Glutoxim solution for injection. 3%, 2ml # 5

• Prevention and treatment of secondary immunodeficiency conditions associated with radiation, chemical and infectious factors;

• restoration of suppressed immune reactions and a depressed state of bone marrow hematopoiesis;

• increasing the body's resistance to various influences (infection, intoxication, radiation);

• as a hepatoprotective agent for chronic viral hepatitis B and C;

• potentiation of the therapeutic effects of antibacterial therapy of chronic obstructive pulmonary diseases;

• prevention of postoperative purulent complications;

• severe, common forms of tuberculosis of various localization (as part of complex therapy);

• drug-resistant tuberculosis;

• prevention of exacerbations of chronic hepatitis in patients with tuberculosis against the background of anti-tuberculosis therapy;

• treatment of toxic complications of anti-tuberculosis therapy;

• as part of complex therapy for uncomplicated forms of psoriasis, incl. as part of the complex therapy of drop-shaped and exudative forms of psoriasis, with psoriatic erythroderma and arthropathic psoriasis, in patients with toxic or viral hepatitis, manifestations of a nonspecific syndrome of chronic diseases;

• as part of the complex therapy of malignant neoplasms - for the prevention and treatment of toxic manifestations of chemotherapy and radiation therapy (helps to reduce hematotoxic and hepatotoxic effects).

  GlutoximЃ promotes effective restoration of the functions of bone marrow hematopoiesis during antitumor therapy. GlutoximЃ eliminates or smoothes the manifestations of a nonspecific disease syndrome (anemia, fatigue, loss of appetite, increased pain sensitivity).

V / v, v / m, s / c. Daily 5-40 mg, depending on the nature of the disease (for 1 course - 50-300 mg). In the treatment of chronic diseases of the respiratory system, diseases of the genitourinary system, atopic allergy, the duration of the course is 2-3 weeks. As part of the complex therapy of tuberculosis - 60 mg / day (30 mg 2 times a day) daily for 2 months. After the transition of specific inflammation to the productive phase, 10Ц20 mg intramuscularly is prescribed 1Ц2 times a day (morning and evening) 3 times a week. A second course, if necessary, in 1Ц6 months.

With psoriasis, daily at 10 mg / day for 15 days, then another 10 injections 2 times a week / m. In uncomplicated forms of psoriasis - 10 ml / day for 10 days in / m.

For prophylactic purposes: 5-10 mg daily, intramuscularly.

Solution for injection is colorless or weakly colored, transparent, odorless or with a faint odor of acetic acid.

1 ml

glutamyl-cysteinyl-glycine disodium 10 or 30 mg

Excipients: sodium acetate, acetic acid (diluted to pH 6.0), water d / i.

• Hypersensitivity

• pregnancy, breastfeeding.

pharmachologic effect

GlutoximЃ has an immunomodulatory, hemostimulating, detoxifying, hepatoprotective effect, suppresses the drug resistance of tumor cells to anthracycline antibiotics, alkylating agents; allows to overcome the drug resistance of Mycobacterium tuberculosis to isoniazid associated with genes katG (catalase-peroxidase gene) and inhA (enol-ACP reductase gene). GlutoximЃ potentiates the effect of doxorubicin on tumor cells, chemotherapy agents (isoniazid, rifampicin, rifabutin, cycloserine, capreomycin, levofloxacin, cationic antimicrobial peptide catalecidin) on Mycobacterium tuberculosis.

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

• survival and functional capacity of tissue macrophages;

• exocytosis of submembrane granules with intracellularly parasitic forms of Mycobacterium tuberculosis;

• activity of lysosomal enzymes;

• the formation of reactive oxygen species;

• absorption and death of microorganisms;

• secretion of cytokines: interleukin 1, interleukin 6, TNF, interferons, erythropoietin, interleukin 2; cationic antimicrobial peptides-defensins, catalecidins.

The hemostimulating effect of GlutoximЃ is due to a receptor-mediated increase in bone marrow hematopoiesis: the processes of erythropoiesis, lymphopoiesis and granulocyto-monocytopoiesis. The action on progenitor cells of different lines of blood corpuscles is mediated by the functioning of MAP- and inositol kinase systems, leads to an increase in the resistance of differentiating hematopoietic cells, restores their sensitivity to the action of endogenous hematopoietic factors.

The detoxifying and hepatoprotective effects of the drug are due to the receptor-mediated increase in the expression of enzymes of the second phase of detoxification of xenobiotics, including glutathione reductase, glutathione peroxidase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase, heme oxygenase-1 actions of radicals.

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

GlutoximЃ initiates the transformation reaction of isoniazid - a prodrug, into a pharmacologically active form - isonicotinic acid, which has a bacteriostatic effect on Mycobacterium tuberculosis, which makes it possible to overcome the drug resistance of Mycobacterium tuberculosis caused by the negative transformation of the genes katG (gene of catalase and inAh -reductase).

GlutoximЃ stimulates the processes of exocytosis of vesicles from macrophages with intracellularly parasitic microorganisms, including Mycobacterium tuberculosis, ensuring their removal from the pharmacological shelter and making antibacterial drugs available for the action of antibacterial drugs, including isoniazid, rifampicin, rifabutin, cycloserine, levofreomycin.

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

Pharmacokinetics

Suction

It belongs to the group of natural metabolites, which determines the characteristics of its metabolism by existing cellular enzymatic systems. After intramuscular, intravenous or subcutaneous administration, bioavailability exceeds 90%. There is a linear relationship between the dose and the concentration of the drug in the blood plasma. Cmax after intravenous administration is achieved within 2-5 minutes, after intramuscular administration - within 7-10 minutes.

Metabolism and excretion

As a natural product of peptide nature, it is metabolized in the organs and tissues of the body. It is excreted in the urine.

Side effect

Perhaps: in some cases - an increase in body temperature (37.1-37.5 ? C), soreness at the injection site (to reduce pain, it is possible to administer the drug simultaneously with 1-2 ml of 0.5% novocaine solution).

Application during pregnancy and lactation

Clinical studies of the use of the drug GlutoximЃ during pregnancy and lactation (breastfeeding) have not been conducted.

special instructions

GlutoximЃ is an innovative Russian drug, a representative of a new class of drugs - innate defense regulators (IDR). The drugs of this group, according to their pharmacological activity, belong to antibiotic adjuvants: the main effect of Glutoxim is the potentiation of anti-tuberculosis chemotherapy, incl. increasing the availability of mycobacterium tuberculosis to the action of drugs and overcoming the drug resistance of the pathogen.

According to the results of basic and clinical studies, GlutoximЃ enhances the secretion of endogenous antibiotics by macrophages - cationic antimicrobial peptides (CAP) (defensins and catalecidins), stimulates their absorption by mycobacteria. The action of CAP leads, mainly, to disruption of the structure and functions of the cytoplasmic membrane of the pathogen, which, in turn, leads to the death of the latter. The antibacterial activity of the GlutoximЃ drug is manifested when it is administered in vivo, requires for its implementation the presence of a pool of endogenous CAPs capable of mobilization, i.e., in relation to the action of the drug, CAPs act as effector molecules, predetermining its indirect antibacterial effect.

The effect of the drug is complemented by the effect of overcoming the drug resistance of Mycobacterium tuberculosis to isoniazid. GlutoximЃ initiates the transformation reaction of isoniazid (prodrug) into a pharmacologically active form - isonicotinic acid, which has an antimycobacterial effect against the pathogen, which makes it possible to overcome the drug resistance of Mycobacterium tuberculosis caused by negative transformation of the katG genes (catalase-peroxidase gene (gene -reductase). The action of the drug is accompanied by an increase in the production of peroxynitrite and nitozoglutathione - compounds with an independent bactericidal effect.

It has also been shown that GlutoximЃ limits the possibilities of intracellular parasitism of Mycobacterium tuberculosis. The drug stimulates the exocytosis (excretion) of vesicles with intracellularly parasitic mycobacteria from macrophages, ensuring their removal from the pharmacological shelter and making them available for the action of antibacterial drugs, including isoniazid, rifampicin, rifabutin, cycloserine, capreomycin, levofloxacin. The pharmacological effect of Glutoxim in relation to the antibacterial activity of the listed antibiotics is potentiating, because increases the availability of the target (microorganisms) to the action of the drug.

GlutoximЃ increases the frequency of bacterial excretion cessation and shortens the period of sputum abacillation. By the end of the 2nd month of treatment among patients receiving GlutoximЃ, bacterial excretion had ceased in 91.1% of patients with drug-susceptible tuberculosis (vs 61.1% in the control group) and in 75.1% of patients with drug-resistant tuberculosis (vs 38.9% in the control) (p <0.05). Acceleration of the termination of bacterial excretion determines the high clinical and economic efficiency of the drug. When using the drug GlutoximЃ, the terms of resorption of infiltrative and focal changes in the lungs are reduced: by the end of the 2nd month of treatment, resorption of infiltrative and focal changes was detected in 93.2% of patients who received GlutoximЃ along with chemotherapy (vs 62.2% of patients in the control group) ( p <0.05).At the end of 4 months of polychemotherapy, closure of the decay cavities occurred in 88.3% of patients receiving GlutoximЃ (vs 70.8% of patients in the control group) (p <0.05).

GlutoximЃ improves the tolerance of anti-tuberculosis chemotherapy: toxic reactions (increased activity of ALT, ACT, bilirubin, serum creatinine) were observed in only 4.3% of patients, while in the control group - in 11.1% of patients (p <0.05). Toxic-allergic reactions (eosinophilia, decreased appetite, severity and pain in the right hypochondrium, nausea caused by the use of rifampicin and high doses of isoniazid) were significantly less common when GlutoximЃ was prescribed - in 6.4% of patients, with 20% in the control group (p < 0.05). Symptoms of intoxication (fever, weakness, feeling unwell, etc.) in patients receiving GlutoximЃ were eliminated mainly in the first 2 months of treatment. GlutoximЃ prevents exacerbation of chronic hepatitis during chemotherapy for tuberculosis,and in case of already developed drug-induced liver damage, it allows to continue chemotherapy in full, without resorting to its temporary cancellation. GlutoximЃ reduces the incidence of toxic hepatitis by more than 4 times.

GlutoximЃ in combination with chemotherapy makes it possible to quickly prepare patients for surgical treatment - the drug increases the frequency of sputum abacillation and contributes to the disappearance or significant reduction in the frequency and intensity of clinical and laboratory symptoms of the disease in patients who are to undergo surgical treatment. In patients with drug-resistant tuberculosis who received in the preoperative period along with anti-tuberculosis chemotherapy GlutoximЃ, a positive dynamics of clinical and laboratory symptoms of the disease is observed 2 times more often (59.6% vs 28.9%), cessation of bacterial excretion is observed 1.9 times more often (38.3% vs 20% - in control). GlutoximЃ improves the immediate results of surgical treatment. Restoration of pneumatization of the lung tissue by 21 days of the postoperative period occurs in 82% of patients,who received GlutoximЃ along with anti-tuberculosis chemotherapy, and only in 35% of patients who received chemotherapy alone. Postoperative complications (pleural empyema, progression of a specific process, nonspecific pneumonia) in patients treated with GlutoximЃ develop 4.5 times less frequently (6.9% vs 32%) than in patients treated with chemotherapy alone (p <0.05). Recovery without complications was noted in 64.9% of the operated patients, while in the control group - only in 41.4% (p <0.05). The average hospital stay in patients receiving GlutoximЃ was 1.5 times shorter and amounted to 42.1 ± 1.7 bed-days, and in patients receiving only chemotherapy - 62.3 ± 8.1 bed-days (p <0.05).Postoperative complications (pleural empyema, progression of a specific process, nonspecific pneumonia) in patients treated with GlutoximЃ develop 4.5 times less frequently (6.9% vs 32%) than in patients treated with chemotherapy alone (p <0.05). Recovery without complications was noted in 64.9% of the operated patients, while in the control group - only in 41.4% (p <0.05). The average length of hospital stay in patients receiving GlutoximЃ was 1.5 times shorter and amounted to 42.1 ± 1.7 bed-days, and in patients who received only chemotherapy - 62.3 ± 8.1 bed-days (p <0.05).Postoperative complications (pleural empyema, progression of a specific process, nonspecific pneumonia) in patients treated with GlutoximЃ develop 4.5 times less frequently (6.9% vs 32%) than in patients treated with chemotherapy alone (p <0.05). Recovery without complications was noted in 64.9% of the operated patients, while in the control group - only in 41.4% (p <0.05). The average hospital stay in patients receiving GlutoximЃ was 1.5 times shorter and amounted to 42.1 ± 1.7 bed-days, and in patients receiving only chemotherapy - 62.3 ± 8.1 bed-days (p <0.05).whereas in the control group it was only in 41.4% (p <0.05). The average length of hospital stay in patients receiving GlutoximЃ was 1.5 times shorter and amounted to 42.1 ± 1.7 bed-days, and in patients receiving only chemotherapy - 62.3 ± 8.1 bed-days (p <0.05).whereas in the control group it was only in 41.4% (p <0.05). The average hospital stay in patients receiving GlutoximЃ was 1.5 times shorter and amounted to 42.1 ± 1.7 bed-days, and in patients receiving only chemotherapy - 62.3 ± 8.1 bed-days (p <0.05).

GlutoximЃ improves the tolerance of chemotherapy, radiation and chemoradiation therapy in oncology. GlutoximЃ restores the sensitivity of stem cell receptors to endogenous and exogenous colony-stimulating factors and erythropoietins, suppressed by chemotherapy and cancer intoxication. Due to this, the restoration of leukocyte, platelet and erythrocyte hematopoiesis takes place. The drug can reduce the incidence of leukopenia and thrombocytopenia, or shift deep hematological toxicity to moderate. The addition of Glutoxim during chemotherapy in patients with morphologically confirmed stage IIIb-IV NSCLC according to the etoposide + cisplatin scheme, who had not previously received chemotherapy and radiation therapy, made it possible to reduce the incidence of deep neutropenia (3 and 4 degrees of toxicity according to WHO) by 2.5 times (р = 0.002),the incidence of general thrombocytopenia was 1.6 times (p <0.04). In patients with cervical cancer receiving a radical course of radiation therapy, against the background of Glutoxim, the number of leukocytes in the peripheral blood was significantly higher than in the control group receiving only standard radiation therapy.

GlutoximЃ helps prevent or reduce the severity of skin reactions (dermatitis) and mucous membranes (mucositis, stomatitis, rectitis, cervicitis) to radiation and exposure to chemotherapy. Complications in the form of early radiation rectitis in patients with stage III cervical cancer with the use of GlutoximЃ develop less frequently (6.15% vs 16.0%), recovery of the functions of the pelvic organs is faster (p <0.04). The use of GlutoximЃ in patients with tumors of the oropharyngeal region contributes to a significant decrease in the severity of subjective manifestations of radioepithelitis - the frequency of bleeding of the gums and the occurrence of focal epitheliitis are significantly reduced. The frequency of complaints such as dry mouth, pain when swallowing, and changes in taste decreased.

GlutoximЃ contributes to the improvement or maintenance of the quality of life of patients receiving CT / RT, and ensures the possibility of carrying out all the required courses of CT. In patients with stage III-IV tumors of the oropharyngeal region who received radiation therapy, GlutoximЃ helps to restore the quality of life - the Karnovsky index increases to 90% (with 50-60% in the control) (p <0.05). By improving the tolerance, GlutoximЃ promotes the conduct of chemotherapy, radiation and chemoradiation therapy in full, without reducing the planned courses. Clinical studies have shown an increase in the frequency of positive responses to a radical course of radiation therapy for locally advanced cervical cancer. The frequency of achieving complete remission was 77% (in the control group - 38%).A more rapid recovery of peripheral blood parameters and an improvement in the general condition of patients on the background of radiation therapy were noted.

GlutoximЃ promotes an increase in the frequency of complete (including morphological) remission and disease-free survival. The rate of positive responses to radiation therapy in patients with stage III-IV oropharyngeal cancer (complete + partial remission) in the group of patients receiving GlutoximЃ was significantly higher than in the control group - 83.4% and 61.5%, respectively. In patients with HER-2 (-) stage II-III breast cancer, the addition of GlutoximЃ to neoadjuvant therapy led to a doubling of the previously achieved frequency of complete morphological remission. In chemotherapy of patients with platinum-resistant ovarian cancer with the inclusion of GlutoximЃ, the median relapse-free survival was 15.4 weeks, while without the use of the drug, according to historical control,this indicator was 8 weeks in patients with the same intensity of treatment. The median disease-free survival was 19.4 weeks. The inclusion of GlutoximЃ in the chemotherapy regimen showed clinical feasibility (complete remission + partial remission + stabilization) in 60% of patients.

When GlutoximЃ was prescribed to patients with psoriasis, according to the results of clinical studies, patients showed a faster (on days 5-6 of therapy) and complete regression of rashes (infiltration, peeling, swelling), itching decreased and the quality of life improved: the PASI index decreased from 39.5 ± 4.0 to 11.7 ± 5.2, while in patients receiving standard therapy - from 26.1 ± 2.6 only to 21.0 ± 2.9 (p <0.05). In the arthropathic form, the intensity of arthralgias decreased. With concomitant liver damage to psoriasis, GlutoximЃ demonstrated a hepatoprotective and toxicomodifying effect: after 7-10 days of therapy, a decrease in liver symptoms was noted - pain and / or severity in the right hypochondrium decreased or stopped, ALT transaminase values ??normalized from 65.9 ± 34.5 U / L to 45.9 ± 15.0, AST from 98.1 ± 25.4 E / L to 45.5 ± 13.4 U / L (p <0.03), the duration of hospital stay was reduced by an average of 14.2 ± 5.8 days (p <0.05). A significant increase in psoriasis remission was demonstrated: when GlutoximЃ was added to therapy, the remission period was within 6 months - in 19% of patients, within a year - in 20.8% of patients, more than 1 year - in 51.2% of patients, 1.5 years and more - in 9% of patients.

As part of the complex therapy of sexually transmitted infections, GlutoximЃ, as an antibiotic adjuvant, helps to increase the effectiveness (potentiation) of etiotropic antibacterial therapy of urogenital infections (UGI), one of the factors in the formation of deep reproductive disorders (up to infertility), reduces the risk of subsequent relapses of IGO. According to the results of clinical studies, the effectiveness of UHI therapy 1 month after the end of treatment based on the results of PCR (elimination of the pathogen) in the group of patients receiving only antibiotic therapy was 64.5-73.6%, and in the group receiving along with antibacterial therapy GlutoximЃ - 97.4% -98.7%. When the drug GlutoximЃ was included in the regimen, relapses of infection were also significantly less often detected,moreover, there was a decrease in the likelihood of re-development of IHI (with re-infection or reinfection) during the 12 months of follow-up following therapy.

GlutoximЃ helps to increase the effectiveness of complex therapy for chronic inflammatory diseases of the internal genital organs of women. The inclusion of GlutoximЃ in the treatment regimens for the chronic inflammatory process of the internal genital organs in women of reproductive age increases the effectiveness of treatment. The restoration of the function of the immune system is noted, incl. at the local level: activation and normalization of indicators of nonspecific protection occurs - for example, the concentration of secretory IgA and IgA of cervical mucus. The manifestations of the inflammatory reaction are stopped (rapid regression of the pain syndrome during the first 7 days), there is an improvement in the quality of life of patients and a stable clinical recovery in 96.8% of patients.

GlutoximЃ helps to increase the effectiveness of complex therapy for chronic inflammatory diseases of the male genital organs, incl. complicated by excretory toxic infertility. As a result of the conducted studies of the effectiveness of the inclusion of the drug GlutoximЃ in the treatment regimens, a pronounced anti-inflammatory effect was revealed: with light microscopy of prostate secretion before treatment, leukocytes are 91.3 ± 11.2 in the field of view, after treatment - a decrease to 11.9 ± 1.8 (p <0.05), elimination of pathogenic microorganisms from the secretion in 91.4% of patients after a course of treatment, improvement of the main indicators of spermogram - a significant increase in ejaculate volume and sperm count, disappearance of pyospermia in 82.9% of patients.The quality of life of patients is improved due to the practical normalization of urination and a decrease in negative sensations in terms of IPSS indices and quality of life. The introduction of GlutoximЃ into the treatment regimens for chronic bacterial prostatitis (CKD) reduces the therapy time to 3 weeks (versus the standard 4-6 weeks). In the complex therapy of CKD in combination with UGI, the inclusion of GlutoximЃ allows to increase the duration of remission and reduce the frequency of relapses by 3 times. The inclusion of GlutoximЃ in CKD treatment regimens improves the erection and ejaculatory components of the male copulatory cycle.In the complex therapy of CKD in combination with UGI, the inclusion of GlutoximЃ allows to increase the duration of remission and reduce the frequency of relapses by 3 times. The inclusion of GlutoximЃ in CKD treatment regimens improves the erection and ejaculatory components of the male copulatory cycle.In the complex therapy of CKD in combination with UGI, the inclusion of the drug GlutoximЃ allows to increase the duration of remission and reduce the frequency of relapses by 3 times. The inclusion of GlutoximЃ in CKD treatment regimens improves the erection and ejaculatory components of the male copulatory cycle.

Overdose

Currently, no cases of an overdose of GlutoximЃ have been reported.

Drug interactions

When combined, GlutoximЃ potentiates the bacteriostatic effect of isoniazid, rifampicin, rifabutin, cycloserine, capreomycin, levofloxacin on Mycobacterium tuberculosis, the anthracycline antibiotic doxorubicin, an alkylating agent - etoposide on tumor cells.

GlutoximЃ reduces the therapeutic effect of nifedipine and verapamil.

Inhibitors of the cyclooxygenase pathway of arachidonic acid oxidation - indomethacin, meloxicam - reduce or completely suppress the pharmacological action of GlutoximЃ.

Isotonic sodium chloride solution or 5% glucose solution is used as a carrier solution for infusion administration.