asymptomatic and all patients recovered with no sequelae. Occasionally, acute overdosage has been followed by adverse reactions consistent with those listed in the ADVERSE REACTIONS section except in one case where transient urticaria and lethargy were observed. Based on the poor aqueous solubility and extensive erythrocyte and plasma protein binding, it is anticipated that tacrolimus is not dialyzable to any significant extent; there is no experience with charcoal hemoperfusion. The oral use of activated charcoal has been reported in treating acute overdoses, but experience has not been sufficient to warrant recommending its use. General supportive measures and treatment of specific symptoms should be followed in all cases of overdosage.
In acute oral and IV toxicity studies, mortalities were seen at or above the following doses: in adult rats, 52X the recommended human oral dose; in immature rats, 16X the recommended oral dose; and in adult rats, 16X the recommended human IV dose (all based on body surface area corrections).
DOSAGE AND ADMINISTRATION
NOTE: Anaphylactic reactions have occurred with injectables containing castor oil derivatives. See WARNINGS.
Tacrolimus Capsules Summary of Initial Oral Dosage Recommendations and Observed Whole Blood Trough Concentrations
Patient Population Recommended Initial Oral Dosagea Typical Whole Blood Trough Concentrations
Adult kidney transplant patients In combination with azathioprine 0.2 mg/kg/day month 1 to 3 : 7 to 20 ng/mL
month 4 to12 : 5 to15 ng/mL
In combination with MMF/IL-2 receptor antagonist b 0.1 mg/kg/day month 1 to12 : 4 to11 ng/mL
Adult liver transplant patients 0.10 to 0.15 mg/kg/day month 1 to 12 : 5 to 20 ng/mL
Pediatric liver transplant patients 0.15 to 0.20 mg/kg/day month 1 to 12 : 5 to 20 ng/mL
a) Note : two divided doses, q12h
b) In a second smaller study, the initial dose of tacrolimus was 0.15 to 0.2 mg/kg/day and observed tacrolimus concentrations were 6 to 16 ng/mL during month 1 to 3 and 5 to 12 ng/mL during month 4 to 12 (see CLINICAL STUDIES ).
Liver Transplantation
It is recommended that patients initiate oral therapy with tacrolimus capsules if possible. If IV therapy is necessary, conversion from IV to oral tacrolimus is recommended as soon as oral therapy can be tolerated. This usually occurs within 2 to 3 days. The initial dose of tacrolimus should be administered no sooner than 6 hours after transplantation. In a patient receiving an IV infusion, the first dose of oral therapy should be given 8 to 12 hours after discontinuing the IV infusion. The recommended starting oral dose of tacrolimus capsules is 0.10 to 0.15 mg/kg/day administered in two divided daily doses every 12 hours. Co-administered grapefruit juice has been reported to increase tacrolimus blood trough concentrations in liver transplant patients. (See Drugs that May Alter Tacrolimus Concentrations ).
Dosing should be titrated based on clinical assessments of rejection and tolerability. Lower tacrolimus dosages may be sufficient as maintenance therapy. Adjunct therapy with adrenal corticosteroids is recommended early post-transplant.
Dosage and typical tacrolimus whole blood trough concentrations are shown in the table above; blood concentration details are described in Blood Concentration Monitoring: Liver Transplantation below.
Kidney Transplantation
The recommended
