Usual Adult Dose for Organ Transplant - Rejection Prophylaxis

KIDNEY TRANSPLANT:
IMMEDIATE RELEASE:

• In combination with azathioprine: Initial dose: 0.1 mg/kg orally every 12 hours; initiate within 24 hours of surgery but delay until renal function has recovered
• In combination with mycophenolate mofetil (MMF)/interleukin-2 (IL-2) receptor antagonist: Initial dose: 0.05 mg/kg orally every 12 hours; initiate within 24 hours of surgery, but delay until renal function has recovered

Comments:

• Should be taken consistently either with or without food because the presence and composition of food decreases the bioavailability.

Use: Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney or heart transplants; use concomitantly with adrenal corticosteroids; in kidney and heart transplant, use in conjunction with azathioprine or MMF

EXTENDED-RELEASE:

• With Basiliximab Induction, MMF, and Corticosteroids: Initial dose: 0.15 to 0.2 mg/kg/day orally as a single dose. Give first dose prior to or within 48 hours of transplant completion. May delay initiation until renal function has recovered.
• With MMF and Corticosteroids, but Without Basiliximab Induction: Pre-operative dose: 0.1 mg/kg/day orally as a single dose within 12 hours prior to reperfusion; Post-operative dose: 0.2 mg/kg/day orally as a single dose. Give first post-operative dose within 12 hours after reperfusion but not less than 4 hours after the pre-operative dose.

Comments:

• Extended-release capsules are not interchangeable or substitutable with immediate-release capsules.
• Concomitant use with cyclosporine is not recommended.
• If switching from tacrolimus infusion, administer 8 to 12 hours after discontinuing infusion.

Use: Prophylaxis of organ rejection in patients receiving a kidney transplant with MMF and corticosteroids, with or without basiliximab induction

IV:

• Initial dose: 0.03 to 0.05 mg/kg/day as a continuous IV infusion

Comments:

• Adult patients should receive doses at the lower end of the dosing range.
• IV administration should be reserved only for initiation in patients unable to take oral therapy.
• Convert to oral therapy as soon as it can be tolerated, usually within 2 to 3 days.

Use: Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney or heart transplants; use concomitantly with adrenal corticosteroids; in kidney and heart transplant, use in conjunction with azathioprine or MMF

LIVER TRANSPLANT:
IMMEDIATE-RELEASE:

• Initial dose: 0.05 to 0.075 mg/kg orally every 12 hours. Initiate no sooner than 6 hours after surgery.

Comments:

• Should be taken consistently either with or without food because the presence and composition of food decreases the bioavailability.

Use: Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney or heart transplants; use concomitantly with adrenal corticosteroids; in kidney and heart transplant, use in conjunction with azathioprine or MMF

IV:

• Initial dose: 0.03 to 0.05 mg/kg/day as a continuous IV infusion

Comments:

• Adult patients should receive doses at the lower end of the dosing range.
• IV administration should be reserved only for initiation in patients unable to take oral therapy.
• Convert to oral therapy as soon as it can be tolerated, usually within 2 to 3 days.

Use: Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney or heart transplants; use concomitantly with adrenal corticosteroids; in kidney and heart transplant, use in conjunction with azathioprine or MMF

HEART TRANSPLANT:
IMMEDIATE-RELEASE:

• Initial dose: 0.0375 mg/kg orally every 12 hours. Initiate no sooner than 6 hours after surgery

Comments:

• Should be taken consistently either with or without food because the presence and composition of food decreases the bioavailability.

Use: Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney or heart transplants; use concomitantly with adrenal corticosteroids; in kidney and heart transplant, use in conjunction with azathioprine or MMF

IV:

• Initial dose: 0.01 mg/kg/day as a continuous IV infusion

Comments:

• Adult patients should receive doses at the lower end of the dosing range.
• IV administration should be reserved only for initiation in patients unable to take oral therapy.
• Convert to oral therapy as soon as it can be tolerated, usually within 2 to 3 days.

Use: Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney or heart transplants; use concomitantly with adrenal corticosteroids; in kidney and heart transplant, use in conjunction with azathioprine or MMF

Usual Pediatric Dose for Organ Transplant - Rejection Reversal

LIVER TRANSPLANT:
IMMEDIATE RELEASE:

• Initial dose: 0.075 to 0.1 mg/kg orally every 12 hours

Comments:

• Should be taken consistently either with or without food because the presence and composition of food decreases the bioavailability.

Use: Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney or heart transplants; use concomitantly with adrenal corticosteroids; in kidney and heart transplant, use in conjunction with azathioprine or mycophenolate mofetil (MMF)

INTRAVENOUS:

• Initial dose: 0.03 to 0.05 mg/kg/day as a continuous IV infusion

Comments:

• Pediatric patients without pre-existing renal or hepatic dysfunction have required and tolerated higher doses than adults to achieve similar blood concentrations.
• IV administration should be reserved only for initiation in patients unable to take oral therapy.
• Convert to oral therapy as soon as it can be tolerated, usually within 2 to 3 days.

Use: Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney or heart transplants; use concomitantly with adrenal corticosteroids; in kidney and heart transplant, use in conjunction with azathioprine or MMF

Renal Dose Adjustments

KIDNEY TRANSPLANT:
IMMEDIATE-RELEASE/GRANULES:

• Initial dose: 0.15 mg/kg orally every 12 hours; initiate within 24 hours of surgery but delay until renal function has recovered
• In combination with mycophenolate mofetil (MMF)/interleukin-2 (IL-2) receptor antagonist: Initial dose: 0.05 mg/kg orally every 12 hours; initiate within 24 hours of surgery, but delay until renal function has recovered

LIVER TRANSPLANT:
IMMEDIATE-RELEASE/GRANULES:

• Initial dose: 0.075 to 0.1 mg/kg orally every 12 hours

Comments:

• Should be taken consistently either with or without food because the presence and composition of food decreases the bioavailability.

Use: Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney or heart transplants; use concomitantly with adrenal corticosteroids; in kidney and heart transplant, use in conjunction with azathioprine or mycophenolate mofetil (MMF)

HEART TRANSPLANT:
IMMEDIATE-RELEASE/GRANULES:

• Initial dose: 0.15 mg/kg orally every 12 hours

Comments:

• Should be taken consistently either with or without food because the presence and composition of food decreases the bioavailability.

Use: Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney or heart transplants; use concomitantly with adrenal corticosteroids; in kidney and heart transplant, use in conjunction with azathioprine or MMF

IV:

• Initial dose: 0.03 to 0.05 mg/kg/day as a continuous IV infusion

Comments:

• Pediatric patients in general need higher doses compared to adults; the higher dose requirements may decrease as the child grows older.
• Pediatric patients without pre-existing renal or hepatic dysfunction have required and tolerated higher doses than adults to achieve similar blood concentrations.
• IV administration should be reserved only for initiation in patients unable to take oral therapy.
• Convert to oral therapy as soon as it can be tolerated, usually within 2 to 3 days.

Use: Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney or heart transplants; use concomitantly with adrenal corticosteroids; in kidney and heart transplant, use in conjunction with azathioprine or MMF

Liver Dose Adjustments

Severe liver impairment (Child-Pugh 10 or greater): May require lower doses

LIVER TRANSPLANT:
Patients experiencing post-transplant hepatic impairment may be associated with an increased risk of developing renal insufficiency related to high blood levels of this drug. Monitor closely and consider dose adjustments.

Dose Adjustments

Concomitant use of cyclosporine: Avoid concomitant use; discontinue tacrolimus or cyclosporine at least 24 hours prior to initiating the other. In the presence of elevated tacrolimus or cyclosporine concentrations, further delay dosing with the other drug.

Precautions

US BOXED WARNINGS:
Malignancies/Serious Infections:

• This drug increases the risk of development of lymphoma and other malignancies, particularly of the skin, due to immunosuppression. This may lead to hospitalization or death.
• This drug increases susceptibility to bacterial, viral, fungal, and protozoal infections, including opportunistic infections.
• Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe this drug.
• Patients should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources.
• The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients
• In patients hypersensitive to HCO-60 (polyoxyl 60 hydrogenated castor oil)

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Tacrolimus should not be used simultaneously with cyclosporine. Tacrolimus may be initiated at least 24 hours after stopping cyclosporine; however, dosing should be delayed if cyclosporine blood levels are elevated.
• Dosing should be titrated based on clinical assessments of rejection and tolerability, and to maintain recommended trough concentration ranges.
• Patients should not eat grapefruit or drink grapefruit juice with this drug.

Extended release:

• Should be taken once daily in the morning, preferably on an empty stomach at least 1 hour before or 2 hours after a meal; do not take with an alcoholic beverage; do not chew, divide, or crush.
• Take a missed dose as soon as possible but not more than 14 hours after the scheduled time. Beyond the 14-hour timeframe, the patient should wait until the usual scheduled time the following morning to take the next scheduled dose. Do not take 2 doses at the same time.

General:

• The capsule formulation and the oral suspension of this drug are not interchangeable or substitutable with other tacrolimus extended-release products because the rate of absorption following the administration of an extended-release product is not equivalent to that of an immediate-release product. Under-or overexposure to this drug may result in graft rejection or other serious adverse reactions.
• The capsule formulation should not be used without supervision of a physician with experience in immunosuppressive therapy.
• Therapeutic drug monitoring is recommended for all patients receiving this drug.

Monitoring:

• Frequent monitoring of tacrolimus whole blood trough concentrations is recommended; the manufacturer product information should be consulted.
• Whole blood trough concentrations usually range from 5 to 20 ng/mL. Extra caution and closer monitoring are recommended when graft function changes or drug interactions are suspected.
• Monitoring of cyclosporine blood concentrations should be continued post-conversion as tacrolimus may affect the clearance of cyclosporine.
• Renal and liver function and tissue biopsies should be monitored regularly.
• Blood glucose and serum potassium should be monitored.
• Consider obtaining electrocardiograms and monitoring electrolytes periodically in patients at increased risk for QT prolongation.

Patient advice: Since this drug may cause visual and/or neurological disturbances, patients should be cautioned against driving or operating machinery if they are affected.