AZZALURE

Warning! Keep the leaflet. Information on the immediate packaging in a foreign language
Azzalure, 125 Speywood units, powder for solution for injection
Botulinum toxin (type A) for injection
Please read the entire leaflet before using this medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any doubts, consult your doctor.
• If the patient experiences any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Leaflet contents:

1. What Azzalure is and what it is used for
2. What you need to know before receiving Azzalure
3. How to use Azzalure
4. Possible side effects
5. How to store Azzalure
6. Contents of the package and other information

1. WHAT AZZALURE IS AND WHAT IT IS USED FOR

Azzalure contains botulinum toxin type A, which causes muscle relaxation. Azzalure acts at the junction between nerves and muscles by preventing the release of the chemical messenger acetylcholine from nerve endings. This prevents muscle contraction. Muscle relaxation is temporary and gradually wears off.
Some people are concerned about facial wrinkles. Azzalure may be used in adults under 65 years of age for the temporary improvement in the appearance of moderate to severe glabellar lines (vertical wrinkles between the eyebrows) and lateral periorbital lines (crow’s feet).

2. IMPORTANT INFORMATION BEFORE USING AZZALURE INJECTIONS

When not to use Azzalure injections

• if the patient is allergic to Clostridium botulinum toxin type A or to any of the other ingredients of this medicine (listed in section 6);
• in case of infection at the proposed injection site;
• in case of myasthenia gravis, Lambert-Eaton syndrome, or amyotrophic lateral sclerosis.

Warnings and precautions
Before receiving Azzalure injections, discuss the following with your doctor:

• if the patient has neuromuscular disorders;
• if the patient frequently experiences difficulty swallowing (dysphagia);
• if the patient frequently chokes on food or drink, causing coughing or choking;
• if there is inflammation at the proposed injection site;
• if the muscles at the proposed injection site are weak;
• if the patient has bleeding disorders, meaning prolonged clotting time, such as haemophilia (inherited blood clotting disorders due to deficiency of clotting factors);

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• if the patient has undergone facial surgery or if such surgery or other surgical procedures are planned in the near future;
• if the patient has previously received injections of another botulinum toxin;
• if there was no significant improvement in wrinkles after the last botulinum toxin treatment.

Dry eyes may occur during treatment with Azzalure. Azzalure may cause reduced blinking frequency or decreased tear production, which may damage the eye surface.
This information will help the doctor make an appropriate decision regarding the risks and benefits of treatment.
Special warnings
Very rarely, botulinum toxin may cause weakening of muscles distant from the injection site.
When botulinum toxins are used more frequently than every 12 weeks or at higher doses for the treatment of other conditions, the formation of antibodies in patients has been rarely observed. The development of neutralizing antibodies may reduce the effectiveness of treatment.
Whenever visiting a doctor (regardless of the reason for the visit), inform the doctor about prior treatment with Azzalure.
Children and adolescents
The use of Azzalure is not recommended in individuals under 18 years of age.
Azzalure and other medicines
Tell your doctor about all medicines currently taken or recently used, as well as any medicines the patient plans to take, because Azzalure may affect the action of other medicines, particularly:

• antibiotics used to treat infections (e.g. aminoglycoside antibiotics such as gentamicin or amikacin), or
• other muscle relaxants.

Use of Azzalure with food and drink
Azzalure injections may be administered before or after eating or drinking.
Pregnancy and breastfeeding
Azzalure should not be used during pregnancy.
The use of Azzalure is not recommended in breastfeeding women. If the patient is pregnant, planning to become pregnant, or breastfeeding, consult a doctor before using any medicine.
Driving and operating machinery
After receiving Azzalure injections, transient blurred vision, muscle weakness, or general fatigue may occur. If such effects occur, the patient must not drive or operate machinery.

3. HOW TO USE THE MEDICINAL PRODUCT AZZALURE

Azzalure must be administered only by physicians who have appropriate qualifications and experience in this type of treatment, as well as the required equipment. The physician will prepare and administer the medicine to the patient. The Azzalure vial should be used for only one patient during a single treatment session.
The recommended dose of Azzalure is:
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• Glabellar lines: 50 units, administered as 10 units at each of 5 injection sites in the forehead area above the nose and eyebrows;
• Periocular wrinkles: 60 units, administered as 10 units at each of 6 injection sites bilaterally in the crow's feet area.

Units used for other botulinum toxin products are not equivalent. Speywood units of Azzalure must not be interchanged with units of other botulinum toxin products.
The effect of treatment should become apparent within a few days after injection.
The interval between subsequent Azzalure injections will be determined by the physician.
Azzalure must not be used more frequently than every 12 weeks.
Azzalure is not indicated for use in patients under 18 years of age.
Use of a higher than recommended dose of Azzalure
Administration of a higher than recommended dose of Azzalure may cause weakening of certain muscles located outside the injection site. This may occur after some delay. If such a situation occurs, contact your physician immediately.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, Azzalure may cause adverse reactions, although not everyone experiences them.
Seek immediate medical attention if:

• difficulty breathing, swallowing or speaking occurs;
• facial swelling, skin redness or itchy, lumpy rash develops. These symptoms may indicate an allergic reaction to Azzalure.

Inform your doctor if the patient experiences any of the following adverse reactions:
Glabellar lines:
Very common (affects more than 1 in 10 people)

• Redness, swelling, irritation, rash, itching, tingling, pain, discomfort, stinging or bruising at the injection site
• Headache

Common (affects 1 to 10 in 100 people)

• Eye fatigue or blurred vision, drooping of the upper eyelid, eyelid swelling, watery eyes, dry eye syndrome, muscle twitching around the eye
• Transient facial paralysis

Uncommon (affects 1 to 10 in 1,000 people)

• Impaired, blurred or double vision
• Dizziness
• Itching, rash
• Allergic reactions

Rare (affects 1 to 10 in 10,000 people)

• Itchy, lumpy rash
• Eye movement disorders

Unknown (frequency cannot be estimated from available data)

• Numbness
• Decreased muscle mass
• Generalized weakness
• Fatigue
• Influenza-like symptoms

Crow’s feet (lateral canthal lines):
Common (affects 1 to 10 in 100 people)
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• Headache
• Eyelid swelling
• Bruising, itching and swelling around the eyes
• Drooping of the upper eyelid
• Transient facial paralysis

Uncommon (affects 1 to 10 in 1,000 people)

• Dry eye

Unknown (frequency cannot be estimated from available data)

• Allergic reactions
• Numbness
• Decreased muscle mass
• Generalized weakness
• Fatigue
• Influenza-like symptoms

These adverse reactions usually occurred within the first week after injections and resolved quickly. They were generally mild or moderate in severity.
Very rarely, adverse effects affecting muscles other than those injected with botulinum toxin have been reported. These include increased muscle weakness, difficulty swallowing, coughing and choking during swallowing (when food or liquids enter the airways during swallowing, respiratory disturbances such as lung infections may occur). If any of these effects occur, seek immediate medical attention.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. 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
Tel: +48 22 49 21 301, Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to provide more information on the safety of this medicine.

5. HOW TO STORE AZZALURE

Keep out of the sight and reach of children.
Do not use Azzalure after the expiry date stated on the container.
The expiry date refers to the last day of the stated month.
Store Azzalure in a refrigerator (2°C–8°C). Do not freeze.
Your doctor will reconstitute Azzalure and prepare the solution for injection.
Chemical and physical stability of the solution has been demonstrated for 24 hours at 2°C–8°C.
From a microbiological point of view, the solution should be used immediately unless the method
of reconstitution excludes the risk of microbiological contamination. If the product is not used
immediately, the user is responsible for the storage conditions and duration prior to use.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how
to dispose of medicines no longer required. Such measures help protect the environment.
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6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION

What Azzalure contains

• The active substance is botulinum toxin (type A) for injection*. One vial contains 125 Speywood units.
• The other ingredients are human albumin 200 g/l and monohydrate lactose.

*Complex of Clostridium botulinum (bacterium) type A toxin with hemagglutinin
Speywood units of Azzalure are specific to this product and cannot be interchanged with
other preparations containing botulinum toxin.

What Azzalure looks like and contents of the pack
Azzalure is a powder for solution for injection. It is available in packs containing 1 vial.
Azzalure is a white powder.

For more detailed information, please contact the Marketing Authorisation Holder or the Parallel Importer.

Marketing Authorisation Holder in Italy, country of export:
Ipsen Pharma
65 quai Georges Gorse
92100 Boulogne Billancourt
France

Manufacturer:
Ipsen Manufacturing Ireland Limited
Blanchardstown Industrial Park
Blanchardstown
Dublin 15, Ireland

Parallel Importer:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Poland

Repackaged in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Poland

Marketing Authorisation number in Italy, country of export: 039063019
Parallel Import Authorisation number: 18/26

The following information is intended exclusively for medical professionals:

Azzalure, 125 Speywood units, powder for solution for injection
Botulinum toxin (type A) for injection
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Dosage and method of administration:
See section 3 of the Patient Leaflet.

Special precautions regarding disposal and preparation of the medicinal product for use
Strictly follow instructions concerning the use, preparation, and disposal of the medicinal product.
Reconstitution must be performed in accordance with good practice, particularly with respect to aseptic technique.

The Azzalure medicinal product must be dissolved in 0.9% sodium chloride solution (9 mg/ml) for injection.
According to the reconstitution table below, the required volume of 0.9% sodium chloride solution (9 mg/ml) for injection should be drawn into a syringe to obtain a clear, colourless solution with the following concentration:

| Volume of solvent (0.9% sodium chloride solution) added to vial containing 125 units | Final concentration | |----------------------------------------------------------------------------------------|---------------------| | 0.63 ml | 10 units per 0.05 ml | | 1.25 ml | 10 units per 0.1 ml |

Accurate measurement of 0.63 ml or 1.25 ml can be achieved using syringes calibrated in 0.1 ml and 0.01 ml increments.

RECOMMENDATIONS FOR DISPOSAL OF CONTAMINATED MATERIALS
Immediately after use and before disposal, any unused reconstituted Azzalure medicinal product (in vial or syringe) must be inactivated using 2 ml of diluted sodium hypochlorite solution at a concentration of 0.55% or 1% (Dakin's solution).
Do not empty used vials, syringes, or materials. They must be discarded into appropriate containers and disposed of in accordance with local requirements.

RECOMMENDATIONS IN CASE OF INCIDENT DURING PREPARATION OF BOTULINUM TOXIN

• Spilled product should be wiped up: using an absorbent material soaked in sodium hypochlorite solution (bleach) in the case of powder, or using dry absorbent material in the case of reconstituted product.
• Contaminated surfaces should be cleaned with an absorbent material soaked in sodium hypochlorite solution (bleach), then dried.
• In case of broken vial, follow the above instructions. Carefully collect fragments of broken glass and wipe up the product, taking care not to cut the skin.
• If the product comes into contact with the skin, wash the contaminated area with sodium hypochlorite solution (bleach), then rinse thoroughly with water.
• If the product comes into contact with the eyes, rinse the eyes thoroughly with abundant amounts of water or ophthalmic irrigation solution.
• If the product comes into contact with a wound, abrasion, or damaged skin, the contaminated area should be thoroughly rinsed with abundant amounts of water, and appropriate medical actions should be taken depending on the injected dose.

Strictly follow instructions concerning the use, preparation, and disposal of the medicinal product.
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