Medicinal reference book geotar. Interferons and their role in clinical medicine. From the treatment of influenza to the treatment of complex viral and bacterial infections Interferon - what is it

Suction

With s / c or / m administration of interferon alfa-2b, its bioavailability ranges from 80% to 100%. After the introduction of interferon alpha-2b, Tmax in plasma is 4-12 hours, T1 / 2 - 2-6 hours. 16-24 hours after administration, recombinant interferon in blood serum is not detected.

Metabolism

Metabolism is carried out in the liver.

Alpha interferons are able to disrupt oxidative metabolic processes, reducing the activity of microsomal liver enzymes of the cytochrome P450 system.

breeding

It is excreted mainly by the kidneys by glomerular filtration.

Overdose

Data on an overdose of the drug Altevir® are not provided.

Storage conditions

The drug should be stored out of the reach of children, in accordance with SP 3.3.2-1248-03 at a temperature of 2° to 8°C; do not freeze.

Interaction with other drugs

Drug interactions between Altevir and other drugs have not been fully studied. Altevir® should be used with caution simultaneously with hypnotics and sedatives, narcotic analgesics and drugs that have a potential myelodepressive effect.

With the simultaneous appointment of Altevir and theophylline, the concentration of the latter in the blood serum should be monitored and, if necessary, the dosage regimen should be changed.

When using Altevir in combination with chemotherapy drugs (cytarabine, cyclophosphamide, doxorubicin, teniposide), the risk of developing toxic effects increases.

Side effect

General reactions: very often - fever, weakness (they are dose-dependent and reversible reactions, disappear within 72 hours after a break in treatment or its termination), chills; less often - malaise.

From the side of the central nervous system: very often - headache; less often - asthenia, drowsiness, dizziness, irritability, insomnia, depression, suicidal thoughts and attempts; rarely - nervousness, anxiety.

From the musculoskeletal system: very often - myalgia; less often - arthralgia.

From the digestive system: very often - loss of appetite, nausea; less often - vomiting, diarrhea, dry mouth, change in taste; rarely - abdominal pain, dyspepsia; possibly a reversible increase in liver enzymes.

From the side of the cardiovascular system: often - a decrease in blood pressure; rarely - tachycardia.

Dermatological reactions: less often - alopecia, increased sweating; rarely - skin rash, skin itching.

On the part of the hematopoietic system: reversible leukopenia, granulocytopenia, decreased hemoglobin levels, thrombocytopenia are possible.

Other: rarely - weight loss, autoimmune thyroiditis.

Compound

human recombinant interferon alpha-2b 3 million IU

Excipients: sodium acetate, sodium chloride, ethylenediamine tetraacetic acid disodium salt, tween-80, dextran 40, water for injections.

Dosage and administration

Apply s / c, / m and / in. Treatment must be started by a doctor. Further, with the permission of the doctor, the patient can administer a maintenance dose to himself (in cases where the drug is prescribed s / c or / m).

Chronic hepatitis B: Altevir® is administered SC or IM at a dose of 5-10 million IU 3 times a week for 16-24 weeks. Treatment is stopped after 3-4 months of use in the absence of positive dynamics (according to the DNA study of the hepatitis B virus).

Chronic hepatitis C: Altevir® is administered s.c. or IM at a dose of 3 million IU 3 times a week for 24-48 weeks. In patients with a relapsing course of the disease and patients who have not previously received treatment with interferon alfa-2b, the effectiveness of treatment increases with combination therapy with ribavirin. The duration of combination therapy is at least 24 weeks. Altevir therapy should be carried out for 48 weeks in patients with chronic hepatitis C and the 1st genotype of the virus with a high viral load, in which, by the end of the first 24 weeks of treatment, hepatitis C virus RNA is not detected in the blood serum.

Papillomatosis of the larynx: Altevir® is administered s / c at a dose of 3 million IU / m2 3 times a week. Treatment begins after surgical (or laser) removal of tumor tissue. The dose is selected taking into account the tolerability of the drug. Achieving a positive response may require treatment for 6 months.

Hairy cell leukemia: The recommended dose of Altevir for subcutaneous administration in patients with or without splenectomy is 2 million IU/m2 3 times a week. In most cases, the normalization of one or more hematological parameters occurs after 1-2 months of treatment, it is possible to increase the duration of treatment up to 6 months. This dosing regimen should be followed continuously unless there is rapid progression of the disease or symptoms of severe intolerance to the drug.

Chronic myelogenous leukemia: the recommended dose of Altevir as monotherapy is 4-5 million IU / m2 per day s / c daily. To maintain the number of leukocytes, it may be necessary to use a dose of 0.5-10 million IU / m2. If treatment can achieve control of the number of leukocytes, then the drug should be used at the maximum tolerated dose (4-10 million IU / m2 daily) to maintain hematological remission. The drug should be discontinued after 8-12 weeks if therapy has not resulted in partial hematological remission or a clinically significant decrease in the number of leukocytes.

Non-Hodgkin's lymphoma: Altevir® is used as adjuvant therapy in combination with standard chemotherapy regimens. The drug is administered s / c at a dose of 5 million IU / m2 3 times a week for 2-3 months. The dose must be adjusted depending on the tolerability of the drug.

Melanoma: Altevir® is used as adjuvant therapy in adults with a high risk of recurrence after tumor removal. Altevir® is administered intravenously at a dose of 15 million IU/m2 5 times a week for 4 weeks, then s/c at a dose of 10 million IU/m2 3 times a week for 48 weeks. The dose must be adjusted depending on the tolerability of the drug.

Multiple myeloma: Altevir® is prescribed during the period of achieving a stable remission at a dose of 3 million IU / m2 3 times a week s / c.

Kaposi's sarcoma on the background of AIDS: the optimal dose has not been established. The drug can be used in doses of 10-12 million IU / m2 / day s / c or / m. In case of stabilization of the disease or response to treatment, therapy is continued until the tumor regresses or drug withdrawal is required.

Kidney cancer: the optimal dose and regimen have not been established. It is recommended to use the drug s / c in doses of 3 to 10 million IU / m2 3 times a week.

Preparation of a solution for intravenous administration

The volume of Altevira solution necessary to prepare the required dose is collected, added to 100 ml of sterile 0.9% sodium chloride solution and administered over 20 minutes.

Product description

Solution for injection is clear, colorless.

With caution (Precautions)

Application for violations of liver function

Application for violations of kidney function

The drug is contraindicated in severe renal and / or hepatic insufficiency (including those caused by the presence of metastases).

special instructions

Prior to treatment with Altevir for chronic viral hepatitis B and C, a liver biopsy is recommended to assess the degree of liver damage (signs of an active inflammatory process and / or fibrosis). The effectiveness of the treatment of chronic hepatitis C is increased with combination therapy with Altavir and ribavirin. The use of Altevira is not effective in the development of decompensated liver cirrhosis or hepatic coma.

In case of side effects during treatment with Altevir, the dose of the drug should be reduced by 50% or the drug should be temporarily discontinued until they disappear. If side effects persist or reappear after a dose reduction, or progression of the disease is observed, then treatment with Altevir should be discontinued.

With a decrease in platelet levels below 50x109 / l or granulocyte levels below 0.75x109 / l, it is recommended to reduce the dose of Altevir by 2 times with a blood test control after 1 week. If these changes persist, the drug should be discontinued.

With a decrease in the platelet level below 25x109 / l or the level of granulocytes below 0.5 x109 / l, it is recommended that Altevir® be discontinued with a blood test control after 1 week.

In patients receiving interferon alfa-2b preparations, antibodies can be detected in the blood serum that neutralize its antiviral activity. In almost all cases, antibody titers are low, their appearance does not lead to a decrease in the effectiveness of treatment or the occurrence of other autoimmune disorders.

Use during pregnancy and lactation

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

Release form

Solution for injection is clear, colorless.
1 ml
human recombinant interferon alpha-2b 3 million IU
Excipients: sodium acetate, sodium chloride, ethylenediamine tetraacetic acid disodium salt, tween-80, dextran 40, water

Expiry date from date of manufacture

18 months

Indications for use

As part of complex therapy in adults:

In chronic viral hepatitis B without signs of liver cirrhosis;

In chronic viral hepatitis C in the absence of symptoms of liver failure (monotherapy or combination therapy with ribavirin);

With papillomatosis of the larynx;

With genital warts;

With hairy cell leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma, melanoma, multiple myeloma, Kaposi's sarcoma on the background of AIDS, progressive kidney cancer.

Contraindications

Severe cardiovascular diseases in history (uncontrolled chronic heart failure, recent myocardial infarction, marked cardiac arrhythmias);

Severe renal and / or liver failure (including those caused by the presence of metastases);

Epilepsy, as well as severe disorders of the central nervous system, especially expressed by depression, suicidal thoughts and attempts (including history);

Chronic hepatitis with decompensated liver cirrhosis and in patients receiving or recently treated with immunosuppressants (with the exception of a completed short-term course of treatment with corticosteroids);

Autoimmune hepatitis or other autoimmune disease;

Treatment with immunosuppressants after transplantation;

Thyroid disease that is not controlled by conventional therapeutic methods;

Decompensated lung diseases (including COPD);

Decompensated diabetes mellitus;

Hypercoagulability (including thrombophlebitis, pulmonary embolism);

Severe myelodepression;

Pregnancy;

lactation period (breastfeeding);

Hypersensitivity to the components of the drug.

pharmachologic effect

Interferon. Altevir® has antiviral, immunomodulatory, antiproliferative and antitumor effects.

Interferon alpha-2b, interacting with specific receptors on the cell surface, initiates a complex chain of changes inside the cell, including the induction of the synthesis of a number of specific cytokines and enzymes, disrupts the synthesis of viral RNA and viral proteins in the cell. The result of these changes is nonspecific antiviral and antiproliferative activity associated with the prevention of viral replication in the cell, inhibition of cell proliferation and the immunomodulatory effect of interferon. Interferon alpha-2b stimulates the process of antigen presentation to immunocompetent cells, has the ability to stimulate the phagocytic activity of macrophages, as well as the cytotoxic activity of T-cells and natural killers involved in antiviral immunity.

Prevents cell proliferation, especially tumor cells. It has a depressing effect on the synthesis of certain oncogenes, leading to inhibition of tumor growth.

Altevir (Altevir), Alfarona (Alfarona), Viferon (Viferon), Intron-A (Intron-A), Realdiron (Realdiron), Eberon alpha R (Eberon alfa R).

Composition and form of release

Interferon alfa-2b. Lyophilized powder for injection (in 1 vial - 3 million IU, 5 million IU, 10 million IU, 30 million IU). Recombinant interferon alfa-2b.

Solution for injection (pen-syringe - 10 million IU, 18 million IU, 25 million IU; in 1 vial - 10 million IU, 18 million IU, 25 million IU; 1 dose - 3 million IU, 5 million IU, 10 million ME). Human recombinant interferon alfa-2b. Rectal suppositories (150,000 ME, 500,000 ME).

pharmachologic effect

The drug is a highly purified recombinant interferon alfa-2b for parenteral administration. Obtained from a clone of Escherichia coli by hybridization of a bacterial plasmid with the human leukocyte gene encoding the synthesis of interferon. It is a water-soluble protein with a molecular weight of 19,300 daltons.

The biological activity of interferons is manifested by binding them to specific membrane receptors of cells. Interferon alpha-2b has an antiproliferative effect on tumor cells, as well as an antiviral and immunomodulatory effect.

Pharmacokinetics

With s / c and / m administration, bioavailability is 100%. - with s / c administration 2-3 hours, with intramuscular injection - 6-7 hours, with intravenous - 2 hours. Plasma interferon concentration was not determined after 16.24 and 4 hours, respectively. Alpha interferons are capable of disrupting oxidative metabolic processes, reducing the activity of microsomal liver enzymes of the cytochrome P450 system. Excreted with urine.

Indications

Multiple myeloma (generalized forms), hairy cell leukemia, chronic myeloid leukemia, malignant melanoma, bladder cancer, superficially located genital condylomatosis, laringopapillomatosis, Kaposi's sarcoma, AIDS, chronic hepatitis C, chronic hepatitis B.

Application

The use and treatment regimen depend on the type of disease. During pregnancy, interferon alfa-2b is used only in cases where the expected effect of treatment on the mother outweighs the potential risk to the fetus.

The components of the drug penetrate into the GRM. Therefore, during lactation, based on the importance of the use of interferon alfa-2b for the mother, either breastfeeding or treatment with the drug is stopped. The experience of using the drug in children is small: the appointment of the drug to children should be carefully justified.

Side effect

On the central nervous system, the psyche: often - a feeling of fatigue, headache; possible disturbances of consciousness, dizziness, ataxia, anxiety, depression, irritability, drowsiness, paresthesia; rarely - insomnia; isolated cases of development of paralysis of the oculomotor nerves, visual impairments are described.

On the CCC: possible hypertension or hypotension; rarely - tachycardia; isolated cases of development of orthostatic hypotension, shortness of breath are described.

On PS: often - anorexia, nausea, increased levels of ACT and ALT (when using a dose of the drug in excess of 100 million IU / day), alkaline phosphatase; possible vomiting; rarely - constipation, stomatitis; described individual cases of dyspepsia, increased salivation, ulcerative stomatitis, flatulence.

On the UK: often - thrombocytopenia, granulocytopenia; in some cases - coagulation disorders (increase in prothrombin and partial thromboplastin time), epistaxis; separate cases of development of purpura are described.

On the skin: alopecia, transient rash, itching; rarely - urticaria, furunculosis, herpetic eruptions, vesicular lichen; isolated cases of erythema development are described.

Local reactions: isolated cases of inflammation at the injection site are described.

Other: often - fever, myalgia; possible arthralgia; rarely - cramps of the calf muscles, paroxysmal sensation of heat, dehydration, cough, increased creatinine content; described isolated cases of sneezing, violations of the outflow of secretions from the nose, hyperglycemia.

The composition of interferon preparations depends on their form of release.

Release form

Interferon preparations have the following release forms:

• lyophilized powder for the preparation of eye and nasal drops, injection solution;
• injection solution;
• eye drops;
• eye films;
• nasal drops and spray;
• ointment;
• dermatological gel;
• liposomes;
• spray can;
• oral solution;
• rectal suppositories;
• vaginal suppositories;
• implants;
• microclysters;
• tablets (in tablets, interferon is produced under the brand name Entalferon).

pharmachologic effect

IFN preparations belong to the group of antiviral and immunomodulatory drugs.

All IFNs have antiviral and antitumor activity. Equally important is their ability to stimulate action. macrophages - cells that play an important role in initiation.

IFNs contribute to an increase in the body's resistance to penetration viruses and block reproduction viruses when they enter the cell. The latter is due to the ability of IFN to suppress translation of the messenger (messenger) RNA of the virus .

At the same time, the antiviral effect of IFN is not directed against certain viruses , that is, IFNs are not characterized by virus specificity. This explains their versatility and a wide range of antiviral activity.

Interferon - what is it?

Interferons are a class with similar properties glycoproteins , which are produced by vertebrate cells in response to exposure to various types of inducers, both viral and non-viral in nature.

According to Wikipedia, in order for a biologically active substance to be qualified as an interferon, it must be of a protein nature, have a pronounced antiviral activity in relation to various viruses , at least in homologous (similar) cells, "mediated by cellular metabolic processes, including RNA and protein synthesis."

The classification of IFNs proposed by the WHO and the Interferon Committee is based on differences in their antigenic, physical, chemical and biological properties. In addition, it takes into account their species and cellular origin.

According to antigenicity (antigenic specificity), IFN is usually divided into acid-resistant and acid-labile. Alpha and beta interferons (also called type I IFNs) are acid-fast. Interferon gamma (γ-IFN) is acid-labile.

α-IFN produce peripheral blood leukocytes (B- and T-type leukocytes), so it was previously designated as leukocyte interferon . Currently, there are at least 14 of its varieties.

β-IFN is produced fibroblasts , so it is also called fibroblastic .

Former designation γ-IFN - immune interferon , but its stimulated T-type lymphocytes , NK cells (normal (natural) killers; from the English “natural killer”) and (presumably) macrophages .

Main properties and mechanism of action of IFN

Without exception, all IFNs are characterized by polyfunctional activity against target cells. Their most common property is the ability to induce in them antiviral state .

Interferon is used as a therapeutic and prophylactic agent for various viral infections . A feature of IFN preparations is that their effect weakens with repeated injections.

The mechanism of action of IFN is related to its ability to inhibit viral infections . As a result of treatment with interferon drugs in the patient's body around focus of infection a kind of barrier is formed from resistant to virus uninfected cells, which prevents further spread of the infection.

Interacting with still intact (intact) cells, it prevents the implementation of the reproductive cycle viruses by activating certain cellular enzymes ( protein kinases ).

The most important function of interferons is the ability to suppress hematopoiesis ; modulate the body's immune response and inflammatory response; regulate the processes of cell proliferation and differentiation; inhibit growth and prevent reproduction viral cells ; stimulate the expression of surface antigens ; suppress individual functions B- and T-type leukocytes to stimulate activity NK cells etc..

Use of IFN in biotechnology

Development of methods for synthesis and high-performance purification leukocyte and recombinant interferons in quantities sufficient for the production of drugs, made it possible to open the possibility of using IFN preparations for the treatment of patients diagnosed with viral hepatitis .

A distinctive feature of recombinant IFNs is that they are produced outside the human body.

For example, recombinant interferon beta-1a (IFN β-1a) obtained from mammalian cells (in particular, from Chinese hamster ovary cells), and similar in its properties interferon beta-1b (IFN β-1b) produced by a member of the Enterobacteriaceae family coli (Escherichia coli).

Interferon inducing drugs - what is it?

IFN inducers are drugs that do not themselves contain interferon, but at the same time stimulate its production.

Pharmacodynamics and pharmacokinetics

The main biological effect of α-IFN is inhibition of viral protein synthesis . The antiviral state of the cell develops within a few hours after the application of the drug or the induction of IFN production in the body.

At the same time, IFN does not affect the early stages replication cycle, that is, at the stage of adsorption, penetration virus into the cell (penetration) and release of the internal component virus in the process of undressing him.

Antivirus action α-IFN is manifested even in the case of cell infection infectious RNA . IFN does not enter the cell, but only interacts with specific receptors on cell membranes (gangliosides or similar structures containing oligosugar ).

The mechanism of activity of IFN alpha resembles the action of individual glycopeptide hormones . It stimulates activity genes , some of which are involved in coding the formation of products with direct antiviral action .

β interferons also have antiviral action , which is associated with several mechanisms of action at once. Beta interferon activates NO-synthetase, which in turn increases the concentration of nitric oxide inside the cell. The latter plays a key role in the suppression of reproduction viruses .

β-IFN activates secondary, effector functions natural killerosin , B-type lymphocytes , blood monocytes , tissue macrophages (mononuclear phagocytes) and neutrophilic , which are characterized by antibody-dependent and antibody-independent cytotoxicity.

In addition, β-IFN blocks the release of the internal component virus and disrupts methylation processes virus RNA .

γ-IFN is involved in the regulation of the immune response and regulates the severity inflammatory reactions. Although he has his own antiviral and antitumor effect , gamma interferon very weak. At the same time, it significantly enhances the activity of α- and β-IFN.

After parenteral administration, the maximum concentration of IFN in is observed after 3-12 hours. The bioavailability index is 100% (both after injection under the skin and after injection into the muscle).

The duration of the half-life T½ is from 2 to 7 hours. Trace concentrations of IFN in plasma are not detected after 16-24 hours.

Indications for use

IFN is designed to treat viral diseases that hit respiratory tract .

In addition, interferon preparations are prescribed for patients with chronic forms hepatitis, and Delta .

For treatment viral diseases and, in particular, IFN-α is predominantly used (both of which are IFN-alpha 2b and IFN-alpha 2a). The "gold standard" of treatment hepatitis C considered to be pegylated interferons alpha-2b and alpha-2a. In comparison with them, conventional interferons are less effective.

The genetic polymorphism noted in the IL28B gene, which is responsible for encoding IFN lambda-3, causes significant differences in the effect of treatment.

Patients with genotype 1 hepatitis C with common alleles of this gene are more likely to achieve longer and more pronounced treatment results compared to other patients.

IFN is also often given to patients with oncological diseases : malignant , pancreatic endocrine tumors , non-Hodgkin's lymphoma , carcinoid tumors ; Kaposi's sarcoma , due to ; hairy cell leukemia ,multiple myeloma , kidney cancer etc..

Contraindications

Interferon is not prescribed to patients with hypersensitivity to it, as well as to children and adolescents suffering from severe mental disorders and nervous system disorders , which are accompanied by thoughts of suicide and suicide attempts, severe and protracted.

In combination with antiviral drug ribavirin IFN is contraindicated in patients diagnosed with severe impairment kidney (conditions in which CC is less than 50 ml / min).

Interferon preparations are contraindicated in case of (in cases where the appropriate therapy does not give the expected clinical effect).

Side effects

Interferon belongs to the category of drugs that can cause a large number of adverse reactions from various systems and organs. In most cases, they are the result of the introduction of interferon in / in, s / c or / m, but other pharmaceutical forms of the drug can also provoke them.

The most common adverse reactions to taking IFN are:

• anorexia;
• nausea;
• chills;
• trembling in the body.

Vomiting, increased, feeling of dry mouth, hair loss (), asthenia ; non-specific symptoms resembling flu symptoms ; backache, depressive states , musculoskeletal pain , thoughts of suicide and suicide attempt, general malaise, impaired taste and concentration, increased irritability, sleep disorders (often), arterial hypotension , confusion.

Rare side effects include: pain on the right in the upper abdomen, rashes on the body (erythematous and maculopapular), increased nervousness, soreness and severe inflammation at the injection site, secondary viral infection (including infection herpes simplex virus ), increased dryness of the skin, , pain in the eyes , conjunctivitis blurred vision, dysfunction lacrimal glands , anxiety, mood lability; psychotic disorders , including increased aggression, etc.; hyperthermia , dyspeptic symptoms , respiratory disorders, weight loss, loose stools, hyper or hypothyroidism , hearing impairment (up to its complete loss), the formation of infiltrates in the lungs, increased appetite, bleeding gums, in the limbs, dyspnea , renal dysfunction and development of renal failure , peripheral ischemia , hyperuricemia , neuropathy etc..

Treatment with IFN drugs can cause reproductive dysfunction . Studies in primates have shown that interferon disturbs the menstrual cycle in women . In addition, in women treated with IFN-α, the level of and in.

For this reason, when prescribing interferon, women of childbearing age should use barrier contraceptives . Men of reproductive age are also advised to be informed of potential side effects.

In rare cases, treatment with interferon may be accompanied by ophthalmic disorders, which are expressed as hemorrhages in the retina , retinopathy (including but not limited to macular edema ), focal changes in the retina, decreased visual acuity and / or limited visual fields, papilledema , neuritis of the ophthalmic (second cranial) nerve , arterial obstruction or retinal veins .

Sometimes against the background of taking interferon can develop hyperglycemia , symptoms of nephrotic syndrome , . In patients with diabetes may worsen the clinical picture of the disease.

It cannot be ruled out that the possibility of cerebrovascular hemorrhage , erythema multiforme , tissue necrosis at the injection site cardiac and cerebrovascular ischemia , hypertriglyceridermia , sarcoidosis (or exacerbation of its course), Lyell's syndromes and Stevens-Johnson .

The use of interferon alone or in combination with Ribavirin in rare cases, it can cause aplastic anemia (AA) or even PAKKM ( complete aplasia of the red bone marrow ).

There were also cases when, on the background of treatment with interferon preparations, the patient developed various autoimmune and immune-mediated disorders (including Werlhof's disease and Moszkowitz's disease ).

Interferon, instructions for use (Method and dosage)

Instructions for the use of interferons alpha, beta and gamma indicate that before prescribing a drug to a patient, it is recommended to determine how sensitive to it that caused the disease.

The method of administration of human leukocyte interferon is determined depending on the diagnosis made to the patient. In most cases, it is prescribed in the form of subcutaneous injections, but in some cases the drug can be injected into a muscle or vein.

The dose for treatment, the maintenance dose and the duration of treatment are determined depending on the clinical situation and the response of the patient's body to the therapy prescribed to him.

By "children's" interferon is meant a drug in the form of suppositories, drops and ointments.

Instructions for the use of interferon for children recommends the use of this drug as a therapeutic and prophylactic agent. The dose for infants and older children is selected by the attending physician.

For prophylactic purposes, INF is used in the form of a solution, for the preparation of which distilled or boiled water at room temperature is used. The finished solution is colored red and opalescent. It should be stored in the cold for no more than 24-48 hours. The drug is instilled into the nose of children and adults.

At viral ophthalmic diseases the drug is prescribed in the form of drops for the eyes.

As soon as the severity of the symptoms of the disease decreases, the volume of instillations should be reduced to one drop. The course of treatment is from 7 to 10 days.

For the treatment of lesions caused by herpesviruses , the ointment is applied with a thin layer to the affected areas of the skin and mucous membranes twice a day, maintaining 12-hour intervals. The course of treatment is from 3 to 5 days (until the integrity of the damaged skin and mucous membranes is completely restored).

For prevention ORZ and must be lubricated nasal passages . The frequency of procedures during the 1st and 3rd week of the course is 2 times a day. During the 2nd week, it is recommended to take a break. For prophylactic purposes, interferon should be used throughout the entire period epidemics of respiratory diseases .

The duration of the rehabilitation course in children who often have recurrent viral and bacterial infections of the respiratory tract , ENT organs , recurrent infection caused by herpes simplex virus , is two months.

How to breed and how to use interferon in ampoules?

Instructions for the use of interferon in ampoules indicate that before use, the ampoule must be opened, poured into it with water (distilled or boiled) at room temperature up to the mark on the ampoule corresponding to 2 ml.

The contents are gently shaken until completely dissolved. The solution is injected into each nasal passage twice a day, five drops, maintaining intervals of at least six hours between injections.

For therapeutic purposes, IFN is started when the first flu symptoms . The effectiveness of the drug is higher, the sooner the patient starts taking it.

The most effective is the inhalation method (through the nose or mouth). For one inhalation, it is recommended to take the contents of three ampoules of the drug, dissolved in 10 ml of water.

Water is preheated to a temperature not exceeding +37 °C. Inhalation procedures are carried out twice a day, maintaining an interval of at least one to two hours between them.

When spraying or instillation, the contents of the ampoule are dissolved in two milliliters of water and injected 0.25 ml (or five drops) into each nasal passage three to six times a day. The duration of treatment is 2-3 days.

For preventive purposes, nose drops for children are instilled (5 drops) twice a day, at the initial stage of the development of the disease, the frequency of instillations is increased: the drug should be administered at least five to six times a day every hour or two.

Many are interested in whether it is possible to drip a solution of interferon into the eyes. The answer to this question is in the affirmative.

Overdose

Cases of overdose with interferon are not described.

Interaction

β-IFN is compatible with corticosteroid drugs and ACTH. Should not be taken during treatment myelosuppressive drugs , incl. cytostatics (this may cause additive effect ).

With caution, IFN-β is prescribed with agents whose clearance is largely dependent on cytochrome P450 systems (antiepileptic drugs , some antidepressants and etc.).

Do not take IFN-alpha and Telbivudine . The simultaneous use of α-IFN provokes a mutual enhancement of action in relation to. When used together with phosphazide can mutually increase myelotoxicity both drugs (it is recommended to carefully monitor changes in the amount granulocytes and;

IFN is also used in therapy, the purpose of which is the rehabilitation of frequently ill patients. respiratory infections children.

The most optimal option for taking children is nasal drops: interferon does not penetrate the gastrointestinal tract with this use (before diluting the drug for the nose, the water should be heated to a temperature of 37 ° C).

For infants, interferon is prescribed in the form of suppositories (150 thousand IU). Candles for children should be administered one at a time, 2 times a day, maintaining 12-hour intervals between injections. The course of treatment is 5 days. To fully cure a child SARS As a rule, one course is enough.

For treatment, take 0.5 g of ointment twice a day. Treatment lasts an average of 2 weeks. Over the next 2-4 weeks, the ointment is applied 3 times a week.

Numerous positive reviews about the drug indicate that in this dosage form it has also established itself as an effective treatment for stomatitis and inflamed tonsils . No less effective are inhalations with interferon for children.

The effect of using the drug increases significantly if a nebulizer is used for its administration (it is necessary to use a device that sprays particles with a diameter of more than 5 microns). Inhalations through a nebulizer have their own specifics.

First, interferon must be inhaled through the nose. Secondly, before using the device, it is necessary to turn off the heating function in it (IFN is a protein, it is destroyed at a temperature of more than 37 ° C).

For inhalation in a nebulizer, the contents of one ampoule are diluted in 2-3 ml of distilled or mineral water (you can also use saline for this purpose). The resulting volume is enough for one procedure. The frequency of procedures during the day is from 2 to 4.

It is important to remember that long-term treatment of children with interferon is not recommended, since addiction develops to it and, therefore, the expected effect does not develop.

Interferon during pregnancy

An exception may be cases where the expected benefit of therapy for the expectant mother will outweigh the risk of adverse reactions and adverse effects on fetal development.

The possibility of isolating the components of recombinant IFN with breast milk is not ruled out. Due to the fact that the possibility of exposure to the fetus through milk cannot be excluded, IFN is not prescribed for lactating women.

In extreme cases, when it is impossible to avoid the appointment of IFN, it is recommended that a woman refuse to breastfeed during therapy. To mitigate the side effect of the drug (the occurrence of symptoms similar to those of the flu), it is recommended to co-administer with IFN .

substance-solution: packs Reg. No.: LSR-007009/08

Clinico-pharmacological group:

Release form, composition and packaging

substance -solution.

bottles (1) - packs of cardboard.

Description of the active ingredients of the drug Interferon alfa-2b»

pharmachologic effect

Interferon. It is a highly purified recombinant protein with a molecular weight of 19,300 daltons. Obtained from a clone of Escherichia coli by hybridization of bacterial plasmids with the gene of human leukocytes encoding the synthesis of interferon. Unlike interferon, alpha-2a has arginine at position 23.

It has an antiviral effect, which is due to interaction with specific membrane receptors and induction of RNA synthesis and, ultimately, proteins. The latter, in turn, prevent the normal reproduction of the virus or its release.

It has immunomodulatory activity, which is associated with the activation of phagocytosis, stimulation of the formation of antibodies and lymphokines.

It has an antiproliferative effect on tumor cells.

Indications

Acute hepatitis B, chronic hepatitis B, chronic hepatitis C.

Hairy cell leukemia, chronic myeloid leukemia, renal cell carcinoma, Kaposi's sarcoma on the background of AIDS, cutaneous T-cell lymphoma (mycosis fungoides and Cesari's syndrome), malignant melanoma.

Dosing regimen

Enter in / in or s / c. The dose and treatment regimen is set individually, depending on the indications.

Side effect

Flu-like symptoms: often - fever, chills, pain in the bones, joints, eyes, myalgia, headache, increased sweating, dizziness.

From the digestive system: possible decrease in appetite, nausea, vomiting, diarrhea, constipation, taste disturbance, dry mouth, weight loss, mild abdominal pain, slight changes in liver function tests (usually normal after treatment ends).

From the side of the central nervous system and peripheral nervous system: rarely - dizziness, mental deterioration, sleep disturbance, memory impairment, anxiety, nervousness, aggressiveness, euphoria, depression (after prolonged treatment), paresthesia, neuropathy, tremor; in some cases - a tendency to suicide, drowsiness.

From the side of the cardiovascular system: possible - tachycardia (with fever), arterial hypotension or hypertension, arrhythmia; in some cases - violations of the cardiovascular system, coronary artery disease, myocardial infarction.

From the respiratory system: rarely - chest pain, cough, slight shortness of breath; in some cases - pneumonia, pulmonary edema.

From the hematopoietic system: possible slight leukopenia, thrombocytopenia, granulocytopenia.

Dermatological reactions: possible itching, reversible alopecia.

Others: rarely - muscle stiffness; in isolated cases - antibodies to natural or recombinant interferons.

Contraindications

Severe cardiovascular disease, decompensated cirrhosis of the liver, severe depression, psychosis, alcohol or drug dependence, hypersensitivity to interferon alfa-2b.

Pregnancy and lactation

Use during pregnancy is possible only if the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

It is not known if interferon alfa-2b is excreted in breast milk. If necessary, use during lactation should decide on the termination of breastfeeding.

Women of childbearing age should use reliable contraception during treatment.

Application for violations of liver function

Contraindicated in decompensated cirrhosis of the liver. Use with caution in patients with impaired liver function.

Application for violations of kidney function

Use with caution in patients with impaired renal function.

special instructions

Use with caution in patients with impaired renal, hepatic, bone marrow hematopoiesis, with a tendency to suicidal attempts.

In patients with diseases of the cardiovascular system, arrhythmia is possible. If the arrhythmia does not decrease or increases, the dose should be reduced by 2 times, or treatment should be stopped.

During the period of treatment, it is necessary to control the neurological and mental status.

With severe inhibition of bone marrow hematopoiesis, a regular study of the composition of peripheral blood is necessary.

Interferon alfa-2b has a stimulating effect on the immune system and therefore should be used with caution in patients prone to autoimmune diseases due to an increased risk of autoimmune reactions.

drug interaction

drug interaction

Interferon alfa-2b inhibits theophylline metabolism and reduces its clearance.

The drug is synthesized by bacterial cells of the Escherichia coli SG-20050/pIF16 strain, in the genetic apparatus of which the human interferon alpha-2b gene is inserted. The drug is a protein that contains 165 amino acids, it is identical in properties and characteristics to human leukocyte interferon alpha-2b. The antiviral effect is manifested during the reproduction of the virus, there is an active inclusion of the drug in the metabolic processes of cells. Reacting with specific receptors on the cell surface, the drug initiates a number of intracellular changes, including the production of specific enzymes (protein kinases and 2-5-adenylate synthetase) and cytokines, the action of which slows down the synthesis of the ribonucleic acid of the virus in the cell and the viral protein. Increases the phagocytic activity of macrophages, enhances the specific cytotoxic effect of lymphocytes on target cells. Changes the functional activity of immunocompetent cells, the qualitative and quantitative composition of the decreed cytokines, the formation and secretion of intracellular proteins. Suppresses the proliferation of tumor cells and the formation of certain oncogenes, which inhibits tumor growth.
The maximum concentration of the drug when administered parenterally is achieved after 2 to 4 hours. 20-24 hours after administration, the drug in the blood plasma is not determined. The concentration of the drug in the blood serum directly depends on the frequency and dose of administration. Metabolized in the liver, excreted mainly through the kidneys, partly unchanged.

Indications

Therapy and prevention of influenza and acute respiratory viral infections; emergency prevention of tick-borne encephalitis together with anti-tick immunoglobulin; atopic diseases, allergic rhinoconjunctivitis, bronchial asthma during specific immunotherapy.
Complex treatment in adults: acute viral hepatitis B (moderate and severe forms at the beginning of the icteric period until the fifth day of jaundice (in the later stages, the drug is less effective; with a cholestatic course of the disease and developing hepatic coma, the drug is not effective); acute prolonged hepatitis B and C, chronic active hepatitis B and C, chronic hepatitis B with a delta agent; hairy cell leukemia, stage IV kidney cancer, malignant skin lymphomas (primary reticulosis, mycosis fungoides, reticulosarcomatosis), basal cell and squamous cell colon cancer, Kaposi's sarcoma, subleukemic myelosis, keratoacanthoma, histiocytosis from Langerhans cells, chronic myeloid leukemia, essential thrombocythemia; viral conjunctivitis, keratitis, keratoconjunctivitis, keratouveitis, keratoiridocyclitis; urogenital chlamydial infection; febrile and meningeal form of tick-borne encephalitis.
Complex treatment in children from 1 year old: respiratory papillomatosis of the larynx, starting from the next day after the removal of papillomas; acute lymphoblastic leukemia in remission after the end of induction chemotherapy (4-5 months of remission).

Method of application of interferon alfa-2b human recombinant and dose

Interferon alpha-2b human recombinant is administered intramuscularly, subcutaneously, into the lesion, subconjunctivally, taken orally, used topically. The method of application, doses, regimen and duration of treatment are set individually depending on the indications, age, condition of the patient, tolerability of the drug.
During treatment, general clinical blood tests should be performed every 2 weeks, biochemical - every 4 weeks. With a decrease in the absolute number of neutrophils less than 0.50 X 10^9/l, and the number of platelets less than 25 X 10^9/l, therapy should be discontinued. With a decrease in the absolute number of neutrophils less than 0.75 X 10^9 / l, and the number of platelets less than 50 X 10^9 / l, it is recommended to temporarily reduce the dose of the drug by 2 times and repeat the analysis after 1-2 weeks; if changes persist, it is recommended to cancel therapy.
The patient should be closely monitored if there are signs of a violation of the functional state of the liver. The use of the drug should be discontinued when symptoms progress.
With the development of hypersensitivity reactions (angioneurotic edema, urticaria, anaphylaxis, bronchospasm), the drug is canceled and the appropriate drug treatment is immediately prescribed.
It is necessary to carefully monitor the functional state of the kidneys in the presence of mild and moderate renal impairment.
With prolonged use of the drug, the development of pneumonia and pneumonitis is possible. The relief of pulmonary syndromes is facilitated by the timely withdrawal of the drug and the appointment of glucocorticosteroids.
If there are changes in the central nervous system or / and the psyche, including depression, it is necessary to observe a psychiatrist during treatment and within six months after its completion. After stopping treatment, these disorders are usually quickly reversible, but sometimes it takes up to 3 weeks for their complete reverse development. It is recommended to consult a psychiatrist and stop therapy with the drug if aggressive behavior directed at other people or suicidal thoughts appear, the symptoms of the mental disorder worsen or do not regress. Suicidal thoughts and attempts are more common in children and adolescents than in adults. If treatment with the drug is considered necessary in adult patients with serious mental disorders (including a history), then it should be initiated only if the mental disorder is treated and appropriate individual screening is carried out. The use of the drug in patients under 18 years of age with serious mental disorders (including history) is contraindicated.
In patients with thyroid pathology, prior to the start of therapy, it is necessary to determine the level of thyroid-stimulating hormone, in the future, its content should be monitored at least once every 6 months, as well as when signs of thyroid dysfunction appear. The use of the drug in such patients should be carried out under the supervision of an endocrinologist. With the appearance of thyroid dysfunction or worsening of the course of existing diseases that cannot be treated, it is necessary to cancel the drug.
With prolonged use of the drug, violations of the organ of vision are possible. An ophthalmologic examination is recommended prior to treatment. For any complaints from the organ of vision, an immediate consultation with an ophthalmologist is necessary. Patients with diseases in which changes in the retina can occur (arterial hypertension, diabetes mellitus, and others) should undergo an ophthalmological examination at least once every six months. With the aggravation or appearance of visual disorders, it is necessary to consider the abolition of therapy.
Patients with advanced oncological diseases and / or pathology of the cardiovascular system need careful monitoring and control of the electrocardiogram. When arterial hypotension occurs, appropriate treatment and adequate hydration should be provided.
In elderly patients who receive the drug in high doses, coma, impaired consciousness, encephalopathy, convulsions are possible. With the development of these disorders and the ineffectiveness of dose reduction, therapy is canceled.
With prolonged use of the drug, some patients may develop antibodies to interferon. Typically, antibody titers are low, their appearance does not reduce the effectiveness of treatment.
In transplant patients, medical immunosuppression may be less effective because interferon stimulates the immune system.
Be wary appoint patients with a predisposition to autoimmune diseases. With the development of symptoms of an autoimmune disease, it is necessary to conduct a thorough examination and evaluate the possibility of continuing treatment with interferon. Sometimes treatment with the drug is associated with exacerbation or the occurrence of psoriasis, sarcoidosis.
During treatment, care should be taken when engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions (including driving vehicles), and if fatigue, drowsiness, disorientation or other adverse reactions develop, such activities should be abandoned.

Contraindications for use

Hypersensitivity, severe diseases of the cardiovascular system (recent myocardial infarction, heart failure in the stage of decompensation, severe cardiac arrhythmias), severe allergic diseases, severe liver or / kidney failure, autoimmune hepatitis, chronic hepatitis with decompensated liver cirrhosis, mental illness and disorders in children and adolescents, epilepsy and other disorders of the central nervous system, a history of autoimmune diseases, the use of immunosuppressants after transplantation, thyroid pathology that cannot be controlled by conventional therapeutic methods; pregnancy, breastfeeding period, use in men whose partners are pregnant.

Application restrictions

Severe myelosuppression, liver and / or kidney failure, thyroid disease, psoriasis, sarcoidosis, chronic obstructive pulmonary disease, diabetes mellitus, a tendency to ketoacidosis, blood clotting disorders, mental disorders, especially expressed by depression, suicidal thoughts and history of attempts.

Use during pregnancy and lactation

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

Side effects of interferon alfa-2b human recombinant

Cardiovascular system and blood: transient reversible cardiomyopathy, arrhythmias, arterial hypotension, myocardial infarction, leukopenia, lymphopenia, thrombocytopenia, anemia.
Digestive system: dry mouth, abdominal pain, nausea, dyspepsia, weight loss, appetite disorders, diarrhea, vomiting, pancreatitis, hepatotoxicity, increased activity of alanine aminotransferase, alkaline phosphatase.
Nervous system and sense organs: irritability; depression; vision, optic neuritis, retinal hemorrhage, thrombosis of the arteries and veins of the retina, papilledema.
Skin covers: increased sweating, rash, itching, hair loss, local inflammatory reaction.
Endocrine system: changes in the thyroid gland, diabetes mellitus.
Musculoskeletal system: rhabdomyolysis, back pain, leg cramps, myositis, myalgia.
Respiratory system: pharyngitis, dyspnea, cough, pneumonia.
Urinary system: renal failure, increased concentration of creatinine, urea.
The immune system: autoimmune pathology (rheumatoid arthritis, vasculitis, lupus-like syndrome), sarcoidosis, anaphylaxis, angioedema allergic, swelling of the face.
Others: flu-like syndrome (fever, chills, asthenia, fatigue, fatigue, arthralgia, myalgia, headaches).

Interaction of interferon alpha-2b human recombinant with other substances

The drug reduces clearance and 2 times increases the concentration of aminophylline in plasma.
When used together with amphotericin B, the risk of developing kidney damage, hypotension, bronchospasm increases; with busulfan - veno-occlusive liver disease; with dacarbazine - hepatotoxicity; with zidovudine - neutropenia.
The drug enhances the toxicity of doxorubicin.
When combined with levothyroxine sodium changes the effect, dose adjustment may be required.
When used together with pegaspargase, the risk of side effects increases mutually.
The drug can reduce the activity of cytochrome P-450 isoenzymes and, thereby, affect the metabolism of phenytoin, cimetidine, chimes, diazepam, warfarin, theophylline, propranolol, and some cytostatics.
May enhance the myelotoxic, neurotoxic, cardiotoxic effect of drugs that were previously or jointly prescribed.
Avoid simultaneous use with drugs that depress the central nervous system, immunosuppressive agents (including glucocorticosteroids).
Drinking alcohol during therapy is not recommended.
When combined with hydroxyurea, the incidence of cutaneous vasculitis may increase.
When used together with theophylline, it is necessary to control the concentration of theophylline in the blood plasma and, if necessary, adjust the dosing regimen.

Overdose

With an overdose of the drug, side effects increase. It is necessary to cancel the drug, conduct symptomatic and supportive treatment.

Trade names of drugs with the active substance interferon alfa-2b human recombinant

Combined drugs:
Interferon alpha-2b human recombinant + Diphenhydramine: Ophthalmoferon®.