Molecule botulinum toxin type A consists of a disulfide-linked heavy (with a molecular weight 100,000 daltons) and light (with a molecular weight of 50,000 Da) chains. The heavy chain has a high affinity of binding to specific receptors on the surface of target neurons. The light chain has Zn 2 + -dependent protease activity specific to the cytoplasmic portions sinaptosomalnosvyazannogo protein having a molecular weight of 25,000 Da (SNAP-25) and processes involved in exocytosis.
The first phase of action of botulinum toxin type A – specific binding molecule to the presynaptic membrane. This process takes 30 minutes.
Second stage – penetration of the toxin into the cytosol associated nerve by endocytosis. Intracellularly light chain acts as Zn 2 + -dependent protease cytosol selectively cleave SNAP-25, which in the third phase leads to the blockade of acetylcholine release from presynaptic terminals of cholinergic neurons. The net effect of this process is resistant hemodenervatsiya.
Intramuscular administration of Botox 2 develop the effect: direct inhibition extrafusal muscle fibers by inhibiting alpha motor neurons at the neuromuscular junction and inhibition of muscle spindles by braking the gamma motor neurons in the cholinergic synapse intrafusal fiber.
Reducing gamma activity leads to the relaxation of the intrafusal fibers of the muscle spindle and reduces the activity of 1a-afferents. This leads to reduced activity of the muscle stretch receptors, and the activity to efferent alpha motor neurons and gamma. Clinically it is manifested pronounced relaxation of the injected muscles and a significant reduction in pain in them. Along with these process denervation muscle reinnervation process proceeds by the appearance of side branches of the nerve endings, which leads to the restoration of the muscle contractions after 4-6 months after the injection.
For local administration at therapeutic doses Botox does not penetrate the BBB and does not cause significant systemic effects. Apparently, there is a minimal presynaptic capture and reverse axonal transport from the site of administration.
Antibodies to botulinum toxin complex type A with hemagglutinin formed at 1-5% of patients after repeated injections of BOTOX. antibodies promote the formation of administering the drug at high doses (> 250 units) and the repeated injections of small doses at short intervals. In the case of formation of antibodies to botulinum toxin type A subsequent reaction effect can be reduced.
Data on the pharmacokinetics of the drug Botox is not available.
Botulinum toxin type A hemagglutinin complex
For adults on prescription
1 vial of lyophilisate for solution for intramuscular injection contains:
Botulinum toxin complex type A – 100 hemagglutinin units,
human plasma albumin – 500 mcg;
sodium chloride – 900 mcg
- hemifacial spasm;
- paralytic strabismus;
- cervical dystonia (spasmodic torticollis);
- the local muscle spasm;
- and smoothing of glabellar brow wrinkles.
For children over 2 years: a local muscle spasm with cerebral palsy.
- hypersensitivity to the drug Botox;
- and miastenopodobnye myasthenic syndromes (including Lambert-Eaton syndrome);
- inflammation at the injection site;
- the acute phase of infectious diseases;
- a high degree of myopia (on the conclusion of an ophthalmologist);
- allergic history (especially hypersensitivity to preparations containing proteins);
- aminoglycoside antibiotics, macrolides, tetracyclines, polymyxin, the reinforcing effect of the toxin (if not passed more than 2 weeks after a course of therapy) as well as drugs that increase the intracellular calcium concentration, benzodiazepines, anticoagulants and antiplatelet agents;
- a pronounced gravitational ptosis of facial tissue;
- expressed hernia in the upper and lower eyelids;
- for less than 3 months after undergoing surgery on his face.
Local reactions: 2-5% of cases – mikrogematomy (up to 7 days), pain at the injection site (up to 1 day).
Systemic reactions: slight weakness within 1 week (arise when using the drug in doses exceeding the maximum permissible – 250 U).
Reactions associated with the spread of the drug on the muscle groups located near the injection site: very rare – ptosis of the eyelids, drooping brow area, the lateral parts of the eyebrows, a violation of accommodation, the asymmetry of the angles of the mouth, impaired articulation, numbness of the lips.
Typically, these side effects do not require additional therapy and regress within 1 month after injection.
Complications after injection are extremely rare and can occur at a trauma needle nerves or blood vessels in case of improper execution of the procedure. Complications of anaphylaxis are not described, however during the injection must have a means for immediate relief of anaphylactic reactions.
How to accept, acceptance rate and dosage
Botox and dose for injection points are determined individually for each patient in accordance with the nature, severity and localization of muscle hyperactivity. In some cases, control of electromyographic (EMG) is used for the more precise localization of injectable muscle.
In the treatment of bilateral blepharospasm Botox solution was administered intramuscularly into the upper surface, lateral and bottom circular muscles of the eye from both sides. Additional sites for injection are pretarzalnaya part circular muscles of the eye, and eyebrow area of the frontal region. Each point should be administered 2,5-5 ED drug. The average initial dose – 15-25 units per side. The effect of the drug occurs 2-7 days after the procedure and lasts for 3-6 months. For stable clinical effect of the drug must be administered in the indicated dose every 3-6 months. In the treatment of blepharospasm total dose for 12 weeks, should not exceed 100 units.
Treatment of patients with hemifacial spasm is also done, as in unilateral blepharospasm.
In the treatment of spasmodic torticollis solution preparation administered in the most strained muscles of the neck in a total dose of 25-75 IU 2-3 points of each muscle. When the rotational torticollis preparation is administered in the sternocleidomastoid muscle contralateral rotation in the belt muscle ipsilateral rotation. In cases involving lifting arm further requires administering the drug in homolateral trapezius muscle and levator scapulae muscle. In the presence of head tilt back requires the introduction of the drug in both belt and both trapezius muscles. When the head is tilted forward the drug is injected into both sternocleidomastoid muscle. Bilateral injections may increase the risk of weak neck muscles.
At the subsequent administration of the dose can be brought to the optimum according to the prior clinical effect and there are side effects. Muscle relaxant effect after the injection occurs after 7-14 days (possibly up to 21 days) and stored 3-6 months, followed by a repetitive administration of the drug. torticollis Treatment depends on the clinical experience of the expert. In all cases, torticollis complex shapes or in case of a low required injection effect EMG holding the neck muscles for a more accurate localization of strained muscles.
In cerebral palsy spasticity and equine-varus deformity of the foot and walking on tiptoe idiopathic drug solution was injected into two points of each head gastrocnemius; with hemiplegia may be administered in the flexor forearm; with further systems cross thighs may be administered the drug in causing thigh muscle. The total dose of 1 procedure is 4-6 U / kg body weight (but not > 300 IU procedure 1), evenly distributed on all interested muscle. In severe spasticity total dose can be 10-12 U / kg. Clinical improvement was observed after 7-14 days and may persist for up to 6-12 months. Repeated injections should be done with a decrease in clinical effect by half. Orthopedic correction tensile physiotherapy help to improve the clinical effect of drug administration.
In order to eliminate glabellar wrinkles drug usually injected into m.corrugator supercilii and m.procerus, which are involved in their formation. To determine the patient’s injection site frown asked at this point is well palpated m.corrugator, at this point most pronounced muscle activity should be at 0.5cm upward from the upper edge of the medial eyebrows. Similarly produce the marks on the other side. The needle is inserted into the interior of the abdomen, the direction of the needle – or at an angle of 45 ° from front to back, medially, or at an angle of 90 °. The depth of insertion of the needle – 7-10 mm.
If the needle touches the periosteum, it is necessary to draw on the 1 mm and then enter the drug. In some patients (the majority of men and some women) m.procerus in its medial part is very wide, and forms a deep furrow long glabella, which requires the additional introduction of 2.5-5 U in points located 5-7 mm above the primary points . The depth of insertion of the needle – 3.2 mm, the direction – vertically downwards. the introduction of a point in m.procerus located in the line connecting the medial edge of the eyebrow. Each base point administered from 2.5 to 7.5 IU of the preparation depending on age and sex. The needle position – front to back, the depth of insertion of the needle – 2-3 mm. Total amount of the preparation introduced into this area usually does not exceed 25 units.
The action of the drug develops 2-7 days after the procedure and lasts 3-6 months. For stable clinical effect of the drug must be administered at the indicated doses in 3-6 months.
Maximum total dose should not exceed 250 units per procedure.
Rules for formulation and administration for injection
At a dilution of the drug may not open a bottle by removing the plug. Before dilution of the contents of the vial central portion of the rubber stopper should be treated with alcohol. To puncture using a sterile needle size 23-25 G. in volume 2-4 ml vial to reconstitute the contents using 0.9% sodium chloride solution for injection.
The solvent to be administered neat, easy rotational movement of the vial, mixing the powder with the solvent for one minute. The amount of solvent used must be capable of entering all the recommended dose (in IU) of the drug. Coarse shaking and foam formation can lead to denaturation of the drug. If there is no retraction of the solvent into the vial under vacuum, the vial is destroyed. The resulting solution is a clear, colorless or slightly yellowish liquid without extraneous inclusions, it is possible slight opalescence.
After dilution of the drug can be stored in a refrigerator at 2 to 8 ° C not more than 4 hours before use. The prepared injection solution administered insulin syringe with a fixed needle diameter of 0,27-0,29 mm. The position of the patient upon administration of the drug into the muscles of the face and neck – sitting on a chair, his head is fixed.
At a temperature of 2-8 ° C and – 5 ° C and below. Keep out of the reach of children.
Botulinum toxin type A hemagglutinin complex
The action of Botox is amplified while aminoglycoside antibiotics, erythromycin, tetracycline, lincomycin, polymyxins; means reducing neuromuscular transmission (including curariform relaxants).
Botox must carry out highly qualified doctors with special training and permission from the manufacturer. Injections can be performed on an outpatient basis in a treatment room.
Botox is released, stored and applied only in specialized medical institutions. The drug is stored in a separate closed box marked in the refrigerator.
Immediately after the injection remaining in the vial or syringe solution should inactivate sodium hypochlorite solution (containing 1% available chlorine). All support materials that were in contact with the product must be disposed of in accordance with biological waste disposal regulations. Spilled drug solution must be wiped absorbent cloth soaked in dilute sodium hypochlorite solution.
Effects on ability to drive vehicles and management mechanisms
There was no effect of the drug on the ability to engage in potentially hazardous activities that require increased attention and psychomotor speed reactions.
The free sale of Botox through pharmacy network is not received and released only in specialized medical institutions.
Pregnancy and lactation
Botox is contraindicated during pregnancy and lactation.
Symptoms: weakness, paresis of the injected muscles.
Treatment: constant monitoring of the dynamics of symptoms; appointment anticholinesterases, conduct resuscitation if necessary.
Introduction of specific antitoxin (protivobotulinicheskoy serum type A) in accordance with instructions for use effectively within 30 min after injection of botulinum toxin.