What it's for (Indications)
- Tacrolimus is indicated for the prophylaxis of organ rejection in patients receiving kidney or liver transplants.
- For kidney transplant, it can be used with azathioprine or with mycophenolate mofetil (MMF)/IL-2 receptor antagonist.
- For liver transplant, it can be used with corticosteroids.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | For patients unable to tolerate oral formulations, intravenous (IV) use is recommended. Oral capsules or suspension should be administered consistently with or without food. Therapeutic drug monitoring is essential. Patients must avoid grapefruit and grapefruit juice. Dosage adjustments are necessary for African-American patients, as well as those with hepatic and renal impairment. **Adult Kidney Transplant:** * **With azathioprine:** Initial oral dosage of 0.2 mg/kg/day, divided into two doses every 12 hours. Whole blood trough concentration target: Month 1-3: 7-20 ng/mL; Month 4-12: 5-15 ng/mL. * **With MMF/IL-2 receptor antagonist:** Initial oral dosage of 0.1 mg/kg/day, divided into two doses every 12 hours. Whole blood trough concentration target: Month 1-12: 4-11 ng/mL. **Adult Liver Transplant:** * **With corticosteroids only:** Initial oral dosage of 0.1-0.15 mg/kg/day, divided into two doses every 12 hours. |
Safety & Warnings
Common Side Effects
- Common adverse reactions (≥ 15%) include abnormal renal function.
- Serious adverse reactions reported include lymphoma and other malignancies, serious infections, new onset diabetes after transplant, nephrotoxicity, neurotoxicity, hyperkalemia, hypertension, anaphylactic reactions (especially with PROGRAF Injection), myocardial hypertrophy, pure red cell aplasia, and thrombotic microangiopathy (including hemolytic uremic syndrome and thrombotic thrombocytopenic purpura).
Serious Warnings
- Black Box Warning: WARNING: MALIGNANCIES AND SERIOUS INFECTIONS. Increased risk for developing serious infections and malignancies with PROGRAF or other immunosuppressants that may lead to hospitalization or death.
- Patients receiving tacrolimus have an increased risk for developing serious infections and malignancies, which can lead to hospitalization or death.
- These include lymphomas and other malignancies (e.
- g.
- , skin cancers, post-transplant lymphoproliferative disorder).
- Other serious risks include new onset diabetes after transplant, nephrotoxicity, neurotoxicity, hyperkalemia, and hypertension.
- Anaphylactic reactions, particularly with PROGRAF Injection, due to sensitivity to HCO-60 (polyoxyl 60 hydrogenated castor oil) can occur.
- Myocardial hypertrophy and pure red cell aplasia have also been observed.
- Thrombotic microangiopathy, including hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, is another potential serious complication.
- Patients should avoid eating grapefruit or drinking grapefruit juice while on tacrolimus therapy.
How it Works (Mechanism of Action)
Tacrolimus binds to the intracellular protein FKBP-12. This complex, along with calcium, calmodulin, and calcineurin, inhibits the phosphatase activity of calcineurin. This inhibition prevents dephosphorylation and translocation of various factors like NF-AT and NF-κB, thereby inhibiting the expression and/or production of numerous cytokines (e.g., IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, gamma interferon, TNF-alpha, GM-CSF). It also inhibits IL-2 receptor expression, nitric oxide release, induces apoptosis, and produces transforming growth factor beta, leading to overall immunosuppressive activity and inhibition of T-lymphocyte activation.
Commercial Brands (Alternatives)
No other brands found for this formula.