Efficacy and safety of once daily tacrolimus compared to twice daily tacrolimus after liver transplantation

Abstract

BACKGROUND

Once daily tacrolimus regimen was found to exhibits similar bioavailability, safety and efficacy properties compared to twice-daily tacrolimus in kidney transplantation patients.

AIM

To compare the efficacy and safety of once-daily prolonged release tacrolimus compared to twice-daily tacrolimus in liver transplantation patients.

METHODS

MEDLINE, EMBASE, CENTRAL databases were searched for clinical trials until December 2020. Efficacy outcome measured as the rate of treatment failure indicated by biopsy-proven acute rejection, Serum creatinine, graft loss, or death. Two reviewers independently selected studies, collected data and assessed risk of bias. The results are reported as risk ratio with 95% confidence interval (CI) for dichotomous data.

RESULTS

Seven studies included with 965 patients. All the included studies were of moderate quality according to the risk of bias assessment using Cochrane Risk of Bias tool. Biopsy-proven acute rejection was reported in four studies, and pooled analysis of those studies indicated similar rejections in both twice daily and once daily tacrolimus groups (risk ratio: 1.06, 95%CI: 0.84-1.34, n = 758, I² = 0%) and also we found no significant difference between both groups for renal outcome (serum creatinine; mean difference, 0.001 mg/dL, 95%CI: -0.042 to 0.043, n = 846, I² = 18.6%). Similarly, there was similar number of adverse events such as hypertension, headache, back pain, blood related disorders, infections and nausea observed in both groups.

CONCLUSION

The analysis findings confirm that both once daily and twice daily tacrolimus formulations are comparable in terms of efficacy and safety outcomes.

Keywords: Prolonged release; Tacrolimus; Liver transplantation; Graft rejection; Renal impairment; FK level

Core Tip: Tacrolimus, a calcineurin inhibitor is an important component of the immunosuppressive regimens post liver transplantation. Compliance to immuno-suppression treatment generally is important and non-adherence is a major risk factor of graft rejection and loss. Compliance to medication declines over the course of time in patients after liver transplantation due to several factors and this contributes to about 20% of late acute rejection. The efficacy of once daily tacrolimus regimens has been reported in many studies and this systematic review/meta-analysis confirmed the evidence of comparable efficacy and safety of prolonged release tacrolimus to the twice daily immediate release formulation.