Mechanism of Action of Tacrolimus, Its Uses, Contraindications, Side Effects, Effectiveness, Precautions, Dosage

What is Tacrolimus?

Tacrolimus is a drug that is used to suppress the immune system of the body after an organ transplantation surgery or in auto-immune diseases. This happens due to the fact that for the body the newly transplanted organ is a foreign substance and so the body’s immune system tries to reject it. Therefore, tacrolimus is basically used to control that overthrowing reaction of the body and preserve the organ. These kinds of drugs which suppress body’s immune response are known as immunosuppressive drugs.

Tacrolimus is a macrolide lactone molecule. Tacrolimus was first discovered when a sample of Japanese soil was fermented and the fermented broth consisted of Streptomyces tsukubaensis bacterium. It was first discovered in 1987.

Tacrolimus is also known by some other names. Some of these are FK-506 and fujimycin. Some commercial names for the drug include Prograf, Advagraf, Astragraf XL, Envarsus XR and Protopic.

Mechanism of Action of Tacrolimus

Mechanism of Action of Tacrolimus

Mechanism of action of tacrolimus includes suppression of the immune system by inhibiting the production of Interleukin-2. Our body has a type of immune response called acquired immune response which creates a memory for the body after an infection from a certain pathogen, so that when the body suffers from the same infection again, it will be able to fight against the infection even more vigorously.

T-cells which are a type of lymphocytes or White Blood Cells (WBC) are actually quite necessary for the body’s acquired immune response and interleukin-2 promotes the development and proliferation of T-cells. Tacrolimus by inhibiting interleukin-2; which is a protein and a cytokine signaling molecule of the immune system, also inhibits body’s immune response. Thus it helps the body in retaining newly transplanted organs.

So the mechanism of action of tacrolimus is actually focused on the inhibition of interleukin-2.

Uses of Tacrolimus

Tacrolimus is used for a variety of diseases. Apart from oral use and injections, tacrolimus is also used topically for curing some skin diseases. Some of the uses of tacrolimus are given here:

Use of Tacrolimus after Organ Transplantation

Tacrolimus is used as an immunosuppressant drug after organ transplantation such as kidney transplantation, heart transplantation and liver transplantation. It is usually given along with some other drugs including steroids. Even though drug cyclosporine is also prescribed as an immunosuppressant after transplantation, it is found that tacrolimus is more effective than cyclosporine. For use as an immunosuppressive drug, tacrolimus is given either orally or patient is injected with it.

Dermatological Use of Tacrolimus

Tacrolimus is used for the treatment of eczema. It is especially effective in the treatment of atopic eczema. Tacrolimus is as effective in the treatment of eczema as a steroid of medium potential. Tacrolimus also works in the same way as steroids.

The only difference is that it does not cause atrophy or thinning of the skin, which is a side effect related to the use of steroid for the treatment of eczema.

For dermatological use, tacrolimus is used as an ointment and applied over the lesions until they heal.

Use of Tacrolimus for Ulcerative Colitis

Ulcerative colitis is a type of inflammatory bowel disease and tacrolimus has been found to be quite effective for the treatment of ulcerative colitis. But the use of tacrolimus for the treatment of ulcerative colitis is only limited to trial cases and has not yet been used in regular cases.

Contraindications of Tacrolimus

There are some contraindications of tacrolimus as well. There are some conditions in which tacrolimus may prove to be quite harmful and sometimes even lethal, so the people who have these conditions are advised to discuss their problems with their doctors and should not use this drug. Some of the contraindications of Tacrolimus include:

  • One contraindication is that tacrolimus should not be taken by pregnant or breast feeding ladies.
  • Tacrolimus should not be given to infants.
  • Those who are already suffering from some type of cancer should not take tacrolimus.
  • Tacrolimus should not be used topically by those who have malignant lesions.
  • People suffering from hepatic disease should also not use tacrolimus.

Dosage of Tacrolimus

Different doctors may prescribe different dosage of tacrolimus based on your medical condition, your weight and your response to the drug. Some tests are also done to determine the dosage of tacrolimus. These tests usually evaluate how much tacrolimus is present in your blood. But in most of the cases it is given orally twice a day at an interval of about 12 hours.

Injection of tacrolimus is only given to those patients who are unable to tolerate tacrolimus orally. The amount of tacrolimus dose given varies from patient to patient.

Side-Effects of Tacrolimus

Tacrolimus drug is actually associated with many side effects but remember that a doctor only prescribes a potentially harmful drug when the benefits far outweigh the danger. So even though the drug has many side effects, it is still very much in practice. Some of these side effects of Tacrolimus are as follows:

  • Use of tacrolimus can lead to infection.
  • Tacrolimus use can also lead to such side effects as cardiac damage, lung damage and various problems of kidney and liver.
  • Hyperkalemia, hypomagnesemia and hypertension are also some of the side effects associated with tacrolimus use.
  • Apart from these side effects, tacrolimus can also cause hyperglycemia and diabetes mellitus.
  • Tacrolimus side effects also include neuropsychiatric problems such as seizures, tremors, loss of appetite, insomnia, posterior reversible encephalopathy syndrome, confusion, weakness, depression and catatonia.
  • Tacrolimus also poses a higher risk of cancer as it is found that people who are taking immunosuppressant drugs have a higher risk of getting cancer.
  • Topical use of tacrolimus can lead to an itching or burning sensation and higher sensitivity at the area of application.
  • Topical application of tacrolimus can also cause flu like symptoms, headache and cough etc.
  • It may also worsen the condition of already existing fungal or any other type of infections.
  • The most common types of cancers usually caused by tacrolimus are skin cancer and lymphoma.
  • Tacrolimus can also lead to upset stomach, stomachache, nausea, vomiting or diarrhea.
  • Some hearing problems such as hearing loss or ringing in the ears can also be caused by tacrolimus use.

Precautions of Tacrolimus

Certain precautions should also be taken by people who are using tacrolimus as there are some things associated with this drug which can prove to be very harmful if due attention is not paid to them. Some of these precautions are as follows:

  • Listen to your doctor carefully and follow their instructions.
  • Fix a time for your tacrolimus medicine and always take it at the same time.
  • If you miss a dose of tacrolimus, take it as soon as you remember but if it is time for the next dose, miss the first one. Do not take it twice at the same time.
  • You can take tacrolimus with or without food. Food can keep the body from absorbing more of the medicine, especially fatty foods and thus keeps its concentration in the blood to a minimum.
  • Make sure you are taking tacrolimus in the same way, whether it is with food or without food and taking it in the same way everyday so as to keep its quantity roughly same in your body.
  • Do not increase or decrease your dosage of tacrolimus without consulting your doctor.
  • In case of an over-dosage of tacrolimus, consult your doctor or emergency medical services of your country immediately.
  • Do not stop taking tacrolimus without asking your physician.
  • Do not eat grapefruit, its juice or anything made from it as it can increase the quantity of tacrolimus in blood by absorbing more of it.
  • Consult your doctor immediately if you experience any of the above mentioned side effects as well as any other problem.

Effectiveness of Tacrolimus

Tacrolimus is actually quite effective as an immunosuppressant. But as with any other medicine, tacrolimus also is not without its own fair share of side-effects. So before you start taking tacrolimus, you should be sure that you absolutely need it.

As far as topical application of tacrolimus is concerned, it is actually more effective than steroid as it does not cause as many side effects as steroids.

In the treatment of ulcerative colitis also, tacrolimus has been found to be quite effective. Even though it is still at the trial stage, all the trials have so far been successful and effective.

So these are some of the common things related with tacrolimus use and hopefully it will help you in making a correct and informed decision regarding the use of tacrolimus.

Pramod Kerkar, M.D., FFARCSI, DA
Pramod Kerkar, M.D., FFARCSI, DA
Written, Edited or Reviewed By: Pramod Kerkar, M.D., FFARCSI, DA Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:August 3, 2017

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