Table 3. Summary of Initial Oral Dosage Recommendations and Observed Whole Blood Trough Concentrations in Children

Patient Population Recommended Tacrolimus Initial Oral Dosage Observed Tacrolimus Whole Blood Trough Concentrations
  Note: daily doses should be administered as two divided doses, every 12 hours  
Pediatric liver transplant patients 0.15 to 0.20 mg/kg/day Month 1 to 12: 5 to 20 ng/mL

Pediatric liver transplantation patients without pre-existing renal or hepatic dysfunction have required and tolerated higher doses than adults to achieve similar blood concentrations.

Experience in pediatric kidney and heart transplantation patients is limited.

2.3 Dosage Adjustment in Patients with Renal Impairment
Due to its potential for nephrotoxicity, consideration should be given to dosing Tacrolimus capsules at the lower end of the therapeutic dosing range in patients who have received a liver transplant and have pre-existing renal impairment. Further reductions in dose below the targeted range may be required.

In kidney transplant patients with post-operative oliguria, the initial dose of Tacrolimus capsules should be administered no sooner than 6 hours and within 24 hours of transplantation, but may be delayed until renal function shows evidence of recovery.

2.4 Dosage Adjustments in Patients with Hepatic Impairment
Due to the reduced clearance and prolonged half-life, patients with severe hepatic impairment (Child Pugh ≥ 10) may require lower doses of Tacrolimus capsules. Close monitoring of blood concentrations is warranted.

The use of Tacrolimus capsules in liver transplant recipients experiencing post-transplant hepatic impairment may be associated with increased risk of developing renal insufficiency related to high whole-blood concentrations of Tacrolimus. These patients should be monitored closely and dosage adjustments should be considered. Some evidence suggests that lower doses should be used in these patients [see Dosage and Administration (2.1), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

2.5 Administration Instructions
It is recommended that patients initiate oral therapy with Tacrolimus capsules if possible.

Initial dosage and observed Tacrolimus whole blood trough concentrations for adults are shown in Table 1 and for pediatrics in Table 3 [see Dosage and Administration (2.1, 2.2)]; for blood concentration monitoring details in kidney transplant patients [see Dosage and Administration (2.1)].

It is important to take Tacrolimus capsules consistently every day either with or without food because the presence and composition of food decreases the bioavailability of Tacrolimus capsules [see Clinical Pharmacology (12.3)].

Patients should not eat grapefruit or drink grapefruit juice in combination with Tacrolimus capsules [see Drug Interactions (7.2)].

Tacrolimus capsules should not be used simultaneously with cyclosporine. Tacrolimus capsules or cyclosporine should be discontinued at least 24 hours before initiating the other. In the presence of elevated Tacrolimus capsules or cyclosporine concentrations, dosing with the other drug usually should be fu