Interview with an immunologist: answers to questions about vaccination

Lycopid

Lykopid (glucosaminylmuramyl dipeptide) is an immunotropic drug of the muramyl dipeptide series. This group of drugs was introduced into medical practice in the 70s of the last century, but until now only two such drugs are used: the Japanese Romurtide and the Russian Likopid. The latter is an original development of domestic scientists, which turned out to be a by-product of research into the antitumor drug blastolysin. Lykopid is a pronounced immunostimulant with a weak pyrogenic effect, which has a multidirectional effect on the immune system. The drug is endowed with the ability to stimulate both the cellular and humoral components of the immune response. The clinical trial of the drug in leading Russian clinics was carried out in three stages in accordance with the standards of Good Clinical Practice. The drug passed all testing procedures with honor and was indicated for use in medical practice in the combined treatment of secondary immunodeficiency conditions, including chronic nonspecific diseases of the respiratory tract, postoperative or post-traumatic inflammatory processes with abundant exudation, genitourinary tract infections, herpetic infections, cytomegalovirus, candidiasis, etc. .d. For chronic nonspecific diseases of the respiratory tract, the drug significantly increases the period of remission after a course of drug therapy. When treating complications that developed after surgical interventions, Lykopid prevented their further progression, and when used as a prophylactic agent, it did not allow them to develop. Likopid increases the level of neutrophils, reduces the concentration of creatinine, urea, and bilirubin. In patients with trophic ulcers, the drug suppresses inflammatory processes, promotes cleansing and closure of the wound by the beginning of the third week of pharmacotherapy.

It is important that in some cases the drug provided the necessary therapeutic effect without the use of antibiotics. This fact proves that Lykopid is capable of stimulating repair processes. The drug also shows good results in the treatment of herpetic lesions of the cervix, both in complex treatment and as part of monotherapy: a decrease in the number of relapses, the disappearance of koilocytosis, and an increase in the number of fully recovered patients were noted. The effectiveness of Lykopid increases when used in combination with antibiotics and antiviral drugs. With the combined treatment of herpesvirus infections, a significant improvement in the clinical situation is observed already on the 3-4th day of pharmacotherapy. The peak concentration of the active component of the drug is observed 1.5 hours after administration. The drug has a relatively low bioavailability - about 10% when taken orally. The half-life of Lykopid is 4.3 hours. Elimination from the body is carried out by the kidneys. The optimal time to take it is half an hour before meals. Method of administration: sublingual (sublingual) or orally by swallowing. At the initial stage of pharmacotherapy, it is possible for the temperature to rise to a subfebrile level, which goes away on its own and does not require stopping the medication course. The use of Licopid during pregnancy and breastfeeding is not allowed. The drug can be used in pediatric practice after the child reaches one year of age. Tetracyclines and sulfonamides are not suitable for combination with Lykopid.

Interview with an immunologist: answers to questions about vaccination

Dear friends, today we have an unusual guest in our “Interview with a Doctor” column. Our director, geneticist and candidate of medical sciences. Oksana Alekseevna Makeeva talked with Elena Georgievna Churina, MD, professor, immunologist-allergist. The topic is very relevant and will be devoted to vaccination against the new coronavirus infection.

O.A.: Elena Georgievna, let’s start right away with the main question. Please tell us whether everyone can be vaccinated, what are the contraindications, what are the complications?

E.G.: Of course, it’s impossible to vaccinate everyone. Absolute contraindications for vaccination are pregnancy, autoimmune diseases, cancer, allergic diseases in the acute stage, any history of anaphylactic reactions. There are still many relative contraindications; in this case, the issue is decided by the patient’s attending physician.

The vaccination that is now being actively proposed and implemented is in fact a continuation of the third phase of testing - clinical studies. Clinical research is a very long and important stage and its main goals are: obtaining objective and complete data on the safety and effectiveness of the vaccine, identifying side effects, including long-term effects, assessing the risk-benefit ratio when using the vaccine being studied. And this cycle usually lasts for 3-5 years! Recently, information has emerged about thromboembolic complications, including the development of strokes, in people after vaccination with the Astra Zeneca vaccine in several European countries. Let me remind you that this vaccine, similar to the Sputnik V vaccine, was also developed on an adenoviral platform.

Thus, the Sputnik V vaccine did not go through the expanded and full-scale third phase and entered into civilian circulation prematurely, with accelerated early registration and with the motivation of active vaccination of the population, to create collective immunity and protection against the virus. In fact, everything is much more complicated. Vaccination will never protect against the virus entering the body. It is needed in order to avoid severe infection and fatal complications. Antibodies remain in the bloodstream for some time and, if they are neutralizing, they can bind to certain proteins of the virus, for example, the S protein of the coronavirus. But this protection will only work when the virus bypasses the first line of defense on the mucous membrane of the oropharynx and enters the bloodstream. In the vast majority of patients, the entire dynamics of ARVI, from the penetration of the virus into the body to recovery, unfolds in the upper respiratory tract.

O.A.: Let's differentiate between the basic vaccination of a child according to the national calendar and the vaccination of the adult population against respiratory viral infections, that is, against influenza and now, against COVID-19.

E.G.: The characteristics of the immune response are different for each person, in this regard we are all unique. Where does the immune response begin? The virus enters the body and immediately lands on the mucous membrane of the nasopharynx and oropharynx - the entrance gate for infection. The innate immune system is activated, its key cells—macrophages—and inflammation immediately starts. Why do we vaccinate? In order for a pool of protective antibodies to form in the blood, which will block viral proteins and prevent the virus from multiplying and infecting other cells, already in the lower parts of the respiratory tract. They will work only when the infection generalizes, and not in the first 5-7 days, when the whole process occurs on the mucous membranes of the upper respiratory tract; this requires effective local defense mechanisms - secretory IgA, macrophages, local T-killer cells and antimicrobial proteins . Thus, the vaccine will not protect against infection, it will protect against possible complications, and only if neutralizing antibodies to the S-protein are produced.

As for vaccinating children against especially dangerous infections in accordance with the national calendar of preventive vaccinations, there are completely different mechanisms for implementing the immune response to infection initially. These infections have an early and persistent stage of viremia - the presence of the virus in the blood and a long incubation period, unlike respiratory viruses. And after such vaccination, stable lifelong immunity is formed, T- and B-memory cells are formed, which live with us all our lives.

O.A.: How does natural immunity after illness differ from artificial immunity achieved through vaccination? In the first case, the mucous membranes are protected, but not in the second?

E.G.: Not exactly. The mucous membranes can never be fully protected. Natural or innate immunity is very powerful and comprehensive; the majority of living beings on earth survive well only with innate mechanisms. Highly specific adaptive immunity is a later evolutionary acquisition in mammals and is associated with the unique, selective specificity of antigen recognition receptors on T and B lymphocytes. If there is even a slight change in the genome of the microbe, then the immune response will again develop as before. And all respiratory viruses, as a rule, contain RNA and mutate very quickly. Have you already read about different mutations of COVID-19? Italian, Brazilian, British, etc. mutations, and there will be a lot of them. The coronavirus still has several mutations, but it is highly mutable, and each genomic sequence will have a different specificity of lymphocyte receptors. So what, should you vaccinate against each strain? Therefore, it is quite problematic to create an effective vaccine against any respiratory viruses.

When a person has already realized a natural immune response to a certain virus, even if there were no clinical signs of the disease, then a wide variety of protective factors have been developed, and these are not only antibodies! It is incorrect to evaluate the antiviral immune response as antibody or humoral. The antiviral response is, first of all, a T-cell immune response, the first line of defense on the mucous membranes, macrophages, numerous antimicrobial proteins, contact interactions between cells, reactions that determine the further scenario of the immune response as a whole. It’s good if there are antibodies, but they will not be able to completely protect the body, and vice versa, if they are not there, this does not mean that we are without protection from coronavirus.

O.A.: If we administer the vaccine subcutaneously, will this only stimulate the antibody response and there will be no other immunity?

E.G.: No, different immune responses will develop. The antigen in the vaccine structure has entered the circulation, the necessary processes of forming a T-cell response will definitely be launched. But it is impossible to absolutely extrapolate this situation to the natural penetration of the virus through the mucous membranes of the upper respiratory tract. Why do we constantly talk about the fact that there are so many “asymptomatic patients” and patients with mild infections? Yes, precisely because our unique internal immune defense mechanisms work in time and block the replication of the virus. The situation with the vaccine is a little different - we introduce an antigen into the body in the structure of an adenovirus (Sputnik V) and cannot say for sure what mechanism the immune response will take. If antibodies are already present, very severe adverse reactions can occur, such as antibody-dependent enhancement of infection (ADI).

O.A.: Is this the body’s reaction to vaccination or a reaction to re-infection, when the body already has antibodies and there is a collision with the virus?

E.G.: It may be both situations. If a person has been ill asymptomatically, although I really don’t like this strange formulation “asymptomatic patient,” that is, he simply encountered the virus somewhere, and he already has active protective immunity, memory cells and antibodies. When the vaccine is administered in this case, a very acute course of the disease with complications is possible. I would recommend that you conduct a study for the presence of all types of antibodies to COVID-19 before deciding to vaccinate. ADUI occurs because an immune complex is immediately formed: antibodies that are already in the body, plus the virus and proteins of the complement system, and acute inflammation is triggered. If there are a lot of antibodies, then these complexes will be absorbed into cells by macrophages, interact with certain receptors, but, instead of collapsing and dying, the virus will continue to multiply in macrophages. And in this situation, the development of a cytokine storm is possible. Therefore, I would not recommend getting vaccinated for those who have already been ill.

O.A.: Please tell us, do everyone develop antibodies after a coronavirus infection? Is it possible to get sick and not have antibodies?

E.G.: Antibodies will always be there initially, but there may be few of them, and after some time, they simply will not be detected by enzyme immunoassay, in other words, trace amounts of antibodies will remain. And this has an important biological meaning that antibodies undergo rapid degradation. This is an immunoregulatory mechanism aimed at preventing potential autoimmune processes. There is nothing good in the constant circulation of any antibodies throughout the body; these are canonical principles of immunology, you can read them in any textbook.

In addition, as a rule, there is no correlation between the clinical course of the disease and the titer of antibodies in the blood during any viral infections. In my practice, there are patients with recurrent herpes infections, but with very low levels of antibodies to herpes viruses.

Establishing a clinical diagnosis is, first of all, the clinical thinking of a doctor. And today we see a picture where all diagnostics are reduced to laboratory and instrumental methods. For example, CT. It is surprising how easily this serious examination, with a very high radiation dose, is prescribed. And what do we see? For example, 90% of lung damage according to CT? This is just a picture of ground glass, pneumonitis, systemic inflammation of small vessels and edema, this is not a lesion of the alveoli, if it were so, then the person would no longer live. We must focus on the objective status and general condition of the patient, his mood, well-being, and activity. If a person is doing well and feels great, and a CT scan shows, for example, 30% damage to the lungs, in some cases he was still recommended for urgent hospitalization, as a result, a practically healthy person fell ill with hospital-acquired bacterial pneumonia, and everything ended fatally.

O.A.: For a cytokine storm to occur, a person must simultaneously receive a large number of coronavirus particles?

E.G.: A large number of viral particles, approximately 1000, must be obtained in order to get sick with Covid. A cytokine storm develops with the activation syndrome of macrophages, the most important cells of the innate immune system, and this is not such a common complication, but it can be provoked by the use of interferons and drugs such as Kagocel and Ingavirin. What happened a year ago, from the very beginning of the epidemic? At the first stage, even asymptomatic patients with only a positive PCR test for coronavirus were taken to hospitals, everyone lay together. In this way, foci of infection were formed inside hospitals, the antigenic load on the immune system of patients increased exponentially, and the worst thing was that nosocomial bacterial superinfection developed, resistant to all antibiotics that exist today.

When I saw the first protocols for the treatment of COVID-19, I realized that, as far as possible, I would protect people from hospitalization. Several types of antibiotics, antimalarial drugs and drugs for HIV infection - even a healthy and young person can die from the side effects of such treatment.

O.A.: If a person receives a small amount of coronavirus, will he cope with it easier than if he receives a lot at once?

E.G.: Yes, of course. When there are few viral particles, most likely there will be no manifestations of infection at all; a high viral load is much more dangerous.

O.A.: Is it useful to receive and survive this small dose?

E.G.: Very useful! Each person's microbiota is unique, and the more diverse it is, the better. The components of the microbiome produce physiological micro-vaccination, constantly stimulate innate immune cells, and keep them at a low start so that immunity quickly works when necessary. It is imperative to come into contact with antigens. Children who do not attend kindergarten will still get sick from major viral infections, but at school until they develop an adaptive immune response.

O.A.: In hygienic theory, this is what they say about vaccination - it gives the immune system an opportunity to work. This is wrong?

E.G.: No, this is artificial training. The hygiene theory has led to a sharp increase in allergic and autoimmune diseases! It is impossible to reproduce all the mechanisms of the natural immune response by vaccination. Preparations of microbial products or autovaccines work much better in this aspect - this is vaccination at the level of local immunity. In this way, we help the cells of the immune system to become activated by taking bacterial lysates. There may even be a high temperature, but this is always good, because, for example, in people who are often sick, chronic inflammation occurs without fever and drags on, since there is no active immune response.

O.A.: So, we are for basic vaccination of a child according to the national calendar, but are against a vaccine against a respiratory virus that has not been fully studied?

E.G.: Of course. My child is fully vaccinated against dangerous infections according to the calendar, and I even additionally vaccinated him against meningococcal infection. We will definitely vaccinate, because, at least with regard to tuberculosis, our situation is still not very good. But when we talk about mass annual vaccination of the adult population against ARVI, especially about people aged 40+, with increased risks of autoimmune, cardiovascular, and oncological diseases, with already accumulated somatic mutations in cells, we need to be extremely careful. People working in occupational risk groups may need to be vaccinated, but only after a thorough history and examination.

The article presents the results of a blind, placebo-controlled study of the effectiveness and safety of Likopid (ZAO PEPTEK, Russia) in reducing seasonal morbidity in 150 residents of Nizhny Tagil. It was shown that the use of Licopid 1 mg 3 times a day sublingually for 10 days led to positive dynamics of morbidity in 94% of patients, of which 63% had no episodes of acute respiratory infections (ARI) during a year of observation. When using placebo, positive dynamics of morbidity were noted in 36% of patients, absence of episodes of ARI - in 8% of patients.

GMDP (Likopid) in reducing the seasonal morbidity in adults (data of blind, placebo-controlled study)

The results of a blind, placebo-controlled study of the efficacy and safety of LikopidÒ (JSC “PEPTEK”, Russia) in reducing the seasonal incidence of 150 residents of Nizhny Tagil are presented. It is shown that the use of LikopidÒ 1 mg 3 times a day sublingually for 10 days led to positive dynamics of disease in 94% of patients, of whom 63% noted the lack of episodes of acute respiratory infections (ARI) in the year of observation For placebo — the positive dynamics of disease was observed in 36% of patients, no episodes of ARI — 8% of patients.

The issues of diagnosis, treatment and prevention of acute respiratory infections (ARI) of the respiratory tract have received considerable attention in the literature of recent years [1-2]. Vaccine prevention of respiratory infections is currently recognized as the most effective method of preventing influenza and a number of other ARIs [1, 3]. However, the capabilities of the method are limited by a wider range of respiratory pathogens and the lack of specific immunotherapy for most of them. According to Rospotrebnadzor, in 2010 (January-May) the incidence of influenza in the Russian Federation was 24,962 cases, while acute upper respiratory tract infections of multiple or unspecified localization were recorded in 13,917,422 cases [4]. In addition, the current low vaccination coverage of the general population does not always make it possible to achieve the epidemiological effect observed when vaccinating at least 70-80% of the population. According to some authors, in the etiology of ARVI, up to 40% of all cases are due to activation of herpesvirus infections, which must be taken into account when prescribing antiviral therapy [5].

One of the important factors influencing the frequency of colds is living in environmentally unfavorable areas. An increase in the content of various xenobiotics in air, water, and food leads to disturbances in homeostasis and immune defense [6].

The maximum reduction in the incidence of ARI can be achieved with the use of vaccination and nonspecific immunoprophylaxis [3]. From this point of view, among immunotropic drugs, of significant interest are drugs not only with proven safe effectiveness, but also with a mechanism studied at the molecular level and a predictable effect on the immune system, which can fully include Likopid® (PEPTEK CJSC, Russia, registration number LS-001438). Likopid is a medicinal form of GMDP (glucosaminyl muramyl dipeptide), belongs to the immunomodulators of microbial origin, containing minimal biologically active fragments, namely the universal fragment of peptidoglycan of the cell wall of Gram+ and Gram-bacteria [7]. GMDP (LykopidÒ) as a structural component of the bacterial wall is recognized by the innate immune system receptor NOD2, which is expressed by phagocytic cells and epithelial cells of the respiratory tract [8]. By acting on a molecular target (receptor) in the immune system, GMDP (LicopidÒ) activates primarily the phagocytic component of the immune system, as well as the humoral and cellular components of the immune system.

Under natural conditions, glycopeptides (GMDPs) are released from the bacterial cell wall as a result of enzymatic hydrolysis both during infection with pathogenic microflora and during degradation of normal and opportunistic microflora of the gastrointestinal tract [7]. Thus, the action of Lycopid (HMDP) is closest to the process of natural immunoregulation.

Based on the sum of the clinical studies conducted, Likopid is approved for use in pulmonology and therapy for chronic infections of the upper and lower respiratory tract and in the complex therapy of herpesvirus infections, including ophthalmic herpes. In addition to the previously mentioned immunomodulatory capabilities of the drug, the literature describes the effect of Licopid on the mechanism of allergic inflammation and the effectiveness of its use in atopic diseases, antitumor effect, protective capabilities in conditions of septic shock and adjuvant effect when vaccinating experimental animals with a dose-dependent increase in antibody formation [9-11].

The purpose of this study was to evaluate the safety and effectiveness of reducing the seasonal incidence of ARI and exacerbations of chronic nonspecific respiratory diseases when using Likopid 1 mg tablets in adults living in an environmentally unfavorable region.

Materials and methods: A blind, placebo-controlled study was carried out in the city of Nizhny Tagil, where respiratory diseases occupy the first place in the morbidity structure. The study was conducted jointly by the State Scientific Center “Institute of Immunology” of the Federal Medical and Biological Agency of the Russian Federation with the city laboratory of immunology and the city health department.

The study included 150 people with continuous work experience in hazardous coke production for more than 5 years, with a frequency of episodes of ARI or exacerbations of chronic inflammatory diseases of the upper respiratory tract 4 times a year or more (during the year preceding the study). At the time of taking the study drug (Licopid or placebo), all patients were free of the disease or in remission.

All patients received identical Licopid tablets or placebo according to the following regimen: sublingually, 1 tablet (containing 1 mg GMDP or placebo) 3 times a day for 10 days. Preparations with the active substance and placebo were manufactured by PEPTEK CJSC (Moscow, Russia) taking into account the requirements of GMP (Good Manufacturing Practice).

All patients were divided into two groups. The first group consisted of 100 people who received immunotherapy with Lykopid, the second group consisted of 50 people who received placebo.

On day 0, examination, medical history, assessment of inclusion and exclusion criteria, and laboratory and immunological studies were performed. Day 1 was considered the first day of study drug or placebo administration. Laboratory immunological studies after treatment were carried out on days 20–22, i.e. 10-12 days after the end of therapy. The observation period for patients was one year.

The safety of treatment was assessed by the occurrence of adverse reactions noted while taking Licopid or placebo.

The main criterion of effectiveness is the frequency of episodes of acute respiratory infections and exacerbations of chronic nonspecific diseases one year after therapy with Likopid and placebo. Additional criteria are the dynamics of the absolute number of lymphocytes and their subpopulations, immunoglobulins of classes A, M, G and E, phagocytic activity.

Results: The use of Licopid led to a significant decrease in the level of respiratory morbidity within one year after the course of immunotherapy (Table 1).

Table 1.

Dynamics of morbidity in groups 1 year after treatment

After a course of treatment with Likopid (total course dose - 30 mg), 63% of patients showed no episodes of ARI over the next year. During the placebo course, the absence of diseases was noted in only 8% of patients.

When assessing the overall effectiveness in groups, positive dynamics (a decrease in the number of diseases one year after treatment compared to the initial data before treatment) was noted in 94% of patients taking Likopid, and only in 36% in the placebo group.

The condition did not change in 6% of patients receiving immunotherapy and in 64% of patients receiving placebo.

The patients tolerated the therapy well, and no adverse reactions were identified.

When assessing additional criteria, a significant improvement in a number of immunological parameters was revealed in the Lykopid group, in contrast to the placebo group, the studied immunological parameters of which remained unchanged (Figure 1).

Figure 1. Frequency of deviations from the reference values ​​of immune status indicators before and after treatment in the Lykopid and placebo groups (in %).

Note. Lymphocytes - absolute number of lymphocytes, FA - phagocytic activity

After the course of immunotherapy, the level of CD3+ and CD4+ lymphocytes, the phagocytic activity of neutrophils and the level of IgA normalized, a decrease in the level of which was detected before the start of the study. Under the influence of Lycopid, the number of people with elevated IgE levels decreased by 3 times.

Discussion . The results of the study are fully consistent with the clinical data obtained in studies with placebo control of the effectiveness of Lykopid in chronic nonspecific lung diseases in adults and recurrent respiratory tract infections in children [12, 13]. The clinical and immunological effect of Lykopid in patients with chronic nonspecific bronchitis was statistically significant in comparison with placebo, prolonging the remission of the disease and improving the functional state of phagocytic cells. A pharmacoepidemiological study conducted in one of the districts of Vladimir showed that the incidence of children with recurrent respiratory tract infections attending organized groups and receiving Lykopid was 2-2.5 times lower compared to this indicator in the district during a year of observation [13].

In addition, early studies on a model of experimental influenza infection (virus strain A/Leningrad/399/76 (H3N2) showed an increase in antibody titer with the introduction of GMDP against the background of a single vaccination. An increase in antibody titer in relation to the control was recorded with the introduction of GMDP for a week before vaccination, and 1-4 days after it [11].

GMDP (Lykopid) did not reduce the incidence of viremia, but it did reduce the accumulation of virus in the liver and lungs of each individual mouse.

Thus, the clinical and experimental data presented in the article indicate the prospects of using Lykopid for recurrent respiratory tract infections in adults. The presented results of a placebo-controlled study showed that the use of Licopid in the studied regimen (1 mg 3 times a day sublingually for 10 days) led to a reduction in the seasonal incidence of ARI by more than 50% and normalization of impaired parameters of the immune status in residents living and working in conditions of environmental distress.

E.V. Voronina,

medical director

CJSC "PEPTEC", Russia

Literature:

1. Markova T.P., Chuvirov G.N. Vaccine prevention and antiviral therapy of influenza // RMJ, 2007. - T. 15. - No. 2.

2. Kazyukova T.V., Pankratov I.V., Aleev A.S., Dudina T.A. Family prevention of influenza and acute respiratory infections during the period of rising seasonal morbidity // RMJ, 2011. - T. 19. - No. 2.

3. Zaplatnikov A.L. Immunoprophylaxis and immunotherapy of acute respiratory infections in children // Attending physician, 2006. - No. 9. - P. 50-56.

4. Information on infectious and parasitic diseases (Form 1) for January-December 2010. Federal Service for Surveillance on Consumer Rights Protection and Human Welfare. https://rospotrebnadzor.ru/

5. Kokoreva S.P. Optimization of an integrated approach to the health improvement of preschool children in organized groups in a large industrial center // Abstract of thesis. ... MD — Voronezh, 2008.

6. Tokmakova O.G. Changes in the state of the immune system of children under the influence of unfavorable environmental factors and possible ways of their correction: Abstract of thesis. dis. ...cand. honey. Sci. - Perm, 2003. - 23 p.

7. Nesmeyanov V.A. Glucosaminylmuramoyl peptides: towards understanding the molecular mechanism of biological activity // International Journal of Immunorehabilitation, 1998. - No. 10. - P. 19-29.

8. Gomez MI, Prince A. Airway Epithelial Cell signaling in response to bacterial pathogens // Pediatric Pulmonology, 2008, 43: 11-19.

9. Revyakina V.A., Kozlov I.G., Voronina E.V. and others. Possibilities of glucosaminylmuramyl dipeptide in the treatment of atopic diseases in children // Questions of practical pediatrics, 2009. - T. 4. - No. 4. - P. 42-49.

10. Kozlov I.G., Voronina E.V., Valyakina T.I. and others. Lykopid in the immunotherapy of tumors: a review of experimental data // Questions of hematology/oncology and immunopathology in pediatrics, 2011. - T. 10. - No. 2. - P. 32-38.

11. Report on laboratory tests of the immunostimulating and antiviral activity of the drug GMDP against experimental influenza infection. — Leningrad Research Institute of Epidemiology and Microbiology named after. Pasteur, 1988

12. Setdikova N.Kh., Borisova A.M., Golubeva N.M., Andronova T.M., Pinegin B.V. Functional activity of phagocytic cells in the peripheral blood of patients with chronic nonspecific lung diseases when treated with the new domestic immunomodulator Lykopid // Immunology, 1995. - No. 3. - P. 59-62.

13. Kiryukhin A.V., Parfenova N.A., Maksimova T.A. Optimization of treatment for frequently and long-term ill children: immunocorrection with Lycopid // Russian Pediatric Journal, 2001. - No. 5. - P. 27-29.

Likopid tablets 10 mg in bottle pack. №10x1

Name

Likopid tablet 10 mg in bottle pack. №10x1

Description

Tablets are white, round, flat-cylindrical, with a chamfer and a score.

Main active ingredient

Glucosaminylmuramyl dipeptide

Release form

Tablets are white, round, flat-cylindrical, with a chamfer and a score. 1 tab. GMDP (glucosaminylmuramyl dipeptide) 10 mg Excipients: lactose, sucrose, potato starch, methylcellulose, calcium stearate. 10 pieces. — cellular contour packages (1) — cardboard packs. 10 pieces. — contour cell packaging (2) — cardboard packs.

Dosage

For the prevention of postoperative complications, Likopid® is prescribed sublingually for adults at a dose of 1 mg 1 time/day for 10 days. For the treatment of purulent-septic processes of the skin and soft tissues of moderate severity (including postoperative ones), Likopid® is prescribed sublingually at a dose of 2 mg 2-3 times a day for 10 days. For the treatment of severe forms of purulent-septic processes of the skin and soft tissues, Likopid® is prescribed orally at a dose of 10 mg 1 time per day for 10 days. For chronic infections of the upper and lower respiratory tract, Likopid® is prescribed sublingually at a dose of 1-2 mg 1 time/day for 10 days. For pulmonary tuberculosis, Licopid® is prescribed orally at a dose of 10 mg 1 time/day for 10 days. For a mild form of herpetic infection, Likopid® is prescribed sublingually 2 mg 1-2 times a day for 6 days; in severe forms - sublingually 10 mg 1-2 times a day for 6 days. For ophthalmoherpes, Licopid® is administered orally at a dose of 10 mg 2 times a day for 3 days. After a break of 3 days, the course of treatment is repeated. If the cervix is ​​affected by the human papillomavirus, Likopid® is prescribed orally at a dose of 10 mg 1 time/day for 10 days. For the treatment of psoriasis, Licopid® is prescribed orally at a dose of 10-20 mg 1-2 times a day for 10 days and then every other day, 10-20 mg for the next 10 days, in severe forms and a large affected area (including for arthropathic form) - orally 10 mg 2 times a day for 20 days. For children aged 1 to 16 years, Likopid® is prescribed in the form of 1 mg tablets. For the treatment of chronic respiratory tract infections and purulent-inflammatory skin diseases, Likopid® is prescribed orally at a dose of 1 mg 1 time per day for 10 days. When treating herpes infection, the drug is prescribed orally at a dose of 1 mg 3 times a day for 10 days. In the treatment of chronic viral hepatitis B and C - orally at a dose of 1 mg 3 times a day for 20 days. For newborns with a protracted course of infectious diseases (including pneumonia, bronchitis, enterocolitis, sepsis, postoperative complications), Licopid® is prescribed orally at a dose of 500 mcg 2 times a day for 7-10 days.

special instructions

It is not advisable to co-prescribe Licopid with sulfonamide drugs and tetracyclines. Effect on the ability to drive vehicles and operate machinery The use of the drug Licopid® does not affect the ability to perform work that requires increased attention and speed of psychomotor reactions.

pharmachologic effect

An immunostimulating drug, the biological activity of which is due to the presence of specific binding centers (receptors) for GMDP, localized in the endoplasm of phagocytes and T-lymphocytes. The drug stimulates the functional (bactericidal, cytotoxic) activity of phagocytes (neutrophils, macrophages), enhances the proliferation of T- and B-lymphocytes, and increases the synthesis of specific antibodies. The pharmacological action is carried out by enhancing the production of interleukins (interleukin-1, interleukin-6, interleukin-12), tumor necrosis factor-alpha, interferon gamma, colony-stimulating factors. The drug increases the activity of natural killer cells.

Pharmacokinetics

Absorption and distribution of Cmax of the active substance in plasma is achieved 1.5 hours after administration. Oral bioavailability is 7-13%. The degree of binding to blood albumin is weak. Metabolism and excretion Does not form active metabolites. T1/2 is 4.29 hours. It is excreted unchanged, mainly in the urine.

Indications for use

As part of complex therapy for conditions accompanied by secondary immunodeficiencies, including: Tablets 1 mg and 10 mg (for adults)

• for chronic lung infections;
• for acute and chronic purulent-inflammatory diseases of the skin and soft tissues (including purulent-septic postoperative complications);
• for herpes infection (including ophthalmic herpes);
• for papillomavirus infection;
• for chronic viral hepatitis B and C;
• for psoriasis (including arthropathic form);
• with pulmonary tuberculosis.

Tablets 1 mg (for children)

• for acute and chronic purulent-inflammatory diseases of the skin and soft tissues;
• for chronic infections of the upper and lower respiratory tract, both in the acute stage and in the remission stage;
• for herpetic infection of any localization;
• for chronic viral hepatitis B and C.

Directions for use and doses

Likopid® is prescribed sublingually or orally on an empty stomach, 30 minutes before meals. For the prevention of postoperative complications, Likopid® is prescribed sublingually for adults at a dose of 1 mg 1 time/day for 10 days. For the treatment of purulent-septic processes of the skin and soft tissues of moderate severity (including postoperative ones), Likopid® is prescribed sublingually at a dose of 2 mg 2-3 times a day for 10 days. For the treatment of severe forms of purulent-septic processes of the skin and soft tissues, Likopid® is prescribed orally at a dose of 10 mg 1 time per day for 10 days. For chronic infections of the upper and lower respiratory tract, Likopid® is prescribed sublingually at a dose of 1-2 mg 1 time/day for 10 days. For pulmonary tuberculosis, Licopid® is prescribed orally at a dose of 10 mg 1 time/day for 10 days. For a mild form of herpetic infection, Likopid® is prescribed sublingually 2 mg 1-2 times a day for 6 days; in severe forms - sublingually 10 mg 1-2 times a day for 6 days. For ophthalmoherpes, Licopid® is administered orally at a dose of 10 mg 2 times a day for 3 days. After a break of 3 days, the course of treatment is repeated. If the cervix is ​​affected by the human papillomavirus, Likopid® is prescribed orally at a dose of 10 mg 1 time/day for 10 days. For the treatment of psoriasis, Licopid® is prescribed orally at a dose of 10-20 mg 1-2 times a day for 10 days and then every other day, 10-20 mg for the next 10 days, in severe forms and a large affected area (including for arthropathic form) - orally 10 mg 2 times a day for 20 days. For children aged 1 to 16 years, Likopid® is prescribed in the form of 1 mg tablets. For the treatment of chronic respiratory tract infections and purulent-inflammatory skin diseases, Likopid® is prescribed orally at a dose of 1 mg 1 time per day for 10 days. When treating herpes infection, the drug is prescribed orally at a dose of 1 mg 3 times a day for 10 days. In the treatment of chronic viral hepatitis B and C - orally at a dose of 1 mg 3 times a day for 20 days. For newborns with a protracted course of infectious diseases (including pneumonia, bronchitis, enterocolitis, sepsis, postoperative complications), Licopid® is prescribed orally at a dose of 500 mcg 2 times a day for 7-10 days.

Use during pregnancy and lactation

The use of the drug during pregnancy and lactation (breastfeeding) is contraindicated.

Precautionary measures

For children aged 1 to 16 years, Likopid® is prescribed in the form of 1 mg tablets.

Interaction with other drugs

With simultaneous use, Likopid® increases the effect of antibiotics from the group of semisynthetic penicillins, cephalosporins, polyene derivatives, fluoroquinolones, and there is synergism with antiviral and antifungal drugs. Antacids and adsorbents, when used simultaneously with Lykopid, significantly reduce its bioavailability. GCS, when used simultaneously, reduces the effectiveness of Lykopid.

Contraindications

• autoimmune thyroiditis in the acute phase;
• diseases accompanied by high fever or hyperthermia (>38°C);
• pregnancy;
• lactation period (breastfeeding);
• hypersensitivity to the drug.

Compound

GMDP (glucosaminylmuramyl dipeptide) 10 mg Excipients: lactose, sucrose, potato starch, methylcellulose, calcium stearate.

Overdose

Likopid® is prescribed sublingually or orally on an empty stomach, 30 minutes before meals. For the prevention of postoperative complications, Likopid® is prescribed sublingually for adults at a dose of 1 mg 1 time/day for 10 days. For the treatment of purulent-septic processes of the skin and soft tissues of moderate severity (including postoperative ones), Likopid® is prescribed sublingually at a dose of 2 mg 2-3 times a day for 10 days. For the treatment of severe forms of purulent-septic processes of the skin and soft tissues, Likopid® is prescribed orally at a dose of 10 mg 1 time per day for 10 days. For chronic infections of the upper and lower respiratory tract, Likopid® is prescribed sublingually at a dose of 1-2 mg 1 time/day for 10 days. For pulmonary tuberculosis, Licopid® is prescribed orally at a dose of 10 mg 1 time/day for 10 days. For a mild form of herpetic infection, Likopid® is prescribed sublingually 2 mg 1-2 times a day for 6 days; in severe forms - sublingually 10 mg 1-2 times a day for 6 days. For ophthalmoherpes, Licopid® is administered orally at a dose of 10 mg 2 times a day for 3 days. After a break of 3 days, the course of treatment is repeated. If the cervix is ​​affected by the human papillomavirus, Likopid® is prescribed orally at a dose of 10 mg 1 time/day for 10 days. For the treatment of psoriasis, Licopid® is prescribed orally at a dose of 10-20 mg 1-2 times a day for 10 days and then every other day, 10-20 mg for the next 10 days, in severe forms and a large affected area (including for arthropathic form) - orally 10 mg 2 times a day for 20 days. For children aged 1 to 16 years, Likopid® is prescribed in the form of 1 mg tablets. For the treatment of chronic respiratory tract infections and purulent-inflammatory skin diseases, Likopid® is prescribed orally at a dose of 1 mg 1 time per day for 10 days. When treating herpes infection, the drug is prescribed orally at a dose of 1 mg 3 times a day for 10 days. In the treatment of chronic viral hepatitis B and C - orally at a dose of 1 mg 3 times a day for 20 days. For newborns with a protracted course of infectious diseases (including pneumonia, bronchitis, enterocolitis, sepsis, postoperative complications), Licopid® is prescribed orally at a dose of 500 mcg 2 times a day for 7-10 days.

Side effect

Possible: at the beginning of treatment - an increase in body temperature to 37.9°C (it is short-term, goes away on its own and does not require discontinuation of the drug).

Storage conditions

The drug should be stored in a dry place, protected from light, out of reach of children, at a temperature not exceeding 25°C.