Glutoxim, Ampoules 1%, 1ml, 5pcs

Composition

Active ingredient:

disodium glutamyl-cysteinyl-glycine

Auxiliary substances:

sodium acetate,

acetic acid (diluted to pH 6.0),

d/i water.

Pharmacological action

Glutoxim-normalizes metabolic processes, regulates redox processes, and immunostimulates.

It affects the intracellular processes of thiol metabolism, the redox state of cells. The immunomodulatory and systemic cytoprotective effects are determined by the new level of redox systems and the dynamics of phosphorylation of key proteins of signal-transmitting systems and transcription factors (NFkB and AP-1), primarily in immunocompetent cells.

It has a differentiated effect on normal (stimulation of proliferation and differentiation) and transformed (induction of apoptosis — genetically programmed cell death) cells.

It has a high tropicity to the cells of the central immune organs and the lymphoid tissue system; it stimulates the processes of erythropoiesis, lymphopoiesis and granulocyte-monocytopoiesis; activates the phagocytosis system (including in conditions of immunodeficiency), helps restore the level of neutrophils, monocytes, lymphocytes and functional activity of tissue macrophages in peripheral blood.

It has a stimulating effect on the cascade mechanisms of phosphate modification of the main proteins of signal-transmitting systems; it causes the initiation of the cytokine system (including endogenous production of interleukin-1, interleukin-6, tumor necrosis factor, erythropoietin), reproduction of the effects of interleukin−2 by inducing the expression of its receptors.

Bioavailability is 90%. The time to reach_cmax with intravenous use is 2-5 minutes, with intravenous use-7-10 minutes. Distribution by organs and tissues of the body: maximum accumulation — in the liver, kidneys, organs of immunogenesis and hematopoiesis, minimum-in adipose tissue. It is metabolized to amino acids. It is excreted by the kidneys in the form of metabolites.

Indications

Secondary immunodeficiency conditions associated with radiation, chemical and infectious factors (prevention and treatment); restoration of immune responses and bone marrow hematopoiesis, increasing the body’s resistance to various pathological effects — infectious agents, chemical and/or physical factors (including intoxication, radiation); Acute respiratory viral infections, influenza, viral hepatitis (B and C), drug-induced hepatitis, metastatic liver damage, hepatocellular carcinoma, alcoholic disease liver, urogenital infections, pulmonary tuberculosis, sepsis, autoimmune diseases; prevention of postoperative purulent complications; to increase the effectiveness of antibacterial therapy in chronic obstructive pulmonary diseases.

Use during pregnancy and lactation

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

Contraindications

Hypersensitivity, pregnancy, breast-feeding.

Side effects

Subfebrility, soreness at the injection site.

Interaction

Glutoxim®, when used in combination, potentiates the bacteriostatic effect of isoniazid, rifampicin, rifabutin, cycloserine, capreomycin, levofloxacin on Mycobacterium tuberculosis, the anthracycline antibiotic doxorubicin, and the alkylating agent etoposide on tumor cells.

Glutoxim ® reduces the therapeutic effect of nifedipine and verapamil.

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

An isotonic sodium chloride solution or 5% glucose solution is used as a carrier solution for infusion use.

How to take, course of use and dosage

In / in, in / m, p / k adults 5-40 mg (depending on the nature and severity of the disease) daily. The course lasts for 10 days. If necessary, a second course is carried out after 1-6 months. Prophylaxis — i. m 5-10 mg / day.

For metastatic liver lesions, hepatocellular carcinoma-intravascular (in the hepatic artery or portal vein) through a catheter, bolus, in a daily dose of 90-150 mg for 5-6 days, in 2-4 days-in combination with chemotherapy drugs. If necessary, the course is repeated after 2-3 months.

Overdose

Currently, no cases of overdose of Glutoxim® have been reported.

Special instructions

Glutoxim® is a Russian innovative drug, representative of a new class of medicines-innate defense regulators (IDR). Drugs of this group, according to their pharmacological activity, belong to antibiotic adjuvants: the main effect of Glutoxim is to potentiate antitubercular chemotherapy, including increasing the availability of Mycobacterium tuberculosis to the action of drugs and overcoming drug resistance of the pathogen.

According to the results of basic and clinical studies, Glutoxim ® enhances macrophage secretion of endogenous antibiotics – cationic antimicrobial peptides (CAP) (defensins and catalecidins), and stimulates their uptake by mycobacteria. The action of CAP leads mainly to a violation 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 drug Glutoxim® is manifested when it is administered in vivo, requires for its implementation the presence of a pool of endogenous CAP capable of mobilization, i. e. in relation to the action of the drug, CAP 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. Glutoxim® 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 due to the negative transformation of the katG (catalase-peroxidase gene) and inhA (enol-APB reductase gene) genes. The effect of the drug is accompanied by an increase in the production of peroxynitrite and nitozoglutathione-compounds that have an independent bactericidal effect.

Glutoxim® has also been shown to limit the possibility of intracellular parasitization of Mycobacterium tuberculosis. The drug stimulates exocytosis (removal) of vesicles with intracellularly parasitizing 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, since it increases the availability of the target (microorganisms) to the action of the drug.

Glutoxim ® increases the frequency of cessation of bacterial excretion and reduces the time of sputum abacillation. By the end of the 2nd month of treatment among patients receiving Glutoxim®, bacterial excretion was stopped in 91.1% of patients with drug-sensitive tuberculosis (vs 61.1% in the control group) and 75.1% of patients with drug-resistant tuberculosis (vs 38.9% in controls) (p®reduced the resorption of focal and infiltrative changes in the lungs by the end of the 2nd month of treatment, resorption of infiltration and focal changes were detected in 93.2% of patients receiving along with chemotherapy Glutoxim® (vs 62.2% of patients in the control group) (R® (vs. 70.8% of patients in the control group) (p

Glutoxim improves the tolerability of antituberculous chemotherapy: toxic reactions (increased ALT, ACT, bilirubin, serum creatinine) were observed only in 4.3% of patients, while in the control group – in 11.1% of patients (p® were significantly less common – in 6.4% of patients, and 20% in the control group (p®, stopped mainly in the first 2 months of treatment. Glutoxim® prevents exacerbation of chronic hepatitis during chemotherapy for tuberculosis, and with already developed drug – induced liver damage, it allows you to continue chemotherapy in full, without resorting to its temporary cancellation. Glutoxim® reduces the incidence of toxic hepatitis by more than 4 times.

Glutoxim® in combination with chemotherapy makes it possible to prepare patients for surgical treatment in a short time – the drug increases the frequency of sputum abacillation and contributes to the disappearance or significant reduction of the frequency and intensity of clinical and laboratory symptoms of the disease in patients undergoing surgical treatment. In patients with drug-resistant tuberculosis who received Glutoxim® in the preoperative period along with antitubercular chemotherapy, a positive dynamics of clinical and laboratory symptoms of the disease is observed 2 times more often (59.6% vs 28.9%), and the cessation of bacterial excretion is observed 1.9 times more often (38.3% vs 20% in the control group). Glutoxim ® improves the immediate results of surgical treatment. Recovery of pneumatization of the lung tissue by 21 days of the postoperative period occurs in 82% of patients who received Glutoxim® along with antitubercular chemotherapy, and only in 35% of patients who received chemotherapy alone.Postoperative complications (empyema, the progression of the specific process, nonspecific pneumonia) in patients receiving Glutoxim®, developed in 4.5 times less likely (6.9% vs. 32%) than in patients who received only chemotherapy (p® was shorter than 1.5 times and amounted to 42.1±1.7 a bed day, and patients who received only chemotherapy – 62.3±8.1 bed days (p

Glutoxim ® improves the tolerability of chemo-, radiation and chemoradiotherapy in oncology. Glutoxim ® restores the sensitivity of stem cell receptors to endogenous and exogenous colony-stimulating factors and erythropoietins inhibited by chemotherapy and cancer intoxication. Due to this, the restoration of leukocyte, platelet and erythrocyte sprouts of hematopoiesis occurs. The drug can reduce the incidence of leukopenia and thrombocytopenia or shift deep hematological toxicity to moderate. Accession Glutoxim during chemotherapy in patients with biopsy-proven NSCLC IIIb-IV stage according to the scheme of etoposide + cisplatin who had not previously received chemotherapy and radiation therapy have reduced the incidence of profound neutropenia (grade 3 and 4 toxicity according to who) 2.5 times (p=0.002), the incidence of total thrombocytopenia – 1.6 times (p

Glutoxim® helps prevent or reduce the severity of skin reactions (dermatitis) and mucous membranes (mucositis, stomatitis, rectitis, cervicitis) to radiation and chemotherapy. Complications in the form of early radiation rectitis in patients with stage III cervical cancer against the background of the use of Glutoxim® develop less frequently (6.15% vs 16.0%), restoration of pelvic organ functions occurs faster (p® in patients with tumors of the oropharyngeal region contributes to a significant decrease in the severity of subjective manifestations of radioepithelitis – significantly reduces the frequency of bleeding gums, the occurrence of focal epithelitis. The frequency of complaints such as dry mouth, pain when swallowing, and changes in taste decreased.

Glutoxim ® helps to improve or maintain the quality of life of patients receiving CT/LT, provides the possibility of conducting all the required courses of CT. In patients with stage III-IV oropharyngeal tumors treated with radiation therapy, Glutoxim ® helps restore the quality of life – the Karnovsky index increases to 90% (with 50-60% in the control) (p® promotes chemo-, radiation and chemoradiotherapy in full, without reducing the planned courses. Clinical studies have demonstrated an increase in the frequency of positive responses to radical radiation therapy for locally advanced cervical cancer. The frequency of achieving complete remission was 77% (in the control group-38%). More rapid recovery of peripheral blood parameters and improvement of the general condition of patients during radiation therapy were noted.

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

When Glutoxim® was administered to patients with psoriasis, according to the results of clinical studies, patients experienced a faster (on day 5-6 of therapy) and complete regression of rashes (infiltration, peeling, swelling), itching decreased and 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® demonstrated hepatoprotective and toxicomodifying effect: after 7-10 days of therapy, there was a decrease in liver symptoms – pain and/or severity in the right hypochondrium decreased or stopped, ALT transaminases normalized from 65.9 ±34.5 U/l to 45.9±15.0, AST from 98.1±25.4 U/l to 45.5±13.4 U/l (p® remission period was 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 or more – in 9% of patients.

As part of the complex therapy of sexually transmitted infections, Glutoxim®, as an antibiotic adjuvant, increases the effectiveness (potentiation) of etiotropic antibacterial therapy for urogenital infections (UHI), one of the factors in the formation of deep reproductive disorders (up to infertility), reduces the risk of subsequent recurrences of UHI. According to the results of clinical studies, the effectiveness of UHI therapy in 1 month after the end of treatment according to PCR (pathogen elimination) results in the group of patients receiving only antibacterial therapy was 64.5-73.6%, and in the group receiving along with antibacterial therapy Glutoxim® – 97.4%-98.7%. When Glutoxim® was added to the regimen, relapses of infection were also significantly less frequently detected, and there was a decrease in the probability of recurrent UHI (with repeated infection or reinfection) during the 12 months of follow-up that followed therapy.

Glutoxim ® increases the effectiveness of complex therapy of chronic inflammatory diseases of the internal genital organs of women. Inclusion of the drug Glutoxim® in the treatment regimens for chronic inflammatory process of the internal genital organs in women of reproductive age increases the effectiveness of treatment. The immune system function is restored, including at the local level: activation and normalization of indicators of non – specific protection occurs-for example, the concentration of secretory IgA and IgA of cervical mucus. The manifestations of the inflammatory reaction (rapid regression of pain syndrome during the first 7 days) are stopped, the quality of life of patients is improved and a stable clinical recovery is noted in 96.8% of patients.

Glutoxim ® increases the effectiveness of complex therapy of chronic inflammatory diseases of the male genital organs, including those complicated by excretory-toxic infertility. As a result of studies on the effectiveness of including Glutoxim® in treatment regimens, a pronounced anti-inflammatory effect was revealed: with light microscopy of prostate secretions before treatment, leukocytes 91.3±11.2 in the field of vision, after treatment – a decrease to 11.9±1.8 (p® in treatment regimens for chronic bacterial prostatitis (CKD) reduces the treatment time to 3 weeks (against the standard 4-6 weeks). In the complex therapy of CKD in combination with UGI, the inclusion of the drug Glutoxim® can increase the remission time and reduce the relapse rate by 3 times. The inclusion of Glutoxim® in CKD treatment regimens improves the erectile and ejaculatory components of a man’s copulatory cycle.

Product form

solution for injection

Storage conditions

In a dark place, at a temperature not exceeding 25 °C

Shelf life

2 years

Active ingredient

Glutoxim

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Purpose

For adults as directed by your doctor

Indications

Chronic infections, Psoriasis, Immunodeficiency, Poisoning, Hepatitis, Liver damage