Ribomunil gran.d/prepared solution d/pr.vn.in pack.500mg in pack No.4

Nosological classification (ICD-10)

• H66 Suppurative and unspecified otitis media
• H70 Mastoiditis and related conditions
• J01 Acute sinusitis
• J02.9 Acute pharyngitis, unspecified
• J03.9 Acute tonsillitis, unspecified (angina agranulocytic)
• J04 Acute laryngitis and tracheitis
• J06 Acute upper respiratory tract infections of multiple and unspecified localization
• J18 Pneumonia without specifying the pathogen
• J22 Acute respiratory infection of the lower respiratory tract, unspecified
• J31.0 Chronic rhinitis
• J42 Chronic bronchitis, unspecified
• J45.8 Mixed asthma

Acute and chronic respiratory tract infections play an important role in pediatrics. Features of these diseases: 1) high incidence rate; 2) significant risk of complications; 3) the difficulty of differential diagnosis and identification of certain nosological forms, especially streptococcal pharyngitis, sinusitis and acute otitis media; 4) frequent and unjustified use of antibiotics; 5) significant contribution to health care costs and indirect social costs.

Acute respiratory tract infections (RTIs) remain one of the leading causes of child mortality. The proportion of deaths directly attributable to acute RDTIs accounts for 19% of all deaths in children under five years of age, mostly in low-income countries, namely Africa, Asia and Latin America. Although the etiological agents causing RTIs are not always well identified, viruses are considered the main cause. The most commonly identified pathogens are respiratory syncytial virus, adenovirus, parainfluenza and influenza viruses, as well as bacteria: Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae and S. pyogenes [1].

In high-income countries, RTI is one of the most common illnesses, resulting in 20% of medical consultations, 30% of days lost from work and 75% of antibiotic prescriptions. In the United States, the total cost of economic losses associated with FDW, excluding influenza, is approximately $40 billion per year [2]. More than 50% of outpatient consultations for children in the Russian Federation are related to respiratory tract infections [3].

Uncomplicated upper respiratory tract infections usually do not require antibiotics. However, some bacterial complications can occur against the background of acute respiratory viral infections (ARVI), such as acute otitis media, sinusitis and bronchitis. A study by R. Cohen [4] showed that the complication rate was 16.8% (10.9% - acute otitis media, 4% - laryngitis or bronchitis, 1.9% - pulmonary infections).

Excessive antibacterial therapy leads to an increase in bacterial resistance, limits the use of antibacterial agents, and increases the number of allergic reactions. Widespread use of antibiotics increases the risk of toxic reactions and the level of treatment costs. Thus, the rational use of antibiotics is still an important task for pediatricians [5].

The high level of IDPs in children of early and preschool age is explained by: 1) the high level of urbanization of the population (children in cities get sick more often than in rural areas); 2) exposure to harmful environmental factors; 3) non-compliance with hygiene rules in children's institutions; 4) exposure to respiratory pathogens within the family (siblings, caregivers); 5) defects of the immune system; 6) passive smoking.

Family predisposition serves as a risk factor for recurrent and severe forms of the disease. This genetic predisposition is associated with the anatomical, physiological and/or immunological characteristics of the child’s respiratory system [6]. Immune system defects are well known and may be associated with frequent RTIs. It was shown that 57% of children with recurrent RTIs (at least three episodes per year for at least 2 years) had a deficiency of one of the immunoglobulin (Ig) G subclasses, and 17% had an IgA deficiency [7]. Deficiencies of IgG subclasses are often detected in young children, but rarely in older children, which may be caused by transient immaturity of the immune system. Immune system defects, such as common variable immune deficiency and selective IgA deficiency, typically manifest as repeated episodes of respiratory infections caused by bacteria and viruses [8].

Prevention

The strategy for preventing IDPs consists of several activities: 1) informing parents about methods for preventing respiratory infections, the need to examine the child in the event of repeated episodes of respiratory infections and severe illness, about frequent cases of IDPs in the family, and the inadmissibility of frequent and uncontrolled use of antibacterial agents; 2) immunization in accordance with the National Vaccination Calendar; 3) physical education and sports, hardening procedures; 4) specific and nonspecific immunostimulation.

Vaccines represent the best opportunity to reduce morbidity and mortality caused by RTIs. The use of vaccines against influenza viruses, pneumococcus, and Haemophilus influenzae reduces the incidence of these infections. The use of antibiotics for the purpose of chemoprophylaxis should currently be strictly limited and relate to severe chronic diseases, for example, HIV infection, systemic immunodeficiency diseases, cystic fibrosis, common lung malformations and some others, because the occurrence of ARVI leads to an exacerbation of the underlying disease. The risk of the emergence of resistant forms of bacteria and the selection of sensitive strains remains a serious limitation to the widespread use of antibiotics. The effectiveness of surgical methods for the prevention of respiratory diseases (removal of tonsils, adenoids) is currently being actively discussed, and the frequency of these interventions is decreasing [9].

The correlation between recurrent UTIs and immune system defects mentioned above provides a rationale for nonspecific immunostimulatory therapy for patients with recurrent UTIs. For this purpose, bacterial immunostimulants are used. Over the past 3–4 decades, extensive clinical experience has been accumulated in the use of these drugs. It is known that bacterial ribosomes are highly immunogenic, while bacterial membrane proteoglycans act as excipients.

Ribomunil is a ribosomal immunomodulator of bacterial origin, which has been successfully used in clinical practice in recent years. The effectiveness of Ribomunil is due to its complex immunomodulatory effect. It contains ribosomal fractions of S. pneumoniae, S. pyogenes, H. influenzae, K. pneumoniae, as well as proteoglycans of the K. pneumoniae cell wall. An analysis of the effectiveness of including Ribomunil in a complex of rehabilitation measures for frequently ill children indicates the following: the rate of their recovery was significantly ahead of the similar indicators of the comparison groups [10, 11].

Ribomunil has been shown to be taken up by M cells in the intestine in contact with lymphocytes and dendritic cells. Specific lymphocytes can move to other places in the body, in particular to the respiratory system [12, 13]. Adhesion processes are important both for movement and for the performance of other functions by these cells. These processes involve several ligands and receptors expressed on phagocytes and endothelial cells. Ribomunil increased the expression of adhesion molecules not only in in vitro experiments, but also in placebo-controlled studies in humans [14].

In addition, the effect of Ribomunil on dendritic cells was noted. The drug induces membrane expression of CD83, CD86 and class II human leukocyte antigen molecules on dendritic cells, which is a marker of maturity for them. Additionally, increased production of interleukin-12 (IL-12) has been demonstrated [15], which may indicate that Ribomunyl-stimulated dendritic cells may also trigger a type I T helper cell response [16].

This immunostimulant has been shown to increase the production of various cytokines involved in the inflammatory response, such as tumor necrosis factor-α, monocyte chemotactic protein, IL-8 and -6.

Ribomunil also induces the production of interferon-γ by natural killer cells [17]. Finally, if Ribomunil triggers the TLR-2 pathway, it can stimulate the production of class 1 interferon (viral interferon) by antigen-presenting cells [18]. An increase in the titer of serum antibodies specific to four bacterial strains presented in Ribomunil was found, most of all Ig isotype A [19]. Moreover, IgA production in saliva increased sharply after two weeks of treatment, while the total amount of IgA remained unchanged. These specific IgA isotypes can completely inhibit bacterial adhesion to epithelial cells in vivo, and in a fairly physiological way [20]. Thus, as a result of a unique combination, this ribosomal vaccine has a dual mechanism of action, which allows it to be effectively used as a prophylaxis for bacterial and viral infections. All of the above data support the immunostimulating properties of Ribomunil and confirm its effectiveness in preventing recurrent infections or superinfections of the respiratory tract.

Clinical practice

A series of controlled clinical studies of children and adults has been published on the effectiveness of Ribomunil in respiratory diseases. These were studies that were conducted to an adequate level of compliance with Good Clinical Practice (GCP) standards and were sufficiently statistically representative. All these studies also assessed the effectiveness of prescribing Ribomunil according to official indications: for the prevention of IDPs in patients at risk of developing them at recommended doses. The use of ribosomal immunotherapy for 3 months led children with ENT infections to a statistically significant decrease in the frequency of respiratory infections compared to placebo (27 and 68%, respectively); the duration of episodes of IDP in patients receiving Ribomunil was lower than in the placebo group. The significance of the differences ranged from 0.05 to <0.001. As a result, fewer patients in the Ribomunil treatment groups required antibiotics than in the control groups, and there were fewer antibacterial courses per patient in the treatment groups than in the placebo group. After 6 months of treatment, these positive results were confirmed and in some cases improved, particularly with regard to the number of antibacterial courses and days of antibiotic use. When taking into account secondary criteria for the effectiveness of treatment, a significant difference was observed in such specific criteria as the percentage of children who required surgical interventions, such as tympanotomy or tonsillectomy (in the group receiving Ribomunil - 2%, in the placebo group - 21%, p = 0.02) , the average number of days missed from school. In studies conducted in children with mixed ENT/bronchopulmonary infections (318 children), similar results were obtained, with a significant reduction in the mean number of infections in patients receiving ribosomal immunotherapy compared with placebo. There was also a significant reduction in the average number of days with high fever in patients receiving ribosomal immunotherapy compared with placebo. Significantly less use of expectorants (p = 0.016) compared with placebo and an overall decrease in use of other drugs [21–23]. The use of Ribomunil for 1 to 6 months can successfully control the course of recurrent stenotic laryngotracheitis, promoting long-term (more than 3 years) remission of the disease [24]. Two double-blind studies were conducted among 475 patients with acute otitis media. Again, patients receiving ribosomal immunotherapy compared with placebo had fewer recurrent infections per patient (53% and 10% fewer in the two studies, respectively), and fewer antibiotic prescriptions (52 [p = 0.0018] and 26% fewer) [p = 0.05] respectively) and a significant reduction in the rate of adenoidectomy (p = 0.01 in one study) [22, 23]. Summarizing the data presented above, it can be noted: as a result of clinical studies, Ribomunil demonstrated effectiveness in the prevention of IDPs in children.

Many double-blind, placebo-controlled studies have been devoted to the use of Ribomunil in adults. The frequency of recurrent respiratory infections, as well as the number and duration of courses of antibiotics, were significantly reduced when the drug was prescribed to prevent recurrent respiratory infections [25, 26]. A multicenter study of Ribomunil in patients with chronic bronchitis showed that the drug prevents relapses in such patients [27]. Other double-blind studies reported significant reductions in the incidence of otitis media, sinusitis, and nasopharyngitis [28].

Ribomunil was also used to prevent IDPs in patients with bronchial asthma [29, 30]. I.K. Bogomolova et al. [31] used Ribomunil on 15 children with bronchial asthma aged 3 to 6 years. Clinical data, serum concentrations of Ig A, M, G, E, cytokines IL-1β, IL-4, tumor necrosis factor-α, interferon-γ, duration and frequency of ARVI episodes were assessed. It has been shown that under the influence of Ribomunil, immune defense factors are activated, the frequency and duration of acute respiratory viral infections are reduced, and the severity of clinical symptoms of diseases is reduced.

The use of Ribomunil helped reduce the frequency, severity and duration of acute respiratory viral infections, reduce asthma attacks, and normalize the ventilation capacity of the lungs. The influence of Ribomunil on immunoglobulin-mediated immunity was established, which consisted in the early stages of treatment in the correction of local immunity and acute-phase response, which led to a switch in the direction of immune reactions to inhibit allergic inflammation at later stages of therapy. Treatment with Ribomunil did not have a significant effect on thyroid hormonal status and glucocorticoid levels before and after the course of treatment with Ribomunil.

When studying the immunological parameters of children with asthma, an increase in the level of interferon-γ and a decrease in the level of IL-4 were noted. The clinical effect consisted of a reduction in the number of episodes of acute respiratory viral infections, asthma attacks, improvement in external respiratory function, and elimination of respiratory viruses from the nasopharyngeal epithelium [32, 33].

In his study, JA Hoffman [34] assessed the effectiveness of ribosomal immunotherapy in 338 children (age 4–17 years) with IDP and bronchial asthma. The main evaluation criterion was a clinical disease severity scale, which took into account the frequency of episodes of respiratory infections, the duration of episodes, fever, the need for antibacterial therapy, doctor visits, absences from school and work. Immunological parameters were taken into account as secondary efficacy criteria at the beginning of the study, after 4 and 7 months (end of the study). During the period of treatment with Ribomunil, the percentage of children protected from RTIs increased: the number of infectious episodes decreased (by 76%), the severity of clinical indicators (by 62%) and the need for antibiotics (by 71%) compared with the indicators before treatment. Immunological parameters corresponded to clinical improvements, in particular, there was a significant increase compared to the initial data in IgA at the 4th and 7th months, as well as IgG and IgM at the 7th (p < 0.05). The researchers concluded that these results support the clinical effectiveness of ribosomal immunostimulants for the prevention of RTI in children with bronchospastic syndrome.

Clinical experience with the use of Ribomunil in young children has been published. A study by JM Vautel [35] is devoted to the use of Ribomunil in children 1–4 years old. The purpose of this double-blind, placebo-controlled study was to determine the effectiveness and tolerability of Ribomunil in young children. Sixty-four children were included in the study and received treatment at the recommended dose. Significant decreases in all efficacy indicators were observed after 3 and 6 months in children receiving Ribomunil. After 6 months of treatment, the average number of infectious episodes was 3.39 in the Ribomunil group and 5.56 in the placebo group (39% decrease compared to placebo, p < 0.001), the average number of antibacterial courses was 1.32 in the Ribomunil group and 3.29 in the placebo group (60% reduction compared to placebo, p < 0.001). Other parameters, such as doctor visits (p < 0.01) and parental sick days (p-value not reported), were also better in children receiving ribosomal immunotherapy.

Safety and Tolerability

The clinical tolerability and safety of Ribomunil are considered quite good. Side effects associated with this drug are very rare in frequency and are similar in severity to placebo [23, 25]. In some studies, the percentage of children who had side effects was higher in the placebo groups (3.2%) than in the Ribomunil groups (1.6%). Side effects listed in the drug instructions include rare cases of mild ENT symptoms, fever, skin rashes and nausea. These data confirm that Ribomunil is a well-tolerated drug with side effects similar to placebo.

Conclusion

The use of Ribomunil has shown that its clinical effectiveness is associated with the stimulation of both specific and nonspecific immunity in children and adults, which helps prevent IDPs. A significant effect of Ribomunil on phagocytes and natural killer cells was noted. These cells appear to express receptors for bacterial components contained in Ribomunyl, the stimulation of which causes activation and/or maturation of these cell types. Such stimulation may be the underlying mechanism for most of the drug's biological effects in animals and humans [36]. In all double-blind, placebo-controlled studies, Ribomunil was effective in preventing recurrent ENT and bronchopulmonary infections. The drug reduced the number, severity and duration of infectious episodes, the number of antibacterial courses, concomitant medications (antitussives, expectorants, antipyretics, etc.) and the number of days parents missed school or work. It remains important to reduce the need for antibiotics during treatment with Ribomunil, which reduces the likelihood of developing antibacterial resistance.

Composition and release form

4 pcs in blister; 1 blister in a box.

12 pcs in blister; 1 blister in a box.

in sachets of 500 mg; There are 4 sachets in a box.

Pharmacodynamics

The ribosomal-proteoglycan complex is one of the most common causative agents of infections of the ENT organs and respiratory tract, and is a stimulator of specific and nonspecific immunity. The ribosomes included in its composition contain antigens identical to the surface antigens of bacteria, and when they enter the body they cause the formation of specific antibodies to these pathogens (vaccine effect). Membrane proteoglycans stimulate nonspecific immunity, which manifests itself in increased phagocytic activity of macrophages and polynuclear leukocytes and increased factors of nonspecific resistance. The drug stimulates the function of T- and B-lymphocytes, the production of serum and secretory immunoglobulins such as IgA, IL-1, as well as alpha and gamma interferon. This explains the preventive immunity of Ribomunil against respiratory viral infections. The use of Ribomunil in complex therapy can increase the effectiveness and shorten the duration of treatment, significantly reduce the need for antibiotics and bronchodilators, and increase the period of remission.

Ribomunil

Instructions for use:
RIBOMUNIL tablets
Registration number:

P N011369/01 dated 04/27/2010.

Trade name of the drug:

Ribomunyl.

International nonproprietary name:

does not have.

Dosage form.

Pills.

Compound.

1 tablet contains:

Active substances:

Ribosomal fractions: 0.75 mg (in terms of ribosomal RNA - 0.525 mg), Klebsiellapneumoniae - 3.5 shares, Streptococcuspneumoniae - 3.0 shares, Streptococcuspyogenes - 3.0 shares, Haemophilusinfluenzae - 0.5 shares, Membrane fraction: 1.125 mg, Klebsiellapneumonia - 15 shares.

0.525 mg) Klebsiellapneumoniae - 3.5 shares Streptococcuspneumoniae-3.0 shares Streptococcuspyogenes -3.0 shares

Haemophilusinfluenzae - 0.5 shares

Membrane fraction: 1.125 mg Klebsiellapneumonia - 15 shares

Excipients:

colloidal silicon dioxide -1.5 mg, magnesium stearate - 6.0 mg, sorbitol up to 294.0 mg.

Description.

Tablets are round, biconvex, white or almost white, odorless.

Pharmacotherapeutic group.

Immunostimulating agent of bacterial origin.

ATX Code:

L03AX.

Pharmacological properties.

Pharmacodynamics.

Ribomunil is a ribosomal-proteoglycan complex, which includes the most common pathogens of infections of the ENT organs and respiratory tract and is a stimulant of specific and nonspecific immunity. The ribosomes contained in the composition contain antigens identical to the surface antigens of bacteria, and when they enter the body they cause the formation of specific antibodies to these pathogens (vaccine effect). Membrane proteoglycans stimulate nonspecific immunity, which manifests itself in increased phagocytic activity of macrophages and polynuclear leukocytes and increased factors of nonspecific resistance. The drug stimulates the function of T and B lymphocytes, the production of serum and secretory immunoglobulins such as IgA, interleukin-1, as well as alpha and gamma interferon. This explains the preventive effect of Ribomunil against respiratory viral infections. The use of Ribomunil in complex therapy can increase the effectiveness and shorten the duration of treatment, significantly reduce the need for antibiotics and bronchodilators, and increase the period of remission.

Pharmacokinetics.

Ribomunil has good bioavailability. The macromolecules that make up Ribomunil do not undergo any special metabolism.

Indications for use.

Prevention and/or treatment of recurrent infections of the ENT organs (otitis, sinusitis, rhinitis, pharyngitis, laryngitis, acute tonsillitis) and respiratory tract (chronic bronchitis, tracheitis, pneumonia). Prevention of recurrent infections in patients at risk (frequently and for a long time ill, before the start of the autumn-winter season, especially in environmentally unfavorable regions, patients with chronic diseases of the ENT organs, chronic bronchitis, bronchial asthma).

Contraindications.

Hypersensitivity to the components of the drug, autoimmune diseases; acute intestinal infection; children under 6 years of age.

Carefully.

In patients with bronchial asthma, exacerbation of the disease is possible when taking immunostimulants containing bacterial components. If an asthmatic attack develops, the drug should be immediately discontinued and should not be resumed in the future. Use during pregnancy and breastfeeding.

No special studies have been conducted on the use of Ribomunil during pregnancy and breastfeeding. The use of Ribomunil during pregnancy and breastfeeding is possible only after assessing the expected benefit to the mother and the potential risk to the fetus and child.

Method of administration and dose.

Inside.

Adults and children over 6 years old - 1 time per day on an empty stomach. Single dose: 1 tablet. In the first month of treatment and/or for prophylactic purposes, Ribomunil is taken daily on the first 4 days of each week for 3 weeks; in the next 2-5 months: the first 4 days of each month. For young children, it is recommended to prescribe the drug in the form of granules. Side effect.

Rarely observed, characterized by:

Infectious and parasitic diseases:

rhinopharyngitis, sinusitis, laryngitis and bronchitis.

Immune system disorders:

hypersensitivity (urticaria, angioedema).

Disorders of the respiratory system, chest and mediastinal organs:

cough and exacerbation of bronchial asthma.

Digestive system disorders:

nausea, vomiting, diarrhea and abdominal pain, transient hypersalivation at the beginning of treatment.

Disorders of the skin and subcutaneous tissues:

eczema, erythema simplex and nodosum, vascular purpura.

General disorders and disorders at the injection site:

transient increase in body temperature (> 39 °C) at the beginning of treatment.

Overdose.

No significant adverse reactions were identified in case of drug overdose.

Interaction with other drugs and other types of interactions.

To date, no interaction with other drugs has been established. Ribomunil can be combined with medications such as: antibiotics, bronchodilators, anti-inflammatory drugs.

Special instructions.

A significant increase in body temperature (> 39° C) of unknown origin is possible, in which case the drug should be discontinued. This phenomenon should not be confused with a transient increase in body temperature, which is sometimes observed at the beginning of treatment and may be accompanied by minor and transient symptoms of infections from the ENT organs.

Release form.

Tablets 0.75 mg. 4 tablets in a PVC/aluminum foil blister. One blister along with instructions for use in a cardboard box.

Storage conditions.

At a temperature not exceeding 30° C. Keep out of the reach of children.

Best before date.

3 years. Do not use after expiration date.

, France.

RIBOMUNIL

granules for the preparation of solution for oral administration

Registration number:

P N011369/02 dated 04/27/2010.

Trade name of the drug:

Ribomunyl.

International nonproprietary name:

does not have.

Dosage form.

Granules for the preparation of a solution for oral administration.

Compound.

1 bag of granules contains:

Active substances:

Ribosomal fractions: 0.75 mg (in terms of ribosomal RNA - 0.525 mg), Klebsiellapneumoniae - 3.5 shares, Streptococcuspneumoniae - 3.0 shares, Streptococcuspyogenes - 3.0 shares, Haemophilusinfluenzae - 0.5 shares, Membrane fraction: 1.125 mg, Klebsiellapneumonia - 15 shares.

Excipients:

povidone - 10 mg, mannitol - 500 mg.

Description.

White granules, odorless.

Pharmacotherapeutic group.

Immunostimulating agent of bacterial origin.

ATX Code:

L03AX.

Pharmacological properties.

Pharmacodynamics.

Ribomunil is a ribosomal-proteoglycan complex, which includes the most common pathogens of infections of the ENT organs and respiratory tract and is a stimulant of specific and nonspecific immunity. The ribosomes contained in the composition contain antigens identical to the surface antigens of bacteria, and when they enter the body they cause the formation of specific antibodies to these pathogens (vaccine effect). Membrane proteoglycans stimulate nonspecific immunity, which manifests itself in increased phagocytic activity of macrophages and polynuclear leukocytes and increased factors of nonspecific resistance. The drug stimulates the function of T and B lymphocytes, the production of serum and secretory immunoglobulins such as IgA, interleukin-1, as well as alpha and gamma interferon. This explains the preventive effect of Ribomunil against respiratory viral infections. The use of Ribomunil in complex therapy can increase the effectiveness and shorten the duration of treatment, significantly reduce the need for antibiotics and bronchodilators, and increase the period of remission.

Pharmacokinetics.

Ribomunil has good bioavailability. The macromolecules that make up Ribomunil do not undergo any special metabolism.

Indications for use.

Prevention and/or treatment of recurrent infections of the ENT organs (otitis, sinusitis, rhinitis, pharyngitis, laryngitis, acute tonsillitis) and respiratory tract (chronic bronchitis, tracheitis, pneumonia). Prevention of recurrent infections in patients at risk (frequently and for a long time ill, before the start of the autumn-winter season, especially in environmentally unfavorable regions, patients with chronic diseases of the ENT organs, chronic bronchitis, bronchial asthma).

Contraindications.

Hypersensitivity to the components of the drug, autoimmune diseases; acute intestinal infection; children under 2 years of age.

Carefully.

In patients with bronchial asthma, exacerbation of the disease is possible when taking immunostimulants containing bacterial components. If an asthmatic attack develops, the drug should be immediately discontinued and should not be resumed in the future.

Use during pregnancy and breastfeeding.

No special studies have been conducted on the use of Ribomunil during pregnancy and breastfeeding. The use of Ribomunil during pregnancy and breastfeeding is possible only after assessing the expected benefit to the mother and the potential risk to the fetus and child.

Method of administration and dose.

Inside.

Adults and children over 2 years old - 1 time per day on an empty stomach.

Single dose: 1 bag of granules (granules are pre-dissolved in boiled water at room temperature). In the first month of treatment and/or for prophylactic purposes, Ribomunil is taken daily on the first 4 days of each week for 3 weeks; in the next 2-5 months: the first 4 days of each month.

Side effect.

Rarely observed, characterized by:

Infectious and parasitic diseases:

rhinopharyngitis, sinusitis, laryngitis and bronchitis.

Immune system disorders:

hypersensitivity (urticaria, angioedema).

Disorders of the respiratory system, chest and mediastinal organs:

cough and exacerbation of bronchial asthma.

Digestive system disorders:

nausea, vomiting, diarrhea and abdominal pain, transient hypersalivation at the beginning of treatment.

Disorders of the skin and subcutaneous tissues:

eczema, erythema simplex and nodosum, vascular purpura.

General disorders and disorders at the injection site:

transient increase in body temperature (> 39 °C) at the beginning of treatment.

Overdose.

No significant adverse reactions were identified in case of drug overdose.

Interaction with other drugs and other types of interactions.

To date, no interaction with other drugs has been established. Ribomunil can be combined with medications such as: antibiotics, bronchodilators, anti-inflammatory drugs.

Special instructions.

A significant increase in body temperature (> 39° C) of unknown origin is possible, in which case the drug should be discontinued. This phenomenon should not be confused with a transient increase in body temperature, which is sometimes observed at the beginning of treatment and may be accompanied by minor and transient symptoms of infections from the ENT organs.

Release form.

Granules for the preparation of a solution for oral administration 0.75 mg. 500 mg per laminated paper/aluminium sachet

foil/polyethylene. 4 sachets along with instructions for use in a cardboard box.

Storage conditions.

At a temperature not exceeding 30° C. Keep out of the reach of children.

Best before date.

3 years. Do not use after expiration date.

, France.

Indications for the drug Ribomunil

prevention and/or treatment of recurrent infections of the ENT organs (otitis, sinusitis, rhinitis, pharyngitis, laryngitis, tonsillitis) and respiratory tract (chronic bronchitis, tracheitis, pneumonia, infection-related bronchial asthma) in patients older than 6 months;

prevention of recurrent infections in patients at risk (frequently and for a long time ill, before the start of the autumn-winter season, especially in environmentally unfavorable regions, in patients with chronic diseases of the ENT organs, chronic bronchitis, bronchial asthma, including in children from 6 months and elderly patients).

Ribomunil gran.d/prepared solution d/pr.vn.in pack.500mg in pack No.4

Name

Ribomunyl.

Main active ingredient

Mibp

Release form

granules

Compound

1 sachet contains: Ribosomal fractions 10 parts, including: Ribosomes of Klebsiella pneumoniae 3.5 parts Ribosomes of Streptococcus pneumoniae 3.0 parts Ribosomes of Streptococcus pyogenes (group A) 3.0 parts Ribosomes of Haemophilus influenzae 0.5 parts Membrane fractions of Klebsiella pneumoniae 15 parts Excipients Povidone Yumg D-mannitol qs 500,000 mg

Description

White powder.

Dosage

500mg

Indications for use

This medicine is made from bacterial fractions. It is indicated for the prevention and treatment of recurrent infections of the JIOP organs (otitis, rhinitis, sinusitis, pharyngitis, laryngitis, tonsillitis) and respiratory tract (chronic bronchitis, tracheitis, pneumonia, infection-related bronchial asthma).

Contraindications

This medicine SHOULD NOT BE USED in the following cases: - you have a hypersensitivity (allergy) to the medicine or to one of its components. - in patients suffering from autoimmune disorders. IF YOU ARE IN ANY DOUBT, YOU SHOULD ALWAYS SEEK THE ADVICE OF YOUR DOCTOR OR PHARMACIST BEFORE TAKING ANY MEDICATION.

Directions for use and doses

Take 1 sachet 1 time per day: on an empty stomach in the morning, before meals. Pour the contents of the sachet into a glass, add water and stir. 1st month: 4 days a week for 3 weeks. The next five months: 4 days per month. IN ALL CASES, STRICTLY FOLLOW YOUR DOCTOR'S DIRECTIONS.

Side effect

LIKE ANY OTHER MEDICATION, THIS MEDICATION MAY CAUSE MORE OR LESS STRONG SIDE EFFECTS IN SOME INDIVIDUALS. - Temperature may increase during treatment. In this case, you should contact your doctor as soon as possible. — Rare cases of exacerbations have been described in patients with bronchial asthma after taking a drug containing bacterial extracts to stimulate the immune system. In this case, do not repeat the medication. - In rare cases, nasopharyngitis, sinusitis, laryngitis, bronchitis, and isolated cough may occur. - Allergic skin reactions (such as redness, itching, hives and rash) have been described. — At the beginning of treatment, transient hypersalivation is occasionally possible. - Rarely, gastrointestinal disturbances such as nausea, vomiting, diarrhea and abdominal pain may occur. DO NOT HESITATE TO CONSULT YOUR DOCTOR OR PHARMACIST AND TELL THEM ABOUT ANY UNPLEASANT OR UNWANTED SIDE REACTIONS THAT ARE NOT LISTED IN THE INSERT.

Overdose

If you take more RIBOMUNIL than you should, contact your doctor or pharmacist.

Storage conditions

There are no special storage conditions. Keep out of the reach of children.

Buy Ribomunil gran.d/prepared solution d/pr.vn.v pak.500mg in pack No. 4 in the pharmacy

Price for Ribomunil gran.d/prepared solution d/pr.vn.in pack.500mg in pack No.4

Instructions for use for Ribomunil gran.d/prepared solution d/pr.vn.in pak.500mg in pack No. 4

Directions for use and doses

Orally (for adults and children over 6 months), 1 time per day, in the morning, on an empty stomach. A single dose (regardless of age) is 3 tablets. 0.25 mg (with 1/3 of a single dose) or 1 tablet. 0.75 mg (with 1 dose), or granules from 1 sachet, pre-dissolved in boiled water at room temperature. In the first month of treatment and/or for prophylactic purposes, Ribomunil is taken daily 4 days a week for 3 weeks, in the next 5 months - the first 4 days of each month. It is recommended to use granules for young children.

Immunotherapy: mechanism of action and clinical use of immunocorrective drugs

The number of chronic inflammatory, allergic, autoimmune, endocrine, oncological and other diseases is steadily increasing. Data from epidemiological and statistical studies in recent years indicate a significant deterioration in the nation's health. The experience of world practice in immunoprophylaxis shows that this category of people primarily needs vaccination against infectious diseases. There is evidence that, from a clinical point of view, vaccination of people with various health conditions is safe, but the strength of their immune response is lower than that of practically healthy people. To stimulate the formation of post-vaccination immunity in such patients, various immunomodulatory drugs are prescribed.

It should be noted that Russian researchers have the greatest experience in this area, who have shown that with the correct selection of an immunomodulating drug and its administration regimen, it is possible to obtain a rapid and complete immune response to vaccination in individuals suffering from various pathologies.

One of the main goals when prescribing an immunomodulatory drug during preventive vaccination in persons with various health conditions is not only the prevention of an infectious disease, but also the achievement of positive dynamics in the course of the underlying disease. In this case, the doctor needs to make the right choice of an immunocorrective drug, taking into account not only the nosological form of the disease, but also the initial indicators of the immune status.

The human immune system performs an important function of maintaining the constancy of the internal environment of the body, carried out by recognizing and eliminating from the body foreign substances of an antigenic nature, both endogenously arising (cells modified by viruses, xenobiotics, malignant cells, etc.) and exogenously penetrating ( primarily microbes). This function of the immune system is carried out with the help of factors of innate and acquired (or adaptive) immunity. The first include neutrophils, monocytes, macrophages, dendritic cells, NK and NKT lymphocytes; the second includes T and B cells, which are responsible for the cellular and humoral response, respectively. When the number and functional activity of immune system cells is disrupted, immunological disorders develop: immunodeficiencies, allergic, autoimmune and proliferative processes.

Modern pathology is characterized by the presence of two interrelated and interdependent processes, namely: an increase in the number of chronic infectious diseases caused by opportunistic or opportunistic microbes and a decrease in the immunological reactivity of the population, observed in almost all developed countries.

It is obvious that it is almost impossible to cope with the increase in infectious diseases using antibiotics alone. The antibiotic suppresses the reproduction of the pathogen, but its final elimination from the body is the result of the activity of immune factors. Moreover, long-term uncontrolled use of antibiotics reduces the body's immunological reactivity. Therefore, against the background of suppressed immunoreactivity, the effectiveness of antibiotics, as well as antifungal, antiviral and other chemotherapeutic agents, decreases.

In this regard, doctors' interest in drugs that act on the body's immune system has now sharply increased. The market offers a large number of medicines, food supplements and simply food products that act on the immune system. It is often difficult for a practicing doctor to understand this huge flow of information and proposals and choose the right remedy. In addition, there is currently a lot of confusion in the definitions of what an immunocorrector, an immunomodulator, an immunostimulant is.

The administration of drugs of a chemical or biological nature that have immunotropic activity for therapeutic or prophylactic purposes in diseases associated with immune disorders (the therapeutic effect is associated with their preferential or selective effect on the human immune system) is called immunotherapy, and the drugs themselves can be divided into four large groups:

• immunomodulators;
• immunocorrectors;
• immunostimulants;
• immunosuppressants.

Immunomodulators are drugs with immunotropic activity that, in therapeutic doses, restore the functions of the immune system (effective immune defense).

Immunocorrectors are means and effects (including medicinal ones) that have immunotropism, which normalize a specific disturbed part of the immune system (components or subcomponents of T-cell immunity, B-cell immunity, phagocytosis, complement). Thus, immunocorrectors are immunomodulators of “point” action.

Immunostimulants are drugs that enhance the immune response (medicines, nutritional supplements, adjuvants and other agents of biological or chemical nature that stimulate immune processes).

Immunosuppressants are drugs that suppress the immune response (drugs that have immunotropic or nonspecific effects, and various other agents of biological or chemical nature that suppress immune processes).

In order for a particular drug to be classified as an immunomodulator, its ability to change the body’s immunological reactivity must be proven depending on its initial state, i.e., the ability to increase or decrease, respectively, decreased or increased immunity levels. To do this, the drug under investigation must undergo preclinical trials conducted in accordance with the Methodological Recommendations approved by the State Pharmacological Committee under the Ministry of Health of the Russian Federation dated December 10, 1998. As a result of these tests, its immunomodulatory effect on the components of the immune system must be proven: phagocytosis, complement system, humoral immunity, cellular immunity, cytokine system. Next, the investigational drug must undergo clinical trials in accordance with GCP rules, as a result of which its clinical and immunological effectiveness will be proven based on a double-blind randomized study. Ultimately, the drug is registered by the Federal State Committee of the Russian Ministry of Health as an immunomodulator and permission is issued for its widespread medical use and industrial production.

Only the drug that has passed preclinical and clinical trials according to the rules described above meets the requirements for immunomodulatory drugs.

When analyzing the pharmacological action of immunomodulators, it is necessary to take into account the amazing feature of the functioning of the immune system, which “works” like communicating vessels, i.e. the presence of a load on one “bowl” sets the entire system in motion. In this regard, regardless of the initial direction, under the influence of the immunomodulator, the functional activity of the entire immune system as a whole ultimately changes to one degree or another. An immunomodulator can have a selective effect on the corresponding component of the immune system, but the final effect of its impact on the immune system will always be multifaceted. For example, substance X induces the formation of only one interleukin-2 (IL-2). But this cytokine enhances the proliferation of T, B and NK cells, increases the functional activity of macrophages, NK cells, cytotoxic lymphocytes (CTL), etc. IL-2 is no exception in this regard. All cytokines are the main regulators of immunity, mediating the effect on the immune system of both specific and nonspecific stimuli, and have multiple and diverse effects on the immune system. Currently, no cytokines with strictly specific activity have been identified. Such features of the functioning of the immune system make it almost impossible for an immunomodulator to exist with an absolutely selective final effect on the immune system. This position allows us to formulate the following principle.

Any immunomodulator that selectively acts on the corresponding component of immunity (phagocytosis, cellular or humoral immunity) will, to one degree or another, affect all other components of the immune system.

There are three main groups of immune system diseases: immunodeficiencies, allergic and autoimmune processes. Let's consider for which diseases it is advisable to use immunomodulators.

Allergic diseases. For allergic diseases, the use of immunomodulators is advisable in cases where these diseases are complicated by any manifestations of secondary immune deficiency: for example, atopic dermatitis with pyoderma, bronchial asthma with symptoms of chronic purulent-obstructive bronchitis, recurrent herpetic or cytomegalovirus infection, etc. In these cases, the effect of immunomodulators is aimed at eliminating the infectious focus in a patient with an allergic process. In some cases, this can significantly improve the clinical picture of the underlying disease. For example, the use of immunomodulatory therapy in patients with bronchial asthma can extend the duration of remission to one year. However, in all these cases, immunomodulatory therapy is not aimed at the main cause of the disease, i.e., it is not etiotropic. As is known, in allergic diseases, Th2 cells are activated and the production of cytokines IL-4, IL-5, IL-13 is increased. IL-5 promotes eosinophil maturation and activation. IL-4 and IL-13 induce B cells to synthesize immunoglobulin IgE. Consequently, from an immunological point of view, increased activity of Th2 cells is the main link in the pathogenesis of allergic reactions. From here it becomes obvious that one of the directions in the immunomodulatory therapy of these processes is the use of drugs that reduce the activity of Th2 cells and increase the activity of Th1 cells, i.e. immunomodulators.

Autoimmune diseases. For autoimmune diseases, immunotropic drugs belonging to the group of immunosuppressants, the action of which is aimed at suppressing the autoimmune inflammatory process, are currently widely used. Their use, as a rule, gives a quick and good clinical effect. However, such treatment probably cannot be considered etiotropic, since it is aimed at the pathogenesis, and not at the cause of the disease. Thus, the use of hormonal drugs for multiple sclerosis, which is a Thl-mediated disease, gives a good clinical effect, but does not prolong the duration of remission - an important indicator of the effectiveness of therapy. The etiopathogenesis of many autoimmune diseases, as in allergic processes, is based on a Th1/Th2 imbalance. With multiple sclerosis, rheumatoid arthritis, autoimmune thyroiditis, increased activity of Th1 cells is observed, with systemic lupus erythematosus, autoimmune vasculitis, and some types of anemia - Th2 cells. The basis for the use of immunomodulators in autoimmune processes, as well as in allergies, are infectious processes that complicate the course of the underlying disease.

Immunodeficiencies. Increased infectious morbidity is the main manifestation of both primary and secondary immunodeficiencies. The question arises: is it advisable to use immunomodulatory drugs for primary immunodeficiencies, which are based on a genetic defect. Naturally, it is impossible to correct a genetic defect with the help of these drugs. But anti-infective protection is multicomponent, and it can be expected that with some increase in the functional activity of a normally functioning component of the immune system using immunomodulators, the “poor performance” of the defective component will be compensated, at least partially. A significant improvement in the clinical condition and indicators of immune status is observed in patients with reduced levels of all classes of immunoglobulins (general variable immunological deficiency) when treated with immunomodulatory drugs that activate phagocytosis, in particular Polyoxidonium. Well-thought-out use of immunomodulatory therapy in patients with some forms of primary immunodeficiencies can lead to good clinical results.

The main target for the use of immunomodulatory drugs is secondary immunodeficiencies, which are characterized by frequent, recurrent, difficult-to-treat infectious and inflammatory processes of all localizations and any etiology. Any chronic infectious-inflammatory process is based on certain changes in the immune system, which serve as one of the reasons for the existence of this process. A study of the parameters of the immune system may not always reveal these changes, therefore, if there is a chronic infectious-inflammatory process in the body, the patient can be prescribed immunomodulatory drugs even if the immunodiagnostic study does not reveal significant deviations in the immune status. As a rule, in these processes, depending on the type of pathogen, the doctor prescribes antibiotics, antifungals, antivirals or other chemotherapeutic drugs. We believe that in all cases when a doctor prescribes antimicrobial agents for symptoms of secondary immunological deficiency, immunomodulatory therapy should also be prescribed. When treating processes, immunomodulators are used mainly in complex treatment together with etiotropic chemotherapeutic agents.

Thus, the main criterion for prescribing an immunomodulator is the clinical picture of the disease, manifested by the presence of a chronic infectious-inflammatory process that is difficult to adequately respond to anti-infectious treatment.

The question arises: how to use immunomodulators in the complex treatment of chronic infections. We believe that immunomodulators should be prescribed not after or before taking antibiotics or antiviral drugs, but simultaneously with them. In this case, the pathogen will be dealt a double blow: an antibiotic or other chemotherapeutic agent reduces the functional activity of the microbe, and the immunomodulator increases the functional activity of the cells of the immune system, thereby achieving more effective elimination of the pathogen from the body. The “fashionable” statement about the negative impact of antibiotics on the immune system should be avoided. Currently, doctors have a number of antibiotics that do not have an inhibitory effect on the immune system. All other things being equal, the doctor should give preference to the latter. A separate issue is the use of immunomodulators for acute bacterial and viral infections.

As a rule, their use is not recommended for acute processes, since this can aggravate their course. For example, during a viral infection, activation of CTLs can cause a fatal outcome due to massive destruction of tissues infected by the virus. This should probably be kept in mind when prescribing chemicals, as well as drugs of bacterial origin, which are powerful inducers of pro-inflammatory cytokines. The use of immunomodulators in acute infectious processes, especially of the bronchopulmonary apparatus, may be justified in immunologically compromised people, for example, in people who are often and long-term ill. In these cases, immunomodulators are used to prevent the development of post-infectious complications. The presence of detoxifying and antioxidant properties in Polyoxidonium makes it possible to use it in acute infectious diseases. Clinical practice shows the effectiveness and safety of its use in acute infections. We believe that not only Polyoxidonium, but also other immunomodulators with antioxidant and detoxifying properties can be used in acute infectious processes in immunologically compromised individuals.

The question often arises whether immunomodulation can be performed as monotherapy. R.?V.?Petrov was the first to formulate the concept of “immunorehabilitation”, which is understood as a complex of medicinal and non-medicinal therapeutic measures aimed at restoring the functional activity of the immune system and human health. We believe that during immunorehabilitation measures, immunomodulators can be used as monotherapy and in combination with various restorative agents. This is justified:

• in people with incomplete recovery (presence of bronchitis, laryngitis, tracheitis, etc.) after suffering an acute infectious disease;
• in people who are often and long-term ill before the start of the autumn-winter season, especially in environmentally unfavorable regions;
• in cancer patients to improve quality of life.

In conclusion, we can formulate some general principles for the use of immunomodulators in patients with insufficient anti-infective protection:

• Immunomodulators are prescribed in complex therapy simultaneously with antibiotics, antifungals, antiprotozoals or antivirals.
• It is advisable to early prescribe immunomodulators from the first day of using a chemotherapeutic etiotropic agent.
• Immunomodulators acting on the phagocytic component of immunity can be prescribed to patients with both identified and unidentified disorders of the immune status, i.e., the basis for prescribing the drug is the presence of clinical markers of immunodeficiency.
• If a given medical institution has the appropriate material and technical base, it is advisable to use immunomodulators against the background of immunological monitoring. This monitoring should be carried out regardless of whether initial changes in the immune system are detected or not.
• Immunomodulators can be used as monotherapy when carrying out immunorehabilitation measures, in particular, in case of incomplete recovery after an acute infectious disease.
• A decrease in any parameter of immunity detected during an immunodiagnostic study in a practically healthy person is not necessarily a basis for prescribing immunomodulatory therapy.

Use of immunomodulators in clinical practice

In recent years, Ribomunil, a ribosomal immunomodulator of bacterial origin, has been successfully used. The clinical effectiveness of Ribomunil is due to its complex immunomodulatory effect. Ribomunil contains ribosomal fractions of Streptococcus pneumoniae, S. pyogenes, Haemophilus influenzae, Klebsiella pneumoniae, as well as K. pneumoniae cell wall proteoglycans. The analysis of the effectiveness of including Ribomunil in the complex of rehabilitation measures for frequently ill children indicates that the rate of their recovery was significantly ahead of the similar indicators of the comparison group [8, 9, 10]. It was found that the effect of ribosomal immunization appeared already in the first three months of therapy and subsequently persisted for another 18 months.

At the same time, the frequency of acute respiratory infections during the monitoring period generally decreased by 43.3–53.8%. It should be especially emphasized that, thanks to a decrease in respiratory morbidity, the number of temporary medical exemptions from vaccination within the prescribed periods was significantly reduced. In the observed organized children's groups, this made it possible to achieve a regulated level of vaccination coverage. In addition, it was found that the use of Ribomunil not only prevents the development of respiratory infections, but also significantly affects the effectiveness of vaccination. It was noted that a significant increase in the preventive effectiveness of influenza vaccination in frequently ill children can be achieved if they are vaccinated while taking Ribomunil. Similar results were obtained by V.?F.?Uchaikin et al. (2000) during influenza vaccination in children with various health conditions [10, 11]. The authors showed that in children vaccinated against influenza and simultaneously receiving Ribomunil, the total incidence of influenza and other acute respiratory viral infections was 2.5 times lower than in the group where only active specific immunization was used.

Currently, there are positive results from the use of a drug such as Imunofan as a means of immunorehabilitation. The choice of the drug is due to the fact that Imunofan has virtually no effect on the production of reagin antibodies of the IgE class and thereby does not enhance immediate hypersensitivity reactions. Moreover, in individuals with an initially high level of antibodies of this class (bronchial asthma, atopic dermatitis, hay fever, angioedema), the use of Imunofan led to a decrease in the concentration of IgE with a decrease in the severity of clinical manifestations of diseases [15, 16]. The instructions for the drug Imunofan, approved by the Pharmacological Committee of the Ministry of Health of Russia, regulate the use of the drug in the vaccine prophylaxis scheme.

T.?P.?Markova and D.?G.?Chuvirov (State Educational Establishment Institute for Advanced Studies "Medbioextrem" of the Ministry of Health of Russia, Moscow) used Imunofan for revaccination against diphtheria of 60 long-term and often ill children with a specific antibody titer of 1:20–1 :40 before the II and IV revaccination with ADS-M [12]. It was found that the combined use of Imunofan during revaccination with ADS-M does not lead to an increase in post-vaccination reactions and increases the effectiveness of vaccination by 1.7–1.8 times, the effect of which persists for a year.

The effect of the use of Myelopid and Polyoxidonium (combined use of Polyoxidonium at a dose of 3–6 mg or Myelopid at a dose of 3 mg intranasally within 5 days from the day of vaccination or intramuscularly on the day of vaccination) was also studied during revaccination against diphtheria in 90 children who did not have a protective titer antibodies against diphtheria, before the second and fourth revaccination. The age of children is from 6 to 14 years [13]. The geometric mean antibody titer in children who received Polyoxidonium or Myelopid intranasally simultaneously with revaccination at various periods of the examination was higher than in the control group revaccinated in the usual way (after 45 days; 6 months; 1 year), the difference was statistically significant. Moreover, in the control group, 5 (14%) children 45 days later and 11 (31.8%) children 1 year after revaccination did not have a protective antibody titer, which was not observed in children receiving immunocorrectors.

With combined intranasal or intramuscular use of Myelopid or Polyoxidonium, an increase in macrophage parameters (phagocytosis, chemiluminescence), the absolute number of CD3+, CD4+ T cells, serum immunoglobulins IgG, IgA was also observed compared to the control group. Similar data were obtained by the authors during revaccination against the background of the use of Myelopid and Polyoxidonium for hepatitis B, measles, rubella, and mumps in frequently ill children [13].

S.?M.?Kharit (Research Institute of Childhood Infections of the Ministry of Health and Social Development of the Russian Federation), E.?P.?Nacharova, S.?V.?Petlenko (Military Medical Academy named after S.?M.?Kirov, St. Petersburg) the effect of the drug Thymogen on the effectiveness and safety of vaccination against measles and mumps was assessed [14]. Children of the first group (16 people), 10 days before vaccination, received intranasally the synthetic peptide immunomodulator Thymogen (0.025% solution of glutamyl-tryptophan in 0.9% NaCl in the form of a metered spray) daily for 5 days at a dose of 25 mcg once a day. The use of the drug was completed 5 days before vaccination.

In children of the second group (16 children), a spray with saline solution containing no active substance was used as a placebo according to the same scheme. Observation in the dynamics of the post-vaccination period showed that in the group receiving placebo, two children (14.3%) had normal vaccine reactions from the 6th to the 9th day in the form of hyperemia of the pharynx, rhinitis, low-grade fever 37.2–37. 5 °C.? One child (7.1%) from this group fell ill with an acute respiratory infection on the 17th day after immunization. In the group vaccinated with preliminary use of Thymogen, all children had an asymptomatic course of the post-vaccination period and not a single child fell ill within a month after vaccination. Not a single child had any unusual or pathological reactions to the vaccine.

A study of antibody titers depending on their level showed that preliminary use of Thymogen led to the fact that already on the 14th day, a protective titer of anti-measles antibodies was determined in 100% of those examined, while in the placebo group 35.7% of individuals had specific antibodies were not determined. Moreover, in 87.5% of children in the first group, titers of specific antibodies were higher than when using placebo. The dynamics of anti-mumps antibodies were similar.

The results obtained allowed the authors to conclude that the divaccine is a low-reactogenic drug, and the administration of Thymogen before immunization contributes to a smoother course of the post-vaccination period and has a pronounced stimulating effect on the intensity of specific antibody formation, promoting the formation of protective antibody titers in all vaccinated individuals by the 14th day and the predominance of high antibody titers in 80–100% of those vaccinated on the 30th day after revaccination.

Interesting data were obtained from the use of topical bacterial lysate IRS 19 and the drug Viferon in frequently ill children before vaccination against measles and mumps. The use of IRS 19 in the pre-vaccination period helped to reduce the degree of antigenic load, prepare children for vaccination, reduce intercurrent diseases and reduce adverse reactions in the post-vaccination period, and create specific immunity at a high protective level. Vaccination against the background of Viferon made it possible to avoid the accumulation of intercurrent diseases and also reduce the number of undesirable post-vaccination reactions, contributed to the rapid formation and slower decrease in the level of antibodies to the measles and mumps virus [17].

The use of immunocorrective drugs in patients with impaired health before vaccination and during the post-vaccination period helps to reduce the accumulation of intercurrent diseases, ensures a “smooth” course of the post-vaccination period, promotes the rapid and intense production of specific antibodies, which ultimately leads to an increase in vaccination coverage within the prescribed period and improving the quality of children's health.

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V. P. Afinogenova I. V. Lukachev M. P. Kostinov , Doctor of Medical Sciences, Professor

State Research Institute of Vaccines and Serums named after. I. I. Mechnikova RAMS , Moscow

Contact information for authors for correspondence