Botox

Active material: botulinum toxin type A complex – hemahhlyutynyn
When ATH: M03AX01
CCF: Miorelaksant. The inhibitor of acetylcholine release
ICD-10 codes (testimony): G24.3, G24.5, G80, H50, R25.2
At KFU: 02.10.02
Manufacturer: ALLERGAN PHARMACEUTICALS IRELAND (Ireland)

Pharmaceutical form, composition and packaging

Excipients: human plasma albumin 500 g, sodium chloride 900 g.

bottles (1) – packs cardboard.

Pharmacological action

Miorelaksant. Botulinum toxin type A molecule consists of disul'fidnym bridge-related heavy (molecular weight 100 000 Dalton) and easy (molecular weight 50 000 Dalton) chains. Heavy chain has high affinity binding to specific receptors, located on the surface of neurons-targets. Light chain has Zn²⁺-dependent active protein digesting activity, specific in relation to the cytoplasm protein sinaptosomal'nosvjazannogo sites, having a molecular weight 25 000 Dalton (SNAP-25) and involved in the processes of exocytosis. The first phase of action of botulinum toxin type A – specific binding molecules with the presynaptic membrane, This process takes 30 m. The second stage – penetration of the associated toxin into the cytosol nerve through Endocytosis. Wärmetauscher light chain acts as Zn²⁺-dependent protease cytosol, selectively splitting a SNAP-25, that at the third stage leads to blockade of acetylcholine release of presinapticakih cord cholinergic neurons. The ultimate effect of this process is the proof hemodenervacija.

When the/m introduction of BOTOX^® develop 2 effect: direct inhibition of jekstrafuzal'nyh muscle fibers through inhibition of Alpha motoneurons at the level of the neuromuscular Synapse and inhibition activity of muscle spindles via inhibition of gamma-motonejronnogo holinergicheskogo Synapse on intrafuzal'nom fiber. Decrease gamma activity leads to the relaxation of the muscle spindle fiber intrafuzal'nyh and reduces activity 1a-afferents. This leads to reduced activity of muscle stretch receptors, as well as efferent activity alpha- and gamma motoneurons. This is manifested clinically pronounced relaxing in'ecirovannyh muscles and significantly reducing pain in them. Along with the process of denervation in these muscles process reinnervacii by the emergence of side-shoots nerve endings, that leads to recovery of muscle contractions through 4-6 months after injection.

When the local introduction of therapeutic doses of BOTOX^® It permeates through GEB and causes no significant systemic effects. Apparently, There are minimum presynaptic capture and return transportation from the place of his AX-onal introduction.

Antibodies to botulinum toxin type A gemaggljutininom formed from 1-5% patients after repeated injections of BOTOX^®. Antibodies contribute to the introduction of the drug at high doses (more 250 ED) and repeated injections of low doses at shorter intervals. In case of formation of antibodies to the botulinicheskomu toxin type A the effect of subsequent reactions can be reduced.

Pharmacokinetics

Data for farmakokinetike Botox^® not provided.

Testimony

For adults

- Blepharospasm;

- Hemifacial spasm;

-paralytic strabismus;

-cervical dystonia (spasmodic torticollis);

— local muscle spasm;

-anti-aliasing inter-eyebrow and superciliary wrinkles.

For children over 2 years

— local muscle spasm when the children's cerebral palsy.

Dosage regimen

The Dose Of Botox^® and the point of injection are determined individually for each patient in accordance with the nature of the, the manifestation and localization of muscular hyperactivity. In some cases, more accurate localization of the injectable muscle EMG applies control.

At treatment of bilateral nictitating spasm solution of BOTOX^® injected superficially in/m top, lateral and bottom of circular eye muscles on both sides. Additional areas for injections are pretarzal'naja part of the circular muscle of the eye, the scope of the eyebrows and forehead region. Each point should be 2.5-5 ED drug. The average initial dose of 15-25 U on one side. The effect of the drug is on 2-7 the day after the procedure and maintained for a period of 3-6 Months. For sustainable clinical effect, you must enter the product at the specified dose every 3-6 Months. When treating nictitating spasm total dose for 12 weeks must not exceed 100 ED.

Treatment of patients with gemifacial'nym spasm There is also a, as for unilateral blefarospazme.

When treating spasmodic torticollis solution of the drug is injected into the most tense neck muscles in total dose 25-75 ED 2-3 the point of each muscle. When the drug is injected in the study of rotational grudinno-kljuchichno-soscevidnuju muscle kontralateral'no of rotation and rotational ipsilaterally muscle belt. In cases, involving lifting shoulder, Additionally requires the imposition of a drug in the gomolateral'nuju trapezoid muscle and muscle, the shoulder. In the presence of tilting head back requires a drug in both belt and two trapezoid muscle. When tilting the head forward into both product introduces grudinno-kljuchichno-a mammillary muscles. Bilateral injections may increase the risk of neck muscle weakness.

During the subsequent introduction of the dosage can be brought up to the best in accordance with the preceding clinical effect and side-effects because. Miorelaksiruty effect after injection of the drug comes through 7-14 days (It is possible to 21 day) and stored 3-6 Months, and then you have to make the re-introduction of the drug. Krivoshei treatment depends on the clinical experience of specialist. In all cases of complex forms or in case of low krivoshei effect required injections EMG neck muscles for more precise localization of strained muscles.

At children's cerebral palsy with spastichnost'ju and jekvino-varusnoj deformed feet and c idiopathic walking on tiptoe solution of the drug is injected into the 2 the point of each head gastrocnemius; in hemiplegia drug can be administered into the muscle-flexor forearms; In addition, you can enter the thighs perekreshhivanii drug in the resulting muscles of a hip. The total dose on 1 procedure, component 4-6 U / kg body weight (but not more 300 ED 1 procedure), is evenly distributed to all interested muscle. In severe spasticity total dose may be 10-12 U / kg. Clinical improvement is observed through 7-14 days and may continue to 6-12 Months. Repeated injections should be done at the same time reducing clinical effect by half. Orthopedic correction, tension, physical therapy improves the clinical effect of injection.

To eliminate inter-eyebrow wrinkles preparation, usually, introducing m. corugator and m. supercilii procerus, who are involved in their formation. To determine the location of the injection the patient asked to frown, at this point good palpated m. corrugator, at this point the most pronounced muscle activity must be on 0.5 cm up from the upper medial edges of eyebrows. Similarly produce a markup on the other side. A needle is inserted into the thick of the abdomen, the direction of the needle – either at an angle of 45° from front to back, medially, either at an angle 90°. Needle depth – 7-10 mm. If the needle stops in the periosteum, It is necessary to pull on 1 mm and then enter the drug. A number of patients (in most men and some women) m. procerus in its medial part very wide, It forms a deep and long furrow mezhbrovnuju, that requires additional introduction by 2.5-5 U point, located at 5-7 mm above the primary points. Needle depth – 2-3 mm, direction – vertically down. Point of introduction in m. procerus is situated in the Centre of the line, connecting the medial edge of the eyebrows. In each marked point injected from 2.5 to 7.5 U preparation depending on age and gender. Needle position – front to back, needle depth – 2-3 mm. The total number of drug, entered in this area, usually, less than 25 ED.

The drug develops 2-7 the day after the procedure and stored 3-6 Months. For sustainable clinical effect, you must enter the drug in these doses through 3-6 Months.

The maximum total dose should not exceed 250 U on one procedure.

Rules of preparation and introduction solution for injection

Dilution of the drug may not open a bottle, Remove the plug. Before dilution of the central part of the contents of the vial with a rubber stopper should be processed with alcohol. Use a sterile needle to puncture the size 23-25 G. The contents of the vial for dilution use 0.9% a solution of sodium chloride injection in volume 2.0-4.0 ml. The solvent should be carefully, light rotational movements of the vial with the solvent in the powder and stir for one minute. The amount of solvent used should provide the possibility of introducing all the recommended doses (in units) product. A rough shaking and foaming can lead to denaturation of the drug. If there is no retraction of the solvent in the liquid under the influence of the vacuum, bottle destroy. The resulting solution is a clear, colourless or slightly yellowish liquid without foreign inclusions, possible slight opalescence.

After breeding, medication can be stored in the refrigerator at a temperature from 2° to 8° c for no more 4 h to use. Cooked injectable insulin syringe are injected with a permanently attached needle diameter 0.27-0.29 mm. The position of the patient during the introduction of the drug in the muscles of the face and neck – sitting on a Chair, the neck is fixed.

Side effect

Local reactions: 2-5% cases – mikrogematomy (to 7 days), pain at the site of injection (to 1 d).

Systemic reactions: slight weakness over 1 of the week (arise in applying the drug in doses, exceeding the maximum permissible/more 250 U/).

Reaction, associated with the spread of the drug on muscle groups, located near an injection site: rarely – Ptosis of the eyelid, the omission of wrinkles brow area, lateral brow sites, ccomodation, asymmetry of the corners of the mouth, violation artikulyatsii, numbness of the lips.

Usually, These side effects do not require additional therapy and will regress within 1 months after injection.

Complications of injections are extremely rare and can occur when a needle injury nerves or blood vessels in case of improper execution of the procedure. Complications in the form of anaphylaxis are not described, However, when performing the injections must have means for urgent cupping anaphylactic reactions.

Contraindications

— miastenopodobnye and myasthenic syndromes (incl. Lambert-Eaton syndrome);

— inflammation at the injection site;

-acute phase of infectious diseases;

-high degree of myopia (on the conclusion of an ophthalmologist);

— weighed down by allergic history (especially increased sensitivity to drugs, containing proteins);

— taking antibiotics group aminoglikozidov, macrolides, tetracyclines, polymyxins, augmentative effect of toxin (If not more than 2 weeks after the therapy course), as well as preparations, increasing intracellular calcium concentration, benzodiazepines, anticoagulants and antiplatelet agents;

— alcohol abuse;

is pronounced gravitational PTOSIS facial tissues;

is expressed in the area of hernia upper and lower eyelids;

- A period of at least 3 months recovering from surgery on her face;

- Pregnancy;

- Lactation (breast-feeding);

- Hypersensitivity to the drug.

Pregnancy and lactation

Botox^® contraindicated during pregnancy and lactation.

Cautions

Botox Injections^® should conduct a highly skilled doctor, has special training and a permit from the manufacturer. Injections can be performed on an outpatient basis in terms of procedural Cabinet.

Botox^® is released, stored and applied only in specialized medical institutions. The drug is stored in a separate box marked closed in the refrigerator.

Immediately after the injection, the remaining vial or syringe solution should be inactivated sodium hypochlorite solution (contains 1% chlorine). All auxiliary materials, were in contact with the product, must be disposed of in accordance with the rules of the destruction of biological waste. Spilled solution of the drug should be floors are worn adsorbing cloth, dipped in diluted sodium hypochlorite solution.

Of all cases, increased reactogenicity or postinjection complications must be reported to the State Scientific Research Institute of standardization and control of medical biological preparations they. L.A.Tarasevicha (119002, Moscow, Sivcev Vražek, 41) and address of the official distributor of JSC “Family health”.

Effects on ability to drive vehicles and management mechanisms

No influence on the ability to engage in potentially hazardous activities, require increased attention and psychomotor speed reactions.

Overdose

Symptoms: possible weakness, in'ecirovannyh muscle paresis.

Treatment: constant monitoring of dynamics of symptoms; appointment antiholinesteraznah funds, If necessary, conduct resuscitation. A specific antitoxin (serum protivobotulinicheskoj type a) in accordance with the instructions for use for effectively 30 min after injection of botulinum toxin.

Drug Interactions

Effect Of Botox^® amplified while applying antibiotics group aminoglikozidov, Erythromycin, tetracycline, lincomycin, polymyxins, means, reduce the neuromuscular transmission (incl. kurarepodobnykh miorelaksantov).

Conditions of supply of pharmacies

For sale through pharmacies Botox^® is not received and released only in specialized medical institutions.

Conditions and terms

Botox^® (before breeding) It should be stored and transported at a temperature from 2° to 8° c or -5° c and below in closed, sealed and labelled containers out of reach of children. Shelf life – 2 year.