Ibach,Dennis Eurich,Axel Winter

doi:10.3390/biomedicines10020272

Abstract

Non-adherence to immunosuppressant therapy reduces long-term graft and patient survival after solid organ transplantation. The objective of this 24-month prospective study was to determine adherence, efficacy and safety after conversion of stable liver transplant (LT) recipients from a standard twice-daily immediate release Tacrolimus (IR-Tac) to a novel once-daily life cycle pharma Tacrolimus (LCP-Tac) formulation. We converted a total of 161 LT patients at baseline, collecting Tacrolimus trough levels, laboratories, physical examination data and the BAASIS© questionnaire for self-reported adherence to immunosuppression at regular intervals. With 134 participants completing the study period (17% dropouts), the overall adherence to the BAASIS© increased by 57% until month 24 compared to baseline (51% vs. 80%). Patients who required only a morning dose of their concomitant medications reported the largest improvement in adherence after conversion. The intra-patient variability (IPV) of consecutive Tacrolimus trough levels after conversion did not change significantly compared to pre-conversion levels. Despite reducing the daily dose by 30% at baseline as recommended by the manufacturer, Tac-trough levels remained stable, reflected by an increase in the concentration-dose (C/D) ratio. No episodes of graft rejection or loss occurred. Our data suggest that the use of LCP-Tac in liver transplant patients is safe and can increase adherence to immunosuppression compared to conventional IR-Tac.

Highlights

Introduction iationsThe calcineurin inhibitor (CNI) Tacrolimus (Tac) has remained the standard immunosuppressant after solid organ transplantation for more than two decades [1,2,3]
Multicentric and prospective study in 57 stable liver transplant recipients, the greater bioavailability of life cycle pharma Tacrolimus (LCP-Tac) allowed for once-daily dosing with comparable systemic exposure (AUC) and trough levels at 30% less total daily dosage (TDD) compared to immediate release Tacrolimus (IR-Tac)
59% of the patients were treated with a regimen encompassing a second or third immunosuppressant in addition to Tac (Table 1)

Summary

Introduction

The calcineurin inhibitor (CNI) Tacrolimus (Tac) has remained the standard immunosuppressant after solid organ transplantation for more than two decades [1,2,3]. Apart from its high efficacy in preventing graft rejection, Tac exhibits a narrow therapeutic index with considerable variability in systemic drug exposure [4,5]. Depend on therapeutic drug monitoring via regular Tac-trough concentration measurements and may require dose adjustments to minimize toxicity without compromising efficacy [6]. In patients with high Tac doses, elevated peak concentrations are associated with increased. CNI-toxicity independently of 24-h exposure (AUC—area under the curve) [11].

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Conclusion