Extavia (Extavia®)

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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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  • Extavia
    lyophilizate PC 
    Novartis Pharma AG     Switzerland
    • Dosage form: & nbsplyophilizate for the preparation of a solution for subcutaneous administration
    Composition:

    Per 1 bottle:

    active substance: interferon beta-1b 0.3 mg (one bottle contains 9.6 million. ME active ingredient.

    To prepare the reconstituted solution, 1.2 ml of 0.54% sodium chloride solution is added to the vial, which corresponds to a content of 8 million IU (0.25 mg) of the active substance in 1 ml of the reconstituted solution);

    Excipients: human albumin 15 mg, mannitol 15 mg.

    Solvent: 0,54% solution of sodium chloride.

    Description:

    Lyophilizate: lyophilized white mass.

    Solvent: clear, colorless solution.

    Reconstituted solution: solution from slightly opalescent to opalescent, colorless or light yellow in color.

    Pharmacotherapeutic group:Cytokine
    ATX: & nbsp

    L.03.A.08   Interferon beta-1b

    Pharmacodynamics:

    Interferon beta-1b, used for multiple sclerosis (PC), has antiviral and immunoregulatory activity. Mechanisms of action of interferon beta-1b with multiple sclerosis is not completely established. However, it is known that the biological effect of interferon beta-1b is mediated by its interaction with specific receptors that are found on the surface of human cells. Interferon beta-1 bindingb with these receptors induces the expression of a number of substances that are considered as mediators of the biological effects of interferon beta-1b. The content of some of these substances was determined in the serum and blood cell fractions of patients receiving interferon beta-1b. Interferon beta-1b reduces the binding ability and expression of receptors to interferon gamma, enhances their decay. The drug increases the suppressor activity of peripheral blood mononuclear cells.

    As with remittent, and with secondary-progressive multiple sclerosis, interferon beta-1 treatmentb reduces the frequency (by 30%) and severity of clinical exacerbations of the disease, the number of hospitalizations and the need for treatment with steroids, and also lengthens the duration of remission.

    In patients with secondary-progressive multiple sclerosis, the use of interferon beta-1b allows to delay further progression of the disease and the onset of disability (including severe disability, when patients are forced to constantly use a 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 from 3.0 to 6.5 points on the extended scale of disability EDSS).

    The results of magnetic resonance imaging (MRI) of the brain of patients with remitting and secondary-progressive multiple sclerosis on the background of treatment with interferon beta-1b showed a significant positive effect of the drug on the severity of the pathological process, as well as significant
    Pharmacokinetics:

    After subcutaneous administration of interferon beta-1b in the recommended dose of 0.25 mg, the serum concentrations of the drug are low or not at all determined. In this regard, information about the pharmacokinetics of the drug in patients with multiple sclerosis, receiving interferon beta-1b in the recommended dose, no.

    After subcutaneous administration of 0.5 mg of the drug, the maximum plasma concentration is reached 1-8 hours after the injection and is about 40 IU / ml. Absolute bioavailability with subcutaneous injection is about 50%.

    When intravenous use of interferon beta-1b the clearance and half-life of the drug from the serum averaged 30 ml / min / kg and 5 hours, respectively.

    Introduction of interferon beta-1b in a day does not lead to an increase in the concentration of the drug in the serum, and its pharmacokinetics does not change during the course of therapy.

    When subcutaneous application of interferon beta-1b at a dose of 0.25 mg every other day levels of biological response markers (neopterin, beta2-microglobulin and immunosuppressive cytokine IL) significantly increased as compared to baseline after 6-12 hours after the first dose. They peaked at 40-124 h and remained elevated during the 7-day (168 h) study period.

    Indications:

    - remitting multiple sclerosis (RRMS) - to reduce the frequency and severity of exacerbations in ambulatory patients (i.e. patients who can walk without assistance) with a history of two or more of exacerbations of the disease for the past two years, followed by complete or incomplete recovery of neurologic deficiency.

    - Secondary-progressive multiple sclerosis with an active course of the disease characterized by exacerbations or marked worsening of neurologic functions in the last two years - to reduce the frequency and severity of clinical exacerbations of the disease, and to slow the progression of the disease.

    Contraindications:

    - Hypersensitivity to natural or recombinant beta interferon or human albumin or any other component of the drug;

    - tsevere forms of depression and / or suicidal thoughts (including in history);

    - zliver abortion in the stage of decompensation;

    - bPregnancy and the period of breastfeeding.

    Carefully:

    Carefully should be used in patients with the following diseases:

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

    - monoclonal gammopathy;

    - anemia, thrombocytopenia, leukopenia;

    - abnormal liver function;

    - epileptic seizures in the anamnesis;

    - severe renal dysfunction.

    Due to the lack of sufficient experience of use, caution is necessary when using the drug in patients younger than 18 years of age.

    Pregnancy and lactation:

    Pregnancy

    It is not known whether the drug can cause fetal damage in the treatment of pregnant women or affect the reproductive function of a person. In controlled clinical trials in patients with multiple sclerosis have been cases of spontaneous abortion. In studies in rhesus monkeys, human interferon beta-1b had an embryotoxic effect and in higher doses caused an increase in the frequency of abortions. Women of reproductive age should be treated with safe methods of contraception. In case of pregnancy during the treatment of Ecstasy or pregnancy planning, it is recommended to cancel the drug.

    Lactation

    It is not known whether interferon beta-1b with breast milk. Given the theoretical possibility of developing unwanted reactions in infants who are breastfeeding, it is necessary to stop breastfeeding or to cancel the drug.

    Dosing and Administration:

    Treatment Ecstasy should be started under the supervision of a doctor who has experience in the treatment of this disease.

    The issue of the length of treatment for Ecstasy remains unresolved. In clinical studies, the duration of therapy in patients with remitting and secondary-progressive multiple sclerosis reached 5 years and 3 years, respectively. The duration of the course is determined by the doctor.

    Preparation of injection solution

    To dissolve the lyophilized interferon beta-1 powderb for injections use the supplied ready-made syringe with solvent and needle. In the vial with Ecstasy, 1.2 ml of solvent are introduced (0.54% sodium chloride solution). 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 IU) of interferon beta-1b.

    The drug should be administered subcutaneously immediately after the preparation of the solution. If the injection is postponed, the solution should be stored in the refrigerator and used within 3 hours. The solution should not be frozen.

    Mode of application

    Subcutaneously.

    Dosage

    The recommended dose of Ecstavy 0.25 mg (8 million IU), 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 given after 48 hours.

    Side effects:

    Grippopodobnye symptoms can be weakened by using non-steroidal anti-inflammatory drugs.

    The experience of using the drug for the treatment of patients with multiple sclerosis is rather limited, therefore, negative reactions that occur with a low frequency could not yet be observed.

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

    The following undesirable events observed with a frequency of 2% and higher than in the placebo group in patients who received controlled drug trials at a dose of 0.25 mg / m2 or 0.16 mg / m2 a day lasting up to 3 years.

    General disorders and reactions at the injection site: reactions at the site of administration (including hemorrhages,hypersensitivity reactions, inflammation, swelling, pain, irritation, edema, atrophy at the injection site), asthenia, a complex of influenza-like symptoms (includes flu symptoms and / or a combination of at least two of the following adverse events: fever, chills, myalgia, general malaise , increased sweating), pain of different localization, fever, chills, peripheral swelling, pain in the chest, general malaise, necrosis at the injection site.

    From the cardiovascular system: arterial hypertension.

    From the digestive system: abdominal pain.

    From the hepatobiliary system: an increase in the level of alanine aminotransferase (ALT)˟ more than 5 times as compared to the baseline, an increase in the level of aspartate aminotransferase (ACT)˟ more than 5 times compared with the original.

    From the side of the blood and lymphatic system: lymphopenia (<1500 / mm3), absolute neutropenia (<1500 / mm3), leukopenia (<3000 / mm3), lymphadenopathy.

    From the musculoskeletal system: muscle hypertension, myalgia, myasthenia gravis, back and limb pain, leg cramps.

    From the central and peripheral nervous system: headache, dizziness, insomnia, migraine, paresthesia, impaired coordination.

    From the sense organs: conjunctivitis, impaired vision, pain in the ears.

    On the part of the respiratory system: dyspnea.

    Dermatological reactions: skin reactions, rash.

    From the genitourinary system: mandatory urges to urinate, in premenopausal women - metrorrhagia (acyclic bleeding), in men - impotence.

    ˟ changes in laboratory indicators

    On the background of interferon beta-1 therapyb in clinical practice, regardless of the presence of a cause-and-effect relationship with the use of the drug, the following undesirable phenomena were noted.

    The incidence of adverse events was estimated as follows: "very often" (≥1/10), "often" (≥1 / 100; <1/10), "sometimes" (≥1 / 1000; <1/100), "rarely" (≥1 / 10000; <1/1000), "very rarely" (<1/10000).

    General disorders and reactions at the injection site: very often - a complex of influenza-like symptoms *, chills *, fever *, reactions at the injection site *, inflammation at the injection site *, pain at the injection site; often - necrosis at the site of injection *; rarely - pain in the chest, general malaise, increased sweating,increase or decrease in body weight.

    The frequency of influenza-like syndrome decreases with time.

    From the side of the blood and lymphatic system: sometimes - Anemia, thrombocytopenia, leukopenia; rarely - Lymphadenopathy.

    From the endocrine system: rarely - hyperthyroidism, hypothyroidism, thyroid dysfunction.

    Metabolic and alimentary disorders: rarely hypertriglyceridemia.

    From the central and peripheral system: rarely - convulsions, dizziness.

    Mental disorders: sometimes - depression; rarely - confusion, excitement, emotional lability, suicidal attempts, anorexia.

    From the cardiovascular system: sometimes - arterial hypertension; rarely - cardiomyopathy, tachycardia, severe palpitations; very rarely - vasodilation.

    On the part of the respiratory system: rarely - bronchospasm, shortness of breath.

    From the digestive system: sometimes - nausea, vomiting; rarely - pancreatitis, diarrhea.

    From the hepatobiliary system: sometimes - increased activity ACT and ALT; rarely - Hyperbilirubinemia, increased activity of glutamyltransferase (γ-GT), hepatitis.

    Dermatological reactions: sometimes - hives, rash, itching, alopecia; rarely - a discoloration of the skin.

    From the musculoskeletal system: sometimes - myalgia, muscle hypertonia, arthralgia.

    From the female reproductive system: rarely - violation of the menstrual cycle; very rarely - menorrhagia (prolonged menstrual bleeding).

    Allergic and immunopathological reactions: rarely - anaphylactic reactions.

    * frequency of development of AE data is indicated in accordance with the data of clinical trials
    Overdose:

    With the introduction of interferon beta-1b intravenously in a dose of up to 5.5 mg (176 million IU) three times a week, adult patients with cancer had no serious adverse events.

    Interaction:

    Special studies of the interaction of Ecstavia with other drugs have not been conducted.

    The effect of the drug at 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 backdrop of the use of Ecstavia, glucocorticosteroids and adrenocorticotropic hormone (ACTH), prescribed for up to 28 days in the treatment of exacerbations, are well tolerated.

    The use of Ecstasy simultaneously with other immunomodulators, in addition to glucocorticosteroids or ACTH, has not been studied.

    Interferons reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. Care should be taken when prescribing Ecstavia in combination with medications that have a narrow therapeutic index, the clearance of which is largely dependent on the hepatic cytochrome P450 system (eg, antiepileptics, antidepressants).

    It is also necessary to be careful when using any drugs that affect the hematopoiesis system at the same time.

    In the absence of compatibility studies, this drug should not be mixed with other drugs.

    Special instructions:

    The 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 the management of patients with multiple sclerosis,Before beginning therapy with Ecstasy, and also regularly during the treatment, it is recommended to conduct a detailed blood test, including the determination of the leukocyte formula, platelet count and biochemical blood test, and also check the liver function (for example, activity ACT, ALT and γ-GT). 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.

    Disorders from the digestive system

    In rare cases, against the backdrop of the use of Extavia, 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 treatment with Ecstasy can often lead to an asymptomatic increase in hepatic transaminases, which in most cases is only slightly expressed and transient.

    As with other beta-interferon treatment, severe liver damage (including liver failure) with the use of Extavia is rare.The most severe cases were observed in patients exposed to hepatotoxic drugs or substances, as well as in certain concomitant diseases (for example, malignant diseases with metastasis, severe infections and sepsis, alcohol abuse).

    When treating Ecstasy, it is necessary to monitor liver function (including assessment of the clinical picture). Increasing the level of transaminases in the serum requires careful monitoring and examination. With a significant increase in 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 normalization of the level of liver enzymes, it is possible to resume treatment with Ecstasy with monitoring the liver function.

    Endocrine disorders

    Patients with thyroid dysfunction are recommended to regularly check the function of the thyroid gland (thyroid hormones, thyroid-stimulating hormone), and in other cases - according to clinical indications.

    Diseases of the cardiovascular system

    Ecstasy should be used with caution in patients with heart disease, in particular, with heart failure III-IV stage by classicthe New York Heart Association (NYH), because such patients were not included in the clinical studies.

    If the cardiomyopathy is developing against the backdrop of treatment with Ecstasy and it is supposed that this is due to the use of the drug, then Ecstasy treatment should be discontinued.

    Diseases of the nervous system

    Patients should be informed that the side effect of Ecstasy may be depression and suicidal thoughts, which should immediately be addressed to a doctor.

    In two controlled clinical trials involving 1657 patients with secondary-progressive multiple sclerosis, there was no significant difference in the incidence of depression and suicidal ideation with the use of Extavia or placebo. Nevertheless, caution should be exercised in appointing Ekstavia to patients with depressive disorders and suicidal thoughts in the anamnesis. If such phenomena occur on the background of treatment, the question of whether to discontinue the drug should be considered.

    Ecstasy should be used with caution in patients with epileptic seizures in history.

    General disorders and reactions at the injection site

    Serious allergic reactions can occur (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 Ecstasy.

    Patients who received Ecstasy received cases of necrosis at the injection site. 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 appear, treatment with Ecstasy 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 Ecstasy can be continued, as in some patients, the healing of the necrotic site at the injection site occurred against the background of the drug.

    In order 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, when using Ecstavia, it is possible to form antibodies. In a number of controlled clinical trials, serum analysis was performed every 3 months to detect the development of antibodies to interferon beta-1b.

    In these studies, it was shown that neutralizing antibodies to interferon beta-1b 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-1b.

    It has not been proven that the presence of neutralizing antibodies has any significant effect on clinical outcomes, including data MPT. 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.

    Effect on the ability to drive transp. cf. and fur:

    Special studies have not been 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:Liophilizate for the preparation of a solution for subcutaneous administration, 9.6 million IU.
    Packaging:Lyophilizate, 9.6 million IU, into a glass bottle with a stopper covered with an aluminum cap, with a snap-off lid.
    1.2 ml solvent in a syringe made of glass.
    One syringe per blister.
    For 5 or 15 vials in a plastic pallet and 5 or 15 syringes (each in a blister) together with instructions for medical use in a pack.
    Storage conditions:

    At a temperature of no higher than 25 ° C. Do not freeze.

    The reconstituted solution should be stored for 3 hours at a temperature of 2 ° C to 8 ° C.

    Keep out of the reach of children.

    Shelf life:

    2 years.

    The drug should not be used after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-008908/09
    Date of registration:06.11.2009
    Expiration Date:18.02.2014
    The owner of the registration certificate:Novartis Pharma AGNovartis Pharma AG Switzerland
    Manufacturer: & nbsp
    Representation: & nbspNOVARTIS PHARMA LLCNOVARTIS PHARMA LLC
    Information update date: & nbsp11.01.2017
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