Efficacy and safety of a switch from twice-daily tacrolimus to once-daily generic tacrolimus in stable liver transplant patients.

Background: Once-daily tacrolimus reduces non-compliance relative to twice-daily tacrolimus. However, little is known about the safety and efficacy of conversion from twice-daily tacrolimus to generic once-daily tacrolimus in liver transplantation (LT). Herein, we investigated the efficacy and safety of a switch from twice-daily tacrolimus to generic once-daily tacrolimus in patients with stable liver graft function. Methods: This prospective, multicenter, open-label, single-arm study was conducted in 17 medical centers for 1 year from July 2019 to July 2020 (NCT04069065). Primary endpoint was the incidence of biopsy-proven acute rejection (BPAR) for 24 weeks after conversion. Secondary endpoints were graft failure, patient death, and adverse events (AEs). Results: Of 151 screened LT patients, 144 patients were enrolled. BPAR, graft failure, and patient death did not occur in this patient population. There were no statistical differences in blood tests, liver function tests, or biochemical tests between visits in any of the patients. Median tacrolimus trough level decreased abruptly from 4.7 ng/mL to 3.2 ng/mL after generic once-daily tacrolimus conversion, but median tacrolimus dose increased due to low tacrolimus trough level. Ninety-two adverse events occurred in 54 patients. Liver enzyme levels increased in seven patients (4.9%) after the switch to generic once-daily tacrolimus, but the liver function tests of these patients normalized thereafter. There were three cases of severe AEs not related to investigational drug. Conclusions: Present study suggests that conversion from twice-daily tacrolimus to generic once-daily tacrolimus is effective and safe in stable LT patients.