Botulax (Botulax)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceBotulinum toxin type A - hemagglutinin complexBotulinum toxin type A - hemagglutinin complex
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    • Dosage form: & nbspLiophilizate for the preparation of a solution for intramuscular administration.
    Composition:

    Per one vial:

    For a dosage of 50 units:

    Active substance: botulinum toxin type A - 50 units;

    Excipients: human serum albumin - 0.25 mg, sodium chloride - 0.45 mg.

    For a dosage of 100 units:

    Active substance: botulinum toxin type A - 100 units;

    Excipients: human serum albumin - 0.5 mg, sodium chloride - 0.9 mg.

    Description:Liophilizate white.
    Pharmacotherapeutic group:Mildrelax of peripheral action
    ATX: & nbsp

    M.03.A.X.01   Botulinum toxin

    Pharmacodynamics:

    The botulinum toxin type A molecule consists of two chains: heavy (with a molecular weight of 100,000 Daltons) and light (with a molecular weight of 50,000 Daltons) connected by a disulfide bond.

    The heavy chain has a high affinity for specific receptors localized on the surface of target neurons. Light chain is characterized by Zn+2dependent protease activity. It is specific for the cytoplasmic regions of the synaptosomal-associated protein with a molecular weight of 25,000 Daltons (SNAP-25), taking part in the processes of exocytosis.

    The first stage the action of botulinum toxin type A is the specific binding of the molecule to the presynaptic membrane.

    The second stage - penetration of the bound toxin into the cytoplasm of neurons by endocytosis. Inside the cell, the light chain exhibits Zn+2-dependent protease activity, selectively destroying SNAP-25, that on the third stage leads to a blockade of the release of acetylcholine from the presynaptic endings of the cholinergic neurons. The end result is a prolonged chemodenervation.

    Clinically, there is marked relaxation of the muscles in which the injection was made. In denervated muscles, the process of reinnervation occurs due to the formation of lateral processes of nerve endings 12 weeks after injection, which leads to the restoration of muscle contractions.However, the shoots are effective partially and subsequently regress, while the primary neuromuscular transmission is activated.

    Pharmacokinetics:

    The pharmacological effect of the preparation Botulax develops at the injection site. It is proved that presynaptic seizure and retrograde axonal transport of the drug from the injection site is insignificant.

    In therapeutic doses, Botulinum does not penetrate the blood-brain barrier.

    Antibodies to bogulinic toxin type A can be formed after repeated injections in 1-5% of cases. The production of antibodies contributes to the administration of large doses of the drug, as well as repeated administration in small doses at short intervals (less than 14 days). When forming antibodies to botulinum toxin type A, the effect of its further use can be reduced.

    Indications:

    Temporal correction of appearance of wrinkles of the upper third of the face (interbroken wrinkles) in adults.

    Contraindications:

    - Hypersensitivity in anamnesis to any component of the drug;

    - inflammatory process at the site of the proposed injection (injection);

    - acute phase of infectious diseases;

    - pronounced gravitational ptosis of facial tissues;

    - pronounced "hernia" in the upper and lower eyelids;

    - myasthenia gravis gravis or Liebert-Eaton syndrome;

    - age is 18 and over 65 years.

    Pregnancy and lactation:

    Use of the preparation Botulax is contraindicated in pregnancy and during breastfeeding.

    Dosing and Administration:

    Preparation of solution for injection and a set of solution in a syringe should be carried out on the working surface, covered with a paper towel on a polyethylene lining, which makes it possible to quickly remove the spilled product. Restoration of the Botulax preparation produces only 0.9% solution of sodium chloride for injection. The injection solution is prepared by piercing the stopper with a sterile needle and injecting the necessary amount of the solvent into the vial. If the solvent is not drawn into the vial under the action of a vacuum, the vial is destroyed. Before puncturing, the central part of the rubber plug must be treated with alcohol. To puncture the corks use a sterile needle size 23-25 G.

    Table dilution of the preparation Botulax:

    The volume of solvent per vial containing 50 U (ml)

    The volume of solvent per vial containing 100 units (ml)

    The resulting dose (0.1 ml ED)

    0,25

    0,5

    20

    0,5

    1,0

    10

    1,0

    2,0

    5

    1,25

    2,5

    4

    2,0

    4,0

    2,5

    4,0

    8,0

    1,25

    Carefully insert the solvent into the vial (see table above), with light rotational movements of the vial, mixing the powder with the solvent. Active vortexing of the vial and the formation of foam can lead to denaturation of the drug. The prepared solution is a clear, colorless or slightly yellowish liquid without foreign impurities; slight opalescence can be observed.

    The reconstituted Botulax preparation can be stored in the refrigerator at a temperature of 2-8 ° C for 24 hours. The final solution is injected with an insulin syringe with a non-removable needle. After dilution, the product should be used within 24 hours provided it is properly stored. The unused solution must be disposed of (see section "Special instructions").

    Units of action of botulinum toxin in various preparations are not interchangeable. The recommended doses, expressed in terms of the action for the Botulax preparation, differ from those of other preparations of botulinum toxin.

    Injection of the Botulax preparation should be carried out by a qualified doctor who has undergone a special training course and obtained the permission of the manufacturer.

    It is allowed to perform outpatient injections in a procedural room.

    The dose of Botulinx and the injection points are determined individually for each patient in accordance with the severity and localization of muscular hyperactivity. In some cases, electromyography (EMG) is used to more accurately establish the localizations of the pathological process.

    Solution Botulax (50 units / 1.25 or 100 units / 2.5 ml) is injected with a needle with a size of 30G.

    At 4 units, enter into 5 points for injection: the muscle wrinkling eyebrow (m. corrugator) - 2 points on each side, in the muscle of the proud (m. procerus) Is 1 point (as shown in Figure 1). The total dose is 20 units.

    Fig. 1. Illustration of the introduction of the drug. Before the injection, the thumb and index finger should be pressed firmly against the skin below the edge of the orbit to prevent the drug from spreading below this level. When injecting, the needle should be directed upward and medially. To reduce the risk of developing ptosis, it is necessary to avoid the administration of the drug near the muscle that lifts the upper eyelid, especially in patients with a well expressed muscle that lowers the upper eyelid.When the drug is injected into the muscle, the wrinkling eyebrow (m. corrugator), the injection should be carried out in the central part of the muscle, retreating no less than 1 cm above the arch of the eyebrow. Smoothing of vertical facial wrinkles occurs usually within a week after the procedure. The effect lasts up to 4 months.

    The interval between the procedures should be at least 3 months. If there is no effect from the introduction of the drug or a decrease in its severity after repeated injections, other methods of treatment should be recommended.

    If the first procedure is not effective, i.e. absence of significant clinical improvement, compared with the baseline, 1 month after drug administration, it is necessary:

    - Clinical confirmation of the effect of toxin on the injected muscle (muscle), which may include an EMG study performed by an experienced specialist in a specialized department;

    - analysis of the reasons for the ineffectiveness of the procedure, for example, inadequate selection of injection points, insufficient dose, incorrect injection technique, signs of fixed contracture, weakness of antagonist muscles, formation of neutralizing antibody toxins;

    - a reassessment of the feasibility of treatment with botulinum toxin A;

    - in the absence of any undesirable effects associated with the first administration of the drug, the following conditions must be observed in the repeated procedure: correction of the dose, taking into account the reasons for the ineffectiveness of the previous procedure; EMG-control; the interval between the procedures should be at least 3 months.

    If there is no effect from the introduction of the drug or a decrease in its severity after repeated injections, other methods of treatment should be recommended.

    Side effects:

    As a rule, unwanted reactions appear during the first days after the injection and are transient. In rare cases, the duration of unwanted reactions can be several months or more. Local muscle weakness reflects the expected pharmacological action of botulinum toxin on the muscle. However, large doses can cause muscle weakness in addition to those directly localized at the injection site.

    As with any injection procedure, local soreness, inflammation, paresthesia, hypesgesia, hypersensitivity, swelling, erythema, localized infection, bleeding and / or hematomas associated with injection may be noted at the site of administration.

    Procedure-related pain and / or anxiety can lead to vasovagal reactions, including transient hypotension and syncope.

    A rise in temperature and the appearance of an influenza-like syndrome are described.

    Undesirable reactions

    The following side effects are given according to the following grades of frequency: very often (≥1 / 10), often (≥1 / 100 - <1/10), infrequently (≥1 / 1000 - <1/100), rarely (≥1 / 10000 - <1/1000), very rarely (<1/10 000).

    Infectious and parasitic diseases:

    Infrequently: infections.

    Disorders of the psyche:

    Often: anxiety.

    Disturbances from the nervous system:

    Often: headache, paresthesia.

    Infrequently: dizziness.

    Disturbances on the part of the organ of sight:

    Often: blepharoptosis.

    Infrequent: blepharitis, pain in the eyes, visual impairment (including a decrease in its severity).

    Disorders from the gastrointestinal tract:

    Often: nausea.

    Infrequent: dry mouth.

    Disturbances from the skin and subcutaneous tissues:

    Often: ecchymosis, erythema, a feeling of tightness of the skin.

    Infrequent: puffiness (linden, eyelid, periorbital area), photosensitization, itching, dry skin.

    Disturbances from musculoskeletal and connective tissue:

    Often: local muscle weakness.

    Infrequently: muscle twitching.

    General disorders and disorders at the site of administration:

    Often: pain in the face, swelling of the injection site, pain / burning at the injection site.

    Infrequently: flu-like syndrome, asthenia, fever.

    Additional Information

    The following list includes adverse reactions and other medical adverse events reported in the postmarketing period, regardless of the indications for use, and which may not have been listed above.

    Immune system disorders:

    Anaphylactic shock, Quincke's edema, serum sickness and urticaria.

    Disorders from the metabolism and nutrition:

    Anorexia.

    Disturbances from the nervous system:

    Plexopathy of the brachial plexus, dysphonia, dysarthria, face paresis, hypoesthesia, muscle weakness, myasthenia gravis gravis, peripheral neuropathy, paresthesia, radiculopathy, convulsions, fainting and paralysis of the face.

    Disturbances on the part of the organ of sight:

    Strabism, weakened clarity and other visual impairments.

    Hearing disorders and labyrinthine disorders:

    Deafness, noise in the ears and dizziness.

    Heart Disease:

    Arrhythmia, myocardial infarction.

    Disturbances from the respiratory system, chest and mediastinal organs:

    Aspiration pneumonia (in some cases with a fatal outcome), dyspnea, bronchospasm, respiratory depression and respiratory failure.

    Disorders from the gastrointestinal tract:

    Abdominal pain, diarrhea, constipation, dry mouth, dysphagia, nausea and vomiting.

    Disturbances from the skin and subcutaneous tissues:

    Alopecia, psoriasis dermatitis, erythema multiforme, hyperhidrosis, madarosis, pruritus and rash.

    Disturbances from musculoskeletal and connective tissue:

    Muscular atrophy and myalgia.

    General disorders and disorders at the site of administration:

    Atrophy due to denervation, malaise and fever.

    Overdose:

    Symptoms of overdose appear after a while after the injection. In case of accidental administration or ingestion of Botulax, the patient should be under medical supervision for several days to identify clinical manifestations and symptoms of general weakness or paralysis of the muscles. Excessive doses can cause local or distant, generalized and deep neuromuscular paralysis.

    Patients with symptoms of poisoning with botulinum toxin A (general weakness, ptosis, diplopia, difficulty swallowing and speech disorders or paresis of respiratory muscles) should be hospitalized. A case of severe generalized muscle paralysis is described in case of drug overdose.

    Patients with paralysis of the respiratory musculature require intubation and transfer to artificial ventilation of the lungs before the patient's condition improves. In addition to other measures of general supportive treatment, tracheostomy and prolonged artificial ventilation may be required.

    Interaction:

    Theoretically, the effect of botulinum toxin can be enhanced by simultaneous use with the antibiotic group amigoglycosides or spectinomycin, as well as with other drugs that affect neuromuscular transmission (eg, muscle relaxants).

    The effect of introducing different serotypes of botulinum neurotoxin simultaneously or at intervals of several months is unknown.

    Perhaps aggravation of neuromuscular weakness with the introduction of another botulinum toxin before the disappearance of the effects of the previously introduced botulinum toxin.

    Studies on drug interactions were not conducted.Clinically significant cases of drug interaction are not described.
    Special instructions:

    The preparation Botulaks is used in specialized medical institutions. The drug is stored in a separate closed labeled box in the refrigerator.

    The unused solution of the preparation remaining after the injection, as well as the auxiliary tools and materials in contact with the preparation (syringes, needles, etc.) should be disposed of in accordance with the current rules for the destruction of biological waste.

    The recommended dosage and frequency of administration of Botulax should not be exceeded due to the potential risk of overdose, excessive muscle weakness, distant toxin spreading and the formation of neutralizing antibodies.

    In the initial course, treatment should begin with the lowest recommended dose for a specific indication for use.

    Doctors and patients should be aware that side effects may occur, despite the good tolerability of previous injections. Care must be taken with each procedure.

    Side effects associated with the spread of the toxin from the site of administration, sometimes with a fatal outcome, associated in some cases with dysphagia, pneumonia and / or severe muscle weakness, have been reported. These symptoms are consistent with the mechanism of action of botulinum toxin and occur in the period from several hours to several weeks after the injection. The risk of these side effects is greatest in patients with concomitant diseases and conditions predisposing to the development of these symptoms, including in children and adults receiving treatment for spasticity in high doses.

    Patients receiving the drug in therapeutic doses may also experience severe muscle weakness.

    Older and weaker patients should be treated with caution.

    The risk-benefit ratio for a particular patient should be assessed before starting treatment with Botulax.

    It was reported on the dysphagia that followed injections into areas other than the neck muscles.

    Botulax should be used with extreme caution and under constant monitoring in patients with subclinical or clinical signs of neuromuscular transmission, for example, with myasthenia gravis gravis or Lambert-Eaton syndrome, in patients with peripheral motor neuropathic diseases (eg, amyotrophic lateral sclerosis or motor neuropathy), as well as in patients with concomitant neurological pathology.

    These patients may have increased sensitivity to this group of drugs, even at therapeutic doses, which can lead to the development of severe muscle weakness and a high risk of clinically significant systemic effects, including severe dysphagia and breathing disorders. In such cases, botulinum toxin should be used under the supervision of a specialist and only if the benefit of the treatment exceeds the risk. Patients with dysphagia and aspiration in history should be treated with extreme caution.

    Patients and carers should be advised to seek medical help immediately if swallowing, speech or breathing problems occur.

    As with any method of treatment that gives previously immobilized patients the opportunity to return to physical activity, the patient should be warned about the importance of restoring activity gradually.

    Before Botulax injection, the anatomy of the relevant areas and any changes in anatomy as a result of the preceding operations should be clarified; avoid injections into easily damaged anatomical structures.

    Serious adverse reactions, including fatalities, were noted in patients to whom Botulax was administered on unapproved indications - injections of the drug directly into the salivary glands, oro-lingua-pharyngeal region, esophagus and stomach. Some patients had previous dysphagia or severe weakness.

    The development of serious and / or immediate hypersensitivity reactions during the use of Botulinx, such as anaphylaxis, serum sickness, urticaria, soft tissue edema or dyspnea, has been reported infrequently.

    Reactions have been reported in both monotherapy and in combination with other drugs that can cause such symptoms.

    In case of such reactions further administration of Botulax should be stopped and appropriate medical therapy, in particular epinephrine, should be started immediately.

    As with any injection, there may be complications associated with the procedure. Injections can lead to local infections, soreness, inflammation, paresthesia, kinesthesia, hypersensitivity, edema, erythema, bleeding / hematomas. Injury associated with injection and / or anxiety can lead to vasovagal reactions, for example, fainting, hypotension, etc.

    Care must be taken with weakness or atrophy of the muscles in which the drug is planned to be injected.

    Rare undesirable reactions from the cardiovascular system, including arrhythmias and myocardial infarction, in some cases with a fatal outcome, are described. Some of these patients initially had risk factors, including diseases of the cardiovascular system.

    There were first appeared or repeated epileptic seizures, as a rule, in patients predisposed to these conditions. The exact relationship between these phenomena and the introduction of toxin is not established. Seizures were noted mainly among patients with cerebral palsy.

    The formation of neutralizing antibodies to botulinum toxin can reduce the effectiveness of the preparation Botulax, due to inactivation of the biological activity of the toxin.According to clinical studies, the administration of Botulinx with greater frequency and in high doses can lead to an increase in the occurrence of antibodies. Potential antibody formation can be minimized by administering the lowest effective doses with the maximum clinically acceptable intervals between injections.

    Clinical fluctuations in the repeated use of Botulinx (as for all botulinum toxins) may result from differences in the technique of dilution of the drug, the intervals between injections and injected muscles, as well as small fluctuations in the activity values ​​of the preparation, determined by the biological method.

    Wrinkles of the upper third of the face (brow wrinkles)

    Rare blinking associated with the administration of botulinum toxin to the circular muscle of the eye can lead to corneal damage, persistent epithelial defects and corneal erosions, especially in patients with pathology of the VII pair of cranial nerves.

    Botulax should be used with caution in the following cases:

    - with a pronounced asymmetry of the face,

    - with ptosis, dermatochalasis, deep scars,

    - in patients with dense skin or in the absence of significant smoothing of vertical mimic inter-brow wrinkles during mechanical stretching of the skin.

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

    The preparation Botulaks is able to lead to asthenia, muscle weakness, dizziness and visual disturbances. If such symptoms develop, there may be a danger in driving or working with moving machinery.

    Form release / dosage:Liophilizate for the preparation of a solution for intramuscular administration, 50 units and 100 units.
    Packaging:

    For 50 units or 100 units of the drug in a bottle of borosilicate glass type 1 (Hebrew Pharm.) With a capacity of 5 ml, hermetically sealed with a rubber stopper and an aluminum cap with the control of the first opening.

    1 bottle with instructions for use in a pack of cardboard.

    Storage conditions:

    At a temperature of 2 to 8 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:For hospitals
    Registration number:LP-003978
    Date of registration:23.11.2016
    Expiration Date:23.11.2021
    The owner of the registration certificate:Hugel Inc.Hugel Inc. The Republic of Korea
    Manufacturer: & nbsp
    HUGEL Inc. The Republic of Korea
    Representation: & nbspALLIANCE, LTD.ALLIANCE, LTD.Russia
    Information update date: & nbsp20.02.2017
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