Xeomin 200 units powder for solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: 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

Clostridium botulinum type A neurotoxin (150 kD), free from complexing proteins

Read the entire leaflet carefully before receiving this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, including any side effects not listed in this leaflet. See section 4.

Leaflet contents

1. What XEOMIN is and what it is used for
2. What you need to know before being given XEOMIN
3. How XEOMIN is used
4. Possible side effects
5. How to store XEOMIN
6. Contents of the pack and other information

1. What XEOMIN is and what it is used for

XEOMIN is a medicine that contains the active substance botulinum toxin type A, which relaxes the muscles into which it is injected or reduces saliva flow at the corresponding administration site.

XEOMIN is indicated for the treatment of the following disorders in adults:

• eyelid spasms (blepharospasm) and spasms affecting one side of the face (hemifacial spasm)
• neck twisting (spasmodic torticollis)
• increased muscle tone/involuntary muscle stiffness in shoulders, arms and/or hands (upper limb spasticity)
• chronic drooling (sialorrhea) due to neurological disorders

XEOMIN is indicated for treatment in children and adolescents aged 2 to 17 years and weighing greater than or equal to 12 kg with:

• chronic drooling (sialorrhea) due to neurological disorders / neurological developmental disorders.

2. What you need to know before using XEOMIN

Do not use XEOMIN

?? If you are allergic to botulinum toxin type A or to any of the other components of this medicine (listed in section 6)

?? If you have a generalized disorder of muscle activity (e.g., myasthenia gravis, Lambert-Eaton syndrome)

?? If you have an infection or inflammation at the proposed injection site

Warnings and precautions

Adverse effects may occur due to incorrectly placed injections of botulinum toxin type A, which temporarily paralyze nearby muscle groups. Very rare reports of adverse effects possibly related to the spread of botulinum toxin beyond the injection site and botulism have been reported, causing symptoms consistent with the effects of botulinum toxin type A (e.g., double vision, blurred vision and/or drooping eyelids, difficulty speaking or breathing, excessive muscle weakness, difficulty swallowing, or accidental aspiration of food or liquid into the airways). Patients receiving recommended doses may experience excessive muscle weakness.

If the dose is too high or injections are too frequent, the risk of antibody formation may increase. The formation of antibodies may lead to treatment failure with botulinum toxin type A, regardless of the indication for which it is intended.

Tell your doctor or pharmacist before using XEOMIN:

?? if you have any type of bleeding disorder

?? if you are taking substances that prevent blood clotting (e.g., coumarin, heparin, acetylsalicylic acid, clopidogrel)

?? if the muscles to be injected show pronounced weakness or reduced muscle volume

?? if you have amyotrophic lateral sclerosis (ALS), which may lead to loss of muscle tissue

?? if you have any disease affecting the interaction between nerves and skeletal muscles (peripheral neuromuscular disorder)

?? if you currently have or have previously had difficulty swallowing

?? if you currently suffer or have previously suffered from seizures

?? if you have previously had problems with injections of botulinum toxin type A

?? if you are scheduled to undergo any surgical procedure

If you experience any of the following symptoms, contact your doctor and seek immediate medical attention:

• difficulty breathing, swallowing, or speaking
• hives, swelling including swelling of the face or throat, wheezing,

feeling faint and difficulty breathing (possible symptoms of severe allergic reactions)

Repeated injections with XEOMIN

If you receive repeated injections with XEOMIN, the effect may increase or decrease. Possible reasons include:

?? your physician may use a different procedure when preparing the injection solution

?? different treatment intervals

?? injections into a different muscle

?? minor variation in the efficacy of the active substance in XEOMIN

?? lack of response/failure of therapy during treatment.

Blepharospasm (eyelid spasms) and facial muscle spasms affecting one side of the face (hemifacial spasm)

Tell your doctor before using XEOMIN if:

?? you have previously undergone eye surgery. Your doctor will take appropriate precautions

?? you are at risk of developing a condition called narrow-angle glaucoma. This condition may cause increased internal eye pressure and may lead to optic nerve damage. Your doctor will determine whether you are at risk.

During treatment, small hemorrhagic spots may appear in the soft tissues of the eyelid. Your doctor may minimize this risk by immediately applying gentle pressure at the injection site.

After receiving an injection of XEOMIN into the eye muscle, reduced blinking may occur, leading to prolonged exposure of the transparent front part of the eye (cornea). This exposure may cause surface damage and inflammation (corneal ulceration).

Spasmodic torticollis (neck twisting)

After injection, you may develop mild to severe difficulty swallowing, which may lead to breathing problems and increase the risk of inhaling liquids or foreign substances. Foreign substances in the lungs may cause inflammation or infection (pneumonia). Your doctor will provide special treatment if needed (e.g., artificial nutrition).

Difficulty swallowing may last two to three weeks after injection, but one case lasting up to five months has been reported.

If you have been inactive for a prolonged period, you should gradually resume activity after receiving XEOMIN injection.

Increased muscle tone and/or uncontrolled muscle stiffness

XEOMIN may be used to treat increased muscle tone and stiffness in different parts of the upper limb, for example, your arm or hand. XEOMIN is effective when used in combination with standard treatment methods. XEOMIN should be used together with these other methods.

It is unlikely that this medicine can increase the range of motion in joints where the surrounding muscle has lost its ability to stretch.

If you have been inactive for a prolonged period, you should gradually resume activity after receiving XEOMIN injection.

Chronic drooling (sialorrhea)

Some medications (e.g., clozapine, aripiprazole, pyridostigmine) may cause excessive saliva production. Before using XEOMIN to treat drooling, consideration should first be given to replacing, reducing, or even discontinuing such medication. The use of XEOMIN to reduce medication-induced drooling has not been investigated.

Your physician should consider reducing the dose if dry mouth develops following administration of XEOMIN.

When your saliva flow is reduced by XEOMIN, oral health problems such as dental caries may occur or existing conditions may worsen. Contact a dentist when starting XEOMIN treatment for chronic drooling. If necessary, your dentist may decide to take preventive measures against caries.

Children and adolescents

Do not use this medicine in children under 2 years of age, weighing less than 12 kg, or in children and adolescents for any other treatments besides chronic drooling, as the use of XEOMIN has not been established in this population and is not recommended.

Other medicines and XEOMIN

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

The effect of XEOMIN may be enhanced:

??? by medications used to treat certain infectious diseases (spectinomycin or aminoglycoside antibiotics [e.g., neomycin, kanamycin, tobramycin])

?? by other medications that relax muscles (e.g., tubocurarine-type muscle relaxants). These medications are used, for example, during general anesthesia. Before undergoing surgery, inform your anesthesiologist if you have received XEOMIN.

? when used for the treatment of chronic drooling: with other medications that reduce saliva flow on their own (e.g., anticholinergics such as atropine, glycopyrronium, or scopolamine) or due to therapeutic irradiation of the head and neck, including the salivary glands. Inform your doctor if you are receiving or are scheduled to receive radiotherapy.

In these cases, XEOMIN should be used with caution.

The effect of XEOMIN may be reduced by the use of certain medications for malaria and rheumatism (known as aminoquinolines).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before receiving this medicine.

You should not use XEOMIN during pregnancy unless your doctor determines that the need and potential benefit justify the possible risk to the fetus.

XEOMIN is not recommended during breastfeeding.

Driving and using machines

You should not drive or perform other potentially hazardous activities if you experience drooping eyelids, weakness (asthenia), muscle weakness, dizziness, or vision disturbances.

If you have any doubts, consult your doctor.

3. How to use XEOMIN

XEOMIN can only be administered by healthcare professionals with adequate knowledge and experience in the use of botulinum toxin type A.

Your healthcare provider will determine the optimal dosage, frequency, and number of injection sites for you. The initial treatment outcome with XEOMIN should be evaluated, which may lead to dose adjustments until the desired therapeutic effect is achieved. The treatment intervals will be determined by your healthcare provider based on your actual clinical needs.

If you feel that the effect of XEOMIN is too strong or too weak, inform your healthcare provider. If no therapeutic effect is observed, alternative treatments should be considered.

Eyelid spasms (blepharospasm) and facial muscle spasms affecting one side of the face (hemifacial spasm)

The recommended initial dose is up to 25 units per eye, and the recommended total dose in subsequent treatment sessions is up to 50 units per eye. The initial effect generally appears within four days after injection. The effect of each treatment lasts approximately 3 to 5 months; however, the duration may be significantly longer or shorter. Treatments at intervals shorter than 12 weeks are not recommended.

Treatment administered more frequently than every three months generally does not provide additional benefit.

If you suffer from facial muscle spasms affecting one side of your face (hemifacial spasm), your doctor will follow the treatment recommendations for eyelid spasms (blepharospasm) restricted to one side of the face. Hemifacial spasm will be treated only in the upper part of the face, as XEOMIN injections in the lower part of the face may increase the risk of adverse effects, such as pronounced local muscle weakness.

Neck twisting (spasmodic torticollis)

The recommended dose per injection site is up to 50 units, and the maximum dose for the first treatment session is 200 units. Your doctor may administer doses of up to 300 units in subsequent sessions, depending on your response. The initial effect generally appears within seven days after injection. The effect of each treatment lasts approximately 3 to 4 months; however, the duration may be significantly longer or shorter. The interval between treatment sessions should be at least 10 weeks.

Increased muscle tone and/or uncontrollable muscle stiffness in shoulders, arms, or hands (upper limb spasticity)

The recommended dose is up to 500 units per treatment session, and no more than 250 units should be administered into the shoulder muscles. Patients reported onset of effect within 4 days after treatment initiation. Improvement in muscle tone was observed at 4 weeks. In general, the treatment effect lasted 12 weeks. However, the duration may be significantly longer or shorter. The interval between treatment sessions should be at least 12 weeks.

Chronic drooling (sialorrhea, adults)

The recommended dose is 100 units per treatment session. This maximum 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 should not exceed 75 units. The interval between treatment sessions should be at least 16 weeks.

Method of administration

Reconstituted XEOMIN is intended for injection into the muscle (intramuscular use) and into the salivary glands (intraglandular use) (see information for healthcare professionals at the end of this leaflet). Regarding the location of the salivary glands in adults, both anatomical landmarks and ultrasound guidance are possible; however, ultrasound guidance is preferred for reasons of efficacy. For children and adolescents, ultrasound guidance should be used. Prior to injection, local anesthetics (such as anesthetic creams), sedation, or anesthesia combined with sedation may be used.

If you are injected with more XEOMIN than you need

Symptoms of overdose

Overdose symptoms do not appear immediately after injection and may include generalized weakness, eyelid drooping, double vision, difficulty breathing, swallowing, or speaking, and respiratory muscle paralysis or swallowing difficulties that could lead to pneumonia.

Actions to take in case of overdose

If you experience symptoms of overdose, seek immediate emergency medical attention or ask your family to do so, and ensure you are taken to a hospital. Medical supervision for several days may be required, and assisted ventilation may be necessary.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Adverse effects are generally observed during the first week after treatment and are transient. These effects may be related to the medicine, the injection technique, or both. Adverse effects may be limited to the area surrounding the injection site (for example, localized muscle weakness, local pain, swelling, tingling (paresthesia), reduced sensation to touch (hypoesthesia), tenderness on palpation, swelling (general), soft tissue swelling (edema), redness (erythema), itching, localized infection, bruising, bleeding, and/or bruising).

Needle injection may cause pain. This pain or needle-related anxiety may lead to fainting, nausea, tinnitus (ringing in the ears), or a drop in blood pressure.

Adverse effects such as excessive muscle weakness or difficulty swallowing may be caused by relaxation of muscles distant from the XEOMIN injection site. Difficulty swallowing may lead to aspiration of foreign material, resulting in pulmonary inflammation and, in some cases, death.

An allergic reaction to XEOMIN may occur. Immediate and/or severe allergic reactions (anaphylaxis) or serum-related allergic reactions (serum sickness) have been reported rarely and may cause, for example, difficulty breathing (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. These occurred when the toxin was administered alone or in combination with other medicines known to cause similar reactions. An allergic reaction may cause any of the following symptoms:

• difficulty breathing, swallowing, or speaking due to swelling of the face, lips, mouth, or throat
• swelling of the hands, feet, or ankles

If you experience any of these adverse effects, please inform your doctor immediately or ask your family members to do so, and go to the nearest hospital emergency department.

The following adverse effects have been reported with XEOMIN:

Blepharospasm (eyelid spasms)

Very common (may affect more than 1 in 10 people):
Drooping eyelid (ptosis)

Common (may affect up to 1 in 10 people):
Dry eyes, blurred vision, visual disturbances, dry mouth, injection site pain

Uncommon (may affect up to 1 in 100 people):
Headache, facial muscle weakness (facial paralysis), double vision (diplopia), increased tearing, difficulty swallowing (dysphagia), fatigue, muscle weakness, urticaria

Hemifacial spasm (spasm affecting one side of the face)

Similar adverse effects are expected when treating hemifacial spasm as with blepharospasm.

Cervical dystonia (spasmodic torticollis)

Very common (may affect more than 1 in 10 people):
Difficulty swallowing (dysphagia)

Common (may affect up to 1 in 10 people):
Neck pain, muscle weakness, musculoskeletal pain (myalgia), musculoskeletal stiffness, muscle spasms, headache, dizziness, injection site pain, weakness (asthenia), dry mouth, nausea, increased sweating (hyperhidrosis), upper respiratory tract infection, feeling of faintness (presyncope)

Uncommon (may affect up to 1 in 100 people):
Speech disorders (dysphonia), difficulty breathing (dyspnea), urticaria

Treatment of cervical dystonia may cause difficulty swallowing, with varying degrees of severity. This may lead to aspiration of foreign material, which may require medical intervention. Difficulty swallowing may persist for two to three weeks after injection, but in one case it lasted five months. The occurrence of dysphagia appears to be dose-dependent.

Increased muscle tone and/or uncontrolled muscle stiffness in shoulders, arms, or hands (upper limb spasticity)

Common (may affect up to 1 in 10 people):
Dry mouth

Uncommon (may affect up to 1 in 100 people):
Headache, reduced sensation to touch (hypoesthesia), muscle weakness, limb pain, weakness (asthenia), musculoskeletal pain (myalgia), difficulty swallowing (dysphagia), nausea

Frequency not known (cannot be estimated from available data):
Injection site pain

Chronic drooling (sialorrhea) in adults

Common (may affect up to 1 in 10 people):
Dry mouth, difficulty swallowing (dysphagia), tingling sensation (paresthesia)

Uncommon (may affect up to 1 in 100 people):
Thick saliva, speech disorder, taste disturbance (dysgeusia)

Cases of persistent dry mouth (>110 days) of severe intensity have been reported, which could lead to additional complications such as gum inflammation (gingivitis), difficulty swallowing, and dental caries.

Chronic drooling (sialorrhea) in children/adolescents

Uncommon (may affect up to 1 in 100 people):
Difficulty swallowing (dysphagia)

Frequency not known (cannot be estimated from available data):
Dry mouth, thick saliva, oral pain, dental caries

Post-marketing experience

The following adverse reactions have been reported with unknown frequency for XEOMIN use since its launch, regardless of treatment area:

Flu-like symptoms, contraction of the injected muscle, and hypersensitivity reactions such as swelling, soft tissue swelling (edema, also distant from the injection site), redness, itching, rash (localized and generalized), and difficulty breathing.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Conservation of XEOMIN

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and on the label of the vial after "EXP". The expiry date refers to the last day of the month indicated.

Unopened vial: Do not store above 25°C.

Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 24 hours at a temperature of 2°C to 8°C.

From a microbiological standpoint, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should generally not exceed 24 hours at 2°C to 8°C, unless reconstitution has been carried out under controlled and validated aseptic conditions.

The physician must not use XEOMIN if the solution is cloudy or contains flakes or particles.

For instructions on disposal, see information for healthcare professionals at the end of this leaflet.

6. Contents of the pack and other information

Composition of XEOMIN

• The active substance is Clostridium botulinum type A neurotoxin (150 kD),

without complexing proteins.

XEOMIN 50 units powder for solution for injection

One vial contains 50 units of Clostridium botulinum type A neurotoxin (150 kD), without complexing proteins*.

XEOMIN 100 units powder for solution for injection

One vial contains 100 units of Clostridium botulinum type A neurotoxin (150 kD), without complexing proteins*.

XEOMIN 200 units powder for solution for injection

One vial contains 200 units of Clostridium botulinum type A neurotoxin (150 kD), without complexing proteins*.

• Botulinum toxin type A, purified from cultures of Clostridium botulinum (Hall strain)
  • Other components: human albumin, sucrose.

Appearance of the product and contents of the pack

XEOMIN is supplied as a powder for solution for injection. The powder is white.

When reconstituted, it forms a clear, colourless solution.

XEOMIN 50 units powder for solution for injection: packs of 1, 2, 3 or 6 vials

XEOMIN 100 units powder for solution for injection: packs of 1, 2, 3, 4 or 6 vials

XEOMIN 200 units powder for solution for injection: packs of 1, 2, 3, 4 or 6 vials

Only certain pack sizes may be marketed.

Marketing Authorisation Holder

Merz Pharmaceuticals GmbH

Eckenheimer Landstr. 100

D-60318 Frankfurt/Main

Germany

Manufacturer

Merz Pharma GmbH & Co. KgaA

Legal address:

Eckenheimer Landstraße 100

60318 Frankfurt/Main

P.O. Box 11 13 53

60048 Frankfurt/Main

Germany

Telephone: +49-69/15 03-1

Fax: +49-69/15 03-200

Manufacturing address:

Ludwigstraße 22

64354 Reinheim

Germany

Local representative

Merz Therapeutics Iberia, S.L.U.

Avenida de Bruselas 6

28108 Alcobendas - Madrid

This medicinal product is authorised in the European Economic Area Member States 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 latest revision of this leaflet: December 2025

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es)

__________________________________________________________________________

The following information is intended for healthcare professionals only:

Instructions for reconstitution of the injectable solution:

XEOMIN must be reconstituted before use with sodium chloride 9 mg/ml (0.9%) solution for injection.

XEOMIN may only be used for its intended purpose of treating a patient within a single session.

It is recommended that reconstitution of the vial and syringe preparation be performed over plastic-backed absorbent paper towels to contain any spilled material. Using a syringe, withdraw an appropriate amount of sodium chloride solution (see dilution table). A 20–27 G needle is recommended for reconstitution. After vertically inserting the needle through the rubber stopper, the solvent should be carefully injected into the vial to avoid foaming. Discard the vial if the vacuum does not draw the solvent into the vial. Disconnect the syringe from the vial and mix XEOMIN with the solvent by gently swirling or inverting/rotating the vial; do not shake vigorously. If necessary, the reconstitution needle should remain in the vial and the required amount of solution should be withdrawn using a new sterile needle appropriate for injection.

Reconstituted XEOMIN is a clear, colourless solution.

XEOMIN must not be used if the reconstituted solution (prepared as described above) appears cloudy or contains particles.

Care must be taken to use the correct solvent volume for the chosen presentation to prevent accidental overdose. If different XEOMIN presentations are to be used as part of an injection procedure, particular care must be taken to use the correct amount of solvent when reconstituting a given number of units per 0.1 ml. The solvent volume varies between XEOMIN 50 units, XEOMIN 100 units and XEOMIN 200 units. Each syringe must be appropriately labelled.

The possible concentrations of XEOMIN 50, 100 and 200 units are shown in the following table:

Resulting dose (in units per 0.1 ml)	Solvent added (sodium chloride 9 mg/ml (0.9%) injectable solution)
Vial with 50 units	Vial with 100 units	Vial with 200 units
20 units	0.25 ml	0.5 ml	1 ml
10 units	0.5 ml	1 ml	2 ml
8 units	0.625 ml	1.25 ml	2.5 ml
5 units	1 ml	2 ml	4 ml
4 units	1.25 ml	2.5 ml	5 ml
2.5 units	2 ml	4 ml	Not applicable
2 units	2.5 ml	5 ml	Not applicable
1.25 units	4 ml	Not applicable	Not applicable

Disposal Instructions

Any injectable solution that has been stored for more than 24 hours, as well as any unused injectable solution, must be discarded.

Procedure for the safe disposal of vials, syringes, and used materials

Any unused or leftover vial, solution in the vial, and/or syringes must undergo a sterilization process 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 solution (0.1 N NaOH), or diluted sodium hypochlorite solution (at least 0.1% NaOCl).

After inactivation, vials, syringes, and used materials must not be emptied but should be disposed of in appropriate containers and eliminated according to local procedures.

Recommendations for any incident that may occur during handling of botulinum toxin type A

?? Any residual product must be cleaned up, using absorbent material soaked with one of the solutions mentioned above if dealing with powder, or dry absorbent material if dealing with reconstituted product.

?? Contaminated surfaces must be cleaned with absorbent material soaked in one of the above-mentioned solutions and then dried.

?? If a vial breaks, proceed as described above, carefully collecting the broken glass fragments and cleaning up the spilled product, taking care to avoid skin cuts.

?? If the product comes into contact with the skin, rinse the affected area thoroughly with abundant water.

?? If the product comes into contact with the eyes, rinse thoroughly with abundant water or with an ophthalmic irrigation solution.

?? If the product comes into contact with a wound, cut, or non-intact skin, rinse thoroughly with abundant water and take appropriate medical measures according to the injected dose.

These instructions for use, handling, and disposal must be strictly followed.