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G69 TACOLIMUS TOXICITY WITH STANDARD DOSING REGIMENS IN PAEDIATRIC RENAL TRANSPLANT RECIPIENTS
J. Y. Kausman, B. Patel, S. D. Marks.Great Ormond Street Hospital for Children NHS Trust, London, UK
Aims: To determine if paediatric patients receiving oral tacrolimus for renal transplantation were experiencing drug toxicity as a result of excessive dosing within the first three weeks post-transplantation when commenced on a standard dose of 0.3 mg/kg/day in two divided doses, which was titrated to target 12 hour trough levels of 15 ng/ml (with toxicity denoted as >20 ng/ml).
Methods: Retrospective review of all paediatric patients who received tacrolimus therapy as part of their immunosuppressive drug regimen for renal transplantation in a single UK centre during the period from 2002 to 2004. Patients were included if they received oral tacrolimus therapy for the first 21 days and there was complete data on review of case notes, drug charts, and biochemical results (including plasma creatinine and trough tacrolimus blood levels). All patients were prescribed their initial dose of 0.15 mg/kg of tacrolimus pre-transplantation with subsequent doses 12-hourly.
Results: Sixty three children (39 (62%) female) aged 1.9–17.7 (median 13.3) years underwent renal transplantation with tacrolimus therapy as part of their immunosuppressive regimen. As the tacrolimus dose was not capped, the maximum prescribed dose was 24 mg/day. The ethnicity was recorded with 43 (68%) recipients white, nine (15%) of Asian origin, seven (11%) of Middle East origin, and four (6%) Afro-Caribbean. 41 (65%) patients had evidence of tacrolimus toxicity with at least one toxic trough level with high levels in 15% (84 of 570) of all samples. 49% (41 of 84) of toxic levels occurred in days 2–4 post-transplantation. The median (range) of plasma creatinine levels were 97 (13–631), 74 (16–617), and 77 (16–537) μmol/l for weeks 1, 2, and 3 post-transplantation. Tacrolimus toxicity occurred in older children (p = 0.01) of increased height (p = 0.03) and body …