Interferon alpha 2b human what. Interferons and their role in clinical medicine. From the treatment of influenza to the treatment of complex viral and bacterial infections. Interferon-based drugs: indications and contraindications for their use

Release form, composition and packaging

Injection transparent, colorless.

Excipients:

0.5 ml - ampoules (5) - contour cell packaging (1) - cardboard packs.
0.5 ml - ampoules (5) - contour cell packaging (2) - cardboard packs.
0.5 ml - bottles (1) - cardboard packs.
0.5 ml - bottles (5) - contour cell packaging (1) - cardboard packs.
0.5 ml - glass syringes (1) - contour cell packaging (1) - cardboard packs.
0.5 ml - glass syringes (1) - contour cell packaging (3) - cardboard packs.
0.5 ml - glass syringes (3) - contour cell packaging (1) - cardboard packs.
0.5 ml - glass syringes (3) - contour cell packaging (3) - cardboard packs.

Injection transparent, colorless.

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

1 ml - ampoules (5) - contour cell packaging (1) - cardboard packs.
1 ml - ampoules (5) - contour cell packaging (2) - cardboard packs.
1 ml - bottles (1) - cardboard packs.
1 ml - bottles (5) - contour cell packaging (1) - cardboard packs.
1 ml - glass syringes (1) - contour cell packaging (1) - cardboard packs.
1 ml - glass syringes (1) - contour cell packaging (3) - cardboard packs.
1 ml - glass syringes (3) - contour cell packaging (1) - cardboard packs.
1 ml - glass syringes (3) - contour cell packaging (3) - cardboard packs.

Clinical and pharmacological group

pharmachologic effect

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

Interferon alpha-2b, interacting with specific receptors on the cell surface, initiates a complex chain of changes inside the cell, including the induction of the synthesis of a number of specific cytokines and enzymes, 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 the administration of interferon alpha-2b, T max in the blood plasma is 4-12 hours, T 1/2 - 2-6 hours. 16-24 hours after administration, recombinant interferon is not detected in the 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.

Indications for use of the drug

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.

Dosage regimen

Apply subcutaneously, intramuscularly and intravenously. Treatment must be started by a doctor. Then, with the doctor’s permission, the patient can administer a maintenance dose independently (in cases where the drug is prescribed subcutaneously or intramuscularly).

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/m 2 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 splenectomy or without it is 2 million IU/m 2 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 every day. To maintain the number of leukocytes, a dose of 0.5-10 million IU/m2 may be required. If treatment allows you to control 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/m 2 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/m 2 5 times a week for 4 weeks, then subcutaneously at a dose of 10 million IU/m 2 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/m 2 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/m 2 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.

Side effect

General reactions: very often - fever, weakness (they are dose-dependent and reversible reactions, disappear within 72 hours after a break in treatment or its 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: possible reversible leukopenia, granulocytopenia, decreased hemoglobin levels, thrombocytopenia.

Others: rarely - weight loss, autoimmune thyroiditis.

Contraindications to the use of the drug

- 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 dysfunction 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;

- a 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 of the drug during pregnancy and lactation

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).

special instructions

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 50x10 9 /l or the granulocyte level below 0.75x10 9 /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 25x10 9 /l or the granulocyte level below 0.5 x10 9 /l, it is recommended to discontinue the drug 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.

Overdose

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

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.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Storage conditions and periods

The drug should be stored out of the reach of children, in accordance with SP 3.3.2-1248-03 at a temperature of 2° to 8°C; do not freeze. Shelf life - 18 months.

Transport at temperatures from 2° to 8°C; do not freeze.

INN: Interferon alpha 2b

Manufacturer: Sikor Biotech CJSC

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

Registration number in the Republic of Kazakhstan: No. RK-BP-5No. 012842

Registration period: 18.06.2014 - 18.06.2019

KNF (medicine included in the Kazakhstan National Formulary of Medicines)

ALO (Included in the List of free outpatient drug provision)

ED (Included in the List of drugs within the framework of the guaranteed volume of free medical care, subject to purchase from the Single Distributor)

Limit purchase price in the Republic of Kazakhstan: 33 116.64 KZT

Instructions

Tradename

Realdiron

International nonproprietary name

Interferon alpha

Dosage form

Lyophilized powder for solution for injection, 1000,000 IU, 3,000,000 IU, 6,000,000 IU, 9,000,000 IU and 18,000,000 IU

Compound

One bottle contains

active substance: interferon alpha-2b human recombinant

nantnogo 1 million IU, 3 million IU, 6 million IU, 18 million IU

Excipients: dextran 60, sodium chloride, disodium hydrogen phosphate dodecahydrate, sodium dihydrogen phosphate dihydrate

Description

White powder or porous mass

Farmacotherapy group

Immunomodulators. Interferons. Interferon alpha

ATX code L03АВ05

Pharmacological properties

Pharmacokinetics

The time of onset of the maximum concentration of interferon-alpha 2b after intramuscular administration is 2 hours and lasts up to 12 hours, after subcutaneous administration it is 7.3 hours, after 20 hours the drug is not detected.

T1/2 (half-life) when administered intramuscularly is about 2-3 hours. Bioavailability - 80%.

The drug is evenly distributed throughout the organs and tissues. Biotransformed in the kidneys and to a small extent in the liver. Partially excreted unchanged, mainly through the kidneys.

Pharmacodynamics

Interferon alpha-2b is a highly purified protein obtained through recombinant DNA. The polypeptide structure of the molecule, biological activity and pharmacological properties are identical to human leukocyte interferon alpha-2b. It has antiviral, antiproliferative, antitumor and immunomodulatory effects.

The drug, interacting with related receptors on the cell surface, initiates a complex chain of changes inside the cell. It is assumed that these processes are associated with the prevention of viral replication in the cell, inhibition of cell proliferation and the immunomodulatory effect of interferon. Interferon alfa-2b has the ability to stimulate the phagocytic activity of macrophages, as well as the cytotoxic activity of T cells and NK cells (Natural Killers). These properties of interferon determine the therapeutic effect of the drug.

Indications for use

As part of combination therapy in adults. Viral diseases

- chronic active hepatitis B if it is impossible to use

pegylated interferons

— chronic hepatitis C if it is impossible to use

pegylated interferons

Oncological diseases - hairy cell leukemia - chronic myeloid leukemia - kidney cancer - malignant melanoma.

Directions for use and doses

Realdiron solution is administered intramuscularly or subcutaneously. Before use, the contents of the bottle are dissolved in 1 ml of water for injection. The drug solution should be transparent, without foreign inclusions. For chronic active hepatitis B, Realdiron is administered at a dose of 3 million IU three times a week for 6 months. If after therapy there is no clinical, biochemical improvement and/or disappearance of HBsAg within 3 months, the drug is discontinued.

For chronic hepatitis C, Realdiron is prescribed at a dose of 3 million IU 3 times a week for 6 months. If after administration of the drug during a month of therapy there is no decrease in ALT activity in the blood plasma by 50%, the dose of the drug is increased to 6 million IU 3 times a week. If after 3 months of therapy there is no clinical or biochemical improvement, the drug should be discontinued.

For hairy cell leukemia, 3 million IU is administered daily for 2 months; upon achieving hematological remission - 3 million IU 3 times a week.

For chronic myeloid leukemia, the initial dose of the drug is 3 million IU per day, administered intramuscularly or subcutaneously. If well tolerated, the dose of the drug is increased every week to a maximum dose of 9 million IU per day. Once the white blood cell count has stabilized, this dose can be administered three times a week. The course of treatment is carried out indefinitely, except in cases where therapy should be stopped (for example, with rapid progression of the disease or intolerance to the drug).

For kidney cancer, Realdiron is used at a dose of 3 million IU daily for 10 days. If well tolerated, the dose of the drug is increased every week to a maximum dose of 18 million IU per day. After 3 months of treatment, maintenance therapy is started, administering 18 million IU three times a week for 6 months.

For malignant melanoma, the initial dose of the drug is 3 million IU per day, administered intramuscularly or subcutaneously. If well tolerated, the dose of the drug is increased every week to a maximum dose of 9-18 million IU daily. After achieving a clinical effect, they switch to maintenance therapy of 9-18 million IU 3 times a week. Adjuvant therapy with Realdiron after surgical removal of stage I-II malignant melanoma may lengthen the time to relapse.

Side effects

often

Fever, fatigue, malaise, headache, myalgias, chills, trembling, flu-like symptoms

Anorexia, nausea

less often

Changes in taste, stomatitis, dry mouth, damage to the surface of the teeth and oral mucosa, vomiting, diarrhea, constipation, loose stools, abdominal pain

Alopecia, itching, dry skin, rash

Back pain, musculoskeletal pain, chest pain, myositis, arthralgia

Depression, suicidal thoughts and actions, suicide

Increased sweating, especially at night

Irritability, insomnia, drowsiness, anxiety, decreased concentration, emotional lability, dizziness

Arterial hypotension, hypertension

rarely

Inflammation, redness, irritation at the injection site

Excitement, nervousness, psychosis, including hallucinations, aggressive behavior, agitation, impaired consciousness, neuropathies, polyneuropathy, peripheral neuropathies, paresthesia, hypoesthesia, convulsions, loss of consciousness

Viral infection, including herpes simplex

Erythema

Conjunctivitis, eye pain, blurred vision, retinal hemorrhages, retinopathy, focal retinal changes, retinal artery or vein obstruction, decreased visual acuity or limited visual fields, optic neuritis, papilledema

Dysfunction of the lacrimal glands

Nosebleeds, nasal congestion, sinusitis, rhinitis

Migraine

Cough, pharyngitis, pulmonary infiltrates, pneumonia, dyspnea, respiratory disorders

Weight loss

Tachycardia, palpitations

Decreased libido, menstrual irregularities (amenorrhea, menorrhagia)

Increased appetite, glossitis, bleeding gums

Rhabdomyolysis (sometimes severe)

Hearing impairment or loss

Facial edema, renal dysfunction, nephrotic syndrome, renal

deficiency, hyperuricemia

Hyper- and hypothyroidism, hepatotoxicity (including death)

Leukopenia

Dental and periodontal disorders (including those leading to tooth loss)

very rarely

Increased appetite, diabetes mellitus, hyperglycemia, hypertriglyceridemia, colitis, hepatomegaly, pancreatitis

Cerebrovascular ischemia, cerebrovascular hemorrhages

Sarcoidosis or exacerbation of sarcoidosis

Allergic reactions, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis

Thrombocytopenia, lymphocytopenia, aplastic anemia

Lymphadenopathy

Drowsiness

Necrosis at the injection site

Autoimmune and immune-mediated disorders, incl. idiopathic thrombocytopenic purpura, rheumatoid arthritis, systemic lupus erythematosus, vasculitis and Vogt-Kayanagi-Harada syndrome

Noise in ears

Myocardial infarction, arrhythmia (usually in patients with a history of cardiovascular disease or previous therapy with cardiotoxic drugs), reversible transient cardiomyopathy (noted in patients without a significant history of cardiovascular disease)

Pneumonia

very rarely(with monotherapy or in combination with ribavirin)

Complete red bone marrow aplasia

Changes in laboratory parameters (more often noted when prescribing

drug in doses of more than 10 million IU per day): decrease in the number of granulocytes,

decreased hemoglobin levels, increased activity of ALT, AST (noted when used for all indications except chronic viral hepatitis), alkaline phosphatase, LDH, creatinine and serum urea nitrogen levels

In children, including combination therapy with ribavirin (≥ 1% of the number of patients receiving combination therapy with ribavirin)

Often

Anemia, neutropenia

Hypothyroidism

Depression, emotional lability, insomnia, irritability, headache, dizziness

Anorexia, nausea, vomiting, abdominal pain, diarrhea

Alopecia, rash

Arthralgia, myalgia

Inflammatory reactions at the injection site: pain, hyperemia

Weakness, fever, chills, flu-like symptoms, malaise, viral infection, pharyngitis

Delayed physical development (delayed growth and/or weight compared to age levels)

often

Pallor

Nose bleed

Bacterial infection, pneumonia, fungal infection, herpes simplex

Neoplasms, unclassified

Thrombocytopenia, lymphadenopathy

Hyperthyroidism, virilism

Hypertriglyceridemia, hyperuricemia

Agitation, tremor, drowsiness, aggressive reaction, anxiety, apathy, nervousness, behavioral disturbances, somnambulism, suicidal thoughts, confusion, abnormal dreams, difficulty falling asleep, hyperkinesia, dysphonia, paresthesia, hyperesthesia, hypoesthesia, decreased concentration

Conjunctivitis, eye pain, blurred vision, lacrimal gland dysfunction

Raynaud's disease

Cough, dyspnea, otitis media, nasal congestion, irritation of the nasal mucosa, rhinorrhea, sneezing, tachypnea

Gastrointestinal disorders, increased appetite, constipation, loose stools, rectal disorders, dyspepsia, gastroesophageal reflux, gastroenteritis, glossitis, stomatitis, etc. ulcerative, toothache, liver dysfunction

Pain in the chest, in the right upper quadrant of the abdomen

Acne, eczema, changes in nails, dry skin, skin cracks, photosensitivity reactions, maculopapular rash, changes in skin pigmentation, erythema, sweating, hematoma, itching

Urinary tract infections, urinary disorders, enuresis

Menstrual irregularities, amenorrhea, menorrhagia, vaginal disorders, vaginitis, testicular pain (in boys)

Contraindications

Hypersensitivity to the active or any of the excipients

Severe cardiac diseases, including a history (uncontrolled cardiac dysfunction, recent myocardial infarction, severe heart rhythm disturbances)

Severe kidney or liver diseases, including metastases of tumors in them, renal failure with creatinine clearance below 50 ml/min, when prescribed in combination with ribavirin

Decompensated cirrhosis of the liver

Chronic hepatitis in combination with severe forms of cirrhosis or liver failure

Chronic hepatitis treated in the past with immunosuppressants or glucocorticosteroids

Autoimmune diseases, incl. autoimmune hepatitis currently or in history

Thyroid diseases not controlled by standard treatments

Existing or history of mental disorders in children and adolescents

Children under 3 years of age with chronic hepatitis C

Pregnancy and lactation when prescribed in combination with ribavirin

When prescribed in combination with ribavirin, the contraindications listed in the instructions for use of ribavirin should also be taken into account.

Drug interactions

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

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

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

With the simultaneous use of Realdiron and zidovudine, a synergistic effect on reducing the number of leukocytes can be observed. In patients receiving this therapy, more frequent, dose-related cases of neutropenia were observed than expected with zidovudine monotherapy. Patients receiving Realdiron as part of combination therapy with ribavirin or zidovudine have an increased risk of developing anemia.

The effects of using Realdiron in combination with antiretroviral drugs are unknown.

Interferons can influence oxidative metabolic processes. This should be taken into account when used simultaneously with drugs that are metabolized by oxidation (including xanthine derivatives - aminophylline and theophylline). When using Realdiron with theophylline simultaneously, it is necessary to monitor the concentration of the latter in the blood serum and, if necessary, adjust the dosage regimen.

Pharmaceutical interactions

Realdiron cannot be mixed with other medicinal substances except 0.9% sodium chloride solution.

special instructions

Hepatitis B

Before starting treatment for patients with hepatitis B, it is recommended to perform a liver biopsy to confirm chronic hepatitis and determine the extent of damage, as well as to ensure that there is no current or history of encephalopathy, bleeding from esophageal varices, ascites or other clinical signs of decompensation.

Before starting therapy with Realdiron, you need to focus on the following indicators:

bilirubin normal

prothrombin time adults - prolongation by no more than 3 seconds

children - extension no more than 2 seconds

leukocytes ≥ 4,000/mm3

adult platelets ≥ 100,000/mm3

children ≥ 150,000/mm3

Hepatitis C

The optimal treatment route is combination therapy with ribavirin. Monotherapy with Realdiron is carried out mainly in cases of intolerance or in the presence of contraindications to the use of ribavirin.

When using Realdiron as part of combination therapy with ribavirin for chronic hepatitis C, also read the instructions for the medical use of ribavirin.

All patients with chronic hepatitis C are recommended to undergo a liver biopsy, but in certain cases (for example, patients with viral genotype 2 and 3), treatment is possible without histological confirmation.

Adults. Before starting therapy with Realdiron, you must ensure that there is no current or history of encephalopathy, bleeding from esophageal varices, ascites or other clinical signs of decompensation, while focusing on the following indicators:

bilirubin ≤ 2 mg/dl

albumin is stable and within normal limits

prothrombin time is prolonged by no more than 3 seconds in adults, by 2 seconds in children

leukocytes ≥ 3,000/mm3

platelets ≥ 70,000/mm3

serum creatinine is normal or close to normal

When using Realdiron in combination with ribavirin in patients with impaired renal function (creatinine clearance > 50 ml/min), a complete blood count, creatinine level in the blood and urine should be monitored, taking into account the possibility of anemia. In patients over 50 years of age, this monitoring should be carried out once a week.

Monotherapy.

During treatment with Realdiron, dysfunction of the thyroid gland is possible - hypothyroidism or hyperthyroidism. Before starting to use Realdiron, the level of thyroid-stimulating hormone (TSH) in the blood serum should be determined and an ultrasound scan of the thyroid gland should be performed. If any abnormalities are detected, appropriate therapy should be carried out.

Use for co-infection with HIV and hepatitis C virus

Patients who are additionally infected with HIV and receiving highly active antiretroviral therapy (HAART) may have an increased risk of lactic acidosis. Caution should be exercised when adding Realdiron and ribavirin to HAART.

Patients with cirrhosis additionally infected with HIV and hepatitis C virus who are receiving HAART may have an increased risk of hepatic decompensation and death.

Additional use of alpha interferons alone or in combination with ribavirin increases the above-mentioned risk in this category of patients.

Dental and periodontal disorders

Laboratory research

Before starting treatment with Realdiron and periodically during therapy, all patients undergo monitoring of the peripheral blood picture (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 Realdiron, blood levels should be within normal limits.

During therapy for patients with chronic hepatitis, the following scheme for 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 to a value that is twice or more the value that was before the start of therapy, treatment with Realdiron 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.

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

Immediate hypersensitivity

The appearance of a transient skin rash does not require cessation of treatment.

Accompanying illnesses

Realdiron 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 needed when using the drug in patients with bleeding disorders

(thrombophlebitis, pulmonary embolism) or with severe myelosuppression.

Simultaneous chemotherapy

The use of Realdiron in combination with other chemotherapeutic drugs (for example, cytarabine, cyclophosphamide, doxorubicin, teniposide) increases the risk of developing toxic effects (their severity and duration), which, due to joint use, can be life-threatening or cause death. Due to the risk of increased toxicity, doses of Realdiron and concomitant chemotherapeutic agents must be carefully selected.

Autoantibodies and autoimmune diseases

Treatment with Realdiron 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 chronic hepatitis C, antiviral therapy should be discontinued and the need for corticosteroid therapy should be discussed.

Fever

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.

To reduce body temperature and reduce headaches during influenza-like syndrome, which may occur during Realdiron therapy, the use of antipyretic therapy is recommended.

Use for liver dysfunction

Deaths due to toxic hepatitis have rarely been observed. If signs of liver dysfunction appear during the use of Realdiron, the patient needs careful monitoring and, if symptoms progress, discontinuation of the drug.

Patients with chronic hepatitis B who have decreased liver synthetic function (eg, decreased albumin or prolonged prothrombin time) but who meet eligibility criteria for treatment may be at increased risk of developing clinical decompensation if aminotransferase levels rise during treatment. Before treating such patients, the benefits of using Realdiron should be determined over the possible risks.

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 to alpha interferon therapy has not been established.

Hydration

When treating with Realdiron, it is necessary to ensure adequate hydration of the body, since in some cases arterial hypotension caused by dehydration has been observed (which may require additional fluid administration).

The cardiovascular system

Patients with a history of cardiovascular disease (chronic heart failure, myocardial infarction and/or arrhythmias) require careful medical supervision when prescribing Realdiron. Isolated cases of cardiomyopathy have been reported, sometimes with reversible development after discontinuation of treatment with Realdiron. In patients with a history of heart disease, it is recommended that

ECG before and during therapy with Realdiron. Arrhythmias, mainly supraventricular, occurred rarely and predominantly in patients with a history of cardiovascular diseases or with prior treatment with cardiotoxic drugs. Such rhythm disturbances usually respond to standard therapy, but may require dose modification or discontinuation of Realdiron.

Respiratory system

Any patient with fever, cough, shortness of breath, or other respiratory symptoms should have a chest x-ray. If infiltrates are detected or pulmonary function impairment is present, careful monitoring of the patient is necessary, and, if necessary, discontinuation of Realdiron therapy. Such changes occurred more frequently in patients with chronic hepatitis C who were receiving alpha interferon therapy, but there have been reports of their development in patients with cancer who were also receiving alpha interferon therapy. Timely withdrawal of interferon alpha therapy and the use of corticosteroids leads to the disappearance of adverse pulmonary reactions. Additionally, these symptoms have been reported to occur more frequently when Shosaikoto (a Chinese herbal medicine) was used concomitantly with alpha interferon.

Mental disorders and the central nervous system (CNS). Serious central nervous system disorders, in particular depression, suicidal thoughts and suicide attempts, were observed in some patients during treatment with Realdiron and even after treatment, mainly within 6 months. Among children and adolescents taking Realdiron in combination with ribavirin, suicidal thoughts and suicide attempts were observed more often 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 thoughts or aggressive behavior are detected, it is recommended to discontinue treatment and provide the patient with appropriate psychiatric care.

Patients with existing or history of mental disorders. The use of interferon alfa-2b in children and adolescents with existing or a history of psychiatric disorders is contraindicated (see section "Contraindications").

If it has been decided that Realdiron therapy is necessary for adult patients with existing or a history of mental disorders, as well as alcohol and drug dependence, it should only be started after appropriate individual diagnosis and under constant monitoring of mental status.

Treatment with interferon may exacerbate symptoms of mental disorders in patients infected with the hepatitis C virus, with existing or history of mental disorders, as well as with alcohol and drug dependence. If interferon treatment is necessary for patients with such disorders, then appropriate treatment of psychiatric symptoms is provided to achieve successful interferon treatment. In addition, individual screening of patients' behavior and frequency of mental health symptoms is mandatory. Pretreatment is recommended for these patients before the onset or development of psychiatric symptoms.

Ophthalmological disorders

All patients must undergo an ophthalmological examination before starting therapy. Realdiron therapy should be discontinued if new or worsening ophthalmological disorders appear.

Thyroid changes

If there is dysfunction of the thyroid gland, treatment with Realdiron can be started or continued if the TSH level can be maintained at a normal level with drug therapy. Stopping the use of Realdiron does not lead to normalization of thyroid function that was impaired during treatment.

Metabolic disorders

In connection with cases of development or progression of hypertriglyceridemia to severe forms, it is recommended to monitor blood lipid levels.

Other

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

Use in pediatrics

The decision to initiate combination therapy in children should be made individually, taking into account both signs of disease progression (inflammatory activity in the liver and fibrosis) and prognostic factors for the development of virological response, HCV genotype and viral load. It is important to keep in mind that combination therapy may cause growth retardation and weight gain in some children treated for one year, the reversibility of which is not completely clear. In this regard, it is recommended to monitor the physical development of children during therapy and for 6 months after completion of treatment.

To reduce the risk of growth retardation, the child should be treated if possible after rapid growth during puberty. There are no data on the effect of long-term treatment on puberty.

Effect on reproductive function

Decreases in serum concentrations of estradiol and progesterone in women receiving Realdiron have been reported. Therefore, Realdiron can be used in women of reproductive age if they use effective contraception throughout the entire treatment period. Realdiron is also used with caution in men of reproductive age.

Pregnancy and lactation

There are insufficient data on the use of Realdiron during pregnancy. Realdiron should be used during pregnancy if the potential benefit to the mother outweighs the potential threat to the fetus.

Due to the potential for adverse effects on the nursing infant, the decision to discontinue breastfeeding or discontinue the drug should be made taking into account the degree of need for this therapy for the mother.

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 car or using complex equipment.

Overdose

Currently, no cases of drug overdose have been reported.

In case of overdose, symptomatic treatment is indicated.

In clinical studies conducted across a wide range of indications and with a wide range of doses (from 6 million IU/m2 per week in hairy cell leukemia; up to 100 million IU/m2 per week in melanoma), the most common adverse events were fever, fatigue, headache, myalgia. Fever and fatigue resolved 72 hours after discontinuation of the drug. Although fever may be a symptom of the influenza-like syndrome that often occurs with interferon treatment, evaluation should be performed to rule out other possible causes of persistent fever.
The following safety profile was obtained from 4 clinical studies in patients with chronic hepatitis C who received Intron A as monotherapy or in combination with ribavirin for 1 year. All patients received 3 million IU of Intron A 3 times a week.
Table 2 shows adverse events occurring at a frequency greater than or equal to 10% in previously untreated patients receiving Intron A (or Intron A in combination with ribavirin) for 1 year. In general, the observed adverse events were mild or moderate.
Table 2.

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

Clinical and pharmacological group:

Release form, composition and packaging

substance -solution.

bottles (1) - cardboard packs.

Description of the active components of the drug " Interferon alpha-2b»

pharmachologic effect

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

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

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

Has an antiproliferative effect on tumor cells.

Indications

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

Hairy cell leukemia, chronic myeloid leukemia, renal cell carcinoma, Kaposi's sarcoma due to AIDS, cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome), malignant melanoma.

Dosage regimen

Administered intravenously or subcutaneously. The dose and treatment regimen are set individually, depending on the indications.

Side effect

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

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

From the central nervous system and peripheral nervous system: rarely - dizziness, deterioration of mental activity, sleep disturbance, memory impairment, anxiety, nervousness, aggressiveness, euphoria, depression (after long-term treatment), paresthesia, neuropathy, tremor; in some cases - suicidal tendencies, drowsiness.

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

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

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

Dermatological reactions: possible itching, reversible alopecia.

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

Contraindications

Severe cardiovascular diseases, decompensated liver cirrhosis, severe depression, psychosis, alcohol or drug addiction, increased sensitivity to interferon alpha-2b.

Pregnancy and lactation

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

It is not known whether interferon alfa-2b is excreted in breast milk. If it is necessary to use it during lactation, the issue of stopping breastfeeding should be decided.

Women of childbearing age should use reliable contraception during treatment.

Use for liver dysfunction

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

Use for renal impairment

Use with caution in patients with impaired renal function.

special instructions

Use with caution in patients with impaired renal, liver, bone marrow hematopoiesis, or with a tendency to suicide attempts.

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

During the treatment period, monitoring of neurological and mental status is necessary.

In cases of severe suppression of bone marrow hematopoiesis, regular examination of the composition of peripheral blood is necessary.

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

Drug interactions

Drug interactions

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

This section presents instructions for use of interferons alpha 2b and alpha 2a first generation, which are also called linear, simple or short-lived. The only advantage of these preparations is their relatively low price.

Back in 1943, V. and J. Heile discovered the so-called interference phenomenon. The initial idea of ​​interferon was this: a factor that prevents the reproduction of viruses. In 1957, the English scientist Alik Isaacs and the Swiss researcher Jean Lindenman isolated this factor, clearly described it and called it interferon.

Interferon (IFN) is a protein molecule that is produced in the human body. The human genetic apparatus encodes a “recipe” for its synthesis (interferon gene). Interferon is one of the cytokines, signaling molecules that play an important role in the functioning of the immune system.

Over the half century since the discovery of IFN, dozens of properties of this protein have been studied. From a medical point of view, the main ones are antiviral and antitumor functions.

The human body produces about 20 types - a whole family - of interferons. IFN is divided into two types: I and II.

Type I IFNs - alpha, beta, omega, theta - are produced and secreted by most cells of the body in response to the action of viruses and some other agents. Type II IFN includes interferon gamma, which is produced by cells of the immune system in response to the action of foreign agents.

Initially, interferon preparations were obtained only from donor blood cells; They were called that: leukocyte interferons. In 1980, the era of recombinant, or genetically engineered, interferons began. The production of recombinant drugs has become significantly cheaper than producing similar drugs from human donor blood or other biological raw materials; their production does not use donor blood, which can serve as a source of infection. Recombinant drugs do not contain foreign impurities and therefore have fewer side effects. Their healing potential is higher than that of similar natural drugs.

For the treatment of viral diseases, in particular hepatitis C, interferon alpha (IFN-α) is mainly used. There are “simple” (“short-lived”) interferons alpha 2b and alpha 2a and pegylated (peginterferon alfa-2a and peginterferon alfa-2b). “Simple” interferons are practically not used in the EU and the USA, but in our country, due to their comparative cheapness, they are used quite often. In the treatment of hepatitis C, both forms of “short” IFN-α are used: interferon alpha-2a and interferon alpha-2b (differing in one amino acid). Injections with simple interferons are usually done every other day (with peginterferons - once a week). The effectiveness of treatment with short-lived IFNs when administered every other day is lower than with peginterferons. Some experts recommend daily injections of “simple” IFN, since the effectiveness of AVT is slightly higher.

The range of “short” IFNs is quite wide. They are produced by different manufacturers under different names: Roferon-A, Intron A, Laferon, Reaferon-EC, Realdiron, Eberon, Interal, Altevir, Alfarona and others.
The most studied (and therefore expensive) are Roferon-A and Intron-A. The effectiveness of treatment with these IFNs in combination with ribavirin, depending on the genotype of the virus and other factors, ranges from 30% to 60%. A list of the main brands of simple interferon manufacturers and their descriptions are given in the table.

All interferons should be stored refrigerated (from +2 to +8 degrees Celsius). They should not be heated or frozen. Do not shake or expose the product to direct sunlight. It is necessary to transport drugs in special containers.