starting oral dose of tacrolimus (administered every 12 hours in two divided doses) is 0.2 mg/kg/day when used in combination with azathioprine or 0.1 mg/kg/day when used in combination with MMF and IL-2 receptor antagonist (see CLINICAL STUDIES ). The initial dose of tacrolimus may be administered within 24 hours of transplantation, but should be delayed until renal function has recovered (as indicated for example by a serum creatinine ≤ 4 mg/dL). Black patients may require higher doses to achieve comparable blood concentrations. Dosage and typical tacrolimus whole blood trough concentrations are shown in the table above; blood concentration details are described in Blood Concentration Monitoring: Kidney Transplantation below.
The data in kidney transplant patients indicate that the Black patients required a higher dose to attain comparable trough concentrations compared to Caucasian patients.
Time After Transplant Caucasian
n=114 Black
n=56
Dose (mg/kg) Trough Concentrations(ng/mL) Dose(mg/kg) Trough Concentrations(ng/mL)
Day 7 0.18 12.0 0.23 10.9
Month 1 0.17 12.8 0.26 12.9
Month 6 0.14 11.8 0.24 11.5
Month 12 0.13 10.1 0.19 11.0
Pediatric Patients
Pediatric liver transplantation patients without pre-existing renal or hepatic dysfunction have required and tolerated higher doses than adults to achieve similar blood concentrations. Therefore, it is recommended that therapy be initiated in pediatric patients at a starting IV dose of 0.03 to 0.05 mg/kg/day and a starting oral dose of 0.15 to 0.20 mg/kg/day. Dose adjustments may be required. Experience in pediatric kidney transplantation patients is limited.
Patients with Hepatic or Renal Dysfunction
Due to the reduced clearance and prolonged half-life, patients with severe hepatic impairment (Pugh ≥ 10) may require lower doses of tacrolimus. Close monitoring of blood concentrations is warranted.
Due to the potential for nephrotoxicity, patients with renal or hepatic impairment should receive doses at the lowest value of the recommended IV and oral dosing ranges. Further reductions in dose below these ranges may be required. Tacrolimus therapy usually should be delayed up to 48 hours or longer in patients with post-operative oliguria.
Conversion from One Immunosuppressive Regimen to Another
Tacrolimus should not be used simultaneously with cyclosporine. Tacrolimus or cyclosporine should be discontinued at least 24 hours before initiating the other. In the presence of elevated tacrolimus or cyclosporine concentrations, dosing with the other drug usually should be further delayed.
Blood Concentration Monitoring
Monitoring of tacrolimus blood concentrations in conjunction with other laboratory and clinical parameters is considered an essential aid to patient management for the eva luation of rejection, toxicity, dose adjustments and compliance. Factors influencing frequency of monitoring include but are not limited to hepatic or renal dysfunction, the addition or discontinuation of potentially interacting drugs and the posttransplant time. Blood concentration monitoring is not a replacement for renal and liver function monitoring and tissue biopsies.
Two methods have been used for the assay of tacrolimus, a microparti
