Composition, form of production and packaging
Lyophilizate for the preparation of a solution for intravenous administration 1 fl.
botulinum toxin type A 100 U
100 ED - bottles (1) - polymer containers (1) or polymer cans (1) - cardboard packs.
Lyophilizate for the preparation of a solution for intravenous administration 1 fl.
botulinum toxin type A 50 U
50 units - bottles (1) - polymer containers (1) or polymer cans (1) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
The botulinum toxin type A molecule consists of a heavy chain (with a molecular weight of 100,000 daltons) and a light chain (with a molecular weight of 50,000 daltons) connected by a disulfide bridge. The heavy chain has a high affinity binding to specific receptors located on the surface of target neurons. The light chain has a Zn 2+ -dependent protease activity specific for the cytoplasmic regions of the synaptosomal-linked protein having a molecular weight of 25,000 daltons (SNAP-25) and participating in exocytosis processes. The first stage of the action of botulinum toxin type A is the specific binding of the molecule to the presynaptic membrane.The second stage is the penetration of the bound toxin into the nerve cytosol through endocytosis. The intracellularly light chain acts as a Zn 2+ -dependent cytosol protease, selectively cleaving SNAP-25, which in the third stage results in a blockade of the release of acetylcholine from the presynaptic terminals of the cholinergic neurons. The final effect of this process is persistent chemodenervation.
With intramuscular injection, two effects develop: direct inhibition of extrafusal muscle fibers by inhibiting alpha-motoneurons at the level of the neuromuscular synapse and inhibiting the activity of muscle spindles by inhibiting the gamma motor neuron cholinergic synapse on the intrafusal fiber. Reduction of gamma activity leads to a relaxation of the spinal cord intrafusal fibers and reduces the activity of Ia-afferent nerve fibers. This leads to a decrease in the activity of muscle stretch receptors, as well as to the efferent activity of alpha and gamma motor neurons. Clinically, this is manifested by a marked relaxation of the injected muscles and a significant reduction in pain in them. Along with the process of de-activation in these muscles, the process of reinnervation proceeds by the appearance of lateral processes of the nerve endings, which leads to the restoration of muscle contractions 4-6 months after the injection.
The pharmacological effect develops at the injection site. Presynaptic capture and retrograde axonal transport from the injection site is insignificant.
The duration of the clinical effect is 4-6 months. Restoration of neuromuscular activity occurs due to the development of new axonal processes, which form new functional active neuromuscular synapses, which leads to the restoration of muscle contractions.
When administered at therapeutic doses, Relatox does not penetrate the hemato-encephalic barrier and does not cause significant systemic effects. It is excreted by the kidneys in the form of non-toxic metabolites.
Antibodies to a complex of botulinum toxin type A with hemagglutinin are formed in 1-5% of patients after repeated injections. The formation of antibodies is facilitated by the administration of the drug in high doses and repeated injections in small doses at short intervals. In the case of antibodies to botulinum toxin type A, the effect of the subsequent reaction can be reduced.
- treatment of blepharospasm;
- correction of hyperkinetic folds of the face (facial wrinkles) in adults.
Before diluting the preparation, the central part of the vial plug is treated with ethyl alcohol. The drug is dissolved by injecting into the vial 1-8 ml of 0.9% sodium chloride solution for injection by puncturing the plug with a sterile needle of 23 or 25 mm in length. Do not open the vial and remove the stopper. The drug solution is a clear, colorless liquid.
The prepared injectable solution is injected with an insulin syringe with a non-removable needle 0.27-0.29 mm in diameter. The position of the patient when injecting the drug into the muscles of the face - sitting on a chair, the back of the head is fixed.
Table 1. Concentrations of the preparation obtained by diluting Relatox 50 U
в„–в„– pp Volume of 0.9% solution of sodium chloride for injection, ml Activity of the drug (ED in 0.1 ml)
1 1 5
2 2 2.5
3 2.5 2.0
4 4 1.25
Table 2. Concentrations of the preparation obtained by dilution of RELATOX 100 U
в„–в„– pp Volume of 0.9% solution of sodium chloride for injection, ml Activity of the preparation (ED in 0.1 ml)
1 2 5
2 4 2.5
3 5 2.0
4 8 1.25
The units of action of botulinum toxin in various preparations are not interchangeable. The recommended doses, expressed in terms of action, for the preparation Relatox differ from those of other preparations of botulinum toxin.
Doses and methods of introducing the drug in correcting facial wrinkles
Smoothing of interbrow wrinkles.
In the process of forming interbrow wrinkles involved m. corrugator supercilii (muscle, wrinkling eyebrow) and m. procerus (muscle of the proud).
To determine the injection site in order to eliminate inter-brow wrinkles, the patient is asked to frown, at this moment it is well palpated m. corrugator supercilii (muscle wrinkling eyebrow), the point of the most pronounced muscular activity should be 0.5 cm up from the upper medial edge of the eyebrow. Similarly, markup on the other side is produced. The needle is inserted into the abdomen, the direction of the needle - either at an angle of 45 В° from the front back, medially, or at an angle of 90 В°. The depth of needle insertion is 7-10 mm. If the needle rests against the periosteum, it should be pulled 1 mm and then injected. The injection point in m.procerus (muscle of the proud) is located in the center of the line connecting the medial edges of the eyebrows. Needle position - from front to back, depth of needle insertion - 2-3 mm.
At each point, the preparation Relatox is administered from 2.5 to 7.5 units, depending on the severity of wrinkles, age and sex. The total amount of the drug introduced into this area should not exceed 25 units.
Smoothing of horizontal wrinkles in the forehead.
In the formation of horizontal wrinkles, m is involved in the forehead region. epicranius (supracranial muscle). To smooth out the frontal wrinkles, the patient is asked to raise his eyebrows and at the maximum of the amplitude, points with the most pronounced mimic activity are noted. To exclude ptosis of the eyebrow, the distance between the injection point and the upper edge of the eyebrow should be at least 2 cm. 5-10 points are used and in each enter from 1.25 ED to 2.5 units of the drug RELATOX. With slightly pronounced wrinkles, 2.0-2.5 units are inserted into the middle of the frontal region of the right and left sides. If the patient wishes to keep the movement of the eyebrows, the injection points can be arranged V-shaped. If the patient has a very high forehead and folds are formed close under the hairline, you can additionally enter 1,25-2,5 ED at 2-3 points in parallel to the hair growth line. The total amount of the drug per given area should not exceed 20 units.
Smoothing wrinkles in the periorbital area.
Wrinkles diverging radially around the eyes, the so-called "crow's feet", arise as a result of the activity of the circular muscle of the eye. To select a dose, the patient should be asked to laugh and at this time delineate the approximate boundaries of the skin area with the maximum number of folds.
To reduce the "crow's feet", several injections (2 to 4 on each side) must be made to the projection area m. orbicularis oculi (eye muscle circular) at a distance of not less than 1 cm from the outer corner of the eye, and also in the region of the lateral part of the lower eyelid in the places of maximum muscle activity. Calculation of the dose is made based on the area of вЂ‹вЂ‹this surface at rest: at each point, 2.0-2.5 units of the drug is injected, diffusion from one point has a radius of 0.5-1.0 cm, therefore, the distance between the points of administration should be on average 1,0-2,0 cm. The maximum permissible amount of units introduced into the periorbital region is not more than 25 units per side. In order not to violate the proportions of the face, it is necessary to carefully monitor the symmetry of the location of the insertion points. The drug in the field of "crow's feet" is not introduced very low, since it is possible to disrupt the symmetry of the corners of the mouth and nasolabial fold due to the diffusion of the drug into the region of m. zygomaticus major (muscle zygomaticus large).
Smoothing wrinkles in the area of вЂ‹вЂ‹the back of the nose.
In the presence of pronounced wrinkles in the area of вЂ‹вЂ‹the back of the nose, the drug is injected directly into m. nasalis (nasal muscle) on each side of 2.5 units of the drug.
Smoothing wrinkles in the lower part of the face.
The wings of the nose. The drug is injected directly into the m. nasalis (nasal muscle) at 2.5 units per side.
Upper lip. Injections are made along the red border of the upper lip intradermically directly into the wrinkles, receding from the edge by 2 mm, at 1.25 units per point, the number of points from 4 to 6.
The corners of the mouth. The drug is administered subcutaneously in an amount of 2.5 units directly into m. depressor anguli oris (muscle that lowers the corner of the mouth).
Chin. The drug is administered subcutaneously in an amount of 2.5 units directly into m. mentalis (the muscle of the chin).
Doses, regimens and route of administration of the drug in the treatment of blepharospasm
In the treatment of blepharospasm, the drug is injected superficially by intramuscular injection with a needle 28-30 caliber into the following points: two points in the upper eyelid, one point on the lateral half of the lower eyelid, and one point at the lateral angle of the eye. At each point should be introduced 2.5-5.0 units. The average initial dose is 15-25 units per side.
The maximum permissible amount of units entered into the periorbital region is not more than 25 units per side.
The pronounced clinical effect from the administration of the drug is manifested in the interval from 2 to 14 days after the injection, depending on the individual characteristics of the organism, and last for 4-6 months.
If the first procedure is ineffective in any of the above described treatments, i. E. absence of significant clinical improvement, compared with the baseline, 1 month after drug administration, it is necessary:
- clinical confirmation of the toxin action on the injected muscle (muscle), which may include electromigraphic (EMG) research performed by an experienced specialist in a specialized department;
- analysis of the reasons for the ineffectiveness of the procedure, for example, inadequate selection of points for infection, insufficient dose, incorrect injection technique, signs of fixed contracture, weakness of antagonist muscles, formation of neutralizing antibody toxins;
- reassessment of the feasibility of treatment with botulinum toxin type 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 x months.
In the absence of effect from the introduction of the drug or a decrease in its severity after repeated injections, other methods of treatment should be recommended.
Local reactions: pain at the injection site, irritation and swelling, compaction, erythema, tightness of the skin, hyperemia at the injection site (in rare cases, spilled hyperemia is possible), microhematomas, ecchymoses, spot keratitis.
With unqualified implementation of the procedure, traumas can be caused by the needle of vital structures (nerves, vessels).
Reactions associated with the spread of the drug to muscle groups located near the injection site: the descent of the intercostal area, the lateral sections of the eyebrows, ptosis, disruption of accommodation, dry eyes, photophobia and increased tear, the difficulty of closing the eyelids, lagophthalmus, paresis of facial muscles, paralysis of facial musculature , asymmetry of the corners of the mouth, violation of articulation, numbness of the lips.
Systemic reactions: general weakness, headache, dizziness, nausea, drowsiness. Perhaps a short-term increase in body temperature to low-grade figures (up to 37.5 В° C).
- age up to 18 years;
- inflammatory process at the site of the proposed injection;
- acute phase of infectious diseases;
- pronounced gravitational ptosis of facial tissues;
- pronounced hernia in the upper and lower eyelids;
- a period of less than 3 months after a surgical operation on the face;
- lactation (breastfeeding);
- Hypersensitivity to the components of the drug.
It should be used with extreme caution and under constant control in patients with subclinical or clinical signs of neuromuscular transmission disorders, for example, in myasthenia gravis or myasthenic-like syndromes (including Lambert-Eaton syndrome), also in patients with pathological corneal changes, ecchymoses ( in the field of drug administration). Patients with neuromuscular diseases may constitute a group at risk of developing clinically pronounced systemic effects, including severe dysphagia and respiratory failure, by administering conventional doses of Relatox. Treatment of such patients should be conducted with caution.
With a high degree of myopia, closed-angle glaucoma, the administration of the drug is determined by the results of the conclusion of the ophthalmologist. The rare blinking associated with the administration of botulinum toxin to the circular muscle of the eye can lead to the appearance of pathological changes in the cornea and requires further monitoring by a specialist.
With an allergic history, especially hypersensitivity to drugs containing proteins, the risk of an allergic reaction should be considered when assessing the possible benefits of treatment.
PREGNANCY AND LACTATION
The use of the drug is contraindicated during pregnancy and during breastfeeding.
APPLICATION FOR CHILDREN
The drug is contraindicated for children under 18 years.
The drug is released, stored and used in specialized medical institutions.
Injections of the drug solution should be carried out by a highly qualified doctor who has special training in specialized hospitals or outpatient, in a procedural room.
Instructions for processing the remnants of the drug solution. Immediately after the injection, the remaining solution of the drug in the vial and in the syringe should be inactivated with a dilute solution of sodium hypochlorite (containing 1% of active chlorine).
The shed solution of the preparation is wiped with an absorbent cloth dipped in a dilute solution of sodium hypochlorite.
Disinfection should be carried out in accordance with the established requirements. All auxiliary materials that were in contact with the solution of the preparation must be disposed of in the ways provided for the destruction of biological waste.
Information about the possible effect of the drug on the ability to drive vehicles, mechanisms
After the administration of the drug may develop muscle weakness, dizziness and visual disturbances, there may be a danger in driving or working with moving machinery.
Patients with symptoms of poisoning with botulinum toxin A (general weakness, ptosis, diplopia, difficulty swallowing and speech disorder, paresis of respiratory muscles) should be hospitalized.
When paralysis of the respiratory muscles requires intubation and transfer to artificial ventilation of the lungs to improve the patient's condition.
The effect of the drug is enhanced with the simultaneous use of antibiotics of the group of aminoglycosides, erythromycin, tetracycline, polymyxins, drugs that reduce neuromuscular transmission (including nondepolarizing muscle relaxants).
TERMS OF RELEASE FROM PHARMACY
For treatment and prevention institutions.
TERMS AND CONDITIONS OF STORAGE
Store and transport in accordance with SP 18.104.22.1688-03 at a temperature of 2 to 8 В° C in a separate closed marked pack. Keep out of the reach of children.
Shelf life - 2 years.