Reafferon-ES, lyophilizate 3000000 me 5 pcs

The drug has antiviral, antitumor, immunomodulatory activity.

Interferon alfa-2b human recombinant, which is the active ingredient of the preparation, is synthesized by bacterial cells of Escherichia coli strain SG-20050/pIF16. The gene of human interferon alfa-2b is built into the genetic apparatus. It is a protein containing 165 amino acids and is identical in its characteristics and properties to human leukocyte interferon alpha-2b.

The antiviral effect of interferon alpha-2b is manifested during the period of virus reproduction by its active inclusion in the metabolic processes of cells. Interferon, interacting with specific receptors on the surface of cells, initiates a number of intracellular changes, including synthesis of specific cytokines and enzymes (2-5-adepylate synthetase and protein kinase), the action of which inhibits formation of viral protein and viral ribonucleic acid in the cell.

The immunomodulatory action of interferon alfa-2b is manifested in the increase of phagocytic activity of macrophages, increase of specific cytotoxic action of lymphocytes on the target cells, changes of quantitative and qualitative composition of secreted cytokines, changes of functional activity of immunocompetent cells, changes of production and secretion of intracellular proteins. Antitumor action of the drug is realized due to suppression of proliferation of tumor cells and synthesis of some oncogenes which leads to inhibition of tumor growth.

Indications

Adults as part of complex therapy:

– acute viral hepatitis B – moderate and severe forms at the beginning of jaundice period until the 5th day of jaundice (in later periods administration of the drug is less effective; the drug is not effective in developing hepatic coma andbr> cholestatic course of disease);

– acute prolonged hepatitis B and C, chronic active hepatitis B and C, chronic hepatitis B with delta agent, without signs of cirrhosis and with appearance of signs of cirrhosis;

– stage IV renal cancer, hairy cell leukemia, malignant skin lymphomas (fungal mycosis, primary reticulosis, reticulosarcomatosis), Kaposi sarcoma,
basal cell and squamous cell skin cancer, keratoacanthoma, chronic myeloleukemia, Langerhans cell histiocytosis, subleukemic myelosis, essential thrombocythemia;

– viral conjunctivitis, keratoconjunctivitis, keratitis, keratoiridocyclitis, keratouveitis.

In the complex therapy for children from 1 year old:

– in acute lymphoblastic leukemia in the period of remission after the end of induction chemotherapy (4-5 months of remission);

– in respiratory papillomatosis of the larynx, starting the day after removal of papillomas.

Active ingredient

Composition

1 ampoule – interferon alpha-2b human recombinant 3,000,000 IU

Supplementary substances:

albumin,

10% infusion solution – 4.5 mg,

sodium chloride – 8.52 mg,

sodium hydrophosphate dodecahydrate – 3.34 mg,

sodium dihydrophosphate dihydrate – 0.49 mg.

How to take, the dosage

The drug is administered in m/m, p/k, in or under the lesion, subconjunctival and topically. Immediately prior to use the contents of the ampoule or bottle shall be dissolved in d/y water or 0.9% sodium chloride solution (1 ml for intravenous, p/c and in the focus, 5 ml for subconjunctival and local administration). The drug solution shall be colorless, transparent or slightly opalescent, without sediment and foreign inclusions. The dissolution time should be about 3 min.

I/m and percutaneous administration

In acute viral hepatitis B the drug is administered by 1 million ME 2 times per day for 5-6 days, then the dose is reduced to 1 million ME/day and administered for another 5 days. If necessary (after controlling blood chemistry) the treatment course can be continued in 1 million ME twice a week for two weeks. The course dose is 15-21 million ME.

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

In chronic viral hepatitis B with delta agent without signs of liver cirrhosis the drug is administered 500 thousand to 1 million ME/day twice a week for 1 month. Repeated course of treatment in 1-6 months.

In chronic viral hepatitis B with delta agent and signs of liver cirrhosis the drug is administered by 250-500 thousand ME/day 2 times a week for 1 month. If there are signs of decompensation, similar repeated courses with intervals of at least 2 months are carried out.

In case of acute prolonged and chronic active hepatitis C without signs of liver cirrhosis the drug is given 3 mln.ME 3 times a week during 6-8 months. If there is no effect, treatment should be prolonged up to 12 months. The course of treatment is repeated in 3-6 months.

In kidney cancer the drug is administered 3 million ME daily for 10 days. Repeated courses of treatment (3-9 and more) are carried out at intervals of 3 weeks. The total amount of the drug ranges from 120 million ME to 300 million ME or more.

In case of hairy cell leukemia the drug is administered daily for 3-6 million ME for 2 months. After normalization of clinical blood count the daily dose of the drug is decreased to 1-2 million ME. Then maintenance therapy of 3 mln ME twice a week for 6-7 weeks is prescribed. The total amount of the drug is 420-600 million ME or more.

In acute lymphoblastic leukemia in children in the period of remission after the end of induction chemotherapy (in the 4th-5th month of remission) – 1 million ME1 once a week for 6 months, then once every 2 weeks for 24 months. At the same time, maintenance chemotherapy is carried out.

In case of malignant lymphomas and Kaposi sarcoma the drug is administered on 3 million ME/daily for 10 days in combination with cytostatics (propridium chloride, cyclophosphamide) and GCS. In the tumor stage of fungal mycosis, primary reticulosis and reticulosarcomatosis it is advisable to alternate between 3 million ME of the drug in a m/m injection and 2 million ME intrafocal injection for 10 days.

In patients with erythrodermic stage of fungal mycosis with fever over 39 ° C and in case of exacerbation of the process, the drug administration should be stopped. In case of insufficient therapeutic effect the second course of treatment shall be prescribed in 10-14 days. After achieving the clinical effect, maintenance therapy of 3 mln.ME once a week for 6-7 weeks is prescribed.

In chronic myeloleukemia the drug is administered 3 million ME daily or 6 million ME every other day. The treatment period is from 10 weeks to 6 months.

In Langerhans cell histiocytosis, the drug is administered 3 million ME daily for 1 month. Repeated courses at 1-2 month intervals for 1-3 years.

In sublepkemic myelosis and essential thrombocythemia for correction of gynertrombocytosis, 1 million ME daily or every 1 day for 20 days.

In respiratory papillomatosis of the larynx the drug is administered in 100-150 thousand ME per kg of body weight daily for 45-50 days, then in the same dosage 3 times a week for 1 month. The second and third course are carried out at an interval of 2-6 months.

In persons with high pyrogenic reaction (39°C or higher) to the drug administration it is recommended to use paracetamol or indomethacin at the same time.

Perifocal administration

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

Interaction

Interferon alfa-2b can decrease the activity of cytochrome P450 isoenzymes and, therefore, affect the metabolism of cimetidine, phenytoin, curantil, theophylline, diazepam, propranolol, warfarin and some cytostatics. It may increase neurotoxic, myelotoxic or cardiotoxic effects of drugs prescribed earlier or simultaneously with it. Co-administration with drugs depressing CNS should be avoided. immunosuppressive drugs (including oral and parenteral forms of GCS).

Interferons may affect oxidative metabolic processes. This should be considered when concomitant use with drugs that are metabolized by oxidation (including xanthine derivatives – aminophylline and theophylline). When concomitant use of Referon-ES with theophylline it is necessary to monitor the concentration of theophylline in blood serum and adjust the dosing regimen, if necessary.

The co-administration of Referon-ES and hydroxyurea may increase the incidence of cutaneous vasculitis.

Alcohol consumption during treatment is not recommended.

Special Instructions

For timely detection of abnormal laboratory values that may occur during therapy, general clinical blood tests should be repeated every 2 weeks, and biochemical tests every 4 weeks.

If the platelet count decreases to less than 50×109/l. the absolute iitrophil count is less than 0.75×109/l, a temporary dose reduction of 2 times and repeating the analysis after 1-2 weeks is recommended. If changes persist, treatment is recommended to be discontinued.

If the platelet count decreases to less than 25×109/L, the absolute neutrophil count to less than 0.50×109/L, treatment should be discontinued.

In case of gynersensitivity reactions of immediate type (urticaria, angioedema, bronchospasm, anaphylaxis) the drug is discontinued and appropriate drug therapy is immediately prescribed. Transient skin rash does not require discontinuation of therapy.

In case of signs of liver dysfunction, the patient should be closely monitored. In case of progression of symptoms the drug should be discontinued.

In case of mild to moderate renal dysfunction, their functional status should be closely monitored.

Patients with severe chronic diseases, such as COPD, diabetes mellitus with predisposition to ketoacidosis, in patients with blood clotting disorders, marked myelosuppression are treated with caution. Rare cases of pneumopitis and pneumonia have been observed in patients receiving Reafferon-EC for a long time. Timely withdrawal of interferon alfa and administration of glucocorticosteroid therapy contribute to relief of pulmonary syndromes.

In patients with thyroid diseases it is necessary to determine the concentration of thyroid hormone before the beginning of treatment, it is recommended to control its level at least once in 6 months. In case of occurrence of thyroid function abnormalities or worsening of the course of existing diseases which cannot be adequately medicated, the drug should be discontinued.

In case of changes in the mental sphere and/or CNS, including the development of depression, psychiatric observation is recommended during the treatment period, as well as for 6 months after its completion. These disorders are usually rapidly reversible after discontinuation of therapy, but in some cases it takes up to 3 weeks for them to fully reverse. If mental health symptoms do not regress or worsen, suicidal ideation or aggressive behavior directed at others appears, it is recommended to stop treatment with Reaferon-EC and to ensure consultation with a psychiatrist. Suicidal thoughts and attempts are more common 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 disorders (including a history of mental illness), it should only be initiated if appropriate individual screening and therapy for the mental disorder is provided. The use of interferon alfa-2b in children and adolescents with serious mental disorders (including a history) is contraindicated.

In long-term use, usually after several months of treatment, visual disturbances may occur. Ophthalmologic examination is recommended before initiation of therapy. Immediate consultation with an ophthalmologist is necessary in case of any ophthalmologic complaints. Patients with diseases that may cause changes in the retina, such as diabetes mellitus or arterial hypertension, should undergo ophthalmologic examination at least once every 6 months. If visual impairment occurs or worsens, consideration should be given to discontinuing therapy with Reaferon-ES.

In elderly patients receiving the drug in high doses, impaired consciousness, coma, seizures, encephalopathies are possible. If these disorders develop and dose reduction is ineffective, treatment should be discontinued.

Patients with cardiovascular disease and/or advanced cancer require close observation and ECG monitoring. If arterial hyyotension develops, adequate hydration and appropriate therapy is recommended.

In patients after transplantation (e.g., kidney or bone marrow transplantation), medication-assisted immunosuppression may be less effective because interferon has a stimulatory effect on the immune system.

In long-term use, interferon alfa may cause individuals to develop antibodies to interferon. As a rule, antibody titers are not high, and their appearance does not lead to a decrease in the effectiveness of treatment.

With caution patients with predisposition to autoimmune diseases. If symptoms of autoimmune disease occur, a thorough examination should be performed and the possibility of continuation of interferon therapy should be evaluated. Interferon alfa therapy is rarely associated with the occurrence or exacerbation of psoriasis, sarcoidosis.

Impact on driving and operating ability

When using the drug, patients who are tired, drowsy, or disoriented should refrain from engaging in potentially dangerous activities that require increased concentration and rapid psychomotor reaction.

Contraindications

– hypersensitivity to the components of the drug;

– severe forms of allergic diseases;

– severe diseases of the cardiovascular system: decompensated heart failure, recent myocardial infarction, marked heart rhythm disorders;

– severe renal and/or hepatic failure, including.ч., caused by the presence of metastases, chronic hepatitis with decompensated liver cirrhosis, autoimmune hepatitis;

– epilepsy and other CNS disorders, mental diseases and disorders in children and adolescents;

– history of autoimmune disease;

– use of immunosuppressants after transplantation;

– Thyroid disease that cannot be controlled with conventional therapies;

– IBC below 50 mL/min (when used in combination with ribavirin),
When used in combination with ribavirin, the contraindications listed in the instructions for ribavirin use should also be considered;

– Use in men whose partners are pregnant;

– Pregnancy and breastfeeding.

With caution

– renal and/or hepatic insufficiency, expressed myelosuppression.

– mental disorders, especially those manifested by depression, suicidal thoughts and attempts in the history.

– patients with psoriasis, sarcoidosis.

Side effects

The frequency of adverse reactions is given according to the WHO classification: “very frequent” – 1/10, “frequent” – more than 1/100 but less than 1/10, “infrequent” – more than 1/1000 but less than 1/100. “Rare” at more than 1/10000 but less than 1/1000 and “very rare” at less than 1/10000 occurrence, including individual reports.

The following adverse events have been observed with Reaferon-ES (in and out of clinical trials):

Often, flu-like syndrome (chills. fever, asthenia, fatigue, fatigue, myalgias, arthralgias, headaches) is observed with parenteral administration of the drug, partially managed with paracetamol, indomethacin. As a rule, the flu-like syndrome appears at the beginning of treatment and decreases with continuation.

Cardiovascular system: rare – arrhythmias, transient reversible cardiomyopathy; very rare – arterial hypotension, myocardial infarction.

The digestive system: rare – dry mouth, nausea, abdominal pain, dyspepsia, appetite disorders, weight loss, vomiting, diarrhea; very rare – pancreatitis, hepatotoxicity.

CNS disorders: rarely – irritability, nervousness, depression, asthenia, insomnia, anxiety, disturbance of concentration, suicidal thoughts, aggressiveness; very rarely – neuropathies, psychosis.

Skin disorders: rarely – skin eruptions and itching. increased sweating, hair loss. When injected into or under the lesion rarely – local inflammatory reaction. These side effects are usually not an obstacle to continued use of the drug.

Endocrine system disorders: during long-term use of the drug, changes of the thyroid gland are possible. Very rarely – diabetes mellitus.

Laboratory disorders: during the use of the drug some deviations from the normal laboratory indices are possible, manifested by leukopenia, lymphopenia, thrombocytopenia, anemia, increased alanine aminotransferase activity, alkaline phosphate, concentration of creatinine, urea. As a rule, these changes are usually minor, asymptomatic, and reversible.

Muscular system disorders: rare – rhabdomyolysis, leg cramps, back pain, myositis, myalgia.

Respiratory system disorders: rarely – pharyngitis, cough, dyspnea, pneumonia.

Additional disorders of the urinary system: very rare – renal failure.

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

In the organs of vision: during local administration of the drug on the ocular mucosa hyperemia, single follicles, edema of the lower vault conjunctiva may occur. Rarely – retinal hemorrhage, focal changes of the fundus, thrombosis of retinal arteries and veins, decreased visual acuity, optic neuritis, edema of the optic disc.

Hearing organs: rare – hearing impairment.

In case of severe local and general adverse reactions, the drug should be discontinued.

Overdose

There have been no cases of overdose. Taking into account that the active substance is interferon alfa-2b, in case of overdose it is possible to increase the severity of dose-dependent side effects.

Treatment: discontinuation of the drug; symptomatic therapy if necessary.

Pregnancy use

Similarities