Tacrolimus (tacrolimus)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Tacrolimus, a calcineurin inhibitor, is a potent immunosuppressive agent.
Tacrolimus is a macrolide antibiotic produced by Streptomyces tsukubaensis. The drug is a potent immunosuppressive agent that is pharmacologically but not structurally related to cyclosporine and that exhibits only limited antimicrobial activity. Tacrolimus is approximately 10- to 200-fold more potent than cyclosporine on a weight basis in various in vitro T-cell test systems of immune function.
In animals, tacrolimus inhibits cell-mediated immune responses such as allograft rejection, delayed hypersensitivity, collagen-induced arthritis, experimental allergic encephalomyelitis, and graft-vs-host disease while humoral immunity is inhibited to a lesser extent. Increased survival of the host and of the transplanted graft of liver, kidney, heart, bone marrow, small bowel, pancreas, lung, trachea, skin, cornea, and limb has been shown in animals receiving the drug.
The exact mechanism(s) of immunosuppressive action of tacrolimus has not been elucidated but appears to involve inhibition of the activation and proliferation of T cells, as well as T helper cell dependent B-cell response. Studies suggest that tacrolimus binds to an intracellular protein, FKBP-12. Binding of the complex of tacrolimus and FKBP-12 with calcium, calmodulin, and calcineurin inhibits the phosphatase activity of calcineurin, which may prevent the dephosphorylation and translocation of nuclear factor of activated T cells (NF-AT).
NF-AT putatively initiates gene transcription for the formation of lymphokines (e.g., interleukin-2, gamma interferon) involved in the activation of T cells.
Tacrolimus immediate-release oral preparations (conventional capsules, granules for oral suspension) are used in combination with other immunosuppressants for the prevention of organ rejection in adult and pediatric patients receiving kidney, liver, heart, or lung allografts. A parenteral preparation of tacrolimus is available for IV use in patients who cannot tolerate oral formulations; patients should be converted from IV to oral therapy as soon as oral therapy is tolerated. Tacrolimus also is available as extended-release capsule and tablet formulations for the prevention of rejection of kidney allografts.
Generic name: tacrolimus
Pronunciation: (ta-KROE-li-mus)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Tacrolimus
Indications
The following indications are listed for Tacrolimus:
- Immunosuppression Maintenance Therapy For Lung Transplantation
- Prevention Of Cardiac Transplant Rejection
- Prevention Of Kidney Transplant Rejection
- Prevention Of Liver Transplant Rejection
Also known as: Cardiac Transplant Rejection Prophylaxis, Heart Transplant Rejection Prophylaxis, Hepatic Transplant Rejection Prophylaxis, Kidney Transplant Rejection Prophylaxis, Liver Transplant Rejection Prophylaxis, Maintenance Immunosuppression Following Lung Transplant, Renal Transplant Rejection Prophylaxis.
Dosing
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.
Tacrolimus is administered orally as immediate-release capsules, granules for oral suspension, or extended-release capsules and tablets; tacrolimus also may be administered by IV infusion. Because of the risk of anaphylaxis, IV administration of the drug should be reserved for patients who cannot tolerate oral administration. If therapy is initiated with the IV formulation, substitute oral therapy as soon as tolerated. Extended-release formulations of the drug are indicated only in kidney transplant patients.
Because of differences in pharmacokinetic properties, extended-release preparations are not interchangeable with each other or with tacrolimus immediate-release capsules or granules for suspension. When converting between immediate-release capsules and granules for suspension, the total daily dosage should remain the same; therapeutic drug monitoring is recommended when switching between tacrolimus formulations.
Store tacrolimus capsules and granules for oral suspension at 20 to 25oC and extended-release capsules and extended-release tablets at 25degreesC; with excursions permitted between 15 to 30degreesC. Store tacrolimus injection between 5 to 25degreesC.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Tacrolimus is metabolized by CYP isoenzymes, principally CYP3A.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity to tacrolimus or any ingredient in the formulation (e.g., polyoxyl 60 hydrogenated castor oil (HCO-60) in the IV formulation). Dyspnea, rash, pruritus, and acute respiratory distress syndrome have been reported.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
There is no enhanced messaging for this drug.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and effectiveness have been established in pediatric liver, kidney, heart, and lung transplant patients in clinical studies. Clinical experience in children suggests that the safety and efficacy of tacrolimus are similar to those in adults.
A randomized, active-controlled study of tacrolimus in primary liver transplantation of pediatric patients <=16 years of age included 91 patients who were randomized to tacrolimus-based therapy and 90 patients receiving cyclosporine-based therapy. At 12 months, the incidence rate of biopsy-proven acute rejection, graft loss, death, or loss to follow-up was 52.7% in the tacrolimus group and 61.1% in the cyclosporine group.
Efficacy and safety of tacrolimus immunosuppression in pediatric lung transplation were also established in 450 patients receiving tacrolimus immediate-release products in combination with mycophenolate mofetil or 72 patients receiving tacrolimus immediate-release products in combination with azathioprine; one-year graft survival estimates from time of discharge were 91.7% and 84.7%, respectively.
Pharmacokinetic studies have been conducted in pediatric patients, with dosage adjustments made based on clinical status and whole blood concentrations. Pediatric patients generally require higher doses of tacrolimus to maintain trough whole blood concentrations similar to adult patients.
Tacrolimus may cause fetal harm if administered to pregnant females. Data from postmarketing surveillance and The Transplantation Pregnancy Registry International (TPRI) suggest that infants exposed to tacrolimus in utero are at a risk of prematurity, birth defects/congenital anomalies, low birth weight, and fetal distress. Females of reproductive potential should use effective birth control prior to intitation and during tacrolimus treatment. Males who have female partners who are able to become pregnant should also use effective birth control before and during treatment with tacrolimus.
TPRI is a voluntary pregnancy exposure registry that monitors outcomes of pregnancy in female transplant recipients and those fathered by male transplant recipients exposed to immunosuppressants including tacrolimus; clinicians are encouraged to advise their patients to register by contacting the TPRI at 1-877-955-6877 or their website https://www.transplantpregnancyregistry.org/.
Tacrolimus may increase hyperglycemia in pregnant females with diabetes; monitor blood glucose levels regularly. Tacrolimus also may exacerbate hypertension in pregnant females and increase the risk of pre-eclampsia, therefore blood pressure should be monitored and controlled.
Tacrolimus has been reported to be distributed into human milk; however, the effects on the infant or milk production has not been assessed. Consider the benefits of breast-feeding along with the importance of tacrolimus to the mother and any potential adverse effects on the breast-fed infant from the drug or the underlying maternal condition.
Insufficient experience in patients >=65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.
If evidence of renal impairment exists or develops, adjust dosage.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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