What are interferons and drugs containing interferon

Are you familiar with one of the most important problems of modern pharmacy?
Do you think that this is the lack of drugs that can defeat the most severe diseases? Actually this is not true. One of the main problems is the resistance of microorganisms to existing drugs. This means that some drugs that were previously effective may no longer work over time as pathogens learn to survive exposure to the drugs. The issue of antibiotic resistance is especially acute now, as confirmed by clinical practice and numerous studies. According to WHO, every year millions of people experience infections that are resistant to one or more antibiotics. The same thing happens with other groups of drugs. One solution to this problem is to search for other universal drugs that would be able to avoid the emergence of resistance to them. Antiviral immunity is provided by interferons, a group of protein molecules.

What are interferons (IFNs)
History of discovery
Interferon therapy: yesterday, today and tomorrow
Types and effects on the body
Preparations containing IFN
Preparations based on IFN for the prevention of ARVI
Complex immunomodulatory drug VIFERON

What are interferons

Interferons (IFNs) are an independent group of cytokines, secreted proteins that play a critical role in the functioning of the immune system of humans and all vertebrates.
They are responsible for antiviral activity, that is, they directly protect the body from the expression of foreign genetic material. IFNs take part in the regulation of a large number of immune processes, which consist of increasing the activity of natural killer cells and stimulating phagocytosis - the process of capturing and absorbing microorganisms and foreign particles, and also support the inhibition of proliferation - the process of reproduction of damaged cells. All this is aimed at the most effective protection against diseases. Scientists were able to prove that the course of the disease and the speed of recovery largely depend on the ability of the interferon system to respond as quickly as possible to the introduction of the pathogen.

History of the discovery of interferon

The scientific world first started talking about IFN more than 60 years ago, when English virologists Alik Isaacs and Jean Lindenmann published materials in one of the journals in which they spoke in detail about the discovery and study of the IFN protein. Legend has it that they came up with the name “interferon” for these proteins themselves, and at first they considered it humorous.

It is also worth noting that long before the work of these virologists, other scientists tried to study the phenomenon of interference, which consists in the mutual suppression of viruses. Then the talk was that the body, infected with viruses of one type, for some reason became immune to viruses of another type. Scientists tried to find an answer to this question, but until the research of Isaac and Lindenmann, the nature of this phenomenon remained shrouded in mystery.

And in the middle of the 20th century, interferon was discovered and it was found that the formation of IFN is one of the very first reactions of the innate immune system to alarm signals associated with the penetration of viral particles into the body. Currently, scientists adhere to the version that the IFN system in vertebrates, including fish, was formed more than 500 million years ago.

In 1959, the Scientific Committee on Interferon was created, where research immediately began on this powerful natural remedy in the fight against viral diseases. The list of the main tasks of this community included the development of the most economically feasible and efficient methods for the production of IFN, as well as its purification.

MEDICAL CENTER

Level of circulating interferon (serum interferon).
Spontaneous production of interferon in vitro.
Induced synthesis of alpha-interferon in vitro.
Induced synthesis of interferon gamma in vitro.

Additional tests:

Determination of sensitivity to interferon drugs (No. 1044 - Ingaron, No. 1045 - Intron, No. 1047 - Reaferon, No. 1048 - Realdiron, No. 1049 - Roferon).
Determination of sensitivity to interferon inducers (No. 1050 - Amiksin, No. 1051 - Kagocel, No. 1052 - Neovir, No. 1053 - Ridostin, No. 1054 - Cycloferon).
Determination of sensitivity to immunomodulators (No. 1055 - Galavit, No. 1056 - Gepon, No. 1057 - Immunal, No. 1058 - Imunofan, No. 1059 - Immunomax, No. 1060 - Likopid, No. 1061 - Polyoxidonium, No. 1062 - Taktivin, No. 1063 - Thymogen, No. 1066 - Imunorix, No. 1148 - Panavir, No. 1064 - Isoprinosine).

Interferons (IFNs) are the most important component of the body’s innate nonspecific defense against infections (the name interferons comes from their ability to interfere with viral infection of cells).
This is a family of proteins of local (autocrine and paracrine) regulation that are capable of activating intracellular processes and intercellular interactions that provide resistance to viral infections, enhance innate and acquired immune responses, modulate the processes of development and death of normal and tumor cells. The body's resistance to viral infections and a number of other diseases largely depends on the activity of a group of genes of the interferon system. Interferon preparations are widely used in medicine. The effects of interferons are indirect - activation of specific receptors by interferons causes a cascade of cellular processes leading to the induction of specific interferon-stimulated genes encoding the synthesis of many proteins, which provide the antiviral effects, antitumor and antiproliferative effects of interferons. Proteins induced by interferons include: enzymes, transcription factors, cell surface glycoproteins, cytokines, chemokines and other factors, the effect of which continues to be studied. The production of interferons by cells is transient, temporary - normally “silent” interferon genes are induced under the influence of products of viral and microbial origin and chemical inducers.

Interferons are divided into three types (α, β and γ), which are associated with specific functions and specific producing cells. Interferons α and β, despite significant structural differences, have common receptors and similar functions. Together they are also called type I interferons, or acid-stable interferons, in contrast to interferon-γ, which has its own receptors and partially different functions (it is also known as interferon II, or acid-labile interferon).

Interferon α (more than 20 of its subtypes have been identified) is the main interferon that is synthesized in a virus-induced leukocyte culture. The main producers of IFN-α are plasmacytoid dendritic cells; monocytes make a significant contribution to the IFN-α-producing ability of the blood. Its main functions are antiviral activity and activation of natural killer cells.

Interferon β is the main interferon produced by double-stranded RNA-induced fibroblast culture. Its main producers are fibroblasts, epithelial cells and macrophages; its main function is antiviral activity.

Interferon γ is the main interferon produced by immunologically stimulated (mitogens or antigens) lymphocyte cultures. The main producing cells of IFN-γ are T-lymphocytes. The main function of interferon gamma is immunoregulation (including activation of macrophages, enhancement of the Th1 response, induction of the expression of major histocompatibility complex type II antigens on antigen-presenting cells, etc.); like other interferons, it exhibits antiviral and antiproliferative activity. All animal cells are capable of producing interferons; certain cells (leukocytes and fibroblasts) can produce more than one type - both IFN-α and IFN-β.

Studying the parameters of interferon status allows us to identify insufficiency of the interferon system. Assessment of detected changes can serve as a guide in the diagnosis, treatment and prognosis of diseases of both viral and non-viral etiology. Healthy people are characterized by low levels of serum interferon and high values of induced interferon synthesis. Stress and acute viral infections, allergic conditions are accompanied by an increase in the level of circulating interferon and a decrease in the level of induced production of alpha and gamma interferons by leukocytes. In bronchial asthma and urticaria, the level of circulating interferon correlates with the severity of the disease.

Chronic viral infections (herpes, hepatitis), multiple sclerosis are accompanied by suppression of all indicators of interferon status. Autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis) are characterized by suppression of inducible production of interferon alpha. Acute lymphocytic leukemia and malignant formations are accompanied by suppression of induced interferon gamma production. The results of the study of interferon status should be considered in conjunction with other laboratory and clinical anamnestic data. A decrease in the production of alpha and gamma interferon, which can be both a cause and a consequence of acute and chronic viral diseases, indicates a congenital or acquired deficiency of the interferon system and can be considered as an indication for interferon-stimulating therapy. Normalization of interferon status indicators usually coincides with the recovery process. In people over 50 years of age, insufficiency of the interferon system is relatively more common. The study of interferon status parameters with determination of sensitivity to drugs is used to select effective therapy when using exogenous interferon drugs, interferon inducers and immunomodulators.

Interferon preparations

Ingaron is a recombinant human interferon-γ.
Intron - recombinant human interferon-α-2b.
Reaferon is a recombinant human interferon-α-2.
Realdiron is a recombinant human interferon-α-2b.
Roferon is a recombinant human interferon-α-2a.

Interferon inducers

Amiksin (international non-patent name - tilorone): dihydrochloride 2,7-bis-[2(diethylamino)-ethoxy]-fluorene-9-OH-dihydrochloride.
Kagocel: active substance - sodium salt of the copolymer (1-4)-6-0-carboxymethyl-bD-glucose, (1-4)-bD-glucose, (21-24)-2,3,14,15,21, 24,29,32-octahydroxy-23-(carboxy-methoxymethyl)-7,10-dimethyl-4,13-di(2-propyl)-19,22,26,30,31-pentaoxaheptacyclo [23.3.2.216.05.28 .08.27.09.1В.012.17] dotriaconta-1,3,5(28),6,8(27),9(18),10,12(17),13,1-decaene.
Neovir – 2-(9-oxo-9,10-dihydroacridin-10-yl) sodium acetate.
Ridostin is a mixture of sodium salts of double-stranded and single-stranded RNA.
Cycloferon – meglumine acridone acetate.

Immunomodulators

Galavit is a phthalhydrazide derivative.
Hepon is a synthetic peptide consisting of 14 amino acid residues.
Immunal is a preparation of Echinacea purpurea juice.
Immunofan is a hexapeptide (arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine).
Immunomax is an acidic peptidoglycan with a molecular weight of 1,000 - 40,000 kDa.
Lykopid - active substance - glucosaminylmuramyl dipeptide - 4-O-(2-acetylamino-2-deoxy-beta-D-glucopyranosyl)-N-acetylmuramyl]-L-alanyl-D-alpha-glutalamide.
Polyoxidonium - international non-proprietary name / composition: Azoximer (Azoximer) - N-oxidized derivative of polyethylene piperazine.
Taktivin is a complex of polypeptides from the thymus gland of cattle.
Thymogen is a polypeptide from the thymus gland of cattle.
Panavir is a purified extract of shoots of the Solanum tuberosum plant, the main active ingredient is a hexose glycoside consisting of glucose, rhamnose, arabinose, mannose, xylose, galactose, uronic acids.

Interferon therapy: yesterday, today and tomorrow

To conduct the first studies of IFN, a group of volunteers was recruited who agreed to inject themselves with IFN obtained from the blood of monkeys. In those days when IFNs were little studied, making such a decision required a certain amount of courage. Therefore, we can say that people agreed to sacrifice themselves for the sake of science. Before the introduction of IFN, they were infected with the Coxsackie virus, which causes the common cold.

After a certain period of time, it was found that only one person from the group of volunteers became ill, despite the fact that the virus was present in all of them in the nasal washes. However, no side effects were found. This study marked the beginning of thousands of subsequent experiments, thanks to which scientists recognized the ability of IFN to protect humans from disease.

At the same time, in the 1960s, Soviet virologists also joined the study of the effect of IFN on the human body. Epidemiologist Soloviev V.D. proposed to produce IFN from placental blood taken from postpartum women. In 1969, an epidemic of Hong Kong influenza was recorded in the USSR, which was first tried to be combated with the help of interferon preparations obtained from human blood. It was found that the effectiveness of such drugs is almost 70%.

IFNs were also widely used in subsequent years - for example, in 1973, when Academician A.A. Smorodintsev began researching this type of protein. In scientific works of those years, the most effective methods of using IFN were analyzed. Thus, through the ongoing study of IFN and its effect on the human immune system, by the end of the 20th century, scientists were able to accumulate enormous experience in the use of human leukocyte IFN for the prevention and treatment of respiratory infections, including influenza, as well as some other viral diseases.

Intranasal interferon preparations have been widely used in many countries around the world, including the UK, USA, Japan and Bulgaria. In recent years, interferon has begun to be widely used in the treatment of children. For adults, this group of drugs has been used for more than half a century. With the beginning of the use of IFN, the effectiveness of protection against ARVI in preschool children, including newborns, has increased significantly. This indicated to scientists that it is necessary to study IFNs more and more deeply and strive to expand the scope of their influence, to try to fight a variety of diseases with the help of IFNs.

However, unfortunately, after the start of mass production of IFN, it quickly became clear that the composition of drugs containing interferon is inconsistent even within the production of one pharmaceutical company. The main disadvantages of drugs obtained from donor blood include the inability to purify the drug at a high level. It turned out to be difficult to remove viral particles from the drug. In addition, donated blood is a very expensive ingredient, available in large quantities only to a few pharmaceutical companies. Therefore, the company has now almost abandoned the production of leukocyte IFN. A small volume of IFN preparations obtained from donor blood is used strictly for life-saving indications, when the expected benefit significantly outweighs the possible risks.

But did scientists really abandon the production of drugs with interferons after learning about the peculiarities of leukocyte IFN? Of course not. In this case, biotechnology came to the rescue - the science of ways to create various substances using natural biological components. Thanks to it, today pharmacists produce recombinant IFNs, absolutely identical to natural ones in amino acid composition, which do not require donor blood. These drugs are produced in large quantities throughout the world and are relatively low in cost, which in turn makes prices in pharmacies quite affordable for most consumers.

IFN preparations today can be produced in the form of dried lyophysiate, which is subsequently used to obtain a solution, suppositories for rectal and vaginal use, a solution for injections and inhalations, drops, ointments, gels, aerosols, tablets and microenemas.

IFN drugs may contain different amounts of the active substance. On drug packaging, this amount is most often indicated in international units, or IU.i

The release form and dosage of the IFN drug is selected by the attending physician, taking into account the patient’s age, condition and medical history.

Help your immune system. Why does the body need interferon after vaccination?

During the period of vaccination against COVID-19, many people have different questions: “How will my body tolerate the vaccine? Is there a risk of getting ARVI? How to protect yourself from coronavirus between doses of the two components of the vaccine? We talked about drugs that help not only fight the virus, but also strengthen the immune system, with Alexander Karaulov, Doctor of Medical Sciences, Academician of the Russian Academy of Sciences, Head of the Department of Clinical Immunology and Allergology, Head of the Laboratory of Immunopathology of the First Moscow State Medical University. I. M. Sechenov.”

— Alexander Viktorovich, how does the body react to the introduction of the vaccine?

- In fact, with the help of a vaccine, we train our immune system for a future meeting with the pathogen. Scientists emphasize that approximately 3% of the population suffers from COVID-19 severely, and 0.3% may have a life-threatening course of the disease. Moreover, if earlier we saw that severe cases were more common among the elderly and patients with concomitant diseases, now the majority of life-threatening conditions occur in patients aged 40 to 60 years. Only 50% of those who have had COVID-19 have developed antibodies.

Vaccination protects against infection, and if it does occur, the infection is mild. However, post-vaccination immunity is formed differently in different groups of people. Its formation can be slowed down in older people or patients with weak immunity, that is, in those whose body’s defenses are weakened by past or concomitant infections, chronic diseases, stress, malnutrition, environmental conditions, etc.

— Nowadays there is a lot of talk about interferons, that they strengthen the immune system. Many studies have already been published on the use of drugs of this group for COVID-19; in Russia they have become part of the standards of medical care. How do interferons work during vaccination?

— Interferons in our body perform a regulatory function. To put it figuratively, interferon is a traffic controller at a crossroads: it directs the immune response in the right direction, thus promoting recovery. This property of interferon is also excellent for preparing for vaccination, which, in essence, is also the body’s immune reaction, but not for the purpose of recovery, but for the purpose of more effectively producing antibodies against the causative agent of the disease.

— How exactly does interferon affect the level of antibody production?

Types of interferons (types). Their effect on the body.

Scientists distinguish three types of interferons: interferons of the first, second and third types. The first type of IFN includes IFN-α, which in turn are divided into several subtypes. Type I IFN also includes IFN-β, IFN-ε, IFN-κ and IFN-ω. One type II IFN is also known – IFN-γ. At the beginning of the 21st century, a new class of interferons was discovered - the third type, represented by IFN-λ, which includes IFN-λ1, IFN-λ2 and IFN-λ3.

The IFN system, which includes interferons alpha, beta and gamma, is able to respond as quickly as possible to signals from the body indicating the penetration of infection and damage to DNA and RNA of cells. Virologists identify four main links in the functioning of the system of these proteins.

The first link is induction. The human body has an ideally tuned signaling system that detects the penetration of infection from the outside within about half an hour. The response of the cellular genome is immediately formed and the second stage begins - production, i.e. production of IFN.

The product consists of the synthesis of interferons by cells of the immune system and their secretion into the environment. Within a few hours after infection, the concentration of functionally active IFNs in the peripheral blood reaches its maximum. Thus, the body becomes fully prepared to fight infection if the immune system functions without failures. As a rule, this only happens in an ideal world, where a person has no problems with the environmental situation, and he always eats right and has no chronic diseases. Otherwise, IFN drugs may be required.

The third link is action. IFNs begin to protect the body's cells from the foreign influence of viruses and bacteria. And then, effects are connected as the fourth link. There are more than three hundred of them in total, among them are antiviral, immunomodulatory, antitoxic effects, as well as activation of natural killer cells, synthesis of prostaglandins and many other activities aimed at the fastest possible recovery.

The wide spectrum of antiviral activity of interferons, combined with their high safety, determines the widespread use of drugs based on recombinant interferon in young children, that is, from birth to 3 years.

However, I think what most parents would like to know is: what is interferon?

Firstly, interferon is not one substance, but a whole group of complex proteins (proteins), under the influence of which in the human body there is an increase in the synthesis of special receptors of macrophages, antigen-presenting cells, which are responsible for recognizing everything foreign in our body, be it a virus, a cell of a pathogenic bacterium - staphylococcus or a tumor cell. That is, with a low level of its own interferon (I am not specifying which groups of this protein are specifically responsible for what), the immune system “slows down” at the very early stage of the development of the immune response, and vice versa: if a little interferon is added at the very early stage of the disease from the outside, then the speed of launching protective immune reactions increases. Actually, the first 2 - 3 days from the onset of an acute infectious disease in the body (regardless of age) are spent on “building up”, and only after the third day of the disease our body is already actively fighting on its own against the invading infection.

In principle, when it comes to an adult patient, the main thing that his body needs in these first 2 - 3 days of illness is not to interfere. That is, you need to take a “sick leave”, sit at home, drink hot tea with raspberries, eat vitamins (ascorbic acid), or cheesecakes with honey, and this will, as a rule, be enough for the body to cope with the infection.

The situation is a little different with young patients. Until the age of 2-3 years, the child’s body still produces very little and very slowly its own interferon, and without it, as we already know, the immune system cannot function fully.

It is for this reason that interferon drugs have firmly occupied the niche of first-line drugs in the treatment of viral infections in children. At the same time, we must not forget that the sooner treatment with interferon drugs was started from the moment of the first signs of the disease, the faster the effect will be. But there is also an inverse relationship: after 5 days of illness, it is absolutely pointless to prescribe these particular drugs, since endogenous (own) interferon has already begun to be produced, and if you continue to feed the child’s body with interferon artificially, then you will only reduce the level of your own interferon, since all our the body works on the principle of negative feedback, that is, the higher the content of something in the body, the less it needs to be synthesized, everything is logical.

What types of interferon preparations are there?

Interferon preparations are available in various forms for internal and external use.

Among pediatricians, and even parents themselves, perhaps the most widespread are suppositories such as Viferon in a dosage of 150 thousand to 500 thousand units, intended for use in children. You can, of course, put a candle on a 5-month-old baby, and it’s easier than cleaning the nose and putting something in there.

But personally, in my practice, I prefer local preparations of viferon (interferon), such as drops (gripferon, genferon) or ointment.

Moreover, if the drops need to be instilled every 3 - 4 hours, then the duration of the ointment is designed for a longer period. Viferon ointment can be put into the nose prophylactically 2 times a day (before and after visiting a child care facility), but for treatment 4 times a day is enough. Dosing Viferon ointment is not very difficult, as it seems at first glance. To do this, you can use a ruler to measure out a pea with a diameter of about 5 millimeters on a plate, which will correspond to one gram of Viferon, that is, 40 thousand units. For children under one year old, this drop can be divided into two, and over one year old, one such half-centimeter dose can be placed in the nose, having previously cleared both nostrils of mucus, or you can also drop in Aqua Maris before Viferon. The procedure for treating a runny nose must be repeated 4 times a day. I remind you that the duration of treatment with Viferon should not exceed 5 days.

You may ask: with what frequency can Viferon and its analogues be used? Answer: in short courses (up to 5 days), Viferon can be used quite often, but preferably no more than once every 2 - 3 months. Although, if you have to use it after 30 days, I mean ointment or drops, it won’t be a big problem. Given the rather high dosage of interferon in them, it is better not to use suppositories more than three times a year.

And of course, treatment with Viferon should not exclude other necessary components of ARVI therapy, such as inhalation for a dry, barking cough or cough with difficult to separate sputum, massage, and therapeutic exercises. Don't forget the three-day rule. For up to 72 hours, a child with ARVI has every right to develop a fever up to high numbers - 39.0 and even higher, which may require the prescription of antipyretic drugs. At the same time, you need to pay attention to possible changes in the child’s behavior: strong crying, forced positioning, severe weakness. If there are such changes in behavior, you should definitely call a doctor at home. If the child is quite alert, eats well, and behaves as usual, then the presence of a high body temperature for three days should not frighten you much. In the case when the temperature persists for more than three days, or you see that the child has a high temperature, but there are no obvious signs of ARVI, such as a runny nose and cough, redness of the eyes and the back of the throat, then this is not only a reason to immediately consult a doctor , but also the need to take general clinical blood and urine tests, but that’s a completely different story.

I wish everyone good health, and take less of any “chemistry”, even if it was Viferon!

Preparations containing interferon and the spectrum of diseases sensitive to IFN

The list of diseases sensitive to IFN is extremely wide. Conventionally, it can be divided into three large groups: viral diseases, cancer and other types of diseases.

For example, interferon drugs are used to treat diseases such as herpes. And in recent years, more and more studies have begun to appear devoted to studying the effectiveness of the use of IFN in the treatment of this disease. Research conducted by scientists confirms that the use of IFN as part of complex therapy accelerates clinical recovery and contributes to the disappearance of subjective and objective symptoms of the disease. ii There was a noticeable reduction in relapse times for herpes zoster and genital herpes, a decrease in discomfort and an increase in inter-relapse periods. This allows us to speak about the high effectiveness of IFN drugs and recommend their use in the practice of dermatovenerologists.

IFNs are also used for herpetic keratitis and keratoconjunctivitis, which leads to a decrease in severity and shorter duration of the disease.

IFNs are widely used in the treatment of acute respiratory viral infections, including colds and flu. Even if the disease is complicated by bacterial infection and pneumonia, IFNs can also help you recover faster. In addition, interferon therapy is used for sexually transmitted diseases, including gardnerellosis, ureaplasmosis, chlamydia, trichomoniasis, candidiasis, vaginosis, mycoplasmosis and other infections.

Almost 80% of existing medications are not suitable for treating newborns. But some IFN drugs are included in the 20% of approved drugs that can be used to treat recently born babies, including premature babies. As part of complex therapy for newborns, IFNs are used for inflammation of the membranes of the brain and spinal cord - meningitis, as well as for sepsis and various intrauterine infections.

IFNs are also used to combat the “gentle killer”. This is what hepatitis C is often called, which skillfully disguises itself as the symptoms of other diseases and, if left untreated, can be fatal. IFN preparations as part of complex treatment improve biochemical and histological parameters, helping to rid cells of the virus. They have a pronounced clinical effect, reduce the intensity and duration of the period of intoxication, reduce the frequency of deaths and normalize the functioning of the body.

Studies have shown that in acute hepatitis C and in patients requiring blood transfusions, interferon alfa-2b drugs improve the biochemical parameters of the liver and help cells fight the virus. IFN drugs are also used in the complex treatment of hepatitis B and D. According to studies, for hepatitis B, the combination of glucocorticoids and IFN alpha can reduce the amount of viral DNA in patient samples.iii

The effectiveness of the use of IFN has been proven for papillomavirus infections (genital warts, laryngeal papillomatosis, warts), purulent-septic diseases, cytomegalovirus infection, mumps and a number of other diseases.

And of course, the attention of all scientists in the world is focused on the development of drugs against cancer and HIV infection. For cancer, IFNs are used as adjunctive therapy, which helps combine the effects of immunity and chemotherapy or other treatment methods. For HIV, IFN drugs as part of complex treatment and in combination with anti-HIV drugs have an effect on the normalization of immunological parameters.iv

Any type of treatment, both with and without the use of IFN drugs, should be used only after consultation with the attending physician.

Interferon for children: scope of application, indications and contraindications, possible forms of release

Nasal agents

This group includes drops and sprays that have already become familiar. The overall impact of nasal medications on a child’s body during ARVI and influenza is minimal. Another advantage is that they act at the very site of the virus introduction - on the mucous membrane of the respiratory tract. That is why experts recommend using nasal medications to prevent ARVI. Unlike vasoconstrictor drops, which only fight symptoms, interferon-based nasal agents act on the cause of the disease, that is, on viruses, blocking their ability to reproduce and thereby preventing the development of the disease.

Drops "Genferon® light" (LSR-009046/10)[2] are intended for children over 14 years of age and have a composition similar to the drops. The interferon content in one dose is 50,000 IU.
Spray "Genferon® light" contains interferon alpha-2b (10,000 IU) [3] and taurine, which functions as an antioxidant and also has antiviral and anti-inflammatory effects. The drug is approved for children from one month.
Grippferon® based on interferon alpha-2b is available in the form of drops (P N000089/01)[4] and spray (LP-001503)[5]. Allowed for use in children from birth. 1 ml of the drug contains at least 10,000 IU of interferon[6].
Ingaro® (LS-001330) [7] based on interferon-gamma (10,000 IU) for intranasal use is available in the form of a powder (lyophilisate), which must be dissolved in a special liquid before use (the ampoule is included in the kit). Allowed for children from seven years old.

Candle products (in the form of suppositories)

This form is most convenient for children of the youngest age group (from birth to two years), since when using a suppository, the child cannot regurgitate the medicine, spit it out, refuse to open his mouth, or interfere with the treatment process in any other way. When a suppository is administered, the active substance is absorbed by the hemorrhoidal vein system and immediately begins to actively work, providing a systemic antiviral effect on the child’s body. In this case, the medicinal substances bypass the gastrointestinal tract, where the aggressive effects of hydrochloric acid and enzymes can significantly reduce the therapeutic effect. Some substances themselves can damage the mucous membrane of the intestines and stomach, but this does not happen when using suppositories.

Today, the following interferon-based drugs in the form of suppositories are registered in the Russian Federation: “Genferon® light”, Viferon® and Kipferon®. All these products are approved for use in children from the first days of life. However, there are significant differences between the drugs.

First of all, they differ in the dosage of interferon:

Genferon® light" - 125,000 IU;
Viferon® - 150,000 IU;
Kipferon® - 500,000 IU.

Such different dosages are due to the fact that under the influence of oxygen, interferon molecules begin to break down, which means that a drug that does not contain antioxidants may lose its activity even during storage. The maximum content of interferon is observed in the drug Kipferon®, which does not contain antioxidants, and therefore, to achieve a therapeutic effect, it uses a high dosage of the active substance. However, the drug load that the body experiences in this case is quite high.

In the drug Viferon®, additional components act as antioxidants - vitamins C and E. This allowed the manufacturer to reduce the dosage to 150,000 IU, but at the same time maintain the therapeutic effect and reduce the drug load.

In the Genferon® Light suppositories, the content of the active substance is the lowest - 125,000 IU, meanwhile, the therapeutic activity of the suppositories remains high. This effect is ensured by the presence of a special amino acid in the composition of the drug - taurine, which has a powerful antioxidant effect and protects interferon molecules from destruction.

Actually, the presence of additional components in the composition is the second difference between the drugs from each other. "Genferon® light" 125,000 IU is the only combination drug with taurine and interferon. Taurine, as already mentioned, has its own antiviral activity and even in maximum concentration does not have a negative effect on the cells of the human body [8]. Scientific studies have shown that the combination of interferon with antioxidants, in particular taurine, has a higher antiviral effect than interferon alone: approximately one and a half times higher for the influenza virus and six times higher for the herpes virus[9].

Interferon-based drugs for the prevention of ARVI

In most countries of the northern hemisphere, ARVI, that is, acute respiratory viral infections, is one of the most widespread infectious diseases. Despite the popularization of vaccination aimed at protecting against influenza, it cannot fully solve the problem of ARVI. The thing is that vaccinated people develop antibodies only to those strains of the influenza virus that are part of the vaccine. But viruses constantly mutate, so you may be offered a vaccine against a certain number of influenza strains, but you will get sick from completely different strains. Scientists cannot create vaccines as quickly as mutation occurs. It is also necessary to take into account the fact that vaccines are not used in the midst of an epidemic.

Preventive protection against ARVI must be comprehensive, including nonspecific prophylaxis, which is not aimed at specific strains, but acts against the majority of ARVI known to science. It is necessary to use antiviral drugs that have a significant impact on preventing the occurrence of diseases and on the favorable outcome of the developed disease.

Features of treatment with interferon drugs

Interferon drugs often cause a flu-like syndrome - fever, chills, weakness, muscle pain. This side effect is easily eliminated by taking paracetamol.

Inducers of interferon synthesis enhance the effect of antiviral, antibacterial and antifungal agents, which makes it possible to take them together.

Enisamium iodide contains iodine, so its use in patients with thyroid diseases can lead to an imbalance of thyroid hormones. Also, the presence of iodine in the composition of the drug is associated with such a side effect as a bitter, metallic taste in the mouth.

ANTIVIRAL DRUGS WITH AN EXTENDED SPECTRUM OF ACTIVITY

MODERN ANTIMICROBIAL CHEMOTHERAPY

L.S. Strachunsky, S.N. Kozlov. Guide for doctors

Content

ANTIBIOTIC.ru

Antiviral drugs

RIBAVIRIN

Virazol, Rebetol

It has a wide spectrum of activity against many DNA and RNA viruses and is highly toxic. The mechanism of antiviral action is not fully understood.

Activity spectrum

Of clinical importance is activity against respiratory syncytial virus, as well as viruses that cause Lassa fever, hemorrhagic fever with renal syndrome and hepatitis C (in combination with interferon-alpha).

Pharmacokinetics

Bioavailability when taken orally is 35-45%. When administered by inhalation, high concentrations are observed in respiratory secretions and significantly lower concentrations in plasma. With repeated administrations it can accumulate in red blood cells. Penetrates through the BBB. Metabolized in the liver, excreted in the urine. T1/2 - 30-60 hours, increases with renal failure.

Adverse reactions

Local - rash, irritation of the skin, mucous membranes of the eyes and respiratory tract, bronchospasm (noted by both patients and medical staff
when using an aerosol dosage form). Ribavirin may crystallize in the respiratory tract and endotracheal tubes.
Hematotoxicity - anemia, lymphocytopenia (in AIDS patients); hemolytic anemia (usually by 4 weeks), reversible, does not require specific treatment, normalization of hemoglobin occurs with a temporary dose reduction.
Neurotoxicity - headaches, fatigue, irritability, insomnia.
Gastrointestinal tract - metallic taste in the mouth, abdominal pain, flatulence, nausea.
Teratogenic effect.

Indications

Infections caused by RSV (serologically confirmed): severe bronchiolitis and pneumonia in newborns and young children at risk (congenital heart defects, immunodeficiency, bronchopulmonary dysplasia), as well as those associated with severe cystic fibrosis or pulmonary hypertension.
Lassa fever.
Hemorrhagic fever with renal syndrome.
Hepatitis C (in combination with interferon-alpha or peginterferon alfa).

Contraindications

Absolute

Pregnancy.
End-stage renal failure.
Anemia.
Hemoglobinopathies.
Severe heart failure.

Relative

Uncontrolled hypertension.
Elderly age.

Warning

Due to its teratogenic effects, it is contraindicated during pregnancy and poses a danger to medical staff if pregnant.

All women receiving ribavirin (and if their partners are receiving it) should be protected against pregnancy during the entire course of therapy and for 4 months after the end of treatment. The pregnancy test must be repeated monthly, as well as for 4 months after the end of treatment. If pregnancy occurs during this period, the patient must be warned about the high risk of teratogenic effects.

In order to “protect” medical staff, inhaled administration of ribavirin is allowed only with the use of a special nebulizer.

Before using ribavirin, mandatory serological confirmation of the presence of RSV infection is required, as well as determination of HCV RNA by polymerase chain reaction (in patients with hepatitis C).

Dosage

Adults

For Lassa fever and hemorrhagic fever: intravenously - the first dose is 2.0 g, then 1.0 g every 6 hours for 4 days and then 0.5 g every 8 hours for 6 days.

For hepatitis C: orally 1.0-1.2 g per day for 12 months.

Newborns and children

For RSV infection: inhalation (using a nebulizer) 20 mg/ml (6.0 g in 300 ml of sterile water) for 18 hours a day, course of treatment - 3-7 days.

Release form

Bottles of 6.0 g of powder for preparing a solution for infusion; capsules 0.2 g.

LAMIVUDINE

Zeffix, Epivir TriTC

Active against retroviruses and hepatitis B virus.

Pharmacodynamics

In cells affected by the virus, it is activated, turning into lamivudine triphosphate, which inhibits hepatitis B virus DNA polymerase and HIV reverse transcriptase. There have been cases of development of hepatitis B virus resistance.

Pharmacokinetics

Bioavailability when taken orally is 86-88%. Distributed into many tissues and secretions, passes through the BBB. Excreted by the kidneys. T1/2 - 5-7 hours, with renal failure it may be extended.

Adverse reactions

Generally well tolerated. In rare cases, it causes lactic acidosis and hepatomegaly with steatosis, which may be associated with impaired mitochondrial function.

Indications

Chronic hepatitis B.

Warning

With monotherapy, resistance to lamivudine of both the hepatitis B virus and HIV can develop quite quickly if double infection occurs.

Dosage

Adults

Orally - 0.1 g once a day for a year; in HIV-infected patients - 0.15 g every 12 hours.

Release form

Tablets 0.1 g.

Interferons are a group of biologically active proteins synthesized by the cell during the protective reaction. Interferon is secreted into the extracellular fluid and acts on other cells through receptors, increasing resistance to intracellular microorganisms, primarily viruses. Interferons do not have specificity and inhibit the replication of various viruses. The main mechanism of the antiviral action of interferon is to suppress the synthesis of viral proteins.

According to their structure and biological properties, interferons are divided into three types: α, β, γ

. According to the method of production, leukocyte, lymphoblastoid and recombinant interferons are distinguished. Recombinant alpha interferons are most widely used as antiviral drugs. In recent years, pegylated interferons (peginterferons) have been developed, obtained by adding polyethylene glycol and having a higher half-life and clinical efficacy.

INTERFERON-ALPHA: GENERAL PROPERTIES

Pharmacokinetics

Being a protein, interferon-alpha is destroyed in the gastrointestinal tract, therefore it is used only parenterally. When administered intramuscularly, the bioavailability is 80%, the maximum concentration in the blood is achieved on average after 3.8 hours. Low concentrations have been noted in the secretions of the respiratory tract, eye tissues, and the central nervous system. It is rapidly inactivated in the kidneys, and to a lesser extent in the liver. T1/2 - 2-4 hours, does not change with renal failure. Peginterferon alfa has a longer T1/2.

Adverse reactions

Adverse reactions of recombinant interferon-alpha are dose-dependent.

Early

(usually in the first week of treatment).

The flu-like syndrome, manifested by fever, myalgia, and soreness of the eyeballs, usually disappears after 4-5 injections and does not require dose reduction or discontinuation of the drug.

Preventive measures:
prescribing paracetamol before administering interferon.

Late

(at 2-6 weeks of therapy, often causes interferon withdrawal).

Hematotoxicity - anemia, thrombocytopenia, agranulocytosis.
Neurotoxicity - drowsiness, lethargy, depression, less often convulsions.
Cardiotoxicity - arrhythmias, transient cardiomyopathy, arterial hypotension.
Autoimmune thyroiditis.
Hyperlipidemia.
Alopecia, skin rashes. Control measures:
control of hematopoiesis, levels of liver enzymes, electrolytes, ECG.

Drug interactions

Interferon alpha inhibits microsomal liver enzymes (cytochrome P-450), and therefore can disrupt the metabolism of many drugs (theophylline, etc.), increasing their concentration in the blood.

Due to the risk of adverse reactions from the central nervous system, narcotic, hypnotic and sedative drugs should be used simultaneously with interferon alpha.

Indications

Chronic hepatitis B (in the presence of viral replication: HBV, DNA, HBeAg, in blood serum) and elevated levels of transaminases.
Acute hepatitis C.
Chronic hepatitis C (HCV RNA in blood serum), elevated levels of transaminases.

Contraindications

Absolute

Psychosis (at the time of treatment or in history).
Severe depression.
Neutropenia or thrombocytopenia.
Severe heart pathology.
Decompensated cirrhosis of the liver.
Uncontrollable seizures.
Organ transplantation (except liver).

Relative

Autoimmune diseases.
Uncontrolled diabetes.

Dosage

Adults

Chronic hepatitis B

5 million IU daily or 10 million IU 3 times a week for 4-6 months.

Acute hepatitis C

High dose regimen - 10 million IU daily until transaminases normalize, then 3 million IU 3 times a week for 6 months.

Medium dose regimen: 5 million IU 3 times a week for 2 months, then 3 million IU 3 times a week for 4-10 months.

If tolerance is poor, switch to a low dose regimen of 3 million IU 3 times a week for 3-6 months.

Chronic hepatitis C

Monotherapy - 3 million IU 3 times a week for 12 months. In the absence of a response (preservation of HCV RNA in the blood serum), combination therapy is advisable after 3 months from the start of therapy.

Combination therapy:

2) Peginterferon alfa-2b + ribavirin. For body weight <65 kg, peginterferon alfa-2b 1.5 gc/kg once a week, ribavirin 0.8 g/day. For a body weight of 65-85 kg, peginterferon alfa-2b 1.5 g/kg once a week, ribavirin 1 g/day. For body weight >85 kg, peginterferon alfa-2b 1.5 mg/kg once a week, ribavirn 1.2 g/day.

For chronic hepatitis C - 3 million IU 3 times a week for 3 months, with normalization of transaminase levels and a decrease in the concentration of HCV RNA - administration at the same dose for 9-15 months. If, after 3 months from the start of therapy, the ALT level remains elevated and HCV RNA continues to be detected, the dose can be increased to 5 million IU 3 times a week.

Children over 1 year old

The effectiveness and safety of interferons in children have not been fully established. Controlled studies completed to date have revealed the effectiveness of the following treatment regimens: chronic hepatitis B - 6 million IU/m2 body surface 3 times a week for 6 months; chronic hepatitis C - 3-5 million IU/m2 3 times a week for 12 months.

INTERFERON ALPHA PREPARATIONS

Recombinant interferons

All commercial drugs in this group are a recombinant form of human α2-interferon, so their pharmacological action is similar. Depending on the amino acid content, interferon alpha-2a and interferon alpha-2b are distinguished, which do not differ significantly in clinical effectiveness and safety.

INTERFERON ALPHA-2a

Roferon-A, Reaferon

Release forms

Vials and ampoules of 3, 9 and 18 million IU ( Roferon-A

) and ampoules of 1 million IU (
Reaferon
) powder for the preparation of a solution for injection.

INTERFERON ALPHA-2b

Intron-A, Realdiron

Release forms

Bottles of 1, 3, 5 and 10 million IU ( Intron-A

) and ampoules of 1, 3 and 6 million IU (
Realdiron
) powder for the preparation of solution for injection.

PEGINTERFERON ALPHA-2b

PegIntron

A compound of interferon alfa-2b with polyethylene glycol (PEGylated interferon alfa-2b). It has a prolonged effect and higher therapeutic activity. Prescribed once a week. Recommended for the treatment of hepatitis C in persons who have contraindications to ribavirin, as well as in case of discontinuation of ribavirin due to the development of anemia.

Release forms

Vials of 50, 80 and 100 mcg of powder for the preparation of solution for injection.

Posted: 05/15/2004

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Last modified date: 05/24/2004 18:56