Generic
Tacrolimus
8 brands available in the market
At a glance
Tacrolimus is a calcineurin-inhibitor immunosuppressant used for the prophylaxis of organ rejection in allogeneic liver, kidney, heart, and lung transplants.
Description
Tacrolimus binds to the intracellular protein FKBP-12. The tacrolimus-FKBP-12 complex inhibits calcineurin phosphatase activity, preventing dephosphorylation and translocation of NF-AT and NF-κB. It inhibits expression and production of multiple cytokines including IL-2, leading to inhibition of T-lymphocyte activation and proliferation.
Indications
- Prophylaxis of organ rejection in allogeneic liver transplants
- Prophylaxis of organ rejection in allogeneic kidney transplants
- Prophylaxis of organ rejection in allogeneic heart transplants
- Prophylaxis of organ rejection in allogeneic lung transplants
Therapeutic class
Drugs Affecting the Immune Response
Pharmacological class
Calcineurin Inhibitor (Immunosuppressant)
Pharmacology
Tacrolimus binds to FKBP-12, inhibiting calcineurin phosphatase activity. This prevents dephosphorylation and translocation of NF-AT and NF-κB, inhibiting expression and production of cytokines including IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α, and GM-CSF. It inhibits T-lymphocyte activation and proliferation.
Mechanism of action
Prevents organ rejection by inhibiting T-lymphocyte activation.
Dosage
Adult Dose (Oral):
- Kidney (with azathioprine): 0.2 mg/kg/day; target trough 7-20 ng/mL (months 1-3)
- Kidney (with MMF/IL-2 antagonist): 0.1 mg/kg/day; target 4-11 ng/mL
- Liver: 0.10-0.15 mg/kg/day; target 5-20 ng/mL
- Heart: 0.075 mg/kg/day; target 10-20 ng/mL (months 1-3)
- Lung: 0.075 mg/kg/day; target 10-15 ng/mL (months 1-3)
Pediatric Dose (Oral):
- Kidney: 0.3 mg/kg/day; target 5-20 ng/mL
- Liver: 0.15-0.2 mg/kg/day; target 5-20 ng/mL
- Heart/Lung: 0.3 mg/kg/day; target 5-20 ng/mL
Administration
- Take twice daily (every 12 hours) with or without food
- Initiate no sooner than 6 hours after transplant (liver/heart/lung)
- Kidney: within 24 hours but after renal function recovery
- Monitor trough concentrations and adjust dose regularly
Missed dose
If you miss a dose, take it as soon as you remember; if almost time for the next dose, skip it; do not double the dose.
Side effects
Common Side Effects (≥15%):
- Abnormal renal function, hypertension
- Diabetes mellitus, fever, CMV infection
- Tremor, hyperglycemia, leukopenia
- Anemia, infection, bronchitis
- Constipation, diarrhea, headache
- Abdominal pain, insomnia, paresthesia
- Peripheral edema, nausea, hyperkalemia
Precautions & warnings
- New-onset diabetes: Monitor blood glucose
- Nephrotoxicity: Reduce dose; caution with other nephrotoxic drugs
- Neurotoxicity (risk of PRES): Monitor neurologic abnormalities; reduce/discontinue
- Hyperkalemia: Monitor serum potassium
- Not recommended with sirolimus (liver/heart)
- Avoid live vaccines
Contraindications
- Hypersensitivity to tacrolimus or HCO-60
Drug interactions
- Mycophenolic acid products: Increase MPA exposure
- Nelfinavir and grapefruit juice: Increase tacrolimus concentrations via CYP3A inhibition; avoid
- CYP3A inhibitors: Increase tacrolimus concentrations; monitor and adjust dose
- CYP3A4 inducers: Decrease tacrolimus concentrations; monitor and adjust dose
Food interactions
Caution is advised when consuming alcohol with Tacrolimus; consult your doctor.
Use in pregnancy
Use in Pregnancy: Can cause fetal harm; advise pregnant women of potential risk; consult your doctor.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Excreted in human milk; due to potential serious reactions, discontinue nursing or the drug; consult your doctor.
Pediatric use
Indicated for pediatric patients (weight-based dosing)
Geriatric use
Same dose adjustments as adults
Renal / hepatic impairment
Renal Impairment: Risk of nephrotoxicity; dose adjustment may be needed; consult your doctor.
Hepatic Impairment: Caution needed; dose adjustment may be needed; consult your doctor.
Overdose effects
Acute overdosage (up to 30 times intended dose) may cause tremors, abnormal renal function, hypertension, peripheral edema; activated charcoal may be used; provide symptomatic treatment.
Storage conditions
Store below 30°C in a dry place, away from light and moisture; keep out of reach of children.
Chemical structure
Tacrolimus