Tacrolimus

What it is and how it works

Mechanism of Action Tacrolimus binds to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin (a ubiquitous mammalian intracellular enzyme) is then formed, after which the phosphatase activity of calcineurin is inhibited. Such inhibition prevents the dephosphorylation and translocation of various factors such as the nuclear factor of activated T-cells (NF-AT), and nuclear factor kappa-light-chain enhancer of activated B-cells (NF-κB).

Indications

Tacrolimus capsules are a calcineurin-inhibitor immunosuppressant indicated for the prophylaxis of organ rejection in adult patients receiving allogeneic liver, kidney, or heart transplants, and pediatric patients receiving allogenic liver transplants in combination with other immunosuppressants. Prophylaxis of Organ Rejection in Kidney, Liver, or Heart Transplant Tacrolimus capsules are indicated for the prophylaxis of organ rejection, in adult patients receiving allogeneic kidney transplant , liver transplant , and heart transplant , and pediatric patients receiving allogeneic liver transplants in combination with other immunosuppressants. Additional pediatric use information is approved for Astellas Pharma US, Inc.’s Prograf (tacrolimus) products. However, due to Astellas Pharma US, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.

Dosage and administration (summary)

• Administer capsules consistently with or without food. • Therapeutic drug monitoring is recommended. ( 2.1 , 2.6 ) • Avoid eating grapefruit or drinking grapefruit juice. • See dosage adjustments for African-American patients , hepatic and renal impaired. ( 2.4 , 2.5 ) • For complete dosing information, see Full Prescribing Information. ADULT Patient Population Initial Oral Dosage Whole Blood Trough Concentration Range Kidney Transplant With azathioprine 0.2 mg/kg/day capsules, divided in two doses, every 12 hours Month 1 to 3: 7 to 20 ng/mL Month 4 to 12: 5 to 15 ng/mL With MMF/IL-2 receptor antagonist 0.1 mg/kg/day capsules, divided in two doses, every 12 hours Month 1 to 12: 4 to 11 ng/…

Contraindications

Tacrolimus capsules are contraindicated in patients with a hypersensitivity to tacrolimus. Hypersensitivity symptoms reported include dyspnea, rash, pruritus, and acute respiratory distress syndrome . • Hypersensitivity to tacrolimus or HCO-60 (polyoxyl 60 hydrogenated castor oil).

Warnings and precautions

• Not Interchangeable with Extended-Release Tacrolimus Products – Medication Errors: Instruct patients or caregivers to recognize the appearance of tacrolimus capsules. • New Onset Diabetes After Transplant: Monitor blood glucose. • Nephrotoxicity (acute and/or chronic): Reduce the dose; use caution with other nephrotoxic drugs. • Neurotoxicity: Including risk of Posterior Reversible Encephalopathy Syndrome (PRES); monitor for neurologic abnormalities; reduce or discontinue tacrolimus. • Hyperkalemia: Monitor serum potassium levels.

Pregnancy

Pregnancy Pregnancy Exposure Registry There is a pregnancy registry that monitors pregnancy outcomes in women exposed to tacrolimus during pregnancy. The Transplantation Pregnancy Registry International (TPRI) is a voluntary pregnancy exposure registry that monitors outcomes of pregnancy in female transplant recipients and those fathered by male tr…

Storage and supply

Tacrolimus Capsules, USP Tacrolimus capsules, USP containing white to off-white powder equivalent to 1 mg of anhydrous tacrolimus, are hard gelatin capsules with white opaque body and brown cap. The body is imprinted ‘644’ and cap is imprinted ‘ ’ in black ink.

Source: Tacrolimus (Tacrolimus) — US FDA prescribing information, 2023-10-01, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.