Composition, form of production and packaging
Solution for n / to the introduction is transparent, from colorless to light yellow color.
1 syringe tube
peginterferon alfa-2a (40 kDa) 135 Ојg
- "- 180 Ојg
Auxiliary substances: sodium chloride - 4 mg, benzyl alcohol - 5 mg, sodium acetate trihydrate - 1.3085 mg, acetic acid ice - 0.0231 mg, polysorbate 80 - 0.025 mg, sodium acetate solution 10% to pH 6.0, acetic acid 10% up to pH 6.0, water d / u - up to 0.5 ml.
0.5 ml - syringe-tubes (1) complete with needle d / and sterile - packs cardboard.
Solution for n / to the introduction is transparent, from colorless to light yellow color.
1 ProKlik в„ў autoinjector
peginterferon alfa-2a (40 kDa) 135 Ојg
- "- 180 Ојg
Auxiliary substances: sodium chloride - 4 mg, benzyl alcohol - 5 mg, sodium acetate trihydrate - 1.3085 mg, acetic acid ice - 0.0231 mg, polysorbate 80 - 0.025 mg, sodium acetate solution 10% to pH 6.0, acetic acid 10% up to pH 6.0, water d / u - up to 0.5 ml.
0.5 ml - ProKlik в„ў auto-injectors with built-in syringe tube with protected needle (1) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
The structure of PEG (bis-monomethoxypolyethylene glycol) directly affects the clinical and pharmacological characteristics of Pegasys В® . In particular, the size and degree of branching of PEG with a molecular mass of 40 kDa determines the absorption, distribution and excretion of peginterferon alfa-2a.
The activity of Pegasys В® should not be compared with other pegylated or unpoedylated proteins of the same therapeutic class.
Just like interferon alfa-2a, Pegasys В® has antiviral and antiproliferative activity in vitro.
In patients with chronic hepatitis C (HCV), a decrease in the level of hepatitis C virus (HCV) RNA in response to Pegasys В® therapy at a dose of 180 Ојg occurs in 2 phases. The first phase is observed 24-36 hours after the first injection of the drug, the second phase occurs within the next 4-16 weeks in patients with a stable virologic response. Ribavirin has no significant effect on the kinetics of the virus during the first 4-6 weeks in those patients who receive combination therapy with ribavirin and peginterferon alfa-2a or interferon alpha.
PHARMACOKINETICS
Suction
After a single administration of 180 μg peginterferon alfa-2a to healthy individuals, the drug is determined in the blood serum after 3-6 hours. After 24 hours, the serum concentration reaches 80% of the maximum. Absorption of peginterferon alfa-2a prolonged, C max in serum is observed 72-96 hours after the administration of the drug. The absolute bioavailability of peginterferon alfa-2a is 84% ​​and is similar to that of interferon alfa-2a.
Distribution
Peginterferon alfa-2a is found primarily in the blood and extracellular fluid. The volume of distribution in the equilibrium state (V ss ) after IV injection is 6-14 liters.According to mass spectrometry, tissue distribution and autoradioluminography obtained in studies on rats, peginterferon alfa-2a is found in high concentrations in the blood and also in the liver, kidneys and bone marrow.
Metabolism
Peculiarities of the metabolism of peginterferon alfa-2a have not been fully studied. In experimental studies, it has been shown that in radio rats the radio-labeled drug is excreted mainly by the kidneys.
Excretion
Systemic clearance of peginterferon alfa-2a in humans is 100 times lower than that for interferon alfa-2a.
After intravenous administration, terminal T 1/2 in healthy volunteers is 60-80 h, compared to 3-4 h for usual interferon. After sc administration, the terminal T 1/2 is about 160 hours (from 84 to 353 hours). The terminal T 1/2 after SC administration may not show excretion, but the duration of absorption of peginterferon alfa-2a.
When peginterferon alfa-2a is administered once a week, a dose-dependent increase in systemic exposure is observed in healthy volunteers and in patients with chronic hepatitis B or C. In patients with chronic hepatitis B or C, 6-8 weeks of therapy with peginterferon alfa-2a once a week is achieved C ss , which is 2-3 times higher than after a single injection. After the 8th week of treatment with the introduction of the drug 1 time per week, further cumulation does not occur. After 48 weeks of therapy, the ratio of C max and C min is 1.5-2. The concentration of peginterferon alfa-2a in the serum is maintained throughout the week (168 h) after administration.
Pharmacokinetics in special populations of patients
Patients with impaired renal function. Impaired renal function is associated with a slight decrease in clearance (CL / F) and an increase in T 1/2 .
In patients with KK of 20-40 ml / min, the clearance of peginterferon alfa-2a is reduced by 25% compared to patients without renal dysfunction. In patients with terminal stage of chronic renal failure who receive hemodialysis sessions, the clearance of peginterferon alfa-2a is reduced by 25-45%. Pharmacokinetics of the drug was similar in the appointment of Pegasys В® in a dose of 135 mkg to patients with terminal stage CRF and with the appointment of 180 mcg to patients without disturbance of renal function.
Floor. After a single injection, pharmacokinetic parameters of Pegasys В® in women and men are comparable.
Elderly age. In patients older than 62 years after a single injection of Pegacis ® at a dose of 180 μg, the absorption of peginterferon alfa-2a was delayed, but stable, compared to young healthy volunteers (T max 115 h compared to T max 82 h). AUC is slightly increased in patients older than 62 years (1663 ng h / ml compared to 1295 ng h / ml), but Cmax values ​​in patients younger and older than 62 years are the same (9.1 ng / ml and 10.3 ng / ml, respectively) . Based on exposure data, pharmacodynamic response and tolerability, there is no need to reduce the initial dose of the drug in such patients.
Patients with cirrhosis and without cirrhosis. Pharmacokinetics of Pegasys В® in healthy individuals and patients with hepatitis B or C is the same. In patients with compensated cirrhosis, pharmacokinetic characteristics are the same as in patients without cirrhosis (class A on the Child-Pugh scale).
Place of injection. The administration of Pegasis ® should be limited to the area of ​​the anterior abdominal wall and thighs, since the degree of absorption, based on the AUC, was 20-30% higher when injected into these areas. The concentration of the drug was lower in studies in which Pegasys ® was injected s / c into the shoulder region.
INDICATIONS
Chronic hepatitis C:
- chronic hepatitis C in adult patients with positive HCV RNA, without cirrhosis or with compensated cirrhosis, incl. and with clinically stable co-infection with HIV (monotherapy or combination with ribavirin).
The combination with ribavirin is indicated in patients with chronic hepatitis C who had not previously received therapy, or with ineffectiveness of previous interferon alpha monotherapy (pegylated or unpaired) or combined with ribavirin therapy.
Monotherapy is indicated in case of intolerance or contraindications to ribavirin.
Chronic hepatitis B:
- chronic hepatitis B HBeAg-positive and HBeAg-negative in adult patients with compensated liver damage and signs of viral replication, increased ALT activity and histologically confirmed liver inflammation and / or fibrosis.
DOSING MODE
For patients over 18 years of age
Treatment with Pegasys В® should be performed under the supervision of a qualified physician experienced in the treatment of chronic hepatitis B and C.
In combination therapy with Pegasys В®, ribavirin should be used according to the instructions for the medical use of ribavirin.
Standard dosing regimen
The drug is injected sc, into the anterior abdominal wall or thigh, once a week.
Before administration, the preparation should be inspected for impurities and discoloration.
Patients should be carefully instructed about the importance of proper storage and disposal of used materials and caution against the reuse of any needles and syringes.
Chronic hepatitis B
With HBeAg-positive and HBeAg-negative chronic hepatitis B, the drug is prescribed in a single dose of 180 Ојg once a week for 48 weeks.
Chronic hepatitis C
Patients who were not previously treated
The recommended dose of Pegasys В® is 180 Ојg 1 time / week in monotherapy or in combination with ribavirin (orally). Ribavirin should be taken with meals.
When combined with ribavirin, the duration of therapy and the dose of ribavirin depend on the genotype of the virus (Table 1).
Table 1. Dosage regimen of Pegasys В® and ribavirin in patients with chronic hepatitis C.
Genotype Dose of Pegasis В® Dose of ribavirin Duration of treatment
Genotype 1 with low viral load and rapid virologic response * 180 Ојg body weight <75 kg = 1000 mg 24 or 48 weeks
body weight? 75 kg = 1200 mg
Genotype 1 with high viral load and rapid virologic response * 180 Ојg body weight <75 kg = 1000 mg 48 weeks
body weight? 75 kg = 1200 mg
Genotype 4 with rapid virologic response * 180 Ојg body weight <75 kg = 1000 mg 24 or 48 weeks
body weight? 75 kg = 1200 mg
Genotype 1 or 4 without rapid virologic response * 180 Ојg body weight <75 kg = 1000 mg 48 weeks
body weight? 75 kg = 1200 mg
Genotype 2 or 3 without rapid virologic response ** 180 Ојg 800 mg 24 weeks
Genotype 2 or 3 with low viral load and rapid virologic response ** 180 Ојg 800 mg 16 or 24 weeks
Genotype 2 or 3 with high viral load and rapid virologic response ** 180 Ојg 800 mg 24 weeks
* Rapid virologic response (HCV RNA not detected) at 4 and 24 weeks of treatment.
** rapid virologic response (result of HCV RNA detection negative) by week 4 of treatment.
Low viral load? 800 000 IU / ml.
High viral load> 800 000 IU / ml.
The duration of therapy in patients with genotype 1, who at 4 weeks of treatment is determined by HCV RNA, should be 48 weeks, regardless of the initial viral load.
The duration of therapy for 24 weeks can be considered in patients:
- with genotype 1 and initially low viral load (? 800 000 IU / ml);
- with genotype 4, at which at week 4 the result of HCV RNA detection is negative and remains negative at week 24.
However, the total duration of therapy for 24 weeks may be associated with a greater risk of recurrence than therapy for 48 weeks. When considering the duration of therapy in such patients, the tolerability of combination therapy and additional prognostic factors such as the degree of fibrosis should be considered. Even more caution should be applied to reducing the duration of therapy in patients with genotype 1 and initially high viral load (> 800,000 IU / mL) who, at 4 weeks, the result of HCV RNA detection is negative and remains negative at week 24, as limited the available data suggest that a shorter duration of therapy may have a very negative impact on a sustained virologic response. In patients with genotype 2 or 3 and detectable HCV RNA at 4 weeks of treatment, regardless of the initial viral load, the duration of therapy should be 24 weeks. It is possible to reduce therapy to 16 weeks in selected groups of patients with genotype 2 or 3, low viral load (initially 800,000 IU / ml), not detectable by HCV RNA by week 4 and remaining negative until week 16. With a 16-week treatment duration, an increased risk of recurrence may be associated with 24-week therapy. When considering the duration of therapy in such patients, the tolerability of combination therapy and additional clinical and prognostic factors, such as the degree of fibrosis, should be considered. Even more caution should be given to reducing the duration of therapy in patients with genotype 2 or 3 and an initially high viral load (> 800,000 IU / mL) who, by 4 weeks, the result of HCV RNA detection is negative, as limited data suggest that shortening the duration of therapy can have a very negative effect on the stability of the virologic response.
Clinical data in patients with genotypes 5 and 6 are limited, combined therapy with Pegasys В® and ribavirin (1000/1200 mg) is recommended for 48 weeks.
The recommended duration of monotherapy with Pegasys В® is 48 weeks.
Patients previously treated
The recommended dose of Pegasys В® in combination with ribavirin is 180 Ојg 1 time / week. The dose of ribavirin is 1000 mg / day (body weight <75 kg) and 1200 mg (body weight? 75 kg).
If a virus is found at week 12 of treatment, therapy should be discontinued. The recommended total duration of therapy is 48 weeks. When deciding on the treatment of patients with genotype 1 who did not respond to previous treatment with pegylated interferon and ribavirin, the recommended total duration of therapy should be 72 weeks.
Co-infection with HIV-HCG
Pegasis В® is administered at a dose of 180 Ојg once a week as monotherapy or in combination with ribavirin (800 mg) for 48 weeks regardless of the genotype. The safety and efficacy of combination therapy with ribavirin at a dose of more than 800 mg and a duration of less than 48 weeks has not been adequately studied.
Predicting the effectiveness of treatment
Patients who were not previously treated
Determination of the early virologic response (reduction of the viral load below the detection threshold or at least 2 log 10 ) at the 12th week of therapy may predict the achievement of a stable virologic response (SVR), as shown in Tables 2 and 3. The predictive value of the absence of SVR in monotherapy with Pegasys В® is 98 %. A similar prognostic value of the absence of SVR was found in patients with co-infection with HIV-HCG who received monotherapy with Pegasys В® or combined therapy with Pegasys В® and ribavirin (100% and 98%, respectively). In the co-infection of HIV-HCG, the prognostic value of SVR of 45% and 70% was found in patients with genotypes 1 and 2/3, who received combination therapy, respectively.
Table 2. Prognostic value (negative result) of the virologic response at week 12 of combination therapy in the recommended regimen.
Genotype Negative result
Lack of response at week 12 Lack of sustainable response Prognostic value
Genotype 1 (n = 569) 102 97 95%
Genotype 2 and 3 (n = 96) 3 3 100%
Table 3. Prognostic value (positive result) of the virologic response at week 12 of combination therapy in the recommended regimen.
Genotype Positive result
Response at week 12 Sustainable response Predictive value
Genotype 1 (n = 569) 467 271 58%
Genotype 2 and 3 (n = 96) 93 81 87%
Patients previously treated
In patients who had not responded to treatment for 48 or 72 weeks, it was shown that suppression of the virus at week 12 (HCV RNA below 50 IU / ml) is a prognostic criterion for SVR. The likelihood of the absence of SVR after 48 or 72 weeks of treatment if the suppression of the virus was not observed at week 12 was 96% and 96%, respectively. The probability of achieving SVR after 48 or 72 weeks of treatment if the suppression of the virus was observed at week 12 was 35% and 57%, respectively.
Guidance on dose adjustment due to side effects
Are common
If dose adjustment is required due to clinical or laboratory reactions of moderate to severe severity, it is usually sufficient to reduce the dose to 135 Ојg. However, in some cases, it is required to reduce the dose to 90 Ојg or 45 Ојg. After resolution of adverse reactions, one may consider increasing the dose of the drug, up to the initial dose.
Hematologic reactions
With a decrease in the number of neutrophils less than 750 cells / Ојl, a dose reduction is recommended. In patients with an absolute neutrophil count (ACH) less than 500 cells / Ојl, treatment should be discontinued until this figure exceeds 1,000 cells / Ојl. The use of Pegasis В® should be resumed at a dose of 90 mcg under periodic monitoring of the number of neutrophils (the frequency of control is determined by the doctor in each case individually).
Dose reduction of up to 90 Ојg is recommended when the platelet count is reduced to less than 50,000 cells / Ојl. Patients with a platelet count of less than 25,000 cells / Ојl should be withdrawn. Recommendations for the treatment of anemia that occurred during therapy:
1) The dose of ribavirin should be reduced to 600 mg / day (200 mg in the morning and 400 mg in the evening) in one of the following situations:
- hemoglobin decreases less than 10 g / dl, but remains more than 8.5 g / dl in patients without concomitant cardiovascular pathology;
- hemoglobin is reduced by 2 g / dl or more during any 4 weeks of therapy in patients with stable cardiovascular disease.
It is not recommended to increase the dose of ribavirin to the original dose.
2) Ribavirin should be discontinued in one of the following situations:
- hemoglobin decreases less than 8.5 g / dl in patients without concomitant cardiovascular pathology;
- hemoglobin remains less than 12 g / dl after 4 weeks, despite the reduction in dose, in patients with stable cardiovascular disease.
After discontinuation of ribavirin and permit side-effects may resume its reception in a dose of 600 mg / day, followed by raising up to 800 mg / day according to the doctor's discretion. It is not recommended to increase the initial dose of ribavirin (1000 mg or 1200 mg).
When hypersensitive ribavirin monotherapy should continue Pegasys В® .
Table 4. Correction dose at side effect occurs (additional information contains the above).
Reducing the dose of ribavirin and 600 mg Suspending receiving ribavirin Reducing the dose of Pegasys В® to 135/90/45 ug suspension of the drug Pegasys В®Cancel combined treatment
Absolute neutrophil count
<750 cells / ml <500 cells / ml
Platelet count
<50,000 cells / 25> 000 cells / ml <25 000 cells / ml
Hemoglobin absence of cardio-vascular disease
<10 g / dL and? 8.5 g / dL <8.5 g / dL
Hemoglobin Having stable cardiovascular disease
reduction of? 2 g / dl during any 4 weeks of therapy <12 g / dl even after 4 weeks of therapy in the reduced dose
reactions associated with impaired liver function
in patients with chronic hepatitis C are characteristic fluctuations in deviations from normal liver function test results. As with other drugs in the treatment of interferon-alpha in the treatment of drug Pegasys В®observed increased activity of ALT higher than before the treatment, including and in patients with virological response.
In clinical studies in 8 of 451 patients with chronic hepatitis C who received the combination therapy, there was isolated increased ALT activity (greater than the ULN is 10 times;? Or greater than the initial level by 2 times for patients with baseline ALT activity 10 times higher CAH? ), which disappeared without changing dose. With progressive increase of ALT activity in comparison with the indices before treatment dose Pegasys В® must first be reduced to 135 micrograms. If ALT activity, despite a dose reduction, continues to increase or accompanied by increased bilirubin concentration, or signs of hepatic decompensation process, the preparation should be discontinued.
Patients with chronic hepatitis B is possible transient increase in ALT activity, sometimes exceeding 10 times ULN in, which may be indicative of immune clearance. Treatment should not normally start if ALT activity exceeds ULN more than 10 times. Continued therapy requires more frequent monitoring of ALT activity. By reducing the dose or time to remove the drug Pegasys В® therapy can be restored after normalization of ALT activity.
Special patient groups
Renal insufficiency
When ESRD is recommended to decrease the dose of Pegasys В® to 135 micrograms. Regardless of the initial dose and degree of severity of renal insufficiency in these patients should be monitored closely and reduce the dose in the case of side reactions.
Liver failure
In patients with compensated cirrhosis (Class A according to Child-Pugh) Pegasys В® effective and safe. In patients with decompensated cirrhosis (class B / C in Child-Pugh or bleeding esophageal varicose veins ) application Pegasys В® was not studied.
Advanced age
At elderly patients correction recommended dose (180 ug 1 time / week.) Is required.
Children
Safety and efficacy in persons under 18 years of age have not been established. The solution of Pegasys В® is contraindicated in infants and children up to 3 yearsBecause it contains benzyl alcohol that can cause in this age category of patients with neurological and other complications, sometimes fatal.
Patients after transplantation
Safety and efficacy monotherapy Pegasys В® or its combination with ribavirin in patients after liver transplantation and other organs and tissues are not established. As the appointment other alpha interferons, when using the drug Pegasys В® as monotherapy or in combination with ribavirin identified cases of rejection of liver and kidney transplants.
Instructions for use autoinjector ProKlik в„ў
device is intended for single use only and then be disposed of.
Before applying autoinjector ProKlik в„ў should carefully read the instructions.
You should not do the following:
- try to open or disassemble the autoinjector ProKlik в„ў ;
- expose autoinjector ProKlik в„ў to extreme force or shock;
- to introduce the drug through the clothes that cover the skin;
- use autoinjector damaged ProKlik в„ў ;
- use autoinjector ProKlik в„ў at turbidity of the solution, the color change or the presence of extraneous visible particles;
- Do not shake;
- remove the cap until you are ready for the introduction of the drug;
- re-use autoinjector ProKlik в„ў ;
- manipulate protecting the needle cylinder, before, during or after use autoinjector, since this component is a safety device.
Components autoinjector ProKlik в„ў
1. Protective cap.
2. The inspection window.
3. Activation button.
4. Protecting the needle cylinder.
1. Inspection autoinjector ProKlik в„ў
Remove the autoinjector ProKlik в„ў from the refrigerator. Examine it and a drug contained therein, through the control window. Do not shake!
If there is foam again put the autoinjector ProKlik в„ў in the refrigerator, and use it later.
Autoinjector ProKlik в„ў must be disposed of and used other auto-injector in the following situations:
- if the solution becomes cloudy;
- the presence in the formulation of extraneous visible particles;
- if the solution has a color different from that specified in the section "Description";
- in case of damage of any parts autoinjector ProKlik в„ў ;
- after the expiry date (best before ...) printed on the carton box and on the label autoinjector ProKlik в„ў .
Do not remove the cap autoinjector ProKlik в„ў earlier Phase 5.
2. Bringing autoinjector ProKlik в„ў to room temperature
Leave autoinjector ProKlik в„ў at room temperature for about 20 minutes. Should not warm the autoinjector ProKlik в„ў in any other way.
3. Processing of hands
Wash your hands with soap and water.
4. Selection and preparation of the injection site
preparation may be administered into the stomach or thigh. Do not use for this navel and areas that could be subject to irritation strap or belt wear.
Is necessary each time to inject the drug in different places. In order to minimize discomfort during the injection can be carefully knock at the proposed injection site.
Wipe the intended area with an alcohol swab. Let the skin dry for 10 seconds. Do not touch the art prior to injection.
5. Preparation autoinjector ProKlik в„ў
Hold the autoinjector ProKlik в„ў with one hand and with the other hand remove the protective cap.
Note: The cap includes a movable metal tube.
After removal of the cap should be used immediately autoinjector ProKlik в„ў . If autoinjector ProKlik в„ў has not been used for 5 minutes after removal of the cap, it is recyclable, and should be used instead a new autoinjector ProKlik в„ў . Do not wear a protective cap after it took off.
6. Location autoinjector ProKlik в„ў to place the proposed injection
two fingers to collect the skin in the fold in place of the proposed injection. Conveniently hold autoinjector ProKlik в„ў with your other hand, firmly attach a needle protecting the cylinder to the top of the skin fold.
Position autoinjector ProKlik в„ў at a right angle (90 В°) to the point of administration.
Note: do not press the activation button.
Firmly press down autoinjector ProKlik в„ў to the skin as long as protecting the needle cylinder is not completely gone inside the autoinjector.
Only then autoinjector ProKlik в„ў is activated and becomes ready to perform an injection.
7. Introduction of the drug
Hold the autoinjector ProKlik в„ў in place, press the activation button with your thumb and immediately release it .
Audible click indicates the beginning of an injection.
During injection control window is gradually filled with red LEDs.
Do not release the autoinjector ProKlik в„ў for 10 seconds for the completion of the injection.
During the return button is activated in the initial position may hear a second click.
After completion of the injection control window will be completely red.
Make sure the thumb removed from the activation button autoinjector ProKlik в„ў. Holding the autoinjector at a right angle (90 В°) to the skin, remove it.
Protecting the needle cylinder automatically closes it, that prevent the possibility of damage caused by the needle.
Caution: if the red light does not completely fill the control window:
- it is possible that protects the needle cylinder is not completely closed - in this case, do not touch the tip of the autoinjector ProKlik в„ў , because in this situation possible damage caused by a needle;
- possibly incomplete administration of the drug - do not try to re-use autoinjector ProKlik в„ў , do not repeat the injection, contact your health care professional watching you.
After introduction of the injection preparation wipe with an alcohol swab.
8. Disposal autoinjector ProKlik в„ў
Wear protective cap on the autoinjector ProKlik в„ў is not required. Autoinjector ProKlik в„ў and cap should be placed in a container protected from puncture (container). The container (capacity) should be kept out of the reach of children. The filled container must be disposed of in accordance with the recommendations of medical specialist.
SIDE EFFECT
Clinical Trials Data
Chronic hepatitis C
The frequency and severity of the most common adverse events in the treatment of drug Pegasys В® and interferon alpha-2a are identical.
The most common adverse events in the treatment of drug Pegasys В® 180 mcg expressed generally easy to moderate and do not require a dosage adjustment or withdrawal of the drug.
Chronic hepatitis B
throughout the course of therapy (48 weeks) and the time of observation without treatment (24 weeks) safety profile of Pegasys В® was similar to that in CHC, although the frequency of side effects with chronic hepatitis B were significantly reduced except for the incidence of fever. In 88% of patients receiving Pegasys В®It was marked adverse events compared with 53% of patients treated with lamivudine. Serious adverse events were reported in 6% and 4% of patients, respectively. About 5% of patients treated with Pegasys В® , and less than 1% of patients treated with lamivudine therapy has been canceled due to adverse events. Drug withdrawal frequency in patients with cirrhosis and without cirrhosis was similar.
Chronic hepatitis C - patients who have not previously responded to treatment
Overall safety profile of Pegasys В® in combination with ribavirin in patients who had not previously responded to treatment was similar to that of patients not previously treated.
In a clinical study involving 72- and 48-week treatment of patients who failed to respond to a previously received therapy with pegylated interferon alfa-2b / ribavirin laboratory abnormalities or adverse events led to cancellation of Pegasys В® 12% of patients, and the cancellation of ribavirin in 13% patients treated for 72 weeks. In the group of patients treated for 48 weeks, laboratory abnormalities or adverse events led to cancellation of Pegasys В® 6%, and the cancellation of Ribavirin - 7%. Similarly, in patients with cirrhosis of abolition frequency therapy with Pegasys В®and ribavirin was higher in the group of patients treated for 72 weeks (13% and 15%) than in patients treated for 48 weeks (6% and 6%). The study excluded patients with cancellation of prior therapy (pegylated interferon alfa-2b / ribavirin) due to hematological toxicity.
In another 48-week clinical trial were included patients with fibrosis or cirrhosis (3 to 6 on a scale Ishak), not previously responded to the therapy, and had initial platelet count 50,000 cells / .mu.l. In the first 20 weeks of the study, the following laboratory abnormalities were observed by hematological parameters: anemia (hemoglobin less than 10 g / dl in 26% of patients); neutropenia (absolute neutrophil count below 750 cells / ml in 30% of patients); thrombocytopenia (platelet count of less than 50 000 cells / ml in 13% of patients).
Co-infection with HIV-HCV
safety profile of the drug Pegasys В®(alone or in combination with ribavirin) in patients co-infected with HIV-HCV was similar to that in patients with CHC. ? Other adverse events occurs in 1% - 2% of patients co-infected with HIV-HCV in the treatment of drug Pegasys В® / ribavirin include: giperlaktatsidemiya / lactic acidosis, influenza, pneumonia, emotional lability, apathy, tinnitus, pain throat and larynx, cheilitis, acquired lipodystrophy and chromaturia.
Therapy with Pegasys В® was associated with a reduction in absolute number of CD4 + lymphocytes in the first 4 weeks of treatment, without changing the percentage content. The number of CD4 + lymphocytes returned to baseline with a decrease in the dose or upon discontinuation. Use of the drug Pegasys В®no adverse effect on HIV viral load during therapy and during follow-up after treatment.
Data for use in patients with the number of CD4 + lymphocyte count of less than 200 cells / mm limited.
Side reactions during monotherapy Pegasys В® chronic hepatitis B and chronic hepatitis C, as well as drug therapy Pegasys В® in combination with ribavirin for chronic hepatitis C
Determination of the frequency of adverse reactions: very often (1/10?), Often (1/100;? <1/10), uncommon (1/1000;? <1/100), rarely (1/10 000;? <1/1000), very rare (<1/10 000).
infections:often - upper respiratory tract infections, bronchitis, oral candidiasis, herpes simplex, fungal and bacterial infections; infrequently - pneumonia, skin infections; rare - endocarditis, otitis externa.
Benign and malignant tumors: Infrequent - neoplasm of the liver.
From the blood and lymphatic system: often - thrombocytopenia, anemia, lymphadenopathy; rarely - pancytopenia; very rarely - aplastic anemia.
Immune system: Infrequent - Sarcoidosis, thyroiditis; rare - anaphylaxis, systemic lupus erythematosus, rheumatoid arthritis; very rarely - or idiopathic thrombotic thrombocytopenic purpura, angioedema.
From endocrine system:often - Hypothyroidism, hyperthyroidism; seldom - diabetes; rarely - diabetic ketoacidosis.
Metabolic disorders: very often - anorexia; infrequently - dehydration.
Psychiatric disorders: very often - depression *, anxiety, insomnia *; often - emotional disorders, mood changes, aggression, nervousness, decreased libido;infrequently - suicidal thoughts, hallucinations; rarely - suicide, mental disorders.
From the nervous system: very often - headache, dizziness *, impaired concentration; often - memory impairment, syncope, weakness, migraine, hypoesthesia, hyperesthesia, paresthesia, tremor, taste disturbance, nightmares, somnolence; rare - Peripheral neuropathy
