Section 07 · Monograph
Tacrolimus
Reviewed Nov 2026FDA label
PrografCalcineurin inhibitor
- Forms
- Cap: 0.5, 1, 5mg
- Dose
- 0.1mg/kg/day divided BID
- MOA
- Blocks T-cell activation (calcineurin)
Black Box Warning
- Increased risk of developing serious infections and malignancies (e.g., lymphoma, skin cancers) that may lead to hospitalization or death, due to immunosuppression
- Only physicians experienced in immunosuppressive therapy and management of transplant patients should prescribe tacrolimus
Indications
- Prophylaxis of organ rejection in adult and pediatric patients receiving allogeneic kidney transplants, in combination with other immunosuppressantsFDA-labeled
- Prophylaxis of organ rejection in liver, heart, and (adults) lung transplants, in combination with other immunosuppressantsFDA-labeled
Off-Label Uses
- Steroid-sparing immunosuppressant for myasthenia gravis, particularly with evidence supporting use in anti-MuSK and anti-AChR antibody-positive MG (more robust trial data from Japan); typical MG dosing is low, fixed doses of approximately 3 mg/day (range ~2-5 mg/day), substantially lower and less weight-based than transplant regimensOff-label
- May allow more rapid steroid tapering than mycophenolateOff-label
Mechanism of Action
- Calcineurin inhibitor structurally distinct from cyclosporine (macrolide lactone) but with similar downstream mechanism
- Binds to the intracellular protein FKBP-12, forming a complex that inhibits calcineurin phosphatase activity
- Inhibition of calcineurin prevents dephosphorylation and nuclear translocation of NFAT, blocking transcription of IL-2 and other T-cell cytokine genes
- Suppresses T-lymphocyte activation and proliferation, reducing cell-mediated immune responses implicated in graft rejection and in autoantibody-driven neuromuscular junction disease
- Approximately 10-100 times more potent than cyclosporine on a weight basis in vitro
Full Dosing
Adult / usual
- Kidney transplant (with azathioprine): 0.2 mg/kg/day PO divided every 12 hours; target trough 7-20 ng/mL months 1-3, 5-15 ng/mL months 4-12
- Kidney transplant (with MMF/IL-2 receptor antagonist): 0.1 mg/kg/day PO divided every 12 hours
- Liver transplant: 0.1-0.15 mg/kg/day PO divided every 12 hours
- Heart transplant: 0.075 mg/kg/day PO divided every 12 hours
- MG off-label: typically 3 mg/day fixed dose (low-dose, non-weight-based) once or twice daily, without the intensive trough-targeting protocols used in transplant
- Take consistently either with or without food; avoid grapefruit/grapefruit juice; not interchangeable between formulations without monitoring
Contraindications
- Hypersensitivity to tacrolimus
- Hypersensitivity to HCO-60 (polyoxyl 60 hydrogenated castor oil) — relevant to injectable formulation
Drug Interactions
- Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) markedly increase tacrolimus levels — dose reduction and frequent monitoring required
- CYP3A4 inducers (rifampin, rifabutin, phenytoin, carbamazepine, St. John's Wort) decrease tacrolimus levels
- Cannabidiol may increase tacrolimus levels
- Sirolimus co-administration not recommended, particularly in liver and heart transplant populations
- Nephrotoxic drugs increase risk of additive nephrotoxicity
- Calcium channel blockers (diltiazem, nifedipine, verapamil) can increase tacrolimus levels
- Grapefruit/grapefruit juice and nelfinavir should be avoided — significantly increase tacrolimus exposure
Adverse Effects
- Nephrotoxicity — common and dose-related
- New-onset diabetes mellitus/hyperglycemia — more common than with cyclosporine
- Hypertension
- Neurotoxicity: tremor, headache, paresthesias, insomnia; less commonly seizures or PRES
- Hyperkalemia, hypomagnesemia, hyperlipidemia
- Increased risk of infections and malignancy due to immunosuppression
- GI effects: diarrhea, nausea, abdominal pain, constipation
- Anemia, leukopenia
- QT prolongation
Monitoring Parameters
- Whole blood tacrolimus trough concentration regularly (use EDTA tubes)
- Renal function: serum creatinine, BUN, potassium
- Blood glucose/HbA1c — risk of new-onset diabetes
- Liver function tests
- Blood pressure
- Magnesium and lipid panel periodically
- ECG/QT interval monitoring as clinically indicated
- Infection surveillance, including EBV serology in at-risk patients
Pregnancy & Lactation
- Can cause fetal harm; animal data show increased embryo-fetal mortality and adverse effects at maternally toxic doses
- Pregnant transplant recipients on tacrolimus have increased risk of pre-term delivery and low birth weight
- Pregnancy exposure registry exists for organ transplant recipients on immunosuppressants including tacrolimus
- Present in human breast milk
- Women are advised not to breastfeed during treatment given potential for serious adverse reactions in nursing infants