VISTABEL

Patient Information Leaflet

VISTABEL, 4 Allergan units/0.1 ml, powder for solution for injection
botulinum toxin type A
Please read all of this leaflet carefully before using this medicine, because 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.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of Contents

1. What VISTABEL is and what it is used for
2. Important information before using VISTABEL
3. How to use VISTABEL
4. Possible side effects
5. How to store VISTABEL
6. Contents of the pack and other information

1. What VISTABEL is and what it is used for

VISTABEL is a peripherally acting muscle-relaxing agent.
VISTABEL works by blocking nerve signals to all muscles into which it is injected.
In this way, it prevents muscles from contracting, leading to their temporary and reversible weakness.
VISTABEL is indicated for the temporary improvement in the appearance of the following facial lines:

• vertical frown lines between the eyebrows visible at maximum frown, and/or
• radial lines around the lateral canthus of the eye (crow’s feet) visible at full smile, and/or
• horizontal forehead lines visible at maximum eyebrow elevation,

in adult patients for whom the severity of these lines has a significant psychological impact.

2. Important information before using VISTABEL

When not to use VISTABEL

• if the patient is allergic (hypersensitive) to botulinum toxin type A or to any of the other ingredients of this medicine (listed in section 6)
• if the patient has been diagnosed with muscle weakness or Eaton-Lambert syndrome (chronic muscle disorders)
• if there is an infection at the proposed injection sites.

Warnings and precautions
Talk to your doctor or pharmacist before using VISTABEL.
Very rarely, adverse effects have been reported after administration of botulinum toxin, probably related to the spread of toxin to distant sites from the injection site (e.g. muscle weakness, difficulty swallowing, or pneumonia caused by food or liquid entering the airways). In patients receiving recommended doses, severe muscle weakness may occur.
Seek medical help immediately if the patient experiences difficulty swallowing, speaking, or breathing after treatment.

• Use of VISTABEL is not recommended in patients with a history of dysphagia (difficulty swallowing) or other swallowing disorders.
• Use of VISTABEL is not recommended in individuals under 18 years of age.
• Data on the use of VISTABEL in patients over 65 years of age are limited.
• Too frequent use of the medicine or excessively high doses may increase the risk of antibody formation. Development of antibodies may lead to treatment failure with botulinum toxin type A, even in other indications. To minimize this risk, the interval between therapeutic procedures must not be shorter than three months.
• Very rarely, an allergic reaction may occur after injection of botulinum toxin.
• After injection of the medicine, eyelid ptosis (drooping) may occur.

Inform your doctor:

• if the patient previously experienced problems after botulinum toxin injections,
• if there is no noticeable improvement in the appearance of forehead wrinkles one month after the first treatment cycle,
• if the patient has any neurological disorders (such as amyotrophic lateral sclerosis or peripheral neuromuscular disorders),
• if there is inflammation at the proposed injection sites,
• if the muscles intended for injection are weakened or damaged,
• if the patient has undergone surgery or sustained injury to the head, neck, or chest,
• if the patient is scheduled for surgery soon.

VISTABEL and other medicines
Concomitant use of botulinum toxin with aminoglycoside antibiotics, spectinomycin, or other drugs affecting neuromuscular transmission is not recommended.
Inform your doctor if a medicine containing botulinum toxin (the active substance in VISTABEL) has recently been administered, as this may significantly enhance the effect of VISTABEL.
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.

Pregnancy and breastfeeding
Use of VISTABEL is not recommended during pregnancy or in women of childbearing potential who are not using contraception.
Use of VISTABEL is not recommended in breastfeeding women.
Contact your doctor if the patient is pregnant, planning pregnancy, or becomes pregnant during treatment. The doctor will discuss whether treatment should be continued.
Before using any medicine, consult a doctor or pharmacist.

Driving and operating machinery
Caution is advised for drivers and operators of machinery due to the risk of generalized weakness and/or muscle weakness, dizziness, and visual disturbances associated with this medicine, which could pose a danger when driving vehicles or operating mechanical equipment. Do not drive or operate machinery until these symptoms have resolved.

Vistabel contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per vial, meaning the medicine is considered "sodium-free".

3. How to use VISTABEL

Method and route of administration
VISTABEL must be administered only by qualified physicians
with appropriate experience in this type of treatment and with access to required equipment.

Vertical frown lines visible during maximum frowning
VISTABEL is administered by intramuscular injection directly into the affected area between the eyebrows.
The standard dose is 20 units. The recommended volume of 0.1 ml (4 units) of VISTABEL will be injected into each of 5 injection sites.
Improvement in the appearance of frown lines usually occurs within one week after treatment,
with maximum effect observed 5–6 weeks after injection. The therapeutic effect lasts
for up to 4 months after injection.

Crow’s feet lines visible during full smile
The physician will inject VISTABEL directly into the affected areas laterally to each eye.
The recommended dose is 24 units. A volume of 0.1 ml (4 units) of VISTABEL is administered into each of 6 injection sites (3 injection sites laterally to each eye).
Improvement in the appearance of crow’s feet lines usually occurs within one week after administration.
The therapeutic effect lasts for up to 4 months after injection.

Horizontal forehead lines visible during maximum eyebrow elevation
VISTABEL is administered by intramuscular injection directly into the affected forehead area.
The standard dose is 20 units. The recommended volume of 0.1 ml (4 units) of VISTABEL will be injected into each of 5 injection sites.
The total dose for treatment of horizontal forehead lines (20 units) together with vertical frown lines (20 units) is 40 units.
Improvement in the severity of horizontal forehead lines visible during maximum eyebrow elevation
usually occurs within one week after treatment. The therapeutic effect lasts
for up to 4 months after injection.

General notes
If forehead lines are also being treated simultaneously, the total dose of the medicinal product is
44 units.
If a patient is being treated for all three types of wrinkles simultaneously (crow’s feet lines radiating from the outer eye corners visible during full smile, vertical frown lines visible during maximum frowning, and horizontal forehead lines visible during maximum eyebrow elevation), the total dose of the medicinal product is 64 units.
The interval between two treatment cycles must not be shorter than three months. The safety and efficacy of repeated VISTABEL injections administered over a period longer than 12 months have not been studied.
If you have any doubts regarding the use of this medicinal product, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicinal product may cause adverse reactions, although not everybody will experience them.
Adverse reactions usually occur within the first few days after injection and are transient in nature. Most reported adverse events were mild to moderate in severity.

Adverse reactions may occur in approximately 1 in 4 patients following injection of VISTABEL for the treatment of glabellar lines (vertical frown lines). Adverse reactions following injection of VISTABEL for the treatment of crow’s feet lines, or for the combined treatment of crow’s feet lines and glabellar lines, occurred in approximately 8% of patients. Adverse reactions may occur in approximately 20% of patients following combined treatment with VISTABEL for horizontal forehead lines visible at maximum eyebrow elevation and vertical glabellar lines visible at maximum frowning. About 14% of patients may experience adverse reactions when treatment of horizontal forehead lines and vertical glabellar lines is combined with treatment of crow’s feet lines radiating from the outer corners of the eyes, visible during full smile.

Adverse reactions may be related to the treatment, to the injection technique, or to both factors simultaneously. Ptosis (drooping eyelid), which may be associated with the injection technique, results from the local action of VISTABEL causing muscle relaxation.

Very rarely, adverse reactions have been reported after use of botulinum toxin, probably related to the spread of toxin to distant sites from the injection site (e.g. muscle weakness, difficulty swallowing, constipation, or aspiration pneumonia caused by food or liquid entering the airways, which may be fatal). Injection of VISTABEL is not recommended in patients with a history of dysphagia (difficulty swallowing) or other swallowing disorders.

If the patient experiences any difficulties with breathing, swallowing, or speech after receiving VISTABEL, medical advice should be sought immediately.

If the patient develops hives, swelling (including facial or throat swelling), wheezing, dizziness, or breathing difficulties, medical advice should be sought immediately.

Spread of botulinum toxin to adjacent muscles is possible when high doses are injected, particularly in the neck area.

As with any injection, the procedure may cause pain, burning, stinging, swelling and/or bruising. If these symptoms are bothersome, the patient should consult their physician.

The likelihood of occurrence of adverse reactions is categorized as follows:

Use for temporary improvement in the appearance of vertical frown lines between the eyebrows

Use for temporary improvement in the appearance of "crow's feet" lines extending
from the outer corners of the eyes, with or without concurrent treatment of glabellar lines
visible with frowning or without such treatment.

*adverse reactions related to the injection procedure.
Injection for temporary improvement in the appearance of horizontal forehead lines visible during maximum eyebrow elevation, and vertical glabellar lines visible during frowning, with or without concurrent treatment of crow's feet lines radiating from the outer corners of the eyes.

1 The median time to onset of eyelid ptosis was 9 days after treatment.
2 The median time to onset of eyebrow ptosis was 5 days after treatment.
*Adverse reactions related to the injection procedure.
The following adverse reactions have been reported after administration of the medicinal product VISTABEL since its market introduction in the treatment of glabellar lines, crow's feet wrinkles, and other clinical indications:

• Severe allergic reactions (subcutaneous swelling, breathing difficulties),
• Urticaria,
• Loss of appetite,
• Nerve damage,
• Difficulties in moving the arm and shoulder,
• Voice and speech problems,
• Facial muscle weakness,
• Reduced skin sensation,
• Muscle weakness,
• Chronic muscle disease (myasthenia gravis),
• Numbness,
• Pain or weakness starting from the spine,
• Fainting,
• Muscle drooping on one side of the face,
• Increased eye pressure,
• Eyelid ptosis,
• Difficulty completely closing the eye,
• Strabismus,
• Vision disorders, decreased visual acuity,
• Hearing loss,
• Tinnitus,
• Dizziness or spinning sensation,
• Aspiration pneumonia (pneumonia caused by accidental inhalation of food, drink, saliva, or vomit),
• Shortness of breath,
• Breathing problems, including respiratory depression and/or respiratory failure,
• Abdominal pain,
• Diarrhea,
• Dry mouth sensation,
• Difficulty swallowing,
• Nausea,
• Vomiting,
• Hair loss,
• Eyebrow ptosis,
• Psoriasis-like skin lesions (red, thick, dry scales),
• Various types of red pinpoint skin rashes,
• Excessive sweating,
• Loss of eyebrows,
• Itching,
• Rash,
• Muscle atrophy,
• Muscle pain,
• Loss of innervation/muscle atrophy at the injection site,
• Apathy,
• General malaise,
• Fever,
• Dry eye,
• Local muscle twitching/involuntary muscle contractions,
• Eyelid swelling.

Reporting of adverse reactions
If any adverse reactions occur, including any possible adverse reactions not listed in this leaflet, consult a physician 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
PL-02 222 Warsaw
Tel.: + 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 VISTABEL

Keep the medicine out of the sight and reach of children.
Do not use VISTABEL after the expiry date stated on the label and carton after EXP. The expiry date refers to the last day of the stated month.
Store in a refrigerator (2°C - 8°C).
After reconstitution, immediate use of the solution is recommended. However, it has been demonstrated that the medicinal product maintains its chemical and physical stability for 24 hours at 2°C - 8°C.
Do not dispose of any medicines via wastewater or household waste. These actions help protect the environment.

6. Contents of the package and other information

What VISTABEL contains

• The active substance is: botulinum toxin type A from Clostridium botulinum (0.1 ml of reconstituted injection solution contains 4 Allergan units).
• Other components are: human albumin and sodium chloride.

What VISTABEL looks like and contents of the pack
VISTABEL powder for solution for injection is a fine white powder for preparation of an injection solution, which may be almost invisible at the bottom of a clear glass vial. Before injection, the product must be reconstituted with sterile saline solution without preservatives (0.9% sodium chloride injection solution). Each vial contains either 50 or 100 Allergan units of botulinum toxin type A.
Each pack contains 1 or 2 vials.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
AbbVie Sp. z o.o.
ul. Postępu 21B
02-676 Warsaw
Poland
Manufacturer
Allergan Pharmaceuticals Ireland
Castlebar Road
Westport, County Mayo
Ireland
or
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
This medicinal product is authorised in the Member States of the European Economic Area
under the following names:

The following information is intended for healthcare professionals only:

Botulinum toxin units differ depending on the medicinal product and are not interchangeable.
The recommended dosage units of Allergan are not equivalent to the dosage units of other
botulinum toxin products.

VISTABEL is indicated for the temporary improvement in the appearance of the following wrinkles:

• moderate to severe glabellar lines visible at maximum eyebrow contraction (i.e., frown lines) and/or
• moderate to severe lateral periorbital lines visible at full smile (i.e., crow's feet) and/or
• moderate to severe horizontal forehead lines visible at maximum eyebrow elevation, when the severity of the lines has a significant psychological impact on adult patients.

Reconstitution of the product should be performed according to good clinical practice, with particular attention to aseptic techniques. VISTABEL should be reconstituted with sterile saline solution without preservatives (0.9% sodium chloride injection). When using a vial containing 50 units, draw 1.25 mL of 0.9% sodium chloride injection into a syringe to prepare a reconstituted solution for injection with a concentration of 4 units/0.1 mL. When using a vial containing 100 units, draw 2.5 mL of sterile saline solution (0.9% sodium chloride injection) into a syringe to obtain a reconstituted solution for injection with a concentration of 4 units/0.1 mL.

Clean the central part of the rubber stopper with alcohol.
To prevent denaturation of VISTABEL, the diluent should be slowly injected into the vial, and the vial should be gently rotated to avoid formation of bubbles. Discard the vial if negative pressure does not draw the diluent into the vial. After reconstitution, the injectable solution should be visually inspected before use to ensure it is clear, colorless or slightly yellowish, and free from particulate matter.
VISTABEL must be used exclusively for the treatment of a single patient during one procedure.

For the treatment of glabellar lines (vertical lines visible with maximal frowning of eyebrows, moderate or severe in intensity), to prevent diffusion below the orbital rim, the thumb or index finger should be firmly pressed below the orbital rim before injection. During injection, the needle should be directed upward and medially. To minimize the risk of eyelid ptosis, the maximum recommended dose of 4 units per injection site and the recommended number of injection sites must not be exceeded. In addition, injections should be avoided in the area of the levator palpebrae superioris muscle. This is particularly important for patients with well-developed depressor supercilii muscles. Injections into the corrugator muscles should be performed in the central portions of these muscles, at least 1 cm above the eyebrow arch.

For the treatment of crow’s feet lines (moderate or severe lateral periorbital lines visible with full smile), during injection the needle should be directed upward and away from the eye.
To minimize the risk of eyelid ptosis, the maximum recommended dose of 4 units per injection site and the recommended number of injection sites must not be exceeded. In addition, injections should be administered temporally in relation to the orbital rim, thereby maintaining a safe distance from muscles responsible for eyelid elevation.

The total dose for treatment of horizontal forehead lines (20 units) together with vertical glabellar lines (20 units) is 40 units/1 ml. To identify appropriate injection sites within the frontalis muscle, the overall relationship between the patient’s forehead size and the distribution of frontalis muscle activity should be assessed.

Procedure for safe disposal of used vials, syringes, and materials:
Immediately after use and before disposal, any unused reconstituted VISTABEL injectable solution remaining in the vial and/or syringe should be inactivated by adding 2 ml of diluted sodium hypochlorite solution containing 0.5% or 1% available chlorine, and then disposed of according to local requirements.
Used vials, syringes, and materials should not be emptied but discarded directly into appropriate containers and then disposed of in accordance with local regulations.

Recommendations in case of accidents when handling botulinum toxin
In the event of an accident when handling the product, whether in the lyophilized (freeze-dried) form or after reconstitution, the following appropriate actions should be taken immediately:

• Spilled solution should be wiped using absorbent material moistened with sodium hypochlorite solution (Javel solution) for the lyophilized product, or dry absorbent material for the reconstituted product.
• Contaminated surfaces should be cleaned with absorbent material moistened with sodium hypochlorite solution (Javel solution), then dried.
• If a vial is broken, carefully collect the glass fragments and wipe up the product as described above, taking care to avoid skin lacerations.
• If the solution splashes onto the skin, wash with sodium hypochlorite solution (Javel solution), then rinse thoroughly with large amounts of water.
• If the solution gets into the eyes, rinse the eyes thoroughly with large amounts of water or ophthalmic irrigation solution.
• In case of injury (laceration, puncture) to the person performing the above procedures, follow the steps described above, then undertake appropriate medical actions corresponding to the injected dose.

Product identification
To confirm receipt of authentic VISTABEL medicinal product from AbbVie, check the tamper-evident features on the VISTABEL cardboard carton and the presence of a holographic label on the vial. The hologram on the vial should be verified by viewing the vial under desk or fluorescent light. Rotate the vial and look for rainbow-colored horizontal lines on the label containing the word "abbvie".
Do not use the product and contact the local AbbVie office for further information if the rainbow-colored lines with the word "abbvie" are not present on the label.
Additionally, the label contains peel-off stickers including the product name, expiration date, and batch number. The stickers can be peeled off and placed in the patient’s record for identification purposes. After removing the sticker from the label, the word "USED" will become visible, further confirming the authenticity of the VISTABEL product.