Efficacy and safety of oral low-dose tacrolimus treatment in liver transplantation.
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.
Unidad de Trasplante Hepatico, Servicio de Cirugia General, Hospital General Vall de Hebrón, Barcelona, Spain. margarit@.vhebron.es
C
C
Margarit
A
A
Rimola
I
I
Gonzalez-Pinto
V
V
Cuervas-Mons
A
A
Edo
H
H
Andreu
E
E
Moreno-Gonzalez
J L
JL
Calleja
D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007239:Infections / Q000453:epidemiology; D016031:Liver Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016559:Tacrolimus