Xeomin

Leaflet accompanying the packaging: Information for the user

XEOMIN, 50 units, powder for solution for injection

XEOMIN, 100 units, powder for solution for injection

XEOMIN, 200 units, powder for solution for injection

The active substance is botulinum toxin type A (150 kD), free from complexing proteins.

Please read carefully the contents of this leaflet before receiving the medicine, as it contains important information for the patient.

• Please keep this leaflet, so you can read it again if you need to.
• In case of any doubts, please consult your doctor or pharmacist.
• If the patient experiences any side effects, including any not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

• 1. What is XEOMIN and what is it used for
• 2. Important information before using XEOMIN
• 3. How to use XEOMIN
• 4. Possible side effects
• 5. How to store XEOMIN
• 6. Contents of the packaging and other information

1. What is XEOMIN and what is it used for

XEOMIN is a medicine that contains the active substance botulinum toxin type A, which, depending on the site of administration, relaxes muscles or reduces saliva production.
XEOMIN is used to treat the following conditions in adults:

• eyelid spasms (blepharospasm) and facial spasms (hemifacial spasm),
• cervical dystonia (spasmodic torticollis),
• increased muscle tension/uncontrolled stiffness of the arms, hands, and/or fingers (upper limb spasticity),
• chronic drooling (sialorrhea) due to neurological disorders.

XEOMIN is used to treat chronic drooling (sialorrhea) due to neurological or neurodevelopmental disorders in children and adolescents from 2 to 17 years old, with a body weight of ≥ 12 kg:

• chronic drooling (sialorrhea) due to neurological or neurodevelopmental disorders.

2. Important information before using XEOMIN

When not to use XEOMIN

• if the patient is allergic to botulinum toxin type A or any of the other ingredients of this medicine (listed in section 6),
• if the patient has a generalized muscle disorder (e.g., myasthenia gravis, Lambert-Eaton syndrome),
• if the patient has an infection or inflammation at the planned injection site.

Warnings and precautions

Side effects may be the result of injecting botulinum toxin type A into the wrong place, resulting in temporary paralysis of nearby muscle groups. Very rarely, side effects have been reported that occur in connection with the spread of the toxin to distant sites from the injection site, causing symptoms consistent with the action of botulinum toxin type A (e.g., excessive muscle weakness, swallowing disorders, and/or accidental choking on food or liquids). Patients receiving the recommended doses may experience excessive muscle weakness.
If the dose is too high or the medicine is given too frequently, the risk of antibody formation may increase. Antibody formation can result in treatment failure with botulinum toxin type A, regardless of the reason for administration.
Before starting treatment with XEOMIN, the patient should discuss the following with their doctor or pharmacist:

• if the patient has a bleeding disorder,
• if the patient is taking anticoagulant substances (e.g., coumarin, heparin, acetylsalicylic acid, clopidogrel),
• if the patient has significant weakness or muscle mass loss in the muscle to be injected,
• if the patient has amyotrophic lateral sclerosis (ALS), which can lead to generalized muscle atrophy,
• if the patient has any disease that disrupts the interaction between nerves and skeletal muscles (neuromuscular disorder),
• if the patient has had swallowing difficulties,
• if the patient has had seizures,
• if the patient has had problems with botulinum toxin type A injections in the past,
• if the patient is scheduled for surgery.

The patient should contact their doctor or seek medical attention if they notice the following symptoms:

• difficulty breathing, swallowing, or speaking,
• hives, swelling, including swelling of the face or throat, wheezing, feeling of weakness, and shortness of breath (possible severe allergic reaction symptoms).

Repeated injections of XEOMIN

In cases of repeated injections of XEOMIN, the efficacy of the medicine may increase or decrease. Possible causes include:

• different procedures for preparing the solution for injection by the doctor,
• different intervals between treatments,
• injections into a different muscle,
• marginal change in the efficacy of the active substance of XEOMIN,
• lack of response to the treatment. Blepharospasm (eyelid spasms) andhemifacial spasm (facial spasms)The patient should consult their doctor before using XEOMIN if:
• they have had eye surgery. The doctor will take additional precautions,
• they are at risk of developing a disease called narrow-angle glaucoma. This disease can cause increased intraocular pressure, which can lead to optic nerve damage. The doctor should be aware if the patient is at risk.

During treatment, minor bleeding into the soft tissues of the eyelid may occur. The doctor may reduce the risk of this by gently pressing the injection site immediately after administration.
After injecting XEOMIN into the eye muscle, the frequency of blinking may decrease, leading to prolonged exposure of the transparent front part of the eye (cornea).
This exposure can lead to damage to its surface and inflammation (corneal ulcer).
Cervical dystonia (spasmodic torticollis)
After injection, the patient may experience swallowing difficulties, ranging from mild to severe. This can lead to breathing problems and a higher risk of choking on foreign substances or liquids. Foreign substances in the lungs can cause inflammation or infection (pneumonia). The doctor will provide special treatment if necessary (e.g., artificial nutrition).
Swallowing difficulties can last up to two or three weeks after injection, and in one case, they were reported to last up to five months.
If the patient has not been active for a long time, their activity should start gradually after injecting XEOMIN.
Increased muscle tension/uncontrolled stiffness of the arms, hands, or fingers (upper limb spasticity)
XEOMIN may be used to treat increased muscle tension/uncontrolled stiffness that occurs in various parts of the upper limb, such as the arm or hand.
XEOMIN is effective in combination with standard treatment methods.
XEOMIN should be used with these other methods.
It is unlikely that this medicine will improve the range of motion in joints if the surrounding muscles have lost their ability to stretch.
If the patient has not been active for a long time, their activity should start gradually after injecting XEOMIN.
Chronic drooling (sialorrhea)
Some medicines (e.g., clozapine, aripiprazole, pyridostigmine) may cause excessive saliva production. It is recommended to consider replacing, reducing, or even stopping the treatment with the medicine that causes drooling before using XEOMIN to treat drooling.
The efficacy and safety of using XEOMIN in patients with drooling caused by medicines have not been studied.
In case of dry mouth due to XEOMIN, the doctor will consider reducing the dose.
Due to the reduction in saliva production after using XEOMIN, oral health problems may occur, such as tooth decay or worsening of existing problems.
Before starting treatment with XEOMIN for chronic drooling, the patient should consult their dentist. The dentist may decide to use preventive measures against tooth decay if necessary.

Children and adolescents

XEOMIN should not be used in children under 2 years old, in children with a body weight of less than 12 kg, or in children and adolescents for conditions other than chronic drooling, as the use of XEOMIN in these patient groups has not been studied. Therefore, its use is not recommended in these patients.

XEOMIN and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
The effect of XEOMIN may be increased:

• by medicines used to treat certain infectious diseases (e.g., spectinomycin or aminoglycoside antibiotics [e.g., neomycin, kanamycin, tobramycin]),
• by other medicines that relax muscles (e.g., muscle relaxants from the tubocurarine group). These types of medicines are used, among other things, in general anesthesia. Before surgery, the patient should inform the anesthesiologist that they have taken XEOMIN.
• in the case of chronic drooling: by other medicines that reduce saliva production (e.g., anticholinergic medicines, such as atropine, glycopyrronium, or scopolamine) or as a result of radiation therapy to the head and neck, including the salivary glands. The patient should inform their doctor if they are or will be undergoing radiation therapy.

In such cases, the use of XEOMIN requires special caution.
The effect of XEOMIN may be reduced by:

• certain antimalarial and anti-rheumatic medicines (known as aminochinolines).

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before using this medicine.
XEOMIN should not be used during pregnancy, unless the doctor decides that it is absolutely necessary and that the expected benefit of using it outweighs the potential risk to the fetus.
XEOMIN is not recommended for use in breastfeeding women.

Driving and using machines

The patient should not drive vehicles or perform other potentially hazardous activities if they experience drooping eyelids, weakness (asthenia), muscle weakness, dizziness, or vision disturbances. In case of doubts, the patient should consult their doctor.

3. How to use XEOMIN

XEOMIN can only be administered by doctors with the appropriate specialized knowledge in the use of botulinum toxin type A.
The optimal dose, frequency of administration, and number of injection sites will be determined by the doctor individually for the patient. The effect of the initial treatment with XEOMIN should be evaluated, which may lead to adjusting the dose until the desired effect of the medicine is achieved. The intervals between treatments will be determined by the doctor based on the individual needs of the patient.
If the patient feels that the effect of XEOMIN is too strong or too weak, they should contact their doctor. If no effect is visible, alternative treatment should be considered.
Blepharospasm (eyelid spasms)and hemifacial spasm (facial spasms)
The recommended initial dose is up to 25 units per eye, and the recommended total dose per treatment session is up to 50 units per eye. The onset of action of the medicine is usually observed within four days after injection. The effect of the medicine lasts for approximately 3-5 months after each treatment, but may last significantly longer or shorter. The interval between treatment sessions should not be less than 12 weeks.
Using XEOMIN more frequently than every three months does not provide additional benefits.
If the patient has hemifacial spasm, the doctor will follow the recommendations for treating blepharospasm limited to one side of the face. Treatment of hemifacial spasm will concern the upper part of the face, as injecting XEOMIN into the lower part of the face may lead to an increased risk of side effects, such as significant local muscle weakness.
Cervical dystonia (spasmodic torticollis)
The recommended dose per injection site is up to 50 units, and the recommended maximum dose per initial treatment session is up to 200 units. The doctor may use doses of up to 300 units in subsequent treatment sessions, depending on the response to treatment. The onset of action of the medicine is usually observed within seven days after injection. The effect of the medicine lasts for approximately 3-4 months after each treatment, but may last significantly longer or shorter. Treatment can be repeated no earlier than 10 weeks.
Increased muscle tension/uncontrolled stiffness of the arms, hands, or fingers (upper limb spasticity)
The recommended dose is up to 500 units per treatment session. No more than 250 units should be administered to the arm muscles. Patients reported that the onset of action was felt after four days of administration. Reduction in muscle tension was felt within four weeks. The effect of treatment generally lasted 12 weeks, but may last significantly longer or shorter. The interval between treatment sessions should be at least 12 weeks.
Chronic drooling (sialorrhea, adults)
The recommended dose is up to 100 units per treatment session. The recommended dose should not be exceeded. The interval between treatment sessions should be at least 16 weeks.
Chronic drooling (sialorrhea, children/adolescents)
The recommended dose per treatment session depends on body weight. The maximum dose of 75 units should not be exceeded. The interval between treatment sessions should be at least 16 weeks.
Method of administration
XEOMIN in the form of a reconstituted solution is used for intramuscular injections (intramuscular administration) or for injection into the gland (salivary gland) (see information intended for healthcare professionals at the end of this leaflet). In adults, the appropriate salivary glands can be located using anatomical landmarks or ultrasound examination; however, for safety reasons, the ultrasound method is preferred. In children and adolescents, the ultrasound method should be used.
Before injection, children and adolescents may be given a local anesthetic (e.g., topical anesthetic cream), a sedative, or a combination of a sedative and an anesthetic.

Using a higher dose of XEOMIN than recommended

Symptoms of overdose
Symptoms of overdose do not occur immediately after injection and may include general weakness, drooping eyelids, double vision, breathing difficulties, speech disorders, and paralysis of the respiratory muscles or swallowing difficulties, which can lead to pneumonia.
Procedure in case of overdose
In case of symptoms of overdose, the patient or someone from their environment should immediately call for emergency assistance; hospitalization may be required. Medical care and respiratory support may be necessary for several days.
In case of any further doubts related to the use of this medicine, the patient should consult their doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, XEOMIN can cause side effects, although not everybody gets them.
Generally, side effects occur within the first week after treatment and are temporary. Side effects may be related to the medicine, the injection procedure, or both. Side effects may be limited to the area around the injection site (e.g., local muscle weakness, local pain, inflammation, tingling sensation [paresthesia], reduced sensation [hypoesthesia], increased sensitivity to touch, swelling [edema], soft tissue swelling [edema], redness of the skin [erythema], itching, local infection, hematoma, bleeding, and/or bruising).
Injection of the medicine may cause pain. Pain or fear of the needle stick may lead to fainting, nausea, ringing in the ears (tinnitus), or decreased blood pressure.
Side effects, such as excessive muscle weakness or swallowing difficulties, may be caused by a decrease in muscle tension at a distance from the XEOMIN injection site.
Swallowing difficulties can cause aspiration of foreign substances into the respiratory system, resulting in pneumonia, which can be life-threatening.
XEOMIN may cause an allergic reaction. Rarely, severe and/or sudden allergic reactions (anaphylactic shock) or allergic reactions to the serum present in the medicine (serum sickness) have been reported, causing, for example, breathing difficulties (dyspnea), hives (urticaria), or soft tissue swelling (edema). Some of these reactions have been observed after the use of conventional botulinum toxin type A complex. They occurred when the toxin was administered independently or in combination with other medicines that cause similar reactions. An allergic reaction may cause the following symptoms:

• breathing, swallowing, or speech difficulties due to swelling of the face, lips, mouth, or throat,
• swelling of the hands, feet, or ankles.

In case of any of the above symptoms, the patient should immediately inform their doctor or seek help from their loved ones and go to the emergency room of the nearest hospital.

During the use of XEOMIN, the following side effects have been observed.
Blepharospasm (eyelid spasms)
Very common (may occur in more than 1 in 10 patients):
drooping eyelids
Common (may occur in up to 1 in 10 patients):
dry eye syndrome, blurred vision, vision disturbances, dry mouth, pain at the injection site
Uncommon (may occur in up to 1 in 100 patients):
headache, facial muscle weakness (facial nerve palsy), double vision, increased tearing, swallowing difficulties (dysphagia), fatigue, muscle weakness, rash
Hemifacial spasm (facial spasms)
During the treatment of hemifacial spasm, the same side effects can be expected as in the case of blepharospasm.
Cervical dystonia (spasmodic torticollis)
Very common (may occur in more than 1 in 10 patients):
swallowing difficulties (dysphagia)
Common (may occur in up to 1 in 10 patients):
neck pain, muscle weakness, muscle pain, stiffness and muscle spasms, headache, dizziness, pain at the injection site, weakness (asthenia), dry mouth, nausea, increased sweating, upper respiratory tract infections, weakness (pre-syncope)
Uncommon (may occur in up to 1 in 100 patients):
speech disorders (dysphonia), shortness of breath (dyspnea), rash
Treatment of spasmodic torticollis may cause swallowing difficulties of varying severity.
This can lead to the entry of foreign substances into the lungs, which may require medical intervention.
Swallowing difficulties can last for two to three weeks after injection, but one case of persistence for five months has been reported. The occurrence of swallowing difficulties seems to be dose-dependent.
Increased muscle tension/uncontrolled stiffness of the arms, hands, or fingers (upper limb spasticity)
Common (may occur in up to 1 in 10 patients):
dry mouth
Uncommon (may occur in up to 1 in 100 patients):
headache, reduced sensation (hypoesthesia), muscle weakness, limb pain, general weakness (asthenia), muscle pain, swallowing difficulties (dysphagia), nausea
Frequency not known (frequency cannot be estimated from the available data):
pain at the injection site
Chronic drooling (sialorrhea, adults)
Common (may occur in up to 1 in 10 patients):
dry mouth, swallowing difficulties (dysphagia), tingling sensation (paresthesia)
Uncommon (may occur in up to 1 in 100 patients):
thickened saliva, speech disorders, taste disturbances
Severe and persistent dry mouth (lasting more than 110 days) has been reported, which can lead to further complications, such as gum inflammation, swallowing difficulties, and tooth decay.
Chronic drooling (sialorrhea, children/adolescents)
Uncommon (may occur in up to 1 in 100 patients):
swallowing difficulties (dysphagia)
Frequency not known (frequency cannot be estimated from the available data):
dry mouth, thickened saliva, mouth pain, tooth decay

Post-marketing experience

After the marketing of XEOMIN, the following side effects have been observed with an unknown frequency, regardless of the treated area: flu-like symptoms, muscle atrophy after injection, and hypersensitivity reactions, such as swelling, soft tissue swelling (edema, including in areas distant from the injection site), redness, itching, rash (local and generalized), and shortness of breath.

Reporting side effects

If side effects occur, including any not listed in this leaflet, the patient should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C

• 02 - 222 Warszawa Tel.: + 48 22 49 21 301 Faks: + 48 22 49 21 309 Website: https://smz.ezdrowie.gov.pl

Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store XEOMIN

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label of the vial after "EXP". The expiry date refers to the last day of that month.
The abbreviation "Lot" on the packaging indicates the batch number.
Unopened vial: Do not store above 25°C.
Reconstituted solution: Chemical and physical stability of the solution has been demonstrated for 24 hours at a temperature of 2°C to 8°C.
From a microbiological point of view, the medicine should be used immediately. If not used immediately, the responsibility for the storage conditions and duration before reuse lies with the user, and this duration should not exceed 24 hours at a temperature of 2°C to 8°C, unless reconstitution was performed under controlled aseptic conditions.
The doctor should not use XEOMIN if the solution is cloudy or contains undissolved residue.
To learn about the instructions for disposing of the medicine, please look for information in the section intended for healthcare professionals at the end of this leaflet.

6. Contents of the packaging and other information

What XEOMIN contains

• The active substance of XEOMIN is botulinum toxin type A (150 kD), free from complexing proteins. XEOMIN, 50 units, powder for solution for injectionOne vial contains 50 units of botulinum toxin type A (150 kD), free from complexing proteins*. XEOMIN, 100 units, powder for solution for injectionOne vial contains 100 units of botulinum toxin type A (150 kD), free from complexing proteins*. XEOMIN, 200 units, powder for solution for injectionOne vial contains 200 units of botulinum toxin type A (150 kD), free from complexing proteins*. * Botulinum toxin type A, purified from cultures of Clostridium botulinum bacteria(Hall strain).
• Other ingredients of the medicine are: human albumin, sucrose.

What XEOMIN looks like and contents of the packaging

XEOMIN is a powder for solution for injection. The powder is white.
After reconstitution, the solution is clear and colorless.
XEOMIN, 50 units, powder for solution for injection:
Pack sizes: 1, 2, 3, or 6 vials.
XEOMIN, 100 units, powder for solution for injection:
Pack sizes: 1, 2, 3, 4, or 6 vials.
XEOMIN, 200 units, powder for solution for injection:
Pack sizes: 1, 2, 3, 4, or 6 vials.
Not all pack sizes may be marketed.

Marketing authorization holder

Merz Pharmaceuticals GmbH
Eckenheimer Landstrasse 100
60318 Frankfurt/Main
Germany
Tel: +49-69/1503-1
Fax: +49-69/1503-200

Manufacturer

Merz Pharma GmbH & Co. KGaA
Eckenheimer Landstrasse 100
60318 Frankfurt/Main
Germany
Tel: +49-69/1503-1
Fax: +49-69/1503-200

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

XEOMIN: Austria, Bulgaria, Cyprus, Croatia, Czech Republic, Denmark, Estonia, Germany, Greece, Finland, France, Hungary, Ireland, Iceland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden
XEOMEEN: Belgium

Date of last revision of the leaflet: 22.04.2024

Information intended for healthcare professionals only: Instructions for preparing the solution for injection:

XEOMIN is reconstituted before administration using 9 mg/ml (0.9%) sodium chloride solution for injection.
XEOMIN can only be used for the treatment of one patient per treatment session.
Good practice is to prepare the solution and prepare the syringe over a paper towel covered with foil in case of medicine spillage. The syringe should be filled with the appropriate amount of sodium chloride solution (see table of dilutions). To prepare the solution, it is recommended to use a short, cut 20-27 G needle. The needle, at a right angle, should puncture the rubber stopper, after which the solvent will slowly be drawn into the vial by vacuum. The vial should be discarded if the solvent is not drawn into the vial by vacuum. The syringe should be disconnected from the vial and the XEOMIN mixed with the solvent by gently rotating the vial and tapping it/rotating it - no vigorous movements should be performed. If necessary, the needle used to prepare the solution should remain in the vial, and the appropriate amount of solution should be drawn up using a new, sterile syringe suitable for injecting the medicine.
After reconstitution, XEOMIN is a clear, colorless solution.
XEOMIN should not be used if the reconstituted solution (prepared as described above) is cloudy or contains undissolved residue.
Efforts should be made to use the correct volume of solvent required to prepare the desired dose to avoid accidental overdose. If different types of XEOMIN vials are used during one injection procedure, caution should be exercised to use the correct amount of solvent needed to achieve the specific number of units per 0.1 ml. The amount of solvent is different for XEOMIN 50 units, XEOMIN 100 units, and XEOMIN 200 units. Each syringe should also be properly labeled.
Possible concentrations for XEOMIN 50, 100, and 200 units are shown in the following table:

Disposal instructions
Solution for injection stored for more than 24 hours and unused solution for injection should be discarded.
Procedures for the safe disposal of vials, syringes, and used materials
Unused vials, reconstituted solution, and/or syringes should be sterilized in an autoclave. Alternatively, any remaining XEOMIN can be inactivated by adding one of the following solutions: 70% ethanol, 50% isopropanol, 0.1% SDS (anionic detergent), diluted sodium hydroxide (0.1 N NaOH), or diluted sodium hypochlorite solution (at least 0.1% NaOCl).
After inactivation, the used vials, syringes, and materials should not be emptied but should be placed in appropriate containers and disposed of in accordance with local regulations.
Recommendations for procedures in case of unforeseen incidents during the administration of botulinum toxin type A

• Any spillage of the medicine should be immediately removed: in the case of powder using an absorbent material soaked in one of the above solutions, or in the case of the reconstituted medicine using a dry absorbent material.
• The contaminated surface should be wiped with an absorbent material soaked in one of the above solutions and then dried.
• If the vial is broken, the above instructions should be followed. The broken glass should be carefully collected, avoiding cuts, and the remaining medicine should be wiped away.
• If the medicine comes into contact with the skin, the area of contact should be rinsed with a large amount of water.
• In case of eye contact, the eyes should be thoroughly rinsed with a large amount of water or eye wash solution.
• If the medicine gets into a wound, cut, or crack in the skin, the area should be thoroughly rinsed with a large amount of water. Appropriate medical measures should be taken depending on the injected dose. The instructions for preparing and disposing of the medicine should be strictly followed.