Index of drugs

Chronic hepatitis B. Treatment of chronic hepatitis B (pwzw B) with and without the presence of hepatitis B virus envelope antigen (ang-HBeAg), in adult patients with compensated liver disease, with signs of viral replication and with elevated ALT or with histologically confirmed inflammation and (or) liver fibrosis.Chronic hepatitis C. Adults. It is indicated in combination with other medicines for the treatment of chronic hepatitis C (CHC) in patients with compensated liver disease.Children and adolescents aged 5 and above. The preparation in combination with Ribavirin is indicated for the treatment of children aged 5 years and older and adolescents, patients with chronic hepatitis C, previously untreated, and with confirmed HCV RNA. When deciding on the implementation of combination therapy in children, it should be taken into account that this treatment may cause stunted growth. There is no certainty whether the inhibition of growth is reversible. The decision to initiate treatment should be made on a case-by-case basis.

1 amp-syringe. or the pre-filled pen (0.5 ml) contains 90 μg or 135 μg or 180 μg of peginterferon alfa-2a; the drug contains benzyl alcohol.

The pegylated form of Interferon alfa-2a is formed by coupling the interferon alfa-2a molecule with a PEG molecule (polyethylene bis-monomethoxylglycol). Peginterferon alfa-2a shows under conditionsin vitro antiviral and antiproliferative activity typical for interferon alfa-2a. In patients with chronic hepatitis C responding to treatment with peginterferon alfa-2a at a dose of 180 μg, the reduction of HCV RNA titer occurs in 2 phases: in the first phase the titer decreases within 24-36 h after the first dose of the preparation, in phase the second (in the Next 4-16 weeks) to reduce the titre occurs in those patients who eventually achieve a sustained virological response. Ribavirin in combination with peginterferon alfa-2a or interferon alpha does not have a significant effect on viral kinetics during the first 4-6 weeks. After administration of a single dose of 180 μg of the preparation by subcutaneous injection, the drug was detectable in the blood after 3-6 h. 24 h blood concentration reached about 80% of the maximum value. The absorption of the drug is prolonged over time, and the maximum concentration in the blood is reached 72-96 h after administration. The absolute bioavailability of peginterferon alfa-2a is 84%, similar to the bioavailability of interferon alfa-2a. Metabolism of the drug is not fully described, studies on rats indicate that the main organ eliminating radiolabelled preparation are kidneys. After intravenous administration, the half-life of peginterferon alfa-2a is 60-80 h, while the standard interferon is 3-4 h. The half-life after subcutaneous administration is longer and is 160 h on average (84-353 h). The half-life may reflect not only the elimination phase of the compound, but also the prolonged absorption of the preparation.

Hypersensitivity to the active substance, interferon alpha or to any of the excipients. Hepatitis on autoimmune etiology. Severe liver dysfunction or uncorrected liver cirrhosis. Interview with severe cardiac disease, including unstable or under-controlled heart disease over the last 6 months Co-morbid HIV-HCV infection and cirrhosis or Child-Pugh score ≥6, unless the increase in intermediate bilirubin has been caused only by such drugs like atazanavir and indinavir. Combination therapy with telbivudine. Newborns and children <3 years, due to the presence of benzyl alcohol in the preparation. The severe or psychiatric disorders present in the interview, particularly severe depression, suicidal thoughts or suicide attempts - concern children and adolescents.

When planning combination therapy with peginterferon alfa-2a and Ribavirin, please also refer to the Ribavirin SmPC. Patients with concomitant HCV and HIV infection should also be familiar with the SmPC for antiviral drugs that are used concomitantly with peginterferon alfa-2a and / or ribavirin.Due to the risk of psychiatric disorders and o.u.n., patients should be closely observed in this direction. In the event of such symptoms, the attending physician should consider the potential severity of these adverse drug reactions and assess the indications for the use of appropriate therapeutic agents. If psychiatric symptoms persist or become worse or if suicidal thoughts occur, it is recommended to stop the preparation, observe the patient and provide him with appropriate psychiatric help. If treatment with a preparation in a patient who is now or in the past has a serious mental illness is necessary in the physician's opinion, it can only be started if the patient is provided with appropriate, individualized diagnosis and therapy of mental disorders. The use of the preparation in children and adolescents with severe psychiatric conditions present or in the interview is contraindicated. Patients who are infected with HCV, who have comorbidities related to the use of substances (alcohol, cannabis, etc.) are exposed to an increased risk of psychiatric disorders or exacerbation of existing mental disorders during treatment with interferon alpha. If treatment with interferon alpha has been found to be necessary in these patients, prior to initiation of treatment, concomitant mental illness and potential misuse of other substances should be carefully evaluated and properly protected. If necessary, multidisciplinary patient care, including psychiatric care or the care of an addiction specialist, should be considered for the assessment, treatment and observation of the patient. Patients should be carefully monitored during treatment and even after treatment. Early intervention is recommended in the case of the re-emergence or development of mental disorders and the use of the above substances. During treatment with peginterferon alfa-2a in combination with ribavirin, lasting up to 48 weeks, weight loss and growth inhibition were commonly observed in patients aged 5-17 years. The expected benefits of treatment should be carefully weighed against the safety results observed in clinical trials in children and adolescents on a case-by-case basis. It is important to take into account that the combination therapy induced growth inhibition during the therapy period, and the reversibility of this disorder is uncertain. The risk should be considered in the light of the characteristics of the disease occurring in a child, such as symptoms of disease progression (especially 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. In all patients, standard haematological and biochemical tests are recommended prior to initiation of therapy. The following values ​​may be considered initial for the initiation of treatment: platelet count ≥ 90,000 / mm³; absolute neutrophil count ≥ 1500 / mm³; properly controlled thyroid function (TSH and T4). Hematologic tests should be repeated after 2 and 4 weeks, and biochemical tests - in the 4th week of treatment. Additional tests should be performed periodically throughout the therapy. Special care should be taken when administering the preparation together with other medicines that may inhibit bone marrow function. The combination of peginterferon alfa-2a and ribavirin in combination with azathioprine is not recommended due to pancytopenia and myelotoxicity observed during such combination therapy (interaction between ribavirin and azathioprine). There are no adequate studies on combination therapy with peginterferon alfa-2a with ribavirin in chronic hepatitis C in patients with previous therapy failure who discontinued previous therapy for haematopoietic side effects - risk and benefit should be considered before re-introduction. Due to the risk of thyroid dysfunction, the levels of TSH and T4 should be assessed before starting treatment. Treatment can be started or continued when it is possible to maintain TSH levels within the normal range using appropriate pharmacological treatment.During treatment, TSH should be measured if symptoms suggestive of thyroid dysfunction occur. Hypoglycaemia, hyperglycaemia and diabetes have been reported during treatment with interferon. If the above conditions are not adequately controlled by medication, the monotherapy with peginterferon alfa-2a or combination therapy with peginterferon alfa-2a with ribavirin should not be initiated. Patients in whom these conditions develop during treatment and can not be controlled with drugs should discontinue peginterferon alfa-2a or discontinue combination therapy with peginterferon alfa-2a and ribavirin. It is recommended that ECG be performed before starting treatment in patients with previously diagnosed cardiac disease. You should temporarily or completely stop treatment in case of deterioration of cardiovascular function. An indication to reduce the dose of ribavirin or stop administering it to patients with concomitant cardiovascular disease may also be the occurrence of anemia. Before starting treatment, a liver biopsy should be considered; the decision to perform a biopsy should be made in relation to the current recommendations. In patients with normal ALT, the progression of fibrosis is slower than in patients with elevated ALT. Therefore, before taking a decision about treatment, consider other criteria, eg virus genotype, patient's age, presence of extrahepatic manifestations of symptoms, risk of transmission of infection, etc. Treatment should be discontinued in patients with decompensated liver function during therapy. Treatment should be discontinued if the increase in ALT is progressive and clinically relevant despite dose reduction or if it is accompanied by an increase in direct bilirubin. In the event of severe, acute hypersensitivity reactions, treatment should be discontinued and appropriate treatment instituted immediately. Interruptive therapy does not require transient skin rashes. In patients receiving interferon alfa preparations, the development of anti-antibodies and autoimmune disorders was observed. Patients with a predisposition to develop autoimmune disorders may belong to the group of increased risk. Patients with symptoms characteristic of autoimmune disorders should be carefully evaluated; in this group of patients, the benefits and risks of continuing interferon therapy should be re-considered. Interferon therapy should be discontinued if Vogt-Koyanagi-Harada disease is suspected (VKH) and corticosteroid therapy should be considered. Fever may be associated with the syndrome of flu-like symptoms that are frequently reported during interferon treatment; other causes of persistence of fever should be excluded, in particular severe infections, especially in patients with neutropenia. In the case of severe bacterial, viral or fungal infections, appropriate treatment of infection should be implemented and consideration should be given to termination of interferon alpha therapy. All patients should have an ophthalmologic examination before starting treatment. Any patient reporting weakness or blindness must have a proper and complete eye examination. During the therapy, patients with previously diagnosed vision disorders (eg patients with diabetic or hypertensive retinopathy) should have periodic ophthalmologic examination. Treatment with the product should be discontinued in cases of worsening or new visual disturbances. Treatment with interferon should be discontinued in case of persistent infiltrates in the lung tissue, infiltrates of unclear origin or impaired lung function. The preparation should be used with caution in patients with psoriasis; if the symptoms of psoriasis occur or worsen, discontinue therapy. The safety and efficacy of the preparation with ribavirin in patients with transplanted liver and other organs has not been established (there is a risk of rejection of the transplanted organ). In patients with concomitant HIV infection who are on intensive antiretroviral therapy (HAART), there may be an increased risk of developing lactic acidosis - special care should be taken when adding the preparation and ribavirin to HAART (see ribavirin SPC). Patients with HIV infection and advanced cirrhosis who are both treated with HAART and ribavirin in combination with Interferon, including peginterferon alfa-2a, also have an increased risk of developing decompensated liver failure and death.Other factors that may be associated with a higher risk of hepatic decompensation in patients co-infected with HCV and HIV include: increased bilirubin, reduced hemoglobin, increased alkaline phosphatase or reduced platelet counts and didanosine. Patients treated with the preparation and ribavirin in combination with zidovudine have an increased risk of anemia - concomitant administration of ribavirin and zidovudine is not recommended. During treatment of patients infected with HCV and HIV, close observation of signs and symptoms of liver decompensation (including edema, encephalopathy, oesophageal variceal bleeding, dysfunction of liver function) should be carried out - treatment should be discontinued immediately in patients with hepatic decompensation. In patients with concomitant HIV-HCV infection, only limited data on efficacy and safety are available in patients with CD4 counts <200 cells / μl - caution should be used in the treatment of patients with low CD4 counts. Due to the observed tooth and periodontal disturbances in patients receiving peginterferon alfa-2a in combination with ribavirin, it is recommended to thoroughly clean the teeth twice a day and regularly check the condition of the teeth, and in case of vomiting, thorough rinsing of the mouth.

There are no adequate clinical data on the use of peginterferon alfa-2a in pregnant women. The preparation can be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Because of the potential for adverse reactions in breastfed babies, breast-feeding should be discontinued before starting treatment.
Combination therapy with ribavirin: ribavirin is teratogenic and / or embryotoxic. In pregnant women, treatment with ribavirin is contraindicated. Patients and partners of patients treated with the preparation in combination with ribavirin should take special precautions to avoid becoming pregnant. Women of childbearing potential must use effective contraception measures during treatment and for 4 months after treatment. Patients and their partners must use effective contraceptive measures during treatment and for 7 months after treatment (see ribavirin SPC).

Adverse reactions reported during treatment of patients with type B or C monotherapy, when combined with ribavirin in patients with type C and those observed post-marketing. Very common: anorexia, depression, anxiety, insomnia, headache, dizziness, impaired concentration, shortness of breath, cough, diarrhea, nausea, abdominal pain, alopecia, dermatitis, pruritus, dry skin, muscle pain, joint pain, fever, chills, pain, weakness, fatigue, reaction at the injection site, irritability. Common: upper respiratory tract infection, bronchitis, candidiasis of the mouth, herpes, fungal, viral and bacterial infections, thrombocytopenia, anemia, generalized enlargement of the lymph nodes, hypothyroidism, hyperthyroidism, aggression, mood changes, emotional disturbances, nervousness, decreased sex drive, fainting, weakness, migraine, memory disorders, hypoaesthesia, hypertension, paresthesia, tremor, disturbed taste, nightmares, drowsiness, blurred vision, eye pain, eye inflammation, conjunctival sclerosis, dizzy headache, earache, tachycardia , palpitations, peripheral edema, flushing, exercise dyspnea, nasal bleeding, nasopharyngitis, sinus congestion, nasal congestion, rhinitis, sore throat, vomiting, indigestion, dysphagia, mouth ulceration, bleeding from the gums, tongue inflammation, stomatitis, flatulence, dryness of the oral mucosa, psoriasis, urticaria, eczema, rash, increased sweating, skin changes, hypersensitivity to light, night sweats, back pain, arthritis, weakness of muscle strength, bone pain, neck pain, musculoskeletal pain, muscle cramps, impotence, chest pain, flu-like symptoms, malaise, lethargy, hot flushes, increased thirst, weight loss.Uncommon: pneumonia, skin infection, liver cancer, sarcoidosis, thyroiditis, diabetes, dehydration, suicidal thoughts, hallucinations, peripheral neuropathy, retinal haemorrhage, hearing loss, hypertension, wheezing, gastrointestinal bleeding, liver dysfunction. Rare: endocarditis, external otitis, pancytopenia, anaphylaxis, systemic lupus erythematosus, rheumatoid arthritis, diabetic ketoacidosis, suicide, psychotic disorders, coma, convulsions, facial nerve palsy, optic neuropathy, optic nerve edema, retinal vascular disorders , retinopathy, corneal ulceration, myocardial infarction, congestive heart failure, cardiomyopathy, angina, arrhythmias, atrial fibrillation, pericarditis, supraventricular tachycardia, cerebral haemorrhage, vasculitis, interstitial pneumonitis with pulmonary death, pulmonary embolism, peptic ulcer, pancreatitis, hepatic failure, cholangitis, fatty liver, myositis, renal insufficiency, overdose of the drug. Very rare: aplastic anemia, idiopathic or thrombotic thrombocytopenic purpura, loss of vision, toxic epidermal necrolysis, Stevens-Johnson syndrome, angioneurotic edema, erythema multiforme. Not known: sepsis, selective red cell aplasia, rejection of liver and kidney transplants, Vogt-Koyanagi-Harada disease, manic state, bipolar disorder, murderous thoughts, cerebral ischemia, serous retinal detachment, peripheral ischemia, ischemic enterocolitis, rhabdomyolysis. Increased ALT was observed (some patients required dose modification or drug withdrawal due to increased ALT), increased bilirubin, electrolyte disturbances (hypokalaemia, hypocalcaemia, hypophosphataemia), hyperglycaemia, hypoglycaemia and increased triglycerides. Treatment with the product was associated with a decrease in the hematological parameters (leukopenia, neutropenia, lymphopenia, thrombocytopenia and decrease in hemoglobin), which usually improved after dose modification and returned to pre-treatment values ​​4-8 weeks after treatment. Treatment with the preparation was associated with clinically significant deviations in the results of thyroid function tests, which required appropriate treatment. In 1 to 5% of patients treated with the preparation, neutralizing anti-interferon antibodies were produced. With the exception of fever, the incidence of most adverse reactions was noticeably lower in HBV patients treated with the monotherapy as compared to HCV patients treated with the monotherapy. In patients with concomitant HIV-HCV infection, the clinical profile of adverse reactions of the preparation used as monotherapy or in combination with ribavirin was similar to that observed in patients with HCV monoinfective therapy. In patients with co-existing HIV-HCV infection, the following side effects were reported with the frequency ≥ 1% and 2% during ribavirin combination: lactic acidosis, influenza, pneumonia, emotional instability, listlessness, tinnitus, pharyngeal pain, lip gloss, acquired lipodystrophy and chromaturia. Treatment with the preparation was associated with a reduction in the total CD4 + cell count over the first 4 weeks without reducing the percentage of CD4 + lymphocytes. This effect was reversible and resolved after dose reduction or discontinuation of therapy. Application of the preparation had no negative effect on HIV RNA control values ​​during treatment or follow-up after treatment.Children and youth. In general, the safety parameters observed in children and adolescents were similar to those seen in adults. The following adverse reactions were observed in children and adolescents infected with HCV during combination therapy with peginterferon alfa and ribavirin. Very common: reduced appetite, insomnia, headache, gastrointestinal disturbances, rash, pruritus, alopecia, musculoskeletal pain, flu-like symptoms, injection site reaction, irritability, fatigue. Common: infectious mononucleosis, streptococcal pharyngitis, influenza, viral gastroenteritis, candidiasis, gastroenteritis, periodontium abscess, barley, urinary tract infection, nasopharyngitis, anemia, hyperglycemia, type 1 diabetes, depression, anxiety, hallucinations, behavioral disorders, aggression, anger, attention deficit with hyperactivity, dizziness,attention disorders, migraine, transient loss of vision, retinal excursion, visual disturbances eye irritation, eye pain, pruritus of the eyes, earache, shortness of breath, nosebleed, epigastric pain, stomatitis, nausea, abdominal discomfort, abdominal pain, aphthous stomatitis, oral disorders, face edema, drug-induced rash, back pain, limb pain, dysuria, urinary incontinence, urinary tract disorders, vaginal discharge, fever, hematoma at the site of injection into the blood vessel, pain, mental disorders , tooth extraction, cholecystectomy, learning difficulties. In children and adolescents, growth inhibition and delayed weight gain were observed.

Treatment should only be started by a doctor who has experience in the treatment of hepatitis B or C patients. Before using the combination therapy of peginterferon alfa-2a with ribavirin, the Ribavirin SmPC should also be consulted. Monotherapy in the treatment of hepatitis C should be taken into account only in case of contraindications to the use of other medications.Adults. Chronic hepatitis B (with the presence of HBeAg antigen and without): the recommended dose of peginterferon alfa-2a is 180 μg once a week for 48 weeks as a subcutaneous injection into the abdomen or thigh area.Chronic hepatitis C - patients who have not been treated beforeThe recommended dose of peginterferon alfa-2a is 180 μg once a week as a subcutaneous injection into the abdomen or thigh area, in combination with orally administered ribavirin or monotherapy. Ribavirin should be taken during meals; the recommended daily dose of ribavirin should be taken in two divided doses (morning and evening). The recommended daily dose of ribavirin (depending on the patient's weight) and the duration of the combination therapy (depending on the viral genotype) - double therapy with Pegasys and ribavirin are given below. Genotype 1 with viremia before treatment ≤800,000 IU / ml and HCV RNA undetectable at 4 and 24 weeks of treatment: patients with mc. <75 kg - 1000 mg, patients with ≥ 75 kg - 1200 mg, duration of treatment 24 weeks or 48 weeks. Genotype 1 with viral load> 800,000 IU / ml and HCV RNA not detectable at 4 and 24 weeks: patients with <75 kg - 1000 mg, patients with ≥75 kg - 1200 mg, duration of treatment 48 weeks. Genotype 4 with HCV RNA undetectable on 4 and 24 weeks: patients with mc. <75 kg - 1000 mg, patients with ≥75 kg - 1200 mg, duration of treatment 24 weeks or 48 weeks. Genotype 1 or 4 without a rapid virological response on the 4th and 24th weeks: patients with <75 kg - 1000 mg, patients with ≥75 kg - 1200 mg, treatment time 48 weeks Genotype 2 or 3 without rapid virologic response in 4 weeks: 800 mg, duration of treatment 24 weeks. Genotype 2 or 3 with viral load ≤800,000 IU / ml with negative HCV RNA in 4 weeks: 800 mg, duration of treatment 16 weeks or 24 weeks. Genotype 2 or 3 with viral load> 800,000 IU / ml with negative HCV RNA in 4 weeks: 800 mg, duration of treatment 24 weeks. infected with a genotype 5 or 6 virus - recommended dosage of ribavirin: 1000 mg (1200 mg) daily for 48 weeks. The decision on the duration of treatment should be made on the basis of additional factors such as fibrosis degree and tolerability of combination therapy. The recommended duration of treatment with peginterferon alfa-2a monotherapy is 48 weeks.Chronic hepatitis C - previously treated patientsThe recommended dose of peginterferon alfa-2a in combination with ribavirin is 180 μg administered once a week by subcutaneous injection. For patients with mc. <75 kg and ≥ 75 kg, doses of ribavirin should be 1000 mg daily and 1200 mg daily. Patients who have been detected in the 12th week should stop treatment. The recommended total duration of therapy is 48 weeks; in patients infected with genotype 1 of the virus, not responding to previous combination therapy with peginterferon and ribavirin, the recommended total duration of therapy is 72 weeks.Co-existing HIV-HCV infection: the recommended dose of peginterferon alfa-2a used alone or in combination with ribavirin is 180 μg once a week for 48 weeks subcutaneously. For patients infected with HCV genotype 1 and mc. <75 kg and ≥ 75 kg, doses of ribavirin should be 1000 mg daily and 1200 mg daily. Patients infected with HCV with a genotype other than 1 should receive 800 mg ribavirin daily. The treatment time shorter than 48 weeks is not sufficiently studied. Also see the SmPC for use in combination with Pegasys.Dose modification for side effects. If it is necessary to reduce the dose of peginterferon alfa-2a caused by moderate or severe side effects, it is usually sufficient for an initial reduction of 135 μg per week. In some cases, further reduction to 90 μg or 45 μg may be required. Re-increasing the dose or returning to the initial dose may be considered if the severity of side effects decreases.The recommended dose modification in case of haematological toxicity: absolute neutrophil count (ANC) <750 / mm³ - reduce the dose of peginterferon to 135 μg or 90 μg or 45 μg, with a value of <500 mm³ - discontinue peginterferon treatment until the ANC value reaches> 1000 / mm³ (treatment can then be resumed at an initial dose of 90 μg and monitor the number of neutrophils); platelet count <50,000 / mm³ - reduce the dose of peginterferon to 135 μg or 90 μg or 45 μg, with a value of <25,000 / mm³ - discontinue combination treatment; hemoglobin (Hb) in patients without cardiovascular disease <10 g / dl - reduce the dose of ribavirin to 600 mg (reintroduction of the ribavirin initial dose is not recommended), with a value <8.5 g / dl - discontinue ribavirin; reduction of Hb in patients with stable cardiovascular disease ≥2 g / dl during the next 4 weeks in any treatment period - reduce the dose of ribavirin to 600 mg (return to the initial dose of ribavirin is not recommended), while maintaining the concentration Hb <12 g / dl despite treatment for 4 weeks with a reduced dose - discontinue ribavirin. If the abnormality disappears, treatment with ribavirin 600 mg per day may be resumed; further increase of the dose to 800 mg daily depends on the individual decision of the treating physician. A return to the initial dose is not recommended. In the case of ribavirin intolerance, treatment with peginterferon alfa-2a should be continued as monotherapy.The recommended dose modification in case of hepatotoxicity. In patients with type C, there are often variations in abnormal liver function values ​​- if a gradual increase or sustained increase in ALT activity is observed, the dose of peginterferon should initially be reduced to 135 μg; if ALT increases are still despite dose reduction, or if there is an increase in bilirubin or signs of decompensated liver failure in addition to an increase in ALT, treatment should be discontinued. In patients with type B, there is often a transient increase in ALT, sometimes up to 10 times ULN (upper limit of normal). Treatment should not generally be initiated if ALT exceeds 10 x ULN. Consideration should be given to continuing therapy with more frequent monitoring of liver function at the time of ALT increase. If the dose of peginterferon is reduced or the medication is discontinued, treatment can be resumed after the correct values ​​of the parameter discussed have returned.Special groups of patients. Elderly patients do not need to modify the dosage of peginterferon alfa-2a. In patients with end-stage renal disease, treatment should be initiated at 135 μg; regardless of the initial dose and severity of renal insufficiency, patients should be closely monitored and if adverse reactions occur, the dose should be reduced accordingly. The safety and efficacy of peginterferon alfa-2a has been demonstrated when used in patients with compensated cirrhosis (Child-Pugh A group); the safety and efficacy of peginterferon alfa-2a in patients with decompensated cirrhosis (Child-Pugh B or C or those with esophageal varices) has not been evaluated.Children and youth. Peginterferon should be used in ampoules, as only this type of packaging allows for proper dosage modification. In patients who are started on treatment before age 18, pediatric doses should be maintained until the end of therapy. The experience with the use of peginterferon in the treatment of children and adolescents aged 3 to 5 years with HCV infection or children and adolescents in whom previous treatment was inappropriate is very limited. There are no data on children and adolescents with co-existing HCV-HIV infection or with impaired renal function. The weekly dose of peginterferon alfa-2a in children and adolescents aged 5-17 is calculated on the basis of the body surface area (pc.) And is: pc. 0.71-074 m² - 65 μg / week; pc. 075-1.08 m² - 90 μg / wk; pc 1.09-1.51 m² - 135 μg / week; pc. > 1.51 m² - 180 μg / week Peginterferon should not be used in children. <0.71 m²because there is no data available for this subpopulation. The daily dose of ribavirin is calculated on the basis of body weight (body weight) and is about 15 mg / kg / day given in 2 divided doses.The duration of treatment with peginterferon in combination with ribavirin in children and adolescents with type C virus depends on the genotype of the virus. Patients infected with genotype 2 or 3 should take the drug for 24 weeks, whereas patients infected with other genotypes should be treated for 48 weeks. Patients who are still detectable after 24 weeks of treatment with HCV RNA should discontinue them because they have a sustained response Virology is unlikely as a result of further treatment.Dose modification for side effects. If you experience signs of toxicity that may be associated with the administration of peginterferon and / or ribavirin, the dose of one or both of these medicines may be reduced. In addition, ribavirin or combination therapy with peginterferon and ribavirin may be discontinued. Ribavirin should never be used as monotherapy. Unless otherwise stated, all other signs of toxicity should be followed according to the recommendations for adult patients. Depending on the nature of the toxicity symptoms, before discontinuation or final discontinuation of peginterferon alfa-2a is considered, the dosage may be adjusted by up to 3 levels, according to the following schedule: starting dose of peginterferon 65 μg - reduction by one level to 45 μg, by 2 levels up to 30 μg, 3 levels up to 20 μg; starting dose of 90 μg - reduction by one level to 65 μg, by 2 levels to 45 μg, by 3 levels to 20 μg; initial dose of 135 μg - reduction by one level to 90 μg, by 2 levels to 65 μg, by 3 levels to 30 μg; initial dose 180 μg - reduction by one level up to 135 μg, by 2 levels up to 90 μg, by 3 levels up to 45 μg.The recommended dose modification of peginterferon alfa-2a in case of haematological toxicity. Neutropenia 750-999 / mm³: weeks 1-2 - immediate correction of the dosage by 1 level; 3-48 weeks - without modification. Neutropenia 500-749 / mm³: weeks 1-2 - discontinue peginterferon until> 750 / mm³, then re-treat with a dose adjustment by 1 level, evaluate weekly for 3 consecutive weeks to see if the absolute neutrophil count is> 750 / mm³; 3-48 weeks - immediate correction of dosage by one level. Neutropenia 250-499 / mm³: weeks 1-2 - discontinue peginterferon until> 750 / mm³, then resume treatment with a dose correction of 2 levels; 3-48 weeks - discontinue peginterferon until> 750 / mm³, then resume treatment with a dose adjustment of 1 level. Neutropenia <250 / mm³ or neutropenia with fever - stop treatment.The recommended dose modification of peginterferon alfa-2a in case of hepatotoxicity. For prolonged or increasing ALT elevations to ≥5 and <10 x ULN, reduce the dose by one level and control ALT once per week to ensure that it is stable or is reduced. In case of long-term ALT ≥10 x ULN, treatment should be discontinued. In the event of toxicity symptoms associated with ribavirin treatment, such as anemia during treatment, the full dose of ribavirin should be reduced from approximately 15 mg / kg / day to approximately 7.5 mg / kg / day.Method of administration: the drug should be injected subcutaneously in the abdomen or thigh area. Administration in the arm decreases the effectiveness of the dose. After proper training, the drug can be administered by the patient either alone or through a carer.