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, as it contains
important information for the patient.

• 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, tell your doctor or pharmacist. See section 4.

Leaflet contents:

1. What XEOMIN is and what it is 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 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 secretion.
XEOMIN is used to treat the following conditions in adults:

• Blepharospasm (involuntary eyelid muscle contractions) and hemifacial spasm (spasm affecting one side of the face),
• Cervical dystonia (spasmodic torticollis),
• Increased muscle tone/involuntary stiffness of the arm, hand and (or) forearm (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 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 planned injection site.

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 disorder,
• if the patient is taking substances that prevent blood clot formation (e.g. coumarin, heparin, acetylsalicylic acid, clopidogrel),
• if the patient has significant 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 muscle atrophy,
• 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 has 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, weakness, 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 of the injection solution by the physician,
• varying durations of treatment intervals,
• injections into different muscles,
• minor changes in the efficacy of the active substance in XEOMIN,
• lack of response to treatment.

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

• the patient has had eye surgery. The doctor will take additional precautions,
• the patient is at risk of developing 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 hemorrhages (bruising) in the soft tissues of the eyelid may occur during treatment. The doctor may reduce the risk by applying gentle pressure at the injection site immediately after injection.
After injection of XEOMIN into the eye muscle, the frequency of blinking may be reduced, leading to prolonged exposure of the transparent front part of the eye (cornea). This exposure may damage the corneal surface and cause 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 substances in the lungs may cause inflammation or infections (pneumonia). The doctor may initiate special treatment if necessary (e.g. artificial feeding).
Swallowing difficulties may last up to two or three weeks after injection; in one case, they have persisted for up to five months.
If the patient has been inactive for a prolonged period, physical activity should be resumed gradually after injection of XEOMIN.

Increased muscle tone/uncontrolled muscle stiffness
XEOMIN may be used to treat increased muscle tone/uncontrolled stiffness in various parts of the upper limb, such as the hand or forearm.
XEOMIN is effective when used in combination with standard conventional therapies.
XEOMIN should be used together with these other treatments.
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, physical activity should be resumed gradually after injection of XEOMIN.

Chronic sialorrhea (excessive drooling)
Some medicines (e.g. clozapine, aripiprazole, pyridostigmine) may cause excessive saliva production. Consideration should be given primarily to replacing, reducing, or discontinuing the medication causing sialorrhea before using XEOMIN to treat drooling.
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.
Reduced saliva production after XEOMIN administration may lead to oral health problems such as dental caries or worsening of existing conditions.
Before starting XEOMIN treatment for chronic sialorrhea, consult a dentist. The dentist may decide to implement preventive measures against dental caries 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. For this reason, 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 plans to take.
The effect of XEOMIN may be increased by:

• medicines used in certain infectious diseases (spectinomycin or aminoglycoside antibiotics [e.g. neomycin, kanamycin, tobramycin]),
• other medicines that relax muscles (e.g. muscle relaxants such as tubocurarine). Such medicines 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 medicines 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 reduced 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 ptosis (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 by the physician
individually 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, and the total recommended dose
for subsequent treatments is up to 50 units per eye. The onset of effect is usually observed
within four days after injection. The effect lasts after each treatment for approximately 3–5 months,
but may last significantly longer or shorter. The interval between treatment sessions should not be
shorter than 12 weeks.
More frequent administration 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 treatment of 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 a pronounced risk of 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 administer doses up to 300 units
in subsequent sessions, depending on the response to treatment. The onset of effect is usually observed
within seven days after injection. The effect lasts after each treatment typically for 3–4 months,
but 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 feeling the onset of effect
within 4 days after administration. Reduction in muscle tone was felt within 4 weeks. Generally, the therapeutic 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 (into the 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. topical anaesthetic cream), a sedative, or anaesthesia in combination with a sedative.

Administration of a higher than recommended dose of XEOMIN

Symptoms of overdose
Symptoms of overdose do not occur immediately after injection and may include generalised weakness,
ptosis (drooping eyelid), double vision, respiratory disorders, speech disturbances, and paralysis of respiratory muscles or swallowing disorders, 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, consult your doctor, pharmacist or nurse.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although they do not occur in everyone.
Adverse reactions usually occur during the first week after treatment
and are transient in nature. Adverse reactions may be related to the medicine, the injection procedure, or both.
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), skin redness (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 difficulties may result from reduced muscle tone in areas distant from the injection site of XEOMIN.
Swallowing difficulties may lead to aspiration of foreign material into the respiratory tract, resulting in pneumonia, sometimes leading to death.
The medicine XEOMIN may cause an allergic reaction. Rarely, severe and/or sudden allergic reactions (anaphylactic shock) or serum sickness-type reactions to components present in the medicine (serum sickness) have been reported, causing, for example, breathing difficulties (dyspnea), rash (urticaria), or soft tissue swelling (edema). Some of these reactions occurred after administration of conventional botulinum toxin type A complex. These occurred when the toxin was administered 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, mouth, 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 those nearby and go to the emergency department of the nearest hospital.
The following adverse reactions have been observed during treatment with XEOMIN.
Blepharospasm (eyelid spasm)
Very common (may occur in more than 1 in 10 patients):
Ptosis (drooping eyelid)
Common (may occur in up to 1 in 10 patients):
Dry eye syndrome, blurred vision, visual disturbance, dry mouth, injection site pain
Uncommon (may occur in up to 1 in 100 patients):
Headache, facial muscle weakness (facial nerve paralysis), double vision, excessive tearing, swallowing difficulties (dysphagia), fatigue, muscle weakness, 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 difficulties (dysphagia)
Common (may occur in up to 1 in 10 patients):
Neck pain, muscle weakness, musculoskeletal pain (muscle pain), muscle and joint stiffness, muscle spasm, headache, dizziness, injection site pain, 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), rash
Treatment of spasmodic torticollis may cause swallowing difficulties of varying severity. This may lead to aspiration of foreign material into the lungs, which may require medical intervention. Swallowing difficulties may persist for two to three weeks after injection, but one case of persistence for five months has been reported. The occurrence of swallowing difficulties appears to be dose-dependent.
Increased muscle tone/uncontrolled stiffness of arms, hands or forearms (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 difficulties (dysphagia), nausea
Frequency not known (frequency cannot be estimated from available data):
Injection site pain
Chronic drooling (sialorrhea) in adults
Common (may occur in up to 1 in 10 patients):
Dry mouth, swallowing difficulties (dysphagia), prickling and tingling sensations (paresthesias)
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 difficulties, and dental caries.
Chronic drooling (sialorrhea) in children and adolescents
Uncommon (may occur in up to 1 in 100 patients):
Swallowing difficulties (dysphagia)
Frequency not known (frequency cannot be estimated from available data):
Dry mouth, thickened saliva, oral pain, dental caries
Post-marketing experience
After marketing authorization, the following adverse reactions of unknown frequency have been observed during 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, including in areas distant from the injection site), redness, itching, 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 Adverse Drug Reactions of the 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 marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store 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 specified month.
The batch number printed on the packaging is indicated by the abbreviation "Lot".
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 storage conditions and duration prior to use lies with the user and should not exceed 24 hours at a temperature of 2°C to 8°C, unless reconstitution was carried out under strictly controlled aseptic conditions.
The physician should not use XEOMIN if the solution is cloudy or contains undissolved particles.
For information on disposal of unused medicine, please see the section intended for healthcare professionals at the end of this leaflet.

6. Contents of the package 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 European Economic Area countries 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

Information intended exclusively for healthcare professionals:

Instructions for preparation of injection solution:
XEOMIN must be prepared prior to 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 includes preparing the solution and assembling the syringe over a paper towel covered with foil, in case of accidental spillage of the medication. Draw up the appropriate volume of sodium chloride solution into the syringe (see dilution table). A short-bevelled needle of 20–27 G is recommended 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 under vacuum. Detach the syringe from the vial and mix XEOMIN with the diluent by gently shaking and rotating the vial/tapping it—avoid vigorous movements. If necessary, the needle used for reconstitution should 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 required 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

The injection solution stored for longer than 24 hours and any 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 may 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 in 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 spillage of the medication must be immediately cleaned up: in the case of powder, using an absorbent material soaked in one of the above-mentioned solutions; in the case of reconstituted medication, using dry absorbent material.
• Contaminated surfaces should be wiped with an absorbent material soaked in one of the above-mentioned solutions, then dried.
• If a vial is broken, follow the above instructions. 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 fissure, wash the area thoroughly with large amounts of water. Appropriate medical measures should be taken depending on the administered dose.

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