Xeomin lyophilisate d / pr. solution for intramuscular injection of 50ED, No. 1

• Blepharospasm,

• hemifacial spasm,

• paralytic strabismus,

• spastic torticollis,

• local muscle spasm in adults and children over 2 years old (including cerebral palsy and spasticity).

Doses and points for injection are determined individually for each patient in accordance with the nature, severity and localization of muscle hyperactivity. In some cases, EMG control is used to more accurately localize the injected muscles.

The average total doses for injection into the muscles of the face are 25-100 IU, in the muscles of the neck - 100-200 IU, in the muscles of the extremities - 50-300 IU. The interval between repeated injections should be at least 2 months.

The maximum total dose for 1 procedure in adults is 400 U, for 1 procedure in children over 2 years of age - 12 U / kg of body weight (no more than 300 U). The toxic dose is 38-42 U / kg of body weight.

Lyophilisate for the preparation of a white solution for intramuscular administration.

1 fl.

botulinum toxin type A

Excipients: sucrose, human serum albumin.

• Myasthenia gravis,

• myasthenic and myasthenic-like syndromes (including Lambert-Eaton syndrome),

• inflammation at the injection site,

• pregnancy,

• breastfeeding period,

• hypersensitivity to botulinum toxin type A.

pharmachologic effect

Muscle relaxant. The molecule of the active substance consists of heavy (with a molecular weight of 100,000 Daltons) and light (with a molecular weight of 50,000 Daltons) chains linked by a disulfide bridge. The heavy chain has a high affinity for binding to specific receptors located on the surface of target neurons. The light chain has a Zn2 + -dependent protease activity specific to the cytoplasmic regions of a synaptosomal-bound protein with a molecular weight of 25,000 daltons (SNAP-25) and involved in exocytosis. The first stage of action of botulinum toxin type A is the specific binding of the molecule to the presynaptic membrane, this process takes 30 minutes. The second stage is the internalization of the bound toxin into the cytosol through endocytosis.After internalization, the light chain acts as a Zn2 + -dependent cytosolic protease, selectively cleaving SNAP-25, which in the third step leads to a blockade of acetylcholine release from the presynaptic terminals of cholinergic neurons. The end effect of this process is persistent chemodenervation.

With the i / m administration of botulinum toxin type A, 2 effects develop: direct inhibition of extrafusal muscle fibers by inhibition of alpha-motor neurons at the level of the neuromuscular synapse and inhibition of muscle spindle activity by inhibition of the gamma-motor neuron cholinergic synapse on the intrafusal fiber. A decrease in gamma activity leads to relaxation of the intrafusal fibers of the muscle spindle and decreases the activity of 1a-afferents. This leads to a decrease in the activity of muscle stretch receptors, as well as in the efferent activity of alpha and gamma motor neurons. Clinical manifestations are pronounced muscle relaxation at the injection site and a significant decrease in pain in them. Along with the process of denervation in these muscles, the process of reinnervation occurs through the appearance of lateral processes of nerve terminals,which leads to the restoration of muscle contractions 4-6 months after the injection.

With intradermal injection in the area of ??localization of exocrine sweat glands (armpits, palms, feet), a blockade of postganglionic sympathetic nerves develops and hyperhidrosis stops at 6-8 months.

When administered locally in therapeutic doses, the active substance does not penetrate the BBB and does not cause significant systemic effects. Apparently, there is minimal presynaptic uptake and reverse axonal transport from the injection site.

Antibodies to botulinum toxin type A are formed in 1-5% of patients after repeated injections. The formation of antibodies is facilitated by the introduction in high doses (more than 250 U), booster injections (in small doses at short intervals). In the case of the formation of antibodies to botulinum toxin type A, other serological types are used (B, F).

Pharmacokinetics

The hemagglutinin complex of botulinum toxin type A concentrates for some time at the site of its intramuscular injection before entering the systemic circulation. Subsequently, the active substance is very rapidly metabolized with the formation of simpler molecular structures.

It is excreted in the form of metabolites mainly by the kidneys.

Side effect

Local reactions: 2-5% of cases - microhematomas (up to 7 days), pain at the injection site (up to 1 day).

Systemic reactions: occur when used in a high dose (more than 200 units) - slight general weakness within 1 week.

Reactions associated with the spread to muscle groups located near the injection site depend on the area of ??administration of botulinum toxin type A. In the treatment of blepharospasm, hemifacial spasm - ptosis (5-10%), lacrimation (0.5-1%); rarely - ectropion, keratitis, diplopia, entropion, ecchymosis. When injected into both sternocleidomastoid muscles, dysphagia (2-5%). As a rule, these side effects do not require additional therapy and regress within 1 month after injection.

Application during pregnancy and lactation

Contraindicated for use during pregnancy and during breastfeeding.

Application in children

Not recommended for use in children under 2 years of age.

special instructions

Botulinum toxin type A injections should be performed by a highly qualified doctor with special training and permission from the manufacturer.

Complications after injection are extremely rare and can occur with needle trauma to vital structures (nerves, blood vessels, trachea) in the event of an unskilled procedure. Complications in the form of anaphylaxis are not described, nevertheless, during the injection, it is necessary to have funds for the urgent relief of anaphylactic reactions.

Currently, the effectiveness of botulinum toxin type A has been proven in patients with myofascial syndromes, tension headaches, contractures of facial muscles, trismus, bruxism, hyperkinetic facial wrinkles, achalasia of the cardia, spasm of the sphincters of the rectum and urinary bladder, local hyperhidrosis.

Specific botulinum antitoxin is effective within 30 minutes after botulinum toxin injection.

After injection, syringes and needles should be disposed of using bio-waste disposal methods.

Not recommended for use in children under 2 years of age.

Drug interactions

The effect of botulinum toxin type A is enhanced by the simultaneous use of antibiotics of the aminoglycoside group, erythromycin, tetracycline, lincomycin, polymyxins, drugs that reduce neuromuscular transmission (including curariform muscle relaxants).