Chronic hepatitis B
Therapy with PegIntron® should be started by a doctor with experience in the treatment of hepatitis B patients, and further under his supervision.
The PegIntron® preparation is administered subcutaneously at 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 PegIntron® should be started by a doctor with experience in the treatment of patients with hepatitis C, and further under his supervision.
- DOSE
PegIntron ® should be administered subcutaneously once a week. The dose in adults depends on whether the drug is used as monotherapy or in combination therapy (double or triple therapy).
COMBINED THERAPY (DOUBLE OR TROOPS THERAPY)
Double Therapy (PegIntron® and ribavirin): applicable for all adult and pediatric patients (3 years and older).
Triple therapy (PegIntron® preparation, ribavirin and boceprevir): applicable for adult patients with HCV genotype 1.
Adults
PegIntron® is administered once a week at a dose of 1.5 μg / kg in combination with ribavirin in capsules / tablets.
The prescribed dose of PegIntron® 1.5 mg / kg and ribavirin, depending on body weight, can be administered according to Table 1. Capsules / ribavirin tablets are taken orally every day in the morning and evening with food.
Table 1. Dosing for combination therapy *
| Body weight (kg) | PegIntron® | ribavirin |
| Dosage (μg / 0.5 mL) | Dose for administration once a week (ml) | Daily dose (mg) | Number of capsules / tablets of 200 mg (pcs.) |
| <40 | 50 | 0,5 | 800 | 4a |
| 40-50 | 80 | 0,4 | 800 | 4a |
| 51-64 | 80 | 0,5 | 800 | 4a |
| 65-75 | 100 | 0,5 | 1,000 | 5b |
| 76-80 | 120 | 0,5 | 1,000 | 5b |
| 81-85 | 120 | 0,5 | 1,200 | 6c |
| 86-105 | 150 | 0,5 | 1,200 | 6c |
| > 105 | 150 | 0,5 | 1,400 | 7d |
a: 2 in the morning, 2 in the evening; b: 2 in the morning, 3 in the evening; with: 3 in the morning, 3 in the evening; d: 3 in the morning, 4 in the evening
* Information on the dosage of bocepreviir - see the instructions for the medical use of bocetrevira.
Duration of treatment - untreated patients
Triple therapy
See the instructions for the medical use of bocetrevira.
Double Therapy
Assessment of the probability of response to treatment: in patients infected with the genotype 1 virus, after 4-12 weeks of treatment, RNA of the virus is detected or in which there is no adequate virologic response, the need for continuation of therapy should be assessed, since the emergence of a stable virologic response is extremely unlikely.
Genotype 1:
- In patients who have a virologic response after 12 weeks of treatment, treatment should continue for another 9 months (ie, the total duration of treatment is 48 weeks).
- In patients who had no RNA elimination after 12 weeks of treatment, but a 100-fold decrease in the RNA of the virus (a decrease of 2 log10) and more, a second analysis should be performed after 24 weeks of treatment. In case of elimination of RNA virus from serum, therapy should be continued until the end of the full course (ie, up to 48 weeks). However, if after 24 weeks of treatment, the RNA of the virus in the patient's blood is determined, then the possibility of discontinuing therapy should be considered.
- In patients with a low virus concentration (not higher than 600,000 IU / ml) who after 4 weeks of treatment had eliminated RNA virus and the RNA virus was not detected in the following period - up to 24 weeks of treatment, treatment in 24 weeks may be terminated (ie .,the total duration of the course is 24 weeks) or continued for another 24 weeks (ie the total duration of the course 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 co-infection with HCV / HIV 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. Limited clinical data (66 patients) show the possibility of using the same treatment tactics in patients of this group as in the group of patients infected with the virus of genotype 1.
Duration of treatment in patients with co-infection with HCV / HIV
Double Therapy
The recommended duration of treatment is 48 weeks, regardless of the genotype of the virus.
Assessment of the likelihood of response to treatment in patients with co-infection with HCV / HIV
The early virologic response is a decrease in the viral load by at least 100 times (a decrease of 2 log10) or elimination of RNA of the virus in 12 weeks - allows to predict a stable virologic response.A negative predictive index in patients with co-infection who received combination therapy with PegIntron® and ribavirin in a clinical trial was 99% (67/68), and a positive predictive index of 50% (52/104).
The duration of treatment with repeated therapy
Triple therapy
See the instructions for the medical use of bocetrevira.
Double Therapy
Assessment of the probability of response to treatment: all patients, regardless of the genotype of the virus, in whom, after 12 weeks of therapy, the plasma RNA plasma concentration was below the detection limit, treatment should be continued up to 48 weeks. Patients in whom a virologic response was not achieved (ie, the RNA virus concentration was above the detection limit) after 12 weeks of treatment, the appearance of a sustained virologic response with continued treatment to 48 weeks is unlikely.
The duration of repeated therapy for more than 48 weeks in patients with the hepatitis virus of the genotype I, in whom no response has been achieved, has not been studied for combination therapy with peginterferon alfa-2b and ribavirin.
Patients of childhood (3 years and older) (only double therapy)
Doses for children and adolescents are calculated based on body weight (for ribavirin) and body surface area (for peginterferon alfa-2b). The recommended dose of peginterferon alfa-2b is 60 μg / m2 Once a week, subcutaneously in combination with 15 mg / kg of ribavirin per day inside while eating in two divided doses (morning and evening). Patients who, at the time of the combination therapy with PegIntron® and ribavirin, are 18 years old, should remain on the pediatric therapy regimen.
Duration of treatment
Genotype 1:
The recommended duration of dual therapy is 1 year. When extrapolating clinical trials of combined therapy including standard interferon in children (negative predictive index was 96% for interferon-alpha-2b / ribavirin combination), it can be assumed that in patients who did not reach the virologic response at 12 weeks, the probability of obtaining a stable virologic response is extremely small. Thus, in children and adolescents receiving combination therapy with PegIntron® and ribavirin, it is recommended that treatment be discontinued if, after 12 weeks, the reduction in HCV RNA levels is less than 2 log10 (100-fold) in comparison with baseline, or when detecting RNA of the virus after 24 weeks of treatment.
Genotype 2 or 3:
The recommended duration of dual therapy is 24 weeks.
Genotype 4:
In a clinical study, only 5 children and adolescents with the hepatitis virus of genotype 4 received combination therapy with PegIntron® and ribavirin. The recommended duration of dual therapy is 1 year. In children and adolescents receiving combination therapy with PegIntron® and ribavirin, it is recommended that treatment be discontinued if, after 12 weeks, a reduction in HCV RNA levels is less than 2 log10 (in 100 times) in comparison with the baseline level, or in the presence of HCV RNA in the blood after 24 weeks of treatment.
MONOTHERAPY (ADULTS)
The preparation PegIntron ® is administered in a dose of 0.5 or 1.0 mcg / kg once a week. The smallest available dosage of PegIntron® is 50 μg / 0.5 ml. Patients who are prescribed a dose of 0.5 mcg / kg should choose the volume of the drug according to Table 2.1 or 2.2. Patients who are prescribed a dose of 1.0 μg / kg should choose the volume or dosage of the drug according to Table 2.1 or 2.2. Monotherapy with PegIntron® in patients with co-infection with HCV / HIV has not been studied.
Table 2.1. Doses for monotherapy with the use of a syringe pen CLEARCLICK
| | 0.5 μg / kg | 1.0 μg / kg |
| Body weight (kg) | Dosage preparation PegIntron® (μg / 0.5 mL) | The volume for introduction of 1 once in a week (ml) | Dosage preparation PegIntron® (μg / 0.5 mL) | The volume for introduction of 1 time in 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 |
* The minimum delivered volume of the syringe pen CLEARCLICK 0.2 ml. Use vials.
** For patients with a body weight of more than 120 kg, the dose of the drug should be calculated depending on the patient's body weight. A combination of different dosages and volumes of the drug may be required.
Table 2.2. Doses for monotherapy with the use of a syringe pen REDIPEN
| | 0.5 μg / kg | 1.0 μg / kg |
| Body weight (kg) | The dosage of PegIntron® (μg / 0.5 mL) | Volume for administration 1 time per week (ml) | The dosage of PegIntron® (μg / 0.5 mL) | Volume for administration 1 time per week (ml) |
| 30-35 | 50* | 0,15 | 50 | 0,3 |
| 36-45 | 50* | 0,2 | 50 | 0,4 |
| 46-56 | 50* | 0,25 | 50 | 0,5 |
| 57-72 | 50 | 0,3 | 80 | 0,4 |
| 73-88 | 50 | 0,4 | 80 | 0,5 |
| 89-106 | 50 | 0,5 | 100 | 0,5 |
| 106-120** | 80 | 0,4 | 120 | 0,5 |
* The minimum delivered volume of the syringe pen REDIPEN 0.3 ml. Use vials.
** For patients with a body weight of more than 120 kg, the dose of the drug should be calculated depending on the patient's body weight. A combination of different dosages and volumes of the drug may be required.
Duration of treatment
In patients who have a virologic response at 12 weeks, treatment should be extended at least for another 3 months (ie, only 6 months). The decision to increase the duration of therapy to 48 weeks is based on such prognostic factors,as, for example, the genotype of the virus, age over 40, male gender, the presence of bridge fibrosis.
RECOMMENDATIONS FOR CORRECTION OF DOSE (FOR MONOTHERAPY AND COMBINED THERAPY)
In the event of serious adverse events or abnormalities in laboratory performance during the use of PegIntron® or a combination with ribavirin, the dosage of the drugs should be adjusted before cessation of adverse events. Reduction of the dose of bocetrephir is not recommended. Boceprevir should not be taken without the drug PegIntron® and ribavirin.
Since adherence to therapy is very important for the outcome of treatment, the dose of PegIntron® and ribavirin should be kept as close as possible to those recommended. During the clinical trials, a guide to dose adjustment was developed.
GUIDELINES FOR CORRECTION OF DOSE IN COMBINED THERAPY
Table 3. Guidelines for dose adjustment in combination therapy based on laboratory indicators
| Laboratory indicators | Decrease in daily dose only ribavirin (see Note 1) if: | Reduction of the dose of PegIntron® alone (see Note 2) if: | Termination of therapy if: |
| Content hemoglobin | ≥8.5 g / dL and <10 g / dL | - | <8.5 g / dL |
| Adults: the hemoglobin content in patients with heart disease in stable form Children and adolescents: hemoglobin content - not applicable | The hemoglobin content decreased by ≥ 2 g / dl for any 4 weeks during treatment (continuous use at a reduced dose) | <12 g / dL 4 weeks after dose reduction |
| Number of leukocytes | | ≥ 1.0 x 109 and <1.50 x 109 | <1.0 x 109 |
| Number of neutrophils | | ≥ 0.5 x 109 and <0.75 x 109 | <0.5 x 109 |
| Platelet count | | Adults: ≥25 x 109 and <50 x 109 Children and adolescents: ≥50 x 109 and <70 x 109 | Adults: <25x109 Children and adolescents: <50 x 109 |
| Content connected bilirubin | | | 2.5 x VGN * |
| Content free bilirubin | > 5 mg / dL | | > 4 mg / dL (for> 4 weeks) |
| Serum creatinine content | | | > 2.0 mg / dL |
| Creatinine clearance | | | Undo ribavirin, if <50 ml / min |
| Alanine aminotransferase (ALT) or Aspartate aminotransferase (ACT) | | | 2 x (basic value) and> 10 x VGN or 2 x (basic value) and> 10 x VGN |
* - the upper limit of the norm.
Note 1. In adult patients, the first reduction in the dose of ribavirin is 200 mg / day (except for patients receiving the drug at a dose of 1,400 mg, which should reduce the dose by 400 mg / day).If necessary, the second dose reduction of the drug is carried out for another 200 mg / day. Patients in whom the dose of ribavirin was reduced to 600 mg / day should take 200 mg in the morning and 400 mg in the evening.
In children and adolescents, the first dose reduction of ribavirin is carried out to 12 mg / kg per day, the second dose reduction of ribavirin is made up to 8 mg / kg per day.
Note 2. In adult patients, the first dose reduction of PegIntron® produce up to 1 μg / kg per week. If necessary, the dose of PegIntron® further reduce to 0.5 μg / kg per week. In children and adolescents, the first reduction in the dose of PegIntron® spend up to 40 mcg / m2 per week, the second dose reduction is carried out to 20 μg / m2 in Week.
Reduction of the dose of PegIntron® in adults is carried out by reducing the volume of the solution administered or using a drug with a lower dosage, as shown in Table 4.1 or 4.2. Reduction of the dose of PegIntron® in children and adolescents are performed in two stages from the initial dose (60 μg / m2 per week) to 40 mcg / m2 per week, and then to 20 μg / m2 a week if necessary.
Table 4.1. Reduction of the dose of PegIntron® with combined therapy in adults in two stages using the CLEARCLICK syringe pen
| The first step in reducing the dose of PegIntron® to 1 μg / kg | The second stage of reducing the dose of PegIntron® to 0.5 μg / kg |
| Body weight, kg | Dosage (μg / 0.5 ml) | Dose for administration 1 time per week, mcg | Scope solution for introduction of 1 time per week, ml | Body weight, kg | Dosage (μg / 0.5 mL) | Dose for administration once a week, μg | Scope solution for introduction of 1 time per week, 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 |
Table 4.2. Reduction of the dose of PegIntron® with combined therapy in adults in two stages using a REDIPEN syringe pen
| The first step in reducing the dose of PegIntron® to 1 μg / kg | The second stage of reducing the dose of PegIntron® to 0.5 μg / kg |
| Body weight, kg | Dosage (μg / 0.5 ml) | Dose for administration 1 time per week, mcg | Scope solution for introduction of 1 time per week, ml | Body weight, kg | Dosage (μg / 0.5 mL) | Dose for administration 1 time per week, mcg | Scope solution for introduction of 1 time per week, ml |
| <40 | 50 | 35 | 0,35 | <40 | 50* | 20 | 0,2 |
| 40-50 | 45 | 0,45 | 40-50 | 25 | 0,25 |
| 51-64 | 80 | 56 | 0,35 | 51-64 | 50 | 30 | 0,3 |
| 65-75 | 72 | 0,45 | 65-75 | 35 | 0,35 |
| 76-85 | 80 | 0,5 | 76-85 | 45 | 0,45 |
| 86-105 | 120 | 96 | 0,4 | 86-105 | 50 | 0,5 |
| > 105 | 108 | 0,45 | > 105 | 80 | 64 | 0,4 |
* The minimum delivered volume of the syringe-handle REDIPEN 0.3 ml. Use vials.
GUIDELINES FOR CORRECTION OF DOSE IN MONOTHERAPY IN ADULTS
Guidelines for dose adjustment for PegIntron® monotherapy in adult patients are presented in Table 5.
Table 5. Guidelines for dose adjustment in monotherapy based on laboratory indicators
| Laboratory indicators | Reduction of the dose of PegIntron® up to half the therapeutic dose, if | Stopping injections if: |
| Number of neutrophils | > 0.5 x 109/ l and <0.75 x 109/ l | <0.5 x 109/ l |
| Platelet count | > 25 x 109/ l and <50 x 109/ l | <25 x 109/ l |
In adult patients who are prescribed monotherapy with PegIntron® at a dose of 0.5 mcg / kg, a dose reduction can be achieved by a 2-fold decrease in the introduced volume. If you need a volume of less than 0.3 ml instead of a syringe-handle REDIPEN should be used in a bottle with a dosage of 50 mcg / 0.5 ml.
Recommendations for reducing the dose of PegIntron® to 0.25 μg / kg with the use of a syringe pen CLEARCLICK are given in Table 6.
Table 6. Reduction of the dose of the drug to 0.25 μg / kg (with monotherapy in adults at a dose of 0.5 μg / kg) with the use of a syringe pen CLEARCLICK
| Body weight, kg | Dosage (μg / 0.5 mL) | Input quantity preparation (μg) | Input volume preparation (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 |
* The minimum delivered volume of pen syringe is 0.2 ml. Use vials.
** For patients with a body weight of more than 120 kg, the dose of the drug should be calculated depending on the patient's body weight. A combination of different dosages and volumes of the drug may be required.
In adult patients who are prescribed monotherapy with PegIntron® at a dose of 1.0 μg / kg, a dose reduction can be achieved by reducing the administered volume by a factor of 2 or by applying a lower dosage of the drug, as shown in Tables 7.1 and 7.2.
Table 7.1. Reduction of the dose of the drug to 0.5 μg / kg (with monotherapy in adults at a dose of 1.0 μg / kg) with the use of a syringe pen CLEARCLICK
| Body weight, kg | Dosage (μg / 0.5 mL) | Input quantity preparation (μg) | Input volume preparation (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 |
* The minimum delivered volume of the CLEARCLICK syringe pen is 0.2 ml. Use vials.
** For patients with a body weight of more than 120 kg, the dose of the drug should be calculated according to the patient's body weight. A combination of different dosages and volumes of the drug may be required.
Table 7.2. Reduction of the dose of the drug to 0.5 μg / kg (with monotherapy in adults at a dose of 1.0 μg / kg) with the use of a syringe pen REDIPEN
| Weight bodies | Dose of the drug, μg | Dosage (μg / 0.5 mL) | Input amount preparation (ml) | The amount of preparation administered (μg) |
| 30-35 | 15 | 50* | 0,15 | 15 |
| 36-45 | 20 | 50* | 0,20 | 20 |
| 46-56 | 25 | 50* | 0,25 | 25 |
| 57-72 | 32 | 50 | 0,3 | 30 |
| 73-89 | 40 | 50 | 0,4 | 40 |
| 90-106 | 50 | 50 | 0,5 | 50 |
| >106 | 60 | 80 | 0,4 | 64 |
* The minimum delivered volume of the syringe pen REDIPEN 0.3 ml. Use vials.
APPLICATION OF THE PREPARATION FOR SPECIAL GROUPS OF PATIENTS
Correction of dose in renal failure
Monotherapy
PegIntron ® should be used with caution in patients with moderate or severe renal insufficiency. In patients with moderate renal insufficiency (creatinine clearance 30-50 ml / min), the initial dose of PegIntron® 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 PegIntron® should be reduced by 50%. Data on the use of PegIntron ® in patients with creatinine clearance less than 15 ml / min are absent. It should be carefully monitored for patients with severe renal failure, including patients on hemodialysis. If the kidney function decreases during treatment, PegIntron® therapy should be discontinued.
Combination Therapy
Patients whose creatinine clearance is less than 50 ml / min, combined therapy with PegIntron® and ribavirin is contraindicated. It should be carefully monitored for patients with impaired renal function for the development of anemia. Application for liver failure
Effectiveness and safety of drug therapy PegIntron® has not been studied in patients with severe hepatic impairment, therefore, PegIntron® drug should not be used in these patients.
Application in elderly patients (> 65 years old)
There is no visible effect of age on pharmacokinetics. Data obtained with a single administration of elderly patients with PegIntron®, not suggest the need to adjust the dose of PegIntron ®, depending on age.
Use in children of childhood
PegIntron® can be used in combination with ribavirin in children from 3 years of age.
INSTRUCTION FOR PREPARATION OF SOLUTION FOR INJECTION
PegIntron® in syringe pens. The lyophilizate and the solvent are in the pen syringe and mixed prior to administration (procedure described in the package insert).
A drug PegIntron® in vials. The lyophilisate of the PegIntron® preparation should only be diluted with the applied solvent. PegIntron ® should not be mixed with other medications. Using a sterile syringe, the vial PegIntron® administered 0.7 ml of water for injection.The bottle is gently turned upside-down until the powder is completely dissolved. The dissolution time should not exceed 10 minutes (usually the powder dissolves more quickly). The required dose is collected in a sterile syringe. For administration, up to 0.5 ml of the solution is used. 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. The solution remaining after the introduction is not subject to further use and it must be disposed of in accordance with the current procedure.