Index of drugs

Chronic hepatitis B: treatment of adult patients with chronic hepatitis B with confirmed hepatitis B virus replication (presence of HBV-DNA) and hepatitis B antigen (HBeAg), with increased alanine aminotransferase (ALT) and with histologically confirmed active inflammation liver and / or fibrosis.Chronic hepatitis C. Adults: the preparation is indicated for the treatment of adult patients with chronic hepatitis C, with an increased activity of aminotransferases without liver decompensation, which is found in HCV-RNA serum. The best way to use the product in this indication is combined administration with ribavirin.Children and youthThe preparation is intended for use in combination regimen with Ribavirin for the treatment of children and adolescents aged 3 years or more in patients with chronic hepatitis C previously untreated, without signs of liver decompensation and with HCV-RNA found in serum. When deciding not to abstain from treatment until adulthood, it should be taken into account that the combination therapy caused stunted growth. There is no certainty whether the inhibition of growth is transient. The decision to initiate treatment should be made on a case-by-case basis.Hairy cell leukemia: treatment of patients with hairy cell leukemia.Chronic myelogenous leukemia. Monotherapy: treatment of adult patients with chronic myeloid leukemia with Philadelphia chromosome or bcr / abl translocation. Clinical experience indicates that a high or low haematological and cytogenetic response is obtained in the majority of patients treated. A high cytogenetic response is defined as <34% Ph + leukemic cells in the bone marrow, whereas a small response is defined as ≥34% but <90% Ph + leukemic cells in the marrow. Combination therapy: Combined use of Interferon alfa-2b and cytarabine (Ara-C), administered during the first 12 months of treatment, significantly increased the rate of high cytogenetic responses and significantly increased overall survival after 3 years compared to the use of interferon alfa-2b as monotherapy .Multiple myeloma: as maintenance treatment in patients who achieved objective remission (more than 50% reduction in myeloma protein concentration) as a result of induction chemotherapy. Current clinical experience indicates that maintenance treatment with interferon alfa-2b extends the duration of the plateau phase; however, the impact on overall survival has not been definitively demonstrated.Follicular lymphoma: treatment of follicular lymphoma of high tumor mass as a complement to proper, combined, induction chemotherapy, such as in CHOP-like schemes. The large mass of the tumor is determined by the finding of at least one of the following symptoms: one major tumor site (> 7 cm), involvement of three or more lymph node groups (each> 3 cm), general symptoms (weight loss> 10%, fever> 38 ° C for more than 8 days or night sweats), enlargement of the spleen below the navel, obstruction of large organs or pressure syndrome, orbital or epidural space involvement, serous exudate or leukemia.carcinoid: treatment of carcinoids with metastases to lymph nodes or to the liver and with "carcinoid syndrome".Malignant melanoma: as an adjunctive treatment in patients who have had surgery removed, but who have a high risk of generalized relapse, e.g. patients with primary or recurrent (clinically or histologically detected) involvement of the lymph nodes.

1 multidose dispenser (1.2 ml) contains 18 million or 30 million IU interferon alfa-2b. 1 multi-dose vial (2.5 ml) contains 25 million IU interferon alfa-2b.

The preparation is a sterile, stable form of highly purified interferon alfa-2b obtained by recombinant DNA. Recombinant interferon alfa-2b is a water soluble protein with a molecular weight of about 19,300 daltons. It is obtained from the strainE. coliin which the genetically modified plasmid containing the interferon alpha-2b gene derived from human leukocytes was inserted. Interferons act on the cell by binding to specific receptors on the cell surface. After binding to the cell membrane, interferon initiates a sequence of intracellular events, including the induction of specific enzymes. It is believed that this process at least partially determines various cellular responses to Interferon, including inhibition of viral replication in infected cells, suppression of cell proliferation, and immunomodulatory activities such as stimulation of phagocytic activity of macrophages and stimulation of cytotoxic activity of lymphocytes relative to target cells. Each of these mechanisms may consist of a therapeutic effect of interferon. Recombinant interferon alfa-2b showed anti-proliferative activity. In conditionsin vitro high immunomodulatory activity has been demonstrated. Recombinant interferon alfa-2b inhibits viral replication under conditionsin vitro, howin vivo. Although the exact mechanism of action of recombinant interferon alfa-2b is unknown, it appears that the drug changes the metabolism of the host cell. This leads to the inhibition of viral replication, and if it does, the daughter virions are unable to leave the host cell. Maximum concentration C_max after subcutaneous and intramuscular administration occurred 3-12 h after the lowest dose and 6-8 h after the highest dose. The elimination half-life of interferon was approximately 2-3 h and 6-7 h, respectively.

Hypersensitivity to the active substance or to any of the excipients. Previously exposed severe cardiac disease, e.g. untreated congestive heart failure, recent myocardial infarction, severe arrhythmias. Severe renal or hepatic impairment, including metastases. Epilepsy and / or central nervous system disorders. Chronic hepatitis with decompensated liver cirrhosis. Chronic hepatitis in patients receiving current or recent immunosuppressive therapy, except for short-term treatment with corticosteroids. Autoimmune hepatitis; an autoimmune disease in a history; patients after organ transplants, undergoing immunosuppressive therapy. Previously revealed thyroid disease, unless it can be controlled by conventional treatment. Associated use with telbivudine. Children and adolescents: severe psychiatric disorders present or in the interview, especially severe depression, suicidal thoughts or suicide attempts. Combination therapy with ribavirin: see also ribavirin SPC if interferon alfa-2b is used in combination with ribavirin in patients with chronic hepatitis C.

In some patients, severe post-mortem symptoms, in particular depression, suicidal thoughts and suicide attempts have been observed during and even after completion of the treatment, mainly within 6 months of discontinuation of treatment. During treatment with the formulation in combination with ribavirin and 6 months after its completion, suicidal ideation and attempts were more common among children and adolescents than among adults (2.4% vs 1%). As in adults, other psychiatric adverse events were found in children and adolescents (eg depression, emotional lability and drowsiness). Other o.u.n. symptoms have been observed during treatment with alpha interferons, including aggressive behavior (sometimes directed against others, ie images of behaviors that threaten people's lives), bipolar disorder, mania, confusion and mental state disorders. It is recommended to monitor closely whether the patient has any signs or symptoms of mental disorders. If these side effects occur, the treating physician must take into account the risk they may pose and consider the need for appropriate medical treatment. If symptoms of mental disorders persist or worsen or if suicidal ideation is diagnosed, discontinuation of treatment with the preparation is recommended. The patient should undergo psychiatric treatment if necessary. If the need for interferon alfa-2b treatment has been identified in adult patients with severe psychiatric conditions, either present or in history, treatment should only be started once the appropriate individual diagnosis has been made and appropriate medical treatment has been implemented. The use of interferon alfa-2b in children and adolescents with severe or current psychiatric history is contraindicated. In patients infected with HCV who have disorders related to substance abuse (alcohol, cannabis, etc.), there is an increased risk of developing new or exacerbating existing mental disorders during treatment with interferon alpha.If these patients are considered to be required for use of interferon alpha, it should be determined before starting treatment that the patient is free from mental illness and carefully assess the possibility of using other psychoactive substances and implement appropriate measures. If necessary, a multidisciplinary approach to the problem should be considered, including the participation of a specialist in the field of mental health or an addiction specialist in the assessment process, treatment and further observation of the patient. During and after treatment, the patient should be closely monitored. If psychiatric or psychoactive disorders occur or recur, early intervention is recommended. During combination therapy with interferon (standard and pegylated) with Ribavirin, lasting up to 48 weeks in patients from 3 to 17 years of age, weight loss and growth retardation have often been reported. Available data over a longer period of time for children receiving combination therapy with standard interferon with ribavirin also indicate a significant slowdown in growth (15% reduction in height compared to baseline values) in 21% of children, despite not using treatment for more than 5 years. The expected benefits of treatment should be carefully weighed against the safety results observed in clinical trials in children and adolescents. It is important to take into account that the combination therapy induced growth inhibition, it is uncertain whether transient. This risk should be considered in the light of the characteristics of the disease in a child, such as symptoms of disease progression (particularly fibrosis), co-morbidities that may have an adverse effect on disease progression (such as concurrent HIV infection) as well as prognostic factors (HCV genotype). and viral load). If possible, the child should be treated after the end of puberty to reduce the risk of stunting. No data on long-term effects on sexual maturation. If during the course of treatment acute hypersensitivity reactions occur, the drug should be discontinued and appropriate treatment should be given. Any patient who develops liver abnormalities during treatment with the product should be closely monitored and treatment should be discontinued if symptoms improve. The treatment should be discontinued in patients with chronic hepatitis who have an increased prolongation of coagulation time, which may indicate liver decompensation. During the treatment or up to 2 days after the end of treatment, there may be a reduction in blood pressure, which may require supportive care. Patients treated with the product should maintain adequate hydration, as some patients have experienced decreases in blood pressure associated with decreased fluid volume. Refilling liquids may be necessary. Caution in patients with a severe general condition, eg with a history of lung disease (eg chronic obstructive pulmonary disease) or diabetes mellitus who are prone to ketoacidosis and in patients with bleeding disorders (eg thrombophlebitis, pulmonary embolism) ) and with severe bone marrow suppression. Lung infiltrates, interstitial pneumonitis and pneumonia, sometimes fatal to the patient, were reported more frequently when shosaikoto, a Chinese herbal medicine, was used concomitantly with interferon alpha. Any patient with a fever, cough, shortness of breath or other respiratory disorders should undergo a chest X-ray. If the pulmonary picture shows pulmonary infiltrates or signs of respiratory distress, the patient should be closely monitored and, if necessary, discontinued with interferon alpha therapy. Discontinuation of the medicinal product should be considered in patients who develop new or worsening existing eye disease. A preliminary ophthalmologic examination should be performed on each patient. Any patient complaining about changes in visual acuity or field of vision or reporting other ophthalmologic symptoms during treatment with the preparation must be promptly subjected to a full ophthalmologic examination. Periodic visual examinations during treatment with the preparation are recommended especially in patients with diseases associated with retinopathy, such as diabetes or hypertension.Adult patients with a history of congestive heart failure should be monitored closely after a history of myocardial infarction and / or previous or current cardiac arrhythmias that require treatment with the preparation. It is recommended that patients with cardiac disease and / or advanced stage cancer should undergo an electrocardiogram before and during treatment. No data on children and adolescents with a history of heart disease. Hyertriglyceridemia (sometimes severe) occurred or increased during treatment - monitoring of blood lipids is recommended. Due to reports that interferon alpha intensifies psoriasis and sarcoidosis, the use of the preparation in patients with psoriasis or sarcoidosis is recommended only if the potential benefits outweigh the risks. Preliminary data suggest that treatment with interferon alpha may be associated with an increase in the rejection rate of the kidney. Liver rejection was also reported. The development of autoantibodies and the development of autoimmune diseases during treatment with alpha interferons has been reported. An increased risk may occur in patients predisposed to the development of autoimmune diseases. Patients with autoimmune disease-related symptoms should be carefully evaluated and the risk / potential repercussions of continued interferon alpha treatment should be re-determined. In patients with hepatitis C treated with interferon, cases of Vogt-Koyanagi-Harada syndrome (VKH) have been reported - if VKH syndrome is suspected, antiviral therapy should be discontinued and further corticosteroid therapy should be considered. In patients who are co-infected with HIV and undergoing HAART, there is an increased risk of developing lactic acidosis. Special care should be taken when adding the preparation and ribavirin to HAART therapy. Patients treated with IntronA and ribavirin in combination with zidovudine may have an increased risk of developing anemia. In patients co-infected with HCV and HIV, with advanced cirrhosis, undergoing HAART, there may be an increased risk of hepatic decompensation and death. Addition of alpha interferon alone or in combination with ribavirin may increase the risk in this subgroup of patients. Administration of the preparation in combination with other chemotherapeutics (eg Ara-C, cyclophosphamide, doxorubicin, teniposide) may lead to an increased risk of toxicity (severity and duration). The concomitant use of these medicines can be life-threatening or fatal. The most commonly reported, potentially life threatening or fatal adverse reactions are: mucositis, diarrhea, neutropenia, kidney damage and electrolyte disturbances. Due to the risk of increased toxicity, it is necessary to adjust the doses of both the preparation and the concurrently administered chemotherapeutic agents. During the concomitant use of interferon alfa-2b and hydroxycarbamide medicines, the incidence and severity of symptoms associated with subcutaneous nodular vasculitis may increase. The level of TSH in the serum should be determined before starting treatment for chronic hepatitis C. Treatment with the preparation can be started if the TSH level can be maintained within the normal range by medication. The TSH level should be determined if the patient develops signs of thyroid dysfunction during treatment. Children and adolescents should be examined every 3 months to detect thyroid dysfunction (eg TSH). If the drug is used in combination with ribavirin, all patients diagnosed with chronic hepatitis C had a biopsy of the liver prior to qualifying for treatment, but in some cases (eg patients with genotype 2 and 3) it may be possible to start treatment without histological confirmation. The current treatment guidelines should clarify whether liver biopsy is required before treatment. The standard hematological and biochemical tests (morphology with smear, platelet count, electrolytes, hepatic enzymes, serum protein, bilirubin and serum creatinine) should be performed before each treatment and periodically during treatment. During the treatment of hepatitis B or C the following pattern is recommended: 1st, 2nd, 4th, 8th, 12th and 16th week and then every 2th.one month to stop treatment. If during treatment with the preparation the ALT activity increases at least twice in relation to the initial value, treatment with the preparation may be continued until subjective and objective symptoms of hepatic failure occur. During the period of increased ALT, tests should be performed every 2 weeks to assess liver function: ALT, prothrombin time, alkaline phosphatase, albumin and bilirubin. In patients treated for malignant melanoma, evaluation of liver function and leukocytosis with a smear must be performed weekly during the induction phase of treatment and monthly in the maintenance phase.

The preparation can be used during pregnancy only if the potential benefits outweigh the potential risk to the fetus. There are no adequate data on the use of interferon alfa-2b in pregnant women. Animal studies have shown reproductive toxicity. In the case of combination therapy with ribavirin, the use of this therapy in pregnant women is contraindicated (ribavirin causes severe congenital malformations). It is not known if the components of the preparation are excreted in human milk. Because of the potential for side effects in fed infants, breast-feeding should be discontinued prior to treatment. Women of childbearing potential must use effective contraception during treatment. Interferon may reduce fertility - in women treated with human leukocyte interferon, there is a reduction in estradiol and Progesterone levels, and caution should be exercised in fertile men. In the case of combination therapy with ribavirin, also 4 months after the end of treatment, use effective contraception in the treatment of women of childbearing age and 7 months after treatment for men and their female partners.

Adults. Very common: pharyngitis, viral infection, leukopenia, anorexia, depression, insomnia, anxiety, emotional instability, agitation, nervousness, dizziness and headache, impaired concentration, dry mouth, blurred vision, shortness of breath, cough, nausea, vomiting , abdominal pain, diarrhea, stomatitis, dyspepsia, alopecia, pruritus, dry skin, rash, increased sweating, muscle pain, joint pain, musculoskeletal pain, injection site inflammation, injection site reaction, fatigue, stiffness, fever , flu-like symptoms, asthenia, irritability, chest pain, malaise, weight loss. Common: bronchitis, sinusitis, herpes simplex, rhinitis, thrombocytopenia, lymphadenopathy, lymphopenia, hyperthyroidism or hypothyroidism, hypocalcaemia, dehydration, hyperuricemia, thirst, confusion, sleep disorders, decreased libido, tremors, paresthesia, hypoesthesia, migraine, hot flushes, drowsiness, taste disturbances, conjunctivitis, abnormal vision, lacrimal gland dysfunction, eye pain, tinnitus, dizziness, palpitation, tachycardia, hypertension, epistaxis, nasal bleeding, respiratory disorders, congestion of the mucous membrane nose, watery nose, dry cough, ulcerative oral mucosa, right upper abdominal pain, tongue inflammation, gingivitis, constipation, loose stools, hepatomegaly, psoriasis or worsening of symptoms, maculopapular rash, lupus rash, eczema , erythema, skin diseases, arthritis, frequent cz, amenorrhea, breast pain, menstrual disorders, bleeding from the genital tract, disturbances of the menstrual cycle, vaginal disorders, pain at the injection site. Uncommon: bacterial infections, peripheral neuropathy. Rarely: pneumonia, sepsis, suicidal thoughts, retinal infiltration, retinopathies (including macular edema), retinal artery or vein occlusion, optic neuritis, congestive disc, loss of visual acuity or visual field, symptom of "cotton wool", cardiomyopathy. Very rare: aplastic anemia, sarcoidosis, exacerbation of sarcoidosis, diabetes, worsening of diabetes, hyperglycemia, hypertriglyceridemia, increased appetite, suicide, suicide, aggressive behavior (sometimes directed against others), psychosis (also with hallucinations), cerebrovascular hemorrhage, ischemia cerebrovascular, convulsions, impaired consciousness, encephalopathy, deafness, impaired hearing, myocardial ischemia or infarction, peripheral ischemia, hypotension, pulmonary infiltrates,pneumonia, pancreatitis, ischemic colitis, ulcerative colitis, bleeding from the gums, toxic liver damage (also fatal), Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, rhabdomyolysis, myositis, leg cramps, back pain, renal dysfunction, renal failure, nephrotic syndrome, injection site necrosis, facial edema. Clinically significant abnormalities in laboratory tests occurring most frequently after administration of doses higher than 10 million IU. daily, there was a reduction in the number of granulocytes and leukocytes; reduction in hemoglobin and platelet counts; increase in alkaline phosphatase and LDH and serum creatinine and urea nitrogen. Aplastic anemia with moderate and usually transient anemia was observed. Increased serum ALT / AST was observed in some patients who did not have hepatitis and hepatitis B, which may be associated with the elimination of viral DNAp.
Children. Very common: viral infections, pharyngitis, anemia, neutropenia, hypothyroidism, anorexia, depression, emotional instability, insomnia, headache, dizziness, abdominal pain, diarrhea, nausea, vomiting, alopecia, rash, joint pain, muscle pain skeletal, muscle pain, injection site inflammation, injection site reaction, fatigue, fever, stiffness, flu-like symptoms, malaise, irritability, decrease in growth rate (decrease in height and / or body weight in relation to age). Common: fungal infections, bacterial infections, lung infections, otitis media, periodontitis, herpes, urinary tract infections, vaginitis, gastroenteritis, cancer (unspecified), thrombocytopenia, lymphadenopathy, hyperthyroidism, virilism, hypertriglyceridaemia, hyperuricemia, increased appetite, suicidal thoughts, aggressive reactions, confusion, behavior disorders, agitation, somnambulism, anxiety, nervousness, sleep disorders, unusual dreams, apathy, hyperkinesia, tremors, dysphonia, paresthesia, hypesthesia, hyperesthesia, concentration disorders, drowsiness, conjunctivitis, eye pain, abnormal vision, abnormalities of the lacrimal gland, hot flushes, paleness, shortness of breath, rapid breathing, nosebleeds, cough, nasal congestion, irritation of the nasal mucosa, watery runny nose, sneezing, mouth ulcer, ulcerative stomatitis oral cavity inflammation oral pain, right upper abdominal pain, dyspepsia, tongue inflammation, gastro-oesophageal reflux, rectal disorders, constipation, loose stools, toothache, tooth disorders, liver dysfunction, photosensitivity reactions, maculopapular rash, eczema, acne, skin disorders, nail disorders, skin discoloration, pruritus, dry skin, erythema, bruising, severe sweating, involuntary urination, urination disorders, urinary incontinence, amenorrhea, bleeding from genital tract, menstrual disorders, vaginal disorders, pain nuclei, chest pain, asthenia, swelling, pain at the injection site, skin damage.

Chronic hepatitis BThe recommended dose is in the range of 5 to 10 million IU. administered subcutaneously 3 times a week (every 2nd day) for a period of 4 to 6 months. The administered dose should be reduced by 50% in case of haematological disorders (white blood cell count <1500 / mm³granulocytes <1000 / mm³, platelets <100,000 / mm³). Treatment should be discontinued in case of severe leukopenia (<1200 / mm³), severe neutropenia (<750 / mm³) or severe thrombocytopenia (<70,000 / mm³). If the patient after 3-4 months of treatment (the maximum tolerated dose of the drug) has no improvement in serum HBV-DNA, treatment with the preparation should be discontinued.
Chronic hepatitis C: the preparation is administered to subcutaneous adults at a dose of 3 million IU. 3 times a week (every other day), both as monotherapy and in combination with ribavirin. Children 3 years of age or older and adolescents: the product is administered subcutaneously at a dose of 3 million IU / m² pc. 3 times a week (every 2nd day) in combination with ribavirin in the form of capsules or oral solution in two divided doses administered with a meal (morning and evening).Patients with relapse (adults): the preparation is given in combination with ribavirin. Based on the results of clinical trials, the data available for treatment for 6 months, it is recommended that patients be treated with the combination in combination with ribavirin for 6 months. Untreated patients: Adults: the effectiveness of the preparation is increased when it is used in combination with ribavirin; the preparation should be administered in monotherapy, mainly in the case of intolerance or contraindications to the use of ribavirin. Combination preparation with ribavirin: based on the results of clinical trials, the data available for treatment over 12 months, it is recommended that patients be treated with Viraferon in combination with ribavirin for at least 6 months. Treatment should continue for another 6 months. (ie a total of 12 months) in patients who do not have HCV-RNA at 6 months of treatment and who had high viral load of genotype 1 before treatment (as determined in a pre-treatment sample). To extend treatment up to 12 months, other negative prognostic factors (age> 40 years, male gender, liver fibrosis with bridging) should be taken into account. During clinical trials in patients who did not show a virological response after 6 months of treatment (HCV-RNA below the lower limit of detection), there was no sustained virological response (HCV-RNA below the lower limit of detection at 6 months after the end of the study). The preparation in monotherapy: the optimal duration of treatment with a single agent is not yet fully defined. It is recommended to use for a period of 12 to 18 months. It is recommended that the preparation is used alone for at least 3-4 months, and then determine HCV-RNA. Treatment should be continued in patients with a negative HCV-RNA test. Children and adolescents: the efficacy and safety of the preparation in combination with ribavirin has been studied in children and adolescents who have not been treated for chronic hepatitis C. Genotype 1: the recommended duration of treatment is 1 year. In patients who have no virological response after 12 weeks of treatment, the likelihood of obtaining a sustained virological response (negative prognostic value of 96%) is very low. It is recommended that children and adolescents receiving combination therapy with IntronA and ribavirin discontinue therapy if week 12 of HCV-RNA falls below <2 log₁₀ compared to the pre-treatment value or when HCV-RNA is detected at week 24 of treatment. Genotype 2/3: the recommended duration of treatment is 24 weeks
Hairy cell leukemia: the recommended dose is 2 million IU² pc., administered subcutaneously 3 times a week (every 2nd day) in both patients after splenectomy and those who did not have a splenectomy. In the majority of patients with hairy cell leukemia, normalization of one or more hematological variables occurs within one to two months of treatment with the preparation. Improvement in all three hematological parameters (granulocyte count, platelet count and hemoglobin) may require 6 or more months. This regimen should be maintained unless the disease is progressing rapidly or symptoms of severe intolerance appear.
Chronic myelogenous leukemia: the recommended dose of the preparation is 4 to 5 million IU² pc., administered subcutaneously daily. Some patients improved after using the product at a dose of 5 million IU² pc, administered subcutaneously daily, in combination with cytarybin (Ara-C) at a dose of 20 mg / m² pc, administered subcutaneously daily for 10 days a month (up to a maximum daily dose of 40 mg). After obtaining control over the number of white blood cells, the maximum tolerated dose of the preparation should be administered (4 to 5 million IU² pc. daily) to maintain haematological remission. The use of the preparation should be discontinued after 8 to 12 weeks if at least partial hematological remission or clinically significant reduction in the number of leukemic cells is not achieved.
Multiple myeloma: maintenance treatment: in patients in the plateau phase (more than 50% reduction in monoclonal protein) after initial induction chemotherapy, interferon alfa-2b can be administered as monotherapy, subcutaneously, at a dose of 3 million IU / m² pc. 3 times a week (every 2nd day).
Follicular lymphoma: in addition to chemotherapy, interferon alfa-2b may be administered subcutaneously at a dose of 5 million IU. three times a week (every other day) for 18 monthsThe use of CHOP-like regimens is recommended, but the clinical experience only applies to the CHVP scheme (cyclophosphamide, doxorubicin, teniposide and prednisolone).
carcinoid: the usual dose is 5 million IU (3 to 9 million IU), administered subcutaneously 3 times a week (every 2, day). Patients with advanced disease may require a daily dose of 5 million IU. Administration of the drug should be discontinued for the duration of the surgery and the postoperative period. Treatment can be continued as long as the patient responds to interferon alfa-2b treatment.
Malignant melanoma: as an induction treatment, interferon alfa-2b is administered intravenously at a dose of 20 million IU / m² pc. every day for 5 days a week for a period of 4 weeks; the calculated dose of interferon alfa-2b is added to 0.9% (9 mg / ml) sodium chloride solution for injection and given as a 20-minute infusion. A 10 million IU dose is recommended for maintenance treatment² pc. administered subcutaneously for 3 days a week (every other day), for 48 weeks If severe adverse reactions occur during interferon alfa-2b treatment, especially if the granulocyte count decreases <500 / mm³ or the ratio of ALT / AST are> 5 times above the upper limit of normal, the drug should be discontinued until the side effects disappear. Administration of interferon alfa-2b can be restarted using 50% of the previous dose. If intolerance persists after the dose adjustment or if the granulocyte count decreases <250 / mm³, or the AlAT / AspAT ratio will increase> 10 times the upper limit of normal, treatment with interferon alfa-2b should be discontinued. Although the optimal (minimum) dose required to achieve full clinical improvement is unknown, patients should be given the recommended doses and if they are toxic, reduce them as described above.