Also known as FK-506 or Prograf, ia an immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient’s immune system and so lower the risk of organ rejection.
Also used in a topical preparation in the treatment of atopic dermatitis, severe refractory uveitis after bone marrow transplants, and vitiligo.
A 23-membered macrolide lactone.
It reduces interleukin-2 (IL-2) production by T-cells.
In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to activate calcineurin.
Calcineurin then dephosphorylates the transcription factor NF-AT (nuclear factor of activated T-cells), which moves to the nucleus of the T-cell and increases the activity of genes coding for IL-2 and related cytokines.
Tacrolimus prevents the dephosphorylation of NF-AT.
In detail, Tacrolimus reduces peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP12 (FK506 binding protein) creating a new complex.
This FKBP12-FK506 complex interacts with and inhibits calcineurin thus inhibiting both T-lymphocyte signal transduction and IL-2 transcription.
Although this activity is similar to cyclosporine, studies have shown that the incidence of acute rejection is reduced by tacrolimus use over cyclosporine.
Although short-term immunosuppression concerning patient and graft survival is found to be similar between the two drugs, tacrolimus results in a more favorable lipid profile.
Dosages are titrated to target blood levels, with starting doses for once daily tacrolimus are 0.15-0.20 mg/kg body weight.
Grapefruit increases plasma-tacrolimus concentration.
Antifungals, especially of the azole class also increase drug levels by competing for degradative enzymes.
Can suppress the inflammation associated with ulcerative colitis.
Side effects include abdominal pain, anorexia, alopecia, anorexia, and bradycardia.
Tacrolimus 0.1% ointment (Protopic), is used in the treatment of eczema, particularly atopic dermatitis, and is equally as effective as a mid-potency steroid.
Unlike steroids, it does not cause skin atrophy or other steroid related side-effects.
Side effects include: infection, cardiac damage, hypertension, blurred vision, liver and kidney problems, hyperkalemia, hypomagnesemia, hyperglycemia, diabetes mellitus, itching, lung damage, loss of appetite, insomnia, Posterior reversible encephalopathy syndrome, confusion, weakness, depression, cramps, neuropathy, seizures, tremors, and catatonia.
Tacrolimus contributes to the frequent development of new diabetes following renal transplantation.
May potentially increase the severity of existing fungal or infectious conditions such as herpes zoster or polyoma viral infections.
Increased risk of malignancy is a recognized complication.
In people receiving this agent as an immunosuppressant, an increase risk of malignancy is a noted complication, with the most common cancers non-Hodgkin’s lymphoma and skin cancers.
The risk of malignancy is related to the intensity and duration of treatment.
The most common adverse events associated with the use of topical tacrolimus, especially if used over a wide area, include a burning or itching sensations and less common flu-like symptoms, headache and cough and burning eyes.
Topical tacrolimus should be avoided in known or suspected malignant lesions.
With topical treatment there should be minimalization of natural or artificial sunlight exposure, and should not be used with occlusive dressings.