Product Information for the User

BOCOUTURE 50Units of Powder for Injectable Solution

BOCOUTURE 100 Units of Powder for Injectable Solution

Toxin Type A Botulinum (150kD), Protein-Free

Read this entire product information carefully before starting to use this medication, as it contains important information for you.

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

1. What is BOCOUTURE and how is it used

2. What you need to know before using BOCOUTURE

3. How to use BOCOUTURE

4. Possible adverse effects

5. Storage of BOCOUTURE

6. Contents of the package and additional information

BOCOUTURE is a medication that contains the active substance botulinum toxin type A, which relaxes the injected muscles.

BOCOUTURE is indicated to temporarily improve facial lines in adults under 65 years of age, when the intensity of these lines has a significant psychological impact on the patient:

• moderate to severe vertical lines between the eyebrows, produced in maximum frowning and/or
• moderate to severe lateral periorbital lines, produced in maximum smiling and/or
• moderate to severe horizontal frontal lines, produced in maximum contraction

No use BOCOUTURE

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

Warnings and precautions

Adverse effects may occur from improperly placed injections of botulinum toxin type A that temporarily paralyze nearby muscle groups. In rare cases, secondary effects have been reported related to the spread of the toxin to distant locations from the injection site, producing symptoms consistent with botulinum toxin type A effects (e.g. excessive muscle weakness, difficulty swallowing or accidental introduction of food or drink into the respiratory tract). Patients receiving 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
• urticaria, swelling including facial or throat swelling, wheezing, feeling of fainting, and difficulty breathing (possible symptoms of severe allergic reactions) (see section 4).

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

Inform your doctor before using BOCOUTURE:

• if you have any type of bleeding disorder
• if you are being treated with substances that prevent blood clotting (e.g. warfarin, heparin, aspirin, clopidogrel)
• if you have pronounced weakness or muscle volume reduction in the muscle where the injection will be administered
• if you have amyotrophic lateral sclerosis (ALS), which may lead to generalized muscle weakness
• if you have any disorder that alters the interaction between nerves and skeletal muscles (peripheral neuromuscular disorder)
• if you have difficulty swallowing
• if you have had problems with botulinum toxin type A injections in the past
• if you are undergoing any type of surgery

Repeated injections with BOCOUTURE

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

• Your doctor may follow a different procedure when preparing the injection solution
• Different treatment intervals
• Injections in another muscle
• Absence of response/treatment failure during the treatment session

Older patients

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

Children and adolescents

Do not administer this medication to children or adolescents under 18 years old because BOCOUTURE is not recommended for use in children or adolescents.

Other medications and BOCOUTURE

Inform your doctor or pharmacist if you are taking, have taken recently, or may take other medications.

The effect of BOCOUTURE may be potentiated by:

• Medications used to treat certain infectious diseases (e.g. spectinomycin or aminoglycoside antibiotics [e.g. neomycin, kanamycin, tobramycin])
• Other medications that relax muscles (e.g. tubocurarine-type muscle relaxants). These medications are used, for example, in general anesthesia. Inform your anesthesiologist if you have received BOCOUTURE before undergoing surgery.

BOCOUTURE should be used with caution in these cases.

The effect of BOCOUTURE may be reduced by certain medications 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 this medication is administered.

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

Driving and operating machinery

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

Consult your doctor if you are unsure.

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

Vertical Lines between the Eyebrows produced at maximum frown (Glabellar Lines)

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

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

Horizontal Lines around the Eyes produced at maximum smile (Crow's Feet)

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

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

Horizontal Lines on the Forehead produced at maximum contraction

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

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

Method of administration

BOCOUTURE dissolved 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 administered more BOCOUTURE than you should

Symptoms of overdose:

Symptoms of overdose are not apparent immediately after injection and may include general weakness, eyelid drooping, double vision, difficulty breathing, difficulty speaking, and paralysis of respiratory muscles or difficulty swallowing that may lead to pneumonia.

Measures to take in case of overdose:

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

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

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

A reaction to BOCOUTURE may occur.Rarely, immediate and/or severe allergic reactions (anaphylaxis) or serum sickness reactions have been reported, which cause, for example, difficulty breathing (dyspnea), hives (urticaria), or swelling of soft tissue (edema). Some of these reactions have been observed after the use of the conventional complex of type A botulinum toxin. 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.

A reaction to BOCOUTURE may cause some 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 notice any of these side effects, please inform your doctor immediately or ask your family members to do so and seek medical attention at 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 type A botulinum toxin causes localized muscle weakness. Drooping of the eyelid 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
• Itching
• Decreased skin sensation
• Sensitivity
• Pruritus
• General inflammation
• Swelling of soft tissue (edema)
• Redness of the skin (erythema)
• Localized infection
• Hematoma
• Bleeding
• Cardinal signs

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

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

Other possible side effects

The following adverse effects have been observed with BOCOUTURE:

Vertical Lines between the Eyebrows produced in maximum frowning (Glabellar Lines)

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

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

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

• Nasopharyngitis
• Bronchitis
• Flu-like symptoms
• Drop of eyebrows, ptosis of the eyebrow
• Drop of eyelids (ptosis palpebral)
• Accumulation of fluid in the eyelids (edema palpebral)
• Discomfort (sensation of heaviness of the eyelid/eyebrow)
• Blurred vision
• Muscle spasms
• Facial asymmetry
• Sensation of oppression at the injection site
• Fatigue
• Pain or hematomas at the injection site
• Itching
• Hematoma
• Nodules on the skin
• Insomnia

Lateral Periorbital Lines produced in maximum smiling (Crow's Feet)

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

• Inflammation of the eyelid
• Dry eye
• Hematoma at the injection site

Upper Facial Lines

Very frequent (may affect more than 1 in 10 patients)

• Headaches

Frequent (may affect up to 1 in 10 patients)

• Insensitivity
• Ecchymosis at the injection site
• Pain at the injection site
• Redness of the skin around the injection site
• Discomfort (sensation of heaviness of the frontal area)
• Drop of eyelid (ptosis of the eyelid)
• Dry eye
• Drop of eyebrow (ptosis of the eyebrow)
• Facial asymmetry
• Mephisto Effect (lateral elevation of the eyebrows)
• Nausea

Experience after marketing

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

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

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

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

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

Reporting of adverse reactions

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

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

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

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

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

From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage time in use and the conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2°C to 8°C, unless reconstitution was performed in controlled and validated aseptic conditions.

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

Do not dispose of any medication through the drain.

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

BOCOUTURE Composition

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

BOCOUTURE 50 units

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

BOCOUTURE 100 units

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

• The other components are: Human albumin, saccharose.

Appearance of the product and contents of the package

BOCOUTURE is presented in the form of a powder for injectable solution (powder for injection). The powder is white.

When dissolved, BOCOUTURE is a transparent and colorless solution.

Packaging of 1, 2, 3 or 6 vials.

Only some presentations may be commercially available.

Marketing Authorization Holder

Merz Pharmaceuticals GmbH

Eckenheimer Landstr.100

D-60318 Frankfurt/Main

Germany.

–

Manufacturer

Merz Pharma GmbH & Co. KgaA

Legal Address:

Eckenheimer Landstraße 100

60318 Frankfurt/Main

Germany

Telephone: +49-69/15 03-1

Fax: +49-69/15 03-200

Manufacturing Address:

Ludwigstraße 22

64354 Reinheim

Germany

Local Representative

Merz Aesthetics Iberia, S.L.U.

Avenida de Bruselas 5

28108 Alcobendas

Madrid

Last review date of this leaflet: April 2020

-----------------------------------------------------------------------------------------------------------------------------

This information is intended solely for healthcare professionals:

Instructions for reconstitution of the injectable solution:

Reconstitute BOCOUTURE before use with sodium chloride 9 mg/ml (0.9%) injectable solution.

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

It is recommended to carry out the reconstitution of the vial and the preparation of the syringe on paper towels with plastic coating to collect any possible spillage. With a syringe, extract an adequate amount of sodium chloride solution. It is recommended to use a short-bevel needle of caliber 20-27 G (gauges) for reconstitution. After vertical insertion of the needle through the rubber stopper, inject the solvent carefully into the vial 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 removing and inverting/volting the vial, do not shake vigorously. If necessary, the needle used for reconstitution must remain in the vial and the required amount of solution must be extracted with a new sterile syringe suitable for injection.

Reconstituted BOCOUTURE is a transparent and colorless solution.

Do not use BOCOUTURE if the reconstituted solution (prepared according to the instructions above) has a turbid appearance or contains flocculated material or particles.

The 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 safe disposal of vials, syringes, and used materials

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

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

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

• Clean up any product residue, either by using absorbent material impregnated with any of the above solutions in case of powder, or with dry absorbent material, if it is the reconstituted product.
• Contaminated surfaces must 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 up the spilled product, avoiding cuts on the skin.
• If the product comes into contact with the skin, rinse the affected area with plenty of water.
• If the product comes into contact with the eyes, rinse with plenty of water or with an eye wash solution.
• If the product comes into contact with a wound, cut, or non-intact skin, rinse with plenty of water and take appropriate medical measures in accordance with the injected dose.

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