Betaferon® (Betaferon®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceInterferon beta-1bInterferon beta-1b
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    • Dosage form: & nbsplyophilizate for the preparation of a solution for subcutaneous administration
    Composition:
    Each vial with the active ingredient contains:
    Interferon beta-lb (IFN-beta-lb) 0.30 mg (corresponding to 9.6 million IU) human albumin, mannitol
    1 ml of the prepared solution contains 0.25 mg (8.0 million IU) of recombinant interferon beta-lb.
    In 1 ml of an aqueous solvent for solution for injection contains 5.4 mg of sodium chloride.
    Description:

    Lyophilizate: Lyophilized white mass.

    Solvent: Transparent, almost colorless solution.

    The reconstituted solution: The solution is slightly opalescent to opalescent, colorless or light yellow in color.

    Pharmacotherapeutic group:Cytokine. Means for treating multiple sclerosis
    ATX: & nbsp

    L.03.A.08   Interferon beta-1b

    Pharmacodynamics:
    The active substance of the preparation Betaferon (interferon beta-lb) has antiviral and immunomodulating activity. The mechanisms of action of interferon beta-lb in multiple sclerosis (PC) have not been fully established.However, it is known that the biological effect of interferon beta-lb is mediated by its interaction with specific receptors that are found on the surface of human cells. The binding of interferon beta-lb to these receptors induces the expression of a number of substances that are considered as mediators of the biological effects of interferon beta-lb. The content of some of these substances was determined in serum and fractions of blood cells of patients receiving interferon beta-lb. Interferon beta-lb decreases the binding capacity of the interferon gamma receptor and enhances its internalization and degradation. In addition, interferon beta-lb increases the suppressor activity of peripheral blood mononuclear cells.
    Both with remittent and secondary-progressive multiple sclerosis, Betaferon treatment reduces the incidence (by 30%) and severity of clinical exacerbations of the disease, the number of hospitalizations and the need for treatment with glucocorticosteroids, and also lengthens the duration of remission.
    In patients with a second-progressive PC, Betaferon treatment can delay further progression of the disease and the onset of disability, including severe disability (ie, when patients are forced to use the wheelchair) for up to 12 months.This effect is observed in patients with both exacerbations of the disease and without exacerbations, as well as with any index of disability (in the study, patients with an assessment of 3.0 to 6.5 points on the extended scale of assessment of the state of disability) participated.
    The results of magnetic resonance imaging of the brain of patients with remitting and secondarily progressing multiple sclerosis on the background of treatment with Betaferon confirm the significant positive effect of the drug on the severity of the pathological process, as well as a significant reduction in the formation of new active foci.
    Toxicological characteristics
    Acute toxicity studies were not conducted. Since rodents are insensitive to the action of human interferon beta, the risk assessment was based on repeat dose toxicity studies in rhesus monkeys. Transient hyperthermia was observed, along with a pronounced transient increase in lymphocyte concentration and a transient decrease in platelets and segmented neutrophils. Long-term toxicity studies were not conducted. Reproductive toxicity studies in rhesus monkeys have revealed maternal toxicity and increased frequencyspontaneous abortion. The living offspring did not have any developmental defects. Studies of the impact on fertility have not been conducted. There was no effect on the estrous cycle of monkeys.
    In one separate genotoxicity study (Ames test), no mutagenic effects were observed. Carcinogenicity studies have not been conducted. The cell transformation test in vitro did not reveal any carcinogenic potential.
    Pharmacokinetics:
    After subcutaneous administration of Betaferon in a recommended dose of 0.25 mg, serum concentrations of interferon beta-lb are low or not at all determined. In this regard, there is no information on the pharmacokinetics of the drug in patients with multiple sclerosis receiving Betaferon in the recommended dose.
    After subcutaneous administration of 0.5 mg Betaferon, the maximum plasma concentration is reached 1-8 hours after injection and is about 40 IU / ml. Absolute bioavailability of Betaferon with subcutaneous injection is about 50%. With intravenous administration of interferon beta-lb, the clearance and half-life of the drug from the serum averaged 30 ml / min / kg and 5 hours, respectively.
    The introduction of Betaferon in a day does not lead to an increase in the concentration of interferon beta-lb in blood plasma, and its pharmacokinetics does not change during the course of therapy.
    When subcutaneous application of Betaferon in a dose of 0.25 mg every other day, the content of biological response markers (neopterin, beta2-microglobulin and immunosuppressive cytokine,
    interleukin-10) is significantly increased in comparison with baseline values ​​6-12 hours after the administration of the first dose of the drug. They peaked at 40-124 h and remained elevated during the 7-day (168 h) study period.
    Indications:
    - Clinically isolated syndrome (CIC) (the only clinical episode of demyelination that suggests multiple sclerosis, with the exclusion of alternative diagnoses) with a sufficient degree of inflammation for the appointment of intravenous corticosteroids - to slow the transition to clinically significant multiple sclerosis (CVD) in high-risk patients development of the KDRS.
    There is no generally accepted definition of high risk. According to the study, patients with a single-focus KIC (clinical manifestations of one foci in the central nervous system) and > 9 T2-foci on MRI and / or the accumulation of contrast medium foci.Patients with multifocal CIS (clinical manifestations> 1 center in the central nervous system) are at high risk of developing KDRS regardless of the number of lesions on MRI.
    - Remitting multiple sclerosis (RRMS) - to reduce the frequency and severity of exacerbations in ambulatory patients (i.e. patients who can walk unaided) with a history of not less than 2 exacerbations during the last 2 years, followed by complete or incomplete recovery of neurologic deficiency.
    - Secondary progressive multiple sclerosis with active disease characterized by exacerbations or severe deterioration of neurological function over the past two years to reduce the frequency and severity of clinical exacerbations of the disease, as well as to slow the progression of the disease.
    Contraindications:
    - Pregnancy.

    - Lactation.

    - hypersensitivity to natural or recombinant interferon beta or human albumin in history.
    Carefully:
    Betaferon should be used with caution in patients with the following diseases:

    - heart disease, especially heart failure stage III-IV classification of New York Heart Association (NYHA), cardiomyopathy;

    - depression and suicidal thoughts (incl.in the anamnesis), epileptic seizures in the anamnesis;

    - monoclonal gammopathy;

    - anemia, thrombocytopenia, leukopenia;

    - abnormal liver function.

    Due to the lack of sufficient experience of use, caution is necessary when used in patients younger than 18 years of age.
    Pregnancy and lactation:
    - Pregnancy

    It is not known whether Betaferon able to cause damage to the fetus when treating pregnant women or affect the human reproductive function. In controlled clinical trials in patients with multiple sclerosis have been cases of spontaneous abortion. In studies in rhesus macaques human interferon beta-lb has embryotoxic effects in higher doses, causes an increase in the frequency of abortion. Women of reproductive age should be treated with safe methods of contraception. In case of pregnancy during treatment with Betaferon or planning pregnancy, it is recommended to cancel the drug.

    - Lactation

    It is not known whether interferon beta-lb is excreted in breast milk. Given the theoretical possibility of adverse reactions to Betaferon in infants who are breastfedit is necessary to stop breastfeeding or to cancel the drug.
    Dosing and Administration:

    Treatment with Betaferon should be started under the supervision of a physician with experience in the management of multiple sclerosis.

    At present, the question of the duration of Betaferon therapy remains unresolved. In clinical studies, the duration of treatment in patients with remitting and secondarily progressive multiple sclerosis reached 5 and 3 years, respectively. The duration of the course is determined by the doctor.

    Preparation of injection pastvora.

    A. Packaging of the preparation containing vials and pre-filled syringes:

    To dissolve the lyophilized interferon run-lb for injections use the supplied ready-made syringe with solvent and needle.

    B. Packaging of the preparation containing vials, pre-filled syringes, an adapter for a bottle with a needle and alcohol wipes:

    To dissolve the lyophilized interferon run-lb for injections use the supplied ready-made syringe with a solvent and an adapter for a bottle with a needle. In the vial with Betaferon, inject 1.2 ml of solvent (sodium chloride solution 0.54%).The powder must be dissolved completely without shaking. Before use, inspect the finished solution. In the presence of particles or a change in the color of the solution, it can not be used. In 1 ml of the prepared solution contains 0.25 mg (8 million; ME) interferon beta-lb .

    Mode of application

    Subcutaneously

    Dosage

    The recommended dose of Betaferon 0.25 mg (8 million. ME), which is contained in 1 ml of the prepared solution is administered subcutaneously every other day.

    If you forgot to take a shot at the right time, then you need to inject the drug immediately, as soon as you remember it. The next injection is performed at 48 h.

    Side effects:

    The following undesirable phenomena observed with frequency on 2% and higher than in the placebo group (inactive drug) in patients who, in clinical trials, received Betaferon in a dose of 0.25 mg or 0.16 mg / m2 a day lasting up to three years.

    Flu-like symptoms can be weakened by using non-steroidal anti-inflammatory drugs. The experience of using Betaferon for the treatment of patients with multiple sclerosis is rather limited, therefore, negative reactions that occur with a low frequency may not yet be observed.

    To describe a specific reaction, its synonyms and associated states, the most appropriate term is used from the Medical Dictionary for regulatory activity (MedDRA).

    - General reactions

    Reaction at the injection site, asthenia (fatigue), a complex of influenza-like symptoms, headache, fever, chills, peripheral edema, chest pain, pain of different localization, malaise, necrosis at the injection site.

    - The cardiovascular system

    Increase in blood pressure.

    - Digestive system

    Abdominal pain.

    - Blood and lymphatic system

    Lymphocytopenia <1500 / mm3, neutropenia <1500 / mm3, leukopenia <3000 / mm3. Lymphadenopathy.

    - Metabolic and alimentary disorders

    Increase in activity of enzymes in the blood: aspartate aminotransferase (ACT) 5 times from the initial value, alanine aminotransferase (ALT) 5 times from the initial value.

    - Musculoskeletal system Myasthenia gravis, myalgia, leg cramps.

    - Nervous system Insomnia, impaired coordination.

    - Respiratory system Dyspnea.

    - Leather Rashes, skin lesions.

    - Genitourinary system

    Urgency to urinate in females - metrorrhagia (acyclic uterine bleeding) in men - impotence.

    The following list of side effects is based on monitoring the use of Betaferon after market entry.

    Frequency of side effects is classified as follows: very often (> 10%), often (<10% - > 1%), infrequently (1% <- > 0.1%), rarely (<0.1% - > 0.01%) and very rarely (<0.01%).

    - General reactions

    Very often: flu-like symptoms (fever, chills, myalgia, headache or excessive sweating) *. The frequency of these symptoms decreases with time. Rarely: general malaise, chest pain, weight loss, weight gain.

    - Local reactions

    Very often: reactions at the injection site (hyperemia, local edema) *, inflammation *, pain *.

    Often: necrosis at the injection site *.

    Over time, with the continuation of treatment, the frequency of reactions at the site of administration of the drug is usually reduced.

    - Blood and lymphatic system

    Infrequent: anemia, thrombocytopenia, leukopenia.

    Rarely: lymphadenopathy.

    - Endocrine disorders

    Rarely: thyroid dysfunction, including hyperthyroidism, hypothyroidism.

    - Metabolic disorders

    Rarely: increased concentration of triglycerides.

    - Nervous system

    Infrequently: muscle hypertonia, depression.

    Rarely: convulsions, confusion, agitation, emotional lability, suicidal attempts, anorexia, dizziness.

    - The cardiovascular system

    Infrequent: increased blood pressure.

    Rarely: cardiomyopathy, tachycardia, severe palpitations.

    Very rarely: vasodilation.

    - Respiratory system

    Rarely: dyspnea, bronchospasm.

    - Gastrointestinal tract

    Infrequent: nausea and vomiting.

    Rarely: pancreatitis, diarrhea.

    - Liver and biliary tract

    Infrequently: increased activity ACT, ALT.

    Rarely: increased activity of gamma-glutamyltransferase, bilirubin concentration, hepatitis.

    - Skin and subcutaneous tissue

    Infrequently: alopecia, hives, itching of the skin, skin rashes.

    Rarely: discoloration of the skin.

    - Skeletal musculature

    Infrequent: myalgia

    Rarely: arthralgia.

    - Female Reproductive System

    Rarely: menstrual irregularities

    Very rarely: menorrhagia (prolonged menstrual bleeding).

    - Allergic reactions

    Rarely: anaphylactic reactions.

    * Frequency is based on clinical trial data

    Overdose:When Betaferon was administered intravenously in a dose of 5.5 mg (176 million ME) three times a week, adult patients with oncological diseases were not found to have serious adverse events.
    Interaction:
    Special studies of the interaction of Betaferon with other drugs have not been conducted. The effect of the use of Betaferon in a dose of 0.25 mg (8 million IU) every other day on the metabolism of drugs in patients with multiple sclerosis is unknown. Against the background of the use of Betaferon glucocorticosteroids and ACTH, appointed for up to 28 days in the treatment of exacerbations, are well tolerated. The use of Betaferon simultaneously with other immunomodulators, in addition to corticosteroids or ACTH, has not been studied. Interferons reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. Caution should be exercised in prescribing Betaferon in combination with medications that have a narrow therapeutic index, the clearance of which is highly dependent on the hepatic cytochrome P450 system (eg antiepileptic drugs, antidepressants). You should also be careful when using any hematopoiesis at the same time.
    Due to the lack of compatibility studies, this medication should not be mixed with other medications.
    Special instructions:
    This drug contains human albumin, and for this reason there is very little risk of transmission of viral diseases. The theoretical risk of transmission of Creutzfeldt-Jakob disease is also considered highly unlikely
    Changes in laboratory indicators
    In addition to standard laboratory tests administered in patients with multiple sclerosis, before starting therapy with Betaferon, as well as regularly during the treatment, it is recommended to conduct a detailed blood test, including determining the leukocyte formula, platelet count and biochemical blood test, and to check the liver function (for example , activity of aspartate aminotransferase (ACT), alanine aminotransferase (AJ1T) and gamma-glutamyltransferase (y-HT)). When managing patients with anemia, thrombocytopenia, or leukopenia (individually or in combination), a more detailed monitoring of the expanded blood test may be required, including the determination of the number of red blood cells, leukocytes, platelets and the leukocyte formula.
    Gastrointestinal disorders
    In rare cases, against the background of the use of Betaferon, there was a development of pancreatitis, in most cases associated with the presence of hypertriglyceridemia.
    Dysfunction of the liver and bile duct
    Clinical studies have shown that Betaferon therapy can often lead to an asymptomatic increase in the activity of "hepatic" transaminases, which in most cases is slightly expressed and transient.
    As with the treatment with other interferons beta, severe liver damage (including liver failure) with the use of Betaferon are rare. The most severe cases were observed in patients exposed to hepatotoxic drugs or substances, as well as in certain concomitant diseases (eg, malignant tumors with metastasis, severe infections and sepsis, alcohol abuse). When treating Betaferon, it is necessary to monitor liver function (including assessment of the clinical picture). Increased activity of transaminases in the serum requires careful monitoring and examination. With a significant increase in the activity of transaminases in the blood serum or the appearance of signs of liver damage (eg, jaundice), the drug should be discontinued. In the absence of clinical signs of liver damage or after the normalization of the activity of "liver" enzymes, it is possibleresumption of Betaferon therapy with monitoring of liver function.
    Endocrine disorders
    Patients with thyroid dysfunction are recommended to check the function of the thyroid gland (thyroid hormones, thyroid-stimulating hormone) regularly, and in other cases - according to clinical indications.
    Diseases of the cardiovascular system
    Betaferon should be used with caution in patients with heart disease, in particular, with cardiac insufficiency III-IV stage according to the classification The New York Heart Association (NYHA), because such patients were not included in the clinical studies. If against the background of treatment with Betaferon develops cardiomyopathy and it is assumed that this is due to the use of the drug, the treatment with Betaferon should be discontinued.
    Diseases of the nervous system
    Patients should be informed that the side effect of Betaferon may be depression and suicidal thoughts, which should immediately be addressed to a doctor. In two controlled clinical trials involving 1657 patients with a secondary progressive PC, there was no significant difference in the incidence of depression and suicidal ideation with Betaferon or placebo.Nevertheless, caution should be exercised in prescribing Betaferon to patients with depressive disorders and suicidal thoughts in the anamnesis. If such phenomena occur on the background of treatment, the question of whether or not Betaferon should be withdrawn should be considered. Betaferon should be used with caution in patients with a history of seizures.
    General violations and violations at the injection site
    Can be observed serious allergic reactions (rare, but manifested in acute and severe form, such as bronchospasm, anaphylaxis and urticaria).
    If signs of damage to the integrity of the skin appear (for example, the flow of fluid from the injection site), the patient should consult a doctor before he continues with the injections of Betaferon.
    In patients who received Betaferon, there were cases of necrosis at the injection site (see "Side Effects"). Necrosis can be extensive and spread to the muscular fascia, as well as adipose tissue and, as a result, lead to the formation of scars. In some cases, it is necessary to remove the necrotic areas or, more rarely, skin transplantation. The healing process can take up to 6 months.When multiple foci of necrosis occur, Betaferon treatment should be discontinued until the damaged areas are completely healed. In the presence of a single focus, if necrosis is not too extensive, the use of Betaferon may be continued, as in some patients the healing of the deadened site at the injection site occurred against the background of the use of Betaferon. To reduce the risk of developing a reaction and necrosis at the injection site, patients should be recommended:
    - to carry out injections, strictly observing the rules of asepsis;
    - each time to change the injection site;
    - administer the drug strictly subcutaneously. Periodically, one should monitor the correctness of performing independent injections, especially when local reactions appear.
    Neutralizing antibodies
    As with any other drug with protein content, the use of Betaferon makes it possible to form antibodies. In a number of controlled clinical trials, serum analysis was performed every 3 months to detect the formation of antibodies to Betaferon. In these studies, it was shown that neutralizing antibodies to interferon beta-lb developed in 23% -41% of patients, which was confirmed by at least two subsequent positive results of laboratory tests.In 43% -55% of these patients, in subsequent laboratory studies, a stable absence of antibodies to interferon beta-lb was detected. In a study involving patients with a clinically isolated syndrome that suggests multiple sclerosis, neutralizing activity, which was measured every 6 months, during the visits, 16.5-25.2% of patients receiving Betaferon were observed. Neutralizing activity was detected at least once in 30% (75) of patients receiving Betaferon; in 23% (17) of them before the study was completed, the status of antibodies again became negative. During the two-year study period, the development of neutralizing activity was not associated with a decrease in clinical efficacy (in terms of time to the onset of clinically significant multiple sclerosis). It has not been proven that the presence of neutralizing antibodies has any significant effect on clinical outcomes. With the development of neutralizing activity, the appearance of any side reactions was not associated. The decision to continue or discontinue therapy should be based on the indicators of the clinical activity of the disease, and not on the status of neutralizing activity.
    Immune disorders
    The use of cytokines in patients with monoclonal gammapathy was sometimes accompanied by a systemic increase in capillary permeability with the development of shock and death.
    Use in children
    A systematic study of the efficacy and safety of Betaferon in children and adolescents under the age of 18 was not carried out.

    Effect on the ability to drive transp. cf. and fur:
    Specials research not conducted. Undesirable effects from the CNS can affect the ability to drive and work with machinery. In this regard, care must be taken when dealing with potentially hazardous activities requiring increased attention.
    Form release / dosage:
    Lyophilizate for the preparation of a solution for subcutaneous administration of 9.6 million ME.
    Packaging:
    Lyophilizate for the preparation of a solution for subcutaneous administration of 9.6 million ME of the preparation in a vial of type 1 glass (Eur. Pharm.) With a stopper covered with an aluminum cap, with a snap-open turquoise-colored cap.

    1) Solvent (sodium chloride solution 0.54%) in 1.2 ml in a syringe of glass type 1 (Hearth.Pharm.) In the cell packaging of PVC / paper (blister).

    5 bottles in a plastic pallet and 5 syringes (each in a blister), along with instructions for use in a cardboard box or 15 bottles in a plastic pallet and 15 syringes (each in a blister) together with instructions for use in a cardboard box.

    2) Solvent (sodium chloride solution 0.54%) in 1.2 ml in a syringe of glass type I (Heb. Pharm.).

    1 bottle, 1 syringe, 1 adapter with a needle for the bottle and 2 alcohol napkins are placed in a single cardboard package with a cardboard insert.

    For 5 or 15 single packages together with the instructions for use in a cardboard box.
    Storage conditions:At a temperature of no higher than 25 ° C. Do not freeze. Keep out of the reach of children.
    Shelf life:Lyophilizate - 2 years. Solvent - 3 years. Do not use after expiry date.
    Terms of leave from pharmacies:On prescription
    Registration number:П N012097 / 01
    Date of registration:10.06.2010
    The owner of the registration certificate: Bayer Schering Pharma AG Bayer Schering Pharma AG Germany
    Manufacturer: & nbsp
    Representation: & nbspBAYER, AOBAYER, AO
    Information update date: & nbsp12.12.2015
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