Improved Medication Adherence with the Use of Extended-Release Tacrolimus in Liver Transplant Recipients: A Pilot Randomized Controlled Trial

Abstract

Background. Nonadherence to immunosuppression in liver transplant recipients (LTRs) leads to deterioration in health outcomes. Once-dailyextended-release tacrolimus (TAC-ER) may improve adherence when compared to twice-dailyimmediate-release tacrolimus (TAC-IR). Methods. We conducted a randomized controlled study to evaluate medication adherence, clinical efficacy, and safety of TAC-ER in stable LTR. All patients >18 years who underwent liver transplantation before 6 months were eligible. Patients were randomized 1 : 1 to continued TAC-IR or conversion to TAC-ER. The primary outcome was change in medication adherence from baseline to 9 months, assessed using BAASIS. Secondary outcomes were tacrolimus trough levels, safety, and quality of life. Results. Thirty-one patients were consented and randomized to either of the two groups: conversion to TAC-ER (n = 15) or continued TAC-IR (n = 16). Six patients in the TAC-ER group withdrew after randomization due to apprehension about switching medication (n = 2), unwillingness to travel (n = 2), and increased liver tests after conversion (n = 2, both were acute rejections despite therapeutic tacrolimus levels and were considered unrelated to TAC-ER). We compared the results of nine patients in the TAC-ER group that completed the study with those of sixteen in the TAC-IR group. At baseline, there was no difference in tacrolimus trough levels between groups. Improved adherence was observed in the TAC-ER group as 100% of patients reported at least one period of full adherence during the study period (100% vs. 62.6%, p = 0.035 ). Tacrolimus trough levels and liver tests were comparable between groups throughout the study. There were no differences in eGFR, HbA1c, or QoL between the groups. Conclusion. TAC-ER improved medication adherence while maintaining comparable trough levels, liver function, and QoL as TAC-IR in LTR.

The effect of tacrolimus conversion from immediate- to extended-release formulation on renal function in renal transplant patients: a meta-analysis

“…It was found that based on the result of Scr, renal function was improved after tacrolimus conversion from immediate-to extended-release formulation in renal transplant patients with a follow-up duration ≥48 weeks but not in patients with a follow-up duration <48 weeks. The possible interpretation would be that, as discussed previously, extended-release tacrolimus was in a once-daily formulation procedure, which increased medication adherence (Hatakeyama et al, 2012;Singh et al, 2015;Oh et al, 2020;Verma et al, 2023); therefore, the long-term effect of conversion to extendedrelease tacrolimus on improving the renal function in renal transplant patients was obvious. Further subgroup analysis discovered that in patients with the tacrolimus dose after conversion ≤4.0 mg/d and patients with the tacrolimus blood trough level after conversion >6.0 ng/mL, the renal function seemed to be improved.…”

Modifying Tacrolimus-related Toxicity After Liver Transplantation Comparing Life Cycle Pharma Tacrolimus Versus Extended-released Tacrolimus: A Multicenter, Randomized Controlled Trial

“…The introduction of once-daily tacrolimus formulations improved the medication adherence in liver transplant recipients. 4 , 5 Around the world, the choice for a tacrolimus formulation varies among transplant centers and no preference is pronounced.…”