Efficacy and safety of oral low-dose tacrolimus treatment in liver transplantation

Abstract

Eighty-four adult patients were recruited from four centres in Spain to evaluate the efficacy and safety of low-dose (0.1 mg/kg per day) oral tacrolimus plus corticosteroid immunosuppression in liver transplantation. The median daily dose of tacrolimus was increased during the first 3 weeks of therapy from an initial dose of 0.1 mg/kg per day to a maximum of 0.145 mg/kg per day and was subsequently decreased gradually to a minimum of 0.076 mg/kg per day at 1 year. At 7 days posttransplantation, 87.7% of patients had trough whole blood levels of tacrolimus within the therapeutic range (5-20 ng/ml), and the median levels remained fairly constant during the rest of the year (10.1-11.8 ng/ml). None of the patients required intravenous administration of tacrolimus. At 1 year, Kaplan-Meier estimates showed that 73.8% of the patients were receiving tacrolimus monotherapy without the need for corticosteroids. One-year patient and graft survival were 75.9% and 72.3%, respectively. The incidence of acute rejection was 51.2%; 9.5% of cases resolved spontaneously without antirejection therapy and 10.7% were corticosteroid resistant. Only 1 patient (1.2%) developed chronic rejection. The most important adverse events were hypertension (45.2%), tremor (44.0%), diabetes mellitus (33.3%), diarrhoea (31%) and nephrotoxicity (29.8%). Severe neurotoxicity-like convulsions (4.8%), dysarthria (9.5%), delirium (1.2%), coma (1.2%) and the need for haemodialysis (3 patients) were uncommon. In conclusion, low-dose oral tacrolimus immunosuppression is associated with low toxicity without compromising efficacy.

Positive T lymphocytotoxic cross-match in living donor liver transplantation

“…1 Incidence of acute rejection is 50% to 75% in patients of cadaveric donor liver transplantation (CLT) under cyclosporine-based immunosuppression 2,3 and is slightly lower in patients treated with tacrolimus (40% to 65%). 4 The targets of activated lymphocytes in acute cellular rejection are bile duct epithelial cells and the endothelium of vein and artery within the liver. The portal infiltrates contain activated lymphoblastoid cells, both B and T cells and plasma cells.…”

Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients

“…In a prospective trial by Steinmiiller et al, no patient treated with tacrolimus developed IDDM after liver transplantation [21]. In contrast, Margarit et al reported that diabetes developed in 33 Yo of liver transplant recipients treated with tacrolimus [13]. In our series, all patients with IDDM responded to conversion, and 15 patients with new-onset IDDM became nondiabetic.…”

Relationships of tacrolimus pharmacokinetic measures and adverse outcomes in stable adult liver transplant recipients

“…In our study, a few patients had active episodes of infection which was evident by active therapy of antibiotic. Although tremor was common with tacrolimus [44% was reported by Margarit et al (31) in liver transplant patients], there was only one patient who experienced slight tremor in our study, which was recorded as tacrolimus-related in medical notes. The low percentage for the occurrence of tremor may be partly influenced by the nature of the symptom which required self-observation and self-reporting to medical team by patients.…”