Azzalure

Warning! Keep the package 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 the 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.

Table of contents of the leaflet:

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

1. WHAT IS AZZALURE AND WHAT IS IT USED FOR

Azzalure contains botulinum toxin type A, which causes muscle relaxation. Azzalure acts at the junction between nerves and muscles, preventing the release of the chemical messenger acetylcholine from nerve endings. This prevents muscle contraction. The resulting muscle relaxation is temporary and gradually resolves.

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 frown lines between the eyebrows) and lateral periorbital lines (crow’s feet).

2. IMPORTANT INFORMATION BEFORE USING AZZALURE

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 an Azzalure injection, 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 fits;
• if there is inflammation at the proposed injection site;
• if the muscles at the proposed injection site are weak;
• if the patient has blood clotting disorders, meaning prolonged clotting time, e.g. haemophilia (inherited blood clotting disorders caused by a deficiency of clotting factors);
• 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 after the last botulinum toxin treatment there was no significant improvement in wrinkles.

During treatment with Azzalure, dry eye may occur. Azzalure may cause
reduced blinking frequency or decreased tear production, which may damage the ocular surface.
Such 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 in higher doses for the treatment of other conditions, the development of antibodies in patients has rarely been observed. The formation of neutralizing antibodies against the toxin may reduce treatment effectiveness.
Whenever visiting a doctor (regardless of the reason for the visit), patients should inform the doctor about previous treatment with Azzalure.
Children and adolescents
Azzalure is not indicated for use in individuals under 18 years of age.
Azzalure and other medicines
Tell your doctor about all medicines currently used, recently used, or planned for use, 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-relaxing medicines.

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

3. HOW TO USE AZZALURE

Azzalure must be administered only by physicians who possess the appropriate qualifications, experience, and required equipment for such treatment. The physician will prepare and administer the medication to the patient. The Azzalure vial should be used for only one patient during a single treatment session.

The recommended dosage of Azzalure is:

• Glabellar forehead lines: 50 units, administered as 10 units at each of 5 injection sites in the forehead area above the nose and eyebrows;
• Periocular wrinkles (crow's feet): 60 units, administered as 10 units at each of 6 injection sites, bilaterally in the crow's feet areas.

Units used for other botulinum toxin products are not equivalent. Speywood units of Azzalure cannot be interchanged with units of other botulinum toxin products.

The therapeutic effect 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 dose higher than recommended may result in weakening of muscles located outside the injection site. This may occur after some delay. In case such a situation occurs, the physician must be notified immediately.

4. POSSIBLE ADVERSE REACTIONS

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

• difficulty breathing, swallowing or speaking occurs;
• swelling of the face, 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 (occurring in more than 1 in 10 patients)

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

Common (occurring in 1 to 10 in 100 patients)

• 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 (occurring in 1 to 10 in 1,000 patients)

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

Rare (occurring in 1 to 10 in 10,000 patients)

• Itchy, lumpy rash
• Eye movement disorders

Not known (frequency cannot be estimated from available data)

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

Crow’s feet:
Common (occurring in 1 to 10 in 100 patients)

• Headache
• Eyelid swelling
• Bruising, itching and swelling around the eyes
• Drooping of the upper eyelid
• Transient facial paralysis

Uncommon (occurring in 1 to 10 in 1,000 patients)

• Dry eye

Not known (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 injection and resolved quickly. They were generally mild or moderate in intensity.

Very rarely, adverse symptoms 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 symptoms occur, contact your doctor immediately.

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 also be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 the medicine out of the sight and reach of children.
Do not use Azzalure after the expiry date stated on the packaging.
The expiry date refers to the last day of the stated month.
Azzalure should be stored 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 responsibility for the storage conditions and duration prior to use falls to the user.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. PACK CONTENTS 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 botulinum toxin from Clostridium botulinum (bacterium) type A 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 packaging containing 1 vial.
Azzalure is a white powder.
For more detailed information, please contact the responsible party or the parallel importer.
Responsible party in the Czech Republic, 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
Repackaged in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Permit number in the Czech Republic, country of export: 63/120/10-C
Parallel import permit number: 62/25

The following information is intended for healthcare professionals only:

Azzalure, 125 Speywood Units, powder for solution for injection
Botulinum toxin (type A) for injection

Dosage and method of administration:
See section 3 of the Patient Leaflet.

Special precautions for disposal and preparation of the medicinal product for administration
Strict adherence to instructions regarding use, preparation, and disposal of the medicinal product is required.
Reconstitution must be performed in accordance with good practice, particularly with regard to aseptic technique.

Azzalure must be reconstituted with 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 diluent (0.9% sodium chloride solution) added to the 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 graduated in 0.1 ml and 0.01 ml increments.

DISPOSAL OF CONTAMINATED MATERIALS
Immediately after use and before disposal, any unused reconstituted Azzalure (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 ACCIDENT DURING PREPARATION OF BOTULINUM TOXIN

• Spilled product should be wiped: using an absorbent material soaked in sodium hypochlorite solution (bleach) in case of powder, or using dry absorbent material in 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 the product, taking care not to cut the skin.
• If the product comes into contact with the skin, wash the affected 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 water or an ophthalmic irrigation solution.
• If the product comes into contact with a wound, cut, or damaged skin, the affected area should be thoroughly rinsed with abundant water and appropriate medical actions should be taken depending on the injected dose.

Strict adherence to instructions regarding use, preparation, and disposal of the medicinal product is required.