Tacrolimus Dosage

Usual Adult Dose for Organ Transplant - Rejection Prophylaxis

For use in the prophylaxis of allograft rejection in transplant recipients:

Initial Dose: 0.03 to 0.05 mg/kg/day as a continuous IV infusion no sooner than 6 hours after transplantation. Adult patients should receive doses at the lower end of the dosing range.

Doses as high as 0.1 mg/kg/day as a continuous IV infusion may be appropriate.

Continuous IV infusion of tacrolimus injection should be continued only until the patient can tolerate oral administration of the capsules.

Initial Oral Dose for kidney transplant patients: 0.2 mg/kg/day administered every 12 hours in 2 divided doses.

Initial Oral Dose for liver transplant patients: 0.1 to 0.15 mg/kg/day administered every 12 hours in 2 divided doses.

Initial Oral Dose for heart transplant patients: 0.075 mg/kg/day administered every 12 hours in 2 divided doses.

Doses as high as 0.3 mg/kg/day administered every 12 hours in 2 divided doses may be appropriate.

Usual Adult Dose for Graft Versus Host Disease

Prevention:
Initial dose: 0.03 mg/kg/day (based on lean body weight) as a continuous infusion. Treatment should begin at least 24 hours prior to stem cell infusion and continued only until oral medication can be tolerated.

Treatment:
Initial dose: 0.03 mg/kg/day (based on lean body weight) as a continuous infusion.

Conversion from IV to oral dose (1:4 ratio): Multiply total daily IV dose times 4 and administer in 2 divided oral doses per day, every 12 hours.

Usual Pediatric Dose for Organ Transplant - Rejection Reversal

Liver transplant:
Oral: Initial dose: 0.15 to 0.2 mg/kg/day divided every 12 hours
IV: 0.03 to 0.05 mg/kg/day as a continuous infusion
Dose adjustments may be required. Doses as high as 0.15 mg/kg/day IV or 0.3 mg/kg/day orally have been used.

Heart transplant:
Oral: Initial dose: 0.1 to 0.3 mg/kg/day divided every 12 hours
IV: 0.01 to 0.03 mg/kg/day as a continuous infusion

Kidney transplant:
Oral: Initial dose: 0.2 to 0.3 mg/kg/day divided every 12 hours
IV: 0.06 mg/kg/day as a continuous infusion

Usual Pediatric Dose for Graft Versus Host Disease

Prevention:
Initial dose: 0.03 mg/kg/day (based on lean body weight) as continuous infusion. Treatment should begin at least 24 hours prior to stem cell infusion and continued only until oral medication can be tolerated.
Conversion from IV to oral dose (1:4 ratio): Multiply total daily IV dose times 4 and administer in 2 divided oral doses per day, every 12 hours.

Renal Dose Adjustments

Due to the potential for nephrotoxicity, patients with renal impairment should receive doses at the lowest value of the recommended IV and/or oral dosing ranges. Further reductions in dose below these ranges may be required.

Liver Dose Adjustments

Tacrolimus undergoes significant hepatic metabolism. One study on six subjects with mild hepatic dysfunction has reported that bioavailability and clearance were not substantially different from that in normal subjects. This study concluded that patients with mild hepatic dysfunction may initially be treated with conventional doses of tacrolimus with subsequent dosage adjustments based on response, toxicity, and therapeutic drug monitoring.

While data are lacking, total body clearance of tacrolimus may be significantly impaired in patients with moderate to severe liver dysfunction. Cautious use and conservative dosing of tacrolimus in this patient population is recommended.

Precautions

Tacrolimus therapy should usually be delayed up to 48 hours or longer in patients with postoperative oliguria.

Dialysis

Data not available

Other Comments

Younger children generally require higher maintenance doses on a mg/kg basis than older children, adolescents, or adults.

Tacrolimus should be used concomitantly with adrenal corticosteroids.

Because of the risk of anaphylaxis, tacrolimus injection should be reserved for patients unable to take the capsules orally.

Typical whole blood trough concentrations usually range from 5 to 20 ng/mL. Monitoring of tacrolimus blood levels is considered an essential component of toxicity evaluation. The incidence of adverse effects increase as blood levels rise above the typical range. Extra caution and closer monitoring are recommended when graft function changes or drug interactions are suspected.

Serum creatinine and potassium should be monitored regularly during tacrolimus therapy. In addition, a complete blood count with differential, platelet count, liver function tests, and metabolic tests should be routinely monitored during tacrolimus therapy if clinically indicated.

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