Глутоксим®

General characteristics. Structure:

Active ingredient: 10 mg, 20 mg, 30 mg or 60 mg dinatrium glutamil-tsisteinil-glycine.

Excipients: sodium acetate, the acetic acid (divorced to pH 6.0), water for and.

Глутоксим® plays an important role in regulation of metabolic processes in cells and fabrics.

Pharmacological properties:

Pharmacodynamics. Глутоксим® renders the immunomodulatory, haemo stimulating, detoksitsiruyushchy, hepatoprotective action, suppresses medicinal resistance of tumor cells to antibiotics of an anthracycline row, the alkylating means; allows to overcome the medicinal resistance of Mycobacterium tuberculosis to an isoniazid associated with katG genes (a catalase peroxidase gene) and inhA (an enol-APB-reduktazy gene). Глутоксим® exponentiates effect of doxorubicine on tumor cells, funds of chemotherapy (an isoniazid, rifampicin, a rifabutin, Cycloserinum, a kapreomitsin, a levofloksatsin, cationic antimicrobic peptide of a kataletsidin) for Mycobacterium tuberculosis.

Immunomodulatory effect of the drug Glutoksim® is caused a receptor - the mediated influence on calcium dependent alarm ways of macrophages that leads to increase:

— survival and functional capacity of fabric macrophages;

— an exocytosis of submembrane granules with intracellularly parasitizing Mycobacterium tuberculosis forms;

— activities of lizosomalny enzymes;

— formations of active forms of oxygen;

— absorption and death of microorganisms;

— secretions of cytokines: Interlaken 1, Interlaken 6, FNO, interferon, erythropoetin,
Interlaken 2; cationic antimicrobic peptides-defensinov, kataletsidin.

The haemo promoting effect of the drug Glutoksim® is caused a receptor - the mediated strengthening of a marrowy hemopoiesis: processes of an erythrogenesis, lymphopoiesis and granulotsito-monocytopoiesis. Action on progenitors of different lines of uniform elements of blood is mediated by functioning of MAP-and inositol kinazny systems, leads to increase in stability of the differentiated hemopoietic cells, recovers their sensitivity to action of internal causes of a hemogenesis.

Detoksitsiruyushchy and hepatoprotective effects of drug are caused a receptor - the mediated strengthening of an expression of enzymes of the second phase of a detoxication of xenobiotics, including glutationreduktaza, glutathione peroxidases, glutathiones-S-transferases, glyukozo-6-fosfatdegidrogenazy, gemoksigenazy-1, increase in intracellular level of the recovered glutathione, the cellular structures providing protection against toxic action of radicals.

Глутоксим® has a direct inhibiting effect on activity of a factor of multiple medicinal resistance of tumor cells - protein the R-glycoprotein (Pgp) which defines resistance of tumor cells to action of means of chemotherapy, including anthracycline antibiotics, drugs of the alkylating action.

Глутоксим® initiates reaction of transformation of an isoniazid - pro-medicine, in pharmacological active form - the isonicotinic acid possessing bacteriostatic action on Mycobacterium tuberculosis that allows to overcome the medicinal resistance of Mycobacterium tuberculosis caused by negative transformation of genes of katG (a catalase peroxidase gene) and inhA (an enol-APB-reduktazy gene).

Глутоксим® stimulates processes of an exocytosis of vesicles of macrophages with intracellularly parasitizing microorganisms, including Mycobacterium tuberculosis, providing their removal from a pharmacological shelter and making available for effect of antibacterial drugs, including an isoniazid, rifampicin, рифабутин, Cycloserinum, капреомицин, levofloxacin.

Глутоксим® strengthens secretion of cationic peptides - defensin and kataletsidin macrophages, stimulates their absorption with tuberculosis mycobacteria, defining the mediated antibacterial effect of drug.

Pharmacokinetics. Absorption. Treats group of natural metabolites that determines features of his metabolism by the existing cellular enzymatic systems. After in oil, in/in or п / to introduction bioavailability exceeds 90%. Linear dependence between a dose and concentration of drug in a blood plasma is noted. Cmax in/in introductions is reached later within 2-5 min., after introduction in oil - within 7-10 min.

Metabolism and removal. As the natural product of the peptide nature is metabolized in bodies and body tissues. It is removed with urine.

Indications to use:

— prevention and treatment of the secondary immunodeficiency connected with radiation, chemical and infectious factors;

— recovery of the suppressed immune responses and depression of a marrowy hemopoiesis;

— increase in resistance of an organism to various influences (infection, intoxication, radiation);

— as hepatoprotective cure for a chronic viral hepatitis In and With;

— potentiation of medical effects of antibacterial therapy of chronic obstructive diseases of lungs;

— prevention of postoperative purulent complications;

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

— tuberculosis, resistant to medicinal therapy;

— prevention of exacerbations of chronic hepatitis at TB patients against the background of antitubercular therapy;

— treatment of toxic complications of antitubercular therapy;

— as a part of complex therapy of uncomplicated forms of psoriasis, including as a part of complex therapy of tear-shaped and exudative forms of psoriasis, at a psoriasis erythrosis and artropatichesky psoriasis, at patients with toxic or viral hepatitises, manifestations of a nonspecific syndrome of chronic diseases;

— as a part of complex therapy of malignant new growths - for prevention and treatment of toxic manifestations himio-and radiation therapy (promotes decrease haemo - and a hepatotoxic action).

Глутоксим® promotes effective recovery of functions of a marrowy hemopoiesis when performing antineoplastic therapy. Глутоксим® eliminates or smoothes manifestations of a nonspecific syndrome of a disease (anemia, fatigue, a loss of appetite, the increased painful sensitivity).

Route of administration and doses:

The adult the drug is administered in/in, in oil and п / to in a dose of 5-40 mg daily depending on disease severity. A course dose - 50-300 mg.

With the preventive purpose drug is used by in oil 5-10 mg in a dose daily within 2 weeks.

At tuberculosis (as a part of complex therapy) drug appoint in oil on 60 mg of 1 times/days daily in the first 10 days, the next 20 days Glutoksim® enter in oil 60 mg in a dose every other day. If necessary carry out a repeated course of treatment in 1-6 months.

As a part of complex therapy of uncomplicated forms of psoriasis of Glutoksim® apply in oil daily in a daily dose of 10 mg within 15 days, then within 5 weeks 2 times a week in a daily dose of 10 mg. Only 25 injections on a course of treatment.

As means of maintenance of chemotherapy in oncology of Glutoksim® enter п / to in a dose of 60 mg for 1.5-2 h before use of antineoplastic means. Further between chemotherapy courses the drug is administered п / to in a dose of 60 mg every other day. At the following course of chemotherapy the scheme of use of drug repeats.

As means of maintenance of radiation therapy of Glutoksim® it is entered п / to in a dose of 60 mg in 0.5-1 h after another session of radiation every other day throughout all course of radiation therapy.

Глутоксим® it is possible to enter in one syringe with water-soluble medicines.

Features of use:

Use at pregnancy and feeding by a breast. Clinical trials of use of the drug Glutoksim® at pregnancy and in the period of a lactation (breastfeeding) were not carried out.

Special instructions. Глутоксим® - the Russian innovative drug, the representative of a new class of medicines - regulators of protective systems of an organism (innate defense regulators, IDR). Drugs of this group, according to their pharmacological activity, belong to antibiotic adjuvants: the main effect of Glutoksim is potentiation of antitubercular chemotherapy, including increase in availability of mycobacteria of tuberculosis to effect of medicines and overcoming medicinal stability of the activator.

According to results of basic and clinical trials, Glutoksim® strengthens secretion by macrophages of endogenous antibiotics - the cationic antimicrobic peptides (CAP) (defensin and kataletsidin), stimulates their absorption with mycobacteria. Action leads the CAP, mainly, to disturbance of structure and functions of a cytoplasmic membrane of the activator that, in turn, leads to death of the last. Antibacterial activity of the drug Glutoksim® is shown at its introduction by in vivo, demands for the implementation of existence of a pool of endogenous MOUTHPIECES, capable to mobilization, i.e. in relation to effect of drug CAP act as effector molecules, predetermining its indirect antibacterial effect.

Effect of drug is supplemented with effect of overcoming medicinal resistance of Mycobacterium tuberculosis to an isoniazid. Глутоксим® initiates reaction of transformation of an isoniazid (pro-medicine) in pharmacological active form – the isonicotinic acid possessing antimikobakterialny action concerning the activator that allows to overcome the medicinal stability of Mycobacterium tuberculosis caused by negative transformation of genes of katG (a catalase peroxidase gene) and inhA (an enol-APB-reduktazy gene). Effect of drug is followed by increase in products of peroxynitrite and a nitozoglutation - the connections possessing independent bactericidal action.

It is shown also that Glutoksim® limits possibilities of intracellular parasitizing of mycobacteria of tuberculosis. Drug stimulates an exocytosis (removal) of vesicles with intracellularly parasitizing mycobacteria from macrophages, providing their removal from a pharmacological shelter and making available for effect of antibacterial drugs, including an isoniazid, rifampicin, рифабутин, Cycloserinum, капреомицин, levofloxacin. The pharmacological effect of Glutoksim in relation to antibacterial activity of the listed antibiotics is exponential as increases availability of a target (microorganisms) to effect of the medicine.

Глутоксим® increases the frequency of the termination of a bakteriovydeleniye and reduces phlegm abatsillirovaniye terms. By the end of the 2nd month of treatment among the patients receiving Glutoksim®, the bakteriovydeleniye stopped at 91.1% of patients with medicinal and sensitive tuberculosis (vs 61.1% in control group) and at 75.1% of patients with drug resistant tuberculosis (vs 38.9% in control) (р <0.05). Acceleration of the termination of a bakteriovydeleniye defines high kliniko-economic efficiency of drug. At use of the drug Glutoksim® terms of a rassasyvaniye of infiltrative and focal changes in lungs are reduced: by the end of the 2nd month of treatment, the rassasyvaniye of infiltrative and focal changes was revealed at 93.2% of the patients receiving along with chemotherapy of Glutoksim® (vs 62.2% of patients of control group) (р <0.05). Upon termination of 4 months of polychemotherapy closing of cavities of disintegration happened at 88.3% of the patients receiving Glutoksim® (vs 70.8% of patients of control group) (р <0.05).

Глутоксим® improves portability of antitubercular chemotherapy: toxic reactions (increase in activity of ALT, ACT, content of bilirubin, creatinine in blood serum) were observed only at 4.3% of patients while to control group - at 11.1% of patients (р <0.05). Toksiko-allergichesky reactions (an eosinophilia, a loss of appetite, weight and pains in right the hypochondrium, nausea caused by use of rifampicin and high doses of an isoniazid) at purpose of the drug Glutoksim® were noted significantly less often - at 6.4% of patients, at 20% in control group (р <0.05). Intoxication symptoms (the increased body temperature, weakness, feeling sick, etc.) at the patients receiving Glutoksim® were stopped preferential in the first 2 months of treatment. Глутоксим® the exacerbation of chronic hepatitis when carrying out chemotherapy at tuberculosis warns, and at already developed medicamentous damage of a liver - allows to continue chemotherapy in full, without resorting to its temporary cancellation. Глутоксим® more than by 4 times reduces the frequency of development of toxic hepatitis.

Глутоксим® in a complex with chemotherapy allows to prepare in a short time patients for operational treatment - drug increases the frequency of an abatsillirovaniye of a phlegm and promotes disappearance or essential reduction of frequency and intensity of clinical laboratory symptoms of a disease at patients to whom surgical treatment is necessary. At the patients with drug resistant tuberculosis receiving in the preoperative period along with antitubercular chemotherapy of Glutoksim®, twice more often (59.6% vs 28.9%) positive dynamics of clinical laboratory symptoms of a disease is noted, the termination of a bakteriovydeleniye is observed 1.9 times more often (38.3% vs 20% - in control). Глутоксим® improves short-term results of surgical treatment. Recovery of a pnevmatization of pulmonary fabric by 21 days of the postoperative period happens at 82% of the patients receiving along with antitubercular chemotherapy of Glutoksim® and only at 35% of the patients receiving only chemotherapy. Postoperative complications (a pleura empyema, progressing of specific process, nonspecific pneumonia) at the patients receiving Glutoksim® develop 4.5 times less often (6.9% vs 32%) than at the patients receiving only chemotherapy (р <0.05). Recovery without complications is noted at 64.9% operated whereas in control group – only at 41.4% (р <0.05). Average terms of stay in a hospital at the patients receiving Glutoksim® were 1.5 times shorter and made 42.1±1.7 koyko-days, and the patients receiving only chemotherapy - 62.3±8.1 koyko-days (р <0.05).

Глутоксим® improves portability himio-, radiation and himioluchevy therapy in oncology. Глутоксим® recovers the sensitivity of receptors of stem cells oppressed by chemotherapy and cancer intoxication to internal and exogenous colony stimulating causes and erythropoetins. Thanks to it there is a recovery of leukocytic, platelet and erythrocyte sprouts of a hemopoiesis. Drug allows to reduce the frequency of development of a leukopenia and thrombocytopenia or to displace deep hematologic toxicity to the area of moderate. Glutoksim's joining when carrying out chemotherapy at patients with morphologically confirmed stage NMRL IIIb-IV according to the scheme этопозид + Cisplatinum, not receiving earlier himio-and radiation therapy, allowed to reduce the frequency of development of a deep neutropenia (3 and 4 degrees of toxicity on WHO) by 2.5 times (р =0.002), the frequency of development of the general thrombocytopenia - by 1.6 times (р <0.04). Cancer patients have necks of uterus, receiving a radical course of radiation therapy, against the background of Glutoksim the quantity of leukocytes in peripheral blood was reliable above, than in the group of control receiving only standard radiation therapy.

Глутоксим® promotes the prevention or reduction of expressiveness of reactions of skin (dermatitis) and mucous (mukozit, stomatitises, rectites, tservitsit) on radiation and influence of himiopreparat. Complications in the form of early beam rectites at patients with cancer of a neck of uterus of the III stage against the background of use of the drug Glutoksim® develop less often (6.15% vs 16.0%), recovery of functions of pelvic bodies happens quicker (р <0.04). Use of Glutoksima® for patients with tumors of oropharyngeal area promotes considerable decrease in expressiveness of subjective manifestations of a radioepithelitis - the frequency of emergence of bleeding of gums, emergence of a focal epithelitis significantly decreases. Frequency of such complaints as dryness in a mouth, pain decreased when swallowing, taste change.

Глутоксим® promotes improvement or preservation of quality of life of the patients receiving HT/LT, provides a possibility of carrying out all required courses HT. Patients with tumors of oropharyngeal area III-IV have stages, receiving radiation therapy, Glutoksim® promotes recovery of quality of life - Karnovsky's index increases up to 90% (at 50-60% in control) (р <0.05). Due to improvement of portability of Glutoksim® promotes carrying out himio-, radiation and himioluchevy therapy in full, without reduction of the planned courses. In clinical trials increase in frequency of affirmative answers at a radical course of radiation therapy of locally-spread cancer of neck of uterus is shown. Frequency of achievement of full remission made 77% (in control group - 38%). More bystry recovery of indicators of peripheral blood and improvement of the general condition of patients against the background of radiation therapy is noted.

Глутоксим® promotes increase in frequency full (including morphological) remission and bezretsidivny survival. Frequency of affirmative answers on radiation therapy at patients with cancer of oropharyngeal area III-IV of a stage (full + partial remission) in group of the patients receiving Glutoksim® was significantly higher, than in control group - 83.4% and 61.5% respectively. At sick HER-2 (-) a breast cancer of the II-III stage accession to neoadyyuvantny therapy of the drug Glutoksim® led to doubling of the frequency of full morphological remission reached earlier. At chemotherapy of patients with ovarian cancer, resistant to platinum drugs, with drug Glutoksim® inclusion the median of bezretsidivny survival made 15.4 weeks while without drug use, according to historical control, this indicator made 8 weeks at patients with the same treatment on intensity. The average period of bezretsidivny survival made 19.4 weeks. Inclusion of the drug Glutoksim® in the scheme of chemotherapy showed clinical expediency (full remission + partial remission + stabilization) at 60% of patients.

At purpose of the drug Glutoksim® to patients with psoriasis, according to results of clinical trials, at patients more bystry was observed (for 5-6 day of therapy) and full regress of rashes (infiltration, a peeling, puffiness), the itch decreased and quality of life improved: the PASI index decreased with 39.5±4.0 to 11.7±5.2 while at the patients receiving standard therapy – with 26.1±2.6 only to 21.0±2.9 (р <0.05). At an artropatichesky form intensity of arthralgias decreased. At the damage of a liver of Glutoksim® accompanying psoriasis showed hepatoprotective and toksikomodifitsiruyushchy action: in 7-10 days of therapy reduction of symptomatology from a liver was noted – pains and/or weight in right hypochondrium decreased or stopped, indicators of ALT transaminases with 65.9 ±34.5 El to 45.9±15.0, nuclear heating plant from 98.1±25.4 El to 45.5±13.4 El were normalized (р <0.03), terms of stay of patients in a hospital on average were reduced by 14.2±5.8 days (р <0.05). Reliable increase in remission of psoriasis is shown: at accession to drug Glutoksim® therapy the term of remission made within 6 months – at 19% of patients, within a year – at 20.8% of patients, more than 1 year - at 51.2% of patients, 1.5 years and more – at 9% of patients.

As a part of complex therapy of infections, sexually transmitted, Glutoksim® as antibiotic adjuvant, promotes increase in efficiency (potentiation) in causal antibacterial treatment of urogenital infections (UGI), one of factors of formation of deep disturbances of the reproductive sphere (up to infertility), reduces risk of development of the subsequent recurrence of UGI. According to results of clinical trials, efficiency of therapy of UGI in 1 month after the end of treatment by results of PTsR (elimination of the activator) in group of the patients receiving only antibacterial therapy made 64.5-73.6%, and in the group receiving along with antibacterial therapy of Glutoksim® – 97.4%-98.7%. At inclusion in the scheme of the drug Glutoksim® also authentically an infection recurrence came to light less often, and decrease in probability of repeated development of UGI (was noted at repeated infection or reinfection) for the 12 months of observation, subsequent to therapy.

Глутоксим® promotes increase in efficiency of complex therapy of chronic inflammatory diseases of internal generative organs of women. Inclusion of the drug Glutoksim® in schemes of treatment of chronic inflammatory process of internal generative organs at women of reproductive age increases efficiency of treatment. Recovery of function of immune system, including at the local level is noted: there is an activation and normalization of indicators of nonspecific protection - for example, concentration of secretory IgA and IgA of cervical slime. Manifestations of inflammatory reaction are stopped (bystry regress of a pain syndrome within the first 7 days), improvement of quality of life of patients and permanent clinical cure at 96.8% of patients is noted.

Глутоксим® promotes increase in efficiency of complex therapy of chronic inflammatory diseases of men's generative organs, including complicated by excretory and toxic infertility. As a result of the conducted researches of efficiency of inclusion of the drug Glutoksim® in schemes of treatment the expressed antiinflammatory effect was revealed: at light microscopy of a secret of a prostate before treatment leukocytes 91.3±11.2 under review, after treatment – decrease to 11.9±1.8 (р <0.05), elimination of pathogenic microorganisms from a secret at 91.4% of patients after a course of treatment, improvement of the main indicators of a spermogram – reliable increase in volume of an ejaculate and quantity of spermatozoa, disappearance of a piospermiya at 82.9% of patients. Quality of life of patients due to practical normalization of an urination and reduction of negative feelings on the IPSS indexes and qualities of life improves. Administration of the drug Glutoksim® in schemes of treatment of the chronic bacterial prostatitis (CBP) reduces therapy time to 3 weeks (against standard 4-6 weeks). In complex therapy of HBP in combination with UGI inclusion of the drug Glutoksim® allows to increase terms of remission and to reduce the frequency of a recurrence by 3 times. Inclusion of the drug Glutoksim® in schemes of treatment of HBP promotes improvement of an erektsionny and eyakulyatorny component of a copulative cycle of the man.

Side effects:

Perhaps: in some cases - fervescence (37.1-37.5 °C), morbidity in a drug injection site (for reduction of morbidity administration of drug along with 1-2 ml of 0.5% of solution of novocaine is possible).

Interaction with other medicines:

Глутоксим® at the combined use exponentiates bacteriostatic effect of an isoniazid, rifampicin, a rifabutin, Cycloserinum, kapreomitsin, levofloksatsin on Mycobacterium tuberculosis, an anthracycline antibiotic of the doxorubicine alkylating means - an etopozid on tumor cells.

Глутоксим® reduces therapeutic effect of nifedipine and verapamil.

Inhibitors of a cyclooxygenase way of oxidation of arachidonic acid — indometacin, to meloksika - reduce or completely suppress pharmacological effect of the drug Glutoksim®.

As solution carrier for infusional introduction use isotonic solution of sodium of chloride or 5% glucose solution.

Contraindications:

— pregnancy;

— period of a lactation (breastfeeding);

— hypersensitivity to drug components.

Overdose:

Now about cases of overdose of the drug Glutoksim® it was not reported.

Storage conditions:

Drug should be stored in protected from light, the place, unavailable to children, at a temperature not above 25 °C. A period of validity - 3 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

1 ml - ampoules glass (5) - planimetric strip packagings (1) - packs cardboard.