Algeron

Treatment of primary chronic active hepatitis C as part of combination therapy with ribavirin in adult patients with positive HCV RNA in the absence of signs of decompensation of liver disease.

P/c, in the area of the anterior abdominal wall or thigh. It is recommended to alternate the injection sites.

Therapy should be initiated by a doctor who has experience in treating patients with hepatitis C, and then carried out under his supervision.

In combination therapy with ribavirin Algeron^® it is used as a n / a injection at a dose of 1.5 mcg/kg 1 time per week. Dosage regimen of the drug Algeron^® listed in table 1.

Table 1

Dosage regimen of the drug Algeron^® in patients with chronic hepatitis C

Each syringe/bottle with the drug Algeron^® intended for single use only. Do not mix the solution contained in the syringe/vial, or inject it in parallel with any other drug. The drug Algeron^® you can not enter in/in.

Recommendations for use in patients

1. Choose a convenient time for the patient to perform the injection. Injections should preferably be done in the evening before going to bed.

2. Before administration of the drug, wash your hands thoroughly with soap and water.

3. Take one contour cell package with a filled syringe / bottle from a cardboard pack that should be stored in the refrigerator, and keep it at room temperature for a few minutes so that the temperature of the drug is equal to the temperature of the surrounding air. If condensation appears on the surface of the syringe/vial, wait a few more minutes until the condensation has evaporated.

4. Before use, it is necessary to inspect the solution in the syringe / vial. In the presence of suspended particles or a change in the color of the solution or damage to the syringe/vial, the drug Algeron^® it should not be used. If there is foam, which happens when the syringe/bottle is shaken or shaken violently, wait until the foam settles.

5. Select the area of the body to inject. Algeron^® it is injected into the subcutaneous fat (the fat layer between the skin and muscle tissue), so it is necessary to use places with loose fiber away from the places of stretching of the skin, nerves, joints and blood vessels (see Figure 1-possible areas for injection):

- thigh (the front surface of the thighs except the groin and knee),

- abdomen (except for the midline and umbilical area).

Figure 1. The layout of the injection sites.

Do not use painful points, discolored, reddened areas of the skin or areas with seals and nodules for injection.

Each time, choose a new place for the injection, so you can reduce unpleasant sensations and pain on the skin area at the injection site. Inside each injection area there are a lot of points to puncture. Constantly change the injection points within a specific area.

6. Preparation for injection

If the patient uses the drug Algeron^® in syringes

Take the prepared syringe in the hand with which the patient writes. Remove the protective cap from the needle.

If the patient uses the drug Algeron^® in vials

Take a bottle of the drug Algeron^® and carefully place the bottle on a flat surface (table). With tweezers (or other convenient device) remove the bottle cap. Disinfect the top of the bottle. Take a sterile syringe in the hand that the patient writes with, remove the protective cap from the needle and, without disturbing the sterility, carefully insert the needle through the rubber cap of the bottle so that the end of the needle (3-4 mm) is visible through the glass of the bottle. Turn the bottle over so that its neck is pointing downwards.

7. The amount of the solution of the drug Algeron^® The amount to be administered during the injection depends on the dose calculated by the doctor. The dose of the drug Algeron^® it is expressed in micrograms and is calculated based on body weight. Do not independently change the dosage of the drug Algeron^® if the doctor didn't tell you to do it. Do not store any drug residues remaining in the syringe / vial for reuse.

If the patient uses the drug Algeron^® in syringes

Depending on the dose prescribed to the patient by the doctor, the patient may need to remove the excess volume of the drug solution from the syringe. If necessary, slowly and gently press the plunger of the syringe to remove the excess amount of solution. Press the plunger until the plunger reaches the desired mark on the surface of the syringe.

If the patient uses the drug Algeron^® in vials

Slowly pull the plunger back and fill the syringe from the bottle with the required volume of solution corresponding to the dose of the drug Algeron^® that the patient was prescribed by the doctor. Then, without disturbing the sterility, remove the bottle from the needle, holding the needle at the base (make sure that the needle does not jump off the syringe). Turning the syringe upside down with the needle and moving the plunger, remove the air bubbles by gently tapping the syringe and pressing on the plunger.

Figure 2.

8. Pre-disinfecting the area of the skin where the drug Algeron will be administered^®, lightly fold the skin into a fold with your thumb and forefinger (fig. 2).

Figure 3.

9. Placing the syringe perpendicular to the injection site, insert the needle into the skin at an angle of 90° (Fig. 3).Inject the drug by evenly pressing the plunger of the syringe down to the end (until it is completely emptied).

10. Remove the syringe with the needle in a vertical upward motion.

11. Dispose of used syringes / vials only in a designated area out of the reach of children.

12. If the patient forgot to administer the drug Algeron^®, give the injection immediately as soon as he remembered it. It is not allowed to enter a double dose of the drug.

Do not stop using the drug Algeron^® without consulting a doctor.

Ribavirin should be taken orally, with meals, daily. The daily dose of ribavirin is calculated based on body weight (see table 2).

Table 2

The dosage regimen of ribavirin in combination therapy with the drug Algeron^® in patients with chronic hepatitis C

The duration of treatment depends on the genotype of the virus.

HCV genotype 1. The presence of an early virological response (disappearance of HCV RNA or a decrease in the viral load by 2 log₁₀ (100 times) and more by the 12th week of treatment) can predict the achievement of a sustained response. In the absence of an early virological response, remission is unlikely to occur. In clinical studies of the use of peginterferon alfa in chronic hepatitis C, a stable response was achieved only in 2% of patients with a negative early response. When an early virological response is achieved, it is recommended to continue therapy for another 9 months (the total duration of treatment is 48 weeks). Discontinuation of therapy should be considered if an early virological response is not achieved after 12 weeks of treatment or if HCV RNA is detectable after 24 weeks of therapy

HCV genotype 2 and 3. If an early virological response is achieved by the 12th week of treatment (disappearance of HCV RNA or a decrease in the viral load by 2 log₁₀ (100 times) and more), it is recommended to carry out treatment for another 12 weeks (the total duration of treatment is 24 weeks). Longer therapy does not have any advantages.

HCV genotype 4. In general, patients with genotype 4 are difficult to treat. The lack of special studies makes it possible to use the same treatment tactics as in genotype 1.

Correction of the dosage regimen

In the event of adverse events or deviations of laboratory parameters of moderate severity, it is necessary to reduce the dose of the drug Algeron^® or ribavirin or suspend treatment. When the condition or laboratory parameters are normalized, you can consider increasing the dose up to the initial one. If the tolerability of therapy does not improve after dose adjustment, treatment is recommended to be discontinued.

Hematological disorders. With a decrease in the peripheral blood number of white blood cells less than 1.5 * 10⁹ /l, neutrophils less than 0.75·10⁹/l, platelet count less than 50·10⁹/l it is recommended to reduce the dose of the drug Algeron^® by an amount equal to 1/3 of the therapeutic dose (1/3 TD). If the number of neutrophils and platelets does not increase, the dose of the drug Algeron^® it is recommended to reduce it by another 1/3 of the TD. It is recommended to increase the dose if the number of white blood cells exceeds 2 * 10⁹/l, neutrophils — 1·10⁹/l, and platelets — 90·10⁹/l for at least 4 weeks.

Correction of the ribavirin dose. With a decrease in hemoglobin to less than 100 g/l, the dose of ribavirin is recommended to be reduced to 600 mg / day. Treatment at the previous dose can be resumed after the hemoglobin level exceeds 100 g / l for at least 4 weeks. With a decrease in the level of hemoglobin less than 85 g/l, Algeron^® ≥20 g / l during any 4 weeks of treatment, it is recommended to reduce the dose of the drug Algeron^® up to half of the therapeutic dose and ribavirin up to 600 mg / day and constantly use a reduced dose. If the level of hemoglobin in patients with CCC diseases (in the compensation phase) is less than 120 g/l 4 weeks after the dose reduction-administration of the drug Algeron^® and the ribavirin is canceled. After discontinuation of ribavirin with normalization of hemoglobin levels, it is possible to resume treatment at a reduced dosage of 600 mg / day, without further increasing the dose.

Violation of the liver. With compensated cirrhosis of the liver, dose adjustment of the drug Algeron^® not required. With decompensation of hepatic function, the use of the drug is not recommended.

If the concentration of free bilirubin increases to 85.5 mmol / l, the dose of ribavirin is recommended to be reduced to 600 mg / day.

With a progressive increase in the activity of ALT or ACT more than 2 times from the initial value or more than 10 times from the ULN administration of the drug Algeron^® and the ribavirin is canceled. If the concentration of bound bilirubin increases by more than 2.5 times the ULN or free bilirubin >68.4 mmol/l for at least 4 weeks with signs of decompensation of liver function, Algeron^® and ribavirin should be discontinued.

Patients with depression. In mild depression, dose adjustment is not required. With the development of moderate depression, the dose of the drug Algeron^® it is recommended to reduce by 1/3 TD, if necessary-by another 1/3 TD. If the condition does not change, it is recommended to continue treatment at a reduced dosage. If there is an improvement, which is noted for at least 4 weeks, you can increase the dose of the drug Algeron^®. With the development of severe depression, as well as suicidal thoughts, it is necessary to cancel Algeron^® and ribavirin and carry out specific treatment under the supervision of a psychiatrist.

Kidney failure. When prescribing combination therapy for mild renal insufficiency (creatinine Cl >50 ml / min), caution should be exercised regarding the development of anemia. When creatinine Cl is less than 50 ml / min, combination therapy with Algeron^® and ribavirin should not be prescribed. If the creatinine concentration increases during therapy >0.177 mmol / L, Algeron^® and ribavirin should be discontinued.

Table 3

Algorithm for dose correction of the drug Algeron^® and ribavirin in the event of adverse reactions

* In patients with CCC diseases (in the compensation phase), if the hemoglobin level decreases by ≥20 g/l during any 4 weeks of treatment, it is recommended to reduce the dose of Algeron^® up to half of TD and ribavirin — up to 600 mg/day and constantly use a reduced dose.

If the level of hemoglobin in patients with CCC diseases (in the compensation phase) is less than 120 g/l 4 weeks after the dose reduction-administration of the drug Algeron^® and the ribavirin is canceled.

** Ribavirin at a dose of 600 mg / day is taken 1 capsule. 200 mg in the morning and 2 capsules. 200 mg in the evening, with meals.

*** The first reduction in the dose of the drug Algeron^® by 1/3 TD (up to 1 mcg / kg / week), the second reduction (if necessary) of the dose of the drug Algeron^® - decrease by another 1/3 TD (up to 0.5 mcg / kg / week).

Use in special groups of patients

Elderly patients. Dose adjustment in the elderly is not required.

Children. In children and adolescents under the age of 18, the efficacy and safety of the drug Algeron^® in combination with ribavirin has not been studied.

Patients after liver and other organ transplantation. The efficacy and safety of peginterferon alfa preparations has not been established.

hypersensitivity to interferon preparations, polyethylene glycol and any other components of the drug Algeron^®,

hypersensitivity to ribavirin or any other component of the drug,

decompensated cirrhosis of the liver (grades B and C on the Child-Pugh scale or bleeding from varicose veins),

cirrhosis of the liver with the presence of liver failure in patients with co-infection with HIV/chronic hepatitis C (Child-Pugh index ≥6),

autoimmune hepatitis or other autoimmune diseases in the anamnesis,

disorders of the thyroid gland that cannot be maintained at a normal level by drug therapy,

epilepsy and/or dysfunction of the Central nervous system,

severe mental illness, in particular depression, suicidal thoughts or attempts (including in the anamnesis),

severe CVD diseases, including unstable and uncontrolled forms that existed for at least 6 months prior to treatment,

severe diseases (including renal failure, creatinine Cl <50 ml / min, the need for hemodialysis),

malignant neoplasms,

rare hereditary diseases, such as lactose intolerance, lactase deficiency, or glucose-galactose malabsorption,

hemoglobinopathies (for example, thalassemia, sickle cell anemia),

conducting therapy in men whose partners are pregnant,

pronounced suppression of bone marrow hematopoiesis (neutrophils <0.5·10⁹/l, platelets <25·10⁹/l, hemoglobin <85 g / l),

pregnancy,

lactation period,

children under 18 years of age.

With caution: severe lung diseases (for example, chronic obstructive pulmonary diseases), diabetes mellitus with a tendency to develop ketoacidotic coma, disorders associated with the blood clotting system (for example, with thrombophlebitis, a previous pulmonary embolism), neutrophils <1.5·10⁹/l, platelets <90·10⁹/ l, hemoglobin <100 g / l, in combination with myelotoxic drugs, in patients with HIV/chronic hepatitis C co-infection-the number of CD4 lymphocytes is less than 200 cells/µl or less than 100 cells / µl with an HIV RNA level of more than 5000 copies/ml.

When conducting combination therapy with the drug Algeron^® at a dose of 1.5 mcg/kg/week and ribavirin, adverse reactions were mostly mild or moderate and did not require discontinuation of treatment.

The following categories were used to describe the frequency of adverse reactions: very common (≥1/10), common (≥1/100, <1/10), infrequent (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000).

Side effects observed during combination therapy with the drug Algeron^® at a dose of 1.5 mcg / kg / week and ribavirin

Most common adverse reactions (≥1/10)

From the central and peripheral nervous system: headache, irritability, depression, emotional lability.

From the gastrointestinal tract: nausea, diarrhea.

From the respiratory system: dry cough.

From the musculoskeletal system: joint pain, muscle pain.

From the skin and subcutaneous fat: dryness and peeling of the skin, itching, rash.

Reactions together of the introduction: inflammation at the injection site.

Common symptoms: fever, flu-like syndrome, asthenia, increased fatigue, weight loss.

From the blood and lymphatic system: leukopenia, neutropenia, anemia, thrombocytopenia. A decrease in hematological parameters, as a rule, was noted in the first 4 weeks of treatment, they improved after dose adjustment within 4-8 weeks. Thrombocytopenia less than 75 * 10⁹/l was observed in approximately 6% of patients. In most cases, changes in blood parameters could be eliminated by reducing the dose, so they did not lead to early termination of treatment. Modification of the ribavirin dose for anemia was required in 2% of patients.

Laboratory parameters: hypoglycemia, hypertriglyceridemia.

Frequent adverse reactions (≥1/100, <1/10)

From the central and peripheral nervous system: vertigo.

From the gastrointestinal tract: decreased appetite, abdominal pain, dry mouth, heartburn.

From the CCC side: tachycardia, hypotension.

From the skin and subcutaneous fat: alopecia.

From the mucous membranes: stomatitis, gingivitis, conjunctivitis, blepharitis.

Reactions at the injection site: pain, infiltration, itching at the injection site.

Laboratory parameters: hyperglycemia, changes in thyroid hormone levels (increased TSH concentration).

When using the drug Algeron^® at a dose of 2 mcg / kg / week in combination with ribavirin, in addition to the adverse events that were observed when using the drug Algeron^® at a dose of 1.5 mcg / kg / week, the following adverse reactions were also noted: pain in the heart (6%), menorrhagia (2%), at the injection sites (2%) — cyanosis, spot hemorrhage, furuncle.

Side effects observed when using similar drugs peginterferon alfa-2b in combination with ribavirin

Most common adverse reactions (≥1/10)

From the central and peripheral nervous system: headache, insomnia, dizziness, impaired concentration, depression, irritability, anxiety.

From the gastrointestinal tract: nausea, diarrhea, abdominal pain, decreased appetite.

From the respiratory system: shortness of breath, cough, pharyngitis.

From the musculoskeletal system: joint pain, musculoskeletal pain.

From the skin and subcutaneous fat: alopecia, itching, dry skin, rash.

Reactions at the injection site: pain and inflammation at the injection site.

Common symptoms: fever, flu-like syndrome, asthenia, increased fatigue, chills, weight loss.

From the blood and lymphatic system: anemia, neutropenia.

Frequent adverse reactions (≥1/100, <1/10)

From the central and peripheral nervous system: violation of taste sensations, ataxia, paresthesia, hypesthesia, emotional lability, aggressive behavior, decreased libido, drowsiness, hyperesthesia, confusion, excitability, apathy, tremor, fainting.

From the gastrointestinal tract: dyspepsia, unstable stools, constipation, vomiting, bloating, dry mouth, bleeding gums, stomatitis, ulcerative stomatitis, glossitis.

From the side of the hepatobiliary system: hepatomegaly, jaundice.

From the CCC side: palpitations, tachycardia, hypertension, hypotension, hot flashes.

From the respiratory system: rhinitis, bronchitis, sinusitis, nasal congestion, respiratory disorders, rhinorrhea, unproductive cough.

From the musculoskeletal system: arthritis.

From the skin and subcutaneous fat: psoriasis, worsening of the course of pre-existing psoriasis, eczema, photosensitization reactions, maculopapular rash, erythematous rash, dermatitis, acne, furunculosis, skin disorders, hematoma, increased sweating, hair structure disorders, nail disorders.

Common symptoms: malaise, chest pain, thirst, pain in the right hypochondrium.

From the blood and lymphatic system: neutropenia, thrombocytopenia, lymphadenopathy. The decrease in CD4 lymphocytes. Treatment with peginterferon alfa in HIV-infected patients was accompanied by a decrease in the absolute number of CD4 lymphocytes without changing their percentage. These changes were completely reversible. The administration of peginterferon alfa did not have a negative effect on the level of HIV viral load in patients with HIV/chronic hepatitis C co-infection during and after treatment.

From the endocrine system: hypothyroidism, hyperthyroidism.

On the part of the visual organs: conjunctivitis, blurred vision, pain in the eye, damage to the lacrimal gland.

On the part of the hearing organs: hearing impairment / loss, tinnitus, otitis media.

From the kidneys and urinary system: frequent urination, polyuria.

On the part of the reproductive system: women — amenorrhea, hypermenorrhea, dysmenorrhea, breast pain, ovarian dysfunction, vaginal disorders, men-impotence, prostatitis, sexual dysfunction (without specifying the exact diagnosis).

Other: viral infections, fungal infections.

Laboratory parameters: increased ALT activity, hyperbilirubinemia, changes in thyroid hormone levels (hypo - and hyperthyroidism), hypo - and hyperglycemia, hyperuricemia, hypocalcemia.

Rare adverse reactions (≥1/10000, <1/1000)

From the central and peripheral nervous system: suicidal thoughts and attempts, aggressive behavior, sometimes directed at others, psychosis, including hallucinations, peripheral neuropathy, convulsive seizures.

From the gastrointestinal tract: pancreatitis.

From the CCC side: arrhythmia, cardiomyopathy.

From the musculoskeletal system: rhabdomyolysis, myositis.

From the kidneys and urinary system: impaired kidney function, kidney failure.

On the part of the visual organs: retinopathy, retinal hemorrhage, blockage of retinal veins or arteries, focal retinal changes, decreased visual acuity or limited visual fields, optic neuritis, edema of the optic disc.

Very rare adverse reactions (<1/10000)

From the central and peripheral nervous system: brain hemorrhage, cerebrovascular ischemia, encephalopathy, polyneuropathy.

From the gastrointestinal tract: ischemic colitis, ulcerative colitis.

From the respiratory system: pulmonary infiltrates, pneumonitis, interstitial pneumonitis.

From the skin and subcutaneous fat: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme exudative.

From the blood and lymphatic system: pancytopenia, aplastic anemia, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura.

From the kidneys and urinary system: nephrotic syndrome.

On the part of the immune system: sarcoidosis (or exacerbation of sarcoidosis).

Laboratory parameters: hypertriglyceridemia, hyperlacticacidemia, lactic acidosis.

Frequency not set

From the central and peripheral nervous system: facial nerve paralysis, neuropathies (including mononeuropathies).

From the gastrointestinal tract: violations on the part of the periodontium, violations of the teeth.

On the part of the immune system: Fogle-Koyanagi-Harada syndrome, systemic lupus erythematosus, rheumatoid arthritis (new onset or worsening), vasculitis, acute hypersensitivity reactions, including urticaria, angioedema, bronchospasm, anaphylaxis.

No serious adverse events were observed with an overdose of peginterferon alfa-2b. Possible increase in dose-dependent side effects. When accidentally taking a dose of peginterferon alfa-2b, exceeding the recommended dose by no more than 2 times, serious symptoms of overdose were not observed. Adverse events pass on their own and do not require the withdrawal of the drug. Cases of overdose of peginterferon alfa-2a have been described when the drug is administered for two consecutive days (without observing the weekly interval) and when it is administered daily for one week (the total dose is 1260 mcg/week). No unusual, serious, or treatment-related adverse events were reported.. There is no specific antidote. Hemodialysis and peritoneal dialysis are ineffective. If necessary, symptomatic therapy is performed

Cepeginterferon alpha-2b is formed by attaching a polymer structure-polyethylene glycol (PEG) with a molecular weight of 20 kDa to the interferon alpha — 2b molecule. Biological effects of the drug Algeron^® caused by interferon alpha-2b. Interferon alpha-2b is produced by a biosynthetic method using recombinant DNA technology and is produced by a bacterial strain Escherichia coli, in which the human interferon alpha-2b gene was introduced by genetic engineering methods. Interferons have antiviral, immunomodulatory and antiproliferative effects. The antiviral effect of interferon alpha-2b is due to its binding to specific cellular receptors, which in turn triggers a complex mechanism of sequential intracellular reactions, including the induction of certain enzymes (protein kinase R, 2'-5' - oligoadenylate synthetase and Mx proteins). As a result, the transcription of the viral genome is suppressed and the synthesis of viral proteins is inhibited. The immunomodulatory effect is primarily manifested by an increase in cell-mediated reactions of the immune system. Interferon increases the cytotoxicity of T-lymphocytes and natural killers, the phagocytic activity of macrophages, promotes the differentiation of T-helper cells, and protects T-cells from apoptosis

The immunomodulatory effect of interferon is also due to the effect on the production of a number of cytokines (IL, interferon gamma). All these effects of interferon can mediate its therapeutic activity.

Pegylated interferon alpha preparations cause an increase in the concentration of effector proteins, such as serum neopterin and 2 ' 5 ' - oligoadenylate synthetase. When studying the pharmacodynamics of the drug Algeron^® with a single administration to volunteers, a dose-dependent increase in the serum concentration of neopterin, C_max which was reached after 48 hours. With the introduction of the drug Algeron^® Once a week at a dose of 1.5 mcg/kg, the serum concentration of neopterin in patients with chronic hepatitis C was maintained at a constantly high level.

As well as unmodified interferon alpha-2b, Algeron^® had antiviral activity in experiments in vitro.

In preclinical experiments, it was shown that pegylation of the interferon alpha-2b molecule leads to a significant slowdown in absorption from the injection site, an increase in V_d, reducing the ground clearance. A decrease in clearance leads to a more than 10-fold increase in the duration of the terminal T_1/2 compared to unmodified interferon alpha-2b (32 vs 2.2 h). Elimination of the drug Algeron^® occurred for >153 hours (6.5 days).

When studying the pharmacokinetics of the drug Algeron^® when administered once to volunteers at a therapeutic dose of 1.5 mcg/kg together with ribavirin, serum C_max it was achieved on average in 31 (18-48) hours after administration and was 1401± 233 (1250-1803) pkg / ml. AUC_{0-168 h} It averaged 144212± 49839 (106845-226062) pkg/ml/h. The average clearance of the drug was 9.9±3.2 (5.2–13 ml·h * kg), T_1/2 — 57.8±8.4 (48-66. 5) h. The value of the elimination constant K_el the average was (0.0124±0.002) h^-1.

With the introduction of the drug Algeron^® once a week as part of the combination therapy of chronic hepatitis C, a dose-dependent gradual increase in the concentration of the drug was observed until the 8th week, after which further accumulation until the 12th week of therapy with the drug Algeron^® was not observed.

Pharmacokinetics in patients with impaired renal function. In studies of peginterferon alpha-2a, no association was found between pharmacokinetic parameters and creatinine Cl in patients with impaired renal function (creatinine Cl from 20 to 100 ml / min). The study of peginterferon alpha-2b revealed an increase in C_max, AUC, and T_1/2 in proportion to the degree of renal failure.

Patients with moderate to severe renal insufficiency should be carefully monitored and, if adverse reactions occur, reduce the dose of the drug Algeron^®.

Pharmacokinetics in patients with impaired liver function. The pharmacokinetic parameters of peginterferon alfa preparations in healthy individuals and patients with hepatitis C are the same. In patients with compensated cirrhosis of the liver, the pharmacokinetic characteristics are the same as in patients without cirrhosis. In patients with severe hepatic impairment, the pharmacokinetics of peginterferon alfa preparations have not been studied, therefore, the use of the drug Algeron in this group of patients^® not recommended.

Pharmacokinetics in the elderly. The pharmacokinetic parameters of peginterferon alfa preparations do not depend on age, therefore, dose changes in the elderly are not required. Pharmacokinetics in patients older than 70 years have not been studied.

• Cytokine [Antiviral (excluding HIV) agents]
• Cytokine [Interferon]

There was no pharmacokinetic interaction between peginterferon alfa and ribavirin.

Peginterferon alpha-2a therapy at a dose of 180 mcg / week for 4 weeks did not affect the pharmacokinetic profile of tolbutamide (CYP 2C9), mephenytoin (CYP2C19), debrisoquine (CYP2D6) and dapsone (CYP3A4) in healthy male volunteers. Peginterferon alpha-2b therapy (1.5 mg / kg / week for 4 weeks) did not affect the activity of CYP1A2, CYP3A4, or N-acetyltransferase isoenzymes, but there was an increase in the activity of CYP2C8/C9 and CYP2D6 isoenzymes.

Therefore, caution should be exercised when prescribing the drug Algeron^® together with drugs, the metabolism of which involves the isoenzymes CYP2C8/C9 or CYP2D6.

Given the property of peginterferon alpha to inhibit the activity of the cytochrome P450 isoenzyme 1A2 and increase the AUC of theophylline (by about 25%) when taking the drug Algeron^® and theophylline, it is necessary to monitor the concentration of theophylline in the serum and make appropriate adjustments to its dose.

Peginterferon alpha-2a therapy at a dose of 180 mcg / week was associated with an increase in the average levels of methadone metabolites by 10-15%. Although the clinical significance of this interaction is not determined, it is recommended to carefully monitor the symptoms of methadone intoxication during treatment with Algeron^®. HIV patients receiving highly active antiretroviral therapy (HAART) have an increased risk of developing lactic acidosis. Therefore, when adding the combination of Algeron^® and ribavirin to VAART should be treated with caution.

There was no interaction between ribavirin and nucleoside reverse transcriptase inhibitors (lamivudine, zidovudine, stavudine).

A combination of didanosine and ribavirin is not recommended. Ribavirin increases the exposure of didanosine and its active metabolite (dideoxyadenosine-5-triphosphate), which can lead to the development of fatal liver failure, peripheral neuropathy, pancreatitis, symptomatic lactic acidosis.

In a dark place, at a temperature of 2-8 °C (do not freeze).

Keep out of reach of children.

Do not use after the expiration date indicated on the package.

Solution for subcutaneous administration, 200 mcg/ml. 0.4, 0.5, 0.6, 0.8 or 1 ml each in three-component sterile syringes made of colorless neutral glass. 1 syringe in a contour cell package made of polymer film.

1 or 4 contour cell packages are placed in a pack of cardboard.

1 ml each in bottles made of colorless neutral glass, capped with teflon-coated stoppers, compressed aluminum caps. 1 or 4 fl. in a contour cell package made of polymer film is placed in a pack of cardboard.

Peginterferon-alpha preparations should not be prescribed during pregnancy. Teratogenic effects of peginterferon-alpha preparations have not been studied. The use of interferon alpha-2a in high doses led to a significant increase in the number of spontaneous abortions in animals. No teratogenic effects were observed in the offspring born at term. However, when treating with interferon alpha drugs, women of childbearing age should use effective methods of contraception. There is no data on the penetration of peginterferon alpha into breast milk, so to avoid undesirable effects on the child, either breastfeeding or therapy should be discontinued, taking into account the potential benefits for the mother. The combination of peginterferon alfa with ribavirin is contraindicated for use during pregnancy

In animal studies, ribavirin had a pronounced teratogenic effects and caused the death of the fetus. Ribavirin is contraindicated in pregnant women and men whose partners are pregnant. Ribavirin therapy should not be prescribed until a negative pregnancy test is obtained immediately before the start of therapy. Women who are able to procreate, or men whose partners are able to procreate, should be informed about the teratogenic effects of ribavirin and the need for effective contraception (at least 2 methods) during treatment and for 7 months after the end of therapy.

According to the recipe.

Efficacy and safety of the drug Algeron^® the use of monotherapy or combination with ribavirin in persons under 18 years of age, as well as in patients after liver or other organ transplantation has not been established.

Algeron^® it should be used with caution in diseases such as chronic obstructive pulmonary disease or diabetes mellitus with a tendency to develop ketoacidosis. Caution should also be exercised in patients with impaired blood clotting (for example, with thrombophlebitis, pulmonary embolism) or severe myelosuppression.

The mental sphere and the central nervous system. If necessary, prescribe the drug Algeron^® patients with severe mental disorders (in t.tsch. patients with a history of such disorders) treatment can only be initiated after a thorough individual examination and appropriate therapy for the mental disorder. Patients receiving interferons may develop severe side effects from the psyche, in particular depression, suicidal mood and suicidal attempts. In some patients, especially the elderly, who took increased doses of interferon alpha-2b, there was a noticeable decrease in pain sensitivity, coma, encephalopathy. Although these phenomena are mostly reversible, in some patients it may take up to 3 weeks to fully recover. Patients with a history of depression should be monitored for signs of depression during treatment and for 6 months after its end. Patients should immediately report any sign of depression to their doctor. If symptoms persist or increase, especially depression, suicidal intentions or aggressive behavior, treatment should be discontinued and timely intervention by a psychiatrist should be provided

SSS. Patients with heart failure, myocardial infarction and / or arrhythmias (including in the anamnesis) should be under constant supervision. In patients with heart disease, an ECG is recommended before and during treatment. Arrhythmias (mainly supraventricular) are usually amenable to conventional therapy, but may require discontinuation of the drug Algeron^®. Anemia caused by taking ribavirin can worsen the course of cardiovascular diseases. In case of worsening of the course of cardiovascular diseases, therapy should be interrupted or canceled.

Hypersensitivity. In rare cases, therapy with peginterferon alfa was complicated by immediate hypersensitivity reactions. With the development of anaphylactic reactions, urticaria, angioedema, bronchospasm, the drug is canceled and appropriate therapy is immediately prescribed. A transient rash does not require discontinuation of therapy.

The function of the kidneys. It is recommended to conduct a study of renal function in all patients before starting therapy with Algeron^®. When creatinine Cl is less than 50 ml / min, combination therapy with Algeron^® and ribavirin should not be used.

In the case of an increase in creatinine concentration >0.177 mmol/l during therapy, administration of the drug Algeron^® and ribavirin should be discontinued.

In patients with reduced renal function, as well as over the age of 50 years when using the drug Algeron^® in combination with ribavirin should closely monitor their status with respect to the possible development of anemia.

The function of the liver. With the development of hepatic insufficiency, treatment with the drug Algeron^® and ribavirin is canceled.

Fever. Fever may occur within the framework of the flu-like syndrome, which is often recorded in the treatment of interferons, however, it is necessary to exclude other causes of persistent fever.

Hydration. It is recommended to ensure adequate hydration of patients, since some patients with peginterferon alfa-2b have experienced arterial hypotension associated with a decrease in the volume of fluid in the body.

Lung diseases. In rare cases, patients treated with interferon alpha developed infiltrates of unknown etiology, pneumonitis or pneumonia, including with a fatal outcome. If fever, cough, shortness of breath, and other respiratory symptoms occur, all patients should have a chest X-ray. If there are infiltrates on the X-ray of the lungs or signs of impaired lung function, more careful monitoring of patients should be established and, if necessary, Algeron should be discontinued^®. Immediate withdrawal of interferon and the appointment of corticosteroids lead to the disappearance of adverse events from the lungs.

Autoimmune disorders. When treated with interferon alpha, the appearance of autoantibodies was noted in some cases. Clinical manifestations of autoimmune diseases often occur in the treatment of patients predisposed to the development of autoimmune disorders. An exacerbation or occurrence of psoriasis, sarcoidosis, and other autoimmune diseases has been described. In patients with psoriasis and sarcoidosis, Algeron^® it should be used with caution, and in case of exacerbation of the disease, consider discontinuing the drug.

Changes on the part of the visual organ. If you have complaints about decreased visual acuity or limited visual fields, an ophthalmological examination should be performed. Such disorders often occur in the presence of concomitant diseases, so patients with diabetes mellitus or arterial hypertension are recommended to conduct an examination before starting treatment. Patients with diseases of the visual organ are recommended to conduct regular examinations during treatment.

Changes in the teeth and periodontium. In patients receiving combined therapy with peginterferon alfa-2b and ribavirin, pathological changes in the teeth and parotid tissues were noted. Dryness of the mouth during long-term therapy can also damage teeth and the mucous membranes of the oral cavity. Patients are advised to follow the oral hygiene and regularly undergo examination at the dentist.

The state of the thyroid gland. The mechanism of influence of interferon alpha on thyroid function is unknown. Patients with chronic hepatitis C treated with interferon alpha-2b developed hypothyroidism or hyperthyroidism in 2.8% of cases. These disorders were controlled using standard therapy. Before starting treatment with Algeron^® In patients, serum TSH concentrations should be determined and standard therapy should be prescribed if thyroid function disorders are detected. The TSH concentration should also be determined when symptoms of thyroid dysfunction occur during treatment with interferon alpha. Treatment with the drug Algeron^® it should not be performed if TSH activity cannot be maintained at a normal level.

Laboratory tests. Before starting treatment with Algeron^® standard clinical and biochemical blood tests should be performed. They are also recommended to be performed during therapy every 2 weeks (clinical blood test) and every 4 weeks (biochemical blood test).

Algeron^® it can be used in the following laboratory parameters: hemoglobin ≥120 g/l (women) and ≥130 g/l (men), platelet count >90 * 10⁹/l (in patients with cirrhosis or transition to cirrhosis - >75 * 10⁹/l), the absolute number of neutrophils - >1.5·10⁹/l, TSH and thyroxine concentrations are within normal limits, or thyroid function is medically monitored. In severe hypertriglyceridemia, before adjusting the dose of the drug Algeron^®, it is necessary to prescribe a diet or drug therapy, taking into account the concentration of triglycerides in the fasting blood serum. After discontinuation of the drug, hypertriglyceridemia quickly disappears.

Interferon alpha therapy may be accompanied by the development of ulcerative and hemorrhagic and/or ischemic colitis within 12 weeks from the start of therapy. Abdominal pain, the presence of blood in the feces, fever-typical symptoms of the manifestation of colitis. When appropriate complaints appear, Algeron^® must be cancelled immediately. Recovery usually occurs in 1-3 weeks after discontinuation of the drug.

When treated with peginterferon alfa-2a in combination with ribavirin, cases of pancreatitis, sometimes fatal, have been reported. With the development of symptoms of pancreatitis, therapy with the drug Algeron^® and ribavirin should be discontinued.

When taking interferon alpha drugs, serious infectious complications (bacterial, viral, fungal), sometimes fatal, are described. Some of them were accompanied by the development of neutropenia. If severe infectious complications occur, therapy should be discontinued and appropriate treatment should be prescribed.

Influence on the ability to drive vehicles, mechanisms. During treatment, there may be weakness, dizziness,drowsiness, confusion. If these phenomena occur, you should refrain from driving a car or working with machines and mechanisms.

L03AB Interferons

• B18. 2 Chronic viral hepatitis C

Transparent, colorless to light yellow solution.