Xeomin 1 00 IU 1 Vial

Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

· Keep this leaflet. You may need to read it again.

· If you have any further questions, ask your doctor or pharmacist.

· This medicine has been prescribed for you personally. Do not give it to others. It may harm them, even if their signs of illness are the same as yours.

· If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What does this leaflet contain?

1. What is XEOMIN 100 units, powder for solution for injection and what is it used for?

2. What you need to know before you use XEOMIN 100 units, powder for solution for injection?

3. How to use XEOMIN 100 units, powder for solution for injection?

4. What are the possible side effects?

5. How to store XEOMIN 100 units, powder for solution for injection?

6. Package contents and other information.

1. WHAT IS XEOMIN 100 units, powder for solution for injection AND WHAT IS IT USED FOR?  

Pharmacotherapeutic group: M03AX01

XEOMIN 100 units, powder for solution for injection is a medicine that contains as active ingredient Botulinum Neurotoxin Type A which relaxes the injected muscles or reduces salivary flow depending on the site of administration.

XEOMIN 100 units, powder for solution for injection is used in adults for the treatment of:

· eyelid spasm (blepharospasm) and spasm affecting one side of the face (hemifacial spasm)

· spasmodic torticollis

· muscle hyperactivity or uncontrollable stiffness of the muscles of the shoulder, arm and/or hand. (upper limb spasticity)

· excess saliva (sialorrhea) due to neurological disorders.

XEOMIN is indicated for the symptomatic treatment of children and adolescents aged 2 to 17 years and weighing ≥ 12 kg.

· excess salivation (sialorrhea) due to neurological disorders / neurodevelopmental disorders

2. WHAT YOU NEED TO KNOW BEFORE YOU USE XEOMIN 100 units, powder for solution for injection?  

Never use XEOMIN 100 units, powder for solution for injection:

· if you are allergic to botulinum neurotoxin type A or any of the other ingredients of this medicine (listed in section 6);

· if you suffer from generalized disorders of muscle activity (e.g. myasthenia gravis, Lambert-Eaton syndrome);

· if you have an infection or inflammation at the injection site.

Warnings and precautions

In case of poorly targeted injection of botulinum neurotoxin type A, adverse effects temporarily paralyzing the muscles near the injection site may be observed. These adverse effects, related to a real diffusion of the toxin away from the injection site, have been very rarely reported (e.g., excessive muscle weakness, difficulty or disorders of swallowing causing false passage of drinks or food into the airways). Patients treated at the recommended doses may experience excessive muscle weakness.

If the dose is too high or the injections are given too frequently, the risk of antibody formation may be increased. Antibody formation can cause treatment failure with botulinum toxin type A, regardless of its indication.

Talk to your doctor or pharmacist before any treatment with XEOMIN 100 units, powder for solution for injection:

· if you suffer from any type of bleeding disorder;

· if you are receiving substances that prevent blood clotting such as coumarins, heparin, aspirin or clopidogrel;

· if you suffer from severe weakness or a decrease in the volume of the muscle into which the injections are given;

· if you have amyotrophic lateral sclerosis (ALS) which can cause widespread muscle wasting;

· if you suffer from other diseases that affect the nerves and skeletal muscles (peripheral neuromuscular dysfunction);

· if you have or have had difficulty swallowing;

· if you suffer or have suffered from seizures

· if you have had problems in the past with botulinum toxin type A injections;

· if you are going to have surgery.

Contact your doctor immediately for medical supervision if you experience any of the following symptoms:

· difficulty breathing, swallowing, or speaking.

· if you experience hives, swelling, including of the face or throat, wheezing, feeling faint, shortness of breath (possible symptoms of a severe allergic reaction).

Repeated injections of XEOMIN 100 units, powder for solution for injection

In case of repeated injections, the therapeutic effect of XEOMIN 100 units, powder for solution for injection may vary. Possible reasons for an increase or decrease in effectiveness may result from:

· differences in the technique of reconstitution of the solution by your doctor;

· differences in treatment intervals;

· injections into other muscles;

· very small differences in the effectiveness of the active substance of XEOMIN 100 units, powder for solution for injection ;

· lack of response or therapeutic failure.

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

Please inform your doctor before any treatment with XEOMIN 100 units, powder for solution for injection , if you:

· have had eye surgery. Your doctor will take the necessary precautions.

· are at risk of developing a condition called angle-closure glaucoma. This condition can cause increased intraocular pressure and damage the optic nerve. Your doctor will know if you are at risk.

During treatment, small bleeding points may occur on the eyelid. Your doctor can limit these by immediately applying gentle pressure to the injection site.

After injecting XEOMIN 100 units, powder for solution for injection into the muscles around your eye, blinking may be slowed. This can lead to prolonged exposure of part of the eye (the cornea). This exposure can damage the surface of the eye and cause inflammation (corneal ulceration).

Spasmodic torticollis

You may experience swallowing difficulties of varying severity. This can cause breathing difficulties and a higher risk of choking. Foreign substances inhaled into your lungs can cause inflammation or infection (pneumonia). Your doctor will give you special medical treatment if necessary (e.g., artificial feeding).

Swallowing difficulties can last up to two to three weeks after the injection (up to five months for one patient).

If you have been inactive for a long time, all activity should be resumed gradually after injecting XEOMIN 100 units, powder for solution for injection .

Muscle hyperactivity or uncontrollable muscle stiffness

XEOMIN 100 units, powder for solution for injection can be used to treat muscle overactivity or uncontrollable stiffness in parts of the upper limbs such as the arm or hand. XEOMIN 100 units, powder for solution for injection is effective in combination with standard treatments. XEOMIN 100 units, powder for solution for injection should be used in combination with these other treatments.

This medication is unlikely to improve joint movement if the muscle surrounding them has lost its ability to stretch.

If you have been inactive for a long time, all activity should be resumed gradually after injecting XEOMIN 100 units, powder for solution for injection .

Excess saliva (salivation)

Certain medications (clozapine, aripiprazole, pyridostigmine) can cause excessive saliva production. To begin with, the possibility of replacing, reducing, or even stopping the offending medication should be considered before using XEOMIN as a treatment for excessive salivation. The use of XEOMIN to reduce drug-induced salivation has not been studied.

If cases of dry mouth develop in association with the administration of XEOMIN, your doctor will consider a dose reduction.

When your saliva flow is reduced by XEOMIN, oral health problems such as tooth decay may develop or existing problems may progress. Contact a dentist when you start using XEOMIN to treat excess saliva. If necessary, your dentist may decide to take measures to prevent cavities.

Children and adolescents

Do not administer this medicine to children under 2 years of age, children weighing less than 12 kg, and children and adolescents for treatments other than excess saliva as the use of XEOMIN has not been established in this population and is therefore not recommended.

Other medicines and XEOMIN 100 units, powder for solution for injection

If you are taking, have recently taken or might take any other medicines, tell your doctor or pharmacist.

The effect of XEOMIN 100 units, powder for solution for injection may be increased:

· by drugs indicated to treat certain infections such as spectinomycin or antibiotics from the aminoglycoside group (e.g. neomycin, kanamycin, tobramycin);

· by other medicines that relax muscles, such as tubocurarine muscle relaxants. These products are used, for example, during anesthesia. Before any surgery, inform your anesthesiologist of your treatment with XEOMIN 100 units, powder for solution for injection.

· by other medicines that themselves reduce saliva flow (e.g., anticholinergics such as atropine, glycopyrronium, or scopolamine) or by therapeutic irradiation of the head and neck, including the salivary glands when used for the treatment of excess saliva. Tell your doctor if you are receiving or are planning to have radiotherapy.

In these cases, XEOMIN 100 units, powder for solution for injection should be used with caution.

The effect of XEOMIN 100 units, powder for solution for injection may be reduced by:

· certain antimalarial/antirheumatic drugs (amino-4-quinolines).

XEOMIN 100 units, powder for solution for injection with food and drink

Not applicable.

Pregnancy and breastfeeding and fertility

If you are pregnant, breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

XEOMIN 100 units, powder for solution for injection should not be used during pregnancy unless your doctor considers it necessary and the potential benefit justifies the possible risk to the fetus.

XEOMIN 100 units, powder for solution for injection should not be used during breastfeeding.

Driving vehicles and using machines

You should not drive or engage in potentially hazardous activities if you experience drooping eyelids, weakness (asthenia), muscle weakness, or vision disturbances. If in doubt, seek medical advice.

XEOMIN 100 units, powder for solution for injection contains sucrose and human albumin

3. HOW TO USE XEOMIN 100 units, powder for solution for injection?  

XEOMIN 100 units, powder for solution for injection should only be administered by physicians experienced in the use of botulinum toxin type A.

The optimal dose, frequency, and number of injection sites will be specifically determined by your doctor. The results of an initial treatment with XEOMIN 100 units, powder for solution for injection should be evaluated and may lead to dose adjustments until the desired therapeutic effect is achieved. Treatment intervals will be determined by your doctor based on your actual clinical needs.

If you feel that the effect of XEOMIN 100 units, powder for solution for injection is too strong or too weak, inform your doctor. If no therapeutic effect appears, another treatment should be considered.

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

The recommended initial dose is a maximum of 25 units per eye, and the total recommended dose for subsequent treatment sessions is a maximum of 50 units per eye. Generally, the first effects are observed within four days of the injection. The effect of each treatment lasts approximately 3 to 5 months; however, it may last more or less. A treatment interval of less than 12 weeks is not recommended.

Normally, there is no benefit in treating more often than every 3 months.

If you have spasms affecting one side of your face (hemifacial spasm), your doctor will follow the treatment recommendations for eyelid spasm (blepharospasm) limited to one side of the face. Spasm affecting one side of your face (hemifacial spasm) will only be treated in the upper part of the face, as XEOMIN injections in the lower part of the face may increase the risk of side effects, such as a pronounced risk of local weakness.

Torticollis sp a semodic

The recommended dose per injection site is a maximum of 50 units, and the maximum recommended dose for the first treatment session is 200 units. Doses up to 300 units may be indicated by your doctor for subsequent sessions depending on the response to treatment. Generally, the first effects are observed within seven days after the injection. The effect of each treatment lasts approximately 3 to 4 months; however, it may last more or less. Although treatment intervals of less than 10 weeks are not recommended, treatment intervals will be individually adapted by your doctor to your actual needs.

Muscle hyperactivity or uncontrollable stiffness of the muscles of the shoulder, arm or hand (upper limb spasticity).

The maximum recommended dose is 500 units per treatment and should not exceed 250 units in the shoulder muscles. Patients have noted clinical efficacy within 4 days with improvement in muscle tone within 4 weeks following the injection. As the treatment effect persists, generally 12 weeks, reinjections can be spaced at least 12 weeks apart. However, it can be shorter or longer, therefore, treatment intervals will be individually adapted by your doctor to your actual needs.

Excess saliva (salivation, adults)

The recommended dose is 100 units per treatment session. This maximum dose should not be exceeded. Although treatment intervals of less than 16 weeks are not recommended, treatment intervals should be tailored to your actual, individual clinical needs.

Excess saliva (salivation, 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.

Mode of administration

XEOMIN 100 units powder for solution for injection is intended for injection into the muscle (intramuscular route) and into the salivary glands (intraglandular use) (see information for healthcare professionals at the end of this leaflet). For gland location, in adults, both anatomical location and ultrasound guidance are possible; however, ultrasound guidance should be preferred for reasons of effectiveness. In children and adolescents, ultrasound guidance should be used.

Before the injection, children and adolescents may receive a local anesthetic (such as an anesthetic cream), a sedative, or an anesthetic combined with a sedative.

If you use more XEOMIN 100 units, powder for solution for injection than you should:

Consult your doctor or pharmacist immediately.

Overdose symptoms

Symptoms of overdose do not appear immediately after injection and may include generalized weakness, drooping of the eyelids, double vision, difficulty breathing or speaking, paralysis of the respiratory muscles, or difficulty swallowing, which may lead to pneumonia.

Measures in case of overdose

If you experience symptoms of an overdose, contact emergency medical services immediately or ask someone to do so for you and seek hospitalization. Medical monitoring for several days and respiratory support may be necessary.

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

If you forget to use XEOMIN 100 units, powder for solution for injection:

Not applicable.

If you stop using XEOMIN 100 units, powder for solution for injection:

Not applicable.

4. WHAT ARE THE POSSIBLE SIDE EFFECTS?  

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Generally, adverse reactions occur within the first week after treatment and are transient in nature. They may be due to the drug, the injection technique, or both. Effects may be limited to the area around the injection site (e.g., localized muscle weakness, local pain, inflammation, tingling and pins and needles (paresthesia), decreased sensitivity to touch (hypoesthesia), tenderness, swelling (general), soft tissue swelling (edema), skin reddening (erythema), pruritus, localized infection, hematoma, hemorrhage, bleeding, or bruising).

The sting may be painful. Pain or anxiety from the sting may cause 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 muscle relaxation at the site of injection of XEOMIN 100 units, powder for solution for injection . Difficulty swallowing may cause aspiration, which can lead to inflammation of the lungs and, in some cases, death.

Allergic reactions with XEOMIN 100 units, powder for solution for injection may occur. Severe and/or immediate allergic reactions (anaphylaxis) or allergic reactions to the albumin contained in this medicine (serum sickness) which may, for example, cause breathing difficulties (dyspnea), hives or swelling of soft tissues (oedema), have been reported rarely. Some of these reactions have been observed following treatment with conventional botulinum toxin type A 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 side effects, contact an emergency service immediately or ask those around you to do so.

The following side effects have been noted with XEOMIN 100 units, powder for solution for injection :

Eyelid spasm (blephosis spasm )

Very common (may affect more than 1 in 10 people): drooping of the eyelid (ptosis)

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

Uncommon (may affect up to 1 in 10 people): Headache, facial muscle weakness (facial paresis), double vision (diplopia), increased tearing , difficulty swallowing (dysphagia), fatigue, muscle weakness, rash

Spasm affecting one side of the face (hemifacial spasm)

Side effects similar to those of eyelid spasm can be expected when treating spasms affecting one side of the face.

Neck torsion (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, muscle pain (myalgia), muscle stiffness, muscle spasms, headache, dizziness, injection site pain, weakness (asthenia), dry mouth, nausea, excessive sweating (hyperhidrosis), upper respiratory tract infection, feeling unwell (presyncope).

Uncommon (may affect up to 1 in 100 people): speech disorders, dysphonia, slowed breathing (dyspnea), rash.

Treatment of spasmodic torticollis can cause swallowing difficulties of varying severity, which can lead to aspiration and require medical intervention. Swallowing difficulties can persist for up to two to three weeks after injection (five months reported in one case). These swallowing difficulties appear to be dose-related.

Muscle hyperactivity or uncontrollable stiffness of the muscles of the shoulder, arm or hand (upper limb spasticity).

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

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

Frequency unknown (cannot be estimated based on current data) : injection site pain

Some of these adverse events may be due to the disease.

Excess saliva (sialorrhea) in adults

Common (may affect up to 1 in 10 people): dry mouth, difficulty swallowing (dysphagia), pins and needles sensation (paraesthesia)

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

Cases of persistent dry mouth (> 110 days) of severe intensity have been reported, which could lead to other complications such as inflammation of the gums (gingivitis), difficulty swallowing (dysphagia) and cavities.

Excessive salivation (sialorrhoea) in children/adolescents

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

Unknown (cannot be estimated from the available data): dry mouth, thickened saliva, mouth pain, tooth decay

Post-market experience

Since XEOMIN was marketed, the following adverse reactions have been reported at an unknown frequency: flu-like symptoms, decrease in the volume of the injected muscle and hypersensitivity reactions, such as swelling, soft tissue edema (also distant from the injection site), redness, itching, rash (localized or generalized) and breathing difficulties.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centers – Website: https://signalement.social-sante.gouv.fr/ .

By reporting side effects you can help provide more information on the safety of this medicine.

5. HOW TO STORE XEOMIN 100 units, powder for solution for injection?  

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

Do not use this medicine after the expiry date which is stated on the carton and bottle after the word “EXP”. The expiry date refers to the last day of that month.

Closed bottle: store at a temperature not exceeding 25°C

Reconstituted solution : Physical and chemical stability in use has been demonstrated for 24 hours between 2°C and 8°C.

From a microbiological point of view, the product must be used immediately. Otherwise, the storage time and conditions of the reconstituted solution are the responsibility of the user and should not exceed 24 hours at a temperature between +2°C and +8°C, unless reconstitution has been carried out under controlled and validated aseptic conditions.

Your doctor should not use XEOMIN 100 units, powder for solution for injection if the reconstituted solution is cloudy or contains visible particles.

The procedure for disposal is given at the end of this leaflet, in the section reserved for healthcare professionals.

6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION  

What XEOMIN 100 units, powder for solution for injection contains  

· The active substance is:

Clostridium botulinum neurotoxin type A (150 kD), without complexing proteins.

XEOMIN 100 units powder for solution for injection

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

*Botulinum neurotoxin type A, purified from cultures of Clostridium botulinum (Hall strain)

· The other ingredients are: human albumin, sucrose.

What XEOMIN 100 units, powder for solution for injection looks like and contents of the outer packaging  

XEOMIN 100 units, powder for solution for injection is presented as a powder for solution for injection. The powder is white.

Reconstitution of the powder gives a clear, colorless solution.

Boxes of 1, 2, 3, 4 and 6 bottles.

Not all presentations may be marketed.

Marketing Authorisation Holder  

MERZ PHARMACEUTICALS GMBH

ECKENHEIMER LANDSTRASSE 100

60318 FRANKFURT / MAIN

GERMANY

Marketing Authorization Operator  

MERZ PHARMA FRANCE

EQHO TOWER

2, AVENUE GAMBETTA

92400 COURBEVOIE

Manufacturer  

MERZ PHARMA GMBH & CO. KGAA

ECKENHEIMER LANDSTRASSE 100

60318 FRANKFURT / MAIN

GERMANY

Names of the medicine in the member states of the European Economic Area  

This medicine is authorized in the member states of the European Economic Area under the following names: In accordance with current regulations.

[to be completed later by the holder]

The last date this notice was revised

[to be completed later by the holder]

{month YYYY}.

Others  

Detailed information on this medicine is available on the ANSM (France) website.

The following information is intended exclusively for healthcare professionals:

Instructions for reconstituting the solution

XEOMIN 100 units, powder for solution for injection is reconstituted before use with sodium chloride 9 mg/ml (0.9%) solution for injection.

XEOMIN 100 units, powder for solution for injection should be used to treat a single patient during a single session.

It is good practice to reconstitute the product and prepare syringes on plastic-lined paper supports to accommodate any accidental spillage. An appropriate volume of sodium chloride is drawn into a syringe (see dilution table). A short, beveled 20-27G needle is recommended for reconstitution. After vertical insertion of the needle through the rubber stopper, the solvent is gently injected into the vial to avoid foaming. Discard the vial if the vacuum does not draw the solvent into the vial. Remove the syringe from the vial and gently mix XEOMIN 100 units, powder for solution for injection with the solvent by circular movements and by inverting the vial. Do not mix vigorously. If necessary, the needle used for reconstitution of the solution may remain in the vial. The required volume of product is drawn into a new sterile syringe suitable for injection.

The reconstituted solution of XEOMIN 100 units, powder for solution for injection is clear and colorless.

XEOMIN 100 units, powder for solution for injection should not be used if the reconstituted solution (prepared as described above) appears cloudy or contains particles or flaky molecules.

To prevent accidental overdose, care should be taken when reconstituting the product to ensure that the volume of solvent is appropriate for the selected presentation. If different presentations are used during the same injection session, it should be ensured that the volume of solvent used when reconstituting the product provides the correct number of units per 0.1 ml. The volume of solvent to be added differs between XEOMIN 50 units, XEOMIN 100 units and XEOMIN 200 units. Each syringe used must be identified accordingly.

The possible concentrations for XEOMIN 100 units are shown in the following table:

Precautions for disposal

Any reconstituted solution that has been stored for more than 24 hours and any remaining or unused portion of injectable solution must be discarded.

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

Any unused vial or vial containing reconstituted solution and/or syringes may be autoclaved

It is also possible to inactivate any remaining fraction of XEOMIN 100 units, powder for solution for injection by adding 70% ethanol, 50% isopropanol, 0.1% sodium lauryl sulfate (anionic detergent), dilute sodium hydroxide solution (0.1 N NaOH) or dilute sodium hypochlorite solution (at least 0.1% NaOCl).

Used bottles, syringes and materials must not be emptied but must be disposed of in suitable containers and in accordance with local regulations.

Recommendations in the event of an incident when handling botulinum toxin type A

Any spillage should be wiped up with absorbent material soaked in one of the solutions listed above for the powder or with dry absorbent material for the reconstituted product.

Contaminated surfaces are cleaned with absorbent material, soaked in one of the solutions listed above and then dried.

If the bottle is broken, proceed as indicated above to carefully collect the glass particles and wipe off the product, avoiding any skin cuts.

In case of skin contact, rinse the affected area thoroughly with water.

In case of contact with eyes, rinse thoroughly with water or eye wash solution.

If the product comes into contact with a wound, cut or puncture, rinse thoroughly with water and take appropriate medical measures depending on the dose injected.

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