XEOMIN

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
Please read all of this 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 further questions, please ask your doctor or pharmacist.
• If you experience any side effects, including any not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

Leaflet contents:

1. What XEOMIN is and what it is used for
2. What you need to know before using XEOMIN
3. How to use XEOMIN
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 containing the active substance botulinum neurotoxin 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:

• Blepharospasm (involuntary eyelid spasms) and hemifacial spasm (involuntary muscle contractions affecting one side of the face),
• Cervical dystonia (spasmodic torticollis),
• Increased muscle tone/uncontrolled stiffness in the arms, hands and (or) forearms (upper limb spasticity),
• Chronic drooling (sialorrhea) due to neurological disorders.

XEOMIN is used to treat the following condition in children and adolescents aged 2 to 17 years, with body weight ≥ 12 kg:

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

2. Information before using XEOMIN

When not to use XEOMIN

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

Warnings and precautions
Adverse effects may result from injecting botulinum toxin type A into an incorrect location, leading to temporary paralysis of nearby muscle groups. Very rarely, adverse effects have been reported due to the spread of the toxin to sites distant from the injection site, causing botulism-like symptoms consistent with the action of botulinum toxin type A (e.g. double vision, blurred vision and/or drooping eyelids, difficulty speaking or breathing, excessive muscle weakness, swallowing difficulties and/or accidental choking on food or drinks). Patients receiving recommended doses may experience excessive muscle weakness.
If the dose is too high or the medicine is administered too frequently, the risk of antibody formation may increase. The development of antibodies may lead to treatment failure with botulinum toxin type A, regardless of the reason for administration.
Before starting treatment with XEOMIN, discuss the following with your doctor or pharmacist:

• if the patient has any blood clotting disorders,
• if the patient is taking medications that prevent blood clotting (e.g. warfarin, heparin, acetylsalicylic acid, clopidogrel),
• if the patient has marked weakness or reduced muscle mass in the muscle to be injected,
• if the patient suffers from amyotrophic lateral sclerosis (ALS), which may lead to generalized atrophy of muscle tissue,
• if the patient has any disease affecting nerve-muscle interactions (neuromuscular disorder),
• if the patient currently has or has previously had swallowing difficulties,
• if the patient currently has or has previously had seizures,
• if the patient previously experienced problems related to botulinum toxin type A injections,
• if the patient is scheduled for surgery.

Contact your doctor or seek medical help immediately if the patient experiences any of the following symptoms:

• difficulty breathing, swallowing, or speaking,
• hives, swelling including facial or throat swelling, wheezing, feeling weak, or shortness of breath (possible severe allergic reactions).

Repeated injections of XEOMIN
With repeated injections of XEOMIN, the effect of the medicine may increase or decrease. Possible reasons include:

• different preparation procedures for the injection solution performed by the doctor,
• varying durations of treatment intervals,
• injections into a different muscle,
• minor changes in the efficacy of the active substance in XEOMIN,
• lack of response to treatment.

Blepharospasm (eyelid twitching) and hemifacial spasm (spasm affecting one side of the face)
Consult your doctor before using XEOMIN if:

• the patient has undergone eye surgery. The doctor will take additional precautions,
• the patient is at risk of developing a condition called narrow-angle glaucoma. This condition may cause increased intraocular pressure, potentially leading to optic nerve damage. The doctor should be informed if the patient is at risk.

Small bleeding spots (petechiae) may appear in the soft tissues of the eyelid during treatment. The doctor may reduce the risk of their occurrence by applying gentle pressure at the injection site immediately after injection.
After injecting XEOMIN into an eye muscle, blinking frequency may decrease, leading to prolonged exposure of the transparent front part of the eye (cornea). This exposure may cause corneal surface damage and inflammation (corneal ulceration).

Cervical dystonia (spasmodic torticollis)
After injection, the patient may experience swallowing difficulties ranging from mild to severe. This may lead to breathing problems and an increased risk of aspiration of foreign substances or fluids. Foreign material in the lungs may cause inflammation or infections (pneumonia). The doctor will initiate appropriate treatment if necessary (e.g. artificial feeding).
Swallowing difficulties may last up to two or three weeks after injection; in one reported case, they persisted for five months.
If the patient has been inactive for a prolonged period, activity should be resumed gradually after XEOMIN injection.

Increased muscle tone/uncontrolled muscle stiffness
XEOMIN may be used to treat increased muscle tone or uncontrolled stiffness in various parts of the upper limb, such as the hand or fingers.
XEOMIN is effective when used in combination with standard treatment methods.
XEOMIN should be used together with these other therapies.
It is unlikely that this medicine will improve joint range of motion if the surrounding muscles have lost their ability to stretch.
If the patient has been inactive for a prolonged period, activity should be resumed gradually after XEOMIN injection.

Chronic drooling (sialorrhea)
Some medications (e.g. clozapine, aripiprazole, pyridostigmine) may cause excessive saliva production. Consideration should be given to replacing, reducing, or discontinuing the medication causing drooling before using XEOMIN to treat sialorrhea.
The efficacy and safety of XEOMIN have not been studied in patients with drug-induced sialorrhea.
If dry mouth occurs as a result of XEOMIN treatment, the doctor may consider reducing the dose.
Due to reduced saliva production following XEOMIN administration, oral health problems such as dental caries or worsening of existing conditions may occur.
Before starting XEOMIN treatment for chronic sialorrhea, consult a dentist. The dentist may decide to implement preventive measures against tooth decay if necessary.

Children and adolescents
This medicine must not be used in children under 2 years of age, in children weighing less than 12 kg, or in children and adolescents for conditions other than chronic sialorrhea, as the use of XEOMIN has not been studied in these patient groups. Therefore, its use is not recommended in these patients.

XEOMIN and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or might take in the future.
The effect of XEOMIN may be increased by:

• medications used in certain infectious diseases (spectinomycin or aminoglycoside antibiotics such as neomycin, kanamycin, tobramycin),
• other medicines that relax muscles (e.g. tubocurarine-type muscle relaxants). Such drugs are used, for example, during general anesthesia. Inform the anesthesiologist before surgery that the patient has received XEOMIN.
• in the treatment of chronic sialorrhea: by other drugs that reduce saliva production (e.g. anticholinergic drugs such as atropine, glycopyrronium, or scopolamine) or as a result of therapeutic irradiation of the head and neck, including the salivary glands. Inform the doctor if the patient is or will be undergoing radiotherapy.

In such cases, special caution is required when using XEOMIN.
The effect of XEOMIN may be weakened by:

• certain antimalarial and antirheumatic drugs (known as aminoquinolines).

Pregnancy, breastfeeding, and fertility
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before using this medicine.
XEOMIN should not be used during pregnancy unless the doctor decides it is absolutely necessary and the expected benefit outweighs the potential risk to the fetus.
Use of XEOMIN is not recommended in breastfeeding women.

Driving and operating machinery
Do not drive or operate machinery or perform other potentially hazardous activities if drooping eyelids, weakness (asthenia), muscle weakness, dizziness, or visual disturbances occur. If in doubt, consult your doctor.

3. How to use XEOMIN

XEOMIN must only be administered by physicians with appropriate specialist knowledge
in the use of botulinum toxin type A.
The optimal dose, frequency of administration, and number of injection sites will be determined individually
by the physician for each patient. The effect of initial treatment with XEOMIN should be assessed, which may
lead to dose adjustment until the desired therapeutic effect is achieved. The intervals between treatments
will be determined by the physician based on the individual patient's actual needs.
If the patient feels that the effect of XEOMIN is too strong or too weak, they should
contact their physician. If no effect is observed, alternative treatments should be considered.

Blepharospasm (eyelid spasms) and hemifacial spasm (spasms affecting one side of the face)
The recommended initial dose is up to 25 units per eye, with a total recommended dose of up to 50 units per eye in subsequent treatments. The onset of effect is usually observed within four days after injection. The effect lasts after each treatment for approximately 3–5 months, although it may last significantly longer or shorter. The interval between treatment sessions should not be less than 12 weeks.
Treatment more frequently than every three months usually does not provide additional benefit.

If the patient has hemifacial spasm (spasms affecting one side of the face), the physician will follow recommendations for treating unilateral blepharospasm. Treatment of hemifacial spasm will focus on the upper part of the face, as injection of XEOMIN into the lower part of the face may increase the risk of adverse 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 for the first treatment session is up to 200 units. The physician may use doses up to 300 units in subsequent sessions, depending on the treatment response. The onset of effect is usually observed within seven days after injection. The effect lasts after each treatment typically for 3–4 months, although it may last significantly longer or shorter. Treatment may be repeated no sooner than 10 weeks after the previous session.

Increased muscle tone/uncontrolled stiffness of arms, hands and forearms (upper limb spasticity)
The recommended dose is up to 500 units per treatment session. No more than 250 units should be administered into arm muscles. Patients have reported onset of effect within 4 days after administration. Reduction in muscle tone was felt within 4 weeks. Generally, the treatment effect lasted 12 weeks, although it may last significantly longer or shorter. The interval between treatment sessions should be at least 12 weeks.

Chronic sialorrhea (excessive drooling, 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 sialorrhea (excessive drooling, 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
Reconstituted XEOMIN is administered by intramuscular injection (intramuscular administration) or into the gland (salivary gland) (see information for healthcare professionals at the end of this leaflet). In adults, the appropriate salivary glands can be localized using anatomical landmarks or ultrasound imaging; however, for safety reasons, the ultrasound-guided method is preferred. In children and adolescents, the ultrasound-guided method should be used.
Before injection, children and adolescents may be given a local anaesthetic (e.g. local anaesthetic cream), a sedative, or anaesthesia combined with a sedative.

Use of a higher than recommended dose of XEOMIN

Symptoms of overdose
Symptoms of overdose do not occur immediately after injection and may include generalized weakness, ptosis (drooping eyelid), double vision, respiratory disorders, speech disturbances, and paralysis of respiratory muscles or swallowing difficulties, which may lead to pneumonia.

Management in case of overdose
If symptoms of overdose occur, the patient or someone nearby should immediately call emergency services; hospitalization may be required. Several days of medical care and respiratory support may be necessary.

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

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
Adverse reactions usually occur within the first week after treatment and are transient in nature. Adverse reactions may be related to the medicine, the injection procedure, or both. Adverse reactions may be limited to the area around the injection site (e.g. local muscle weakness, local pain, inflammation, tingling sensation (paresthesia), reduced sense of touch (hypoesthesia), hypersensitivity to touch, swelling (generalized), soft tissue swelling (edema), redness of the skin (erythema), itching, local infection, bruising, bleeding and/or discoloration).
Injection of the medicine may cause pain. Pain or fear of the injection may lead to fainting, nausea, ringing in the ears (tinnitus), or low blood pressure.
Adverse reactions such as excessive muscle weakness or swallowing disorders may result from reduced muscle tone in areas distant from the injection site of XEOMIN.
Swallowing disorders may lead to aspiration of foreign bodies into the respiratory tract, resulting in pneumonia, sometimes leading to death.
XEOMIN may cause an allergic reaction. Severe and/or sudden allergic reactions (anaphylactic shock) or serum-related allergic reactions (serum sickness) have been rarely reported, causing, for example, breathing difficulties (dyspnea), skin rash (urticaria), or soft tissue swelling (edema). Some of these reactions were observed after administration of the conventional botulinum toxin type A complex. They occurred when the toxin was administered either alone or in combination with other medicines causing similar reactions. An allergic reaction may cause the following symptoms:

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

If any of the above symptoms occur, contact your doctor immediately or ask for help from people nearby and go to the emergency department of the nearest hospital.
The following adverse reactions have been observed during the use of XEOMIN.

Blepharospasm (eyelid spasm)
Very common (may occur in more than 1 in 10 patients):
Drooping eyelid (ptosis)
Common (may occur in up to 1 in 10 patients):
Dry eye syndrome, blurred vision, visual disturbance, dry mouth, pain at injection site
Uncommon (may occur in up to 1 in 100 patients):
Headache, facial muscle weakness (facial nerve paralysis), double vision, excessive tearing, swallowing disorders (dysphagia), fatigue, muscle weakness, skin rash

Hemifacial spasm (spasm affecting one side of the face)
During treatment of hemifacial spasm, the same adverse reactions as in blepharospasm may be expected.

Cervical dystonia (spasmodic torticollis)
Very common (may occur in more than 1 in 10 patients):
Swallowing disorders (dysphagia)
Common (may occur in up to 1 in 10 patients):
Neck pain, muscle weakness, musculoskeletal pain (muscle pain), stiffness of muscles and joints, muscle spasms, headache, dizziness, pain at injection site, weakness (asthenia), dry mouth, nausea, excessive 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), skin rash

Treatment of spasmodic torticollis may cause swallowing disorders of varying severity. This may lead to aspiration of foreign material into the lungs, which may require medical intervention. Swallowing disorders may last for two to three weeks after injection, but one case of persistence for five months has been reported. The occurrence of swallowing disorders appears to be dose-dependent.

Increased muscle tone/uncontrolled stiffness of 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 sense of touch (hypoesthesia), muscle weakness, limb pain, general weakness (asthenia), muscle pain, swallowing disorders (dysphagia), nausea
Frequency unknown (frequency cannot be determined from available data):
Pain at injection site

Chronic drooling (sialorrhea) in adults
Common (may occur in up to 1 in 10 patients):
Dry mouth, swallowing disorders (dysphagia), prickling and tingling sensation (paresthesia)
Uncommon (may occur in up to 1 in 100 patients):
Thickened saliva, speech disorders, taste disturbances
Cases of severe, persistent dry mouth (lasting longer than 110 days) have been reported, which may lead to further complications such as gingivitis, swallowing disorders, and dental caries.

Chronic drooling (sialorrhea) in children and adolescents
Uncommon (may occur in up to 1 in 100 patients):
Swallowing disorders (dysphagia)
Frequency unknown (frequency cannot be determined from available data):
Dry mouth, thickened saliva, pain in the oral cavity, dental caries

Post-marketing experience
After marketing authorization, the following adverse reactions of unknown frequency have been observed during the use of XEOMIN, regardless of the treated area: influenza-like symptoms, muscle atrophy after injection, and hypersensitivity reactions such as: swelling, soft tissue swelling (edema, also at sites distant from the injection site), redness, itching, skin rash (local and generalized), dyspnea.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02 - 222 Warsaw
Phone: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the responsible entity.
Reporting adverse reactions helps to gather more information on the safety of the medicine.

5. How to store XEOMIN

The medicine should be stored out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the vial label after
"EXP". The expiry date refers to the last day of the specified month.
The abbreviation "Lot" indicated on the packaging refers to the batch number.
Unopened vial: Do not store above 25°C.
Prepared 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 storage conditions and duration prior to use falls to the user, and this period should not exceed 24 hours at a temperature of 2°C to 8°C, unless reconstitution was carried out under controlled aseptic conditions.
The physician must not use XEOMIN if the solution is cloudy or contains undissolved particles.
For information on how to dispose of the medicine, please refer to the section intended for healthcare professionals located at the end of this leaflet.

6. Contents of the pack and other information

What XEOMIN contains

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

What XEOMIN looks like and contents of the pack
XEOMIN is a powder for solution for injection. The powder is white.
After reconstitution, the solution is clear and colourless.
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 Authorisation 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 authorised in the member countries 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, the Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden
XEOMEEN: Belgium

Information intended exclusively for healthcare professionals:

Instructions for preparation of the injection solution:
The medicinal product XEOMIN should be reconstituted before administration using 9 mg/ml (0.9%) sodium chloride solution for injection.
Xeomin must be used only as intended, for the treatment of a single patient during one procedure.
Good practice is to prepare the solution and assemble the syringe over a paper towel covered with a plastic-backed drape, in case of spillage. Draw up the appropriate volume of sodium chloride solution into the syringe (see dilution table). It is recommended to use a short-bevelled needle of 20–27 G for reconstitution. Insert the needle perpendicularly through the rubber stopper; the diluent will then be drawn into the vial slowly by vacuum. Discard the vial if the diluent is not drawn into the vial by vacuum. Detach the syringe from the vial and mix Xeomin with the diluent by gently swirling or rotating the vial and tapping it—do not shake vigorously. If necessary, the needle used for reconstitution may remain in the vial, and the required volume of solution should be withdrawn using a new, sterile syringe suitable for drug injection.

After reconstitution, Xeomin is a clear, colourless solution.
Do not use Xeomin if the prepared solution (prepared as described above) is cloudy or contains particulate matter.
Care should be taken to use the correct volume of diluent required to prepare the appropriate dose to prevent accidental overdose. If different types of Xeomin vials are used within a single injection procedure, caution must be exercised to ensure the correct volume of diluent is used to achieve the specific number of units per 0.1 ml. The volume of diluent differs for Xeomin 50 units, Xeomin 100 units, and Xeomin 200 units. Each syringe should also be appropriately labelled.
Possible concentrations for Xeomin 50, 100, and 200 units are shown in the table below:

Instructions for Disposal
Injection solution stored for longer than 24 hours and unused injection solution
must be discarded.
Safe disposal procedures for vials, syringes, and used materials
Unused vials, leftover prepared solution, and/or syringes should be sterilized
in an autoclave. Alternatively, any residual XEOMIN medication 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, used vials, syringes, and materials must not be emptied, but should
be placed into appropriate containers and disposed of in accordance with local regulations.
Recommendations for procedures in case of unexpected incidents during administration of botulinum toxin type A

• Any leakage of the medication must be immediately cleaned up: in the case of powder, use an absorbent material soaked in one of the above-mentioned solutions; in the case of reconstituted medication, use dry absorbent material.
• The contaminated surface should be wiped with an absorbent material soaked in one of the above-mentioned solutions, then dried.
• If a vial is broken, follow the instructions above. Carefully collect the broken glass fragments and, avoiding cuts, wipe up any remaining medication.
• If the medication comes into contact with the skin, wash the affected area thoroughly with large amounts of water.
• If the medication gets into the eyes, rinse the eyes thoroughly with large amounts of water or eye irrigation solution.
• If the medication enters a wound, cut, or skin crack, wash the area thoroughly with large amounts of water. Appropriate medical measures should be taken depending on the injected dose.

Strict adherence to instructions regarding preparation and disposal of the medication is essential.