Interferon. Instructions for the drug, use, price, release forms. Possible side effects. Approximate cost of the medicine

Instructions for use

Altevir instructions for use

Dosage form

Solution for injections transparent, colorless

Compound

Human recombinant interferon alpha-2b 5 million IU/1ML

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

Pharmacodynamics

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, and 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 killer” cells involved in antiviral immunity.

Prevents cell proliferation, especially tumor cells. It has an inhibitory effect on the synthesis of some oncogenes, leading to inhibition of tumor growth.

Pharmacokinetics

Suction

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

Metabolism

Metabolism occurs in the liver.

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

Removal

It is excreted mainly by the kidneys by glomerular filtration.

Side effects

General reactions: very often - fever, weakness (they are dose-dependent and reversible reactions, disappear within 72 hours after a break in treatment or its cessation), 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; a reversible increase in liver enzyme activity is possible.

From the cardiovascular system: often - decreased blood pressure; rarely - tachycardia.

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

From the hematopoietic system: reversible leukopenia, granulocytopenia, decreased hemoglobin levels, thrombocytopenia are possible.

Other: rarely - weight loss, autoimmune thyroiditis.

Selling Features

prescription

Special conditions

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

If side effects occur 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 recur after dose reduction, or disease progression is observed, treatment with Altevir should be discontinued.

If the platelet level decreases below 50x109/l or the granulocyte level below 0.75x109/l, it is recommended to reduce the Altevir dose by 2 times with blood test monitoring after 1 week. If these changes persist, the drug should be discontinued.

If the platelet level decreases below 25x109/l or the granulocyte level below 0.5x109/l, it is recommended to discontinue Altevir® with blood test monitoring after 1 week.

In patients receiving interferon alpha-2b preparations, antibodies that neutralize its antiviral activity can be detected in the blood serum. 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.

Indications

As part of complex therapy in adults:

With chronic viral hepatitis B without signs of liver cirrhosis;

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

With papillomatosis of the larynx;

For genital warts;

For hairy cell leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma, melanoma, multiple myeloma, Kaposi's sarcoma due to AIDS, progressive kidney cancer.

Contraindications

History of severe cardiovascular disease (uncontrolled chronic heart failure, recent myocardial infarction, severe heart rhythm disturbances);

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 a history);

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

Autoimmune hepatitis or other autoimmune disease;

Treatment with immunosuppressants after transplantation;

Disease of the thyroid gland that cannot be controlled by generally accepted therapeutic methods;

Decompensated lung diseases (including COPD);

Decompensated diabetes mellitus;

Hypercoagulation (including thrombophlebitis, pulmonary embolism);

Severe myelodepression;

Pregnancy;

Lactation period (breastfeeding);

Hypersensitivity to the components of the drug.

Use during pregnancy and breastfeeding

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

Use for liver dysfunction

Use for renal impairment

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

Drug interactions

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 potentially have a myelosuppressive effect.

When Altevir and theophylline are prescribed simultaneously, the concentration of the latter in the blood serum should be monitored and, if necessary, its dosage regimen should be changed.

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

Prices for Altevir in other cities

Mode of application

Dosage

Chronic hepatitis B: Altevir® is administered subcutaneously or intramuscularly 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 a study of hepatitis B virus DNA).

Chronic hepatitis C: Altevir® is administered subcutaneously or intramuscularly 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. Therapy with Altevir 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 whom hepatitis C virus RNA is not detected in the blood serum by the end of the first 24 weeks of treatment.

Laryngeal papillomatosis: Altevir® is administered subcutaneously at a dose of 3 million IU/m2 3 times a week. Treatment begins after surgical (or laser) removal of the 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 to patients after or without splenectomy is 2 million IU/m2 3 times a week. In most cases, normalization of one or more hematological parameters occurs after 1-2 months of treatment; it is possible to increase the treatment period to 6 months. This dosage regimen should be followed continuously unless rapid progression of the disease or symptoms of severe intolerance to the drug occur.

Chronic myeloid leukemia: the recommended dose of Altevir as monotherapy is 4-5 million IU/m2 per day subcutaneously daily. To maintain the number of leukocytes, a dose of 0.5-10 million IU/m2 may be required. If treatment allows to achieve control of the number of leukocytes, then to maintain hematological remission the drug should be used at the maximum tolerated dose (4-10 million IU/m2 daily). The drug should be discontinued after 8-12 weeks if therapy does not lead to 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 subcutaneously 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 when there is a high risk of relapse in adults after tumor removal. Altevir® is administered intravenously at a dose of 15 million IU/m2 5 times a week for 4 weeks, then subcutaneously 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 stable remission at a dose of 3 million IU/m2 3 times a week subcutaneously.

Kaposi's sarcoma due to AIDS: the optimal dose has not been established. The drug can be used in doses of 10-12 million IU/m2/day subcutaneously or intramuscularly. If the disease stabilizes or responds to treatment, therapy is continued until tumor regression occurs or drug discontinuation is required.

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

Preparation of solution for intravenous administration

Draw up the volume of Altevir solution required to prepare the required dose, add it to 100 ml of sterile 0.9% sodium chloride solution and administer it over 20 minutes.

Overdose

Included in the preparations

VED

ONLS

L.03.A.B.01 Interferon alpha

Hepatitis B and viral active hepatitis C;

- multiple myeloma;

- hairy cell leukemia;

- genital warts;

- Kaposi's sarcoma in patients with AIDS who do not have a history of acute infections;

- prevention/treatment of influenzaand acute respiratory viral infection;

-Griboid mycosis;

- malignant melanoma;

- renal carcinoma;

- chronic myeloid leukemia;

- primary (essential) and secondary thrombocytosis;

- transitional form of chronic granulocytic leukemia and myelofibrosis;

Kidney cancer;

- reticulosarcoma;

-Rmultiple sclerosis.

I.A50-A64.A63.0 Anogenital (venereal) warts

I.A80-A89.A84 Tick-borne viral encephalitis

I.B15-B19.B16 Acute hepatitis B

I.B15-B19.B17.1 Acute hepatitis C

I.B15-B19.B18.1 Chronic viral hepatitis B without delta agent

I.B15-B19.B18.2 Chronic viral hepatitis C

I.B20-B24 Human immunodeficiency virus disease [HIV]

I.B20-B24.B21.0 Disease caused by HIV with manifestations of Kaposi's sarcoma

I.B35-B49.B37 Candidiasis

I.B35-B49.B37.2 Candidiasis of the skin and nails

II.C15-C26.C20 Malignant neoplasm of the rectum

II.C43-C44.C43 Malignant melanoma of the skin

II.C43-C44.C44 Other malignant neoplasms of the skin

II.C51-C58.C57.9 Malignant neoplasm of the female genital organs of unspecified localization

II.C64-C68.C64 Malignant neoplasm of the kidney other than the renal pelvis

II.C81-C96.C82 Follicular [nodular] non-Hodgkin's lymphoma

II.C81-C96.C83 Diffuse non-Hodgkin's lymphoma

II.C81-C96.C84.0 Mycosis fungoides

II.C81-C96.C90.0 Multiple myeloma

II.C81-C96.C91.4 Hairy cell leukemia (Leukemic reticuloendotheliosis)

II.C81-C96.C92.1 Chronic myeloid leukemia

III.D80-D89.D84.9 Immunodeficiency, unspecified

VI.G35-G37.G35 Multiple sclerosis

X.J00-J06.J06.9 Acute upper respiratory tract infection, unspecified

X.J10-J18.J10 Influenza caused by an identified influenza virus

XI.K70-K77.K73 Chronic hepatitis, not elsewhere classified

XIV.N70-N77.N71 Inflammatory diseases of the uterus, except the cervix

XIV.N80-N98.N80 Endometriosis

XXI.Z20-Z29.Z29.1 Preventive immunotherapy

XXI.Z40-Z54.Z54 State of recovery

- hypersensitivity;

- impaired liver and kidney function;

- severe organic heart disease;

- autoimmune hepatitis;

- thyroid diseases;

- epilepsy/disorders of the central nervous system;

- chronic hepatitis with symptoms of liver failure;

- chronic hepatitis with previous immunosuppressant therapy.

- myocardial infarction;

- blood clotting disorder;

Myelodepression;

- simultaneous use of sleeping pills, opioid analgesics, sedatives.

Not described.

Manufacturer: Schering-Plough (Brinny) Company

Anatomical-therapeutic-chemical classification: Interferon alfa-2b

Registration number: No. RK-LS-5 No. 010813

Registration date: 04.02.2013 - 04.02.2018

Instructions

• Russian

Tradename

Intron A®

International nonproprietary name

Interferon alpha

Dosage form

Solution for injection 18 million IU/3 ml (6 doses of 3 million IU),

18 million IU/1.2 ml (6 doses of 3 million IU)

Compound

1 ml of solution contains

active substance - interferon alpha-2b 6 million IU, 10 million IU or 15 million IU,

Excipients: disodium hydrogen phosphate anhydrous, sodium dihydrogen phosphate monohydrate, sodium edetate, sodium chloride, m-cresol (m-cresol), polysorbate-80, water for injection.

Description

Transparent colorless liquid without visible mechanical inclusions.

Pharmacotherapeutic group

Immunostimulants. Interferons. Interferon alpha-2b.

ATX code L03AB05

Pharmacological properties

Pharmacokinetics

Adults.

The pharmacokinetics of interferon alfa-2b were studied in healthy volunteers with single doses of 5 million IU/m2 and 10 million IU/m2 intramuscularly, subcutaneously and by intravenous infusion over 30 minutes. Mean serum interferon concentrations were comparable after subcutaneous and intramuscular administration. In this case, maximum serum concentrations were achieved after 3-12 hours (5 million IU/m2) and 6-8 hours (10 million IU/m2); the half-life of both intramuscular and subcutaneous administration was approximately 2-3 hours and 6-7 hours, according to the doses; the interferon content in the blood serum was not determined after 16-24 hours. The bioavailability of the drug after subcutaneous and intramuscular administration was 100%. After intravenous administration, the concentration of interferon in plasma reached maximum values ​​(135-273 IU/ml) at the end of the infusion, then decreased somewhat faster than after subcutaneous or intramuscular injections, and was not determined 4 hours after the end of the infusion; The half-life was approximately 2 hours.

The concentration of interferon in urine was below the detectable value, regardless of the route of administration. Interferon-neutralizing antibodies were measured in patients receiving interferon alfa-2b during controlled clinical trials. The frequency of their detection was 2.9% in patients receiving interferon alfa-2b therapy for cancer, and 6.2% in patients with chronic hepatitis. The detection of interferon-neutralizing antibodies did not affect the effectiveness of therapy and is not associated with other autoimmune disorders.

Children and teenagers.

Data on the pharmacokinetics of interferon alfa-2b injection solution with ribavirin (RBV), capsules when prescribed to children and adolescents aged 5 to 16 years with chronic hepatitis C (CHC) are presented in Table 1. Pharmacokinetics of interferon alfa-2b injection solution with RBV capsules is similar between adults and children or adolescents.

Table 1. Pharmacokinetic parameters of the drug Intron A® and RBV capsules when prescribed to children and adolescents with CHC

* AUC12h (ng.hour/ml) for RBV, AUC0-24h (IU.hour/ml) for Intron A®.

Pharmacodynamics

Intron A® is a preparation of recombinant highly purified interferon alpha-2b, which is a water-soluble protein with a molecular weight of about 19,300 daltons. It is produced from a clone Escherichia coli, containing a plasmid hybrid obtained by genetic engineering methods and including the interferon alpha-2b gene from human leukocytes.

The activity of the drug Intron A® is expressed in international units (IU); 1 mg of recombinant interferon alpha-2b corresponds to 2.6×108 IU. International units are determined by comparing the activity of recombinant interferon alpha-2b with the activity of the World Health Organization (WHO) standard preparation of human leukocyte interferon.

Interferons are protein molecules with a molecular weight of 15,000 to 21,000 daltons. Interferons are produced and secreted by cells in response to viral infection or other pathogens. There are three main classes of interferons: alpha, beta and gamma, which have differences in the interferon molecule. More than 14 types of human interferon-alpha have been identified. Intron A® is classified as recombinant interferon alpha-2b.

Interferons act on cells by binding to specific membrane receptors on the cell surface. Human interferon receptors isolated from human lymphoblastoid cells (Daudi) are highly asymmetric proteins. They demonstrate selectivity for human, but not mouse, interferons, indicating species specificity. Studies with other interferons have demonstrated species specificity. However, certain species of monkeys, such as rhesus monkeys, are sensitive to pharmacodynamic stimulation by human type 1 interferons.

Several studies suggest that after binding to the cell membrane, interferon initiates a complex sequence of intracellular reactions, including the induction of certain enzymes. It is assumed that, at least partially, these processes determine the various cellular effects of interferon, including inhibition of viral replication in infected cells, inhibition of cell proliferation, as well as such immunomodulatory properties of interferon as increased phagocytic activity of macrophages and increased specific cytotoxicity of lymphocytes relative to target cells. Some or all of these effects may determine the therapeutic effect of interferon.

Recombinant interferon alpha-2b has demonstrated antiproliferative effects in studies using animal and human cell cultures, as well as human tumor xenografts in animals. The drug demonstrated significant immunomodulatory activity in vitro.

Recombinant interferon alpha-2b also inhibits viral replication in vitro And in vivo. Although the exact antiviral mechanism of action of recombinant interferon alpha-2b has not been established, the drug is known to alter metabolism in host cells. As a result, viral replication is inhibited or, if replication has occurred, the progeny virions are unable to leave the cell.

Chronic hepatitis B (CHB).

Studies have shown that patients receiving interferon alfa-2b for 4 to 6 months had a decrease/absence of hepatitis B virus DNA (HBV-DNA) in the blood serum and an improvement in liver histology. Significant reductions in morbidity and mortality were observed in adult patients negative for hepatitis E antigen (HBeAg) and HBV DNA.

Pediatric patients with active CHB who received interferon alfa-2b at a dose of 6 IU/m2 3 times a week for 6 months experienced decreased growth and, in some cases, depression. Due to methodological flaws, it is impossible to determine the effectiveness of therapy.

CHC in adult patients. In adult patients receiving interferon alfa-2b in combination with RBV, a sustained virologic response (SVR) rate of 47% was observed. However, better efficacy was observed with the combination of pegylated interferon alfa-2b with RBV (PegIFN + RBV) (SVR rate of 61% was achieved in adult patients with RBV dose >10.6 mg/kg).

Co-administration of interferon alfa-2b with RBV increases the effectiveness of HCV therapy with Intron A® by 2 times in patients who have not previously received treatment. Predictors of treatment effectiveness and the development of virological response are the initial viral load and HCV genotype. The sustainability of the virological response depends on patient adherence to therapy. Patients who completed ≥80% of the course of interferon alfa-2b plus RBV combination therapy had a higher SVR rate at 6 to 12 months after completion of therapy compared with patients who completed< 80% курса комбинированной терапии, вне зависимости от генотипа ВГС.

Patients co-infected with hepatitis C virus/human immunodeficiency virus (HCV/HIV).

Treatment of patients with HCV and HIV co-infection with the combination of Intron A® and RBV is less effective compared to the combination of PegIFN + RBV.

Patients who relapsed after previous interferon alfa-2 monotherapyb.

345 patients received Intron A® as monotherapy or in combination with RBV for relapse in the studies. In cases of treatment of relapse, Intron A® in combination with RBV is 10 times more effective than monotherapy with Intron A® (48.6% versus 4.7%). The criteria for assessing effectiveness were considered to be a decrease in HCV titer in the serum (<100 копий/мл в ПЦР), нормализацию аланинаминотрансферазы (АЛТ), уменьшение воспалительных процессов в печени по истечении 6 месяцев после окончания терапии.

A clinical trial of 1,071 patients receiving non-pegylated interferon alfa-2b monotherapy or non-pegylated interferon alfa-2b/RBV combination therapy was conducted to determine the duration of SVR after completion of therapy and the clinical effect of viral clearance on treatment efficacy. Of the 492 patients, only 12 patients experienced a relapse of CHC (462 patients were followed for five years) after completion of therapy. The presence of SVR after treatment with non-pegylated interferon alfa-2b alone or in combination with RBV led to long-term clearance of viral infection, ensuring resolution of liver infection and clinical recovery of patients with CHC. The possibility of developing hepatic complications in patients with liver cirrhosis, including the development of hepatocarcinoma, should be considered.

CHC in children and adolescents.

Clinical studies in children and adolescents receiving combination therapy with standard interferon with RBV or PegIFN with RBV found that combination therapy with Intron A® with RBV was less effective than therapy with pegylated interferon alfa-2b with RBV.

Children and adolescents aged 3 to 16 years with compensated CHC and hepatitis C virus RNA (HCV-RNA) positive, showed treatment results similar to the results of therapy in adults after treatment with Intron A® in the amount of 3 million IU/m2 3 times a week with RBV at a dose of 15 mg/kg per day for 1 year (patients were monitored for 6 months).

Data on the duration of therapy effectiveness.

At 5-year follow-up of 97 children who completed treatment with standard interferon, 75% of children maintained SVR (70% of children completed the study). The objective of the clinical trial was to determine the duration of SVR and the clinical effect of viral load clearance on treatment response in patients with SVR at week 24 during 48 weeks of interferon alfa-2b or RBV therapy. Only one child experienced disease relapse after completing combination therapy with interferon alfa-2b and RBV.

The presence of SVR after therapy with non-pegylated interferon alfa-2b in combination with RBV led to long-term clearance of viral infection, ensuring resolution of liver infection and clinical recovery of patients with CHC. The possibility of developing hepatic complications in patients with liver cirrhosis, including the development of hepatocarcinoma, should be considered.

Indications for use

chronic hepatitis B in the presence of HBV DNA and HBeAg in the blood, increased ALT activity and histologically proven active liver inflammation and/or fibrosis in adult patients

chronic hepatitis C (before starting therapy with Intron A®, it is necessary to take into account the results of a comparison of clinical studies between Intron A® and pegylated interferon)

Adults

as part of complex therapy with Intron A® with ribavirin with increased transaminase activity without signs of liver decompensation and in the presence of HCV RNA in the blood (combination therapy with ribavirin is recommended)

Children over 3 years of age and teenagers

as part of complex therapy with Intron A® with ribavirin in children over 3 years of age and adolescents with chronic hepatitis C who have not previously received treatment, in the absence of signs of liver decompensation and the presence of HCV RNA in the blood (it should be taken into account that in some patients the prescription combination therapy may reduce height, so the decision to prescribe therapy should be made on an individual basis)

hairy cell leukemia

chronic myeloid leukemia

Monotherapy in adult patients with Philadelphia chromosome (Ph+) or BCR/ABL translocation (clinical experience shows that hematological remission and cytogenetic response (major/minor) is achieved in the majority of patients, with major cytogenetic response defined as the number of Ph+ leukemia cells< 34 %, а малый, от 34 до90 % Ph+ лейкозных клеток

Combination therapy with cytarabine (in the first 12 months can significantly increase the number of large cytogenetic responses and significantly increase survival compared with interferon alfa-2b monotherapy)

multiple myeloma

as maintenance therapy in patients who have achieved remission (more than 50% reduction in myeloma protein levels) after initial induction chemotherapy. Clinical experience shows that maintenance therapy with interferon alfa-2b prolongs the stabilization phase, although data on improved survival have not yet been fully confirmed.

follicular lymphoma

as adjuvant therapy in combination with appropriate chemotherapy, such as a CHOP regimen, in the presence of at least one of the following: large tumor size (> 7 cm), involvement of more than 3 lymph nodes (each > 3 cm), presence of systemic manifestations (loss of body weight > 10%, increased body temperature > 38°C for more than 8 days or night sweats), splenomegaly (spleen extends beyond the umbilical area), compression of vital organs, development of compression syndrome, involvement of the epidural space or orbital areas, leukemia or significant effusion

renal cell carcinoma

malignant melanoma (as adjuvant therapy for high risk of recurrence after surgical removal of the tumor)

carcinoid tumor with metastases to lymph nodes or liver and carcinoid syndrome

Directions for use and doses

The drug should only be prescribed by doctors with relevant experience. If adverse events occur during treatment with Intron A® for any indication, the dose should be adjusted or treatment should be temporarily discontinued until the adverse events cease. If persistent or recurrent intolerance develops after appropriate dose adjustment or due to disease progression, Intron A® treatment should be discontinued. At the discretion of the physician, the patient may self-administer the dose during a maintenance regimen in which the drug is administered subcutaneously.

Chronic hepatitis B.

The recommended dose of Intron A® is from 5 to 10 million IU, subcutaneously 3 times a week (every other day) for 4-6 months. In case of hematological disorders such as a decrease in the number of leukocytes<1 500/мм3, числа гранулоцитов < 1 000/мм3 и числа тромбоцитов < 100 000/мм3 доза должна быть снижена на 50 %. Лечение необходимо прекратить в случае возникновения тяжелых форм лейкопении (<1200/мм3), нейтропении (<750/мм3) или тромбоцитопении (<70 000/мм3). Лечение препаратом Интрон А® прекращают, если после 3-4 месяцев лечения не наблюдается вирусологического ответа в виде исчезновения ДНК-ВГВ в сыворотке крови.

Chronic hepatitis C

Adults. Intron A® is prescribed to adults at a dose of 3 million IU 3 times a week (every other day), subcutaneously as monotherapy or in combination with RBV.

Children over 3 years old and teenagers. Intron A® is used at a dose of 3 million IU/m2 3 times a week (every other day), subcutaneously, in combination with capsules or RBV solution taken orally with meals, in two doses - morning and evening (see instructions for medical use and modifications of RBV capsules. For children weighing less than 47 kg, see the instructions for medical use of the oral solution).

Patients with recurrent disease (adults).

Intron A® is prescribed only in combination with RBV. Based on the results of clinical studies conducted over a 6-month period, the recommended duration of combination treatment with RBV is 6 months.

® .

The effectiveness of Intron A® increases when used simultaneously with RBV. Monotherapy with the drug is carried out only if there are contraindications to the use or intolerance to RBV.

Intron A® in combination withR.B.V.

Based on the results of clinical studies conducted over a 12-month period, the recommended duration of combination therapy with RBV is at least 6 months. In patients with genotype 1 and a high level of HCV RNA (based on the results of a study conducted before the start of therapy), in whom hepatitis C virus RNA (HCV RNA) is not detected in the blood serum at the end of the first 6 months of therapy, treatment is continued for another 6 months (a total of 12 months). When deciding whether to carry out combination therapy for 12 months, other negative prognostic factors should also be taken into account: age over 40 years, male gender, bridging fibrosis. During clinical trials, it was found that in the absence of a virological response after 6 months of therapy (HCV RNA is below the detection level), SVR, as a rule, is not formed (HCV RNA level is below the detection level 6 months after cessation of therapy).

MonotherapydrugIntron A® .

The optimal duration of Intron A® monotherapy has not been established, but the recommended duration is 12 to 18 months.

Monotherapy with Intron A® is discontinued if after 3-4 months of treatment there is no virological response in the form of disappearance of HCV RNA in the blood serum.

Patients who have not previously received Intron A® (children and teenagers). Duration of treatment for children and adults:

Genotype 1 - the recommended duration of therapy is one year. Patients who do not achieve a virologic response after 12 weeks of therapy are unlikely to become sustained virologic responders (negative predictive value 96%). Therefore, in children and adolescents receiving Intron A®/RBV combination therapy, it is recommended to discontinue therapy if HCV RNA levels have decreased at week 12< 2 log10 по сравнению с показателями до терапии или если РНК-ВГС определяется после 24 недель лечения.

Hairy cellleukemia

The recommended dose of Intron A® for subcutaneous administration 3 times a week (every other day) to patients after and without splenectomy is 2 million IU/m2. In most cases, normalization of one or more hematological parameters occurs after 1-2 months of treatment. Normalization of peripheral blood parameters (white blood cell count, platelet count and hemoglobin level) may require up to 6 months of treatment. This dosage regimen should be followed continuously, unless the disease rapidly progresses or severe intolerance to the drug develops.

Chronic myeloid leukemia (CML).

The recommended dose of Intron A® is 4 to 5 million IU/m2 subcutaneously daily. Once the target stable leukocyte count is achieved, the maximum tolerated dose (4 to 5 million IU/m2 every day) should be used to maintain hematologic remission. Intron A® should be discontinued after 8-12 weeks of treatment, unless partial hematological remission or a clinically significant decrease in the number of leukocytes is achieved before this time.

Multiple myeloma

Maintenance therapy. In patients in the stabilization phase (more than 50% reduction in myeloma protein levels), after initial induction chemotherapy, interferon alfa-2b can be administered as monotherapy, subcutaneously, at a dose of 3 million IU/m2 three times a week (every other day).

Follicular lymphoma

In combination with chemotherapy, Intron A® is prescribed subcutaneously at a dose of 5 million IU 3 times a week (every other day) for 18 months. It is recommended to use CHOP chemotherapy regimens. Clinical data are only available for the use of CHVP (a combination of cyclophosphamide, doxorubicin, teniposide and prednisolone).

Renal cellcarcinoma

Monotherapy. Intron A® is prescribed both intravenously and subcutaneously, in doses from 3 to 30 million IU/m2 3 or 5 times a week, or every day. The maximum effect is observed with subcutaneous administration of the drug Intron A® at a dose of 3 to 10 million IU/m2 3 times a week for 6 months.

Combination therapy with other drugs such as interleukin-2. The optimal dose has not been established. Intron A® is used subcutaneously in doses from 3 to 20 million IU/m2 in combination with interleukin-2. The maximum effect is observed when using Intron A® at a dose of 6 million IU/m2 3 times a week, subcutaneously.

Carcinoid tumors.

The standard dose of Intron A® is 5 million IU (3-9 million IU) subcutaneously 3 times a week (every other day). In patients with an advanced process, doses of up to 5 million IU may be required daily. During surgical treatment, therapy with Intron A® is temporarily suspended for the duration of the operation and the recovery period after it. Therapy with the drug is continued until a clinical response to treatment with interferon alfa-2b is observed.

Malignant melanoma.

To induce remission, a solution of the drug Intron A® is used intravenously at a dose of 20 million IU/m2 5 times a week for 4 weeks; followed by a maintenance dose of 10 million IU/m2 subcutaneously 3 times a week (every other day) for 48 weeks. A dose of interferon alfa-2b is administered over 20 minutes along with 0.9% sodium chloride solution (9 mg/ml).

If severe side effects develop during therapy with Intron A®, especially when the granulocyte count decreases to less than 500/mm3 or alanine aminotransferase/aspartate aminotransferase (ALT/AST) increases to values ​​that exceed the upper limit of normal (ULN) by 5 times, use the drug temporarily stop until the side effects disappear. Treatment with Intron A® is resumed using a preliminary dose reduced by 50%. The drug is discontinued if, after reducing the dose, intolerance persists and the number of granulocytes decreases to the value<250/мм3 или увеличение активности АЛТ/АСТ до значений, превышающих ВГН в 10 раз. Currently, the optimal (minimum) dose to achieve clinical effect has not been established, so patients should be prescribed the recommended dose with a dose reduction in case of development of a toxic effect of the drug.

Methods of administration.

Before administration, it is necessary to visually verify that there are no visible particles or changes in the color of the solution. The solution of the drug Intron A® in vials and syringe pens should be colorless and transparent. Not all dosage forms and concentrations correspond to some of the indications. Make sure to select the correct dosage form and concentration. Intron A® solution for injection or infusion must be administered immediately after removing the required dose from the vial using a sterile needle.

The syringe pen must be removed from the refrigerator 30 minutes before. Before injection, allow the solution to warm to room temperature (not higher than 25 °C). Each pen is intended to be used for a maximum of 4 weeks; After this period, the drug cannot be used. A new needle must be used for each subsequent injection. After the injection, the needle must be thrown away (in compliance with safety rules), and the syringe pen must be immediately placed in the refrigerator. The total duration of exposure of the pen syringe outside the refrigerator at a temperature of 25 ° C should not exceed 48 hours (two days) during the 4-week period of its use.

The required number of needles and napkins is placed in a cardboard box with a syringe pen based on the number of injections stated on the package. The patient should be instructed to dispose of needles and wipes after administering the last dose from the pen.

Preparation of solution for intravenous administration should be carried out immediately before use. The final concentration of interferon alpha-2b in a 0.9% sodium chloride solution should be at least 0.3 million IU/ml. The appropriate dose of the drug is taken from the bottle(s), added to 50 ml of 0.9% sodium chloride solution in a polyvinyl chloride (PVC) bag or glass bottle for infusion and administered intravenously (drip) over 20 minutes.

SIMULTANEOUS ADMINISTRATION OF OTHER DRUGS WITH INTRON A® IN THE SAME SYRINGE IS NOT ALLOWED!

Side effects

Clinical studies using a wide range of doses for different indications (from 6 million IU/m2 per week for hairy cell leukemia to 100 million IU/m2 per week for melanoma) found that the most common adverse reactions were fever, fatigue, headache, myalgia. The fever and fatigue resolved 72 hours after stopping the drug administration.

Frequency is defined as very often (≥1/10), often (≥1/100,<1/10), нечасто (≥1/1 000, <1/100), редко (≥1/10 000, <1/1 000), очень редко (<1/10 000) или неизвестно (не поддающееся оценке по доступным данным).

In adults

Often

Pharyngitis*, viral infection*, leukopenia, anorexia

Depression, insomnia, agitation, emotional lability*, agitation, nervousness

Dizziness, headache, difficulty concentrating, dry mouth

Visual impairment

Dyspnea*, cough*

Nausea, vomiting, abdominal pain, diarrhea, stomatitis, dyspepsia

Alopecia, itching*, dry skin*, rash*, sweating

Myalgia, arthralgia, musculoskeletal pain

Inflammation and local reactions at the injection site*, fatigue, chills, pyrexia§, flu-like state§, asthenia, irritability, chest pain, malaise, weight loss

Often

bronchitis, sinusitis, herpes simplex (resistant), rhinitis

thrombocytopenia, lymphadenopathy, lymphopenia

hypothyroidism§, hyperthyroidism§

hypocalcemia, dehydration, hyperuricemia, thirst

confusion, sleep disturbance, decreased libido

tremor, paresthesia, hypoesthesia, migraine, hot flashes, insomnia, taste perversion

conjunctivitis, blurred vision, lacrimal gland disorders, eye pain

vertigo, ringing in the ears

palpitations, tachycardia, hypertension

nosebleeds, respiratory distress, nasal congestion, rhinorrhea, nonproductive cough

ulcerative stomatitis, pain in the right upper quadrant, inflammation of the tongue, gingivitis, constipation, loose stools, hepatomegaly

psoriasis (newly acquired or worsened)§, maculopapular rash, erymatous rash, eczema, erythema, skin inflammation

• frequent urination

  amenorrhea, chest pain, dysmenorrhea, menorrhagia, menstrual irregularities, vaginal diseases

  pain at the injection site

Infrequently

bacterial infection, peripheral neuropathy

Rarely

pneumonia§, sepsis

suicidal ideation

retinal hemorrhages§, retinopathy (including macular edema), retinal artery or vein thrombosis§, optic neuritis, papilledema, decreased visual acuity or limited visual fields, cotton spots§

cardiomyopathy

Very rarely

aplastic anemia, sarcoidosis, exacerbation of sarcoidosis

hyperglycemia, hypertriglyceridemia§, increased appetite

suicide, suicide attempts, aggressive behavior (sometimes directed against others), psychosis, including hallucinations

cerebrovascular hemorrhage, cerebrovascular ischemia, epileptic seizure, impaired consciousness, encephalopathy

hearing loss, hearing loss

myocardial infarction, cardiac ischemia, peripheral ischemia, hypotension§

pancreatitis, ischemic colitis, ulcerative colitis, bleeding gums

hepatotoxicity (sometimes fatal)

Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, rhabdomyolysis, myositis, calf muscle cramp, low back pain

renal failure, including decompensated renal failure, nephrotic syndrome

necrosis of the injection site, facial swelling

pulmonary infiltrates§, pneumonitis§

Unknown

true erythrocyte aplasia, idiopathic thrombocytopenic purpura, thrombocytopenic thrombohemolytic purpura

systemic erythematous lupus, vasculitis, rheumatic arthritis (new or worsened), Vogt-Koyanagi-Harada syndrome, acute hypersensitivity reactions, including urticaria, Quincke's edema, bronchoconstriction, anaphylaxis§

Homicidal ideation, altered mental status§, mania, bipolar disorder

coronary heart disease, exudative pericarditis, arrhythmia

serous retinal detachment

pulmonary fibrosis

* These side effects developed during monotherapy with Intron A®

§ See section Special Instructions

Adverse events that occurred during monotherapy with Intron A® .

Adverse reactions observed with hepatitis C are similar to reactions with the use of Intron A® for other indications, with some predicted dose-dependent increase in the frequency of their occurrence. For example, in a study of the adjunctive use of high-dose Intron A® in the treatment of patients with melanoma, the incidence of reactions such as fatigue, pyrexia, myalgia, neutropenia/anemia, nausea and vomiting, diarrhea, chills, flu-like symptoms, depression, alopecia, change taste sensations, dizziness, were higher than in studies of hepatitis C. The severity of reactions also increased with high-dose therapy (WHO grade 3 and 4 in 66 and 14% of patients, respectively), compared with mild and moderate severity with used in low doses. Adverse reactions were usually managed by dose adjustment.

Adverse reactions from the cardiovascular system, in particular arrhythmia, were mainly associated with pre-existing cardiovascular disease and with previous treatment with cardiotoxic drugs. Cardiomyopathy, which may be reversible after discontinuation of interferon alfa, has been rarely reported in patients without evidence of cardiac disease.

Various autoimmune and immune-mediated disorders have been reported with the use of interferon alfa, including thyroid disorders, systemic lupus erythematosus, rheumatoid arthritis (new or worsening), idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathy, including mononeuropathy.

Clinically significant abnormalities in laboratory parameters (occurring more often when using doses above 10 million IU per day) included: a decrease in the number of granulocytes and leukocytes; decreased hemoglobin levels and platelet counts; increased levels of alkaline phosphatase, LDH, serum creatinine and serum urea nitrogen. Pancytopenia has been reported to be moderate in severity and usually reversible. There has been an abnormal increase in serum ALT/AST levels in some patients without hepatitis and in some patients with chronic hepatitis B, coinciding with clearance of viral DNA polymerase.

Children and teenagers

Combination therapy withRBVwith CHC. During 48 weeks of combined treatment with Intron A® and RBV, growth retardation was observed, which is unlikely to be reversible. Specifically, the decline in mean height percentile at 1-year long-term follow-up was more pronounced in prepubertal children.

Often

viral infection, pharyngitis, anemia, neutropenia

hypothyroidism§, anorexia

depression, emotional lability, insomnia, headache, dizziness

diarrhea, vomiting, nausea, abdominal pain

alopecia, rash

injection site inflammation, injection site reaction, fatigue, shakiness, pyrexia§, flu-like symptoms§, malaise, irritability, decreased growth rate (decreased height and/or weight according to age)

arthralgia, myalgia, musculoskeletal pain

Often

fungal infection, bacterial infection, pulmonary infection, otitis media, dental abscess, herpes simplex, urinary tract infection, vaginitis, gastroenteritis

neoplasm (unspecified), thrombocytopenia, lymphadenopathy

hyperthyroidism§, virilism

hypertriglyceridemia§, hyperuricemia, increased appetite

suicidal ideation, aggressive reaction, confusion, behavior disorder, agitation, somnambulism, anxiety, nervousness, sleep disturbances, pathological dreams, apathy

hyperkinesia, tremor, dysphonia, paresthesia, hypoesthesia, hyperesthesia, decreased concentration, drowsiness

conjunctivitis, eye pain, blurred vision, lacrimal gland disorders

flushing, pallor

dyspnea, tachypnea, nosebleeds, cough, nasal congestion, nasal irritation, rhinorrhea, sneezing

oral ulcerations, ulcerative stomatitis, stomatitis, pain in the upper right quadrant of the abdomen, dyspepsia, glossitis, gastroesophageal reflux, rectal disorders, gastrointestinal disorders, constipation, loose stools, dental pain, dental diseases

pathological change in liver function

photosensitivity reactions, maculopapular rash, eczema, acne, skin disorders, nail disorders, skin discoloration, itching, dry skin, erythema, bruising, increased sweating

enuresis, urinary dysfunction, urinary incontinence

girls - amenorrhea, menorrhagia, menstrual irregularities, vaginal disorders, boys - testicular pain

chest pain, asthenia, edema, injection site pain, skin wounds

§ See section Special Instructions

Contraindications

hypersensitivity to the active substance or any of the excipients

severe cardiac diseases, incl. history (uncontrolled congestive heart failure, recent myocardial infarction, severe cardiac arrhythmias)

severe renal or hepatic dysfunction, including those caused by metastases

epilepsy and/or other severe disorders of the central nervous system (CNS)

chronic hepatitis with decompensated cirrhosis of the liver

chronic hepatitis treated in the past with immunosuppressants or glucocorticosteroids

autoimmune diseases, incl. autoimmune hepatitis currently or in history; immunosuppression in organ transplant patients

thyroid disease, with the exception of diseases controlled by standard therapy

combination of Intron A® and telbivudine

pregnancy and lactation when prescribed in combination with ribavirin

Children and teenagers:

history of mental illness, especially severe depression, suicidal ideation, or suicide attempts

age up to 3 years with chronic hepatitis C

Combination therapy with ribavirin:

When prescribing Intron A® in combination with ribavirin, see the contraindications in the instructions for use of ribavirin if this drug will be used in combination with Intron A® for the treatment of patients with chronic hepatitis C

Drug interactions

Intron A® should be used with caution simultaneously with narcotics, hypnotics and sedatives.

Drug interactions between Intron A® and other drugs have not been fully studied. Intron A® should be used with caution in combination with drugs that potentially have a myelosuppressive effect.

Interferons can influence the oxidative metabolic process. This should be taken into account during simultaneous therapy with drugs metabolized in the same way (for example, xanthine derivatives - theophylline or aminophylline). When used simultaneously with xanthine derivatives, serum theophylline levels should be monitored and the dose adjusted if necessary.

Rarely, patients treated with interferon alfa, including Intron A®, have developed pulmonary infiltrates, pneumonitis and pneumonia, sometimes with fatal outcome. The etiology in these cases has not been established. The occurrence of these symptoms was most often noted during the use of sho-saiko-to (a Chinese herbal preparation) simultaneously with interferon alpha.

The use of Intron A® in combination with other chemotherapeutic drugs (for example, cytarabine, cyclophosphamide, doxirubicin, teniposide) increases the risk of developing toxic effects (their severity and duration).

It is also necessary to read the instructions for RBV if this drug is used in combination with the drug Intron A® to treat patients with CHC. A clinical study that studied the combination of telbivudine (600 mg per day) with PegIFN (180 mcg once a week subcutaneously ), showed that this combination is associated with an increased risk of developing peripheral neuropathy. The mechanism of such reactions is not known (see instructions for telbivudine). Moreover, the safety and effectiveness of telbivudine in combination with interferons for the treatment of chronic hepatitis B has not been demonstrated. For this reason, the combination of Intron A® and telbivudine is contraindicated.

special instructions

Mental disorders and central nervous system.

Serious disorders of the central nervous system, in particular depression, suicidal ideation and suicide attempts, were observed in some patients during treatment with Intron A® and even after the end of treatment, mainly within 6 months. Among children and adolescents taking Intron A® in combination with RBV, suicidal ideation and suicide attempts were observed more frequently compared to adult patients (2.4% versus 1%). Other mental disorders, such as depression, emotional lability, and drowsiness, have also been observed in adult patients, children and adolescents. If such symptoms occur, the potential severity of such adverse events should be considered. If symptoms persist or increase, or if suicidal or homicidal thoughts or aggressive behavior are detected, it is recommended to discontinue treatment and provide the patient with appropriate psychiatric care.

Patients with current or history of severe mental conditions.

If treatment with interferon alfa-2b is necessary for a patient with a severe mental condition (current or past history), it should be initiated only after appropriate individual diagnostic and therapeutic monitoring of the mental condition has been ensured.

The use of interferon alfa-2b in children and adolescents with severe psychiatric conditions (current or past) is contraindicated.

Patients who use/abuse psychoactive substances.

Patients with viral hepatitis C who simultaneously use psychoactive substances (alcohol, marijuana, etc.) have a high risk of developing mental disorders or exacerbation of existing mental disorders when treated with interferon alfa. If interferon alfa treatment is necessary in such patients, the presence of psychiatric comorbidities and the potential for use of other substances should be carefully assessed and appropriate measures taken before initiating therapy. If necessary, a multidisciplinary approach, including a psychologist or addiction specialist, should be considered for assessment, treatment and follow-up. The patient's condition should be carefully monitored during therapy and also after discontinuation of treatment. Early intervention regarding the recurrence or development of psychiatric disorders and substance use is recommended.

Children and adolescents: growth and development (chronic hepatitis C).

During a 48-week course of interferon (standard and pegylated)/RBV combination treatment, decreased weight gain (13% decrease in mean percentile) and slower growth (9% decrease in mean percentile) were common in patients aged 3 to 17 years. . An overall worsening of these scores was noted during the 24-week post-treatment period. Available data from longer periods of treatment of children with the interferon/RBV combination also show significant growth decline (decrease in height percentile of >15 percentile compared with baseline) in 21% of children, even if treatment ended more than 5 years ago, resulting in a decrease final height in adulthood in some patients.

Individual benefit/risk assessment in children.

The expected benefits of treatment should be carefully compared with the safety data obtained in clinical studies in children and adolescents. It is important to consider that combination therapy induces growth retardation, and the reversibility of this process is questionable. Risk should be weighed against characteristics of the child's disease, such as signs of disease progression (severe fibrosis), comorbidities that may adversely affect disease progression (eg, concomitant HIV infection), and prognostic factors for virologic response (hepatitis virus genotype). C and viral load). If possible, the child should be treated after the pubertal growth spurt to reduce the risk of growth retardation. There are no data regarding long-term effects on puberty.

Immediate hypersensitivity.

Immediate hypersensitivity reactions (such as urticaria, angioedema, bronchospasm, anaphylaxis) to interferon alfa-2b have been observed rarely during therapy with Intron A®. If such reactions occur, the drug should be discontinued and appropriate medical treatment should be prescribed. A transient skin rash does not require discontinuation of the drug.

Adverse reactions, including prolongation of blood clotting parameters and liver pathology.

If moderate or severe adverse reactions occur, dose modification or, in some cases, discontinuation of Intron A® treatment may be necessary. As with all interferons, Intron A® should be discontinued if blood clotting time is prolonged, which may indicate decompensation of liver function.

All patients who experience liver abnormalities during treatment with Intron A® should be closely monitored and treatment should be discontinued if signs and symptoms worsen. Liver function should be monitored by measuring serum bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) levels at 2, 8, and 12 weeks after initiation of Intron A® therapy, and every 6 months during therapy time. Therapy with Intron A® should be discontinued if severe liver failure (grade 3) or hepatic decompensation (class B and C, Child-Pugh > 6) develops.

Arterial hypotension.

Arterial hypotension may occur during therapy with Intron A® and for 2 days after its completion, which may require maintenance treatment.

Need for adequate hydration.

In patients receiving therapy with Intron A®, it is necessary to ensure adequate hydration, as some patients have experienced arterial hypotension associated with a decrease in fluid volume in the body. In such cases, rehydration may be necessary.

Fever may be a manifestation of a flu-like syndrome, which often occurs during interferon therapy, but other causes of its occurrence should be excluded.

Accompanying illnesses.

Intron A® is prescribed with caution to patients with a history of severe chronic diseases: chronic obstructive pulmonary disease, diabetes mellitus with a tendency to ketoacidosis. Particular caution is required when using the drug in patients with bleeding disorders (thrombophlebitis, pulmonary embolism) or with severe myelosuppression.

Lung diseases.

Pulmonary infiltrates, pneumonitis and pneumonia, sometimes fatal, have rarely been observed in patients treated with Intron A®. The etiology of these diseases is unknown. The occurrence of these symptoms was most often noted during the use of sho-saiko-to (a Chinese herbal preparation) simultaneously with interferon alpha. All patients who develop fever, cough, shortness of breath, or other respiratory symptoms should have a chest x-ray. If infiltrates are visible on radiographs or there are signs of deterioration in pulmonary function, the patient should be closely monitored and, if necessary, interferon alfa should be discontinued. Although such changes occurred more frequently in patients with CHC who were receiving interferon alfa therapy, there have been reports of their development in patients with cancer who were also receiving interferon alfa therapy. Immediate discontinuation of interferon alfa and treatment with corticosteroids lead to the disappearance of pulmonary side effects.

Changes in vision.

Ophthalmic abnormalities, including retinal hemorrhage, serous retinal detachment, cotton spots, and retinal artery or vein thrombosis, have been rarely reported following treatment with alpha interferons. All patients should undergo an ophthalmological examination before treatment. All patients who complain of changes in visual acuity or visual fields, as well as patients who experience other ophthalmological symptoms during treatment with Intron A®, should immediately undergo a complete ophthalmological examination. During treatment with Intron A®, it is recommended to periodically check vision, especially in patients with disorders that may be associated with retinopathy, for example, diabetes mellitus or arterial hypertension. Consideration should be given to discontinuing Intron A® in patients who develop or worsen the course of an ophthalmological disease.

Stunning, coma and encephalopathy.

More significant adverse reactions, such as stunned consciousness and coma, including cases of encephalopathy, were observed in some patients (usually elderly) receiving high doses of the drug. Because these effects are usually reversible, several patients experienced complete recovery within 3 weeks. Very rarely, when using the drug Intron A® in high doses, convulsions were observed.

Patients with heart pathology.

Adult patients with a history of congestive heart failure, myocardial infarction and/or current or history of cardiac arrhythmias receiving treatment with Intron A® should be closely monitored. Patients with cardiac pathology and/or terminal stage cancer are recommended to undergo ECG examinations before starting treatment and during therapy. Cardiac arrhythmias (mainly supraventricular), as a rule, respond to standard therapy, but discontinuation of Intron A® may be required. There are no data available in children or adolescents with a history of heart disease.

Hypertriglyceridemia.

Hypertriglyceridemia and increased severity of hypertriglyceridemia, sometimes in severe form, were observed; for this reason, monitoring lipid levels is recommended.

Patients with psoriasis and sarcoidosis.

Considering the described cases of exacerbation of psoriasis and sarcoidosis during treatment with interferon alfa, Intron A® should be used in such patients only if the expected benefit outweighs the possible risk.

Allograft rejection.

Preliminary evidence suggests that interferon alfa therapy may increase the risk of renal transplant rejection. Liver graft rejection has also been reported, although a causal relationship with interferon alfa therapy has not been established.

Autoantibodies and autoimmune diseases.

Treatment with Intron A® may lead to the appearance of autoantibodies and the development of autoimmune diseases. Patients with a hereditary predisposition or suspicion of developing symptoms of autoimmune diseases should be constantly monitored for early diagnosis. If Vogt-Koyanagi-Harada syndrome is suspected in patients with CHC, antiviral therapy should be discontinued and the need for corticosteroid therapy should be discussed. To reduce body temperature and reduce headaches during influenza-like syndrome, which may occur during therapy with Intron A®, the use of antipyretic therapy is recommended.

Concomitant chemotherapy.

The use of Intron A® in combination with other chemotherapeutic drugs (for example, cytarabine, cyclophosphamide, doxirubicin, teniposide) increases the risk of developing toxic effects (their severity and duration), which, due to simultaneous use, can be life-threatening or cause death. The most frequently reported side effects were potentially life-threatening or fatal: mucosal inflammation, diarrhea, neutropenia, renal dysfunction, and electrolyte imbalance. Due to the risk of increased toxicity, dosages of Intron A® and concomitant chemotherapy drugs must be carefully adjusted. If Intron A® is used with hydroxyurea, the incidence and severity of cutaneous vasculitis may increase.

Combination therapy withRBVwith CHC.

See also the instructions for RBV when used with Intron A® in patients with CHC. All patients in the CHC studies underwent liver biopsy before enrollment, but in some cases (eg, patients with genotype 2 and 3), treatment was possible without histological confirmation. Current guidelines should be followed when deciding whether to perform a liver biopsy before starting treatment.

Monotherapy.

Infrequently, adult patients receiving Intron A® for the treatment of CHC developed thyroid disorders - hypothyroidism or hyperthyroidism. In clinical studies of the use of Intron A®, pathological changes in the thyroid gland occurred in 2.8% of patients. Thyroid dysfunction was controlled with appropriate conventional therapy. The mechanism by which the drug Intron A® can affect thyroid status is unknown. Before starting the use of Intron A® for the treatment of CHC, the level of TSH in the blood serum should be determined. If any abnormalities are detected, conventional therapy should be carried out. If TSH levels can be maintained at normal levels with drug therapy, treatment with Intron A® can be started. TSH levels should be determined if, during the course of treatment, the patient experiences symptoms indicating possible thyroid dysfunction. In case of thyroid dysfunction, the use of Intron A® can be continued, provided that TSH levels can be maintained within normal limits during drug treatment. Discontinuation of Intron A® does not lead to reversibility of thyroid dysfunction that occurred during treatment (see below, “Additional thyroid monitoring in children and adolescents”).

Additional monitoring of thyroid function in children and adolescents.

Approximately 12% of children receiving combined interferon alfa-2b/RBV treatment experienced an increase in TSH levels, and approximately 4% of patients experienced a transient decrease in hormone levels (below the lower limit of normal). Before starting to use the drug Intron A®, TSH levels should be determined and, if any pathology of the thyroid gland is detected, standard treatment should be carried out. If TSH levels can be maintained at normal levels with drug therapy, treatment with Intron A® can be started. Thyroid dysfunction has been observed during treatment with interferon alfa-2b/RBV. If a pathology of the thyroid gland is detected, the thyroid status should be determined and appropriate treatment should be carried out. In children and adolescents, thyroid function should be monitored every 3 months (eg, TSH levels).

HCV/HIV co-infection.

Patients with concomitant HIV infection receiving highly active antiretroviral therapy are at higher risk of developing lactic acidosis. Precautions should be taken if Intron A® and RBV are prescribed during highly active antiretroviral therapy (see instructions for use of RBV). Patients receiving the Intron A®/RBV combination and zidovudine may be at increased risk of developing anemia.

Patients with coinfection and advanced cirrhosis receiving highly active antiviral therapy may be at high risk of liver decompensation and death. Adjunctive treatment with interferon alfa alone or in combination with RBV may increase the risk in this group of patients.

Dental and periodontalviolations.

Dental and periodontal disorders that may lead to tooth loss have been reported in patients receiving combination treatment with Intron A® and RBV. In addition, dry mouth can have a damaging effect on the teeth and mucous membranes of the oral cavity during long-term treatment with the combination of Intron A® and RBV. Patients should brush their teeth thoroughly twice a day and undergo regular dental examinations. In addition, some patients may vomit, after which the mouth should be rinsed thoroughly.

Laboratory research.

Before starting treatment with Intron A® and periodically during therapy, peripheral blood is monitored in all patients (with determination of the leukocyte formula and platelet count), biochemical blood parameters (determination of the level of electrolytes, liver enzymes, including ALT, bilirubin, total protein and fractions, including albumin and creatinine). Before and during treatment with Intron A®, blood counts should be within normal limits.

During therapy for patients with chronic hepatitis, the following frequency of monitoring laboratory parameters is recommended: 1, 2, 4, 8, 12, 16 weeks and then once a month, during the entire course of treatment. If ALT increases by half or more from the initial value recorded before the start of therapy, treatment with Intron A® can be continued, unless signs of liver failure appear. In this case, determination of ALT, prothrombin time, alkaline phosphatase, albumin and bilirubin must be carried out every 2 weeks and the patient's condition must be carefully monitored.

In patients with malignant melanoma, liver function and white blood cell count (with expanded formula) should be monitored weekly during induction of remission and monthly during maintenance therapy.

Effect on fertility.

Interferon may affect fertility.

Important information about some of the excipients included in the drug Intron A® .

The drug contains less than 1 mmol sodium (23 mg) per 0.5 ml and is essentially virtually sodium-free.

Pregnancy and lactation

Women of childbearing age/contraception for men and women. Women of childbearing age should use effective methods of contraception throughout the course of treatment. Decreases in serum concentrations of estradiol and progesterone have been reported in women treated with human leukocyte interferon.

Intron A® should be used with caution in fertile men.

Combination therapy withRBV during pregnancy leads to serious congenital pathology. To prevent pregnancy, patients and women whose partners are receiving Intron A® in combination with RBV must use extremely reliable contraceptive measures. Women of childbearing potential should use effective contraception during the treatment period and for 4 months after the end of treatment. Male patients and their female partners should use effective contraception during the treatment period and for 7 months after the end of treatment (see instructions on RBV).

Pregnancy.

There are no adequate data on the use of interferon alfa-2b in pregnant women. Animal studies have demonstrated reproductive toxicity. The potential risk to humans is unknown.

Combination therapy withRBV Contraindicated for pregnant women.

Lactation.

It is not known whether the components of the drug pass into breast milk in humans. Since there is a possibility of adverse reactions in breastfed children, breastfeeding should be discontinued before starting treatment.

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms.

It is necessary to warn the patient about the possible development of weakness, drowsiness, and disturbances of consciousness during therapy and recommend avoiding driving a vehicle or complex equipment.

Overdose

No cases of overdose accompanied by acute clinical manifestations have been reported. However, as with an overdose of any pharmacologically active substance, it is recommended to carry out symptomatic therapy with frequent monitoring of the functions of vital organs and careful monitoring of the patient's condition.

Release form and packaging

Intron A®, solution for injection, 18 million IU/3 ml (6 doses of 3 million IU),

25 million IU/2.5 ml (5 doses of 5 million IU),

18 million IU/1.2 ml (6 doses of 3 million IU).

3 ml of the drug (18 million IU/3 ml (6 doses of 3 million IU)) or 2.5 ml of the drug (25 million IU/2.5 ml (5 doses of 5 million IU)) are placed in glass bottles with a capacity of 5 ml.

1 bottle along with instructions for medical use in the state and Russian languages ​​is placed in a cardboard box.

1.2 ml of the drug (18 million IU/1.2 ml (6 doses of 3 million IU)) are placed in syringe pens.

1 syringe pen complete with 6 injection needles and 6 skin disinfection wipes is placed in a plastic tray.

The pallet, along with instructions for medical use in the state and Russian languages, is placed in a cardboard box.

Storage conditions

Store at temperatures between 2 °C and 8 °C.

Do not freeze.

Keep out of the reach of children.

Transport at temperatures from 2 °C to 8 °C. Transportation at temperatures up to 25 °C is allowed for no more than 7 days. During this period, the drug can be returned for further storage in the refrigerator (storage temperature from 2 ° C to 8 ° C), while the shelf life of the drug is preserved. If the drug has not been used and has not been stored in the refrigerator for 7 days, then it is not subject to further use.

The composition of interferon preparations depends on their release form.

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;
• aerosol;
• oral solution;
• rectal suppositories;
• vaginal suppositories;
• implants;
• microenemas;
• tablets (interferon tablets are available under the brand name Entalferon).

pharmachologic effect

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

All IFNs have antiviral and antitumor effects . No less important is their property of stimulating action. macrophages - cells that play an important role in initiation.

IFNs contribute to increasing the body's resistance to penetration viruses , and also block reproduction viruses when they penetrate the cell. The latter is due to the ability of IFN to suppress translation of the messenger RNA of the virus .

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

Pharmacodynamics and pharmacokinetics

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

However, IFN has no effect on the early stages replicative 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 appears even when cells are infected infectious RNAs . IFN does not penetrate the cell, but only interacts with specific receptors on cell membranes (gangliosides or similar structures containing oligosugars ).

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

β interferons also have antiviral effect , which is associated with several mechanisms of action. Beta interferon activates NO synthetase, which in turn helps to increase the concentration of nitric oxide inside the cell. The latter plays a key role in suppressing reproduction viruses .

β-IFN activates secondary, effector functions natural killersV , 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 RNA virus .

γ-IFN is involved in the regulation of the immune response and regulates the expression inflammatory reactions. Despite the fact that he has independent antivirus 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 is observed after 3-12 hours. The bioavailability indicator is 100% (both after injection under the skin and after injection into the muscle).

The half-life T½ ranges from 2 to 7 hours. Trace concentrations of IFN in blood plasma are not detectable after 16–24 hours.

Indications for use

IFN is intended to treat viral diseases , striking respiratory tract .

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

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

Genetic polymorphisms observed in the IL28B gene, which is responsible for encoding IFN lambda-3, cause significant differences in the effect of treatment.

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

IFN is also often prescribed to patients with oncological diseases : malignant , pancreatic endocrine tumors , non-Hodgkin's lymphoma , carcinoid tumors ; Kaposi's sarcoma , conditioned; 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 (in cases where appropriate therapy does not produce 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 a consequence of the administration of interferon intravenously, subcutaneously or intramuscularly, but they can also be provoked by other pharmaceutical forms of the drug.

The most common adverse reactions to taking IFN are:

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

Somewhat less common are vomiting, increased blood pressure, a feeling of dry mouth, hair loss (), asthenia ; nonspecific symptoms reminiscent of flu symptoms ; backache, depressive states , musculoskeletal pain , thoughts of suicide and attempted suicide, general malaise, impaired taste and concentration, increased irritability, sleep disorders (often), arterial hypotension , confusion.

Rare side effects include: pain on the right side of the upper abdomen, rashes on the body (erythematous and maculopapular), increased nervousness, pain and severe inflammation at the injection site of the drug, 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, unformed stools, hyper- or hypothyroidism , hearing impairment (up to its complete loss), the formation of infiltrates in the lungs, increased appetite, bleeding gums, convulsions in the limbs, dyspnea , renal dysfunction and development of renal failure , peripheral ischemia , hyperuricemia , neuropathy etc..

Treatment with IFN drugs may cause reproductive dysfunction . Studies in primates have shown that interferon disrupts the menstrual cycle in women . In addition, in women undergoing treatment with IFN-α drugs, the level of .

For this reason, if interferon is prescribed, women of childbearing age should use barrier contraception . Men of reproductive age are also advised to be informed of potential side effects.

In rare cases, treatment with interferon may be accompanied by ophthalmological disorders, which are expressed as hemorrhages in the retina of the eye , 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 optic (second cranial) nerve , arterial obstruction or retinal veins .

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

The possibility of occurrence cannot be excluded cerebrovascular hemorrhage , erythema multiforme , tissue necrosis at the injection site, cardiac and cerebrovascular ischemia , hypertriglyceridermia , sarcoidosis (or aggravation of its course), Lyell's syndromes And Stevens-Johnson .

The use of interferon in monotherapy or in combination with Ribavirin in isolated cases it can provoke aplastic anemia (AA) or even PAKKM ( complete red bone marrow aplasia ).

There have also been cases where, during treatment with interferon drugs, a patient developed various autoimmune And immune-mediated disorders (including Werlhof's disease And Moschkowitz disease ).

Interferon, instructions for use

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

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

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

“Children’s” interferon is suppositories, drops and ointment.

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

For preventive 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 refrigerated 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 eye drops.

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 herpes viruses , the ointment is applied in 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 acute respiratory infections and needs to be lubricated with ointment nasal passages . The frequency of procedures during the 1st and 3rd weeks of the course is 2 times a day. It is recommended to take a break during the 2nd week. For preventive purposes, interferon should be used throughout the entire period epidemics of respiratory diseases .

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

How to dilute and how to use interferon in ampoules?

The instructions for using interferon in ampoules indicate that before use, the ampoule must be opened, water (distilled or boiled) at room temperature must be poured into it 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 administrations.

For therapeutic purposes, IFN begins to be taken when the first symptoms appear. flu symptoms . The earlier the patient starts taking it, the higher the effectiveness of the drug.

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

The water is preheated to a temperature of no more than +37 °C. Inhalation procedures are carried out twice a day, maintaining an interval of at least one to two hours between them.

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

For preventive purposes, nasal drops for children are instilled (5 drops) twice a day; at the initial stage 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 people are interested in whether interferon solution can be dripped into the eyes. The answer to this question is yes.

Overdose

Cases of interferon overdose have not been described.

Interaction

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

Beta-IFN should be administered with caution with agents whose clearance is largely dependent on cytochrome P450 system (antiepileptic drugs , some antidepressants and etc.).

You should not take α-IFN and Telbivudin . 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 level ).

Terms of sale

A prescription is required to dispense the drug.

Storage conditions

Interferon is stored in a cool place, protected from sunlight, at a temperature of +2 to +8°C. List B.

Best before date

24 months. The prepared interferon solution remains stable for 3 days at room temperature.

special instructions

Interferon - what is it?

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

According to Wikipedia, in order for a biologically active substance to be qualified as interferon, it must be of a protein nature and have a pronounced antiviral activity in relation to various viruses , at a minimum, 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.

Based on antigenicity (antigen specificity), IFNs are usually divided into acid-stable and acid-labile. The acid-fast ones include alpha and beta interferons (they are also called type I IFN). Interferon gamma (γ-IFN) is acid labile.

α-IFN is produced peripheral blood leukocytes (B- and T-type leukocytes), therefore it was previously designated as leukocyte interferon . There are currently at least 14 varieties of it.

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

The former designation of γ-IFN is immune interferon , it is produced by stimulated T-type lymphocytes , NK cells (normal (natural) killers; from English “natural killer”) and (presumably) macrophages .

Basic properties and mechanism of action of IFN

Without exception, all IFNs are characterized by multifunctional 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 drugs 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 source of infection a kind of barrier is formed from resistant to virus uninfected cells, which prevents further spread of infection.

By interacting with still undamaged (intact) cells, it prevents the implementation of the reproductive cycle viruses due to the activation of certain cellular enzymes ( protein kinases ).

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

Use of IFN in biotechnology

Development of synthesis methods and highly efficient purification leukocyte and recombinant interferons in quantities sufficient for the production of drugs, made it possible to use IFN drugs to treat patients diagnosed with viral hepatitis .

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

Each type of interferon has analogues. Interferon alpha-2a preparations - Reaferon , Roferon . Recombinant human interferon alpha 2b is available under the brand names Intron-A , Intrack , .

Interferon alpha-2C preparations used in the clinic are Berofor , Egiferon , Welferon .

β-IFN drugs: Betaseron , Fron .

γ-IFN drugs: Gammaferon , Immunoferon , Imukan .

Interferon for children

According to the instructions, interferon preparations are indicated for children:

• at infectious and inflammatory diseases of the respiratory system ;
• at ;
• at sepsis ;
• for the treatment of children viral infections (for example, or);
• for treatment chronic viral hepatitis .

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

The most optimal option for children is nasal drops: when used in this way, interferon does not penetrate the gastrointestinal tract (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). Suppositories for children should be administered one at a time 2 times a day, maintaining 12-hour intervals between administrations. The course of treatment is 5 days. To completely cure a child ARVI As a rule, one course is enough.

For treatment, you should take 0.5 g of ointment twice a day. Treatment lasts on average 2 weeks. Over the next 2-4 weeks, the ointment is used 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 . Interferon inhalations for children are no less effective.

The effect of using the drug increases significantly if a nebulizer is used to administer it (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, you must turn off the heating function (IFN is a protein; at temperatures above 37°C it is destroyed).

For inhalation in a nebulizer, the contents of one ampoule are diluted in 2-3 ml of distilled or mineral water (saline solution can also be used for these purposes). 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 when the expected benefit of therapy for the expectant mother exceeds the risk of adverse reactions and harmful effects on the development of the fetus.

The possibility of isolating recombinant IFN components in breast milk cannot be ruled out. Due to the possibility of exposure to the fetus through milk, IFN is not prescribed to nursing women.

As a last resort, when the administration of IFN cannot be avoided, the woman is advised not to breastfeed during therapy. To mitigate the side effects of the drug (the occurrence of flu-like symptoms), simultaneous administration with IFN is recommended. .

Types of medication, commercial names of analogues, release forms

Different types of interferon can be found on sale under other names - Interferal, Interal, Viferon, Altevir, Inferon, Rebif, Extavia, etc.

Interferon manufacturing companies

The mechanism of therapeutic action of the drug

Interferon can have the following types of effects on the body:

• antiviral effect;
• antitumor effect.

Antitumor effect carried out due to the action of the p53 protein. This protein becomes active due to DNA damage and can be produced by any cells in the body. Subsequently, the p53 protein stops the cell cycle of development of the damaged cell, and if there are significant and irreversible defects in the genetic material, it causes its apoptosis. It is worth noting that in case of malignant neoplasms ( cancerous tumors) in approximately half of cases there is a dysfunction of the p53 protein.

Regardless of the release form ( intramuscular or subcutaneous injections) the body absolutely completely absorbs this medicine ( bioavailability 100%). Already 4–12 hours after application, the maximum concentration of interferon is observed in the blood.

For what pathologies is it prescribed?

Interferon use

How to use the medicine?

Interferon is used in the treatment of the following pathologies:

• viral hepatitis;
• tumor diseases;
• diseases of the central nervous system.

Viral hepatitis

For the treatment of hepatitis B, a weekly dosage of 30–35 million international units of interferon is prescribed. It is worth noting that there are two treatment regimens for chronic hepatitis B. The first regimen involves daily administration of the drug in 5 million units, and in the second regimen, interferon is administered in 10 million IU doses three times a week ( in one day). The duration of therapy is 4 – 6 months.

Treatment of chronic hepatitis C can be carried out together with another antiviral drug - ribavirin or use interferon as monotherapy ( single medication treatment). The weekly dosage is 9 – 10 million IU. Interferon is administered subcutaneously or intramuscularly at a dose of 3 million three times a week. The course of treatment is selected by the attending physician.

It is worth noting that hepatitis D can only occur together with hepatitis B. Treatment for hepatitis D involves the use of 15 million units of the drug per week. 5 million units are administered subcutaneously ( three times a week). Treatment lasts from 3 to 4 months.

Tumor diseases

Interferon is used in the treatment of the following tumor diseases:

• Non-Hodgkin's lymphoma. Treatment of non-Hodgkin's lymphoma must be carried out in combination with chemotherapy. As a rule, interferon is administered subcutaneously at 5 million IU. The drug should be used 3 times a week ( in one day).
• Hairy cell leukemia. Interferon is used in single doses of 3 million units every other day ( three times a week). The medication can be administered either intramuscularly or subcutaneously. The course of treatment is selected by the attending physician.
• Malignant melanoma. The weekly dosage of interferon is 80 – 100 million units. The drug must be used 4–5 times a week. The duration of treatment is 30 days, after which they switch to maintenance therapy - 10 million units 3 times a week. The average course of treatment using maintenance therapy is 11–12 months.
• Carcinoid tumors. Interferon is administered subcutaneously at 3–9 million units 3 times a week. If there is no effect, they switch to another treatment regimen - 5 million units of interferon daily ( 35 million IU per week).
• Carcinoid tumors with metastasis. Treatment is carried out daily in the form of subcutaneous injections of 3–4 million units of interferon. Gradually, every two weeks, the single dose is increased to 5, 7, 10 million units. The course of treatment is selected by the doctor.
• Multiple myeloma. Subcutaneously, 5 million units of interferon three times a week. The duration of treatment can only be determined by the attending physician.
• Renal cell carcinoma. Interferon is taken three times a week, 3–10 million units. The course of treatment is individual.

Diseases of the central nervous system

For the treatment and prevention of various acute respiratory viral diseases, interferon is used in the form of a spray or nasal drops. To treat ARVI, a few drops of interferon should be instilled into each nasal passage ( 2 – 3 drops) from 3 to 5 times a day. To prevent ARVI, interferon is recommended to be taken throughout the winter period. To do this, each nasal passage is lubricated with an ointment that contains interferon 2 to 3 times a day. After the first week of treatment, it is necessary to take a seven-day break, and then resume taking interferon again.

Possible side effects

Interferon can lead to the following adverse reactions:

• disorders of the digestive tract;
• disorders of the nervous system;
• allergic manifestations;
• disorders of the cardiovascular system;
• disorders of the hematopoietic system;
• disorders of the upper and lower respiratory tract.

Digestive tract disorders

The following side effects may occur from the digestive system:
The toxic effect of interferon on liver tissue is also often observed. This is manifested by an increase in some indicators of biochemical blood tests. As a rule, there is an increase in the level of liver transaminases ( enzymes involved in the transformation of certain amino acids).

Nervous system disorders

The following side effects may occur from the nervous system:

• anxiety;
• headache;
• dizziness;
• disturbance of consciousness;
• suicidal thoughts ( rarely);
• hallucinations ( very rarely).

Interferon can also affect vision. Irritation of the optic nerve leads to deterioration of vision. Sometimes taking interferon may be accompanied by inflammation of the ocular mucosa ( conjunctivitis). Conjunctivitis is characterized by symptoms such as swelling of the eyelids and mucous membrane of the eye, itching of the eyes, lacrimation, photophobia ( photophobia), as well as redness of the whites of the eyes.

Allergic manifestations

Taking interferon can lead to the following allergic manifestations:

• erythema;
• Stevens-Johnson syndrome;
• toxic epidermal necrolysis ( Lyell's syndrome).

Erythema is a pronounced redness of the skin. Erythema occurs due to increased permeability of small skin vessels, as a result of which blood flows in large quantities to the surface of the skin.

Quincke's edema is also a fairly common form of drug allergy, which affects the fatty tissue of the skin ( subcutaneous fat). Most often swelling can occur on the face ( lips, eyelids, cheeks, and oral cavity). Sometimes the limbs and genitals may swell. As a rule, 3 to 4 hours after the onset of swelling disappears without a trace. A rare complication of Quincke's edema is obstruction of the upper respiratory tract. This happens due to the fact that the swelling spreads from the oral cavity to the mucous membrane of the larynx, resulting in suffocation. This condition is extremely dangerous and can lead to coma.

Stevens–Johnson syndrome is an extremely severe form of erythema. This syndrome is characterized by the appearance of large blisters on the mucous membranes ( eyes, pharynx, oral cavity) and on the skin. At the first stage of the disease, as a rule, severe pain occurs in large joints. Body temperature, in turn, rises up to 39ºС. After a couple of hours, the general condition worsens sharply, and blisters appear on the mucous membrane of the tongue, cheeks, as well as on the lips, larynx and skin. After opening, very painful and bleeding areas with erosions form in their place.

Toxic epidermal necrolysis is a very life-threatening condition. Within 2 to 4 hours after the drug is administered to the body, the general condition of the body deteriorates sharply. Body temperature rises to 39 – 40ºС. A rash appears on the skin in the form of small dots, which resembles the rash of scarlet fever. Subsequently, instead of these rashes, rather large bubbles with transparent contents form, which quickly open. In place of the blisters, erosive areas of the skin open, which can merge and form large erosions. It is worth noting that toxic epidermal necrolysis can affect internal organs such as the kidneys, liver, heart and intestines. If medical assistance is not provided in a timely manner, people with this pathology very often die.

Disorders of the cardiovascular system

Disorders of the hematopoietic system

Taking interferon can lead to the following disorders of the hematopoietic system:

• leukopenia.

Thrombocytopenia manifested by a decrease in the total number of blood platelets ( platelets). Platelets are needed for the normal blood clotting process ( coagulation). Most often, thrombocytopenia is manifested by bleeding gums. In some cases, thrombocytopenia can lead to serious bleeding in various internal organs ( bleeding in the brain is especially dangerous).

Leukopenia represents a decrease in the number of white blood cells ( leukocytes). These cells are capable of protecting the human body from various pathogens. With leukopenia, a person becomes extremely vulnerable to bacterial infections. This pathological condition often leads to an increase in the size of the spleen and tonsils ( hypertrophy).

Upper and lower respiratory tract disorders

Interferon can also lead to the following respiratory diseases (rare):
Sinusitis is an inflammation of the mucous membrane of the paranasal sinuses. Sinusitis can occur due to a runny nose or ARVI ( flu). This pathology is characterized by symptoms such as heaviness in the paranasal sinus, fever, nasal discharge ( thick), painful sensations in the sinus when turning the head sharply. Most often the maxillary sinuses are involved in the inflammatory process ( maxillary) and frontal sinuses.

Pneumonia is an inflammation of the lung tissue, which most often affects the alveoli ( structural and functional elements of the lung in which the process of gas exchange occurs). Depending on the volume of damage to the lung tissue, focal ( inflammation of several alveoli), segmental ( inflammatory process within one segment of the lung), fractional ( damage to one lobe of the lung) and lobar pneumonia ( involvement of both lungs in the process). Pneumonia is characterized by symptoms such as fever, shortness of breath ( appears when inflammatory fluid accumulates in the alveoli), chest pain, respiratory failure. With lobar pneumonia, severe intoxication is also observed, which is manifested by headache, dizziness, general malaise and confusion. Most often, uncomplicated pneumonia lasts about a month.

Approximate cost of the medicine