Peguferon (Peginferon)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substancePeginterferon alfa-2bPeginterferon alfa-2b
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    • Dosage form: & nbspLiophilizate for the preparation of a solution for subcutaneous administration.
    Composition:

    Active substance:

    Peginterferon alfa-2b 50 μg / 0.5 ml, 80 μg / 0.5 ml, 100 μg / 0.5 ml, 120 μg / 0.5 ml, 150 μg / 0.5 ml.

    Excipients:

    Sodium hydrophosphate anhydrous - 0.75 mg, sodium dihydrogen phosphate dihydrate - 0.75 mg, sucrose - 40.00 mg, polysorbate-80 - 0.05 mg.

    Description:

    Mass or powder from white to almost white.

    After dissolving the lyophilizate in water for injection, a clear, colorless solution is formed.

    Pharmacotherapeutic group:cytokine
    ATX: & nbsp

    L.03.A.B   Interferons

    L.03.A.B.10   Peginterferon alfa-2b

    Pharmacodynamics:

    Peguferferon is a preparation of pegylated interferon alfa-2b, which is obtained by covalent conjugation of recombinant interferon alpha-2b and monomethoxypolyethylene glycol with a molecular weight of approximately 31.3 kDa. Pharmacodynamics.

    Biological activity of the preparation Peguferon is due to interferon alpha-2b. Recombinant interferon alfa-2b derived from a clone Escherichia coli, which contains a genetically engineered plasmid hybrid encoding interferon alfa-2b of human leukocytes. Interferon alfa-2b has antiviral, immunomodulatory and antiproliferative action. The antiviral effect is due to binding to specific receptors on the cell surface and initiation of a sequence of intracellular reactions involving the induction of certain enzymes (protein kinase R, 2'-5 'oligoadenylate synthetase, proteins Mx). This leads to suppression of the transcription of the viral genome and inhibition of the synthesis of viral proteins. Immunomodulating effect is associated with increased cytotoxicity of T-lymphocytes and natural killers and phagocytic activity of macrophages. In addition, interferon alfa-2b promotes the differentiation of T-helpers, protects T cells from apoptosis and affects the production of a number of cytokines (interleukins, interferon gamma). All these effects can mediate the therapeutic activity of interferon.

    Pharmacodynamics of the preparation Peginferon was studied from the concentration in the blood of effector protein neopterin, which is a marker of activation of human cellular immunity. After a single subcutaneous injection of the preparation Peginferon and a comparator of healthy volunteers at a dose of 1.5μg / kg body weight, there was a comparable dynamics of neopterin concentration in blood, the maximum value of which (CmOh) was achieved in 48 hours.

    In the pre-clinical study of biological activity, there were no significant differences between the preparations of Peginferon and the reference preparation.
    Pharmacokinetics:

    Peginterferon alfa-2b is a well-studied pegylated derivative of interferon alfa-2b and consists mainly of mono-pegylated molecules. Pegylation of the interferon alpha-2 moleculeb leads to a significant slowing of absorption from the injection site, an increase in the volume of distribution and a decrease in clearance. The decrease in clearance leads to a significant increase in the half-life (T1/2) as compared to unmodified interferon alpha-2b.

    Pharmacokinetics of the preparation Peguferon was studied in comparison with the reference preparation. In the pre-clinical study, there were no statistically significant differences. With a single subcutaneous injection at a dose of 1.0 μg / kg to healthy volunteers, the main pharmacokinetic parameters were also comparable.

    The maximum concentration (Cmax) peginterferon alfa-2b after a single subcutaneous administration of the preparation Peginferon was achieved, on average, after 15-44 hours and was about 0.842 ng / ml. The volume of distribution (the conditional volume of fluid necessary for the uniform distribution of peginterferon alfa-2b detected in the therapeutic plasma concentration (Vd) in it was, on the average, 0.99 l / kg.

    The half-life (T1/2) was, on average, 27.3 hours; the elimination constant (Kel) is 0,0276 hours-1; clearance (the rate of purification of blood from peginterferon alfa-2b (C1), on average, 22.0 ml / h-kg.) The mechanisms of clearance of interferons are not fully understood.Kidney clearance is 30% of the total clearance of peginterferon alfa-2b.

    Pharmacokinetics in patients with impaired renal function

    In studies of peginterferon alfa-2b, an increase in Cmax, AUC, T1/2 in proportion to the degree of renal failure. When applied at a dose of 1.0 mcg / kg for 4 weeks (1 injection per week), a decrease in the clearance of peginterferon alfa-2b by 17% in patients with moderate renal insufficiency (creatinine clearance 30-49 ml / min) and 44% in patients with severe renal failure (creatinine clearance 15-29 ml / min) compared with those with normal renal function.According to the data obtained with the administration of one dose in the group of patients with severe renal insufficiency, the creatinine clearance was the same in patients on hemodialysis and in patients who did not undergo hemodialysis.

    With monotherapy, it is necessary to reduce the dose of peginterferon alfa-2b in patients with moderate and severe renal insufficiency.

    Patients who have a creatinine clearance of less than 50 ml / min, combined therapy with the drug Peguferon and ribavirin is contraindicated.

    Due to the large variability in pharmacokinetics, patients with severe renal failure who receive Peguferon preparation should be carefully monitored in different patients.

    Pharmacokinetics in patients with impaired hepatic function

    The pharmacokinetics of peginterferon alfa-2b in patients with severe impairment of liver function has not been studied.

    Pharmacokinetics in children

    In children and adolescents receiving peginterferon alfa-2b in a dose of 60 mcg / m2/ week, the log-transformed exposure ratio during the dosing interval is expected to be 58% (90% confidence interval: 141-177%) higher than in adults receiving peginterferon alfa-2 at a dose of 1.5 mcg / kg / week.

    Pharmacokinetics in the elderly

    The pharmacokinetics of peginterferon alfa-2b2 does not depend on age, so a change in the dose of Peguferferone in elderly people is not required. Pharmacokinetics in patients older than 70 years have not been studied.

    Neutralizing antibodies to interferon

    Neutralizing antibodies to interferon were analyzed in serum samples from patients treated with Peguferon and a reference preparation in a clinical trial. These antibodies neutralize the antiviral activity of interferon. The detection rate of neutralizing antibodies in patients treated with Peginferon was 5.1%, the reference drug was 7.9%.

    Indications:

    Chronic hepatitis B

    Treatment of patients with chronic hepatitis B at the age of 18 years in the absence of decompensation of liver disease.

    Chronic hepatitis C

    Adults (triple therapy)

    Treatment of chronic hepatitis C, genotype 1, preparation Peginferon in combination with ribavirin and a protease inhibitor NS3/4A in adult patients with compensated liver disease who had not previously received antiviral therapy or with unsuccessful experience of antiviral therapy.

    Adults (dual therapy and monotherapy)

    Treatment of chronic hepatitis C with Peginferon in adult patients seropositive for hepatitis C virus RNA, including patients with compensated cirrhosis and / or in combination with clinically stable HIV infection.

    Treatment of chronic hepatitis C with Peguferon in combination with ribavirin in adult patients who have not previously received antiviral therapy, including patients with concomitant clinically stable HIV infection, and in adult patients who previously had unsuccessful experience with antiviral therapy with a combination of interferon alfa (pegylated or non-pegylated) with ribavirin or interferon alfa monotherapy.

    Monotherapy with Peginferon for chronic hepatitis C is indicated only in case of intolerance or contraindications for the appointment of ribavirin.

    Children (double therapy)

    Treatment of chronic hepatitis C with Peguferon in combination with ribavirin in children aged 3 years and older who have not previously received antiviral therapy, with compensated liver disease and seropositive for hepatitis C virus RNA.

    If a decision is made not to delay treatment to adulthood, it must be borne in mind that combination therapy can cause growth retardation. The reversibility of growth retardation is not known. The decision on the appointment of treatment should be taken individually.

    Contraindications:

    - Hypersensitivity to any interferon or component of the drug;

    - a serious history of the cardiovascular system, including a disease with unstable or uncontrolled course for the last 6 months;

    - Patients with severe debilitating diseases;

    - autoimmune hepatitis or other autoimmune disease in the anamnesis;

    severe liver dysfunction or decompensated liver cirrhosis;

    - dysfunction of the thyroid gland, which can not be maintained at a normal level by drug therapy;

    - epilepsy and / or dysfunction of the central nervous system;

    - hepatic cirrhosis with hepatic insufficiency (Child-Pugh index> 6) in patients with HCV / HIV co-infection;

    - simultaneous administration of Peguferon with Telbivudine.

    - severe mental illness or severe mental disorders, including history,in particular severe depression, suicidal ideation or attempted suicide in pediatric patients;

    - the period of breastfeeding;

    - Children under 18 years of age (triple therapy, monotherapy);

    - Children under 3 years old (double therapy);

    - pregnancy, including among women partners of men who are supposed to prescribe Pegginferon treatment (monotherapy, double or triple therapy);

    - rare hereditary diseases - intolerance to fructose, glucose-galactose malabsorption, insufficiency of sucrose-isomaltase (due to the presence of sucrose in the formulation);

    - impaired renal function - creatinine clearance less than 50 ml / min (when used in combination with ribavirin).

    When the drug Peginferon in combination with ribavirin and a protease inhibitor NS3/4A it is necessary to familiarize yourself with the instructions for the medical use of these drugs.

    Carefully:

    Preparation Peguferonon should be used with caution in the following categories of patients: women of reproductive age, male partners of women of reproductive age, children over 3 years and adolescents (double therapy),patients with moderate and severe renal insufficiency (in the case of monotherapy), HIV-infected patients, patients receiving drugs metabolized with the participation of cytochrome P450 isoenzymes CYP2D6 and CYP2C8/9, especially drugs with a narrow therapeutic window, patients receiving methadone, adults with mental disorders, patients abusing substances (alcohol, marijuana or other substances), patients with compensated diseases of the cardiovascular system, patients, predisposed to autoimmune disorders, patients with eye diseases, patients with compensated thyroid diseases, patients with metabolic disorders, patients who underwent a transplant ation bodies, patients with psoriasis, sarcoidosis patients to drive a car or other machinery.

    Pregnancy and lactation:

    Women of reproductive age / contraception in men and women

    Peguferferon may be given to women of reproductive age only if effective contraception is used during treatment.

    Combination therapy with ribavirin

    In female patients or female partners of male patients receiving the Peguferon preparation in combination with ribavirin, special precautionary measures should be taken to prevent the onset of pregnancy. Women of reproductive age should use effective methods of contraception during the entire period of treatment and within 4 months after its completion.

    Male patients or their female partners should use effective contraceptive methods throughout the treatment period and within 7 months after completion.

    Pregnancy

    Data on the use of interferon alfa-2b in pregnant women is not enough. The animals demonstrated its reproductive toxicity. Primates showed abortive action. Most likely, the preparation of Peguferon has the same effect.

    Potential risk in humans is not known. The use of the drug Peguferon during pregnancy is contraindicated.

    Combination therapy with ribavirin

    Ribavirin causes serious malformations of the fetus when administered during pregnancy.Thus, the appointment of ribavirin is contraindicated in pregnant women.

    Breast-feeding

    On the isolation of components of the drug Peguferferon with breast milk is not known. In connection with the potential risk of side effects in children who are breastfed, before breast-feeding therapy should be stopped.

    Reproductive function

    Information on the effect of the drug Peguferon on reproductive function in men and women there.

    Dosing and Administration:

    Chronic hepatitis B

    Therapy with Peginferon should be started by a doctor who has experience in the treatment of patients with hepatitis B, and further under his supervision.

    Peguferferon is administered subcutaneously in a dose of 1.0 to 1.5 μg / kg once a week for 24 to 52 weeks. The dose should be selected individually, based on the expected efficacy and safety of the drug.

    Patients with hard-to-treat chronic hepatitis B caused by the genotype C virus or D, to achieve a therapeutic effect may require higher doses of the drug and a longer course of treatment.

    It is recommended to alternate the injection site.

    Chronic hepatitis C

    Therapy with Peginferon should be started by a doctor who has experience in treating patients with hepatitis C, and further under his supervision.

    The drug Peguferon is administered as a subcutaneous injection once a week. The dose of the drug in adults depends on whether it is prescribed as a combination therapy (double or triple) or monotherapy.

    Combination therapy with Peguferon (double or triple)

    Double therapy (preparation Peginterferon with ribavirin): is prescribed for adult patients and children from 3 years and older.

    Triple therapy (preparation Peginferon with ribavirin and protease inhibitor NS3/4A): is assigned to adult patients infected with the hepatitis C virus, genotype 1.

    Adults

    In combination therapy with ribavirin, the preparation Peginferon is administered in the form of a subcutaneous injection at a dose of 1.5 μg per 1 kg of body weight once a week. It is recommended to alternate the injection site.

    Ribavirin should be taken orally daily. The intake of ribavirin is combined with the intake of food. The daily dose of ribavirin for combination therapy is calculated according to body weight.

    When combined therapy can be guided by a combined table for dosing of drugs Peginferon and ribavirin:

    Body weight (kg)

    Peguferon

    ribavirin

    Concentration (μg / 0.5 mL)

    Volume / per week (ml)

    Daily dose (mg)

    The number of capsules / tablets (200 mg each)

    <40

    50

    0,5

    800 mg / day

    4a

    40-50

    80

    0,4

    800 mg / day

    4a

    51-64

    80

    0,5

    800 mg / day

    4a

    65-75

    100

    0,5

    1000 mg / day

    5b

    76-80

    120

    0,5

    1000 mg / day

    5b

    81-85

    120

    0,5

    1200 mg / day

    6AT

    86-105

    150

    0,5

    1200 mg / day

    6AT

    >105

    150

    0,5

    1400 mg / day

    7D

    a: 2 in the morning + 2 in the evening

    b: 2 in the morning + 3 in the evening

    in: 3 in the morning + 3 in the evening

    r: 3 in the morning + 4 in the evening

    When prescribing Peguferon as a part of triple therapy, it is necessary to read the instructions for the medical use of a protease inhibitor NS3/4A.

    Duration of treatment the adults who were not treated

    Triple therapy: it is necessary to read the instructions for the medical use of a protease inhibitor NS3/4A.

    Double therapy: In patients infected with the hepatitis C virus of genotype 1, who can not reach an undetectable level of viral RNA or an adequate virologic response at 4 or 12 weeks of antiviral therapy, the likelihood of achieving a stable virologic response is extremely low and they should assess the feasibility of discontinuing treatment.

    Genotype 1:

    • In patients with undetectable levels of viral RNA after 12 weeks of antiviral therapy, treatment should continue for another 9 months (the total course duration is 48 weeks).
    • In patients in whom viral RNA is determined after 12 weeks of antiviral therapy, but its level has decreased by ≥ 2 log from the baseline, a reassessment of treatment efficacy at 24 weeks of therapy is necessary. If viral RNA is not detected after 24 weeks of antiviral therapy, it is necessary to continue the full course of treatment (the total duration of the course is 48 weeks); If viral RNA continues to be determined, consideration should be given to the desirability of discontinuing treatment.
    • Patients with a low virus concentration (<600,000 IU / ml) who had eliminated the virus after 4 weeks of treatment and the virus RNA was not detected until the 24th week of therapy, treatment after 24 weeks may be discontinued (the total duration of the course is 24 weeks) or continued for another 24 weeks (the total course duration is 48 weeks). However, it should be borne in mind that the risk of relapse after a 24-week course of treatment is higher than after a 48-week course.

    Genotype 2 or 3:

    • The recommended duration of treatment for all patients in this group is 24 weeks, excluding patients with HCV / HIV co-infection who should be treated within 48 weeks.

    Genotype 4:

    In general, it is noted that patients of this group can not be treated with difficulty. Patients in this group may use the same treatment tactics as in the group of patients infected with the genotype 1 virus.

    Duration of treatment in adults with HCV / HIV co-infection

    Double therapy: The recommended duration of treatment is 48 weeks, regardless of the genotype of the virus. The early virologic response - a decrease in viral RNA ≥ 2 log from baseline or an undetectable level of RNA after 12 weeks of treatment is a predictor of achieving a sustained virologic response.

    Duration of treatment in adults who did not respond to treatment (repeated course)

    Triple therapy: It is necessary to read the instructions for the medical use of a protease inhibitor NS3/4A.

    Double therapy: In all patients, regardless of the genotype, reached undetectable levels of viral RNA after 12 weeks of therapy, treatment should last 48 weeks. In the absence of a virologic response at 12 weeks of therapy, the probability of achieving a sustained virologic response after 48 weeks of therapy is low.

    The duration of re-therapy with peginterferon alfa-2b and ribavirin for more than 48 weeks in patients with hepatitis C virus of the genotype, the answer in which was not achieved, has not been studied.

    Dosing regimen the children (only double therapy)

    The dosage regimen in children from 3 years and older and adolescents is determined by the surface area of ​​the body for the preparation Peginferon and the body weight for ribavirin. The recommended dose of Peguferferon is 60 μg / m2/ wk. subcutaneously in combination with ribavirin at a dose of 15 mg / kg / day. Inside, divided into two meals with food (morning and evening).

    Duration of treatment in children (only double therapy)

    Genotype 1:

    • The recommended duration of treatment is 48 weeks. When extrapolating clinical trials of combination therapy, including standard interferon, in children (a negative predictive index of 96% for interferon-alpha-2b / ribavirin combination), it can be assumed that in patients who did not achieve a virologic response at 12 weeks, the likelihood of achieving a sustained virologic response is extremely small.Thus, in children and adolescents receiving combination therapy with ribavirin and drug Peginferon, it is recommended to stop the treatment if at 12 weeks reduction in viral RNA level was <2 log compared with the initial value, or when the blood detection of viral RNA after 24 weeks of treatment.

    Genotypes 2 or 3:

    The recommended duration of treatment is 24 weeks.

    Genotype 4:

    The recommended duration of treatment is 48 weeks. In children and adolescents receiving combination therapy with ribavirin and drug Peginferon, it is recommended to discontinue treatment if 12 weeks reduction in viral RNA levels of <2 log in comparison with the baseline level, or when a hepatitis C virus is detected in the bloodstream after 24 weeks of treatment.

    Monotherapy with Peguferferon (adults)

    Dosing regimen

    The drug Peguferon is administered subcutaneously in a dose of 0.5 or 1.0 μg / kg once a week:

    Body weight (kg)

    0.5 μg / kg

    1.0 μg / kg

    Dosage vial (μg / 0.5 mL)

    The dose for administration once a week (ml)

    Dosage vial (μg / 0.5 mL)

    The dose for administration once a week (ml)

    30-35

    50

    0,15

    80

    0,2

    36-45

    50

    0,2

    50

    0,4

    46-56

    50

    0,25

    50

    0,5

    57-72

    80

    0,2

    80

    0,4

    73-88

    50

    0,4

    80

    0,5

    89-106

    50

    0,5

    100

    0,5

    107-120*

    80

    0,4

    120

    0,5

    * In patients with a body weight> 120 kg, the dose of Peguferferon is calculated by body weight.

    Monotherapy with Peginferon in patients with HCV / HIV co-infection has not been studied.

    Duration of treatment

    In patients who have a virologic response after 12 weeks, treatment should continue for another 3 months (the total course duration is 6 months). Prolongation of therapy up to 1 year (48 weeks) can be based on prognostic factors (genotype of the virus, age> 40 years, male sex, the presence of bridge fibrosis).

    Correction of dose in all patients (monotherapy and combination therapy)

    In the event of serious adverse events or abnormalities in laboratory indicators against a background of monotherapy or combination therapy, including the preparation Peginferon, correction of the dose of Peginferon and / or ribavirin is required before the termination of undesirable events. Reduction of the dose of the protease inhibitor NS3/4A Not recommended. Inhibitor NS3/4A should not be prescribed without the drug Peginferon and ribavirin.

    Since the doses of Peguferferone and ribavirin affect the outcome of treatment, they should, as far as possible, remain approximated to the recommended standard doses.

    Recommendations for dose adjustment in combinationof therapy

    Laboratory indicators

    Reduction of the dose of ribavirin alone, if1:

    Dose reduction only peginterferon alfa-2b, if2:

    Termination of therapy if:

    Hemoglobin content

    ≥ 85 g / l and <100 g / l

    -

    <85 g / l

    Adults: hemoglobin content in patients with heart disease in stable form

    The hemoglobin content decreased by> 20 g / l for any 4 weeks during treatment (continuous use of a reduced dose)

    <120 g / L 4 weeks after dose reduction

    Children: hemoglobin content

    Not applicable (see "Special instructions")

    Number of leukocytes

    -

    ≥1,0х109/ l and <

    1,5х109/l

    <1.0х109/l

    Number of neutrophils

    -

    ≥0.5х109/l and

    <0.75x109/l

    <0.5x109/l

    Platelet count

    -

    Adults:

    > 25x109/ l and

    <50 х109/ l

    Children and adolescents:

    ≥50 х109/ l and

    <70 x109/l

    Adults:

    <25 х109/ l

    Children and adolescents:

    <50 х109/l

    Content of bound bilirubin

    -

    -

    2.5 x VGN *

    Free bilirubin content

    > 0.05 g / l

    -

    > 0.04 g / l

    (for> 4 weeks)

    Serum creatinine content

    -

    -

    > 0.02 g / l

    Laboratory indicators

    Reduction of the dose of ribavirin alone, if1:

    Dose reduction only peginterferon alfa-2b, if2:

    Termination of therapy if:

    Creatinine clearance

    -

    -

    Undo ribavirin, if

    <50 ml / min.

    ALT /ACT **

    -

    -

    2 x (basic value) and

    > 10х VGN *

    Notes:

    1 In adults, the first dose reduction of ribavirin is carried out at 200 mg / day. (in those who received 1,400 mg - at 400 mg / day.). If necessary, a second dose reduction of ribavirin is performed for another 200 mg / day. Patients in whom a dose of ribavirin is reduced to 600 mg / day should receive one capsule / tablet of the drug (200 mg) in the morning and two capsules / tablets (200 mg) in the evening.

    In children and adolescents, the first dose reduction of ribavirin is made up to 12 mg / kg / day, the second dose of ribavirin is reduced to 8 mg / kg / day.

    2 In adults, the first reduction in the dose of Peginferon is carried out to 1.0 μg / kg / week. If necessary, a second reduction in the dose of Peginferon is carried out to 0.5 μg / kg / week.

    In children and adolescents, the first reduction in the dose of Peginferon is given up to 40 μg / m2/ week, the second reduction in the dose of Peginferon is given up to 20 μg / m2/ wk.

    * - the upper limit of the norm.

    ** - Alanine aminotransferase / Aspartate aminotransferase.

    Reduction in the dose of Peginferon in adults can be achieved by reducing the volume of the administered solution or by using a drug with a lower dosage. In children and adolescents - by correcting the recommended dose in two stages: from a starting dose of 60 mcg / m2/ per week up to 40 mcg / m2/ per week, then, if necessary, up to - 20 μg / m2 in Week.

    Recommendations for reducing the dose of the drug are presented in the table.

    Recommendations for reducing the dose of Peguferon in two stages with combined therapy in adults

    First dose reduction Pegineferon up to 1 mcg / kg

    Second dose reduction Pegineferon to 0.5 mcg / kg

    Weight bodies (kg)

    Dosage bottle (μg / 0.5 ml)

    amount preparation Peguferon (μg)

    Scope preparation Peguferon (ml)

    Weight bodies (kg)

    Dosage bottle (μg / 0.5 ml)

    amount preparation Peguferon (μg)

    Scope preparation Peguferon (ml)

    <40

    50

    35

    0,35

    <40

    50

    20

    0,2

    40-50

    120

    48

    0,2

    40-50

    50

    25

    0.25

    51-64

    80

    56

    0,35

    51-64

    80

    32

    0,2

    65-75

    100

    70

    0,35

    65-75

    50

    35

    0,35

    76-85

    80

    80

    0,5

    76-85

    120

    48

    0,2

    86-105

    120

    96

    0,4

    86-105

    50

    50

    0,5

    >105

    150

    105

    0,35

    >105

    80

    64

    0,4

    Recommendations for reducing the dose of Peginferon for monotherapy in adults

    Laboratory indicators

    Reduction of the dose of peginterferon alfa-2b up to half the therapeutic dose, if

    Stopping injections of peginterferon alfa-2b if

    Number of neutrophils

    ≥0,5 x109/l and < 0,75 x109/l

    <0.5 x109/l

    Platelet count

    ≥25 x109/l and <50 x109/l

    <25 x109/l

    In adults receiving Peguferonone monotherapy with a dose of 0.5 μg / kg, a dose reduction can be achieved by reducing the volume of the drug solution administered halfway:

    Body weight (kg)

    Dosage of the vial (μg / 0.5 ml)

    Quantity (Peguferon, μg)

    Volume (Pegineferon, ml)

    30-35

    50

    8

    0,08

    36-45

    50

    10

    0,1

    46-56

    50

    13

    0,13

    57-72

    80

    16

    0,1

    73 -88

    50

    20

    0,2

    89-106

    50

    25

    0,25

    107-120*

    80

    32

    0,2

    * In patients with a body weight> 120 kg, the dose of Peguferon is calculated by body weight.This may require a combination of different volumes and doses of the drug.

    In adults receiving Peginferon monotherapy with a dose of 1.0 μg / kg, a dose reduction can be achieved by reducing the volume of the drug solution administered by half or reducing its concentration:

    Body weight (kg)

    Dosage of the vial (μg / 0.5 ml)

    The amount of the drug Peguferon (μg)

    Volume of the preparation Pegineferon (ml)

    30-35

    50

    15

    0,15

    36-45

    50

    20

    0.20

    46-56

    50

    25

    0,25

    57-72

    80

    32

    0,2

    73-88

    50

    40

    0,4

    89-106

    50

    50

    0,5

    107-120*

    80

    64

    0,4

    * In patients with a body weight> 120 kg, the dose of Peginferon is calculated by body weight. This may require a combination of different volumes and doses of the drug.

    Special populations of patients

    Correction of dose in renal failure

    Monotherapy

    The drug Peguferonon should be used with caution in patients with moderate renal insufficiency and severe renal failure.

    In patients with moderate renal insufficiency (creatinine clearance 30-50 ml / min.), The initial dose of Peguferferon should be reduced by 25%. In patients with severe renal failure (creatinine clearance 15-29 ml / min.), including patients undergoing hemodialysis, the initial dose of Peguferferon should be reduced by 50%. Data on the use of peginterferon alfa-2b in patients with creatinine clearance <15 ml / min.Patients with severe renal failure, including those on hemodialysis, should be closely monitored. If, during treatment, there is a decrease in kidney function, therapy with Peguferon should be discontinued.

    Combination Therapy

    Patients with creatinine clearance <50 ml / min. administration of the drug Peguferon in combination with ribavirin is contraindicated. When prescribing combination therapy for patients with renal insufficiency, careful monitoring should be made regarding the development of anemia.

    Liver failure

    The safety and efficacy of treatment with Peginferon for patients with severe liver dysfunction has not been studied, therefore, Peginferon should not be used in such patients.

    Patients of advanced age (65 years and older)

    Dependence of the pharmacokinetics of peginterferon alfa-2b from age it is not revealed. Data on the results of the study of pharmacokinetics in the elderly after a single subcutaneous injection of peginterferon alfa-2b suggest that the selection of a dose of the drug with age is not required. In patients older than 70 years, the pharmacokinetics of peginterferon alfa-2b not studied.

    Children

    Peguferon in combination with ribavirin can be given to children aged 3 years and older.

    Instructions for preparing a solution for injection

    Peguferon preparation in vials

    Peguferferon should not be mixed with other medications. Using a sterile syringe, 0.7 ml of water for injection is injected into a vial of Peginferon. The bottle is gently rocked until the powder is completely dissolved. The dissolution time should not exceed 10 minutes; usually the powder dissolves more quickly. The required volume is collected in a sterile syringe. For administration, up to 0.5 ml of the solution is used.

    Like any other preparations for parenteral use, the prepared solution should be inspected before administration. The solution must be clear, colorless and free of visible particles. In case of discoloration or appearance of visible particles, the solution should not be used. The finished solution should be used immediately.

    If you can not immediately use the prepared solution, it can be stored for no more than 24 hours at a temperature of 2 ° C to 8 ° C. Do not freeze the finished solution.The solution remaining after the introduction is not subject to further use and it must be disposed of in accordance with the current procedure.

    Side effects:

    Adults

    Triple therapy

    It is necessary to read the instructions for the medical use of a protease inhibitor NS3/4A.

    Dual therapy and monotherapy

    Security Profile Overview

    The most frequent (according to the results of clinical studies in more than half of patients) are side effects of combination therapy with peginterferon alfa-2b and ribavirin were weakness, headache and skin reaction at the injection site. More than 25% of cases were nausea, chills, insomnia, anemia, fever, myalgia, asthenia, pain, alopecia, anorexia, weight loss, depression, rash and irritability. As a rule, the side effects were mild or moderate, they were well controlled and did not require a reduction in the dose of drugs or withdrawal of therapy. Weakness, alopecia, itching, nausea, anorexia, weight loss, irritability and insomnia were less common with peginterferon alfa-2 monotherapyb, than with combined treatment.

    Side effects

    The following side effects noted with the use of peginterferon alfa-2b (according to the results of clinical studies and post-marketing surveillance in monotherapy and in combination with ribavirin) are listed according to the system-organ classes and frequency, according to the following gradation: very often ≥ 1/10, often ≥ 1/100 and <1/10, infrequently ≥ 1/1000 and <1/100, rarely ≥ 1/10 000 and <1/1000, very rarely <1/10 000, unspecified frequency (can not be calculated from available data).

    Within each frequency group, side effects are in order of decreasing clinical importance.

    Infectious and parasitic diseases

    Often:

    Viral infection *, pharyngitis *

    Often:

    Bacterial infection (including sepsis), fungal infection, influenza, upper respiratory tract infections, bronchitis, infection caused by the herpes simplex virus, sinusitis, otitis media, rhinitis

    Infrequently:

    Infection at the injection site, infection of the lower respiratory tract

    Violations of the blood and lymphatic system

    Often:

    Anemia, neutropenia

    Often:

    Hemolytic anemia, leukopenia, thrombocytopenia, enlarged lymph nodes

    Rarely:

    Aplastic anemia

    Unknown:

    True erythrocyte aplasia

    Immune system disorders

    Infrequently:

    Hypersensitivity reactions

    Rarely:

    Sarcoidosis

    Unknown:

    Acute immediate hypersensitivity reactions, including angioneurotic edema, anaphylaxis and anaphylactoid reactions including anaphylactic shock, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, systemic lupus erythematosus

    Disorders from the endocrine system

    Often:

    Hypothyroidism, hyperthyroidism

    Disorders from the metabolism and nutrition

    Often:

    Anorexia

    Often:

    Hypocalcemia, hyperuricemia, dehydration, increased appetite

    Infrequently:

    Diabetes mellitus, hypertriglyceridemia

    Rarely:

    Diabetic ketoacidosis

    Disorders from the psyche

    Often:

    Depression, anxiety *, emotional lability *, impaired concentration, insomnia

    Often:

    Aggression, agitation, anger, mood changes, behavioral disorders, nervousness, insomnia, decreased libido, apathy, abnormal dreams, crying

    Infrequently:

    Suicide, attempted suicide, suicidal thoughts, psychosis, hallucinations, panic attacks

    Rarely:

    Bipolar disorders

    Unknown:

    Thoughts on murder, mania

    Disturbances from the nervous system

    Often:

    Headache, dizziness

    Often:

    Amnesia, memory impairment, syncope, migraine, ataxia, confusion, neuralgia, paresthesia, hypoesthesia, hyperesthesia, hypertension, drowsiness, attention disturbance, tremor, dysgeusia

    Infrequently:

    Neuropathy, peripheral neuropathy

    Rarely:

    Convulsions

    Rarely:

    Cerebrovascular bleeding, cerebrovascular ischemia, encephalopathy

    Unknown:

    Paresis of the facial nerve, mononeuropathy

    Disturbances on the part of the organ of sight

    Often:

    Visual impairment, blurred vision, photophobia, conjunctivitis, eye irritation, tearing, eye pain, dry eye mucosa

    Infrequently:

    Retinal exudates

    Rarely:

    Decreased visual acuity or loss of visual fields, retinal hemorrhage, retinopathy, retinal artery occlusion, retinal vein occlusion, optic neuritis, optic nerve edema, edema of the macula

    Unknown:

    Serous retinal detachment

    Hearing and balance disorders

    Often:

    Hearing impairment / hearing loss, tinnitus, dizziness

    Infrequently:

    Earache

    Heart Disease

    Often:

    Palpitation, tachycardia

    Infrequently:

    Myocardial infarction

    Rare:

    Heart failure, cardiomyopathy, arrhythmia, pericarditis

    Rarely:

    Ischemia of the heart

    Unknown:

    Exudative pericarditis

    Violation of the cardiovascular system

    Often:

    Hypotension, hypertension, hot flashes

    Rarely:

    Vasculitis

    Disturbances from the respiratory system, chest and mediastinal organs

    Often:

    Shortness of breath *, cough *

    Often:

    Dysphonia, nosebleeds, respiratory system disorders, respiratory failure, sinus congestion, nasal congestion, rhinorrhea, increased secretion of the upper respiratory tract, pain in the pharynx and larynx

    Rarely:

    Interstitial pulmonary disease

    Disorders from the gastrointestinal tract

    Often:

    Vomiting, nausea *, abdominal pain, diarrhea, dry mouth *

    Often:

    Dyspepsia, gastroesophageal reflux disease, stomatitis, ulcerative stomatitis, glossodynia, gum bleeding, constipation, flatulence, hemorrhoids, cheilitis, bloating, gingivitis, glossitis,dental abnormalities

    Infrequently:

    Pancreatitis, pain in the oral cavity

    Rarely:

    Ischemic colitis

    Rarely:

    Ulcerative colitis

    Disturbances from the liver and bile ducts

    Often:

    Hyperbilirubinemia, hepatomegaly

    Disturbances from the skin and subcutaneous tissues

    Often:

    Allopecia, itching *, dry skin *, rash *

    Often:

    Psoriasis, photosensitivity reaction, maculopapular rash, dermatitis, erythematous rash, eczema, night sweats, hyperhidrosis, acne, furunculosis, erythema, urticaria, violation of hair structure, disorders of the nails

    Rarely:

    Sarcoidosis of the skin

    Rarely:

    Stevens-Johnson syndrome, toxic epidermal necrolysis, multiforme exudative erythema

    Disturbances from musculoskeletal and connective tissue

    Often:

    Myalgia, arthralgia, musculoskeletal pain

    Often:

    Arthritis, back pain, muscle spasms, pain in the limbs

    Infrequently:

    Bone pain, muscle weakness

    Rarely:

    Rhabdomyolysis, myositis, rheumatoid arthritis

    Disorders from the kidneys and urinary tract

    Often:

    Increased urination, polyuria, impairment of urine indicators

    Rarely:

    Impaired renal function, renal failure

    Violations of the genitals and mammary gland

    Often:

    Amenorrhea, chest pain, menorrhagia, menstrual irregularities, ovarian dysfunction, vaginal disorders, sexual dysfunction (including erectile dysfunction), prostatitis,

    Complications of a general nature and reaction at the site of administration

    Often:

    Reactions at the injection site *, inflammation at the injection site, increased fatigue, asthenia, irritability, chills, hyperthermia, flu-like syndrome, pain

    Often:

    Chest pain, chest discomfort, pain at the injection site, malaise, facial edema, peripheral edema, discomfort, thirst

    Rarely:

    Necrosis at the site of administration

    Laboratory and instrumental data

    Often:

    Weight loss

    * Adverse events that occur frequently (> 1/100 and <1/10) with monotherapy with peginterferon alfa-2b.

    Description of selected side effects in adults

    In most cases, neutropenia and thrombocytopenia are mild (grade 1 or grade 2.) Several cases of more severe neutropenia have been reported in patients receiving recommended doses of peginterferon alfa-2b and ribavirin.Approximately 1.2% of patients treated with peginterferon alfa-2b or interferon alfa-2b in combination with ribavirin had life-threatening mental disorders, such as suicidal thoughts and suicide attempts.

    Side effects from the cardiovascular system (CVS), in particular, arrhythmia, are most likely related to the previous CAS disease and previous therapy with cardiotoxic agents. Rarely, patients who did not have a CVD history in history have cardiomyopathy, which can be reversible after discontinuing interferon alfa therapy.

    Ophthalmic disorders, such as retinopathy (including macular edema), retinal hemorrhage, occlusion of the artery or retinal vein, exudates on the retina, reduced visual acuity or visual field impairment, optic neuritis and optic disc edema, with peginterferon alfa therapy -2b were rare.

    Against the background of treatment with peginterferon alfa-2b a large number of autoimmune and immune disorders, including thyroid pathology,systemic lupus erythematosus, rheumatoid arthritis (newly diagnosed or exacerbated), idiopathic and thrombotic thrombocytopenic purpura, vasculitis, neuropathies, including mononeuropathy and Vogt-Koyanagi-Harada syndrome.

    According to the clinical study, a spectrum of adverse events recorded with the use of Peginferon and ribavirin, did not differ from therapy with PegIntron® and ribavirin, as well as literary data.

    Combination therapy of chronic hepatitis C with ribavirin in HIV-infected patients

    Security Profile Overview

    Side effects

    In HIV-infected patients with chronic hepatitis C who received peginterferon alfa-2b in combination with ribavirin, the following adverse events were observed with a frequency above 5% that were absent in patients with a monoinfection: oral candidiasis (14%), acquired lipodystrophy (13%), a decrease in the number CD(8%), decreased appetite (8%), increased activity of gamma-glutamyltranspeptidase (9%), back pain (5%), increased blood amylase (6%), increased levels of lactic acid in the blood ( 5%), hepatitis with cytolysis (6%), increased lipase activity (6%) and pain in the extremities (6%).

    Certain side effects

    Mitochondrial toxicity:

    In HIV-infected patients with chronic hepatitis C who received nucleoside reverse transcriptase inhibitors in combination with ribavirin, cases of mitochondrial toxicity and lactate acidosis are described.

    Laboratory indicators:

    Although neutropenia, thrombocytopenia and anemia were more common in HIV-infected patients with chronic hepatitis C, in most cases, blood changes could be eliminated by lowering the dose, so they rarely led to early termination of treatment. When treating peginterferon alfa-2b in combination with ribavirin, changes in the blood developed more often than with interferon alfa-2b and ribavirin.

    The decrease in the number CD4-lymphocytes:

    Treatment with peginterferon alfa-2b in combination with ribavirin was accompanied by a reversible decrease in the absolute number Cd4+ cells, which did not combine with a decrease in the percentage of these cells. Number Cd4+ cells increased after a dose reduction or discontinuation of therapy. Combined therapy with peginterferon alfa-2b and ribavirin did not exert a clear negative influence on the level of HIV RNA both during treatment and after its completion. Data on the safety of treatment in HIV-infected hepatitis C patients with the number Cd4+ cells <200 / μL are limited. When prescribing antiviral therapy for HCV in patients infected with HIV, it is necessary to read the instruction for the medical use of the relevant antiretroviral drugs.

    Combination therapy of chronic hepatitis C with ribavirin in children and adolescents

    Security Profile Overview

    Against the background of combined therapy with peginterferon and ribavirin in children and adolescents, correction of the dose is required in 25% of cases. The main causes are anemia, neutropenia and weight loss. In general, the profile of side effects in children and adolescents is similar to that of adults, with the exception of growth-specific child-specific depression. The most common side effects are fever (80%), headache (62%), neutropenia (33%), weakness (30%), anorexia (29%) and erythema at the injection site (29%). As a rule, side effects have an easy or moderate severity.

    Side effects

    The following side effects noted with the use of peginterferon alfa-2b (according to the results of clinical trials in combination with ribavirin),are listed according to the system-organ classes and frequency, according to the following gradation: very often ≥1 / 10, often ≥1 / 100 and <1/10, infrequently ≥ 1/1000 and <1/100, rarely ≥ 1 / 10 000 and <1/1000, very rarely <1/10 000, unspecified frequency (can not be calculated from available data). Within each frequency group, side effects are in order of decreasing clinical importance.

    Infectious and parasitic diseases

    Often:

    Fungal infections, influenza, infection caused by the herpes simplex virus, otitis media, streptococcal pharyngitis, nasopharyngitis, sinusitis

    Infrequently:

    Pneumonia, ascariasis, enterobiasis, shingles, cellulitis, urinary tract infections, gastroenteritis

    Violations of the blood and lymphatic system

    Often:

    Anemia, leukopenia, neutropenia

    Often:

    Thrombocytopenia, lymphadenopathy

    Disorders from the endocrine system

    Often:

    Hypothyroidism

    Disorders from the metabolism and nutrition

    Often:

    Anorexia, decreased appetite

    Disorders of the psyche

    Often:

    Suicidal thoughts, attempted suicide, depression, aggressive behavior, emotional lability, anger, agitation, anxiety, anxiety, mood changes, nervousness, insomnia

    Infrequently:

    Violation of behavior, depressed mood, emotional disorders, fear, nightmares

    Disturbances from the nervous system

    Often:

    Headache, vertigo

    Often:

    Dysgeusia, syncope, impaired concentration, drowsiness, poor sleep quality

    Infrequently:

    Neuralgia, lethargy, paresthesia, hypoesthesia, psychomotor agitation, tremor

    Disturbances on the part of the organ of sight

    Often:

    Pain in the eyes

    Infrequently:

    Hemorrhage in the conjunctiva, itching in the eyes, keratitis, blurred vision, photophobia

    Hearing and balance disorders

    Often:

    Dizziness

    Heart Disease

    Often:

    Palpitation, tachycardia

    Violation of the cardiovascular system

    Often:

    Tides

    Infrequently:

    Hypotension, pallor

    Disturbances from the respiratory system, chest and mediastinal organs

    Often:

    Cough, epistaxis, pain in the pharynx and larynx

    Infrequently:

    Difficulty breathing, discomfort in the nasal cavity, rhinorrhea

    Disorders from the gastrointestinal tract

    Often:

    Abdominal pain, upper abdominal pain, vomiting, nausea

    Often:

    Diarrhea, aphthous stomatitis, cheilosis, ulcerative stomatitis, discomfort in the stomach, pain in the oral cavity

    Infrequently:

    Dyspepsia, gingivitis

    Violations from cmoRliver and bile ducts

    Infrequently:

    Hepatomegaly

    Violations from one hundredRskin and subcutaneous tissue

    Often:

    Alopecia, dry skin

    Often:

    Itching, rash, erythematous rash, eczema, acne, erythema

    Infrequently:

    Photosensitivity reaction, five histo-papular rash, skin peeling, pathological pigmentation, atopic dermatitis, skin discoloration

    Disturbances from the skin and subcutaneous tissues

    Often:

    Myalgia, arthralgia

    Often:

    Musculoskeletal pain, pain in the limbs, back pain

    Infrequently:

    Muscular contractures, twitching of muscles

    Violations from one hundredRthe kidney and urinary tract

    Infrequently:

    Proteinuria

    Violations of the genitals and mammary gland

    Infrequently:

    Women: dysmenorrhea

    Complications of a general nature and reaction at the site of administration

    Often:

    Erythema at the injection site, fatigue, fever, chills, flu-like syndrome, asthenia, pain, malaise, irritability

    Often:

    Reactions at the injection site: itching, rash, dry skin, pain, cold sensation

    Infrequently:

    Pain in the chest, chest discomfort, facial pain

    Laboratory and instrumental data

    Often:

    Slowing down the growth rate (decrease in height and / or body weight within the age limit)

    Often:

    Increase in thyroid-stimulating hormone concentration in the blood, increase in thyroglobulin concentration

    Infrequently:

    The appearance of antithyroid antibodies

    Injuries and poisonings

    Infrequently:

    Stunning

    Description of selected side effects in children and adolescents

    Deviations of laboratory indicators, in most cases, are mild or moderate. A decrease in hemoglobin, leukocyte count, platelet count and neutrophil count, an increase in bilirubin level may require a reduction in dose or cancellation of therapy (See "Method of administration and dose"). The changes in laboratory parameters detected in the clinical trial in patients who received ribavirin and peginterferon alfa-2b, returned to baseline values ​​within a few weeks after the end of therapy.

    Overdose:

    Cases of the use of peginterferon alfa-2b in doses exceeding the recommended 10.5 times. The maximum daily dose reported was 1200 μg.In general, the undesirable events observed during an overdose corresponded to the available data on the safety profile of peginterferon alfa-2b, but their severity may be higher.

    The standard methods used to accelerate the elimination of the drug, for example dialysis, are ineffective. There is no specific antidote. When an overdose is recommended, symptomatic treatment and a complete examination of the patient.

    Interaction:

    Due to the fact that the metabolism of peginterferon alfa-2b is accompanied by an increase in the activity of cytochrome P450 isoenzymes CYP2D6 and CYP2C8/9, with the joint administration of the drug Peguferon and drugs metabolized with the participation of these isoenzymes, you should be careful. Especially when prescribing drugs with a narrow therapeutic window, such as warfarin, phenytoin (CYP2C9) and flecainide (CYP2D6).

    This may be partly due to the improvement in the metabolic function due to the arrest of the inflammatory process against the background of peginterferon alfa-2 therapyb. Thus, caution is required in the appointment of peginterferon alfa-2b patients receiving medications with a narrow therapeutic window, whose metabolism may change with moderate liver damage.

    With repeated joint use of the drug Peginferon and ribavirin, there are no signs of pharmacokinetic interaction between them.

    Methadone

    In patients who received maintenance therapy with methadone, which was first assigned peginterferon alfa-2b in a dose of 1.5 μg / kg / week. there was an increase AUC methadone by approximately 15%. The clinical significance of this effect is not clear. However, with the appointment of Peguferferone, such patients need monitoring of sedation, respiratory depression and lengthening of the interval QT.

    Chronic hepatitis C in HIV-infected patients

    The use of nucleoside analogues alone or in combination with other nucleosides led to the development of lactic acidosis. In vitro ribavirin caused an increase in the levels of phosphorylated metabolites of purine nucleosides. This effect may increase the risk of developing lactic acidosis by the action of purine nucleoside analogues (eg, didanosine or abacavir).Combined use of ribavirin and didanosine is not recommended. Mitochondrial toxicity, in particular lactic acidosis and pancreatitis, has been reported, in some cases fatal (see instructions for ribavirin use).

    There are cases of worsening of the course of anemia caused by the appointment of ribavirin, with zidovudine, although the exact mechanism of this effect is not clear. Thus, due to the increased risk of anemia, the combination of ribavirin with zidovudine is not recommended. In patients receiving combined antiretroviral therapy, especially with an anemia due to zidovudine, a history of zidovudine should be considered.

    Telbivudine

    Co-administration of telbivudine with peginterferon alfa-2b is associated with an increased risk of peripheral neuropathy. The mechanism of this effect is not clear. Combination of the drug Peguferon with telbivudine is contraindicated.

    Special instructions:

    The psychic sphere and the central nervous system (CNS)

    In some patients during therapy with peginterferon alfa-2b and within 6 months after its cancellation severe violations from the central nervous system, in particular depression, suicidal thoughts and suicide attempts can be observed.Other disorders from the central nervous system may also occur, including aggressive behavior (sometimes, thoughts of murder), bipolar disorders, mania, confusion and alteration of consciousness. Patients should be carefully monitored for symptoms of mental disorders. With the development of these side effects, due to their potential seriousness, the need for therapeutic correction should be assessed. If mental symptoms persist or build up or suicidal intentions occur, the treatment with Peguferon should be reversed and provide timely advice to the psychiatrist.

    Patients with severe mental disorders, including a history

    If it is necessary to prescribe Peginferon to patients with severe mental disorders (including patients who have indicated such a history of the disorder), treatment can be started only after a thorough examination and appropriate therapy of a mental disorder.

    Children and adolescents with severe mental disorders at present or in the history should not be prescribed ribavirin in combination with peginterferon alfa-2b. When combined therapy with interferon alpha-2b there was a higher incidence of suicidal thoughts and suicide attempts than in adults, both during treatment and in the following 6 months. As in adults, other side effects from the psyche (such as depression, emotional lability, drowsiness) can be noted in children and adolescents.

    Patients who abuse substances

    Patients who are infected with the hepatitis C virus, abusing substances (alcohol, marijuana or other substances), have an increased risk of developing and / or exacerbating psychiatric disorders with interferon alfa-2b. If it is necessary to prescribe interferon therapy for such patients, a thorough examination before treatment for psychiatric disorders and other substance abuse is indicated, as well as close observation during and after treatment. It is recommended to intervene earlier to prevent the recurrence or development of mental disorders and drug use.

    Growth and development (children and adolescents)

    Combination therapy causes growth retardation, the reversibility of which is not clear. The risk-benefit ratio should be assessed individually in each case, taking into account the progression of the disease (especially the degree of fibrosis), the presence of concomitant diseases (eg HIV coinfection), and the predictors of the virologic response (virus genotype and viral load). Whenever possible, children should receive treatment after a puberty growth jump. There are no data on the long-term effect on puberty.

    Cases of confusion and coma, including cases of encephalopathy, are more common in some patients, usually elderly, taking high doses of interferon alfa-2b on oncological indications. While these effects are generally reversible, it can sometimes take up to 3 weeks for a complete recovery. Very rarely, against a background of high doses of interferon alfa-2b there may be cramps.

    Hypersensitivity immediate type

    In rare cases, interferon alpha-2 therapyb complicated by immediate-type hypersensitivity reactions (urticaria, angioneurotic edema, bronchospasm, anaphylaxis).If such reactions occur, Peguferon should be discontinued and immediate symptomatic therapy should be prescribed. Transient rash does not require discontinuation of treatment.

    The cardiovascular system

    When treating Peginferon, patients who are currently or in an anamnesis heart failure, myocardial infarction and / or arrhythmia, should be under constant supervision. In patients with heart disease, electrocardiography is recommended before and during treatment. Arrhythmias (mostly supraventricular) tend to be amenable to conventional therapy, but may require the withdrawal of Peguferon. Data on children and adolescents with diseases of the cardiovascular system are absent.

    Liver function

    When signs of decompensation of liver disease should be discontinued treatment with the drug Peguferon.

    Increased body temperature

    Although a rise in body temperature can be observed within the influenza-like syndrome, which is often recorded in interferon treatment, nevertheless, other causes of persistent elevation of body temperature need to be excluded.

    Hydration

    In patients receiving therapy with Peguferon, it is necessary to provide adequate hydration, since in some patients who received peginterferon alfa-2b, hypotension was observed, associated with a decrease in the volume of fluid in the body. In such cases, a substitution fluid may be required.

    Changes in the lungs

    In rare cases, patients who received interferon alfa-2b, the lungs developed infiltrates of unclear etiology, pneumonitis or pneumonia, sometimes with a fatal outcome. When fever, cough, dyspnea and other respiratory symptoms occur, all patients should be given a chest x-ray. In the presence of infiltrates on the chest radiograph or signs of pulmonary dysfunction, such patients should be monitored more closely and, if necessary, abolished interferon alfa-2b. Immediate withdrawal of interferon alfa-2b and treatment with glucocorticosteroids lead to the disappearance of unwanted phenomena from the lungs.

    Autoimmune diseases

    When treating interferon alfa-2 preparationsb noted the occurrence of autoantibodies and the occurrence of autoimmune diseases.Clinical manifestations of autoimmune diseases appear to arise more often when interferon is treated in patients predisposed to the development of autoimmune disorders. In patients with suspected autoimmune disease, a thorough examination and evaluation of the benefit / risk of continued interferon therapy should be undertaken.

    In patients with CHC who received interferon therapy, cases of Vogt-Kayanagi-Harada syndrome were registered. The syndrome is based on granulomatous inflammation with damage to the eyes, hearing organ, meninges and skin. If Vogt-Kayanagi-Harad syndrome is suspected, antiviral treatment should be discontinued and the question of prescribing glucocorticosteroids should be resolved.

    Changes from the organ of vision

    Ophthalmic disorders including retinal hemorrhage, exudates in the retina, occlusion of the artery or vein of the retina on the background of interferon alfa-2b are rare. All patients should undergo an ophthalmological examination before starting therapy. If you identify any symptoms, including reduced visual acuity or changes in the visual fields, you need to conduct a more complete ophthalmological examination.Against the background of therapy with the drug Peginferon it is recommended to conduct a periodic ophthalmological examination, especially in patients with diseases associated with the development of retinopathy, such as diabetes mellitus or hypertension. With the development of new or worsening of the current ophthalmic disorders, Peguferonone should be withdrawn.

    Changes in the thyroid gland

    Sometimes in patients with CHC receiving interferon alfa develops hypothyroidism or hyperthyroidism. Before the beginning of therapy with the preparation Peginferon it is necessary to determine the concentration of thyrotropic hormone (TSH), if any abnormalities of thyroid function are revealed, appropriate treatment should be prescribed. When the symptoms of possible thyroid dysfunction appear on the background of therapy, the concentration of TSH is determined. In case of thyroid dysfunction, combined therapy with Peginferon can be continued if it is possible to medically maintain the concentration of TSH within the limits of normal values. In children and adolescents, the function of the thyroid gland (for example, to determine the concentration of TSH) should be investigated every 3 months.

    Metabolic disorders

    There may be hypertriglyceridemia and its progression. Monitoring of the lipid profile is recommended.

    Chronic hepatitis C in HIV-infected patients

    Mitochondrial toxicity and lactate acidosis.

    In HIV-infected patients receiving highly active antiretroviral therapy (HAART), the risk of developing lactic acidosis is increased. Caution should be exercised when adding the drug Peguferon and ribavirin to HAART (see instructions for the use of ribavirin).

    Decompensation of liver disease in patients with co-infection with HCV / HIV

    In HIV-infected patients with far-reaching liver cirrhosis caused by the hepatitis C virus receiving HAART, the risk of decompensation of liver disease and death is increased. Use of interferon alfa-2b in the form of monotherapy or in combination with ribavirin may lead to an increase in the above-described risk in this group of patients. Other risk factors for decompensating liver disease in HIV-infected patients include didanosine treatment and elevated serum bilirubin levels. It is necessary to constantly monitor patients with co-infection receiving antiretroviral therapy and treatment for hepatitis C, and periodically evaluate the Child-Pugh index.When decompensating liver disease should immediately stop treatment of hepatitis C and revise antiretroviral therapy.

    Changes in blood in HIV-infected patients with hepatitis C

    In HIV-infected patients with chronic hepatitis C receiving combined treatment with peginterferon alfa-2b and ribavirin concurrent with HAART, the risk of developing neutropenia, thrombocytopenia and anemia is higher than in patients infected with HCV alone. These changes in most cases can be eliminated by reducing the dose, but this category of patients should carefully monitor blood counts. Patients receiving combination therapy with Peginferon and ribavirin together with zidovudine have an increased risk of developing anemia, therefore, the combination of this combination with zidovudine is not recommended.

    Patients with low CD4-cells

    Information on the efficacy and safety of treatment of HIV-infected patients with hepatitis C with a number CD4 cells <200 / μL are limited, so caution is necessary in such cases. Information on the toxic effects of antiretroviral drugs, which are planned to be used in combination with Peguferferone and ribavirin, and possible cross-toxic reactions -in instructions for the use of appropriate drugs.

    Changes in the teeth and periodontium

    Patients receiving combination therapy with peginterferon alfa-2b and ribavirin, there were pathological changes in the teeth and peri-toothed tissues that could lead to tooth loss. Dryness in the oral cavity with long-term combination therapy with ribavirin and peginterferon alfa-2b can contribute to damage to the teeth and mucous membrane of the oral cavity. Patients should brush their teeth 2 times a day and have regular check-ups at the dentist.

    Patients who are vomiting should then thoroughly rinse the oral cavity.

    Recipients of organs

    The efficacy and safety of the use of PEGINFERON in the recipients of the organs have not been studied. Preliminary data suggest that interferon alpha therapy can increase the incidence of rejection of kidney and liver transplants.

    Psoriasis and sarcoidosis

    Due to the fact that cases of exacerbation of psoriasis and sarcoidosis are described against interferon alpha therapy, the appointment of Peguferferone to such patients is only shown if the potential benefit exceeds the potential risk.

    Laboratory research

    All patients before the start of treatment with the drug Peginferon is recommended to perform general and biochemical blood tests, as well as research of thyroid function.

    The following initial blood values ​​are acceptable:

    Platelets ≥ 100 x 109/ l;

    Neutrophils ≥ 1.5 x 109/ l;

    A thyroid-stimulating hormone within the limits of norm.

    Follow-up laboratory tests are recommended at the 2nd and 4th weeks of treatment and then regularly, as needed. Periodically, on the background of treatment should determine the level of RNA of hepatitis C virus.

    Long-term maintenance therapy

    Due to the lack of appropriate clinical trial data for pegylated interferon alfa-2b, Peguferonone should not be used for long-term maintenance monotherapy.

    Rare hereditary diseases

    Patients with intolerance to fructose, glucose-galactose malabsorption or sucrose-isomaltase deficiency drug Peguferon is contraindicated.

    Effect on the ability to drive transp. cf. and fur:

    When fatigue, drowsiness, or confusion occurs, it is not recommended to drive the car or other equipment with Pegginferon.

    Form release / dosage:

    Lyophilizate for the preparation of a solution for subcutaneous administration, 50 μg, 80 μg, 100 μg, 120 μg and 150 μg.

    Packaging:

    50, 80, 100, 120 or 150 μg of active substance into a bottle of colorless glass (type I) with a capacity of 2 ml, sealed with a bromobutyl stopper and rolled with an aluminum type cap "flip-off"A self-adhesive label is applied to the bottle.

    One bottle is placed in a contoured tray of white shock-resistant polystyrene, closed with a transparent PVC lid.

    1 contour pallet together with instructions for medical use put in a pack of cardboard.

    Storage conditions:

    At a temperature of 2 ° C to 8 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003437
    Date of registration:02.02.2016
    Expiration Date:02.02.2021
    The owner of the registration certificate:FARMAKTIV, LLC FARMAKTIV, LLC Russia
    Manufacturer: & nbsp
    Representation: & nbspPharmaceutiv, Open CompanyPharmaceutiv, Open Company
    Information update date: & nbsp03.08.2016
    Illustrated instructions
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