Composition and release form
| Solution for subcutaneous administration | 1 ml |
| active substance: | |
| interferon beta-1b | 8 million IU |
| excipients: mannitol; dextran 50–70 thousand; disodium edetate; polysorbate 80; sodium acetate trihydrate; glacial acetic acid; water for injections |
1 ml in colorless glass bottles, sealed with rubber stoppers, with rolled aluminum caps; in blister packs made of PVC film, 5 or 10 bottles each; in a cardboard box 1 or 3 packages with instructions for use.
| Solution for subcutaneous administration | 1 ml |
| interferon beta-1b | 16 million IU |
| excipients: mannitol; dextran 50–70 thousand; disodium edetate; polysorbate 80; sodium acetate trihydrate; glacial acetic acid; water for injections |
0.5 ml in three-component sterile syringes made of colorless neutral glass; 1 syringe in a blister pack made of PVC film; in a cardboard pack there are 1, 5 or 15 packages with instructions for use.
Pharmacodynamics
Interferon beta-1b has antiviral and immunomodulatory activity. The effect of interferon beta-1b in multiple sclerosis is due to binding to high-affinity receptors on the cell surface and triggering the expression of a number of proteins that have antiviral, antiproliferative and anti-inflammatory effects. The therapeutic effect of interferon beta-1b in multiple sclerosis is due to a shift in the cytokine balance in favor of anti-inflammatory cytokines, inhibition of leukocyte proliferation and disruption of the presentation of autoantigens. An important mechanism of action of interferon beta-1b is a decrease in the rate of migration of leukocytes across the BBB due to a decrease in the expression of metalloproteases, which increase the permeability of the BBB. Interferon beta-1b reduces the binding capacity and expression of interferon-gamma receptors, and also increases their degradation. Thus, interferon beta-1b is an antagonist of interferon-gamma, which plays an important role in the pathogenesis of multiple sclerosis. In addition, interferon beta-1b increases the suppressor activity of peripheral blood mononuclear cells and reduces the resistance of T lymphocytes to apoptosis, causing the death of autoreactive clones.
Pharmacokinetics
After subcutaneous administration of interferon beta-1b at the recommended dose of 0.25 mg, its serum concentrations are low or not detectable at all. In this regard, there is no information on the pharmacokinetics of the drug in patients with multiple sclerosis receiving interferon beta-1b at the recommended dose. After subcutaneous administration of 0.5 mg interferon beta-1b, maximum plasma levels are approximately 40 IU/ml 1–8 hours after injection. The absolute bioavailability of interferon beta-1b when administered subcutaneously is approximately 50%. With intravenous use of interferon beta-1b, clearance and T1/2 of the drug from serum average 30 ml/min/kg and 5 hours, respectively. Administration of interferon beta-1b every other day does not lead to an increase in plasma levels of the drug, and its pharmacokinetics do not appear to change during the course of therapy. With subcutaneous administration of interferon beta-1b at a dose of 0.25 mg every other day, the levels of biological response markers (neopterin, beta2-microglobulin and the immunosuppressive cytokine IL-10) increased significantly compared with baseline values 6-12 hours after the first dose. drug. They peaked at 40–124 hours and remained elevated throughout the 7-day (168 hour) study period. The relationship between plasma levels of interferon beta-1b or levels of interferon-induced markers and the mechanism of action of interferon beta-1b in multiple sclerosis has not been established.
Use of interferon drugs in medicine
Interferon drugs are actively used in the treatment of a wide range of viral diseases. In particular, we are talking about the human papillomavirus, viral hepatitis, herpes infection, as well as influenza and colds. An important factor in the selection of drugs containing interferon for the treatment of a particular disease will be the concentration of interferon in the drug, how it is obtained and what type of interferon (α, β, γ or λ) it contains. Despite the fact that there are interferon preparations that are available without a prescription, it is still better to consult a doctor in advance, since there are a number of contraindications for these drugs. Based on the method of preparation, interferon preparations can be divided into 4 types6,7:
- Leukocyte interferon is obtained from donor blood.
- Lymphoblastic interferon is obtained from a culture of lymphoblastic cells.
- Recombinant interferon is obtained from bacterial or fungal cultures into which the human gene responsible for the production of interferon has previously been inserted. Most often, interferon preparations contain recombinant interferon.
- Pegylated interferons are produced by combining recombinant interferon with polyethylene glycol. This is done to ensure that the drug lasts longer in the body.
Contraindications
hypersensitivity to recombinant interferon-beta or other components of the drug;
liver diseases in the stage of decompensation;
history of severe depressive illness and/or suicidal ideation;
epilepsy (not adequately controlled);
pregnancy.
Carefully. Patients with a history of depression or seizures, as well as patients receiving anticonvulsants, should use Ronbetal® with caution. The drug should be used with caution in patients with heart failure stages III–IV according to the NYHA classification and in patients with cardiomyopathy. Caution must be exercised when treating patients with bone marrow dysfunction, anemia or thrombocytopenia with Ronbetal®. Due to insufficient data on use, caution is required when prescribing to patients under 18 years of age.
Interferon beta-1b 8 million IU/0.5 ml 5 pcs. solution for subcutaneous administration
Composition and release form Interferon beta-1b 8 million IU/0.5 ml 5 pcs. solution for subcutaneous administration
Solution - 0.5 ml:
- Active substance: human recombinant interferon beta-1b 8 million IU.
- Excipients: sodium acetate trihydrate - 0.408 mg, glacial acetic acid - up to pH 4.0, dextran 50-70 thousand - 15 mg, polysorbate 80 - 0.04 mg, mannitol - 50 mg, disodium edetate dihydrate - 0.0555 mg, water d/i - up to 1 ml.
0.5 ml - syringes (1) - contour cell packaging (5) (complete with alcohol wipes No. 5) - cardboard packs.
Description of the dosage form
The solution for subcutaneous administration is transparent, colorless or yellowish.
Directions for use and doses
Treatment with interferon beta-1b should be initiated under the supervision of a physician experienced in the treatment of multiple sclerosis.
Adults
The recommended dose of interferon beta-1b is 8 million IU, administered subcutaneously every other day.
Children
No formal clinical and pharmacokinetic studies have been conducted in pediatric and adolescent populations. Limited published data indicate a comparable safety profile for interferon beta-1b at a dose of 8 million IU subcutaneously every other day in patients 12 to 16 years of age compared with the adult population. There is no information on the use of interferon beta-1b in persons under 12 years of age; the drug cannot be used in this group of patients.
At the beginning of treatment, it is usually recommended to titrate the dose. Treatment should begin with the administration of 2 million IU subcutaneously every other day, gradually increasing the dose to 8 million IU, also administered every other day. The dose titration period may vary depending on individual tolerability of the drug.
Table 2. Dose titration scheme*
| Treatment day | Dose, million IU | Volume of the drug, ml depending on the dosage form used | |
| 8 million IU/0.5 ml | 8 million IU/0.5 ml | ||
| 1, 3, 5 | 2 | 0.125 | 0.25 |
| 7, 9, 11 | 4 | 0.25 | 0.5 |
| 13, 15, 17 | 6 | 0.375 | 0.75 |
| ≥19 | 8 | 0.5 | 1.0 |
* The titration period may be extended if adverse reactions develop
The duration of treatment has not yet been established. There are results of clinical studies in which the duration of treatment in patients with relapsing-remitting and secondary progressive multiple sclerosis reached 5 and 3 years, respectively. In the group of patients with relapsing multiple sclerosis, high efficacy is shown during the first 2 years. A further three-year follow-up showed continued effectiveness throughout the entire treatment period. In patients with clinically isolated syndrome, there was a significant delay in transformation into definite multiple sclerosis for more than 5 years.
Interferon beta-1b therapy is not indicated for patients with relapsing-remitting multiple sclerosis who have had fewer than 2 exacerbations in the past 2 years, or for patients with secondary progressive multiple sclerosis who have not progressed in the past 2 years.
For patients who do not experience disease stabilization (e.g., persistent disease progression on the EDSS scale within 6 months or the need for 3 or more courses of corticotropin or corticosteroid therapy) within 1 year, treatment with interferon beta-1b is recommended to be discontinued.
Recommendations for use for patients
1. Choose a time for the injection that is convenient for you. It is advisable to do injections in the evening before bedtime.
2. Before administering the drug, wash your hands thoroughly with soap and water.
3. Take one contour blister pack with a filled syringe/vial from a cardboard box, which should be stored in the refrigerator, and keep it at room temperature for several minutes so that the temperature of the drug is equal to the ambient temperature. If condensation appears on the surface of the syringe/vial, wait a few more minutes until the condensation evaporates.
4. Before use, you should inspect the solution in the syringe/vial. If there are suspended particles or a change in the color of the solution or damage to the syringe/vial, the drug should not be used. If foam appears, which happens when the syringe/vial is shaken or shaken vigorously, wait until the foam settles.
5. Select the area of the body to be injected. Interferon beta-1b is injected into the subcutaneous fat (the fatty layer between the skin and muscle tissue), so use areas with loose fiber away from areas of stretching of the skin, nerves, joints and blood vessels:
- thighs (front surface of thighs except groin and knee);
- abdomen (except for the midline and umbilical region);
- outer surface of the shoulders;
- buttocks (upper outer quadrant).
Do not inject into painful spots, discolored or red areas of the skin, or areas with lumps or lumps.
Choose a different injection site each time, so you can reduce discomfort and pain in the area of skin at the injection site. There are many injection points within each injection area. Constantly change injection points within a specific area.
6. Preparation for injection.
If the patient is using interferon beta-1b syringes
Take the prepared syringe into the hand you are writing with. Remove the protective cap from the needle.
If the patient is using interferon beta-1b vials
Take a bottle of interferon beta-1b and carefully place the bottle on a flat surface (table). Use tweezers (or another convenient device) to remove the cap of the bottle. Disinfect the top of the bottle. Take a sterile syringe in the hand you are writing with, remove the protective cap from the needle and, without violating 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 its neck is facing down.
7. The amount of interferon beta-1b solution that must be administered during the injection depends on the dose recommended by your doctor. Do not store any remaining medication left in the syringe/vial for reuse.
If the patient uses the drug interferon beta-1b in syringes
Depending on the dose prescribed by your doctor. You may need to remove excess drug solution from the syringe. If necessary, slowly and gently press the syringe plunger to remove excess solution. Press down on the plunger until the plunger reaches the desired mark on the syringe label.
If the patient is using the drug interferon beta-1b in vials
Slowly pull the plunger back and draw the required volume of solution into the syringe from the bottle, corresponding to the dose of interferon beta-lb prescribed by your doctor. Then, without compromising sterility, remove the vial from the needle, holding the needle at the base (make sure that the needle does not come off the syringe). Turning the syringe upside down with the needle and moving the piston, remove any air bubbles by gently tapping the syringe and pressing on the piston. Replace the needle on the syringe and remove the cap.
8. Pre-disinfect the area of skin where interferon beta-1b will be injected. When the skin is dry, lightly gather the skin into a fold with your thumb and forefinger.
9. Positioning the syringe perpendicular to the injection site, insert the needle into the skin at an angle of 90°. The recommended depth of needle insertion is 6 mm from the skin surface. The depth is selected depending on the body type and the thickness of the subcutaneous fat. Inject the drug by evenly pressing the syringe plunger down to the end (until it is completely empty).
10. Remove the syringe with the needle by moving vertically upward.
11. Dispose of used syringes/vias only in a specially designated place, out of the reach of children.
12. If you forget to inject interferon beta-1b, inject it immediately as soon as you remember. The next injection is given after 48 hours. A double dose of the drug is not allowed. Do not stop using Interferon beta-1b without consulting your doctor.
Indications for use Interferon beta-1b 8 million IU/0.5 ml 5 pcs. solution for subcutaneous administration
- Clinically isolated syndrome (CIS) (a single clinical episode of demyelination suggestive of multiple sclerosis, subject to the exclusion of alternative diagnoses) with sufficient severity of the inflammatory process to prescribe intravenous corticosteroids to slow the transition to CDRS in patients at high risk of developing CDRS.
There is no generally accepted definition of high risk. According to the study, patients with monofocal CIS (clinical manifestations of 1 lesion in the central nervous system) and ≥T2 lesions on MRI and/or lesions accumulating contrast agent are considered to be at high risk for developing CDRS. Patients with multifocal CIS (clinical manifestations of >1 lesion in the central nervous system) are at high risk of developing CDRS, regardless of the number of lesions on MRI;
- relapsing-remitting multiple sclerosis - to reduce the frequency and severity of exacerbations of multiple sclerosis in patients who are able to walk without assistance, with a history of at least 2 exacerbations of the disease over the past 2 years, followed by complete or incomplete recovery of the neurological deficit;
- secondary progressive multiple sclerosis with an active course of the disease, characterized by exacerbations or marked deterioration of neurological functions over the past 2 years - to reduce the frequency and severity of clinical exacerbations of the disease, as well as to slow down the rate of progression of the disease.
Use strictly as prescribed by your doctor.
Contraindications
- Hypersensitivity to recombinant ipterferon-beta or other components of the drug;
- liver diseases in the stage of decompensation;
- history of severe depressive illness and/or suicidal ideation;
- epilepsy (not adequately controlled);
- pregnancy;
- children under 18 years of age (information on the effectiveness and safety of the use of interferon beta-1b in children is limited. The effectiveness of use in children has not been proven).
Interferon beta-1b should be used with caution in patients with a history of depression or seizures, or in patients receiving anticonvulsants. The drug should be used with caution in patients with heart failure stage III-IV according to the NYHA classification and in patients with cardiomyopathy. Caution must be exercised when treating patients with bone marrow dysfunction, anemia or thrombocytopenia with interferon beta-lb.
Side effects Interferon beta-1b 8 million IU/0.5 ml 5 pcs. solution for subcutaneous administration
Adverse reactions often occur in the initial stages of treatment, however, during subsequent treatment their frequency and intensity decrease. The most common reactions are flu-like symptoms (fever, chills, joint pain, malaise, sweating, headache or muscle pain) and injection site reactions, which are largely due to the pharmacological properties of interferon beta-1b. Reactions at the injection site are common after the use of interferon beta-1b: redness, swelling, discoloration, inflammation, pain, hypersensitivity, necrosis, and unspecific reactions. To improve tolerability, it is recommended to begin interferon beta-1b therapy with titration (see dose titration scheme in the “Dosage Regimen” section); flu-like syndrome can also be corrected by prescribing NSAIDs. The incidence of injection site reactions may be reduced with the use of an auto-injector.
Below are lists of adverse events identified in clinical studies (Table 3. Adverse events and laboratory abnormalities) and according to post-registration data on the use of interferon bega-1b (Table 4, frequencies calculated based on pooled data from clinical studies (very common (> 10%), often (1%), infrequently (0.1%), rarely (0.01%) and very rarely (
Table 3. Adverse events and laboratory abnormalities with an incidence >10% compared with the incidence of the corresponding event on placebo; significant drug-related side effects
| Organ system Adverse events and laboratory abnormalities and laboratory abnormalities | Clinically isolated syndrome (BENEFIT) | Secondary progressive multiple sclerosis (European study) | Secondary progressive multiple sclerosis (North American Study) | Relapsing multiple sclerosis |
| Interferon beta-1b 250 mcg (placebo) n=292 (n=176) | Interferon beta-1b 250 mcg (placebo) n=360 (n=358) | Interferon beta-1b 250 mcg (placebo) n=317 (n=308) | Interferon beta-1b 250 mcg (placebo) n=124 (n=123) | |
| Infections | ||||
| Infections | 6% (3%) | 13% (11%) | 11% (10%) | 14% (13%) |
| Abscess | 0% (1%) | 4% (2%) | 4% (5%) | 1% (6%) |
| Blood and lymphatic system | ||||
| Lymphopenia (3)1,2,4 | 79% (45%) | 53% (28%) | 88% (68%) | 82% (67%) |
| Neutropenia (3)1,2,3,4 | 11% (2%) | 18% (5%) | 4% (10%) | 18% (5%) |
| Leukopenia (3)1,2,3,4 | 11% (2%) | 13% (4%) | 13% (4%) | 16% (4%) |
| Lymphadenopathy | 1% (1%) | 3% (1%) | 11% (5%) | 14% (11%) |
| Metabolic disorders | ||||
| Hypoglycemia ( | 3% (5%) | 27% (27%) | 5% (3%) | 15% (13%) |
| Mental disorders | ||||
| Depression | 10% (11%) | 24% (31%) | 44% (41%) | 25% (24%) |
| Anxiety | 3% (5%) | 6% (5%) | 10% (11%) | 15% (13%) |
| Nervous system | ||||
| Headache2 | 27% (17%) | 47% (41%) | 55% (46%) | 84% (77%) |
| Dizziness | 3% (4%) | 14% (14%) | 28% (26%) | 35% (28%) |
| Insomnia | 8% (5%) | 12% (8%) | 26% (25%) | 31% (33%) |
| Migraine | 2% (2%) | 4% (3%) | 5% (4%) | 12% (7%) |
| Paresthesia | 16% (17%) | 35% (39%) | 40% (43%) | 19% (21%) |
| Organs of vision | ||||
| Conjunctivitis | 1% (1%) | 2% (3%) | 6% (6%) | 12% (10%) |
| Visual impairment2 | 3% (1%) | 11% (15%) | 11% (11%) | 7% (4%) |
| Hearing organs | ||||
| Ear pain | 0% (1%) | 6% (8%) | 16% (15%) | |
| Heart diseases | ||||
| Feeling of heartbeat3 | 1% (1%) | 2% (3%) | 5% (2%) | 8% (2%) |
| Vascular system | ||||
| Vasodilation | 0% (0%) | 6% (4%) | 13% (8%) | 18% (17%) |
| Arterial hypertension4 | 2% (0%) | 4% (2%) | 9% (8%) | 7% (2%) |
| Respiratory system | ||||
| Upper respiratory tract infections | 18% (19%) | 3% (2%) | ||
| Sinusitis | 4% (6%) | 6% (6%) | 16% (18%) | 36% (26%) |
| Cough | 2% (2%) | 5% (10%) | 11% (15%) | 31% (23%) |
| Shortness of breath3 | 0% (0%) | 3% (2%) | 8% (6%) | 8% (2%) |
| Gastrointestinal tract | ||||
| Diarrhea | 4% (2%) | 7% (10%) | 21% (19%) | 35% (29%) |
| Constipation | 1% (1%) | 12% (12%) | 22% (24%) | 24% (18%) |
| Nausea | 3% (4%) | 13% (13%) | 32% (30%) | 48% (49%) |
| Vomit2 | 5% (1%) | 4% (6%) | 10% (12%) | 21% (19%) |
| Abdominal pain4 | 5% (3%) | 11% (6%) | 18% (16%) | 32% (24%) |
| Liver and yellow tract | ||||
| Increased ALT (>5 times compared to baseline)1,2,3,4 | 18% (5%) | 14% (5%) | 4% (2%) | 19% (6%) |
| Increased AST (>5 times compared to baseline)1,2,3,4 | 6% (1%) | 4% (1%) | 2% (1%) | 4% (0%) |
| Skin and subcutaneous fat tissue | ||||
| Skin reactions | 1% (0%) | 4% (4%) | 19% (17%) | 6% (8%) |
| Rash2.4 | 11% (3%) | 20% (12%) | 26% (20%) | 27% (32%) |
| Musculoskeletal system disorders | ||||
| Hypertonicity4 | 2% (1%) | 41% (31%) | 57% (57%) | 26% (24%) |
| Myalgia3,4 | 8% (8%) | 23% (9%) | 19% (29%) | 44% (28%) |
| Myasthenia gravis | 2% (2%) | 39% (40%) | 57% (60%) | 13% (10%) |
| Backache | 10% (7%) | 24% (26%) | 31% (32%) | 36% (37%) |
| Pain in limbs | 6% (3%) | 14% (12%) | 0% (0%) | |
| urinary system | ||||
| Urinary retention | 1% (1%) | 4% (6%) | 15% (13%) | |
| Proteinuria (>1)1 | 25% (26%) | 14% (11%) | 5% (5%) | 5% (3%) |
| Frequent urination | 1% (1%) | 6% (5%) | 12% (11%) | 3% (5%) |
| Urinary incontinence | 1% (1%) | 8% (15%) | 20% (19%) | 2% (1%) |
| Imperative urges | 1% (1%) | 8% (7%) | 21% (17%) | 4% (2%) |
| Reproductive system | ||||
| Dysmenorrhea | 2% (0%) | 6% (5%) | 18% (11%) | |
| Menstrual irregularities3 | 1% (2%) | 9% (13%) | 10% (8%) | 17% (8%) |
| Metrorargy | 2% (0%) | 12% (6%) | 10% (10%) | 15% (8%) |
| Impotence | 1% (0%) | 7% (4%) | 10% (11%) | 2% (1%) |
| General reactions and reactions at the injection site | ||||
| Injection site reactions (various types)2,3,4,5 | 52% (11%) | 78% (20%) | 89% (37%) | 85% (37%) |
| Necrosis at the injection site3 | 1% (0%) | 5% (0%) | 6% (0%) | 5% (0%) |
| Influenza-like syndrome3,4 | 44% (18%) | 61% (40%) | 43% (33%) | 52% (48%) |
| Fever2,3,4 | 13% (5%) | 40% (13%) | 29% (24%) | 59% (41%) |
| Pain | 4% (4%) | 31% (25%) | 59% (59%) | 52% (48%) |
| Chest pain4 | 1% (0%) | 5% (4%) | 15% (8%) | 15% (15%) |
| Peripheral edema | 0% (0%) | 7% (7%) | 21% (18%) | 7% (8%) |
| Asthenia3 | 22% (17%) | 63% (58%) | 64% (59%) | 49% (35%) |
| Chills2,3,4 | 5% (1%) | 23% (7%) | 22% (12%) | 46% (19%) |
| Sweating3 | 2% (1%) | 6% (6%) | 10% (10%) | 23% (11%) |
| Malaise3 | 0% (1%) | 8% (5%) | 6% (2%) | 15% (3%) |
1 Deviation of laboratory value 2 Significantly associated with interferon beta-1b therapy in patients with CIS, p 3 Significantly associated with interferon beta-1b therapy in patients with RRMS. p 4 Significantly associated with interferon beta-1b therapy in patients with SPMS, p 5 Injection site reactions may include any adverse event occurring at the injection site, for example: injection site bleeding, hypersensitivity, injection site inflammation, injection site swelling injection site, necrosis at the injection site, pain at the injection site. swelling at the injection site, and atrophy at the injection site; “Flu-like syndrome” refers to a combination of at least two of the following symptoms: fever, chills, myalgia, malaise, sweating.
Table 4. (Frequency is indicated according to the classification given: very common (>10%), common (1%), uncommon (0.1%), rare (0.01%) and very rare (
| Organ system class | Very common ≥1/10 | Often ≥1/100 to | Uncommon ≥1/1000 to | Rarely ≥1/10000 to | Very rarely |
| Blood and lymphatic system | Anemia | Thrombocytopenia | Bleeding** | ||
| Immune system disorders | Anaphylactic reactions | Capillary hyperpermeability syndrome in the presence of monoclonal gammopathy | |||
| Endocrine disorders | Hypothyroidism | Hyperthyroidism Pathology of the thyroid gland | |||
| Metabolic disorders | Weight gain Weight loss | Increased blood triglyceride levels | Anorexia | ||
| Mental disorders | Confusion | Emotional lability Suicidal attempts | |||
| Nervous system disorders | Convulsions | ||||
| Heart disorders | Tachycardia | Cardiomyopathy | |||
| Vascular disorders | Hypertension | Decreased blood pressure** | |||
| Respiratory, thoracic and mediastinal disorders | Bronchospasm | ||||
| Gastrointestinal disorders | Pancreatitis | ||||
| Hepatobiliary tract disorders | Increased blood bilirubin levels | Increased levels of gamma-glutamine transpeptidase Hepatitis | Liver disorders, including hepatitis Liver failure | ||
| Skin and subcutaneous fat | Urticaria Itching Alopecia | Change in skin color | |||
| Musculoskeletal and connective tissue disorders | Arthralgia | ||||
| Reproductive system and breast disorders | Menorrhagia |
*frequency established in clinical studies.
** data from Biocard CJSC.
Use during pregnancy and breastfeeding
It is unknown whether interferon beta-1b can cause fetal harm when treated in pregnant women or affect human reproductive function. In controlled clinical studies, cases of spontaneous abortion have been reported in patients with multiple sclerosis. In studies in rhesus monkeys, human interferon beta-1b was embryotoxic and, at higher doses, caused an increase in abortion rates. Therefore, interferon beta-1b is contraindicated during pregnancy. Women of reproductive age should use adequate methods of contraception when treated with this drug. If pregnancy occurs during treatment with interferon beta-1b or pregnancy is planned, the woman should be informed of the potential risk and advised to discontinue treatment. It is not known whether interferon beta-1b is excreted in breast milk. Given the potential for serious adverse reactions to interferon beta-1b in breastfed infants, breastfeeding should be discontinued or the drug should be discontinued.
How do human interferons work?
Increased production of interferons begins when a cell is infected with a virus. Note that interferon does not act directly on the virus. First of all, interferon is a signaling molecule that affects neighboring cells, triggering processes in them that interfere with the replication of the virus. Under the influence of interferons, specific enzymes are synthesized in cells that interfere with the assembly of viral particles. Accordingly, the virus cannot further multiply, infecting our body. The second main property of interferons is to stimulate the immune system. In particular, some types of interferons present antigenic (foreign) agents to special T-helper cells of the immune system, which further down the chain pass it on to the next links of the immune pathway, ultimately destroying the pathogen5.
The antiviral properties of interferons have aroused great interest among researchers from the point of view of the treatment of a number of diseases. And over time, thanks to various medical and technological capabilities, it was possible to obtain medications that contain interferon.
Side effects
During the registration clinical trial of the drug Ronbetal®, the following adverse events were observed.
General reactions: a complex of flu-like symptoms, increased body temperature, chills.
Local reactions: reaction at the injection site, pain at the injection site.
Cardiovascular system: increased blood pressure.
Blood and lymphatic system: anemia, lymphopenia.
Metabolic and nutritional disorders: increased levels of enzymes in the blood (increased levels of GGT, AST and ALT up to 4 times from the original level).
Nervous system: anxiety states.
Musculoskeletal system: myalgia.
Skin: maculopapular rash.
The following adverse events have been observed with other interferon beta-1b preparations.
General disorders and reactions at the injection site: reaction at the injection site, asthenia (weakness), a complex of flu-like symptoms, headache, fever, chills, abdominal pain, chest pain, pain of various localizations, general malaise, necrosis at the injection site .
Cardiovascular system: peripheral edema, vasodilation, peripheral vascular disease, hypertension, palpitations, tachycardia.
Digestive system: nausea, constipation, diarrhea, dyspeptic symptoms.
Blood and lymphatic system: lymphopenia 3, neutropenia 3, leukopenia 3, lymphadenopathy.
Metabolic and nutritional disorders: increased levels of enzymes in the blood (AST and ALT 5 times from the original), increased body weight.
Musculoskeletal system: myasthenia gravis, arthralgia, myalgia, leg cramps.
Nervous system: hypertonicity, dizziness, insomnia, lack of coordination, anxiety, nervousness.
Respiratory system: shortness of breath.
Skin: rash, skin diseases, increased sweating, alopecia.
Genitourinary system: imperative urge to urinate, frequent urination; in women - metrorrhagia (acyclic bleeding), menorrhagia (prolonged menstrual bleeding), dysmenorrhea (painful periods); in men - impotence, prostate diseases.
The following side effects have been reported in post-marketing studies with other interferon beta-1b products (the incidence of side effects is classified as follows: very common (≥10%), relatively common (
General reactions: very often - flu-like symptoms (fever, chills, myalgia, headache or sweating). The frequency of these symptoms decreases over time. Rarely: general malaise, chest pain, weight loss.
Local reactions: very often - reactions at the injection site (hyperemia, local swelling), inflammation, pain; infrequently - skin necrosis. Over time, with continued treatment, the frequency of reactions at the injection site usually decreases.
Blood and lymphatic system: uncommon - anemia, thrombocytopenia, leukopenia; rarely - lymphadenopathy.
Endocrine disorders: rarely - dysfunction of the thyroid gland, hyperthyroidism, hypothyroidism.
Metabolic disorders: rarely - increased triglyceride levels.
Nervous system: infrequently - muscle hypertonicity, depression; rarely - convulsions, confusion, agitation, emotional lability, suicidal attempts, anorexia.
Cardiovascular system: uncommon: arterial hypertension; rarely - cardiomyopathy, tachycardia, palpitations.
Respiratory organs: rarely - shortness of breath, bronchospasm.
Gastrointestinal tract: uncommon - nausea and vomiting; rarely - pancreatitis.
Liver and biliary tract: uncommon - increased activity of AST, ALT; rarely - increased GGT activity, bilirubin levels, hepatitis.
Skin and subcutaneous tissue: uncommon - alopecia, urticaria, skin itching, skin rashes; rarely - change in skin color, increased sweating.
Skeletal muscles: infrequently - myalgia.
Female reproductive system: rarely - menstrual irregularities.
Allergic reactions: rarely - anaphylactic reactions.
Interaction
When treating exacerbations of the disease in patients receiving interferon beta-1b, corticosteroids or ACTH, which were used for up to 28 days, were well tolerated. Concomitant use with immunosuppressants other than corticosteroids or ACTH has not been studied. Interferons reduced the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. Caution must be exercised when prescribed in combination with drugs that have a narrow therapeutic index, the clearance of which is largely dependent on the hepatic cytochrome P450 system (for example, antiepileptic drugs). Caution must be exercised when simultaneous use of any drugs that affect the hematopoietic system.
special instructions
Treatment is carried out under the supervision of a doctor. Patients should be informed that depression and suicidal thoughts may be side effects of interferon beta-1b therapy, and if they occur, they should immediately consult a doctor. In rare cases, these conditions can lead to suicide attempts. If depression or suicidal thoughts are present, therapy should be discontinued immediately.
Before prescribing interferon beta-1b and during treatment, a detailed blood test should be regularly performed, including determination of the leukocyte formula, as well as determining the activity of AST, ALT and GGT. In case of increased transaminase activity in the blood serum, careful observation and examination of the patient should be carried out. The drug should be discontinued if there is a significant increase in the activity of liver enzymes or the appearance of symptoms of hepatitis. In the absence of clinical signs of liver damage, once liver enzyme levels have normalized, resumption of therapy can be discussed under close monitoring of liver function.
There is no information on the use of Ronbetal® in patients with impaired liver and kidney function.
In clinical studies, some patients with multiple sclerosis observed the appearance of serum antibodies that neutralize interferon beta-1b. The effect of antibody formation on the clinical effectiveness of interferon beta-1b is currently being studied. The available results are contradictory and do not allow us to draw a clear conclusion. There were no signs of a negative effect of neutralizing antibodies on slowing disease progression in secondary progressive multiple sclerosis.
Cases of necrosis at the injection site have been described in patients receiving interferon beta-1b. The area of necrosis can be extensive and deep. If multiple foci of necrosis appear, treatment with interferon beta-1b should be stopped until they are completely healed, which can last up to 6 months. In the presence of a single lesion and in the absence of extensive necrosis, treatment with interferon beta-1b can be continued.
To reduce the risk of necrosis at the injection site, patients should be advised to:
— follow the rules of asepsis when performing injections;
- Constantly change injection sites.
You should periodically monitor the correctness of self-injections, especially if local reactions occur.
If treatment-emergent cardiomyopathy is suspected to be related to interferon beta-1b therapy, treatment should be discontinued.
The use of cytokines in patients with monoclonal gammopathy was sometimes accompanied by the development of systemic increased capillary permeability syndrome with shock-like symptoms and death.
Effect of the drug on the ability to drive vehicles and maintain machinery
Considering the mechanism of pharmacological action of interferon beta-1b, its direct effect on the ability to drive vehicles and operate machinery seems extremely unlikely. However, CNS side effects associated with interferon beta-1b may affect the ability to drive or operate machinery in susceptible individuals.
Emergency immunoprotection against viruses
The effectiveness of natural interferons (produced in the body) has been proven more than once10. For this reason, given the disadvantages of drugs containing interferons, it is more advisable to stimulate the production of the body’s own interferon. Interferon inducers cope with this task. These are drugs that stimulate the production of one’s own (endogenous) interferon. Interferon inducers, unlike introduced interferons, are slightly allergenic, and most importantly, they cause prolonged production of endogenous IFN in physiological doses sufficient to achieve therapeutic and preventive effects11.
A natural activator of the immune system and, in particular, stimulation of its own interferon are bacterial lysates, which stimulate local immunity without affecting the functioning of the general immune system. One of these is the IRS®19 spray, which contains lysates of 18 bacteria that most often cause respiratory diseases. Unlike systemic immunomodulators, IRS®19 acts locally without interfering with the functioning of the general immune system. It is noteworthy that bacterial lysates are destroyed microorganisms that cannot cause disease, but do induce an immune response14. IRS®19 can be used by both adults and children from 3 months12, which indicates its safety profile. This is especially important because children’s immune systems, which have not yet strengthened, are less able to cope with respiratory infections, which is why children get sick more often13.
The advantage of IRS®19 is that in addition to activating the production of its own interferon, the drug naturally enhances other factors of local immune defense of the nasopharyngeal mucosa: phagocytosis, increases the level of lysozyme and the production of local antibodies, in particular, secretory immunoglobulin A, which makes it possible to cope with both viruses and viruses. and with bacteria. This complex effect on local immunity helps speed up the healing process by 2 times1. IRS®19 acts on the cause of the disease, prevents infection from entering the body and reduces the risk of complications by activating antiviral and antibacterial mechanisms of emergency immunoprotection at the entrance gates of infection13. When IRS®19 is sprayed, a fine aerosol is formed that covers the nasal mucosa, which leads to the rapid mobilization of protective mechanisms12,14.
Another important advantage of IRS®19 is the possibility of using the drug for preventive purposes. Immunological memory after a course of IRS®19 application lasts on average about 4 months13. Such prevention is especially relevant during the season of viral attacks for both adults and children.
Our body, in the process of evolution, has adapted to fight viruses, but if necessary, we can help it without interfering too much with its work.
