Composition, form of production and packaging
Liofilizate for the preparation of solution for injection and topical application in the form of powder or porous mass of white, hygroscopic; when diluted, a colorless, transparent or slightly opalescent solution is formed.
1 amp.
interferon alpha-2b human recombinant 500,000 IU
[PRING] albumin, solution for infusions 10% - 4.5 mg, sodium chloride - 9.07 mg, sodium hydrogen phosphate dodecahydrate - 2.74 mg, sodium dihydrogen phosphate dihydrate - 0.37 mg.
500000 IU - ampoules (5) - packings of cellular contour (1) - packs cardboard.
500000 IU - ampoules (5) - packings of cellular contour (2) - packs cardboard.
500000 IU - bottles (5) - packings of cellular contour (1) - packs cardboard.
Liofilizate for the preparation of solution for injection and topical application in the form of powder or porous mass of white, hygroscopic; when diluted, a colorless, transparent or slightly opalescent solution is formed.
1 amp.
interferon alfa-2b human recombinant 1 000 000 IU
[PRING] albumin, infusion solution 10% - 4.5 mg, sodium chloride - 8.96 mg, sodium hydrogen phosphate dodecahydrate - 2.86 mg, sodium dihydrogen phosphate dihydrate - 0.4 mg.
ampoules (5) - packings, cellular planimetric (1) - packs cardboard.
ampoules (5) - packings, cellular contour (2) - packs cardboard.
bottles (5) - packings, cellular outline (1) - packs cardboard.
Liofilizate for the preparation of solution for injection and topical application in the form of powder or porous mass of white, hygroscopic; when diluted, a colorless, transparent or slightly opalescent solution is formed.
1 amp.
interferon alfa-2b human recombinant 3 000 000 IU
[PRING] albumin, solution for infusions 10% - 4.5 mg, sodium chloride - 8.52 mg, sodium hydrogen phosphate dodecahydrate - 3.34 mg, sodium dihydrogen phosphate dihydrate - 0.49 mg.
3000000 ME - ampoules (5) - packings, cellular outline (1) - packs cardboard.
3,000,000 IU - ampoules (5) - packings of cellular contour (2) - packs of cardboard.
3,000,000 IU - bottles (5) - packings of cellular contour (1) - packs of cardboard.
Liofilizate for the preparation of solution for injection and topical application in the form of powder or porous mass of white, hygroscopic; when diluted, a colorless, transparent or slightly opalescent solution is formed.
1 amp.
interferon alfa-2b human recombinant 5,000,000 IU
[PRING] albumin, solution for infusions 10% - 4.5 mg, sodium chloride - 8.09 mg, sodium hydrogen phosphate dodecahydrate - 3.82 mg, sodium dihydrogen phosphate dihydrate - 0.58 mg.
5000000 IU - ampoules (5) - packings, cell planimetric (1) - packs of cardboard.
5000000 IU - ampoules (5) - packings, cell planimetric (2) - packs cardboard.
5000000 IU - bottles (5) - packings of cellular contour (1) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
The drug has antiviral, antitumor, immunomodulating activity.
Interferon alfa-2b human recombinant, which is the active substance in the preparation, is synthesized by bacterial cells of the strain of Escherichia coli SG-20050 / pIF16. in the genetic apparatus of which the human interferon alpha-2b gene is embedded. It is a protein containing 165 amino acids, and is identical in characteristics and properties to human leukocyte interferon alpha-2b.
The antiviral effect of interferon alfa-2b is manifested during the reproduction of the virus by active incorporation into the metabolic processes of the cells. Interferon, interacting with specific receptors on the surface of cells, initiates a number of intracellular changes, including the synthesis of specific cytokines and enzymes (2-5-adipylate 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, enhancement of the specific cytotoxic action of lymphocytes on target cells, changes in the quantitative and qualitative composition of secreted cytokines. changes in the functional activity of immune cells, changes in 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.
PHARMACOKINETICS
C max interferon alpha-2b for parenteral administration of the drug is observed after 2-4 hours. After 20-24 hours after administration, recombinant interferon alpha-2b in serum is not determined. The content of interferon alpha-2b in serum is directly dependent on 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.
INDICATIONS
Adults in the complex therapy:
- Acute viral hepatitis B - moderate and severe forms at the beginning of the icteric period before the 5th day of jaundice (at a later date, the administration of the drug is less effective, the drug is not effective in developing a hepatic coma and
cholestatic course of the 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 the appearance of signs of cirrhosis;
- Stage IV kidney cancer, hairy cell leukemia, malignant skin lymphomas (mushroom mycosis, primary reticulosis, reticulosarcomatosis), Kaposi's sarcoma,
basal cell and squamous cell carcinomas, keratoacanthoma, chronic myeloid leukemia, histiocytosis from Langerhans cells, subleukemic myelosis,
essential thrombocythemia;
- viral conjunctivitis, keratoconjunctivitis, keratitis, keratoiridocyclitis, keratouveitis.
In complex therapy in children from 1 year:
- with acute lymphoblastic leukemia in 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 by papillomas.
DOSING MODE
The drug is used in / m, s / k, in the focus or under the lesion, subconjunctivally and locally. Immediately before use, the contents of the ampoule or vial are dissolved in water d / or 0.9% sodium chloride solution (in 1 ml - with a / m, n / k introduction and into the outbreak, in 5 ml - with subconjunctival and local administration).The drug solution should be colorless, transparent or with weak opalescence, without sediment and foreign inclusions. The dissolution time should be about 3 minutes.
In / m and s / c introduction
In acute viral hepatitis B, the drug is administered 1 million ME 2 daily / for 5-6 days, then the dose is reduced to 1 million ME / day and injected for another 5 days.If necessary (after the control biochemical blood tests), the treatment course can be continued 1 million ME 2 times a week for 2 weeks. The course dose is 15-21 million ME.
In acute prolonged and chronic viral hepatitis B, with the exception of the delta-agent and without signs of liver cirrhosis, the drug is administered 1 million ME 2 times a week for 1-2 months. In the absence of the effect, the treatment should be extended to 3-6 months or after the end of the 1-2 month treatment, 2-3 similar courses should be performed at intervals of 1-6 months.
In chronic viral hepatitis B with a delta-agent without signs of liver cirrhosis, the drug is administered 500,000-1 million ME / day 2 times a week for 1 month.Repeated course of treatment after 1-6 months.
In chronic viral hepatitis B with delta-agent and signs of liver cirrhosis, the drug is administered 250-500 thousand ME / day 2 times a week for 1 month. When there are signs of decompensation, similar repeated courses are conducted at intervals of not less than 2 months.
In acute prolonged and chronic active hepatitis C without signs of cirrhosis, the drug is administered 3 million ME 3 times a week for 6-8 months. If there is no effect, prolong the treatment to 12 months. Repeated course of treatment after 3-6 months.
In kidney cancer, the drug is used for 3 million ME 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 is from 120 million ME to 300 million ME or more.
With hairy cell leukemia, the drug is administered daily for 3-6 million ME for 2 months. After the normalization of the clinical blood test, the daily dose of the drug is reduced to 1-2 million ME. Then, supportive therapy is prescribed for 3 million ME 2 times a week for 6-7 weeks. The total amount of the drug is 420-600 million ME or more.
In acute lymphoblastic leukemia in children in remission after the end of induction chemotherapy (at 4-5 months of remission) - 1 million ME1 once a week for 6 months, then 1 every 2 weeks for 24 months. Simultaneously, supportive chemotherapy is performed.
With malignant lymphomas and Kaposi's sarcoma, the drug is administered 3 million ME / d daily for 10 days in combination with cytostatics (prospidium chloride, cyclophosphamide) and SCS. In the tumor stage of fungal mycosis, primary reticulosis and reticulosarcomatosis, it is advisable to alternate IM in 3 million ME and intrafocal for 2 million ME for 10 days.
In patients with erythrodermic stage of fungal mycosis with increasing temperature above 39 В° C and in case of aggravation of the process, the drug should be discontinued. In case of insufficient therapeutic effect, after 10-14 days a second course of treatment is prescribed. After achieving a clinical effect, a maintenance therapy of 3 million ME is prescribed once a week for 6-7 weeks.
In chronic myelogenous leukemia, the drug is administered 3 million ME per day or 6 million ME through laziness. The treatment period is from 10 weeks to 6 months.
With histiocytosis from Langerhans cells, the drug is administered 3 million ME daily for 1 month. Repeated courses with 1-2-month intervals for 1-3 years.
With subleukemic myelosis and essential thrombocythemia for correction of gynarthrombocytosis - 1 million ME per day or 1 day for 20 days.
With respiratory papillomatosis of the larynx, the drug is administered 100-150 thousand IU per kilogram of body weight daily for 45-50 days, then in the same dosage 3 times per pedum for 1 month. The second and third courses are conducted at intervals of 2-6 months.
In persons with a high pyrogenic reaction (39 В° C and above), the simultaneous use of paracetamol or indomethacin is recommended for drug administration.
Perifocal administration
With basal cell and squamous cell carcinoma, keratoacanthoma, the drug is injected under the lesion by 1 million ME 1 time / day daily for 10 days. In the case of pronounced local inflammatory reactions, the injection under the lesion is carried out after 1-2 days. At the end of the course, if necessary, conduct a cryodestruction.
Subconjunctival administration
With stromal keratitis and keratoiridocyclitis, subconjunctival injections of the drug are given in a dose of 60,000 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 - from 15 to 25 injections.
Local application
For topical application, the contents of the drug's ampoule are dissolved in 5.0 ml of 0.9% sodium chloride solution d / u. In case of storage of the drug solution, it is necessary, in accordance with the rules of aseptic and antiseptic, to transfer the contents of the ampoule into a sterile vial and store the solution in the refrigerator at 4-10 В° C for no more than 12 hours.
With conjunctivitis and superficial keratitis , two drops of a solution of 6-8 times / day are applied to the conjunctiva of the affected eye. With the disappearance of inflammatory phenomena, the number of installations is reduced to 3-4. The course of treatment is 2 weeks.
SIDE EFFECT
The frequency of unwanted reactions is given in accordance with the classification of BOZ: "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" - more than 1/10000, but less than 1/1000 and "very rare" with a occurrence of less than 1/10000, including individual messages.
In the application of Reaferon-EU (in clinical studies and outside clinical studies), the following adverse events were observed:
Often with parenteral administration of the drug, there is a flu-like syndrome (chills, fever, fatigue, fatigue, myalgia, arthralgia, headaches), partially docked with paracetamol, indomethacin. As a rule, the flu-like syndrome manifests itself at the beginning of treatment and decreases with the continuation.
From the cardiovascular system: rarely - arrhythmia, transient reversible cardiomyopathy; very rarely - arterial hypotension, myocardial infarction.
On the part of the digestive system: rarely - dry mouth, nausea, abdominal pain, indigestion, 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 skin: rarely - skin expulsion and itching. increased sweating, hair loss. When injected into the focus or under the lesion is rare - a local inflammatory reaction.These side effects are usually not an obstacle to continued use of the drug.
On the part of the endocrine system: against a background of long-term use of the drug, there may be changes in the thyroid gland. Very rarely - diabetes mellitus.
On the part of laboratory indicators: with the use of the drug deviations from the norm of laboratory indicators, manifested by leukopenia, lymphopenia, thrombocytopenia, anemia, increased activity of alanine aminotransferase, alkaline phosphatase, creatinine concentration, urea are possible. 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 side of the urinary system: very rarely - kidney failure.
From the immune system: rarely - autoimmune pathology (vasculitis, rheumatoid arthritis, lupus-like syndrome); very rarely - sarcoidosis, apneaurovtichesky allergic edema, anaphylaxis, edema of the face.
From the side of the eye: when the drug is applied locally on the mucous membrane of the eye, there may be hyperemia, single follicles, edema of the conjunctiva of the lower arch. Rarely - hemorrhages in the retina, focal changes in the fundus, thrombosis of the arteries and veins of the retina, decreased visual acuity, optic neuritis, edema of the optic nerve.
From the organs of hearing : rarely - hearing impairment.
With severe local and general adverse reactions, the drug should be discontinued.
CONTRAINDICATIONS
hypersensitivity to the components of the drug;
- severe forms of allergic diseases;
- Severe diseases of the cardiovascular system: heart failure in the stage of decompensation, recently suffered myocardial infarction, severe cardiac rhythm disturbances;
- severe renal and / or hepatic insufficiency, including, caused by the presence of metastases, chronic hepatitis with decompensated liver cirrhosis, autoimmune hepatitis;
- epilepsy and other disorders of the central nervous system, mental illness and disorders in children and adolescents;
- an autoimmune disease in the anamnesis;
- use of immunosuppressants after transplantation;
- diseases of the thyroid gland that can not be controlled by conventional therapeutic methods;
- CC below 50 ml / min (when administered in combination with ribavirin),
when used in combination with ribavirin, contraindications in the ribavirin application instructions should also be considered;
- use in men whose partners are pregnant;
- Pregnancy and the period of breastfeeding.
Carefully
- renal and / or hepatic insufficiency, expressed myelosuppression.
- Mental disorders, especially those expressed by depression, suicidal thoughts and attempts in the anamnesis.
- patients with psoriasis, sarcoidosis.
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 occur during therapy, general clinical blood tests should be repeated every 2 weeks, and biochemical - every 4 weeks.
When the number of platelets decreases to less than 50 Г— 10 9 / l. an absolute number of neutrophils less than 0.75 Г— 10 9 / l, a temporary dose reduction of 2 times and repeat analysis after 1-2 weeks is recommended. If the changes persist, treatment is recommended to be discontinued.
With a decrease in the number of platelets to less than 25 Г— 10 9 / l, an absolute number of neutrophils less than 0.50 Г— 10 9 / L treatment is recommended to be discontinued.
In the case of developing immediate-type gyneconcly-responsive reactions (urticaria, angioedema, bronchospasm, anaphylaxis), the drug is withdrawn and immediate appropriate medication is prescribed. Transient skin rash does not require discontinuation of therapy.
In case of signs of a violation of liver function, the patient must be carefully monitored. With the progression of symptoms, the drug should be discontinued.
With mild and moderate impairment of kidney function, their functional state must be carefully monitored.
Be wary appoint patients with severe chronic diseases such as COPD, diabetes mellitus prone to ketoacidosis, patients with bleeding disorders, severe mielosupresiey. In patients receiving long-term IFN-EU, in rare cases, there pnevmopity and pneumonia. Timely cancellation of interferon alpha therapy and the appointment glyukokortikosteriodnoy contribute to relief of pulmonary syndromes.
In patients with thyroid disease before treatment is necessary to determine the concentration tireotroshyugo hormone, it is recommended to control the level not less than 1 time in 6 months. Faults thyroid function or worsening of existing diseases, beyond adequate drug correction necessary to remove the drug.
In the event of changes in the mental sphere and / or central nervous system, including the development of depression, it is recommended psychiatric observation during treatment and for 6 months after graduation. These disorders are usually rapidly reversible upon discontinuation of therapy, but in some cases for their full reverse development is necessary to 3 weeks. If the mental disorder symptoms do not regress or worsen, there are suicidal thoughts or aggressive behavior directed at others, it is recommended to discontinue treatment IFN-EU and provide consultation psychiatrist. Suicidal thoughts and attempts are more frequent in pediatric patients, primarily adolescents (2.4%) than in adults (1%).If therapy with interferon alfa-2b considered necessary in adult patients with severe mental disorders (including history), it should be initiated only if the individual is a suitable screening and treatment of mental disorders. The use of interferon alfa-2b in children and adolescents with severe mental disorders (including history) is contraindicated.
With prolonged use, usually after a few months of treatment, there may be violations of the organ of vision. Before initiation of therapy is recommended to perform ophthalmologic examination. When complaints of any ophthalmic disorders require immediate consultation ophthalmologist. Patients with diseases in which changes may occur in the retina, for example, diabetes or hypertension, it is necessary to pass Ophthalmologic examination is not less than 1 time in 6 months. The appearance of or worsening eye disorders should consider discontinuing therapy IFN-EU.
In elderly patients receiving the drug in high doses, possible impairment of consciousness, coma, seizures, encephalopathy. In the case of such violations and ineffective dose reduction, treatment should be discontinued.
Patients with diseases of the cardiovascular system and / or progressive cancer requires careful monitoring and ECG monitoring. With the development of arterial giiotenzii recommended to ensure adequate hydration and appropriate therapy.
In patients after transplantation (e.g., kidney, or bone marrow) immunosuttressiya drug may be less effective because Interferon has a stimulating effect on the immune system.
With prolonged use of the drug can induce interferon alpha from individuals appearance of antibodies to interferon. Typically, the antibody titers are low, their occurrence does not reduce the effectiveness of treatment.
Precautions are administered to subjects with a predisposition to autoimmune diseases. If you have symptoms of an autoimmune disease, a thorough examination and assess the possibility of continuing interferon therapy. Occasionally interferon alpha therapy is associated with the onset or exacerbation of psoriasis, sarcoidosis.
Impact on the ability to drive vehicles and mechanisms
The period of application of the drug to patients experiencing fatigue, drowsiness or disorientation, should refrain from activities potentially hazardous activities that require high concentration and psychomotor speed reactions.
OVERDOSE
Cases of overdose were observed. Given that the active substance is interferon alpha-2b, the overdose may increase the severity of dose-related side effects.
Treatment: removal of preparation; if necessary, conduct symptomatic therapy.
DRUG INTERACTION
Interferon alpha-2b is able to reduce the activity of cytochrome P450 isoenzymes and therefore affect the metabolism of cimetidine, phenytoin, chimes, theophylline. diazepam , propranolol, warfarin. Some cytostatics. May potentiate neurotoxic, myelotoxic or cardiotoxic action of drugs prescribed previously or simultaneously therewith. Avoid concomitant administration with drugs depressing the central nervous system. immunosuppressive agents (including oral and parenteral forms GCS).
Interferons can affect oxidative metabolic processes. This should be considered while the use of drugs metabolirizuyuschimisya by oxidation (including derivatives with xanthine - theophylline and aminophylline). With simultaneous use of IFN-EU with theophylline is necessary to control the concentration of theophylline in the blood serum and adjust the dosing regimen as needed.
In a joint application IFN-EU and hydroxyurea may increase the incidence of cutaneous vasculitis.
Drinking alcohol during treatment is not recommended.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored protected from light and the reach of children at a temperature not higher than 8 В° C. Shelf life - 3 years.
The drug with expired shelf life is not subject to application.
