BOCOUTURE 100 units powder for injectable solution

2. What you need to know before you are given BOCOUTURE

Do not use BOCOUTURE

• if you are allergic to botulinum toxin type A or any of the other ingredients of this medicine (listed in section 6)
• if you have a generalized disorder of muscle activity (e.g. myasthenia gravis, Lambert-Eaton syndrome)
• if you have an infection or inflammation at the proposed injection site

Warnings and precautions

Adverse effects due to poorly placed injections of botulinum toxin type A may occur, which temporarily paralyze nearby muscle groups. In very rare cases, side effects related to the spread of the toxin to distant sites from the injection site have been reported, producing symptoms consistent with the effects of botulinum toxin type A (e.g. excessive muscle weakness, difficulty swallowing or accidental introduction of food or drink into the airways). Patients who receive the recommended doses may experience excessive muscle weakness.

Contact your doctor and seek immediate medical attention if you experience any of the following effects:

• difficulty breathing, swallowing, or speaking
• hives, swelling including swelling of the face or throat, wheezing, feeling of fainting, and difficulty breathing (possible symptoms of severe allergic reactions) (see section 4).

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

Tell your doctor before using BOCOUTURE:

• if you have any bleeding disorder of any kind
• if you are being treated with substances that prevent blood clotting (e.g. coumarin, heparin, acetylsalicylic acid, clopidogrel)
• if you have pronounced weakness or decreased muscle volume in the muscle where you will receive the injection
• if you have amyotrophic lateral sclerosis (ALS), which can lead to generalized muscle weakness
• if you have any disorder that affects the interaction between nerves and skeletal muscles (peripheral neuromuscular disorder)
• if you have had difficulty swallowing
• if you have had problems in the past with botulinum toxin type A injections
• if you are going to undergo any type of surgery

Repeated injections with BOCOUTURE

If you have received repeated injections with BOCOUTURE, the effect may increase or decrease. The possible reasons for this are:

• your doctor may follow a different procedure when preparing the injection solution
• different treatment intervals
• injections in another muscle
• absence of response/failure of therapy during the treatment session

Elderly patients

There is limited information on the treatment of patients over 65 years of age. Therefore, BOCOUTURE should not be used in patients over 65 years of age.

Children and adolescents

Do not give this medicine to children or adolescents under 18 years of age because the use of BOCOUTURE is not recommended in children or adolescents.

Other medicines and BOCOUTURE

Tell your doctor or pharmacist if you are taking, have recently taken, or might take other medicines.

The effect of BOCOUTURE may be enhanced by:

• medicines used to treat certain infectious diseases (e.g. spectinomycin or aminoglycoside antibiotics [e.g. neomycin, kanamycin, tobramycin])
• other muscle relaxants (e.g. tubocurarine-type muscle relaxants). These medicines are used, for example, in general anesthesia. Before undergoing surgery, tell your anesthesiologist if you have received BOCOUTURE.

In these cases, BOCOUTURE should be used with caution.

The effect of BOCOUTURE may be reduced by certain medicines for malaria and rheumatism (known as aminoquinolines).

Pregnancy, breastfeeding, and fertility

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

BOCOUTURE should not be used during pregnancy unless clearly necessary and the potential benefit of treatment outweighs the possible risk to the fetus. BOCOUTURE is not recommended during breastfeeding.

Driving and using machines

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

In case of doubt, consult your doctor.

3. How to use BOCOUTURE

BOCOUTURE can only be administered by healthcare professionals with experience in the application of botulinum toxin type A.

Vertical Frown Lines produced at maximum frown (Glabellar Lines)

The usual total dose for the treatment of vertical frown lines produced at maximum frown (glabellar lines) is 20 units. Your doctor will inject 4 units into each of the 5 injection points. Your doctor may increase the total dose up to 30 units if required by the individual needs of the patient, with at least 3 months between treatments.

Improvement in vertical frown lines produced at maximum frown is generally observed within 2 or 3 days, with the maximum effect observed on day 30. The effect lasts up to 4 months after injection.

Lateral Periorbital Lines produced at maximum smile (Crow's Feet)

For the treatment of lateral periorbital lines (crow's feet), your doctor will inject a standard dose of 24 units (12 units per eye). 4 units will be applied bilaterally to each of the 3 injection sites.

Improvement in lateral periorbital lines produced at maximum smile is generally observed within 6 days, with the maximum effect observed on day 30. The effect lasts up to 4 months after injection.

Horizontal Forehead Lines produced at maximum contraction

When treating horizontal forehead lines produced at maximum contraction, your doctor will use a dose within the range of 10 to 20 units, according to the individual needs of the patient. The recommended total dose of 10 to 20 units will be injected into the five horizontally aligned injection points (2 units, 3 units, or 4 units per injection point, respectively).

A reduction in horizontal forehead lines produced at maximum contraction is usually observed within 7 days, with the maximum effect observed on day 30. The effect lasts up to 4 months after injection.

Method of administration

Reconstituted BOCOUTURE is injected intramuscularly (intramuscular use, see information for healthcare professionals at the end of this leaflet).

The interval between two treatments should not be less than 3 months.

If you are given more BOCOUTURE than you should

Symptoms of overdose:

Symptoms of overdose may not be apparent immediately after injection and may include general weakness, eyelid drooping, double vision, difficulty breathing, difficulty speaking, and paralysis of the respiratory muscles or difficulty swallowing, which can result in pneumonia.

Measures to be taken in case of overdose:

In case of overdose, contact the emergency medical services immediately or ask your family members to do so and take you to the hospital. Medical supervision may be necessary for several days, and assisted ventilation may be required.

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

4. Possible side effects

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

An allergic reaction may occur with BOCOUTURE. Rarely, immediate and/or severe allergic reactions (anaphylaxis) or allergic reactions to the product serum (serum sickness), which cause, for example, difficulty breathing (dyspnea), hives (urticaria), or soft tissue swelling (edema), have been reported. Some of these reactions have been observed after the use of conventional botulinum toxin type A complex. They occurred when the toxin was administered alone or in combination with other products known to cause similar reactions. These effects cannot be completely ruled out when using BOCOUTURE.

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 hands, feet, or ankles.

If you notice any of these side effects, please inform your doctor immediately or ask your family members to do so and go to the emergency medical services of the nearest hospital.

Normally, side effects occur in the first week after injection and are of a transient nature. Adverse effects may be related to the medicine, the injection technique, or both. At the injection site, the action of botulinum toxin type A causes localized muscle weakness. Eyelid drooping may occur due to the injection technique and the effect of the medicine.

The following reactions may occur around the injection site:

• Localized pain
• Inflammation
• Tingling
• Numbness
• Sensitivity
• Itching
• General inflammation
• Soft tissue swelling (edema)
• Redness of the skin (erythema)
• Localized infection
• Hematoma
• Bleeding
• Bruising

Patient with a fear of injections or pain related to the needle may experience generalized transient reactions, such as:

• Fainting
• Circulatory problems
• Nausea
• Ringing in the ears

Other possible side effects

The following adverse effects have been observed with BOCOUTURE:

Vertical Frown Lines produced at maximum frown (Glabellar Lines)

Frequent (may affect up to 1 in 10 patients):

• Headache
• Mephisto effect (lateral elevation of the eyebrows)

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

• Nasopharyngitis
• Bronchitis
• Flu-like symptoms
• Eye brow drooping, eye brow ptosis
• Eyelid drooping (eyelid ptosis)
• Swelling of the eyelids (eyelid edema)
• Discomfort (feeling of heaviness of the eyelid/eyebrow)
• Blurred vision
• Muscle spasms
• Asymmetry of the eyebrow
• Feeling of pressure at the injection site
• Fatigue
• Pain or bruising at the injection site
• Itching
• Hematoma
• Skin nodules
• Insomnia

Lateral Periorbital Lines produced at maximum smile (Crow's Feet)

Frequent (may affect up to 1 in 10 patients):

• Eyelid inflammation
• Dry eye
• Hematoma at the injection site

Upper Facial Lines

Frequent (may affect up to 1 in 10 patients)

• Headaches
• Hematoma at the injection site

Uncommon (may affect up to 1 in 10 patients)

• Numbness
• Discomfort (feeling of heaviness of the frontal area)
• Eyelid edema
• Eyelid drooping (eyelid ptosis)
• Dry eye
• Eye brow drooping (eye brow ptosis)
• Facial asymmetry
• Mephisto effect (lateral elevation of the eyebrows)
• Nausea

Post-marketing experience

The following adverse reactions have been reported with an unknown frequency for the use of BOCOUTURE since its launch, regardless of the treated area:

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

The following adverse effects have been very rarely observed during treatment with botulinum toxin type A for conditions other than the treatment of upper facial lines (see section 2):

• Excessive muscle weakness
• Difficulty swallowing
• Difficulty swallowing causing inhalation of foreign bodies, which can lead to lung inflammation and, in some cases, death

These adverse effects are caused by the relaxation of muscles distant from the injection site.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of BOCOUTURE

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 on the label of the vial after “EXP”. The expiry date is the last day of the month shown.

Unopened vial: Do not store above 25°C.

Reconstituted solution: Chemical and physical stability has been demonstrated for 24 hours at 2°C to 8°C.

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

Your doctor should not use BOCOUTURE if the solution appears cloudy or contains visible particles.

Do not throw away any medicines via wastewater or household waste.

Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Container contents and additional information

BOCOUTURE composition

• The active substance is botulinum toxin type A (150 kD), without complexing proteins.

BOCOUTURE 50 units

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

BOCOUTURE 100 units

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

• The other components are: human albumin, sucrose.

Appearance of the product and container contents

BOCOUTURE is presented as a powder for solution for injection (powder for injection). The powder is white.

When dissolved, BOCOUTURE is a clear and colorless solution.

Packaging of 1, 2, 3 or 6 vials.

Only some presentations may be marketed.

Marketing authorization holder

Merz Pharmaceuticals GmbH

Eckenheimer Landstraße 100

60318 Frankfurt am Main

Germany

–

Manufacturer

Merz Pharma GmbH & Co. KgaA

Legal address:

Eckenheimer Landstraße 100

60318 Frankfurt am Main

Germany

Manufacturing address:

Ludwigstraße 22

64354 Reinheim

Germany

Local representative

Merz Aesthetics Iberia, S.L.U.

Calle de Anabel Segura 14, Planta 2 Núcleo 1

28108 Alcobendas

Madrid

Date of the last revision of this prospectus: June 2025

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This information is intended solely for healthcare professionals:

Instructions for the reconstitution of the solution for injection:

BOCOUTURE is reconstituted before use with sodium chloride 9 mg/ml (0.9%) solution for injection.

BOCOUTURE can only be applied for the intended use, to treat a single patient and for one session.

It is recommended to carry out the reconstitution of the vial and the preparation of the syringe on paper towels with a plastic coating to collect any possible spilled material. With a syringe, an adequate amount of sodium chloride solution is extracted. A short-bevel needle of 20-27 G (gauges) is recommended for reconstitution. After the vertical insertion of the needle through the rubber stopper, the solvent is carefully injected into the vial in order to avoid foam formation. The vial must be discarded if the vacuum does not aspirate the solvent into the vial. Remove the syringe from the vial and mix BOCOUTURE with the solvent by gently shaking and inverting/turning the vial, do not shake vigorously. If necessary, the needle used for reconstitution should remain in the vial and the required amount of solution should be extracted with a new sterile needle suitable for injection.

Reconstituted BOCOUTURE is a clear and colorless solution.

BOCOUTURE should not be used if the reconstituted solution (prepared according to the above instructions) has a cloudy appearance or if it contains flocculated material or particles.

Possible dilutions for BOCOUTURE 50 and 100 units are indicated in the following table:

Instructions for disposal

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

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

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

After inactivation, the vials, syringes, and used materials should not be emptied, but should be discarded in suitable containers and eliminated according to local procedures.

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

• Any product residue should be cleaned, either using absorbent material impregnated with any of the above solutions in the 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 solutions and then dried.
• If a vial is broken, proceed as mentioned above, carefully collecting the broken glass pieces and cleaning the spilled product, avoiding skin cuts.
• 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 ophthalmic washing 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 according to the injected dose.

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