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Uses

See the MEDWATCH notification at the beginning of the monograph.

Hepatic Allotransplantation

Prevention of hepatic allograft rejection; should be used in conjunction with corticosteroid therapy.

1-year graft and patient survival rates of approximately 73–88%.

Efficacy is comparable to that of a cyclosporine-based regimen in terms of 1-year patient and graft survival.

Renal Allotransplantation

Prevention of renal allograft rejection; should be used in conjunction with corticosteroid therapy.

1-year graft and patient survival rates of approximately 82–100%.

Efficacy is comparable to that of a cyclosporine-based regimen in terms of 1-year patient and graft survival.

Also has been used as “rescue” therapy† for acute or chronic renal allograft rejection or cyclosporine toxicity; overall graft survival following such therapy ranges from 59–86%.

Dosage and Administration

General

Therapeutic Drug Monitoring
• Monitoring whole blood tacrolimus concentrations may be useful in assessing organ rejection and toxicity, adjusting dosage, and determining compliance. Factors influencing frequency of monitoring include hepatic or renal dysfunction, addition or discontinuance of potentially interacting drugs, and time since transplant.
• Monitoring of whole blood trough concentrations is recommended to assist in the clinical evaluation of toxicity.
• Methods for assaying tacrolimus concentrations: microparticle enzyme immunoassay (MEIA) and an enzyme-linked immunosorbent assay (ELISA).
• Whole blood is the matrix of choice; collect specimens in tubes containing ethylene diamine tetraacetic acid (EDTA) anticoagulant. Do not use heparin.
• Typical whole blood trough tacrolimus concentrations for hepatic transplant patients: 5–20 ng/mL (for months 1–12 posttransplant); long term, posttransplant patients are maintained at the lower end of this range.
• Typical whole blood trough tacrolimus concentrations for renal transplant patients: 7–20 ng/mL (for months 1–3 posttransplant) and 5–15 ng/mL (for months 4–12 posttransplant).
• Consult specialized sources for further discussion of the clinical utility of tacrolimus concentration monitoring.

Conversion from One Immunosuppressive Regimen to Another
• To avoid excessive nephrotoxicity, do not use concomitantly with cyclosporine.
• Allow ≥24 hours to elapse between discontinuance of cyclosporine and initiation of tacrolimus, and vice versa. Further delay transfers to the alternative agent if blood cyclosporine or tacrolimus concentrations are elevated.

Administration

Administer orally or by IV infusion.

Initiate therapy with the oral capsules, whenever possible. If therapy is initiated with the IV formulation, substitute oral therapy as soon as tolerated.

Concomitant corticosteroid therapy is recommended by the manufacturer during the early posttransplantation period.

Oral Administration

Administer orally every 12 hours.

Manufacturer makes no specific recommendation regarding administration with meals.

Avoid concomitant administration with grapefruit juice.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Prepare infusion solutions in glass or polyethylene containers; avoid use of PVC containers. Use PVC-free tubing for administration of more-dilute solutions (e.g., those for pediatric patients). (See Storage under Stability.)

Continuously observe patient for ≥30 minutes following initiation of the IV infusion and then at frequent intervals thereafter for possible allergic manifestations. (See Sensitivity Reactions under Cautions.)

Dilution

Must be diluted with 0.9% sodium chloride or 5% dextrose injection to a concentration of 4–20 mcg (0.004–0.02 mg) per mL prior to administration.

Rate of Administration

Administer daily dose over 24 hours by continuous IV infusion.

Dosage

See the MEDWATCH notification at the beginning of the monograph.

Available as anhydrous tacrolimus; dosage expressed in terms of anhydrous drug.

Individualize dosage based on clinical assessments of organ rejection and patient tolerability.

Dosage requirements generally decline with continued therapy; long-term administration is necessary to prevent rejection.

Pediatric Patients

Hepatic Allotransplantation

Children generally appear to require higher dosages than adults on a weight basis to achieve comparable blood concentrations.

Oral

Initially, 150–200 mcg/kg (0.15–0.2 mg/kg) daily, administered in 2 divided doses every 12 hours; initiate therapy no earlier than 6 hours after liver transplantation.

IV

Initially, 30–50 mcg/kg (0.03–0.05 mg/kg) daily commencing after revascularization of the graft.

Continue IV therapy only until the patient can tolerate oral therapy. In most cases, therapy can be switched to the oral route within 2–4 days. Initiate oral tacrolimus 8–12 hours after IV infusion is discontinued.

Adults

Hepatic Allotransplantation

Oral

Initially, 100–150 mcg/kg (0.1–0.15 mg/kg) daily, administered in 2 divided doses every 12 hours; initiate therapy no earlier than 6 hours after liver transplantation.

IV

Initially, 30–50 mcg/kg (0.03–0.05 mg/kg) daily commencing after revascularization of the graft. Adults should receive a dosage at the lower end of this range.

Continue IV therapy only until the patient can tolerate oral therapy. In most cases, therapy can be switched to the oral route within 2–4 days. Initiate oral tacrolimus 8–12 hours after IV infusion is discontinued.

Renal Allotransplantation

Black renal transplant patients may require higher doses than patients of other races to maintain comparable whole blood trough drug concentrations.

Oral

Usual initial dosage: 200 mcg/kg (0.2 mg/kg) daily, administered in 2 divided doses every 12 hours. Therapy may be administered within 24 hours of kidney transplantation, but should be delayed until renal function has recovered (e.g., S_cr ≤4 mg/dL).

IV

Initially, 30–50 mcg/kg (0.03–0.05 mg/kg) daily commencing after revascularization of the graft. Adults should receive a dosage at the lower end of this range.

Continue IV therapy only until the patient can tolerate oral therapy.

Special Populations

Dosage in Hepatic Impairment

Initiate therapy with the lowest dosage in the recommended range.

Further dosage reduction may be required (e.g., in patients with severe hepatic impairment [Child-Pugh score ≥10]).

Dosage in Renal Impairment

Initiate therapy with the lowest dosage in the recommended range. Further dosage reduction may be required.

Delay initiation of therapy for ≥48 hours in patients who develop postoperative oliguria.