Advagraf

Advagraf belongs to the pharmacotherapeutic group of immunosuppressants (immunosuppressants), which are used for artificial suppression of immunity. International non-proprietary name Tacrolimus. Manufacturer - Astellas Pharma Europe BV (Netherlands), Astellas Ireland Co.Ltd. (Ireland).

Other trade names: Tacrolimus, Tacrolimus-Teva, Prograf, Fujimitsin.

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Indications of the advagraf

The drug Advagraf is used in transplantology to prevent the rejection of transplanted donor internal organs - liver, kidney or heart allografts. And also for the treatment of adults with symptoms of rejection of allografts while not taking medication suppression of immunity by other means.

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Release form

Form release: capsules prolonged action of 0.5 mg, 1 mg and 5 mg.

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Pharmacodynamics

Pharmacological action Advagraf provides the active substance tacrolimus - a natural macrolide macrolactam ascomycin (tacrolimus), produced by the actinobacterium Streptomyces tsukubaensis.

The termination of the reaction of rejection by the organism of a transplanted organ or tissue is carried out by suppressing the T-cell reaction against foreign HLA antigens, as well as overlapping the transmission of T-cell signals through the calcium channels.

Tacrolimus binds to the cytosolic protein of T-lymphocyte cells by macrophylline-12 and blocks the enzyme calcineurin (CaN). As a result, the formation of T-cytotoxic lymphocytes and cytokines (in particular, interleukins and interferon gamma, stimulating the cells of the immune system) is suppressed and the intensity of proliferation of B-lymphocytes that produce antibodies decreases.

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Pharmacokinetics

After ingestion, the active substance of the drug Advagraf is absorbed in the upper gastrointestinal tract, enters the bloodstream and binds to blood plasma proteins, the maximum concentration in the blood plasma comes about two hours later.

Biological availability of the drug is 20-25%; the rate of purification of body fluids from tacrolimus ranges from 4 to 6.7 liters per hour (depending on the transplant organ); the half-life is about 43 hours.

Transformation Advagraf occurs in the liver and intestines. Metabolites are excreted with bile. In the unchanged form with urine and feces, no more than 1% of the active substance is eliminated.

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Dosing and administration

The ad-glograph is intended for oral administration: once a day, 1 hour before meals or 2.5 hours after a meal, with water.

The advagraf is used exclusively by the doctor's prescription, which determines the dose of the drug individually. After a kidney or liver transplant, 0.2-0.3 mg per kilogram of body weight (once a day) is prescribed, to prevent rejection of the allograft - 0.1-0.2 mg / kg (once a day, in the morning).

During the administration of the drug, Advagraf should monitor the level of tacrolimus in the blood - to maintain and retain the necessary therapeutic concentration of the drug in the body.

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Use of the advagraf during pregnancy

Use The advagraf during pregnancy is not recommended, since tacrolimus penetrates the placenta, and its safety for the fetus has not been fully established.

Contraindications

Contraindications to the use of this drug is the individual hypersensitivity to tacrolimus, other drugs of the macrolide group or the auxiliary components that make up the capsules of Advagraf.

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Side effects of the advagraf

Among the most frequent side effects of the Advagraf are: headache and joint pain, nausea, diarrhea, increased blood pressure, tremor, sleep disorders, kidney dysfunction, increased levels of glucose and potassium in the blood.

Often side effects of the Advagraf are manifested in the form of dizziness and noise in the ears,

Dyspnea, pharyngitis, cough, rhinitis, cardiac arrhythmias, lowering blood pressure, anemia, peripheral circulation disorders, changes in blood (leukopenia, thrombocytopenia, leukocytosis), seizures and paresthesias, ulcers of the oral mucosa, abdominal pain and inflammation of the gastrointestinal tract.

There may also be vomiting, flatulence, constipation, acute kidney failure (up to toxic nephropathy) and decreased diuresis, damage to liver and gall bladder cells, itchy skin rashes, hair loss, increased sweating. From the side of the central nervous system, depression-anxious states, confusion of consciousness and various psycho-emotional disorders are observed.

It should also be borne in mind that therapy with immunosuppressant drugs significantly increases the risk of malignant neoplasms.

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Overdose

Advagraf shows headache, trembling of the limbs, nausea and vomiting, hives, a violation of protein metabolism (increases the level of urea nitrogen in the blood). Perhaps the onset of lethargy.

When an overdose is symptomatic treatment - after washing the stomach and taking adsorption.

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Interactions with other drugs

Increase the concentration of Advagraf in the blood, simultaneous use of antifungal drugs (fluconazole, ketoconazole, etc.), antibiotics of the macrolide group.

Reduction in the therapeutic level of Advagraf in the blood is promoted by corticosteroids, phenobarbital, rifampicin, phenytoin, carbamazepine, metamizole, isoniazid, preparations based on St. John's Wort.

Slow biotransformation of Advagraf drugs such as lidocaine, mefenitoin, miconazole, quinidine, tamoxifen, ergotamine, gestodene, oleandomycin, cortisone, bromocriptine. Increase the removal time of the Advagraf from the body of magnesium hydroxide and aluminum, cimetidine, cisapride and metoclopramide.

Increase the toxic effect of tacrolimus on the kidneys at the same time taking non-steroidal anti-inflammatory drugs and aminoglycosides.

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Storage conditions

Storage conditions Advagraf: at a temperature not higher than 24-25 ° C.

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Shelf life

Shelf life is 3 years, after the opening of the aluminum package - 12 months.

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