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

Unidad de Trasplante Hepatico, Servicio de Cirugia General, Hospital General Vall de Hebrón, Barcelona, Spain.
Transplant International (Impact Factor: 2.6). 02/1998; 11 Suppl 1:S260-6. DOI: 10.1007/s001470050474
Source: PubMed


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.

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Available from: Valentin Cuervas-Mons, Oct 01, 2015
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    • "Only limited reports on psychiatric symptoms induced by tacrolimus are present in the medical literature. Neurotoxicity and delirium have been reported to occur during tacrolimus treatment in hepatic and kidney allograph [14]; hallucinations , anxiety, paranoid delusions, and dissociative fugues [15] [16] have also been associated with elevated tacrolimus blood concentrations. The differences between the present case and other cases of neuropsychiatric side effects of tacrolimus are mainly two. "
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    ABSTRACT: Several neurological side effects induced by tacrolimus are described in the scientific literature, ranging from mild neurological symptoms to delirium and psychosis. We report the case of a 46-year-old man with no prior psychiatric history who suddenly manifested manic-like psychosis associated with elevated trough tacrolimus blood concentrations 17 years after kidney transplant. The use of antipsychotics may improve the severity of symptoms; but in order to obtain a complete remission, the reduction in the dose of tacrolimus, or its replacement with alternative immunosuppressant therapies, is recommended.
    05/2013; 2013(2):926395. DOI:10.1155/2013/926395
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    ABSTRACT: When tacrolimus side effects persist despite dose reduction, conversion to cyclosporine-based immunosuppression (CyA) is necessary. We characterized tacrolimus side effects that warranted discontinuation of the drug, and outcomes after conversion. Of 388 liver recipients who received tacrolimus as primary immunosuppression, 70 required conversion to CyA. We recorded indication for conversion, whether conversion was early or late after transplantation, tacrolimus dose and trough blood level at conversion, and incidence of rejection after conversion. Conversion was early in 29 patients (41.4%) and late in 41 (58.6%). Indications for early conversion were neurotoxicity (20), (insulin-dependent) diabetes mellitus (IDDM) (5), nephrotoxicity (3), gastrointestinal (GI) toxicity (6), and cardiomyopathy (1), and for late conversion were neurotoxicity (15), IDDM (12), nephrotoxicity (3), GI toxicity (5), hepatotoxicity (6), post-transplant lmphoproliferate disease (PTLD) (2), cardiomyopathy (1), hemolytic anemia (1), and pruritus (1). All early-conversion patients showed improvement/resolution of symptoms. Among late-conversion patients, 37 (90.2%) had improvement/resolution; in 4 (9.8%), adverse effects persisted. The overall rejection rate was 30%. Sixty-two patients (88.6%) are alive with functioning grafts 686 +/- 362 days (range, 154-1433 days) after conversion. When tacrolimus side effects are unresponsive to dose reduction, conversion to CyA can be accomplished safely, with no increased risk of rejection and excellent long-term outcome.
    Transplant International 02/2000; 13(1):73-8. DOI:10.1007/s001470050012 · 2.60 Impact Factor
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