Reaferon-ES 1000000IU vials, 5pcs

Composition

One ampoule or one bottle contains:  

Active ingredient-human recombinant interferon alpha 2b 1 million IU;

Auxiliary substances:

albumin,

infusion solution 10% – 4.50 mg,

sodium chloride-8.96 mg,

sodium hydrophosphate dodecahydrate-2.86 mg,

sodium dihydrophosphate dihydrate-0.40 mg.

Pharmacological action

The drug has antiviral, antitumor, and immunomodulatory activity.

Human recombinant Interferon alfa-2b, which is the 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 human Interferon alfa-2b gene is embedded. It is a protein containing 165 amino acids and is identical in characteristics and properties to human leukocyte Interferon alfa-2b.

The antiviral effect of Interferon alfa-2b is manifested during the period of viral reproduction by active inclusion of cells in the 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-adenylate 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 alfa-2b is manifested in an increase in the phagocytic activity of macrophages, an increase in the specific cytotoxic effect of lymphocytes on target cells, a change in the quantitative and qualitative composition of secreted cytokines, a change in the functional activity of immunocompetent cells, a change 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 certain oncogenes, which leads to inhibition of tumor growth.

Indications

• of acute viral hepatitis In moderate and severe forms at the beginning of the icteric period before the 5th day of jaundice (later the drug less effective; the drug is not effective for developing hepatic coma and cholestatic disease);
• prolonged in acute hepatitis b, chronic active hepatitis b and chronic hepatitis b with Delta-agent without signs of cirrhosis and signs of cirrhosis of the liver;
• in kidney cancer stage IV, hairy cell leukemia, malignant lymphomas of the skin (mycosis fungoides, primary retikulez, reticulosarcoma), Kaposi’s sarcoma, basal cell and squamous cell cancers of the skin, keratoacanthoma, chronic myeloid leukemia, histiocytosis from Langerhans cells, subleukemic myelosis, essential thrombocythemia;
• in case of viral conjunctivitis, keratoconjunctivitis, keratitis, keratomalacia, keratouveitis;

In complex therapy in children from 1 year of age:  

• in acute lymphoblastic leukemia in remission after the end of induction chemotherapy (at 4-5 months of remission);
• in respiratory laryngeal papillomatosis, starting from the next day after the removal of papillomas.

Contraindications

• Severe forms of allergic diseases;
• Severe diseases of the cardiovascular system – heart failure in the stage of decompensation, a recent myocardial infarction, severe cardiac arrhythmias;
• Severe renal and / or hepatic insufficiency, including those caused by the presence of metastases, chronic hepatitis with decompensated cirrhosis of the liver, autoimmune hepatitis;
• Epilepsy and other disorders of the central nervous system, mental illnesses and disorders in children and adolescents;
• A history of autoimmune disease; 
• Use of immunosuppressants after transplantation;
• Thyroid diseases that cannot be controlled by conventional therapeutic methods; 
• Creatinine clearance below 50 ml / min (when administered in combination with ribavirin), when used in combination with ribavirin, the contraindications indicated in the instructions for use of ribavirin should also be taken into account;
• Hypersensitivity
• Use in men whose partners are pregnant;
• Pregnancy and breast-feeding period.

With caution

•  Renal and / or hepatic insufficiency, severe myelosuppression. Mental disorders, especially depression, suicidal thoughts and attempts in the anamnesis. Patients with psoriasis, sarcoidosis.
•  Use during pregnancy and lactation
•  The drug is contraindicated for use during pregnancy and lactation.

Side effects

the incidence of adverse reactions is given in accordance with the who classification: a “very frequent” – 1/10, “common” – 1/100, but less than 1/10, “infrequent” – 1/1000 but less than 1/100, rare – more than 1/10000, but at least 1/1000 and “very rare” occurrence at less than 1/10000, including individual messages.

When using Reaferon-EC (in clinical studies and out of clinical studies), the following adverse events were observed: :  

Often, with parenteral use of the drug, a flu-like syndrome is observed (chills, fever, asthenia, fatigue, fatigue, myalgia, arthralgia, headaches), partially relieved by paracetamol, Indometacin. As a rule, the flu-like syndrome manifests itself at the beginning of treatment and decreases with continuation.

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

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

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

From the skin: rarely-skin rashes and itching, increased sweating, hair loss. When injected into or under the lesion, a local inflammatory reaction is rare. These side effects are usually not an obstacle to continuing the use of the drug.

From the endocrine system: against the background of long-term use of the drug, changes in the thyroid gland may occur. Very rarely – diabetes mellitus.

From the laboratory parameters: when using the drug, deviations from the norm of laboratory parameters are possible, manifested by leukopenia, lymphopenia, thrombocytopenia, anemia, increased activity of alanine aminotransferase, alkaline phosphatase, creatinine and urea concentrations. Generally, these changes are usually minor, asymptomatic, and reversible.

Musculoskeletal disorders: rarely-rhabdomyolysis, leg cramps, back pain, myositis, myalgia.

From the respiratory system: rarely-pharyngitis, cough, dyspnoea, 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, allergic angioedema, anaphylaxis, facial edema.

From the side of the visual organs: with topical application of the drug on the mucous membrane of the eye, hyperemia, single follicles, edema of the conjunctiva of the lower arch are possible. Rarely-retinal hemorrhages, focal fundus changes, retinal artery and vein thrombosis, decreased visual acuity, optic neuritis, and optic disc edema.

From the side of the organs of hearing: rarely-hearing impairment.

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

Interaction

Interferon alfa-2b can reduce the activity of cytochrome P-450 isoenzymes and, consequently, affect the metabolism of cimetidine, phenytoin, Curantyl, theophylline, diazepam, propranolol, warfarin, and some cytostatics. It may increase the neurotoxic, myelotoxic, or cardiotoxic effects of drugs previously administered or concomitantly administered. Co-use with CNS depressants, immunosuppressive drugs (including oral and parenteral forms of glucocorticosteroids) should be avoided.

Interferons can affect oxidative metabolic processes. This should be taken into account when used concomitantly with drugs that are metabolized by oxidation (including xanthine derivatives – aminophylline and theophylline). With simultaneous use of Reaferon-EC with theophylline, it is necessary to monitor 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.

Alcohol consumption during treatment is not recommended.

How to take it, course of use and dosage

The drug is used intramuscularly, subcutaneously, in the lesion or under the lesion, subconjunctivally and locally.Immediately before use, the contents of the ampoule or vial are dissolved in water for injection or 0.9% sodium chlodir solution (in 1 ml-for intramuscular, subcutaneous use and in the focus, in 5 ml – for subconjunctival and local use). The solution of the drug should be colorless, transparent or with a weak opalescence, without sediment and foreign inclusions. The dissolution time should be about 3 minutes.

Intramuscular and subcutaneous use

In acute viral hepatitis B, the drug is administered 1 million IU 2 times a day for 5-6 days, then the dose is reduced to 1 million IU per day and administered for another 5 days. If necessary (after control biochemical blood tests), the course of treatment can be continued at 1 million IU 2 times a week for 2 weeks. The course dose is 15-21 million IU.

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

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

In chronic viral hepatitis B with a delta agent and signs of cirrhosis of the liver, the drug is administered at 250-500 thousand rubles. IU per day 2 times a week for 1 month. If signs of decompensation appear, similar repeated courses are performed at intervals of at least 2 months.

In acute prolonged and chronic active hepatitis C without signs of cirrhosis of the liver, the drug is administered 3 million IU 3 times a week for 6-8 months. If there is no effect, the treatment should be extended to 12 months. Repeat the course of treatment in 3-6 months.

For kidney cancer, the drug is used for 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 IU to 300 million IU or more.

For 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 IU. Then, maintenance therapy is prescribed at 3 million IU 2 times a week for 6-7 weeks. The total amount of the drug is 420-600 million IU or more.

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

For malignant lymphomas and Kaposi’s sarcoma, the drug is administered at 3 million IU per day daily for 10 days in combination with cytostatics (prospidium chloride, cyclophosphamide) and glucocorticosteroids. In the tumor stage of fungal mycosis, primary reticulosis and reticulosarcomatosis, it is advisable to alternate intramuscular use of the drug with 3 million IU and intraocular use with 2 million IU for 10 days.

In patients with an erythrodermic stage of fungal mycosis, if the temperature rises above 39 °C and in case of exacerbation of the process, the drug should be discontinued. If the therapeutic effect is insufficient, a second course of treatment is prescribed after 10-14 days. After achieving a clinical effect, maintenance therapy is prescribed at 3 million IU once a week for 6-7 weeks.

In chronic myeloid leukemia, the drug is administered at 3 million IU daily or 6 million IU every other day. The duration of treatment is from 10 weeks to 6 months.

In histiocytosis from Langerhans cells, the drug is administered at 3 million IU daily for 1 month. Repeat courses at 1-2-month intervals for 1-3 years.

In case of subleukemic myelosis and essential thrombocythemia for correction of hyperthrombocytosis – 1 million IU daily or after 1 day for 20 days.

For respiratory laryngeal papillomatosis, the drug is administered at 100-150 thousand rubles. IU per kilogram of body weight daily for 45-50 days, then in the same dosage 3 times a week for 1 month. The second and third courses are conducted at intervals of 2-6 months.

Concomitant use of paracetamol or Indometacin is recommended in patients with a high pyrogenic reaction (39 °C and above) to the drug use.

Perifocal use

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

Subconjunctival introduction

With stromal keratitis and keratoiridocyclitis, subconjunctival injections of the drug are prescribed in a dose of 60 thousand rubles. 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 a 0.5% solution of dicaine. The course of treatment is from 15 to 25 injections.

Local application

For topical application, the contents of the ampoule of the drug are dissolved in 5.0 ml of 0.9% sodium chloride solution for injection. If the drug solution is stored, it is necessary, following the rules of asepsis and antiseptics, to transfer the contents of the ampoule to a sterile bottle 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 a day. As the inflammatory phenomena disappear, the number of instillations is reduced to 3-4. The course of treatment is 2 weeks.

Overdose

No cases of overdose were observed. Given that the Active ingredient is Interferon alfa-2b, overdose may increase the severity of dose-dependent side effects.

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

Special instructions

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

If the number of platelets decreases to less than 50·109/l, the absolute number of neutrophils is less than 0.75·109/l, it is recommended to temporarily reduce the dose by 2 times and repeat the analysis in 1-2 weeks. If the changes persist, it is recommended to stop treatment.

If the number of platelets decreases to less than 25·109/l, the absolute number of neutrophils is less than 0.50·109/l, treatment is recommended to stop.

In case of immediate hypersensitivity reactions (urticaria, angioedema, bronchospasm, anaphylaxis), the drug is discontinued and 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 should be carefully monitored. If symptoms progress, the drug should be discontinued.

With mild to moderate renal impairment, their functional state should be carefully monitored.

Caution should be used in patients with severe chronic diseases, such as chronic obstructive pulmonary diseases, diabetes mellitus with a tendency to ketoacidosis, in patients with blood clotting disorders expressed by myelosuppression. In patients receiving Reaferon-EC for a long time, pneumonitis and pneumonia are rarely observed. Timely withdrawal of interferon alpha and the appointment of corticosteroid 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-stimulating hormone, it is recommended to monitor its level at least once every 6 months. If there is a violation of thyroid function or a worsening of the course of existing diseases that do not respond to adequate drug correction, it is necessary to cancel the drug.

In case of changes in the mental sphere and/or the central nervous system, including the development of depression, it is recommended to monitor a psychiatrist during treatment, as well as for 6 months after its end. These disorders are usually quickly reversible after discontinuation of therapy, but in some cases it takes up to 3 weeks for their complete reverse development. If the symptoms of a mental disorder do not regress or worsen, suicidal thoughts or aggressive behavior directed at other people appear, it is recommended to stop treatment with Reaferon-EC and consult a psychiatrist. Suicidal thoughts and attempts are more common in children, primarily adolescents (2.4%), than in adults (1%). If Interferon alfa-2b therapy is considered necessary in adult patients with serious mental disorders (including a history), it should be initiated only if appropriate individual screening and therapy for the mental disorder is performed. The use of Interferon alfa-2b in children and adolescents with serious mental disorders (including in the anamnesis) is contraindicated.

With prolonged use, usually after several months of treatment, visual disturbances may occur. Before starting therapy, it is recommended to conduct an ophthalmological examination. If you complain of any ophthalmic disorders, you should immediately consult an optometrist.Patients with diseases that may cause changes in the retina, for example, diabetes mellitus or arterial hypertension, should undergo an ophthalmological examination at least once every 6 months. Discontinuation of Reaferon-EC therapy should be considered if visual disturbances occur or worsen.

Elderly patients receiving the drug in high doses may have impaired consciousness, coma, convulsions, and encephalopathy. In case of development of such disorders and ineffectiveness of dose reduction, treatment should be discontinued.

Patients with cardiovascular diseases and / or advanced cancer require careful monitoring and ECG monitoring. If hypotension develops, adequate hydration and appropriate therapy is recommended.

In patients after transplantation (for example, kidney or bone marrow), drug-induced immunosuppression may be less effective, since interferon has a stimulating effect on the immune system.

With prolonged use, interferon alpha may cause individuals to develop antibodies to interferon. As a rule, antibody titers are low, and their appearance does not lead to a decrease in the effectiveness of treatment.

Use with caution in patients with a predisposition to autoimmune diseases. If symptoms of an autoimmune disease appear, a thorough examination should be performed and the possibility of continuing interferon therapy should be evaluated. Rarely, interferon alpha therapy is associated with the onset or exacerbation of psoriasis, sarcoidosis.

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

Influence on the ability to drive vehicles and mechanisms

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

Form of production

Lyophilizate for solution preparation for injection and topical application.

Storage conditions

Store in a dark place at a temperature not exceeding 8 °C.

Shelf

life is 3 years.

Active ingredient

Interferon alfa-2b

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection