SynnoWex (CinnoVex)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceInterferon beta-1aInterferon beta-1a
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    • Dosage form: & nbsp
    Lyophilizate for the preparation of solution for intramuscular injection.

    Composition:

    Lyophilizate (1 bottle contains):

    Active substance: Interferon beta-1 and 30 μg (6 million ME);

    Excipients: human albumin (15 mg), sodium hydrogen phosphate (5.7 mg), sodium dihydrogen phosphate (1.2 mg), sodium chloride (5.8 mg).

    Solvent (1 ampoule contains): water for injection - 1 ml.

    Description:
    Lyophilizate: lyophilized mass of white or almost white color.

    Solvent: clear, colorless liquid.
    Pharmacotherapeutic group:Cytokine.
    ATX: & nbsp

    L.03.A.B.07   Interferon beta-1a

    Pharmacodynamics:SynnaVex - recombinant interferon beta-1 a is obtained by using recombinant DNA technology on Chinese hamster ovary cells with the built-in human beta interferon genome. It is a glycosylated polypeptide containing 166 amino acids with a molecular weight of 22500.
    The sequence of amino acids corresponds to natural human interferon beta.
    Interferons are natural proteins produced by eukaryotic cells in response to a viral infection and to the effects of other biological factors. Interferons are cytokines, which are the mediators of the antiviral, antiproliferative and immunomodulating systems of the body.
    Beta-interferon is synthesized by various types of cells, including fibroblasts and macrophages. Natural beta interferon and Sinnovex (interferon beta-1a) exist in glycosylated form and have a single complex hydrocarbon fragment bound to the N atom. The glycosylation of proteins affects their stability, activity, biodistribution and half-life.
    The biological properties of SynnaVex are determined by its ability to bind to specific receptors on the surface of cells of the human body and to trigger a complex cascade of intercellular interactions leading to interferon-mediated expression of numerous gene products and markers such as the main histocompatibility complex of the first class, the protein Mx, 2 '/ 5' oligoadenylate synthetase, b2-microglobulin and neopterin.The presence of some of these compounds was found in the serum and cell fractions of the blood of patients who received SynnaVex. After intramuscular administration of a single dose of the drug, the content of these compounds in the serum remained elevated for a minimum of 4-7 days. It is not known whether the mechanism of action of the Sinnovex drug is related to the treatment of multiple sclerosis with the initiation of biological interactions described above, since the pathophysiology of multiple sclerosis has not yet been studied sufficiently. The effect of the Sinnovex preparation in the treatment of multiple sclerosis was demonstrated in a double-blind study of patients with a relapsing form of multiple sclerosis (for the preparation SynnaVex n = 41, for the comparison drug Avonex® n = 43). In accordance with the scheme of the study, patients were observed at different times. 60 participants in the study took the drug "SynnoVex" under supervision for a period of 2 years. It was shown that by the end of the second year, the total number of patients who experienced progression of disability (defined by the Kaplan-Mayer table) was 34% with the appointment of Avonex® and -32% with the use of the drug SynnaVex.Progression of disability was measured as an increase in the disability (on the EDSS scale) by 1.0 point, which lasts for at least 6 months. It was also found that the use of the drug SynnaVex led to a decrease in the frequency of relapses during the year by one third. These data were obtained after treatment lasting more than one year.

    Pharmacokinetics:The pharmacokinetics of interferon beta-1 a have been studied on the basis of measuring the antiviral activity of interferon. With a single intramuscular application of SynnaVex, peak levels of antiviral activity were achieved in plasma in the period from 5 to 15 hours; the half-life was about 10 hours. With the introduction of an appropriate correction for the rate of absorption from the injection site, the calculated bioavailability of the drug is approximately 40%.
    Indications:
    - SynnaVex is intended for the treatment of patients suffering from recurrent multiple sclerosis (RRS), characterized by at least two relapses during the previous three-year period in the absence of signs of disease progression between relapses.SynnaVex slows the progression of disability and increases the interval between relapses for more than two years.

    - Treatment of patients who had a case of demyelination as a result of an active inflammatory process that required intravenous corticosteroids, with the exception of a diagnosis other than multiple sclerosis.
    Contraindications:
    - Known hypersensitivity to natural or recombinant interferon beta, human serum albumin or any other component of the drug;

    - period of pregnancy and lactation;

    - pronounced depressive state

    - severe depression and the appearance of suicidal thoughts;

    - patients with epilepsy with seizures, poorly controlled by therapeutic agents;

    - the age of up to 12 years due to the lack of clinical data on the use of the drug in this group.
    Carefully:
    SynnaVex, like other interferons, should be used with caution in the treatment of patients suffering from depression or depressive disorders. It is known that the use of interferons may cause depression and suicidal thoughts, and in the group of people with multiple sclerosis,the frequency of such phenomena increases. The emergence of depressive states is possible at any time of treatment with Sinnovex. If there are any signs of depression or suicidal thoughts, patients, it is necessary to contact the doctor without delay. For such patients, it is necessary to establish close monitoring during treatment and, if necessary, to urgently apply appropriate medical measures. In some cases, it may be necessary to stop the use of the drug.
    Care should be taken when prescribing Sinnovex to patients who have previously suffered seizures. In the case of patients who have not previously suffered from epileptic seizures, and who are taking anti-epileptic drugs, in particular if the treatment for epilepsy and the use of anti-epileptic drugs are not controlled or monitored inadequately.
    Care should be taken when prescribing, as well as carefully monitor patients suffering from severe renal and hepatic impairment, as well as with oppression of bone marrow hematopoiesis.
    When using interferon beta, the appearance of signs of impaired liver function,such as increasing the level of liver enzymes in the blood serum, the development of hepatitis, including autoimmune, liver failure. However, it is not known whether this is a consequence of taking interferon beta-1a or because of taking other drugs that are usually prescribed by
    patients. Patients should be closely monitored for signs of impaired liver function, especially if interferon is used in conjunction with other hepatotoxic drugs.
    When using the drug SynnaVex should carefully monitor the condition of patients with diseases of the cardiovascular system: angina, myocardial infarction, decompensated heart failure, arrhythmia. Manifestations of influenza-like syndrome caused by the use of the drug may have a stressful effect on such patients.
    With the use of interferons, there are deviations in laboratory indicators, therefore, in addition to the usual laboratory tests conducted by patients with PC, it is recommended to count the blood cells (including platelets) during the treatment, to determine the leukocyte formula and the biochemical blood test (including liver enzymes).Those patients who have signs of bone marrow depression may need a more thorough blood test with the determination of cell elements by fractions and platelets.
    When using Sinnovex in the blood serum interferon-neutralizing antibodies can appear, which can decrease the activity of interferon beta-1 a, and consequently, the clinical effectiveness of the drug. Available data indicate that after 12 months of treatment, approximately 8% of patients in the serum have antibodies to interferon beta-1 a.

    Pregnancy and lactation:In connection with the potential risk of developing adverse reactions, the use of "Sinnovex" during pregnancy is contraindicated. The available data indicate a spontaneous abortion. In connection with the potential risk of developing adverse reactions in the infant, SinnoWex is contraindicated for use during lactation.
    Women with preserved reproductive capacity should use effective methods of contraception. In case of pregnancy or pregnancy planning during the treatment with Sinnovex, the patient should be informed of the potential danger and consider the desirability of canceling the treatment.In patients with a high relapse rate prior to treatment, the risk of severe recurrence should be compared due to the cancellation of Sinnovex in the case of pregnancy, with a possible increase in the risk of spontaneous abortion due to its intake during pregnancy.
    Dosing and Administration:

    The drug should be administered under the guidance and supervision of a physician with experience in the management of multiple sclerosis (PC).

    Adults: The recommended dose of Sinnovex (interferon beta-1a) for PPC is 30 μg (6 million ME), those. 1 ml of the dissolved drug in the vial, and injected intramuscularly once a week.

    Treatment can be started either with a full dose of 30 mcg, or with a half dose once a week gradually increasing it to a full dose of 30 mcg so that the body can get used to the drug. To achieve sufficient efficiency after the initial treatment period, it is necessary to bring the dose to 30 μg once a week and then adhere to this dose.

    The administration of a higher dose (60 μg) once a week does not bring additional benefit.

    Children and teens: Safety profile for prescribing

    Sinnovex 30 mcg intramuscularly once a week for adolescents 12-16 years is similar to the safety profile for adults.Information on the use of the drug in the treatment of children under the age of 12 years is not available, so the Sinnovex drug should not be used for this population of patients.

    Elderly patients: In clinical trials, a sufficient number of patients older than 65 years did not participate to determine the possible difference in response to treatment in this age group compared to younger patients. However, based on the clearance of the active substance, there is no theoretical basis for correcting the dose of this drug for elderly patients.

    Injections of the drug should, if possible, be made at the same time and on the same day of the week. Place of intramuscular injections should be changed every week.

    The duration of the course of therapy is determined individually. After two years of treatment, the patient must undergo a clinical examination and on an individual basis the attending physician may recommend continuing the course of therapy. It is necessary to stop treatment if the patient develops a chronic progressive PC.

    It is possible to perform injections by the patient himself with the permission of the attending physician and after training in the method of intramuscular injections.

    The recommendations below are for those who independently inject the drug:

    - Each package includes four trays with disposable doses of the drug each, and eight antiseptic napkins impregnated with alcohol, in separate hermetically sealed bags. Each tray includes a bottle of lyophilized powder SynnaVex, an ampoule with water for injection 1 ml, a syringe with a needle for solution and an injection needle.

    - Remove the preparation from the refrigerator and leave it at room temperature for 15-30 ° C for about 30 minutes. To heat the ampoule with a solvent, do not use external heat sources such as hot water.

    - After washing your hands, put two antiseptic wipes and a tray with a dose on a clean surface. Carefully open the packaging of the tray and remove the contents. It is desirable to additionally prepare a sterile cotton wool medical, disinfectant solution (for example, ethyl alcohol 70%) and bactericidal plaster.

    - Open the syringe and needle packs. Do not remove the protective cap from the needle, put the needle on the syringe, turning it half turn. - Using an alcohol napkin, open the ampoule with water for injection, breaking the ampoule along the red line on the neck. Remove the cover from the needle without rotating the needle, and draw water for injection into the syringe.Keep the protective cap for later use. If air bubbles get into the syringe, gently dispose of them by holding the syringe vertically up with a needle and gently pushing the piston. Attach the protective cap to the needle.

    - Remove the lid from the vial with the drug. Wipe the upper part of the bottle with the drug with an alcoholic napkin.

    - Remove the protective cap from the needle, pierce the rubber stopper of the bottle with the drug with the needle. Guide the needle to the side wall of the vial and slowly add the solvent (the entire contents of the syringe).

    - Leaving the needle and syringe in place, gently rotate the contents of the vial until all the powder has dissolved. Do not vigorously shake the bottle, as this will lead to foaming. If the solution is clouded or colored or solids are visible in solution, the vial should not be used. A light yellow color of the solution is acceptable.

    - Before taking the solution, the piston must be completely immersed in a syringe to remove air. Then put the bottle on the work surface at a slight angle. The entire needle should be in the vial, and the end of the needle should be permanently immersed in the solution.Slowly remove the solution in a syringe to the mark of 1 ml, located on the side surface of the syringe. A syringe with a needle is extracted from the vial. Put a protective cap on the needle. Rotate the needle from the syringe. Do not touch the syringe outlet!

    - The second needle is intended for the administration of the solution of the drug SynnoVex. It is a standard needle for intramuscular injection. As described above, with the turn, put the needle on the syringe. Remove the plastic protective cap from the needle and set it aside. To remove air, the syringe should be turned with a needle upwards and gently knocked on it so that the bubbles gather at the top. Carefully press the piston so that air is removed, allowing only a small drop of solution to pour out. The protective cover is put in place and the syringe is put aside while preparing the injection site.

    - The chosen site for injection should be cleaned with a new alcoholic napkin. Remove the plastic protective cover from the needle and insert the needle through the skin into the muscle tissue. Injection is slow, then remove the needle with the syringe. Place the injection site with an alcohol sponge and, if necessary, seal the injection site with adhesive tape.

    - The subsequent injection must be done elsewhere on the body.

    - In case of circumstances that do not allow the injection, when the solution is already prepared, it can be placed no more than 5.5 - 6 hours in the refrigerator at a temperature of 2- 8 ° C, after which, after bringing the temperature of the solution to room temperature, make an injection according to the scheme described above.

    A prepared solution that persists for more than 6 hours in a refrigerator or left at room temperature for more than 30 minutes is not suitable for further use.

    Side effects:

    The most frequent manifestation of the side effect of interferons is the flu-like syndrome. It manifests itself in the form of weakness, fatigue, muscle pain, fever, chills, headache, nausea. These symptoms are usually more pronounced at the beginning of treatment, their frequency decreases as the treatment continues. To alleviate these symptoms, an antipyretic analgesic can be prescribed, which should be taken before the introduction of Sinnovex and then every 6 hours, all within 24 hours after each injection. Before taking any drug while taking Sinnovex, you need to consult a doctor. If the doctor recommends taking an antipyretic analgesic, the recommendation should be carefully followed; Do not increase the dose of antipyretic-analgesic in excess of the recommended.

    In any period of treatment, neurologic symptoms similar to exacerbation of multiple sclerosis may occur: transient episodes of muscle hypertension and / or muscle weakness that limit the possibility of voluntary movements. These episodes, limited in duration, are associated with injections and can be repeated in subsequent injections. In some cases, these symptoms are accompanied by influenza-like symptoms.

    In each particular category, side effects are presented in

    order of decrease in severity:

    Very Frequent (>1/10 patient-years)

    Frequent (from 1/100 to 1/10 patient-years)

    Not frequent (1/1000 to 1/100 patient-years)

    Rare (from 1/10 000 to 1/1 000 patient-years)

    Very rare (<1/10 000 patient-years)

    Unknown (based on the available data, the assessment is not possible)

    Where: patient-years is the sum of individual units of time during which the patient participating in the study received the drug before developing an adverse reaction.

    Research:

    Frequent: lymphocytopenia, leukopenia, neutropenia, decreased hematocrit, increased potassium levels in the blood, increased the content of urea nitrogen in the blood.

    Not frequent: thrombocytopenia.

    Unknown: decrease in body weight, increase in body weight, deviation of the parameters of the functional test of the liver from normal.

    Disturbances from the heart and cardiovascular system:

    Unknown: cardiomyopathy, congestive heart failure, pulsation, arrhythmia, tachycardia.

    Violations from the blood and lymphatic system:

    Unknown: pancytopenia, thrombocytopenia.

    Impaired nervous system:

    Very Frequent: headache2.

    Frequent: muscle spasms, hypoesthesia

    Unknown: neurologic symptoms, fainting3, hypertension, dizziness, paresthesia, convulsions, migraine.

    Disturbances from the respiratory system:

    Frequent: rhinorrhea

    Rare: dyspnea.

    Disorders from the gastrointestinal tract:

    Frequent: vomiting, diarrhea, nausea2.

    Disturbances from the skin and subcutaneous tissues:

    Frequent: rash, intense sweating, bruises.

    Not frequent: alopecia.

    Unknown: angioedema, itching, vesicular rash, hives, exacerbation of psoriasis.

    Disturbances from the musculoskeletal and connective tissue:

    Frequent: Muscular spasms, neck pain, myalgia2, arthralgia, pain in limbs, back pain, muscle stiffness, skeletal- muscular rigidity.

    Unknown: systemic lupus erythematosus, muscle weakness, arthritis.

    Disorders from the endocrine system:

    Unknown: hypothyroidism, hyperthyroidism.

    Disorders from the metabolism and nutrition:

    Frequent: anorexia.

    Vascular disorders:

    Frequent: tides to the face

    Unknown: vasodilation

    General disorders and disorders at the site of administration

    Very Frequent: flu-like syndromes, fever2, chills2, sweating2.

    Frequent: pain at the injection site, erythema at the injection site, hematoma at the injection site, asthenia, pain, fatigue, malaise, night sweats.

    Not frequent: burning at the injection site.

    Unknown: abscess at injection site1, cellulite at the injection site, inflammation at the injection site, necrosis at the injection site, bleeding at the injection site, chest pain.

    Immune system disorders:

    Unknown: anaphylactic reaction, anaphylactic shock, hypersensitivity reaction (angioedema, respiratory distress, urticaria, rash, itching rash).

    Disorders from the liver and bile ducts:

    Unknown: hepatic failure, hepatitis, autoimmune hepatitis.

    Disorders from the reproductive system and breast:

    Not frequent: metrorrhagia, menorrhagia.

    From the central nervous system:

    Frequent: depression, insomnia

    Unknown: suicide, psychosis, anxiety, confusion, emotional lability.

    1 The described reactions at the injection site include pain, inflammation and very rare cases of abscess or cellulitis that may require surgery.

    2 The incidence of these side effects is higher at the beginning of the treatment.

    3 After SynnaVex injection, a syncope is possible, as a rule, such fainting turns out to be the only episode at the beginning of treatment and is not verified with subsequent injections.

    If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, inform the doctor about it.

    Overdose:Due to the route of administration and dosage form, an overdose is unlikely. However, an overdose of Sinnovex, like any other drug, should be avoided. In case of an overdose, the patient should be hospitalized for medical follow-up and appropriate therapy.
    Interaction:Special studies on the interaction of Sinnovex (interferon beta-1a) with other drugs, including corticosteroids or ACTH, have not been performed in humans. At the same time, the experience of clinical trials shows that patients with multiple sclerosis can take Sinnovex together with corticosteroids or ACTH during an exacerbation of the disease. It is known that interferons have the ability to reduce the activity of enzymes associated with liver cytochrome P450. In this regard, caution should be exercised in appointing Sinnovex simultaneously with drugs whose clearance is largely dependent on the cytochrome P450 system, for example, antiepileptic drugs and antidepressants.
    Effect on the ability to drive transp. cf. and fur:In the case of side effects from the central nervous system,the ability of sensitive patients to drive and use machinery can be minimized.
    Form release / dosage:
    Lyophilizate, for prig. r-ra for im. 30 μg (6 million ME).
    Packaging:
    Lyophilizate, for the preparation of a solution for intramuscular injection of 30 μg (6 million ME) in a bottle of transparent, colorless neutral glass with a volume of 3 ml, closed with a rubber stopper, an aluminum cap and a plastic cap with a control of the first opening.

    Solvent on 1 ml in an ampoule from colorless neutral glass in volume of 2 ml.

    One vial with lyophilizate, one ampoule with solvent, one disposable empty syringe and 2 needles are packed in a sealed plastic tray.

    4 plastic trays and 8 alcohol wipes are placed in a cardboard box together with instructions for use.

    In order to protect the package from forgery, two protective stickers with a logo and the inscription "CinnaGen Q.A. Approved CinnaGen" are pasted onto a cardboard pack.
    Storage conditions:In the dark place at a temperature of 2 - 8 ° C. Keep out of reach of children.
    Shelf life:
    Lyophilizate: 2 years.

    Shelf life: 3 years

    Do not use after the expiration date.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-009100/10
    Date of registration:31.08.2010
    The owner of the registration certificate:Sia AFS, LLC Sia AFS, LLC Russia
    Manufacturer: & nbsp
    Representation: & nbspSia AFS, LLCSia AFS, LLCRussia
    Information update date: & nbsp12.12.2015
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