Dysport^® (Lyophilisate) Instructions for Use

ATC Code

M03AX01 (Botulinum toxin)

Active Substance

Botulinum toxin A – haemagglutinin complex

Clinical-Pharmacological Group

Muscle relaxant. Acetylcholine release inhibitor

Pharmacotherapeutic Group

Peripheral-acting muscle relaxant

Pharmacological Action

Peripheral-acting muscle relaxant. The active principle is Clostridium botulinum type A toxin, which blocks the release of acetylcholine at the neuromuscular junction, leading to the relief of muscle spasm in the area of injection.

Recovery of nerve impulse transmission occurs gradually, as new nerve endings form and contacts with the postsynaptic motor end plate are restored.

Pharmacokinetics

No data are available on the pharmacokinetics of Dysport^®.

Indications

• Blepharospasm, hemifacial spasm, spasmodic torticollis, post-stroke spasticity of the arm, hyperkinetic facial lines (facial wrinkles) in adults;
• Dynamic foot deformity due to spasticity in cerebral palsy in children aged 2 years and older;
• Axillary hyperhidrosis.

ICD codes

Dosage Regimen

Lyophilisate

Bilateral and unilateral blepharospasm, hemifacial spasm

The contents of a 300 U vial are reconstituted with 1.5 ml of 0.9% sodium chloride injection solution, and the contents of a 500 U vial are reconstituted with 2.5 ml of 0.9% sodium chloride injection solution. 1 ml of either solution contains 200 U of Dysport^®.

For adults and elderly patients for treatment of bilateral blepharospasm, the recommended initial dose is 120 U per eye. The drug is administered subcutaneously in a volume of 0.1 ml (20 U) medially, and in a volume of 0.2 ml (40 U) laterally into the junction between the preseptal and orbital parts of the upper and lower portions of the orbicularis oculi muscle of the affected eye. For injections into the upper eyelid, the needle should be directed away from the center to avoid affecting the levator palpebrae superioris muscle. A diagram showing the injection sites is provided below.

The clinical effect can be expected within 2-4 days, with the maximum therapeutic effect developing within 2 weeks.

Injections should be repeated every 12 weeks or as indicated to prevent recurrence of symptoms. With each subsequent administration, the dose of the drug should be reduced to 80 U per eye. For example, 0.1 ml (20 U) medially and 0.1 ml (20 U) laterally above and below the eye. Subsequently, the dose of the drug can be reduced to 60 U per eye by excluding the medial injection into the lower eyelid. Subsequent doses are determined by the physician in accordance with the effect obtained.

For unilateral blepharospasm, injections should be limited to the area of the affected eye. Similar treatment is carried out for hemifacial spasm.

Spasmodic torticollis

The contents of a 300 U vial are reconstituted with 0.6 ml of 0.9% sodium chloride injection solution, and the contents of a 500 U vial are reconstituted with 1 ml of 0.9% sodium chloride injection solution. 1 ml of either solution contains 500 U of Dysport^®.

The doses recommended for treatment of torticollis are used in adults of all ages with normal body weight and satisfactory development of the neck muscles. A reduction in the drug dose is possible in cases of significant underweight or in elderly individuals with reduced muscle mass.

For the treatment of spasmodic torticollis, the initial total single dose is 500 U. This dose is distributed between the 2 or 3 most active neck muscles.

For rotational torticollis, the drug is administered at a dose of 500 U as follows: 350 U into the splenius capitis muscle, ipsilateral to the direction of head rotation, and 150 U into the sternocleidomastoid muscle, contralateral to the rotation.

For laterocollis (head tilt towards the shoulder), the drug dose of 500 U is distributed as follows: 350 U is administered ipsilaterally into the splenius capitis muscle and 150 U is administered ipsilaterally into the sternocleidomastoid muscle. In cases accompanied by shoulder elevation due to the trapezius muscle or the levator scapulae muscle, treatment may be required according to visible muscle hypertrophy or based on electromyography data.

When administration into 3 muscles is required, the 500 U dose is distributed as follows: 300 U is injected into the splenius capitis muscle, 100 U into the sternocleidomastoid muscle, and 100 U into the third muscle (trapezius or levator scapulae muscle).

For anterocollis (forward head tilt), 150 U is injected into each sternocleidomastoid muscle.

For retrocollis (backward head tilt), the 500 U dose is distributed as follows: 250 U is injected into each splenius capitis muscle. In case of insufficient clinical effect after injection, the drug can be injected into the trapezius muscles bilaterally (at a dose of up to 250 U per muscle) after 6 weeks. Bilateral injections into the splenius capitis muscles may increase the risk of neck muscle weakness.

Upon subsequent prescription of the drug, doses may be adapted according to the clinical effect and any adverse effects that have occurred. Recommended total doses are 250-1000 U. The use of the drug in higher doses may be accompanied by an increase in the frequency of adverse effects, in particular dysphagia.

Clinical improvement in spasmodic torticollis is noted within 1 week after injection. Injections should be repeated every 8-12 weeks or as needed.

For the treatment of other forms of torticollis, the use of electromyography (EMG) is of great importance for identifying and injecting the most active muscles. EMG should be used for diagnosing all complex forms of torticollis or for re-examining patients who show no positive dynamics after drug administration, for injections into deep muscles, and in patients with excess body weight and difficult-to-palpate neck muscles.

Post-stroke spasticity of the arm in adults

Determination of indications for Dysport^® administration in the treatment of post-stroke arm spasticity is made by a neurologist 3 months after the stroke.

0.6 ml of 0.9% sodium chloride solution is added to a vial containing 300 U of the drug, and 1 ml of 0.9% sodium chloride solution is added to a vial containing 500 U of the drug. In both cases, a solution containing 500 U of Dysport^® per 1 ml is obtained.

The maximum total single dose is 1000 U, which is distributed among the following 5 muscles: flexor digitorum profundus, flexor digitorum superficialis, flexor carpi ulnaris, flexor carpi radialis, and biceps brachii.

The injection site should be guided by standard EMG points, and the exact injection site is determined by palpation. Injections are made into one point in all muscles except the biceps brachii. In the biceps brachii muscle, the injection is made at 2 points. The recommended dose distribution among muscles is given in the table.

The initial total dose of the drug may be reduced to 500 U to prevent excessive weakness of the injected muscles in cases where the target muscles are small in volume, when injection into the biceps brachii muscle is not performed, or when the injection is given into several points of one muscle.

Clinical improvement occurs within 2 weeks after injection. Injections can be repeated approximately every 16 weeks or as needed to maintain the effect, but not more frequently than every 12 weeks.

Hyperkinetic facial lines (facial wrinkles)

The main area of application of Dysport^® for cosmetic correction is the upper half of the face. The lower half of the face and neck are corrected by botulinum toxin injection much less frequently.

The contents of a 300 U vial are reconstituted with 1.5 ml of 0.9% sodium chloride injection solution, and the contents of a 500 U vial are reconstituted with 2.5 ml of 0.9% sodium chloride injection solution. With this dilution, 1 ml of either solution contains 200 U of Dysport^®.

The total recommended dose for a single administration into all four areas (glabellar region, forehead, outer canthus, and nasal bridge) should not exceed 200 U of Dysport^®.

For correction of vertical lines in the glabellar region, injections of the drug are made into the corrugator supercilii muscle, 8-10 U at 2-4 points, and the procerus muscle, 5-10 U at 2 points. The total dose ranges from 42 to 100 U.

Elimination of hyperkinetic lines in the forehead area is performed by injecting the drug into the area of maximum tension of the frontalis muscle. The number of injection points can be arbitrary. All of them should be located 2 cm above the eyebrow line, in a straight line or V-shaped. The optimal total dose of Dysport^® in this area is 30-40 U (maximum – 90 U), at 5-15 U per point, with a total of 4-6 points.

Correction of lines in the outer canthus area (“crow’s feet”) is performed by subcutaneous injection into points located 1 cm lateral to the outer canthus, at 5-15 U of Dysport^® per injection point. The number of points is from 2 to 4 per eye. The maximum recommended total dose for both sides is 120 U.

The frequency of repeat injections depends on the timing of restoration of facial muscle activity. The duration of the effect is 3-4 months.

If an adequate dose of the drug was administered during the first injection, then during the second and subsequent injections the total dose of Dysport^® may be reduced by 15-20 U for the corresponding areas. In this case, the interval between drug injections can be increased to 6-9 months. If the initial dose of the drug was insufficient, it should be increased upon repeat injections.

For correction of wrinkles in the nasal bridge area, injections are made into the middle of the belly of the nasalis muscles. The dose is distributed as 5-10 U at 1-2 points into each muscle.

The muscle relaxant effect of Dysport^® on the facial muscles clinically manifests on day 2-3 after administration and reaches its maximum on day 14-15.

The recommended doses of Dysport^® used in aesthetic medicine do not cause systemic side effects.

Dynamic foot deformity due to spasticity in cerebral palsy in children aged 2 years and older

The contents of a 300 U vial are dissolved in 0.6 ml of 0.9% sodium chloride injection solution, and the contents of a 500 U vial are dissolved in 1 ml of 0.9% sodium chloride injection solution, obtaining in both cases a solution containing 500 U per 1 ml.

The drug is administered intramuscularly into the gastrocnemius muscles. The initial recommended dose is 20 U/kg of body weight and is divided equally between the gastrocnemius muscles. If one gastrocnemius muscle is affected, the drug is administered at a dose of 10 U/kg. The optimal dose is determined individually; subsequent treatment should be planned after assessing the results of the initial dose application. To avoid the development of adverse effects, the maximum dose of 1000 U should not be exceeded. The drug is primarily injected into the gastrocnemius muscle, but injection into the soleus muscle and tibialis posterior muscle is possible. Electromyography can be used to identify the most active muscles.

In cases where the patient’s target muscles are small in volume, the initial dose of the drug should be reduced to prevent the development of excessive weakness. Clinical improvement occurs within 2 weeks after drug administration. Injections are repeated as needed at intervals of no less than 12 weeks, with the administered dose varying from 10 to 30 U per 1 kg of body weight depending on the effect of the previous injection.

Treatment of axillary hyperhidrosis

The contents of a 300 U vial are reconstituted with 1.5 ml of 0.9% sodium chloride injection solution, and the contents of a 500 U vial are reconstituted with 2.5 ml of 0.9% sodium chloride injection solution, obtaining in both cases a solution containing 200 U per 1 ml.

The recommended initial dose is 100 U per axillary area. If the desired effect is not achieved, a subsequent increase in dose to 200 U is possible.

The injection area is determined by the Minor’s test. The test is performed before treatment and, if necessary, during follow-up, at room temperature (22-24°C (71.6-75.2°F)) after a 15-minute rest period for the patient. To perform the test, the following are needed: 5% alcoholic iodine solution; potato starch; marker; antiseptic; brush; gauze pads.

The patient is in a supine position, with hands behind the head. The sweating area is treated with a 5% alcoholic iodine solution and after 1 minute, a thin layer of potato starch is applied to this area with a pad or brush. The test results are evaluated after 5 minutes. If sweating is present, the treated surface is visually observed to turn blue. The intensity of the color (from pale blue to blue-black) correlates with the activity of sweating. After the test, the area of hyperhidrosis is marked with a marker, then the starch is washed off with alcohol or another antiseptic.

Intradermal injections are performed at ten points in each axillary area, with 10 U of the drug in a volume of 0.05 ml injected into each point, totaling 100 U per area. The maximum therapeutic effect develops within 2 weeks. In most cases, the recommended initial dose suppresses sweating for up to 48 weeks. The frequency of repeat injections is determined individually upon restoration of the initial level of sweating, but not more frequently than every 12 weeks. If there is any evidence of a cumulative effect with repeated injections, the timing of repeat injections for each patient is determined individually.

Rules for preparation of the injection solution

The protective plastic cap for first opening control is removed from the vial.

When reconstituting the drug, it is forbidden to open the vial by removing the stopper. Immediately before reconstitution of the vial contents, the central part of the stopper must be treated with alcohol. The lyophilisate is reconstituted by injecting the specified volume of 0.9% sodium chloride injection solution into the vial by piercing the stopper with a sterile 23 or 25 gauge needle. The resulting solution is a colorless, clear liquid. Since the drug does not contain a preservative, it is recommended to use it immediately after reconstitution. The reconstituted drug can be stored for no more than 8 hours at a temperature of 2°C (35.6°F) to 8°C (46.4°F).

Rules for instrument processing and waste disposal

Immediately after the injection, the remaining solution in the vial or syringe should be inactivated with a diluted sodium hypochlorite solution containing 1% active chlorine. All auxiliary materials that have been in contact with the drug should be disposed of in accordance with standard hospital practice.

Spilled drug should be removed with an absorbent pad soaked in a 1% sodium hypochlorite solution.

Adverse Reactions

During various clinical studies of Dysport^® involving approximately 7800 patients, adverse reactions occurred with the following frequency: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (<1/1000), very rare (≤1/10,000).

General adverse effects

Nervous system disorders rare – neuralgic amyotrophy.

Dermatological reactions rare – skin rash.

Local reactions: common – pain and hematoma at the injection site; uncommon – irritation, burning sensation at the injection site, lasting 1-2 minutes.

General disorders common – general weakness, fatigue, flu-like syndrome.

Arm spasticity in adults after stroke

Adverse reactions were recorded in 14 clinical studies involving 141 patients.

Gastrointestinal disorders common – dysphagia (was recorded when doses exceeding 2700 U were used, administered into one point or distributed between several injection points).

Musculoskeletal and connective tissue disorders common – muscle weakness in the arm.

Other common – accidental injury/fall.

Dynamic foot deformity due to spasticity in children with cerebral palsy

Adverse reactions were recorded in 14 clinical studies involving approximately 900 patients.

Gastrointestinal disorders common – diarrhea.

Musculoskeletal and connective tissue disorders common – muscle weakness in the leg.

Renal and urinary disorders common – urinary incontinence.

Other common – accidental injury due to falling and abnormal gait, which are a consequence of excessive muscle weakness and/or spread of the toxin’s effect to other muscles close to the injection site, involved or participating in a specific motor act and in maintaining the patient’s body balance in a standing position and when walking.

Spasmodic Torticollis

Adverse reactions were registered in 21 clinical studies involving about 4100 patients.

Nervous system disorders: frequent – dysphonia; infrequent – headache.

Eye disorders: infrequent – diplopia, accommodation disorder.

Respiratory system disorders: rare – respiratory disorders.

Gastrointestinal system disorders: very frequent – dysphagia; infrequent – dry mouth.

Dysphagia has a dose-dependent effect and occurs most frequently when the drug is injected into the sternocleidomastoid muscle. A diet excluding coarse food may be required until symptoms disappear.

Blepharospasm and Hemifacial Spasm

Adverse reactions were registered in 13 clinical studies involving about 1400 patients.

Nervous system disorders: frequent – facial muscle weakness; infrequent – facial paresis.

Eye disorders: very frequent – ptosis; frequent – diplopia, dry eyes, lacrimation; rare – ophthalmoplegia.

Dermatological reactions: frequent – eyelid edema; rare – entropion.

Adverse effects may occur if the physician fails to follow the injection rules (dilution, accurate calculation of the administered dose, correct selection of injection points, needle direction and injection depth) and the associated excessive diffusion of the drug and temporary paralysis of the muscle group near the injection site.

Axillary Hyperhidrosis

Adverse reactions were registered in 4 clinical studies involving about 217 patients.

Dermatological reactions: frequent – compensatory sweating.

Hyperkinetic Facial Lines (Facial Wrinkles)

The following adverse reactions were registered (usually of mild to moderate intensity).

Eye disorders: frequent – eyelid and conjunctival edema; infrequent – dry conjunctiva (dry keratoconjunctivitis).

Musculoskeletal system disorders: frequent – weakness of muscles adjacent to the injection site, which also often leads to eyelid ptosis, asthenopia (visual weakness) or, infrequently, to facial muscle paresis and visual disturbances.

Nervous system disorders: very frequent – headache (also frequently observed in the placebo group).

Dermatological reactions: infrequent – rash, skin itching; rare – urticaria.

Local reactions: very frequent – pain, hematoma, skin itching, paresthesia, erythema, rash at the injection site (which were also frequently noted in the placebo group).

Post-Registration Experience

Most side effects are moderate and transient.

Rare: digestive disorders, skin allergic reactions, dizziness, headaches.

Very rare (1/10,000): severe muscle weakness, dysphagia, aspiration pneumonia, which may be fatal.

Contraindications

• Acute diseases (the drug is administered after recovery);
• Pregnancy;
• Lactation period (breastfeeding);
• Hypersensitivity to the drug components.

Use in Pregnancy and Lactation

Dysport^® is contraindicated for use during pregnancy and lactation (breastfeeding).

Studies on the effect of Dysport^® on reproductive capacity and teratogenicity have not been conducted. The safety of Dysport^® use during pregnancy and breastfeeding has not been confirmed.

Geriatric Use

A dose reduction of the drug may be necessary in elderly patients with reduced muscle mass.

Special Precautions

Treatment with Dysport^® should be carried out by specialists with experience in diagnosing and treating these diseases and who have undergone training in conducting treatment with this drug.

Particular caution should be exercised when re-administering the drug to patients who have experienced allergic reactions to a previous injection.

Side effects resulting from the action of the toxin on muscles distant from the injection site have been registered. Patients receiving Dysport^® in therapeutic doses may experience general muscle weakness. The risk of such side effects can be reduced by following the dosing recommendations and using the drug in the minimum effective doses.

The drug should be prescribed with caution and under strict medical supervision to patients with subclinical or clinical manifestations of neuromuscular transmission disorders (e.g., bulbospinal palsy). Such patients may have increased sensitivity to botulinum toxin drugs, which can cause severe muscle weakness in them.

Dysport^® should be administered with caution to patients with impaired swallowing and respiratory functions, as these impairments may be exacerbated due to the widespread action of the toxin on the corresponding muscles.

In patients suffering from chronic respiratory diseases, aspiration may rarely develop.

Isolated cases of fatal outcome caused by dysphagia (swallowing disorder), pneumopathy or in patients with significant asthenia have been registered during therapy with botulinum toxins type A and B.

Patients and their caregivers should be warned about the need to urgently consult a doctor in cases of swallowing, speech, and breathing disorders.

Formation of anti-botulinum antibodies was noted in a small number of patients who underwent therapy with Dysport^®. Clinically, this was manifested by a decrease in the therapeutic effect, which required a constant increase in drug doses.

In patients with prolonged blood clotting time and inflammation at the intended injection site, Dysport^® should be used only in cases of extreme necessity.

The units of activity of Dysport^® are specific and cannot be compared with those of other drugs containing botulinum toxin.

Effect on ability to drive vehicles and operate machinery

Data on the effect of the drug on the ability to drive vehicles and operate machinery are not available.

Overdose

Symptoms: generalized muscle weakness.

Treatment: supportive therapy is indicated, artificial ventilation in case of respiratory muscle paralysis. In case of overdose, administration of antitoxin (anti-botulinum serum) is advisable within the first 3 hours. As a rule, overdose treatment is aimed at general supportive therapy with constant monitoring of the patient.

Drug Interactions

Caution is required when used concomitantly with drugs affecting neuromuscular transmission, such as aminoglycoside antibiotics.

Storage Conditions

The drug should be stored out of the reach of children, at a temperature from 2°C (35.6°F) to 8°C (46.4°F). Transport at a temperature from -22 to 8°C (46.4°F).

Shelf Life

The shelf life is 2 years. Do not use after the expiration date printed on the packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.