Prospect: information for the user

XEOMIN 50 units powder for injectable solution

XEOMIN 100 units powder for injectable solution

XEOMIN 200 units powder for injectable solution

Toxin fromClostridium botulinumtype A (150 kD), without complex proteins

Read this prospect carefully before receiving this medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist or nurse.
• If you experience adverse effects, consult your doctor, pharmacist or nurse, even if they are not listed in this prospect. See section 4.

1. What is XEOMIN and how it is used

2. What you need to know before starting to use XEOMIN

3. How to use XEOMIN

4. Possible adverse effects

5. Storage of XEOMIN

6. Contents of the package and additional informationl

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

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

• eyelid spasm (blepharospasm) and spasm affecting one side of the face (hemifacial spasm)
• spasmodic torticollis
• increased muscle tension/irreversible muscle rigidity in shoulders, arms, and/or hands (upper limb spasticity)
• chronic sialorrhea due to neurological disorders

XEOMIN is indicated for treatment in children and adolescents aged 2 to 17 years and weighing 12 kg or more of:

• chronic sialorrhea due to neurological disorders/neurodevelopmental disorders.

No use XEOMIN

If you are allergic to botulinum toxin type A or any of the other components of this medication (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 from improperly placed injections of botulinum toxin type A that temporarily paralyze nearby muscle groups. Rare reports have been made of adverse effects that may be related to the spread of the toxin outside the injection site to produce symptoms consistent with botulinum toxin type A effects (e.g., excessive muscle weakness, difficulty swallowing or accidental ingestion of food or drink into the respiratory tract). Patients receiving the 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. Antibody formation may cause the treatment with botulinum toxin type A to fail, 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 receiving substances that prevent blood clotting (e.g., warfarin, heparin, aspirin, clopidogrel)

If the muscles to be injected show pronounced weakness or muscle volume reduction

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

If you have any disease that alters the interaction between nerves and skeletal muscles (peripheral neuromuscular disorder)

If you have or have had difficulty swallowing

If you have or have had seizures

If you have had problems with botulinum toxin type A injections in the past

If you are to undergo any surgical intervention

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

• Difficulty breathing, swallowing, or speaking
• Urticaria, swelling including facial or throat swelling, wheezing, sensation of fainting, and difficulty breathing (possible symptoms of severe allergic reactions)

Sensation of fainting 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 are:

Your doctor may follow a different procedure when preparing the injection solution

Different treatment intervals

Injections in another muscle

Marginal variation in the efficacy of the active principle of XEOMIN

Absence of response/therapy failure during treatment

Eye spasms (blepharospasm) and spasms affecting one side of the face (hemifacial spasm)

Tell your doctor before using XEOMIN if:

You have been previously subjected to eye surgery orcicular. Your doctor will take the necessary precautions

You present a risk of developing a disease called narrow-angle glaucoma. This disease may cause an increase in intraocular pressure and may lead to optic nerve damage. Your doctor will know if you are at risk.

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

After receiving an injection of XEOMIN in the eye muscle, you may experience a decrease in blinking, which may lead to prolonged exposure of the transparent front part of the eye (cornea). This exposure may cause surface damage and inflammation (corneal ulceration).

Neck torsion (torticollis spasm)

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

Difficulty swallowing may last from two to three weeks after the injection, but a case has been described in which it lasted up to five months.

You should gradually resume activity after the XEOMIN injection if you have been inactive for a long period.

Increased muscle tension and/or uncontrolled muscle rigidity

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

This medication is unlikely to increase the range of motion of joints where the surrounding muscle has lost its ability to stretch.

You should gradually resume activity after the XEOMIN injection if you have been inactive for a long period.

Chronic salivation (sialorrhea)

Some medications (e.g., clozapine, aripiprazole, pyridostigmine) may cause excessive salivation. First, consider the possibility of replacing, reducing, or even interrupting this medication before using XEOMIN as a treatment for salivation. XEOMIN has not been investigated for use in reducing medication-induced salivation.

Your doctor will consider reducing the dose if cases of "dry mouth" develop in association with XEOMIN administration.

When your saliva flow is reduced by XEOMIN, oral health problems, such as tooth decay, may occur or existing problems may worsen. Contact a dentist when you start using XEOMIN for chronic salivation treatment. If necessary, your dentist may decide to take measures to prevent tooth decay.

Children and adolescents

Do not use this medication in children under 2 years, with a weight less than 12 kg, or in children and adolescents for other treatments different from chronic salivation, because the use of XEOMIN has not been established in this population and is not recommended.

Other medications and XEOMIN

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

The effect of XEOMIN may be potentiated:

By medications used to treat certain infectious diseases (e.g., 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, for general anesthesia. Before undergoing surgery, inform your anesthesiologist if you have received XEOMIN.

When used for chronic salivation treatment: with other medications that reduce salivation by themselves (e.g., anticholinergics such as atropine, glycopyrrolate, or scopolamine) or by radiation therapy in the head and neck, including salivary glands. Inform your doctor if you are receiving radiation therapy or if it is planned.

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, lactation, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before this medication is administered.

Do not use XEOMIN during pregnancy, unless your doctor decides that the need and potential benefit justify the possible risk to the fetus.

XEOMIN is not recommended during lactation.

Driving and operating machinery

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

If you have any doubts, consult your doctor.

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

The healthcare professional will choose the best dosage for you, frequency, and optimal number of injection points. The result of the initial treatment with XEOMIN should be evaluated, and the dose may be adjusted to achieve the desired therapeutic effect. The treatment intervals will be determined by your healthcare professional based on your real clinical needs.

If you feel that the effect of XEOMIN is too intense or too weak, tell your healthcare professional. In cases where no therapeutic effect is observed, alternative treatments should be considered.

Blepharospasm and hemifacial spasm

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

Normally, treatment used at a frequency greater than every three months does not confer any additional beneficial effect.

If you suffer from hemifacial spasm, your doctor will follow the treatment recommendations for blepharospasm restricted to one side of the face. Hemifacial spasm will be treated only on the upper part of the face since XEOMIN injections in the lower part of the face may increase the risk of adverse effects such as a significant risk of local weakness.

Torticollis spasmodica

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 the response. Generally, the initial effect usually manifests itself within seven days of injection. The effect of each treatment lasts approximately 3 to 4 months; however, the duration may be significantly longer or shorter. The interval between each treatment session should be at least 10 weeks.

Upper limb spasticity (spasticity of the upper limb)

The recommended dose is up to 500 units per treatment session, and no more than 250 units should be administered in the shoulder muscles. Patients reported the onset of the effect at 4 days after the start of treatment. Muscle tone improvement was observed at 4 weeks. Generally, the effect of the treatment lasted 12 weeks. However, the duration may be significantly longer or shorter. The interval between each treatment session should be at least 12 weeks.

Chronic sialorrhea (adults)

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

Chronic sialorrhea (children/adolescents)

The recommended dose per treatment session depends on body weight. The maximum dose should not exceed 75 units. The interval between each treatment session should be at least 16 weeks.

Administration form

XEOMIN dissolved is indicated to be injected 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 localization of salivary glands in adults, both anatomical reference points and ultrasound-guided methods are possible, however, the ultrasound-guided method should be preferred for reasons of efficacy. For children and adolescents, the ultrasound-guided method should be used. Before injection, local anesthetics (such as creams), sedation, or combined anesthesia with sedation may be used.

If you are injected with more XEOMIN than you need

Signs of overdose

The signs of overdose do not appear immediately after injection and may include general weakness, eyelid drooping, double vision, difficulty breathing, swallowing, or speaking, and paralysis of respiratory muscles or difficulty swallowing that may cause pneumonia.

Measures to take in cases of overdose

In the event of signs of overdose, seek immediate medical attention or have your family members do so, and ensure that you are admitted to the hospital. Medical supervision may be required for several days, and assisted ventilation may be used.

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

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

Generally, side effects are observed in the first week after treatment and are transient. These side effects may be related to the medicine, injection technique, or both. Side effects may be limited to the area around the injection site (for example, localized muscle weakness, pain, inflammation, tingling (paresthesia), reduced tactile sensation (hypoesthesia), pain on palpation, general inflammation, soft tissue inflammation (edema), redness (erythema), itching, localized infection, hematoma, hemorrhage, and/or petechiae).

The injection of the needle can cause pain. This pain or anxiety caused by needles can lead to dizziness, nausea, tinnitus (ringing in the ears), or a drop in blood pressure.

Side effects such as excessive muscle weakness or difficulty swallowing may be caused by the relaxation of distant muscles to the XEOMIN injection site. Difficulty swallowing can cause the inhalation of foreign bodies, leading to lung inflammation and, in some cases, death.

A hypersensitivity reaction to XEOMIN may occur. Rarely reported immediate and/or severe (anaphylaxis) or serum product hypersensitivity reactions (serum sickness), which cause, for example, difficulty breathing (dyspnea), hives (urticaria), or soft tissue inflammation (edema). Some of these reactions have been observed after the use of the conventional complex of botulinum toxin type A. They occurred when the toxin was administered alone or in combination with other medications known to cause similar reactions. A hypersensitivity reaction can cause any of the following symptoms:

• Difficulty breathing, swallowing, or speaking due to facial, lip, mouth, or throat inflammation
• Hand, foot, or ankle inflammation

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

The following side effects have been reported with XEOMIN:

Blepharospasm (eyelid spasm)

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

Eye drooping (ptosis)

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

Dry eyes, blurred vision, difficulty seeing, dry mouth, pain at the injection site

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

Facial spasm affecting one side of the face (hemifacial spasm)

Similar side effects are expected when treating facial spasm affecting one side of the face as for blepharospasm.

Torticollis spasmodica (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, pain at the injection site, weakness (asthenia), dry mouth, nausea, increased sweating (hyperhidrosis), upper respiratory tract infection, sensation of fainting (presyncope)

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

Speech disorders (dysphonia), difficulty breathing (dyspnea), urticaria

The treatment of torticollis spasmodica may cause difficulty swallowing, with varying degrees of intensity. This can lead to the inhalation of foreign bodies, which may require medical intervention. Difficulty swallowing may persist for two to three weeks after injection, but in one case, it lasted five months. Difficulty swallowing appears to depend on the dose.

Increased muscle tension and/or uncontrolled muscle rigidity 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 tactile sensation (hypoesthesia), muscle weakness, limb pain, weakness (asthenia), musculoskeletal pain (myalgia), difficulty swallowing (dysphagia), nausea

Unknown frequency (cannot be estimated from available data):

Pain at the injection site

Chronic sialorrhea (drooling) 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):

Dense saliva, speech disorders, taste disorders (dysgeusia)

Persistent dry mouth (> 110 days) of severe intensity has been reported, which may cause additional complications such as gum inflammation (gingivitis), difficulty swallowing, and caries.

Chronic sialorrhea (drooling) in children/adolescents

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

Difficulty swallowing (dysphagia)

Unknown frequency (cannot be estimated from available data):

Dry mouth, dense saliva, oral pain, dental caries

Experience after marketing

The following adverse reactions were reported without known frequency for the use of XEOMIN since its launch, independent of the treatment area:

Symptoms similar to the flu, muscle contraction at the injection site, and hypersensitivity reactions such as swelling, soft tissue inflammation (edema, also distant from the injection site), redness, itching, hives (local and generalized), and difficulty breathing.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor, pharmacist, or nurse, even if it is a possible adverse reaction that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:www.notificaram.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box and on the vial label after “CAD”. The expiration date is the last day of the month indicated.

Unopened vial:Do not store at a temperature above 25 °C.

Reconstituted solution: Chemical and physical stability has been demonstrated for use within 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, storage times in use and pre-use conditions are the responsibility of the user and should normally not exceed 24 hours at 2°C to 8°C, unless reconstitution was performed in controlled and validated aseptic conditions.

Your healthcare provider should notuseXEOMIN if the solution appears cloudy or contains flocculated material or particles.

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

XEOMIN Composition

• The active ingredient is botulinum toxin type A (150 kD),

without complex proteins.

XEOMIN 50 units lyophilisate for injection

One vial contains 50 units of botulinum toxin type A (150kD), without complex proteins*.

XEOMIN 100units lyophilisate for injection

One vial contains 100units of botulinum toxin type A (150kD), without complex proteins*.

XEOMIN 200units lyophilisate for injection

One vial contains 200units of botulinum toxin type A (150kD), without complex proteins*.

* Botulinum toxin type A, purified from Clostridium botulinum (Hall strain)

• The other components are: human albumin, saccharose.

Appearance of the product and contents of the pack

XEOMIN is presented as a lyophilisate for injection. The powder is white.

When reconstituted, a transparent and colourless solution is produced.

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

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

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

Only some pack sizes may be marketed.

Marketing Authorisation Holder

Merz Pharmaceuticals GmbH

Eckenheimer Landstr. 100

D-60318 Frankfurt/Main

Germany

Responsible Person

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 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 the last revision of this leaflet:February 2022

The detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es)

__________________________________________________________________________

The following information is intended solely for healthcare professionals:

Instructions for reconstitution of the injectable solution:

XEOMIN is reconstituted before use with sodium chloride solution, at a concentration of 9 mg/ml (0.9%).

XEOMIN can only be applied for its intended use to treat a patient in a single session.

It is recommended to carry out the reconstitution of the vial and the preparation of the syringe on paper towels with plastic coating, to collect any possible spillage. With a syringe, a suitable amount of sodium chloride solution (see dilution chart) is extracted. It is recommended to use a 20-27 G needle for reconstitution. After vertical insertion of the needle through the rubber stopper, the solvent should be injected carefully into the vial to avoid foam formation. Discard the vial if the vacuum does not aspirate the solvent into the vial. Separate the syringe from the vial and mix XEOMIN with the solvent by gently removing and inverting/shaking the vial, do not vigorously agitate. If necessary, the reconstitution needle should remain in the vial and the required amount of solution should be extracted with a new sterile needle suitable for injection.

XEOMIN reconstituted is a transparent and colourless solution.

XEOMIN should not be used if the reconstituted solution (prepared as mentioned above) has a turbid appearance or contains particles.

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

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

Instructions for disposal:

Any unused injectable solution should be discarded after 24 hours and any unused solution.

Procedure to follow for safe disposal of vials, syringes and materials used

Any unused vial or residue, solution in the vial and/or syringes should be subjected to autoclave sterilisation. Alternatively, the remaining XEOMIN can be inactivated by adding one of the following solutions: ethanol 70%, isopropanol 50%, SDS (anionic detergent) 0.1%, sodium hydroxide solution diluted (NaOH 0.1 N) or sodium hypochlorite solution diluted (NaOCl at least 0.1%).

After inactivation, the vials, syringes and materials used should not be emptied, but discarded in suitable containers and disposed of in accordance with local procedures.

Recommendations in case of any incident that may occur during handlingwith botulinum toxin type A

??Clean any product residue, either using absorbent material impregnated with any of the solutions mentioned above in case of powder, or with dry absorbent material, if it is the reconstituted product.

??Contaminated surfaces should be cleaned with absorbent material soaked in any of the above-mentioned solutions and dried afterwards.

??If a vial is broken, proceed as mentioned above, carefully collecting the broken glass pieces and cleaning the spilled product, avoiding cuts on the skin.

??If the product comes into contact with the skin, rinse the affected area with plenty of water.

??If the product comes into contact with the eyes, rinse with plenty of water or with an eye wash solution.

??If the product comes into contact with a wound, cut or non-intact skin, rinse with plenty of water and take appropriate medical measures in accordance with the injected dose.

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