Reaferon-EC lyophilisate d / prig. solution for d / and 3000000ME, No. 5

• Adults as part of complex therapy: acute viral hepatitis B - moderate and severe forms at the beginning of the icteric period up to the 5th day of jaundice (at a later date, the administration of the drug is less effective;

• the drug is not effective in developing hepatic coma and cholestatic course of the disease);

• acute protracted hepatitis B and C, chronic active hepatitis B and C, chronic hepatitis B with a delta agent, without signs of cirrhosis and with signs of liver cirrhosis;

• stage IV kidney cancer, hairy cell leukemia, malignant skin lymphomas (fungal mycosis, primary reticulosis, reticulosarcomatosis), Kaposi's sarcoma, basal cell and squamous cell carcinomas of the skin, keratoacanthoma, chronic myeloid leukemia, histiocytosis from subcellular leukemia cells, myelogenous leukemia histiocytosis; viral conjunctivitis, keratoconjunctivitis, keratitis, keratoiridocyclitis, keratouveitis. In complex therapy in children from 1 year of age: with acute lymphoblastic leukemia in the period of remission after the end of induction chemotherapy (at 4-5 months of remission);

• with respiratory papillomatosis of the larynx, starting from the next day after removal of papillomas.

The drug is used intramuscularly, subcutaneously, in the focus or under the lesion, subconctive and topically. Immediately before use, the contents of the ampoule or vial are dissolved in water for d / and or 0.9% sodium chlodir solution (in 1 ml - with intramuscular, subcutaneous administration and into the focus, in 5 ml - with subconjunctival and local administration).

The solution of the drug should be colorless, transparent or with a slight opalescence, without sediment and foreign inclusions. The dissolution time should be about 3 minutes. In / m and subcutaneous administration In acute viral hepatitis B, the drug is administered at 1 million ME 2 times / day for 5-6 days, then the dose is reduced to 1 million ME / day and administered for another 5 days.

If necessary (after control biochemical blood tests), the course of treatment can be continued by 1 million IU 2 times a week for 2 weeks. The course dose is 15-21 million ME.

In acute protracted and chronic viral hepatitis B, with the exclusion of the delta agent and without signs of liver cirrhosis, the drug is administered 1 million IU 2 times a week for 1-2 months. If there is no effect, the treatment should be extended to 3-6 months or after the end of 1-2 months of treatment, 2-3 similar courses should be carried out with an interval of 1-6 months.

In chronic viral hepatitis B with a delta agent without signs of liver cirrhosis, the drug is administered at 500 thousand - 1 million ME / day, 2 times a week for 1 month. A second course of treatment in 1-6 months. In chronic viral hepatitis B with a delta agent and signs of liver cirrhosis, the drug is administered at 250-500 thousand IU / day, 2 times a week for 1 month.

When signs of decompensation appear, similar repeated courses are carried out at intervals of at least 2 months. In acute protracted and chronic active hepatitis C without signs of liver cirrhosis, the drug is administered 3 million ME 3 times a week for 6-8 months.

If there is no effect, prolong the treatment up to 12 months. A second course of treatment in 3-6 months. For kidney cancer, the drug is used at 3 million IU daily for 10 days. Repeated courses of treatment (3-9 or more) are carried out at intervals of 3 weeks. The total amount of the drug ranges from 120 million ME to 300 million ME and more.

With hairy cell leukemia, the drug is administered daily at 3-6 million IU for 2 months. After normalization of the clinical blood test, the daily dose of the drug is reduced to 1-2 million ME. Then a maintenance therapy of 3 million ME is prescribed 2 times a week for 6-7 weeks. The total amount of the drug is 420-600 million ME and more. In acute lymphoblastic leukemia in children in remission after the end of induction chemotherapy (at 4-5 months of remission) - 1 million ME1 times a week for 6 months, then once every 2 weeks for 24 months. At the same time, supportive chemotherapy is given.

For malignant lymphomas and Kaposi's sarcoma, the drug is administered at 3 million IU / day daily for 10 days in combination with cytostatics (prospidium chloride, cyclophosphamide) and GCS. In the tumor stage of fungal mycosis, primary reticulosis and reticulosarcomatosis, it is advisable to alternate the intramuscular administration of the drug at 3 million ME and intralesional administration of 2 million ME for 10 days. In patients with the erythrodermic stage of fungal mycosis when the temperature rises above 39 ? C and in case of an exacerbation of the process, the administration of the drug should be discontinued.

If the therapeutic effect is insufficient, a second course of treatment is prescribed after 10-14 days. After the clinical effect is achieved, a maintenance therapy of 3 million ME is prescribed once a week for 6-7 weeks. In chronic myeloid leukemia, the drug is administered at 3 million ME daily or 6 million ME through laziness. The duration of treatment is from 10 weeks to 6 months.

In case of histiocytosis from Langerhans cells, the drug is injected at 3 million IU daily for 1 month. Repeated courses at 1-2 month intervals for 1-3 years.

In case of sublepkemic myelosis and essential thrombocythemia for the correction of hyperthrombocytosis - 1 million ME daily or every 1 day for 20 days.

In case of respiratory papillomatosis of the larynx, the drug is administered at 100-150 thousand IU per kilogram of body weight daily for 45-50 days, then at the same dosage 3 times per week for 1 month. The second and third courses are carried out at intervals of 2-6 months. In persons with a high pyrogenic reaction (39 ? C and above), the simultaneous use of paracetamol or indomethacin is recommended for the administration of the drug.

Perifocal introduction

In basal cell and squamous cell carcinoma, keratoacanthoma, the drug is administered under the lesion at 1 million ME 1 time / day daily for 10 days. In the case of pronounced local inflammatory reactions, the introduction under the lesion is carried out in 1-2 days. At the end of the course, if necessary, cryodestruction is performed.

Subconjunctival introduction

For stromal keratitis and keratoiridocyclitis, subconjunctival injections of the drug are prescribed at a dose of 60 thousand IU in a volume of 0.5 ml daily or every other day, depending on the severity of the process. Injections are performed under local anesthesia with 0.5% dicaine solution. The course of treatment is from 15 to 25 injections.

Local application

For topical use, the contents of the ampoule of the drug are dissolved in 5.0 ml of 0.9% sodium chloride solution d / i. In the case of storing a solution of the drug, it is necessary, observing the rules of asepsis and antiseptics, to transfer the contents of the ampoule to a sterile vial and store the solution in the refrigerator at 4-10 ? C for no more than 12 hours.

With conjunctivitis and superficial keratitis, 2 drops of the solution are applied to the conjunctiva of the affected eye 6-8 times / day. As the inflammation disappears, the number of installations is reduced to 3-4. The course of treatment is 2 weeks.

Lyophilisate for the preparation of a solution for injection and topical application in the form of a powder or a porous mass of white, hygroscopic; when diluted, a colorless transparent or slightly opalescent solution is formed.

1 amp.

interferon alpha-2b human recombinant 3,000,000 IU

Excipients: albumin, solution for infusion 10% - 4.5 mg, sodium chloride - 8.52 mg, sodium hydrogen phosphate dodecahydrate - 3.34 mg, sodium dihydrogen phosphate dihydrate - 0.49 mg.

• Hypersensitivity to drug components;

• severe forms of allergic diseases;

• severe diseases of the cardiovascular system: heart failure in the stage of decompensation, recent myocardial infarction, severe cardiac arrhythmias;

• severe renal and / or hepatic failure, including those caused by the presence of metastases, chronic hepatitis with compensated cirrhosis of the liver, autoimmune hepatitis; epilepsy and other disorders of the central nervous system, mental illness and disorders in children and adolescents;

• a history of autoimmune disease;

• the use of immunosuppressants after transplantation;

• diseases of the thyroid gland that cannot be controlled by conventional therapeutic methods; CC below 50 ml / min (when administered in combination with ribavirin), when used in combination with ribavirin, the contraindications specified in the instructions for use of ribavirin should also be taken into account;

• use in men whose partners are pregnant;

• pregnancy and breastfeeding period.

• With caution, renal and / or hepatic failure, severe myelosuppression. mental disorders, especially expressed by depression, suicidal thoughts and attempts in anamnesis. patients with psoriasis, sarcoidosis.

pharmachologic effect

The drug has antiviral, antitumor, immunomodulatory activity. Human recombinant interferon alpha-2b, which is an active ingredient in the preparation, is synthesized by bacterial cells of the Escherichia coli SG-20050 / pIF16 strain. in the genetic apparatus of which the gene of human interferon alpha-2b is embedded. It is a 165 amino acid protein and is identical in characteristics and properties to human leukocyte interferon alpha-2b. The antiviral effect of interferon alpha-2b is manifested during the reproduction of the virus by actively including cells in metabolic processes. Interferon, interacting with specific receptors on the cell surface, initiates a number of intracellular changes, including the synthesis of specific cytokines and enzymes (2-5-adepilate synthetase and protein kinase),the action of which inhibits the formation of viral protein and viral ribonucleic acid in the cell. The immunomodulatory effect of interferon alpha-2b is manifested in an increase in the phagocytic activity of macrophages, an increase in the specific cytotoxic effect of lymphocytes on target cells, and a change in the quantitative and qualitative composition of secreted cytokines. changes in the functional activity of immunocompromised cells, changes in the production and secretion of intracellular proteins. The antitumor effect of the drug is realized by suppressing the proliferation of tumor cells and the synthesis of some oncogenes, leading to inhibition of tumor growth.enhancing the specific cytotoxic effect of lymphocytes on target cells, changing the quantitative and qualitative composition of secreted cytokines. changes in the functional activity of immunocompromised cells, changes in the production and secretion of intracellular proteins. The antitumor effect of the drug is realized by suppressing the proliferation of tumor cells and the synthesis of some oncogenes, leading to inhibition of tumor growth.enhancing the specific cytotoxic effect of lymphocytes on target cells, changing the quantitative and qualitative composition of secreted cytokines. changes in the functional activity of immunocompromised cells, changes in the production and secretion of intracellular proteins. The antitumor effect of the drug is realized by suppressing the proliferation of tumor cells and the synthesis of some oncogenes, leading to inhibition of tumor growth.leading to inhibition of tumor growth.leading to inhibition of tumor growth.

Pharmacokinetics

Cmax of interferon alpha-2b with parenteral administration of the drug is observed after 2-4 hours. 20-24 hours after administration of recombinant interferon alpha-2b in the blood serum is not detected. The content of interferon alpha-2b in the blood serum is in direct proportion to the dose of the drug administered and the frequency of administration. Metabolism is carried out in the liver, partially excreted unchanged, mainly through the kidneys.

Side effect

From the side of the cardiovascular system: rarely - arrhythmias, transient reversible cardiomyopathy; very rarely - arterial hypotension, myocardial infarction.

From the digestive system: rarely - dry mouth, nausea, abdominal pain, dyspepsia, appetite disorders, weight loss, vomiting, diarrhea; very rarely - pancreatitis, hepatotoxicity.

From the side of the central nervous system: rarely - irritability, nervousness, depression, asthenia, insomnia, anxiety, impaired ability to concentrate, suicidal thoughts, aggressiveness; very rarely - neuropathy, psychosis.

From the side of the skin: rarely - skin expelling and itching. increased sweating, hair loss. When injected into the focus or under the lesion, it is rare - a local inflammatory reaction. These side effects usually do not prevent the continued use of the drug.

From the endocrine system: against the background of prolonged use of the drug, changes in the thyroid gland are possible. Very rarely - diabetes mellitus.

On the part of laboratory parameters: when using the drug, deviations from the norm of laboratory parameters are possible, manifested by leukopenia, lymphopeia, thrombocytopenia, anemia, increased activity of alanine aminotransferase, alkaline phosphatase, concentration of creatinine, urea. Typically, these changes are usually minor, asymptomatic, and reversible.

From the musculoskeletal system: rarely - rhabdomyolysis, leg cramps, back pain, myositis, myalgia.

From the respiratory system: rarely - pharyngitis, cough, dyspnea, pneumonia.

From the urinary system: very rarely - renal failure.

From the immune system: rarely - autoimmune pathology (vasculitis, rheumatoid arthritis, lupus-like syndrome); very rarely - sarcoidosis, apgioneurotic allergic edema, anaphylaxis, facial edema.

From the side of the organs of vision: with local application of the drug on the mucous membrane of the eye, hyperemia, single follicles, edema of the conjunctiva of the lower fornix are possible.

Rarely - hemorrhages in the retina, focal changes in the fundus, thrombosis of the retinal arteries and veins, decreased visual acuity, optic neuritis, edema of the optic nerve head.

On the part of the hearing organs: rarely - hearing impairment. In case of pronounced local and general adverse reactions, the administration of the drug should be discontinued.

Application during pregnancy and lactation

The drug is contraindicated for use during pregnancy and during breastfeeding.

special instructions

For the timely detection of abnormalities in laboratory parameters that may arise during therapy, general clinical blood tests must be repeated every 2 weeks, and biochemical ones - every 4 weeks. With a decrease in the number of platelets to a value of less than 50 ? 109 / l. the absolute number of neutrophils less than 0.75 ? 109 / L is recommended to temporarily reduce the dose by a factor of 2 and repeat the analysis after 1-2 weeks. If the changes persist, it is recommended to stop treatment. With a decrease in the number of platelets to a value of less than 25 ? 109 / L, the absolute number of neutrophils less than 0.50 ? 109 / L, treatment is recommended to be discontinued. In the case of the development of immediate-type hypersensitivity reactions (urticaria, angioedema, bronchospasm, anaphylaxis), the drug is canceled and the appropriate drug therapy is immediately prescribed.A transient skin rash does not require discontinuation of therapy. In case of signs of liver dysfunction, the patient must be closely monitored. With the progression of symptoms, the drug should be discontinued. With mild to moderate renal impairment, their functional state must be carefully monitored. It is prescribed with caution in patients with severe chronic diseases such as COPD, diabetes mellitus with a tendency to ketoacidosis, in patients with bleeding disorders, severe myelosuppression. In patients receiving Reaferon-EC for a long time, in rare cases, pneumopitis and pneumonia are observed. Timely withdrawal of interferon alfa and the appointment of glucocorticosteroid therapy contribute to the relief of pulmonary syndromes.In patients with thyroid diseases, before starting treatment, it is necessary to determine the concentration of thyroid gland hormone, it is recommended to monitor its level at least once every 6 months. In case of dysfunction of the thyroid gland or deterioration of the course of existing diseases that do not lend themselves to adequate drug correction, it is necessary to discontinue the drug. In the event of changes in the mental sphere and / or the central nervous system, including the development of depression, it is recommended to observe a psychiatrist during the treatment period, as well as within 6 months after its termination. These disorders are usually rapidly reversible after discontinuation of therapy, but in some cases, it may take up to 3 weeks for them to fully reverse. If symptoms of the mental disorder do not regress or worsen,suicidal thoughts or aggressive behavior directed at other people appear, it is recommended to discontinue treatment with Reaferon-EC and provide a psychiatrist's consultation. Suicidal thoughts and attempts are more often observed in pediatric patients, primarily adolescents (2.4%) than in adults (1%). If therapy with interferon alfa-2b is deemed necessary in adult patients with severe mental impairment (including a history), it should only be initiated if appropriate individual screening and therapy for the mental disorder is carried out. The use of interferon alfa-2b in children and adolescents with serious mental disorders (including a history) is contraindicated. With prolonged use, usually after several months of treatment, there may be visual disturbances.An ophthalmologic examination is recommended before starting therapy. In case of complaints of any ophthalmic disorders, immediate consultation with an ophthalmologist is required. Patients with diseases in which changes in the retina may occur, for example, diabetes mellitus or arterial hypertension, should undergo an ophthalmological examination at least once every 6 months. If visual impairments appear or worsen, consideration should be given to discontinuing therapy with Reaferon-EC. Elderly patients receiving high doses of the drug may have impaired consciousness, coma, convulsions, encephalopathy. If such disorders develop and the dose reduction is ineffective, treatment should be discontinued.Patients with diseases of the cardiovascular system and / or progressive cancer require careful observation and monitoring of the ECG. With the development of arterial hyotension, it is recommended to provide adequate hydration and appropriate therapy. In patients after transplantation (for example, kidney or bone marrow), drug immunosuppression may be less effective, because interferon has a stimulating effect on the immune system. With prolonged use, the preparation of interferon alfa can cause the appearance of antibodies to interferon in some individuals. As a rule, antibody titers are low, their appearance does not lead to a decrease in the effectiveness of treatment. It is prescribed with caution in patients with a predisposition to autoimmune diseases.If symptoms of an autoimmune disease appear, a thorough examination should be carried out and the possibility of continuing interferon therapy should be evaluated. Rarely, interferon alpha therapy is associated with the onset or exacerbation of psoriasis and sarcoidosis.

Influence on the ability to drive vehicles and mechanisms

During the period of using the drug, patients experiencing fatigue, drowsiness or disorientation should refrain from engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Overdose

Overdose cases were not observed. Considering that the active substance is interferon alpha-2b, an overdose may increase the severity of dose-dependent side effects. Treatment: drug withdrawal; if necessary, symptomatic therapy is carried out.

Drug interactions

Interferon alfa-2b is able to reduce the activity of cytochrome P450 isoenzymes and, therefore, affect the metabolism of cimetidine, phenytoin, curantil, theophylline. diazepam, propranolol, warfarin. some cytostatics. May enhance the neurotoxic, myelotoxic or cardiotoxic effect of drugs previously prescribed or simultaneously with it. Avoid co-administration with drugs that depress the central nervous system. immunosuppressive drugs (including oral and parenteral forms of GCS). Interferons can affect oxidative metabolic processes. This should be taken into account when used simultaneously with drugs metabolized by oxidation (including with xanthine derivatives - aminophylline and theophylline).With the simultaneous use of Reaferon-EC with theophylline, it is necessary to control the concentration of theophylline in the blood serum and, if necessary, adjust the dosage regimen. With the combined use of Reaferon-EC and hydroxyurea, the incidence of cutaneous vasculitis may increase. Drinking alcohol during treatment is not recommended.