Glutoxim

Pharmacological properties

glutoxim has an immunostimulating, hemostimulating, toxic modifying, hepatoprotective effect, suppresses the drug resistance of tumor cells to anthracycline antibiotics, alkylating agents; allows to overcome the drug resistance of micobacterium tuberculosis to isoniazid associated with the genes katg (catalase peroxidase gene) and inha (phenol apb reductase gene). glutoxim potentiates the effect of doxorubicin on tumor cells, chemotherapy agents (isoniazid, rifampicin, rifabutin, cycloserine, capreomycin, levofloxacin, the cationic antimicrobial catalcidin peptide) on micobacterium tuberculosis.

The immunomodulatory effect of the drug Glutoxim is due to receptor-mediated effects on the calcium-dependent signaling pathways of macrophages, which leads to an increase in:

• survival and functional capacity of tissue macrophages;
• exocytosis of submembrane granules with intracellular parasitic forms of Micobacterium tuberculosis;
• lysosomal enzyme activity;
• the formation of reactive oxygen species;
• absorption and death of microorganisms;
• secretion of cytokines: interlekin-1, interleukin-6, tumor necrosis factor, interferons, erythropoietin, interleukin-2; cationic antimicrobial peptides - defensin, catalecidins.

The hemostatic effect of the drug Glutoxim is due to receptor-mediated increased bone marrow hematopoiesis: the processes of erythropoiesis, lymphopoiesis and granulocytomonocytopoiesis. The effect on the progenitor cells of various lines of blood cells is mediated by the functioning of the MAP and inositol kinase systems, which increases the resistance of hematopoietic cells that differentiate, restores their sensitivity to the action of endogenous factors of hematopoiesis.

The toxic-modifying and hepatoprotective effect of the drug is due to receptor-mediated increased expression of xenobiotic detoxification enzymes of the second phase, including glutathione reductases, glutathione peroxidase, glutathione S-transferase, glucose-6-phosphate dehydrogenase, and hematoxigenase-1-level protection, which increases the level of hematoxigenase level 1, which increases actions of radicals.

Glutoxim has a direct inhibitory effect on the activity of the factor of multidrug resistance of tumor cells - the protein P-glycoprotein (Pgp), which determines the resistance of tumor cells to chemotherapy, including anthracycline antibiotics, drugs with an alkylating effect.

Glutoxim initiates the reaction of the transformation of isoniazid (prodrugs) into a pharmacologically active form - isonicotinic acid, which has a bacteriostatic effect on Micobacterium tuberculosis, due to the negative transformation of the katG (catalase peroxidase gene) and inhA (phenol-APB reductase gene).

Glutoxim stimulates the exocytosis of vesicles from macrophages with intracellular parasitic microorganisms, including Micobacterium tuberculosis, ensuring their removal from the pharmacological storage and making antibacterial drugs available, including isoniazid, rifampicin, rifabutin, cycloserine, caprefomycin.

Glutoxim enhances the secretion of cationic peptides - defensins and catalecidins by macrophages, stimulates their absorption by tuberculosis mycobacteria, determining the mediated antibacterial effect of the drug.

Pharmacokinetics Glutoxim belongs to the group of natural metabolites, which determines the features of its metabolism by existing cellular enzymatic systems. After i / m, iv or s / c injection, bioavailability exceeds 90%. A linear relationship between the dose and the concentration of the drug in the blood plasma is noted. C_max drug in blood plasma with a / in the introduction is achieved within 2-5 minutes, with a / m - within 7-10 minutes. As a natural peptide product, Glutoxim is metabolized in the organs and tissues of the body with elimination by the kidneys.

Indications

As a means of prevention and treatment in adults of secondary immunodeficiency conditions associated with radiation, chemical and infectious factors;

• to restore suppressed immune reactions and an oppressed state of bone marrow hematopoiesis;
• to increase the bodys resistance to various pathological effects - infectious agents, chemical and / or physical factors (intoxication, radiation, etc.);
• as a hepatoprotective agent for chronic viral hepatitis B and C;
• to potentiate the therapeutic effects of antibiotic therapy for COPD;
• for the prevention of postoperative purulent complications;
• as part of a comprehensive anti-tuberculosis therapy of severe common forms of tuberculosis of all localizations;
• in the presence of drug resistance of mycobacterium tuberculosis to drugs;
• for the prevention of exacerbations of chronic hepatitis in patients with tuberculosis on the background of anti-tuberculosis therapy;
• for the treatment of toxic complications of anti-TB treatment;
• in the complex therapy of psoriasis, in particular moderate and severe forms with the presence of erythroderma, arthropathy;
• as part of the complex therapy of malignant neoplasms in oncology for the prevention and treatment of toxic manifestations of chemo- and radiation therapy, namely: it helps to reduce hemo- and hepatotoxic effects, effective restoration of the functions of bone marrow hematopoiesis during antitumor therapy. To eliminate the manifestations of the nonspecific syndrome of the disease (anemia, fatigue, decreased appetite, increased pain sensitivity).

Application

The drug glutoxim is administered in / in, in / m, s / c. 5–40 mg are prescribed daily (50–300 mg per course), depending on the nature of the disease.

For prophylactic purposes, the drug is used IM 5-10 mg daily for 2 weeks.

As part of the complex treatment of tuberculosis, Glutoxim 60 mg is administered once a day for the first 10 days daily i / m, the next 20 days Glutoxim 60 mg is administered i / m every other day, 1 injection per day.

If necessary, conduct a second course of treatment after 1-6 months.

As part of the complex therapy of psoriasis, Glutoxim is used IM daily in a daily dose of 10 mg for 15 days, then another 5 weeks 2 times a week in a daily dose of 10 mg. Only 25 injections per treatment course.

As a means of accompanying chemotherapy in oncology, Glutoxim 60 mg is administered subcutaneously 1.5–2 hours before the use of antitumor agents. Then, between the courses of chemotherapy, Glutoxim 60 mg is administered s.c. every other day. In the next course of chemotherapy, the regimen of the drug is repeated.

As a means of accompanying radiation therapy, Glutoxim 60 mg is administered subcutaneously 0.5-1 hours after the next irradiation session every other day throughout the course of radiation therapy.

Contraindications

The use of the drug is contraindicated in cases of individual hypersensitivity to the components of the drug.

Side effects

In some patients, a slight increase in body temperature (up to 37.1–37.5 ° c), pain at the injection site of the drug can be noted. with poor subjective tolerance of pain, glutoxim is administered together with 1-2 ml of 0.5% Novocaine solution. in such cases, taking into account the safety information for the use of Novocaine, before using the drug, it is necessary to carefully collect an allergological history and make skin tests for compatibility.

Allergic reactions in sensitive patients are possible.

special instructions

As a solution carrier for infusion use 0.9% solution of sodium chloride or 5% solution of glucose.

Use during pregnancy or lactation. Do not use.

Children.Do not use.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Adverse effects not established.

Interactions

Glutoxim, when combined, potentiates the bacteriostatic effect of isoniazid, rifampicin, rifabutin, cycloserine, capreomycin, levofloxacin on micobacterium tuberculosis, the anthracycline antibiotic doxorubicin, the etoposide alkylating agent on tumor cells.

Glutoxim reduces the therapeutic effect of nifedipine and verapamil.

Inhibitors of the cyclooxygenase pathway for the oxidation of arachidonic acid - indomethacin, meloxicam - reduce or completely suppress the pharmacological effect of the drug Glutoxim.

Incompatibility. Glutoxim can be administered in the same syringe with water-soluble drugs. The drug is compatible with solvents such as 0.9% sodium chloride solution or 5% glucose solution.

Overdose

No cases of drug overdose have been reported.

Storage conditions

In the dark place at a temperature of no higher than 25 ° c.