Index of drugs

Adults (triple therapy). The preparation, in combination with Ribavirin and boceprevir (triple therapy), is indicated for the treatment of chronic hepatitis C virus (HCV), caused by genotype 1 infection, in adult patients (aged 18 years and over) with compensated liver disease, previously untreated or after previous treatment failure. Before starting combination therapy with ribavirin and boceprevir, refer to the Summary of Product Characteristics (SmPC) of ribavirin and boceprevir.Adults (dual therapy and monotherapy). It is indicated for the treatment of adult patients (18 years and above) with chronic hepatitis C virus who have HCV RNA (HCV-RNA), including patients with compensated cirrhosis and / or concomitant infection HIV, with a clinically stable form of the disease. The preparation in combination with ribavirin (bitherapy) is indicated for the treatment of chronic hepatitis C in adult previously untreated patients, including patients co-infected with HIV, with clinically stable disease, and adult patients who have failed their previously used treatment combination therapy with Interferon alpha (pegylated or non-pegylated) with ribavirin or treatment with interferon alfa monotherapy. Monotherapy with Interferon, including the preparation, is indicated mainly in the case of ribavirin intolerance or contraindications to its use. The ribavirin SmPC should be consulted prior to initiation of combination therapy with ribavirin.Children and adolescents (dual therapy). It is indicated in combination regimen with ribavirin in the treatment of children 3 years of age and above and adolescents, patients with chronic hepatitis C previously untreated, without signs of liver decompensation and with confirmed HCV-RNA. When deciding not to abstain from treatment until adulthood, it should be taken into account that the combination therapy caused growth inhibition, which in some patients may be irreversible. The decision to initiate treatment should be made on a case-by-case basis. Before starting the combination treatment with the preparation and Ribavirin, read the SPC ribavirin capsules or oral solution.

1 pre-filled pen contains 50 μg, 80 μg, 100 μg, 120 μg or 150 μg of peginterferon alfa-2b in 0.5 ml per protein. Each pre-filled pen delivers 50 μg, 80 μg, 100 μg, 120 μg or 150 μg of peginterferon alfa-2b in 0.5 ml when reconstituted as recommended. The product contains sucrose (40 mg / 0.5 ml).

Recombinant interferon alfa-2b, covalently linked to monomethoxypolyethylene glycol. The biological activity of the preparation comes from the interferon alfa-2b molecule contained therein. Interferons work by connecting to specific membrane receptors on the surface of cells. When combined with the cell membrane, interferon initiates a sequence of intracellular reactions involving the induction of certain enzymes. It is believed that this process at least partially determines various types of cellular responses to interferon, including inhibition of viral replication in virus-infected cells, inhibition of cell proliferation, and immunomodulatory effects, such as altering phagocytic activity of macrophages and enhancing specific cytotoxicity of lymphocytes relative to target cells. Each of the mentioned activities, or all together, may determine the healing effects of interferon. Recombinant interferon alfa-2b also inhibits viral replication under conditionsin vitro andin vivo. Although the precise mechanism of antiviral activity of recombinant interferon alfa-2b is unknown, it appears to alter the metabolism of the host cell. This action causes inhibition of viral replication, and if replication occurs, daughter virions are unable to leave the cell. The half-life of the plasma formulation is prolonged compared to the half-life of non-pegylated interferon alfa-2b.Peginterferon has the ability to convert to free interferon alfa-2b by depegylation. The biological activity of pegylated isomers is qualitatively similar but weaker than the activity of free interferon alfa-2b. After subcutaneous administration of preparation C_max occurs between 15 and 44 h after administration and lasts for 48-72 h after administration. Medium T_0,5 preparation in the elimination phase is about 40 hours.

Hypersensitivity to the active substance, to any interferon or to any of the excipients. Severe history of a history of heart disease, including unstable or untreatable heart disease in the last 6 months. Severe, debilitating underlying disease. Autoimmune hepatitis or other autoimmune disorders. Severe dysfunction or decompensated liver cirrhosis. Previously diagnosed thyroid disease that can not be treated with conventional methods. Epilepsy and / or central nervous system dysfunction. Patients co-infected with HCV and HIV with cirrhosis and Child-Pugh score ≥6. 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: if the preparation is used in combination therapy in patients with chronic hepatitis C, see also the SPC of ribavirin and boceprevir.

During treatment with the preparation, or even after its completion, severe symptoms from o.u.n. and mental state disorders. It is recommended to carefully monitor the patient for any signs or symptoms of mental disorders. If these side effects occur, your doctor will consider the need for appropriate medical treatment. If the symptoms of mental disorders persist or worsen or if suicidal thoughts are found, discontinuation of treatment with the preparation is recommended, and the patient should undergo psychiatric treatment, if necessary. If there is a need for peginterferon alfa-2b treatment in patients with a history of severe or recent psychiatric conditions, treatment should be started only after ensuring that the correct individual diagnosis has been made and that the appropriate medical management of this mental state has been implemented. The use of the preparation in children and adolescents with severe psychiatric conditions present or in the interview 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 interferon alpha therapy. 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 treatment lasting up to 48 weeks, in patients from 3 to 17 years of age, weight loss and growth retardation were often observed. Available long-term data on children treated with pegylated interferon in combination with ribavirin indicate a significant inhibition of growth. 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 combined treatment induced growth inhibition, resulting in lower growth in some patients. 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. Despite a limited number of data, no evidence of long-term effects on sexual maturation was found in a 5-year follow up follow-up study. Serious hypersensitivity reactions (eg urticaria, angioneurotic edema, bronchospasm, anaphylaxis) have been reported rarely during treatment with interferon alfa-2b. If such reactions occur during treatment with the preparation, discontinue its use and promptly implement appropriate therapy. Patients with a history of congestive heart failure or myocardial infarction and / or previous or current arrhythmias treated with the product should be closely monitored. Arrhythmias (mainly supraventricular) usually undergo conventional treatment, but it may be necessary to discontinue use. There are no data on children and adolescents with a history of cardiac disease. Treatment with the preparation should be discontinued in patients whose blood coagulation rates increase, as this may indicate liver decompensation. Fever may be associated with the flu-like syndrome, which is often reported during treatment with interferon; other causes of persistent fever should be ruled out. Adequate hydration should be maintained in patients treated with the preparation because hypotension associated with fluid loss has been observed in some patients treated with alpha interferons. In every patient who develops a fever, cough, shortness of breath or other symptoms of the respiratory system, a chest x-ray should be taken. If the X-ray shows visible infiltrates in the lungs or there is evidence of impaired lung function, the patient should be closely monitored and, if warranted, treatment with alpha interferon should be discontinued. Patients with a tendency to develop autoimmune disorders may have an increased risk of developing them during treatment with alpha interferons. Patients with signs and symptoms resembling autoimmune diseases should be carefully evaluated and the risk-benefit ratio for further treatment with interferon should be determined again. If Vogta-Koyanagi-Harada syndrome (VKH) is suspected, antiviral treatment should be discontinued and further corticosteroid therapy should be considered. In each patient reporting loss of visual acuity or narrowing of the field of view, an ophthalmologic examination should be performed. Periodic visual examination during treatment with the preparation is recommended, especially in patients with diseases associated with the development of retinopathy, such as diabetes or hypertension. Discontinuation of treatment should be considered in patients who develop new or worsening eye disease. In the case of thyroid dysfunction, treatment with the preparation may be continued if TSH levels can be maintained within the normal range using appropriate pharmacological treatment. In patients who are co-infected with HIV and undergo antiretroviral therapy (HAART), there is an increased risk of developing lactic acidosis. Special care should be taken when adding peginterferon alfa-2b and ribavirin to HAART (see ribavirin SPC). In patients co-infected with HCV and HIV with advanced cirrhosis who are 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. Other factors that may increase the risk of hepatic decompensation in patients with HCV and HIV include didanosine and increased serum bilirubin. Patients with co-infection with HCV and HIV who also receive antiretroviral therapy (ARV) and anti-viral hepatitis should be closely monitored for the severity of Child-Pugh hepatic insufficiency. In patients who experience an increase in hepatic decompensation, treatment for viral hepatitis should be stopped immediately and ARV should be restarted. In patients receiving concomitant treatment with peginterferon alfa-2b and ribavirin and HAART, there may be an increased risk of haematological abnormalities (such as neutropenia, thrombocytopenia, anemia) compared to HCV-infected patients.Although most of these disorders can be corrected by dose reduction, hematologic parameters should be carefully monitored in this group of patients. Patients being treated with peginterferon alfa-2b in combination with ribavirin and zidovudine have an increased risk of developing anemia - the combination with ribavirin and zidovudine is not recommended. Caution should be exercised when treating patients with HCV and HIV with CD4 cell counts <200 cells / μl, due to limited data on efficacy and safety of treatment in this patient group. The safety and efficacy of the preparation have not been studied as monotherapy or in combination with ribavirin for the treatment of chronic hepatitis C in recipients of the liver or other organs. Preliminary results indicate that treatment with interferon alpha may be associated with an increase in rejection rate of the transplanted kidney. There was also rejection of the transplanted liver. Due to reports of interferon alpha exacerbating pre-existing psoriasis and sarcoidosis, the use of the preparation in patients with psoriasis or sarcoidosis is recommended only if the potential benefit outweighs the potential risk. The preparation should be used with caution in patients with moderate to severe renal impairment; patients with severe renal impairment, including hemodialysis should be carefully monitored. Due to lack of efficacy, peginterferon should not be used in long-term maintenance monotherapy. The product contains sucrose - patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency, should not take this preparation. The product contains less than 1 mmol sodium (23 mg) in 0.7 ml, which means that it is practically 'sodium-free'.

Women of childbearing age treated with the preparation must use effective contraception. There are no adequate data on the use of interferon alfa-2b in pregnant women. It can only be used during pregnancy if the expected benefit to the mother outweighs the potential risk to the fetus. 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.Combination therapy with ribavirin: ribavirin used during pregnancy causes severe birth defects, therefore, in pregnant women treatment with ribavirin is contraindicated. Patients of childbearing potential and their partners 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).

Adults. Triple therapy - see SmPC for boceprevir.Dual therapy and monotherapy. Adverse reactions that occur with both peginterferon alfa-2b monotherapy and combination therapy with ribavirin. Very common: viral infection, pharyngitis, anemia, neutropenia, anorexia, depression, anxiety, emotional lability, impaired concentration, insomnia, headache, dizziness, shortness of breath, cough, vomiting, nausea, abdominal pain, diarrhea, dry mouth, baldness , pruritus, dry skin, rash, muscle pain, joint pain, osteo-muscular pain, injection site reaction, injection site inflammation, fatigue, asthenia, irritability, chills, fever, flu-like symptoms, pain, weight loss. Common: bacterial infection (including sepsis), fungal infections, influenza, upper respiratory tract infection, bronchitis, herpes, sinusitis, otitis media, rhinitis, haemolytic anemia, leukopenia, thrombocytopenia, lymphadenopathy, hypothyroidism, hyperactivity thyroid gland, hypocalcaemia, hyperuricaemia, dehydration, increased appetite, aggression, agitation, anger, mood change, improper behavior, nervousness, sleep disorders, decreased sex drive, apathy, unusual dreams, crying, amnesia, memory impairment, fainting, migraine, ataxia, confusion, neuralgia, paresthesia, weakness in stimuli, hypersensitivity to stimuli, increased tension, drowsiness, attention disorder, tremor, taste disorder, blurred vision, blurred vision, photophobia, conjunctivitis, eye irritation,abnormalities of the lacrimal gland, eye pain, dry eye, impairment or loss of hearing, tinnitus, dizziness, palpitations, tachycardia, hypotension, hypertension, hot flushes, dysphonia, nosebleeds, breathing disorders, congestion of the respiratory tract , sinus congestion, nasal congestion, watery runny nose, increased secretion from the upper respiratory tract, sore throat and larynx, dyspepsia, gastro-oesophageal reflux, oral mucositis, mouth ulcers, tongue and lip mucus inflammation, bleeding from the gums, constipation, bloating, tumors, inflammation of the lips, abdominal distension, gingivitis, inflammation of the tongue, tooth disorders, hyperbilirubinemia, hepatomegaly, psoriasis, hypersensitivity to light, maculopapular rash, dermatitis, erythematous rash, eczema night sweats, nadmi erne sweating, acne, boil, erythema, urticaria, hair structure disorders, nail disorders, arthritis, back pain, muscle spasms, pain in the extremities, frequent urination, polyuria, changes in the urine, amenorrhea, breast pain, hemorrhage menstrual, menstrual disorders, ovarian disorders, vaginal disorders, sexual dysfunction, prostatitis, erectile dysfunction, chest pain, chest discomfort, pain at the injection site, malaise, facial edema, peripheral edema, abnormal feeling, thirst. Uncommon: infection at the injection site, lower respiratory tract infection, hypersensitivity to medication, diabetes, hypertriglyceridaemia, suicide, suicide attempts, suicidal thoughts, psychosis, hallucinations, panic attacks, neuropathy, peripheral neuropathy, exudative retinitis, ear pain, myocardial infarction cardiac inflammation, pancreatitis, oral pain, bone pain, muscle weakness. Rarely: sarcoidosis, diabetic ketoacidosis, bipolar disorder, convulsions, loss of visual acuity or visual field, retinal strokes, retinopathy, retinal artery occlusion, retinal vein closure, optic neuritis, optic nerve edema, macular edema, congestive heart failure heart, cardiomyopathy, arrhythmia, pericarditis, vasculitis, ischemic colitis, cutaneous sarcoidosis, rhabdomyolysis, myositis, rheumatoid arthritis, kidney damage, renal failure, necrosis at the injection site. Very rare: aplastic anemia, cerebrovascular hemorrhage, cerebrovascular ischemia, encephalopathy, myocardial ischemia, interstitial lung disease, ulcerative colitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme. Not known: erythrocortic aplasia, acute hypersensitivity reactions including angioedema, anaphylaxis and anaphylactic reactions including anaphylactic shock, idiopathic thrombocytopenic purpura, thrombocytopenic purpura, systemic lupus erythematosus, life-threatening behaviors, mania, facial nerve palsy, mononeuropathy, serous retinal detachment, pericardial effusion. The Vogta-Koyanagi-Harada team may also appear. In patients with concomitant HCV and HIV co-infected with ribavirin, other adverse events (which were not seen in HCV-infected patients) reported in clinical trials with> 5% incidence were: oral candidiasis , acquired lipodystrophy, decreased CD4 + cell count, decreased appetite, increased gamma-GT activity, back pain, increased serum amylase activity, increased serum lactic acid, cytolytic hepatitis, increased lipase activity, limb pain. Mitochondrial cytotoxicity and lactic acidosis have been reported in HIV infected patients receiving NRTI in combination with ribavirin, used to treat concomitant HCV infection.Children and youth. The profile of side effects in children and adolescents was generally similar to those seen in adults, although children may experience growth retardation. It is not certain whether the inhibition of growth is transient.Adverse reactions during combination therapy with peginterferon alfa-2b and ribavirin. Very common: anemia, leukopenia, neutropenia, anorexia, decreased appetite, headache, dizziness, abdominal pain, epigastric pain, vomiting, nausea, baldness, dry skin, joint pain, muscle pain, erythema at the injection site, fatigue, fever , stiffness, flu-like illness, weakness, pain, malaise, irritability, reduction of the growth rate (decrease in height and / or body weight in relation to age). Common: fungal infections, influenza, cold sores, otitis media, streptococcal pharyngitis, nasopharyngitis, sinusitis, thrombocytopenia, lymphadenopathy, hypothyroidism, suicidal thoughts, suicide attempts, depression, aggression, emotional lability, anger, agitation , anxiety, mood changes, anxiety, nervousness, insomnia, taste disorder, fainting, concentration disorders, drowsiness, poor quality sleep, eye pain, diarrheal headache, palpitations, tachycardia, hot flushes, cough, nosebleeds, pain throat and larynx, diarrhea, aphthous stomatitis, cleft lip, mouth ulcer, discomfort in the stomach, mouth pain, pruritus, rash, erythematous rash, eczema, acne, erythema, osteo-muscular pain, limb pain, back pain , injection site reactions, pruritus at the injection site, rash at the injection site, dry at the injection site, pain at the injection site, feeling cold, increased thyrotropin, increased thyroglobulin. Uncommon: pneumonia, ascariasis, oatosis, shingles, inflammation of the subcutaneous tissue, inflammation of the urinary tract, gastroenteritis, unusual behavior, decreased mood, emotional disturbances, feeling of fear, nightmares, neuralgia, lethargy, paresthesia, hypoesthesia, psychomotor agitation , tremor, conjunctival hemorrhage, pruritus of the eye, keratitis, blurred vision, photophobia, hypotension, paleness, wheezing, nose discomfort, nasal dyspepsia, gingivitis, hepatomegaly, hypersensitivity to light, maculopapular rash, exfoliation skin disorders, pigmentation disorders, atopic dermatitis, skin discoloration, muscle cramps, muscle tremors, proteinuria, women: dysmenorrhea; chest pain, chest discomfort, facial pain, positive test for detecting thyroid antibodies, injuries.

Treatment should only be started and controlled by a doctor who has experience in the treatment of patients with chronic hepatitis C. The product should be given once a week, subcutaneously.Combination therapy (bitherapy and triple therapy). Double therapy (with ribavirin) is intended for adult patients and children aged 3 years and above. Triple therapy (with ribavirin and boceprevir) is intended for adult patients with chronic hepatitis C caused by genotype 1 infection.AdultsThe recommended dose of peginterferon alfa-2b is 1.5 μg / kg / week in combination with ribavirin capsules. The recommended daily dose of ribavirin depends on the patient's body weight: up to 64 kg - 800 mg ribavirin (400 mg in the morning and 400 mg in the evening); mc. 65-80 kg - 1000 mg ribavirin (400 mg in the morning and 600 mg in the evening); mc. 81-105 kg - 1200 mg ribavirin (600 mg in the morning and 600 mg in the evening); mc. > 105 kg - 1400 mg ribavirin (600 mg in the morning and 800 mg in the evening). Detailed information on the dosage of boceprevir in triple-tone therapy can be found in the boceprevir SPC.Adults - duration of treatment - patients who have not been treated before. Triple therapy - SmPC of boceprevir.Double therapy: in patients with genotype 1 virus in whom no detectable HCV-RNA or no virologic response at 4 or 12 weeks of treatment is very unlikely to have a sustained virologic response - discontinuation of treatment should be considered. In patients with genotype 1 virus in whom after 12 weeks of treatment there is no detectable HCV-RNA, treatment should continue for a further 9 months (ie a total of 48 weeks). Patients with a genotype 1 virus who will be HCV-RNA after 12 weeks of treatment but have a ≥2 log decrease in HCV-RNA compared to baseline, should be re-evaluated in the 24th week.treatment; if at this time point HCV-RNA is unambiguous, a full course of treatment should be used in such a patient (ie in total 48 weeks); however, if HCV-RNA is still measurable in the 24th week of treatment, discontinuation of treatment should be considered. In a subgroup of patients infected with genotype 1 virus and low viral load (<600,000 IU / ml) for whom in the fourth week of treatment the HCV-RNA result is negative and who have a negative HCV RNA result in the 24th week. , treatment can be discontinued after 24 weeks of therapy or extended for another 24 weeks (ie the total duration of therapy will be 48 weeks); however, treatment lasting 24 weeks may be associated with a higher risk of relapse than a treatment lasting 48 weeks. Patients with genotype 2 or 3 virus are recommended to be treated for 24 weeks, except for patients co-infected with HCV and HIV, who should receive treatment lasting 48 weeks. It is considered that patients with genotype 4 is more difficult to treat , and limited data indicate that the duration of treatment is comparable to the treatment of patients with genotype 1 virus.Adults - duration of treatment - co-infection with HCV and HIV. The recommended duration of treatment for patients co-infected with HCV and HIV is 48 weeks, regardless of the genotype.Adults - duration of treatment - re-treatment. Triple therapy - SmPC of boceprevir.Double therapy: all patients regardless of viral genotype, in whom serum HCV-RNA is below the limit of quantification in the 12th week of treatment, should receive 48-week treatment. In patients with relapse (HCV-RNA below the limit of quantification) in the 12th week of treatment, a sustained virological response after 48 weeks of treatment is unlikely. Combination therapy with pegylated interferon alfa-2b and ribavirin, used again for more than 48 weeks, in patients with genotype 1 virus, in which no virological response was obtained, has not been studied.Children aged 3 years and above and adolescents (only bipartite therapy): the dosage of peginterferon alfa-2b depends on the body surface, dosages of ribavirin - on body weight. The recommended dose of peginterferon alfa-2b is 60 μg / m² pc / week subcutaneously, in combination with ribavirin 15 mg / kg / day orally in two divided doses with a meal (morning and evening).Children and adolescents (only bipartite therapy) - cduration of treatment: the recommended duration of treatment in patients with genotype 1 virus is 1 year. In patients with genotype 1 virus who do not have a virological response after 12 weeks of treatment, there is very little chance of a sustained virological response. It is recommended to discontinue treatment in children and adolescents if HCV-RNA drops by <2 log in 12 weeks.₁₀ compared to the pre-treatment value or when HCV-RNA is detected in the 24th week of treatment. In patients with genotype 2 or 3 virus, the recommended duration of treatment is 24 weeks. In patients with genotype 4 virus, the recommended duration of treatment is 1 year. It is recommended to discontinue treatment in this group of patients if HCV-RNA drops by <2 log in 12 weeks₁₀ compared to the pre-treatment value or if HCV-RNA is detected in the 24th week of treatment.monotherapy. AdultsThe recommended dose of peginterferon alfa-2b is 0.5 or 1.0 μg / kg / week. Monotherapy with the preparation has not been studied in patients with co-infection with HCV and HIV.Duration of treatment. In patients who have had a virological response in 12 weeks, treatment should continue for at least 3 consecutive months (ie a total of 6 months). The decision to extend treatment to one year should be made on the basis of other prognostic factors (eg genotype, age> 40 years, male sex, sternal fibrosis).Dose modification in all patients (monotherapy and combination therapy). In the event of serious adverse reactions or abnormal laboratory results during treatment with the preparation either as monotherapy or in combination therapy, the doses of peginterferon alfa-2b and / or ribavirin should be adjusted until the side effects decrease. Dose reduction of boceprevir is not recommended. Do not give boceprevir without peginterferon alfa-2b and ribavirin.Dose reduction principles in combination therapy. Hemoglobin concentration: Hb ≥ 8.5 g / dl and <10 g / dl - reduce only the daily dose of ribavirin; Hb concentration <8.5 g / dl - discontinue combination therapy.Hemoglobin concentration in adult patients with a history of cardiac disease: decrease in hemoglobin ≥ 2 g / dl over any 4-week period period during the course of treatment (permanent dose reduction) - reduce the daily dose of ribavirin and the dose of peginterferon alfa-2b; Hb <12 g / dl 4 weeks after dose reduction - discontinue combination therapy. The number of leukocytes: ≥ 1.0 x 10⁹/ l and <1.5 x 10⁹/ l - reduce only the dose of peginterferon alfa-2b; <1.0 x 10⁹/ l - discontinue combination therapy. Number of neutrophils: ≥ 0.5 x 10⁹/ l and <0.75 x 10⁹/ l - reduce only the dose of peginterferon alfa-2b; <0.5 x 10⁹/ l - discontinue combination therapy. Platelet counts ≥ 25 x 10⁹/ l and <50 x 10⁹/ l (adults) or ≥ 50 x 10⁹/ l and <70 x 10⁹/ l (children and adolescents) - reduce only the dose of peginterferon alfa-2b; <25 x 10⁹/ l (adults) or <50 x 10⁹/ l (children and adolescents) - discontinue combination therapy. Concentration of conjugated bilirubin: 2.5 x ULN (upper limit of normal) - discontinue combination therapy. Concentration of free bilirubin:> 5 mg / dl - reduce only the daily dose of ribavirin; > 4 mg / dl (> 4 weeks) - discontinue combination therapy. Serum creatinine concentration:> 2.0 mg / dl - discontinue combination therapy. Creatinine clearance: <50 ml / min - discontinuation of ribavirin. ALT (or AST) activity: 2 x initial value and> 10 x ULN - discontinue combination therapy. In adult patients, the first dose reduction for ribavirin should be about 200 mg / day (except in patients receiving the 1400 mg dose, in which case the dose reduction should be 400 mg / day). If necessary, the dose of ribavirin may be reduced a second time by another 200 mg / day. Patients who receive a dose of ribavirin up to 600 mg daily receive 1 capsule 200 mg in the morning and 2 capsules 200 mg in the evening. In children and adolescents, the dose of ribavirin is first reduced to 12 mg / kg / day and then to 8 mg / kg / day. In adult patients, the first dose reduction of peginterferon alfa-2b should be 1 μg / kg / s. If necessary, the dose of peginterferon alfa-2b may be reduced for the second time by 0.5 μg / kg / week. A reduction in the dose of peginterferon alfa-2b in adults can be achieved by reducing the prescribed volume or by using a lower strength formulation. The reduction of the dose of peginterferon alfa-2b in children and adolescents is achieved by modifying the recommended dose in a 2-step process, starting at 60 μg / m² pc. / week, up to 40 μg / m² pc / s, then up to 20 μg / m² pc / s, if necessary.The principles of reducing the dosage of peginterferon alfa-2b as monotherapy in adults. Neutrophil count ≥ 0.5 x 10⁹/ l and <0.75 x 10⁹/ l - reduce the dose of peginterferon alfa-2b by half; <0.5 x 10⁹/ l - discontinue treatment with the preparation. Platelet counts ≥ 25 x 10⁹/ l and <50 x 10⁹/ l - reduce the dose of peginterferon alfa-2b by half; <25 x 10⁹/ l - discontinue treatment with the preparation.Use in patients with impaired renal function: monotherapy: In patients with moderate renal impairment (creatinine clearance 30-50 ml / min), the initial dose of peginterferon alfa-2b should be reduced by 25%. In patients with severe renal impairment (creatinine clearance 15-29 ml / min), the initial dose of peginterferon alfa-2b should be reduced by 50%. There are no data on administration in patients with creatinine clearance <15 ml / min. If your kidney function is worse when using peginterferon alfa-2b, treatment should be discontinued.Combination therapy: Patients with creatinine clearance <50 ml / min must not be treated with peginterferon alfa-2b in combination with ribavirin (see ribavirin SPC). When used in combination with ribavirin, patients with impaired renal function should be carefully monitored for the possibility of anemia.Use in patients with impaired liver function: do not use in patients with severe hepatic impairment.Use in elderly patients (≥ 65 years of age): no dose adjustment is necessary based on age. The patient can self-inject the medicine, if the treating physician realizes it is the right solution. Medical supervision should be provided if necessary.