Bioavailability and costs of once‐daily and twice‐daily tacrolimus formulations in de novo kidney transplantation

Abstract

The use of once-daily tacrolimus in de novo kidney transplantation is increasingly common. Therefore, we were interested in bioavailability aspects of novel once-daily tacrolimus (LCPT, Envarsus) and once-daily tacrolimus extended-release formulation (ER-Tac, Advagraf) compared with twice-daily immediate-release tacrolimus (IR-Tac, Prograf). Furthermore, we calculated the costs. Kidney allograft recipients on tacrolimus-based immunosuppression within 2 clinical trials were included in a single-center analysis. The tacrolimus formulations were compared with respect to daily doses, doses per body weight, trough levels, and concentration-dose (C/D) ratio over 12 months. Intrapatient variability in trough levels and C/D ratios after 3 months was calculated. For the calculation of tacrolimus costs, German list prices were used. Eighty patients (21 with LCPT, 23 with IR-Tac, and 36 with ER-Tac) were analyzed. Pharmacokinetic comparisons revealed significantly higher bioavailability of LCPT at all visits. The variability of trough levels and C/D ratios in general was high and highest in LCPT patients. Different dose requirements translated into different costs. Median treatment costs during the first year were 7.825€ (IQR 6.195-8.892€) for LCPT, 9.813€ (IQR 7.630-16.832€) for IR-Tac, and 9.838€ (IQR 7.503- 13.541€) for ER-Tac (Kruskal-Wallis test, P = .003). The 3 tacrolimus formulations exhibit different dose requirements, exposure, and costs in favor of LCPT.

Effectiveness and safety of the conversion to MeltDose® extended‐release tacrolimus from other formulations of tacrolimus in stable kidney transplant patients: A retrospective study

“…PR‐Tac is more costly in Spain, and savings after conversion to LCP‐Tac were of 1,927 €/year, a 63% reduction. Reductions in costs after conversion to LCP‐Tac have been observed in other studies in the context of kidney or liver transplantation …”

Influence of different formulations of tacrolimus on dosage regimen and drug exposure within the first year after kidney transplantation

“…Additionally, target therapeutic range of Tac can be diff erent according to transplantation center. In the study of Gleder et al data were gained from two prospective randomized multicenter trials (ClinicalTrials.gov: NCT01187953 and NCT01683331), which had diff erent target range of Tac: (1) 6-11 ng/mL for the fi rst 30 days and 4-11 ng/ mL, aft erwards and (2) 8-12 ng/mL for the fi rst 90 days, then 5-8 ng/mL [14]. In the Symphony study, target levels were even lower, between 3 and 7 ng/mL, and demonstrated lower rates of acute rejection and improved graft function as well [15].…”

Alternatives to immediate release tacrolimus in solid organ transplant recipients: When the gold standard is in short supply

“…Studies performed in Europe have, however, demonstrated a cost-benefit for LCPT due to lower dosing requirements. 31,36 Adherence, as assessed by validated questionnaires, may also be improved with once-daily dosing based on two studies of transplant recipients converted from IR-TAC to XL-TAC. 37,38 As of January 2020, patient assistance remains available through the drug manufacturer of LCPT for qualifying patients in the United States.…”