Релатокс®

General characteristics. Structure:

Active ingredient: 50 PIECES or 100 PIECES of a complex of botulinum toxin of type A and hemagglutinin.

Excipients: gelatin, maltose.

RELATOKS - MIBP, has myorelaxation effect.

Pharmacological properties:

Pharmacodynamics. The molecule of botulinum toxin of type A consists from connected by the disulfide bridge heavy (with a molecular weight of 100000 дальтон) and easy (with a molecular weight of 50000 дальтон) chains. The heavy chain has high affinity of linkng with the specific receptors located on a surface of neurons targets. The light chain has the Zn2+-dependent protease activity specific in relation to cytoplasmatic sites of the sinaptosomalnosvyazanny protein having molecular weight 25000 дальтон (SNAP-25) and participating in processes of an exocytosis. The first stage of effect of botulinum toxin of type A - specific linkng of a molecule with a presynaptic membrane. The second stage - penetration of the connected toxin into nerve cytosol by means of endocytosis. Intracellularly light chain works as Zn2+-dependent protease of cytosol, selectively splitting SNAP-25 that at the third stage leads to blockade of release of acetylcholine from presynaptic bombways of cholinergic neurons. A final effect of this process is the resistant hemodenervation.
At intramuscular introduction 2 effects develop: direct inhibition of extrafusal muscle fibers by means of inhibition of alpha motor-neurons at the level of a neuromuscular synapse and inhibition of activity of muscle spindles by means of braking of a gamma and motor-neural cholinergic synapse on intrafusal fiber. Reduction of gamma activity leads to relaxation of intrafusal fibers of a muscle spindle and reduces activity of Ia-afferent nerve fibrils. It leads to decrease of the activity of muscle receptors of stretching, and also to efferent activity alpha and gamma motor-neurons. Clinically it is shown by the expressed relaxation of the injected muscles and considerable reduction of pain in them. Along with process deuyervatsii in these muscles process of reinnervation by emergence of side shoots of nerve terminations proceeds that leads to recovery of muscular contractions in 4-6 months after an injection.

Pharmacokinetics. The pharmacological effect develops in the place of an injection. Presynaptic capture and retrogadny axonal transport from an injection site is insignificant.
Duration of clinical effect makes 4-6 months. Recovery of neuromuscular activity happens due to development of new aksonny shoots which form new functional active neuromuscular synapses that brings in a result to recovery of muscular contractions.
At introduction in therapeutic doses of Relatoks does not get through a blood-brain barrier and does not cause essential system effects. It is removed by kidneys in the form of non-toxic metabolites.
Antibodies to a complex of botulinum toxin of type A with hemagglutinin are formed at 1-5% of patients after repeated injections. Antibody formation is promoted administration of drug in high doses and repeated injections small doses through short periods. In case of antibody formation to botulinum toxin of type A the effect of the subsequent reaction can be reduced.

Indications to use:

Treatment of a nictitating spasm, correction of hyperkinetic folds of the person (mimic wrinkles) at adults.

Route of administration and doses:

Before drug cultivation the central part of a stopper of a bottle is processed alcohol. Drug is dissolved, entering into a bottle 1-8 ml of 0,9% solution of sodium of chloride for injections by a stopper puncture a sterile needle 23 or 25 mm long. It is forbidden to open a bottle and to delete a stopper.

Solution of drug represents transparent colourless liquid. The prepared injection solution is entered the insulin syringe with a fixed needle with a diameter of 0,27-0,29 mm. Position of the patient at administration of drug in face muscles – sitting on a chair, the nape is recorded.

Units of effect of botulinum toxin in various drugs are not interchanged. The recommended doses expressed in terms of action for the drug RELATOKS® differ from those at other drugs of botulotoxin.

Doses, schemes and ways of administration of drug at correction of mimic wrinkles. Smoothing of mezhbrovny wrinkles. In the course of formation of mezhbrovny wrinkles participate m. corrugator supercilii (the muscle wrinkling an eyebrow) and m. procerus (a muscle of arrogant men).

For definition of the place of injections for the purpose of elimination of mezhbrovny wrinkles of the patient ask to frown, at this moment m. corrugator supercilii (the muscle wrinkling an eyebrow) is well palpated, at the same time the point of the most expressed muscular activity has to be on 0,5 cm up from upper medial edge of an eyebrow.

Similarly make a marking on other party. The needle is entered into thickness of an abdomen, the direction of a needle – or at an angle 45º in front back, medially, or at an angle 90º. Depth of introduction of a needle – 7-10 mm.

If the needle rests against a periosteum, it should be extended on 1 mm and after that to administer the drug. The point of administration of drug in m. procerus (a muscle of arrogant men) is located in the center of the line connecting medial edges of eyebrows.

The provision of a needle – in front back, depth of introduction of a needle – 2-3 mm. In each noted point administer the drug RELATOKS® from 2,5 to 7,5 PIECES depending on expressiveness of wrinkles, age and a floor.

Total quantity of the drug administered to this area should not exceed 25 PIECES.

Smoothing of horizontal wrinkles in a forehead. m. epicranius participates in formation of horizontal wrinkles in a forehead (a muscle nadcherepny).

For smoothing of frontal wrinkles of the patient ask to raise eyebrows and on a maximum of amplitude note points with the most expressed mimic activity.

For the purpose of an eyebrow ptosis exception, the distance between a point of an injection and the upper edge of an eyebrow has to make not less than 2 cm.

5-10 points are used and enter into everyone from 1,25 PIECES to 2,5 PIECES of the drug RELATOKS®. At slightly expressed wrinkles about 2,0-2,5 PIECES are entered into the middle of frontal area of the right and left side.

At desire of the patient to keep the movement of tips of eyebrows, points of an injection it is possible to arrange V-shapedly. If the patient has very high forehead and folds are formed close under the line of hair, it is possible to enter in addition on 1,25-2,5 PIECES into 2-3 points parallel to the line of growth of hair.

Total quantity of drug on this area should not exceed 20 PIECES.

Smoothing of wrinkles in periorbital area. The wrinkles dispersing radially around eyes, so-called "goose pads" result from activity of a circular muscle of an eye.

For the choice of a dose it is necessary to ask the patient to burst out laughing and at this time to outline approximate borders of area of skin with the maximum quantity of folds.

It is necessary to make several injections for reduction of "goose pads" (from 2 to 4 from each party) to the area of a projection m. orbicularis oculi (an eye muscle circular) at distance of not less than 1 cm from an outside corner of an eye, and also to the area of a lateral part of a lower eyelid in places of the maximum muscular activity.

Calculation of a dose is made proceeding from the area of this surface at rest: 2,0-2,5 PIECES of drug are entered into each point, diffusion from one point has the radius of 0,5-1,0 cm, therefore, the distance between points of introduction has to average 1,0-2,0 cm.

The most admissible quantity of units entered into the periorbital area no more than 25 PIECES on one party.

Not to break a face proportion, it is necessary to watch symmetry of an arrangement of points of introduction carefully. The drug in "goose pads" is not administered very low as possibly disturbance of symmetry of corners of a mouth and a nasolabial fold owing to diffusion of drug to the m. zygomaticus major area (a muscle malar big).

Smoothing of wrinkles in the field of a ridge of the nose. In the presence of the expressed wrinkles in the field of a ridge of the nose the drug is administered directly in m. nasalis (a muscle nasal) from each party on 2,5 PIECES of drug.

Smoothing of wrinkles in the lower part of the person.

• Nose wings. The drug is administered directly in a krylny part of m. nasalis (a muscle nasal) on 2,5 PIECES from each party.
• Upper lip. Injections are made along a red border of an upper lip vnutrikozhno directly in wrinkles, receding from edge on 2 mm, on 1,25 PIECES in each point, quantity of points from 4 to 6.
• Mouth corners. The drug is administered subcutaneously in number of 2,5 PIECES directly in m. depressor anguli oris (the muscle lowering a mouth corner).
• Chin. The drug is administered subcutaneously in number of 2,5 PIECES directly in m. mentalis (a muscle mental).

Doses, schemes and way of administration of drug at treatment of a nictitating spasm At treatment of a nictitating spasm drug is entered superficially intramusculary by the syringe with a needle in caliber 28-30 into the following points: two points on an upper eyelid, one point on a lateral half of a lower eyelid and one point at a lateral corner of an eye.

It is necessary to enter 2,5-5,0 PIECES into each point. An average initial dose of 15-25 PIECES on one party. The most admissible quantity of units entered into the periorbital area no more than 25 PIECES on one party.

The expressed clinical effect of administration of drug is shown in the range from 2 up to 14 days after an injection, depending on specific features of an organism and to last for 4-6 months.

At inefficiency of the first procedure at any above the described treatment, i.e. lack of considerable clinical improvement, in comparison with an initial state, in 1 month after administration of drug, it is necessary:

• clinical confirmation of effect of toxin on the injected muscle (muscles) which can include the elektromigrafichesky (EMG) research which is carried out by the experienced specialist in specialized department;
• the analysis of the reasons of inefficiency of the procedure, for example, the inadequate choice of points for an injection, an insufficient dose, the wrong equipment of an injection, signs of the fixed contracture, weakness of antagonistic muscles, formation toxin of neutralized antibodies;
• repeated assessment of expediency of treatment by botulinum toxin of type A;
• in the absence of any undesirable effects connected with the first administration of drug at the repeated procedure the following conditions have to be met: dose adjustment taking into account the analysis of the reasons of inefficiency of the previous procedure;
• EMG-control; the interval between procedures has to make not less than 3 months.

In the absence of effect of administration of drug or decrease in its expressiveness after repeated injections, it is necessary to recommend other methods of treatment.

Features of use:

With care. It is necessary to apply with extreme care and under constant control patients with subclinical or clinical signs of disturbance of neuromuscular transmission, for example at a myasthenia or miastenopodobny syndromes (including Lambert-Eaton's syndrome), also at patients with pathological changes have corneas, ecchymomas (in the field of administration of drug).

Patients with neuromuscular diseases can make risk group of emergence of clinically expressed system effects, including a heavy dysphagy and disturbance of breath, at introduction of usual doses РЕЛАТОКС®.

Treatment of such patients has to be carried out with care. At high degree of a myopia, closed-angle glaucoma administration of drug is determined by results of the conclusion of the ophthalmologist.

The rare blinking connected with administration of botulinum toxin in a circular muscle of an eye can lead to emergence of pathological changes of a cornea and demands further observation from the specialist.

At the allergological anamnesis, especially hypersensitivity to the drugs containing proteins should consider risk of emergence of allergic reaction at assessment of possible advantage of treatment.

Side effects:

Local reactions: pain in the place of an injection, irritation and hypostasis, consolidation, an erythema, tightness of skin, a hyperemia in an injection site (the diffuse hyperemia is seldom or never possible), microhematomas, ecchymomas, a dot keratitis.

At unqualified implementation of the procedure injuries a needle of the vital structures (nerves, vessels) are possible.

The reactions connected with distribution of drug on the muscular groups located near the place of an injection: omission of mezhbrovny area, lateral sites of eyebrows, a ptosis, accommodation disturbance, dryness in eyes, photophobia and the increased slezootdeleniye, difficulty of a smykaniye a century, a lagophthalmia, paresis of mimic muscles, paralysis of mimic muscles, asymmetry of corners of a mouth, disturbance of an articulation, numbness of lips.

System reactions: general weakness, headache, dizziness, nausea, drowsiness. Perhaps short-term fervescence to subfebrile figures (to 37,5 °C).

Interaction with other medicines:

Effect of drug amplifies at simultaneous use of antibiotics of group of the aminoglycosides, erythromycin, tetracycline, polymyxins, means reducing neuromuscular transmission (including not depolarizing muscle relaxants).

Contraindications:

• age up to 18 years;
• inflammatory process in the place of an estimated injection;
• acute phase of infectious diseases;
• the expressed gravitational ptosis of facial tissues;
• the expressed hernias in upper and lower eyelids;
• the period less than 3 months after the undergone surgery on a face;
• pregnancy;
• lactation (breastfeeding);
• hypersensitivity to drug components.

Overdose:

Patients with symptoms of poisoning with botulinum toxin A (the general weakness, a ptosis, a diplopia, difficulty of swallowing and an alalia, paresis of respiratory muscles) have to be hospitalized.
At paralysis of respiratory muscles carrying out an intubation and transfer into artificial ventilation of the lungs before improvement of a condition of the patient is necessary.

Storage conditions:

To store and transport at a temperature from 2 to 8 °C in the separate closed marked pack. To store in the place, unavailable to children. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

Lyophilisate for preparation of solution for intramuscular introduction on 50 or 100 PIECES in bottles. In a pack on 1 bottle in a container or bank polymeric with the application instruction.