How tacrolimus works
Tacrolimus, as an immunosuppressant, prevents the release of cytokines (special proteins) in the T cells – activation of the immune system is suppressed.
The function of the immune system in the human body is mediated mainly by the white blood cells circulating in the blood. A subset of these leukocytes are the so-called T cells or T lymphocytes.
After their formation in the bone marrow, these migrate via the bloodstream to the thymus (gland behind the breastbone) to mature. In the process, they “learn” to distinguish the body’s own from foreign structures.
These foreign structures can be, for example, body cells that are infected with viruses and thus carry foreign proteins on their surface. But also human organs that originate from other people (organ transplants) can be recognized as foreign by immune cells.
Absorption, degradation and excretion
After ingestion of tacrolimus as a tablet, capsule or drink suspension, the active ingredient is absorbed into the blood via the gastrointestinal tract. The highest blood levels occur after one to three hours.
Of the total ingested dose, about one quarter reaches the major bloodstream, with large interindividual variations. The drug is already partially broken down in the intestinal wall, and after absorption into the blood, it is further broken down in the liver. At least nine metabolites (intermediate product of metabolism) are formed.
The so-called half-life – the period of time after which half of the absorbed amount of active ingredient is excreted again – also varies greatly for tacrolimus and is around 43 hours, with an average of 16 hours in kidney-transplanted adults. Excretion occurs mainly through the bile in the stool.
When is tacrolimus used?
As tacrolimus ointment, the active ingredient is used for maintenance therapy or to treat an eczema flare-up in patients with atopic eczema (neurodermatitis) in moderate and severe cases.
Tacrolimus is usually used on a long-term to lifelong basis. In the external treatment of atopic eczema, the duration of treatment depends on the course of the disease.
How tacrolimus is used
Tacrolimus is usually administered under medical supervision at the beginning of internal use. In this process, the doctor checks the individual tacrolimus absorption into the body and measures the blood levels of the immunosuppressant over a few days.
Tacrolimus is taken fasting one hour before or two to three hours after a meal with a glass of water. Simultaneous food intake inhibits tacrolimus absorption into the blood and may limit the immunosuppressive effect.
Tacrolimus ointment should be applied twice daily at the beginning of treatment. After significant improvement of symptoms, application may be reduced.
What are the side effects of tacrolimus?
Side effects occur especially when taken as a tablet, capsule, or drink suspension. In most cases, treatment with tacrolimus ointment leads at most to local irritation and increased sensitivity of the creamed areas to sunlight.
The following side effects are also common: Anemia, low electrolyte levels in the blood, decreased appetite, high blood lipid levels, confusion, anxiety, nightmares, depression or other mental illness, convulsions, sensory disturbances, nerve pain, visual disturbances, ringing in the ears, rapid heartbeat, bleeding, Blood clotting disorders with clot formation, shortness of breath, cough, sore throat, inflammation of the gastrointestinal tract, abdominal pain, vomiting, constipation, indigestion, liver inflammation, altered liver enzymes, sweating, itching, skin rash, and muscle and joint pain.
What should I watch for while taking Tacrolimus?
Drug interactions
Since the level of tacrolimus in the blood is crucial for the effectiveness of the immunosuppressant, the preparation must not be changed during treatment. It must therefore always be obtained from the same company.
Tacrolimus is metabolized in the liver by the cytochrome P450-3A4 enzyme. This also metabolizes numerous other active substances. Concomitant use may therefore lead to changes in blood levels: Some agents can accelerate the degradation of tacrolimus, others delay it, which can have a major impact on its efficacy.
The list of these drugs is extensive, which is why the intake should be clarified with the doctor or pharmacist in each individual case and with each new drug prescription. For example, these include antibiotics, antifungal agents, agents for HIV infections, and also herbal remedies such as St. John’s wort.
Tell your doctor and pharmacist that you are taking tacrolimus. This will help avoid drug interactions from the start.
Age restriction
Tacrolimus ointment is approved for use in children two years of age and older.
Pregnancy and lactation
The use of tacrolimus during pregnancy, because on the one hand the data situation is not sufficient and on the other hand dangerous effects on the child have been shown by the use of the immunosuppressive drug.
However, patients who are stable on tacrolimus should not be switched. In this case, it may continue to be prescribed after a risk-benefit assessment in those who wish to have children and during pregnancy.
Breastfeeding is allowed with tacrolimus.
Tacrolimus ointment may be prescribed during pregnancy and breastfeeding only if clearly necessary due to the lack of data.
How to obtain medication with tacrolimus
Since when is Tacrolimus known?
Tacrolimus was discovered in 1987 in the soil bacterium Streptomyces tsukubaensis. It was the second highly effective immunosuppressant after rapamycin (also known as sirolimus), which had been discovered previously in 1975.
The drug was first approved in the United States in 1994 for the treatment of liver transplant patients, and later for recipients of other donor organs. In Germany, the drug was first approved in 1998. In the meantime, there are numerous generics containing tacrolimus on the German market.
