Kseomin

General characteristics. Structure:

Active ingredient: 100 PIECES of botulinum toxin of type A.

Excipients: sucrose, seralbumin of the person.

Pharmacological properties:

Pharmacodynamics. Kseomin affects selectively peripheral cholinergic nerve terminations, inhibiting allocation of acetylcholine. Implementation in cholinergic nerve terminations happens in three stages: linkng of a molecule with external components of a membrane, internalization of toxin by endocytosis and a translocation of the endopeptidazny domain of toxin from an endosome in cytosol. In cytosol the endopeptidazny domain of a molecule of toxin selectively splits SNAP-25, an important protein component of the mechanism controlling the membrane movement of ekzo-vesicles, stopping, thus, allocation of acetylcholine. A final effect is relaxation of the injected muscle.

Effect of drug begins within four-seven days after an injection. The effect of each procedure lasts, as a rule, three-four months though it can last significantly longer or less.

Indications to use:

Nictitating spasm, idiopathic cervical dystonia (spastic wryneck) of preferential rotational form, spasticity of a hand after a stroke, hyperkinetic folds (mimic wrinkles) of the person.

Route of administration and doses:

Only the doctors possessing special preparation, and also experience of the treatment of botulinum toxin and with the equipment for an electromyography can administer the drug. The doctor establishes a dosage and the number of places of injections in a muscle for each patient individually.

Drug dissolution. At cultivation of drug it is forbidden to open a bottle, deleting a stopper.

From a bottle delete a protective plastic cover. Just before cultivation of contents of a bottle the central part of a stopper is processed alcohol.

Solution for an injection is prepared, puncturing a stopper with a sterile needle and entering into a bottle solution of sodium of chloride of isotonic 0,9% for injections. Carefully turn a bottle, mixing lyophilisate with solvent before full dissolution. Dissolution time no more than 10 sec. After dissolution transparent colourless solution has to be formed.

Drug is not used if after dissolution the received solution is opaque or contains visible flakes and particles.

Drug is dissolved in necessary volume, according to the table.

Solvent volume on a bottle, containing 100 PIECES (ml)	Ml ED/0,1
0,5	20
1,0	10
2,0	5
2,5	4
4,0	2,5
8,0	1,25

The dosages recommended for Kseomin cannot be used for recalculation when using other drugs containing botulinum toxin. As drug does not support antimicrobic agents, it is recommended to use it right after dissolution. In case of need the dissolved drug can be stored in an original bottle to 24 h in the refrigerator at a temperature from 2 to 8 °C provided that dissolution was carried out in aseptic conditions.

Nictitating spasm. After dissolution Kseomin enter a sterile needle 27-30 G. The recommended initial dose of 1,25-2,5 units (0,05-0,1 ml) to each place of an injection; drug is injected in medial and lateral parts of a circular muscle of an eye (m. orbicularis oculi) of an upper eyelid, and in a lateral part of a circular muscle of an eye of a lower eyelid.

If sight is broken because of spasms in a forehead, in lateral sites of a circular muscle of an eye and in an upper part of the face, to these areas additional injections can be made. Effect of drug begins, on average, within four days after an injection. The effect of each procedure lasts, as a rule, three-four months though it can last significantly longer or less.

If the effect of an initial dose was insufficient (duration less than two months), at repeated procedures the dose of drug can be increased twice. The initial dose should not exceed 25 units on one eye. It is not necessary to enter the dose exceeding 5,0 units into each place. At treatment of a nictitating spasm the total dosage in twelve weeks of treatment should not exceed 100 units.

Spastic wryneck. At treatment of a spastic wryneck the dosage has to be selected to each patient individually, depending on position of a neck and the head, localization of pain, volume of muscles (a hypertrophy, an atrophy), the body weight of the patient.

In practice of treatment the maximum dose of drug in the course of one procedure usually should not exceed 200 units, however the dosage up to 300 units is possible. To the same place it is not necessary to administer the dose of the drug exceeding 50 units.

Therapy of a spastic wryneck includes injections in грудино - a clavicular and mastoidal muscle, in the muscle raising a shovel in scalenes, in a belt muscle, and/or in a trapezoidal muscle (muscles).

It is not necessary to do injections in both грудино - clavicular and mastoidal muscles as it increases risk of adverse effects of drug (in particular, dysphagies) which take place at bilateral injections of drug in this muscle, or at the doses exceeding 100 units.

For injections in superficial muscles use needles numbers 25, 27 and 30 G, and for deep muscles – a needle number 22 G.

At a spastic wryneck the electromyography can be necessary for definition of the involved muscles. Carrying out injections to several places allows drug to cover evenly sites of the muscles subject to dystonia (especially at an injection in large muscles). The optimum number of places of injections depends on muscle size. Effect of drug begins, on average, within seven days after an injection. The effect of each procedure lasts about three-four months, however can last significantly longer or less. The interval between procedures has to make at least ten weeks.

Spasticity of a hand after a stroke. The drug is administered using suitable sterile needles (for example, for superficial muscles use needles 26 G with a diameter of 0,45 mm with a length of 37 mm, for the deep-lying muscles 22 G with a length of 75 mm with a diameter of 0,7 mm use needles).

The electromyography can be necessary for definition of the involved muscles. Carrying out injections to several places allows drug to cover evenly sites of the muscles subject to dystonia (especially at an injection in large muscles).

At spasticity treatment the dosage has to be selected to each patient individually, depending on the size, quantity and localization of the involved muscles, stastichnost degree of manifestation, and existence of local muscular weakness.

The offered dosages are presented in the table:
 

Clinical symptom Muscle	Units
The hand bent in a wrist
Beam sgibatel of a brush	50
Elbow sgibatel of a brush	40
The clenched fist
Superficial sgibatel of fingers	40
Deep sgibatel of fingers	40
The hand bent in an elbow
Humeroradial	60
Biceps	80
Humeral	50
Pronirovanny forearm
Square pronator	25
Round pronator	40
The thumb given to a palm
Long sgibatel of a thumb	20
The muscle giving a thumb	10
Short sgibatel of a big finger / the muscle opposing a thumb	10

At spasticity treatment the recommended dosage on a course of treatment makes 170 - 400 PIECES depending on localization of spazmirovanny muscles. Improvement occurs within the first 2 weeks, reaching a maximum by 4th week. The effect lasts usually 12 weeks.

Hyperkinetic folds (mimic wrinkles) of the person. Use of drug for treatment of mimic wrinkles at persons under 18 is also more senior than 65 years it is not recommended due to the lack of clinical experience.

Vertical wrinkles between eyebrows (glabellar wrinkles): the recommended injection volume – 0,1 ml (4 units) – enter into each of 5 sites: 2 injections in m. corrugator on both sides and 1 injection in m.procerus that corresponds to a total dose of 20 units. Increase in a total dose up to 30 units is in some cases possible.

Before an injection and during it it is necessary to put pressure big and index fingers below the upper edge of an eye-socket, preventing diffusion of solution to this area. During an injection the needle should be directed up and medially. For the purpose of decrease in risk of a ptosis a century, it is necessary to avoid injections near the muscle raising an upper eyelid and in the place of an attachment of a circular muscle of an eye. Injections in m. corrugator should be carried out to medial department of a muscle and to the central site of a myogaster, at least, is 1 cm higher than the upper edge of an eye-socket.

Reduction of expressiveness of vertical wrinkles between eyebrows (glabellar wrinkles) usually develops within 2-3 days, the maximum effect is observed by 30th day, and remains up to 4 months after an injection. Intervals between injections should not be less than 3 months. If the result of treatment unsatisfactory is applied by alternative methods of treatment.

Features of use:

Right after carrying out an injection the remained solution in a bottle or in the syringe should be inactivated sodium hydroxide solution (0,1 N NaOH). All auxiliary materials which were in contact with drug have to be autoclaved or inactivated by solution 0,1 N NaOH (during not less than 18 h). The spilled drug has to be wiped by the adsorbing napkin moistened in sodium hydroxide solution.

Effect of drug on ability of management of transport and uses of the machinery and equipment. Because of the nature of the diseases cured by drug, ability of the patient manage various equipment can be reduced. In addition, side effects of drug can negatively affect ability of the patient to manage the equipment; respectively, the patient should abstain from similar activity until his abilities are not recovered fully.

Side effects:

Side reactions are classified by occurrence frequency: very often (≥ 1/10), it is frequent (≥1/100 to <1/10), is not frequent (≥ 1/1,000 to ≤ 1/100), is rare (≥1/10,000 to ≤ 1/1,000), is very rare (≤ 1/10,000).

Nictitating spasm. Often: ptosis (6,1%), xerophthalmus (2,0%). Infrequently: paresthesia, conjunctivitis, dryness in a mouth, skin rash, a headache, muscular weakness.

Besides, when using the similar drug containing botulinum toxin of type A, and applied in clinical tests along with Kseomin the side effects provided below were noted. They are possible also at Kseomin's use.

Often: superficial keratitis, lagophthalmia, irritation of skin, photophobia, dacryagogue. Infrequently: keratitis, ektropiya, diplopia, dizziness, diffusion skin rashes / dermatitis, torsion of a century, focal paralyzes of facial nerves, weakness of facial muscles, fatigue, visual disturbances, sight illegibility. Seldom: local swelling of skin of a century. Very seldom: acute closed-angle glaucoma, keratohelcosis.

Spastic wryneck. Often: dysphagy (10%), muscular weakness (1,7%), dorsodynias (1,3%). Infrequently: an inflammation or the pressing feelings in the place of an injection, a headache, an adynamy, the generalized increased sweating, a tremor, a voice osiplost, colitis, vomiting, diarrhea, dryness in a mouth, an ostealgia, a mialgiya, skin rashes, an itch, a skin peeling, eye pain.
Besides, when using the similar drug containing botulinum toxin of type A, and applied in clinical tests along with Kseomin the side effects provided below were noted. They are possible also at Kseomin's use.

Very often: pain in the place of an injection. Often: dizziness, the increased arterial pressure, feeling of numbness in the place of an injection, the general weakness, grippopodobny symptoms, a febricula, dryness in a mouth, nausea, a headache, rigidity of muscles in the place of an injection, irritation in the place of an injection, rhinitis, upper respiratory tract infections. Infrequently: asthma, diplopia, heat, ptosis, disturbances of the speech.

Degree of manifestation of a dysphagy varies from weak to strong, with a possibility of aspiration; in rare instances at the same time medical care is required. The dysphagy can remain for two-three weeks from the moment of an injection, however the case lasting 3 months is recorded. The dysphagy develops дозозависимо; according to clinical trials, the dysphagy meets seldom if the total dose of drug does not exceed 200 units for one procedure.

Spasticity of a hand after a stroke. Often: headache, sensitivity disturbance, feeling of heat. Besides, when using the similar drug containing botulinum toxin of type A, and applied in clinical tests along with Kseomin the side effects provided below were noted. They are possible also at Kseomin's use. Often: a hyper tone, an ecchymoma, local pain, muscular weakness, irritation or a hemorrhage in the place of an injection. Infrequently: a depression, sleep disorders, paresthesia, an incoordination, amnesia, вертиго, orthostatic hypotonia, nausea, dermatitis, an itch, rash, an arthralgia, a bursitis, an adynamy, pain, hypersensitivity in the place of an injection, concern, peripheral hypostasis. Some side effects can be connected with a basic disease.

Hyperkinetic folds (mimic wrinkles) of the person. Usually undesirable effects are observed on the first week after use of drug and are temporary. Undesirable effects can be connected with active agent and/or with the procedure of introduction.
The expected pharmacological effect of botulinum toxin is the localized muscular weakness. The ptosis can be caused a century by the equipment of injections and is associated with pharmacological effect of drug.

As well as at any injection, in connection with it perhaps local emergence of pain, morbidity, an itch, a swelling and/or a hematoma; development of passing vazo-vagal reactions, such as a syncope, blood circulation disturbances, nausea or a sonitus connected with nervousness before an injection is also possible.

At use of drug it was reported about the following adverse reactions. Often: a skin itch, a headache, disturbances of muscular function in the place of an injection, feeling of weight. Infrequently: grippopodobny symptoms, feeling of tension in the place of an injection, bronchitis, a nasopharyngitis, feeling of "skin nodules", the century, a ptosis, sight misting, an eyebrow raising, nausea, muscular twitchings and spasms, local weakness of facial muscles swelled. In addition to it, drug of the comparison containing a usual complex of botulinum toxin of type A and applied in several clinical trials (the data collected so far allow to assume identical activity of both drugs) is known development of the following undesirable effects which can be probably observed also at Kseomin's use.

Infrequently: an infection, paresthesias, dizziness, a blepharitis, eye pain, dryness in a mouth, a photosensitivity, a xeroderma.

Cumulative side effects. The data given below are based on other drugs given about action containing botulinum toxin of type A. Data on heavy negative effects which can be connected with defeat of warmly vascular system - such as arrhythmia and a myocardial infarction including with a lethal outcome, - are extremely rare. Whether these lethal outcomes were caused by injections of botulinum toxin of type A, or the accompanying cardiovascular diseases, is definitely not established. It is reported about one case of an acute anaphylaxis after administration of the drug containing botulinum toxin of type A.

Such side effects as exudative poliformny erythema, urticaria, psoriazopodobny rashes, itch and allergic reactions, however their conditionality are noted by effect of the complex drug containing botulinum toxin of type A it is not confirmed.

Sometimes after an injection of botulinum toxin of type A changes of an electrophysiologic background in some remote muscles were noted; this side effect is not connected neither with muscular weakness, nor with other electrophysiologic anomalies.

Interaction with other medicines:

Muscle relaxants of peripheral action should be applied with care at simultaneous performing antibiotic treatment by aminoglycosides or spektinomitsina (strengthening of action of Kseomin is possible). The effect of drug can be reduced by action derivative 4 aminoquinolines.

Contraindications:

Drug is contraindicated to people with an allergy to drug components, at neuromuscular transmission disturbances (masteniye гравис, Lambert-Eaton's syndrome, with care appoint at a side amyotrophic sclerosis, at neurologic diseases as a result of a degeneration of motor neurons and other diseases with neuromuscular transmission disturbances).

The drug is not administered at the increased temperature and acute infectious or noninfectious diseases.

Drug is contraindicated at pregnancy and a lactation.

The drug is not administered to children and teenagers up to 18 years.

Overdose:

Symptoms. High doses of Kseomin can lead to development of the expressed muscular paralysis in the places remote from places of injections (in particular: general weakness, ptosis, diplopia, the complicated speech and swallowing, and also the paralysis of respiratory muscles leading to development of aspiration pneumonia).

Treatment. At overdose hospitalization with the general supporting actions is necessary. At paralysis of respiratory muscles the intubation and artificial ventilation of the lungs up to normalization of a state is necessary.

Storage conditions:

At the room temperature (it is not above 25 °C). To store in the place, unavailable to children. A period of validity - 3 years. Drug is not subject to expired use.

Issue conditions:

According to the recipe

Packaging:

On 100 PIECES in a bottle. 1 bottle in the plastic pallet in a cardboard pack together with the application instruction in Russian.