Composition, form of production and packaging
Liofilizate for the preparation of solution for s / w introduction of white or almost white color; solvent - a transparent, colorless liquid without odor and taste.
0.5 ml of finished p-ra
peginterferon alfa-2b 100 Ојg
Auxiliary substances: sodium hydrophosphate (in terms of anhydrous) - 0.75 mg, sodium dihydrogen phosphate dihydrate (in terms of anhydrous) - 0.75 mg, sucrose - 40 mg, polysorbate 80 - 0.05 mg, water d / and - up to 0.5 ml (per dose).
Solvent: water d / u - 0.7 ml *.
* - the solvent is added in an excessive amount to compensate for losses when dissolving the lyophilizate and introducing the prepared solution.
100 Ојg - glass bottles (1) in a set. with a solvent of 0.7 ml amp. 1 PC. - packings of cellular contour (1) - packs cardboard.
Liofilizate for the preparation of solution for s / w introduction of white or almost white color; solvent - a transparent, colorless liquid without odor and taste.
0.5 ml of finished p-ra
peginterferon alfa-2b 120 Ојg
Auxiliary substances: sodium hydrophosphate (in terms of anhydrous) - 0.75 mg, sodium dihydrogen phosphate dihydrate (in terms of anhydrous) - 0.75 mg, sucrose - 40 mg, polysorbate 80 - 0.05 mg, water d / and - up to 0.5 ml (per dose).
Solvent: water d / u - 0.7 ml *.
* - the solvent is added in an excessive amount to compensate for losses when dissolving the lyophilizate and introducing the prepared solution.
120 mcg - bottles of glass (1) in a set. with a solvent of 0.7 ml amp. 1 PC. - packings of cellular contour (1) - packs cardboard.
Liofilizate for the preparation of solution for s / w introduction of white or almost white color; solvent - a transparent, colorless liquid without odor and taste.
0.5 ml of finished p-ra
peginterferon alfa-2b 150 Ојg
Auxiliary substances: sodium hydrophosphate (in terms of anhydrous) - 0.75 mg, sodium dihydrogen phosphate dihydrate (in terms of anhydrous) - 0.75 mg, sucrose - 40 mg, polysorbate 80 - 0.05 mg, water d / and - up to 0.5 ml (per dose).
Solvent: water d / u - 0.7 ml *.
* - the solvent is added in an excessive amount to compensate for losses when dissolving the lyophilizate and introducing the prepared solution.
150 mcg - bottles of glass (1) in a set. with a solvent of 0.7 ml amp. 1 PC. - packings of cellular contour (1) - packs cardboard.
Liofilizate for the preparation of solution for s / w introduction of white or almost white color; solvent - a transparent, colorless liquid without odor and taste.
0.5 ml of finished p-ra
peginterferon alfa-2b 50 Ојg
Auxiliary substances: sodium hydrophosphate (in terms of anhydrous) - 0.75 mg, sodium dihydrogen phosphate dihydrate (in terms of anhydrous) - 0.75 mg, sucrose - 40 mg, polysorbate 80 - 0.05 mg, water d / and - up to 0.5 ml (per dose).
Solvent: water d / u - 0.7 ml *.
* - the solvent is added in an excessive amount to compensate for losses when dissolving the lyophilizate and introducing the prepared solution.
50 mcg - bottles of glass (1) in a set. with a solvent of 0.7 ml amp. 1 PC. - packings of cellular contour (1) - packs cardboard.
Liofilizate for the preparation of solution for s / w introduction of white or almost white color; solvent - a transparent, colorless liquid without odor and taste.
0.5 ml of finished p-ra
peginterferon alfa-2b 80 Ојg
Auxiliary substances: sodium hydrophosphate (in terms of anhydrous) - 0.75 mg, sodium dihydrogen phosphate dihydrate (in terms of anhydrous) - 0.75 mg, sucrose - 40 mg, polysorbate 80 - 0.05 mg, water d / and - up to 0.5 ml (per dose).
Solvent: water d / u - 0.7 ml *.
* - the solvent is added in an excessive amount to compensate for losses when dissolving the lyophilizate and introducing the prepared solution.
80 Ојg - glass bottles (1) in a set. with a solvent of 0.7 ml amp. 1 PC. - packings of cellular contour (1) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Pegaltevir is a preparation of pegylated interferon alfa-2b, which is obtained by covalent conjugation of recombinant interferon alpha-2b and monomethoxypolyethylene glycol.
The biological activity of PegAltivir is due to interferon alpha-2b. Recombinant interferon alpha-2b is obtained from an Escherichia coli clone that contains a genetically engineered plasmid hybrid encoding human leukocyte alpha-2b interferon. 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, Mx proteins). 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 alpha-2b promotes the differentiation of T-helper cells, 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 PegAltevir was studied by 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 PegAtelvir and PegIntron to healthy volunteers at a dose of 1.5 Ојg / kg body weight, a comparable dynamics of neopterin concentration in the blood was observed, Cmax was reached after 48 hours.
A preclinical comparative study of biological activity on the reevaluated groups of animal preparations PegAtelivir and PegIntron produced comparable results.
PHARMACOKINETICS
Pegylation of the interferon alpha-2b molecule leads to an increase in the volume of distribution and a decrease in clearance. A decrease in clearance leads to more than a 10-fold increase in T 1/2 as compared to unmodified interferon alpha-2b.
The pharmacokinetics of PegAltivir was studied in comparison with PegIntron. In the pre-clinical study, no statistically significant differences were found. With a single subcutaneous injection at a dose of 1.5 Ојg / kg to healthy volunteers, the main pharmacokinetic parameters are comparable. With max of peginterferon alfa-2b after a single subcutaneous injection of Pegaltevir, the average was attained in 16.5 hours and was about 579 ng / ml. The volume of distribution (Vd) averaged 2.84 l / kg. T 1/2 was, on average, 26.9 hours; the elimination constant (K el ) is 0.03 hours -1 ; clearance (Cl) (the rate of purification of blood from peginterferon alfa-2b), on average, 90.43 ml / h / kg.
Pharmacokinetics in patients with impaired renal function
Kidney clearance is 30% of the total clearance of peginterferon alfa-2b. According to the study with a single injection (1.0 Ојg / kg) in patients with renal insufficiency, an increase in C max , AUC, T 1/2 is proportional to the degree of renal failure. With repeated administration (1.0 Ојg / kg subcutaneously once a week for four weeks), the clearance of peginterferon alfa-2b is reduced by an average of 17% for renal insufficiency of the middle degree (creatinine clearance 30-49 ml / min) and, on average, 44% - with renal failure of severe degree (creatinine clearance 15-29 ml / min), compared with patients with unchanged kidney function. In patients with severe renal insufficiency, hemodialysis does not affect the clearance of peginterferon alfa-2b. In this regard, in patients with moderate and severe renal insufficiency, the dose of PegAltevir should be reduced when administered as monotherapy.
At clearance of creatinine <50 ml / min combined therapy with PegAltivir and ribavirin is contraindicated. In connection with the individual variability of the pharmacokinetics of interferon, patients with severe renal insufficiency who receive Pegaltevir should be closely monitored.
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 the elderly
The pharmacokinetics of peginterferon alfa-2b does not depend on age, so a change in the dose of Pegaltevir in elderly people is not required. Pharmacokinetics in patients older than 70 years have not been studied.
Pharmacokinetics in children
In children and adolescents receiving peginterferon alfa-2b at a dose of 60 Ојg / m / week, a log-transformed exposure ratio during the dosing interval is expected to be 58% (90% confidence interval: 141-177%) higher than in adults receiving peginterferon alpha-2b at a dose of 1.5 Ојg / kg / week.
Neutralizing antibodies to interferon
Neutralizing antibodies to interferon were analyzed in serum samples from patients treated with PegAtlevir in a clinical trial. These antibodies neutralize the antiviral activity of interferon. The frequency of detection of neutralizing antibodies in patients treated with PegAtlevir at a dose of 1.5 Ојg / kg was 1.9%.
INDICATIONS
Adults (triple therapy)
- treatment of chronic hepatitis C, genotype 1, PegAltevir in combination with ribavirin and NS3 / 4A protease inhibitor in adult patients with compensated liver disease who have not previously received antiviral therapy or have failed antiviral therapy.
Adults (dual therapy and monotherapy)
- Treatment of chronic hepatitis C with PegAltevir 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 PegAltivir in combination with ribavirin in adult patients who had not previously received antiviral therapy, including patients with concomitant clinically stable HIV infection, and in adults who previously had failed antiviral therapy with a combination of interferon alfa (pegylated or unpegilated ) with ribavirin or interferon alpha monotherapy.
- Pegaltevir monotherapy with chronic hepatitis C is indicated only in case of intolerance or contraindications for ribavirin administration.
Children (double therapy)
- Treatment of chronic hepatitis C with PegAltevir 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 is necessary to take into account that combination therapy may cause growth retardation. The reversibility of growth retardation is not known. The decision on the appointment of treatment should be taken individually.
DOSING MODE
Therapy with PegAltivir should be started by a doctor with experience in the treatment of patients with hepatitis C, and further under his supervision.
Pegaltevir 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 PegAltivir (double or triple)
Double therapy (PegAltivir with ribavirin): is prescribed for adults and children 3 years and older.
Triple therapy (PegAltivir with ribavirin and NS3 / 4A protease inhibitor): is assigned to adult patients infected with the hepatitis C virus, genotype 1.
Dosing regimen in adults
With combined therapy with ribavirin, Pegaltevir is administered as a subcutaneous injection at a dose of 1.5 Ојg per 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 PegAltivir and ribavirin:
Body weight (kg) PegAltivir ribavirin
Concentration (Ојg / 0.5 ml) Volume per week (ml) Daily dose (mg) Number of capsules / tablets (200 mg each)
<40 50 0.5 800 mg / day 4 a
40-50 80 0.4 800 mg / day 4 a
51-64 80 0.5 800 mg / day 4 a
65-75 100 0.5 1000 mg / day 5 b
76-80 120 0.5 1000 mg / day 5 b
81-85 120 0.5 1200 mg / day 6 in
86-105 150 0.5 1200 mg / day 6 in
> 105 150 0.5 1400 mg / day 7 g
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: 2 in the morning + 4 in the evening
When prescribing PegAltevir in triple therapy, it is necessary to read the instructions for the medical use of the NS3 / 4A protease inhibitor.
Duration of treatment in adults who did not receive treatment
Triple therapy: it is necessary to read the instructions for the medical use of the NS3 / 4A protease inhibitor.
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 appropriateness of continuing 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 detected after 12 weeks of antiviral therapy, but has its level decreased by? 2 log from the initial value, it is necessary to re-evaluate the effectiveness of treatment after 24 weeks of therapy. 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 low virus concentration (<600000 IU / ml) who had eliminated the virus after 4 weeks of treatment and did not detect RNA of the virus before the 24th week of therapy, treatment after the 24th week may be discontinued (the total duration of the course - 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 is a decrease in viral RNA?2 log from the initial value 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 the NS3 / 4A protease inhibitor. 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 1 genotype, the response in which has not been achieved, has not been studied.
Dosage regimen in children (only dual therapy)
The dosage regimen in children 3 years and older and adolescents is determined by the surface area of ​​the body for PegAltivir and body weight for ribavirin. The recommended dose of PegAltivir is 60 μg / m 2 / ned subcutaneously in combination with ribavirin at a dose of 15 mg / kg / day inward, divided into two doses, along with meals (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), 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 PegAltivir, it is recommended that treatment be discontinued if, after 12 weeks, a decrease in the level of viral RNA is <2 log in comparison with the baseline value, or when blood viral RNA is detected in the blood 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 PegAltevir, it is recommended to discontinue treatment if 12 weeks reduction in viral RNA levels of <2 log compared to baseline, or at detection of viral RNA in the blood after 24 weeks of treatment.
Monotherapy PegAltevir (adults)
Dosage
drug PegAltevir administered subcutaneously at a dose of 0.5 or 1.0 mg / kg 1 time a week
body weight (kg) 0.5 mcg / kg 1.0 mcg / kg
vial Dosage (mcg / 0.5 ml) dose to be administered one time per week (ml) vial Dosage (mg / 0.5ml) dose to be administered once a week 1 (ml)
30-35 50 80 0.2 0.15
36-45 0.2 0.4 50 50
46-56 50 0.25 50 0.5
80 80 0.2 57-72 0.4
73-88 0.4 50 80 0.5
89-106 50 0.5 100 0.5
107-120 120 0.4 * 80 0.5
* In patients with weight body> 120 kg dose PegAltevira calculated by body weight.
PegAltevir monotherapy in patients co-infected with HCV / HIV has not been studied.
Duration of treatment
Patients who have a virological response at week 12, treatment should be continued for a further 3 months (total course length - 6 months). Extension of therapy up to 1 year (48 weeks) may be based on prognostic factors (genotype, age> 40 years, male gender, bridging fibrosis).
Correction dose for all patients (monotherapy and combination therapy)
In the event of serious adverse events or laboratory abnormalities monotherapy or combination therapy, comprising a drug PegAltevir required dose correction PegAltevira and / or ribavirin until termination of adverse events. Reduced doses of NS3 / 4A protease inhibitor is not recommended. NS3 / 4A inhibitor should not be administered without the drug PegAltevir and ribavirin. Since the dose of ribavirin PegAltevir and affect the outcome of treatment, they should as far as possible, to be approximate to the recommended standard dose.
Laboratory findings Reducing the dose of ribavirin only if 1 : Dose reduction is only peginterferon alfa-2b, if 2 : Termination of therapy if:
Hemoglobin > 85 g / l and <100 g / l - <85 g / l
Adults: hemoglobin in patients with heart disease in a stable form hemoglobin dropped to> 20 g / l for any 4 weeks during treatment (permanent the use of low-dose) <120 g / l after 4 weeks of dose reduction
Children: hemoglobin not applicable (see "Special instructions").
The number of white blood cells - ? 1.0 10 9 ? / L and <1.5 Г— 10 9 / L <1.0 10? 9 / l
The number of neutrophils - ? 0.5 10 9 ? / L and <0.75 10 9 / L <0.5 10? 9 / L
Platelet count - Adults: 25 Г— 10 9 / L and <50? 109 / l Children and adolescents: ? 50 10 9 ? / L and <70 10 9 / L Adults: <25 10? 9 / l Children and adolescents <50 10? 9 / l
Content of conjugated bilirubin - - 2.5 * ULN?
The free bilirubin> 0 , 05 g / l -> 0.04 g / l (for> 4 weeks)
creatinine serum - -> 0.02 g / l
creatinine clearance - - Cancel ribavirin if <50 ml / min
ALT / AST * ? * - - 2 (reference value), and> 10 ULN *
Notes:
1In adults, the first dose reduction of ribavirin is carried out on 200 mg / day (for those who received 1400 mg - 400 mg / day). If necessary, a second dose reduction of ribavirin is carried out for 200 mg / day. Patients ribavirin dose reduced to 600 mg / day should receive one capsule / tablet preparation (200 mg) in the morning and two capsules / tablets (200 mg) in the evening.
In children and adolescents the first dose reduction of ribavirin produce up to 12 mg / kg / day, the second dose reduction of ribavirin produce up to 8 mg / kg / day.
2 Adult first dose reduction PegAltevira carried to 1.0 mcg / kg / week. If necessary, the second dose reduction PegAltevira carried to 0.5 mcg / kg / week.
In children and adolescents the first decline dose PegAltevira produce up to 40 g / m 2/ week, the second dose reduction PegAltevira produce up to 20 g / m 2 / wk.
* - the upper limit of normal.
** - Alanine aminotransferase / aspartate aminotransferase.
Reducing the dose PegAltevir drug in adults it can be achieved by reducing the volume of the injected solution, or using a lower dose of the drug. In children and adolescents - by correcting the recommended dose in two stages with a starting dose of 60 mg / m 2 / week to 40 mg / m 2 / week, then, if necessary, up to 20 mcg / m2 / week.
Recommendations to reduce drug dose PegAltevir in two stages in a combination therapy in adults
First dose reduction PegAltevira to 1 ug / kg The second dose reduction PegAltevira to 0.5 mg / kg
body weight (kg) vial Dosage (mg / 0.5ml) Number PegAltevira (g) Displacement PegAltevira (ml) Body weight (kg) vial Dosage (mg / 0.5 ml ) Number PegAltevira (g) Displacement PegAltevira (ml)
<40 50 35 0.35 <0.2 20 40 50
40-50 120 48 50 40-50 0.2 25 0.25
51-64 80 0.35 56 51 80 32 0.2 -64
65-75 65-75 100 70 0.35 50 35 0.35
76-85 80 76-85 80 0.5 120 48 0.2
86-105 0.4 86-105 120 96 50 50 0.5
> 105 150 105 0.35> 105 80 64 0.4
Guidelines for dose reduction PegAltevir drug when monotherapy in adults
Laboratory parameters Dose reduction of peginterferon alfa-2b to half the therapeutic dose, if the termination of injection peginterferon alfa-2b, if the
number of neutrophils? 0.5 Г— 10 9 / L and <0.75 x 10 9 / L <0.5 Г— 10 9 / L
Platelet count? ВЈ 25 10 9 / l <50 10? 9 / l <25 10? 9 / L
in adults who receive monotherapy PegAltevir a dose of 0.5 mg / kg, dose reduction may be achieved by reduction of the volume of drug solution administered half:
weight body (kg) vial Dosage (mg / 0.5ml) Number PegAltevira (g) Displacement PegAltevira (ml)
30-35 8 0.08 50
36-45 50 10 0.1
50 13 0.13 46-56
57-72 80 16 0.1
73-88 50 20 0.2
89-106 50 25 0.25
107-120 * 80 32 0.2
* Patients with body weight> 120 kg , PegAltevira dose is calculated according to body weight. This may require a combination of different volumes and doses.
In adults receiving PegAltevir monotherapy at a dose of 1.0 mg / kg, dose reduction may be achieved by decrease in the volume of the drug solution administered by half or decrease its concentration:
Body weight (kg) vial Dosage (mg / 0.5ml) Number PegAltevira ( g) Displacement PegAltevira (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
50 0.5 50 89-106
107-120 0.4 64 * 80
* Patients with body weight> 120 kg, the dose of the drug PegAltevir calculated by body weight. This may require a combination of different volumes and doses.
Special patient population
dose adjustment in patients with renal insufficiency
Monotherapy:
PegAltevir drug should be used with caution in patients with renal insufficiency, moderate and severe. In patients with moderate renal impairment (creatinine clearance of 30-50 ml / min), the initial dose PegAltevir preparation should be reduced by 25%. Patients with severe renal impairment (creatinine 15-29 ml / min clearance), including patients undergoing hemodialysis, PegAltevir initial dose of the drug should be reduced by 50%. Data on the use of pegylated interferon alfa-2b in patients with creatinine clearance <15 mL / min no. Patients with renal insufficiency mild to severe, including hemodialysis, should be closely monitored. If during the treatment of a decline in renal function,drug therapy should be discontinued PegAltevir.
Combination Therapy:
Patients with creatinine clearance <50 mL / min assignment PegAltevir preparation in combination with ribavirin is contraindicated. In the appointment of combination therapy in patients with renal insufficiency should be closely monitored in relation to the development of anemia.
Liver failure
The safety and efficacy of drug treatment PegAltevir patients with severe hepatic impairment has not been studied, so these patients use the drug should not be PegAltevir.
Elderly patients (65 years and older)
Dependence pharmacokinetics of peginterferon alfa-2b of age is not revealed. Data on the results of pharmacokinetic studies in the elderly after a single subcutaneous injection of peginterferon alfa-2b indicate that the selection of the dose based on age is not required. In patients older than 70 years the pharmacokinetics of peginterferon alfa-2b has not been studied.
Children
PegAltevir drug in combination with ribavirin may be administered to children aged 3 years and older.
Instructions for preparation of injection solution
Lyophilisate PegAltevir drug should be diluted only the supplied solvent. PegAltevir The drug should not be mixed with other medicines. Using a sterile syringe, 0.7 mL of water for injection is introduced into a vial PegAltevir. The vial was gently shake to complete dissolution of the powder. Dissolution time should not exceed 10 minutes; usually a powder dissolves faster. The required dose drawn into a sterile syringe. For administration used 0.5 ml of solution. As with any other drugs for parenteral use prepared solution should be inspected before administration. The solution should be clear, colorless and free from visible particles. In the case of color change or appearance of visible particles, a solution should not be used.
SIDE EFFECT
Adults
Triple therapy
is necessary to read the instructions on the medical application NS3 / 4A protease inhibitor.
Dual therapy and monotherapy
Understanding Security profile:
The most frequent (by the results of clinical trials in more than half of the patients) side effects of combination therapy with peginterferon alfa-2b and ribavirin were fatigue, headache and injection-site reaction. More than 25% of cases observed nausea, chills, insomnia, anemia, fever, myalgia, asthenia, pain, alopecia, anorexia, weight loss, depression, rash and irritability. Typically, the side effects were mild or moderate severity, were well controlled and required no reduction in dose or discontinuation. Fatigue, alopecia, pruritus, nausea, anorexia, weight loss, irritability, and insomnia were less common during monotherapy with peginterferon alfa-2b, than the combined treatment.
Side effects:
The following side effects are marked when using the drug peginterferon alfa-2b, are listed in accordance with system-organ class and frequency, according to the following gradation: very often -? 1/10, often - 1/100 and <1/10, uncommon - 1/1000 and <1/100, rare - 1/10000 and <1/1000, very rarely - <1/10 000, unspecified frequency (can not be calculated from the available data). Within each frequency group the side effects are arranged in descending order of their clinical significance.
Infections and infestations
Very often a viral infection *, pharyngitis *
Often a bacterial infection, influenza, upper respiratory tract infection, bronchitis, infection caused by the herpes simplex virus, sinusitis, otitis media, rhinitis, fungal infection
Infrequently infection at the injection site, lower respiratory tract infection
Violations of the blood system and lymphatic system
Very often, anemia, neutropenia,
often lymphadenopathy, hemolytic anemia, leukopenia, thrombocytopenia
Very rarely, aplastic anemia,
Unspecified frequency of pure red cell aplasia
Violations by the immune system
infrequently hypersensitivity reactions
Rarely sarcoidosis
Unspecified frequency of immediate hypersensitivity reactions, including angioneurotic edema, anaphylaxis and ana prophylactically reactions, including anaphylactic shock, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, systemic lupus erythematosus
Disorders of the endocrine system
is often hypothyroidism, hyperthyroidism,
metabolic disorders and nutrition
Very often anorexia
often hypokalemia, hyperuricemia, dehydration, increased appetite
Uncommon diabetes, hypertriglyceridemia
Rarely diabetic ketoacidosis
violations by the psyche
is often depression, anxiety *, emotional lability *, impaired concentration attention, insomnia
is often aggressive behavior, agitation, anger, mood changes, behavioral disorders, nervousness, sleep disturbances, decreased ibido, apathy, abnormal dreams, crying
Uncommon thoughts of suicide, suicide attempt, suicide, psychosis, hallucinations, panic attacks
Rarely bipolar disorder
Unspecified frequency of thoughts about the murder, mania
disorders of the nervous system
is often a headache, dizziness
often amnesia, memory impairment, syncope, migraine, ataxia, confusion, neuralgia, paresthesia, hypoesthesia, hyperesthesia, hypertension, drowsiness, decreased alertness , tremor, dysgeusia
infrequently, neuropathy, peripheral neuropathy
rarely convulsions
Very rarely cerebrovascular ischemia, cerebrovascular bleeding, encephalopathy
Unspecified frequency facial nerve paresis, m ononeyropatii
Violations of the organs of vision
Often violation of tearing, blurred vision, blurred vision, photophobia, conjunctivitis, eye irritation, eye pain, dryness of the mucous membrane of the eye
Uncommon exudates in the retina
Rarely blurred vision or loss of field of vision, bleeding in the retina, retinopathy, occlusion of retinal artery occlusion of a vein retina, optic neuritis, papilledema, macular edema
Unspecified frequency of serous retinal detachment
Violations of the organ of hearing and balance
are often inappropriate / hearing loss, tinnitus, dizziness
Uncommon earache
Violations of the heart
often tachycardia, palpitations
Uncommon myocardial infarction
Rarely congestive heart failure, cardiomyopathy, arrhythmia, pericarditis
Very rare ischemic heart
Unspecified frequency of pericardial effusion
Violations by vessels
often hypotension, hypertension, flushing
rarely vasculitis
Violations of the respiratory, thoracic and mediastinal disorders
Very often shortness of breath, * cough *
Often, dysphonia, nosebleeds, respiratory disorder, respiratory failure, nasal sinuses, nasal congestion, runny nose, increased secretion of the upper respiratory tract, pain in Chapter Otke and larynx
Very rarely interstitial pulmonary disease
Violations of the digestive system organs
Very often, nausea *, vomiting, abdominal pain, dry mouth *
Often, dyspepsia, gastroesophageal reflux disease, stomatitis, glossitis, glossodiniya, bleeding gums, constipation, flatulence, hemorrhoids, cheilitis, flatulence, gingivitis, disorders of the teeth
Uncommon pancreatitis pain in the mouth
rare ischemic colitis
Very rare ulcerative colitis
Violations of the hepato-biliary system
is often hyperbilirubinemia, hepatomegaly
Violations of the skin and subcutaneous fat
is often alopecia, pruritus *, skin dry *, rash *
