Azzalure

Patient Information Leaflet

Azzalure, 125 Speywood Units, powder for injectable solution

(botulinum toxin type A)
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If you get any side effects, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet:
1 What Azzalure is and what it is used for
2 What you need to know before using Azzalure
3 How to use Azzalure
4 Possible side effects
5 How to store Azzalure
6 Contents of the pack and other information

1. What Azzalure is and what it is used for

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

In some individuals, the appearance of facial wrinkles may have a significant psychological impact.
Azzalure can be used in adult patients under 65 years of age to temporarily improve the appearance of moderate to severe glabellar lines (vertical wrinkles that form between the eyebrows when frowning) and lateral canthal lines (crow's feet).

2. What you should know before using Azzalure

Do not receive an injection of Azzalure:

• if you are allergic to Clostridium botulinum type A toxin or to any of the other ingredients of this medicine (listed in section 6)
• if you have an infection at the site intended for injection
• if you have severe myasthenia gravis, Lambert-Eaton syndrome, or amyotrophic lateral sclerosis.

Warnings and precautions
Talk to your doctor before receiving an injection of Azzalure if:

• you have any neuromuscular disorder
• you frequently have difficulty swallowing food (dysphagia)
• you notice that you often have problems caused by food or drink entering your airways, leading to coughing or choking
• you have inflammation at the site intended for injection
• the muscles at the intended injection site are weak
• you have bleeding disorders, meaning you continue to bleed for longer than normal, such as hemophilia (inherited coagulation disorders caused by deficiencies in coagulation factors)
• you have had facial surgery, or you plan to undergo facial or any other type of surgery in the near future
• you have previously received other botulinum toxin injections
• you did not experience any significant improvement in wrinkles after your last botulinum toxin treatment

This information will help your doctor make an informed decision about the benefits and risks of your treatment.
When you are treated with Azzalure, your eyes may become dry. Azzalure may reduce blinking or tear production, which could damage the surface of your eyes.
Special warnings
Very rarely, the effect of botulinum toxin may result in muscle weakness in an area distant from the injection site.
When botulinum toxins are used at intervals shorter than 12 weeks or at higher doses to treat other conditions, in rare cases the formation of antibodies has been observed in some patients. The development of neutralizing antibodies may reduce the effectiveness of treatment.
If you consult a doctor for any reason, make sure to inform them that you have been treated with Azzalure.
Children and adolescents
Azzalure is not indicated for patients under 18 years of age.
Other medicines and Azzalure
Inform your doctor if you are currently using, have recently used, or might use any other medicines, since Azzalure may interact with other medicines, especially:

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

Azzalure with food and drink
You may receive Azzalure injections either before or after meals and beverages.
Pregnancy and breastfeeding
You must not receive Azzalure treatment during pregnancy. Azzalure treatment is not recommended during breastfeeding. If you are pregnant, planning a pregnancy, or breastfeeding, consult your doctor before using any medicine.
Driving and using machines
After treatment with Azzalure, blurred vision, muscle weakness, or generalized weakness may occur transiently. If this happens, do not drive or operate machinery.

3. How to use Azzalure

Azzalure must only be administered by appropriately qualified physicians, with proven experience in this treatment and equipped with the necessary equipment.
The physician will prepare and administer the injections. One vial of Azzalure must be used only for you and only for a single treatment session.
The recommended dose of Azzalure is:

• For glabellar lines: 50 units administered in 10-unit fractions at each of 5 injection sites on the forehead, in the area above the nose and eyebrows.
• For lateral canthal lines: 60 units administered in 10-unit fractions at each of 6 injection sites in both crow's feet areas.

The units used for different botulinum toxin products are not equivalent. Speywood units of Azzalure are not interchangeable with units of other botulinum toxin products.
The effect of treatment should become visible within a few days after injection.
The interval between treatment sessions with Azzalure will be determined by your physician. Treatments should not be performed at intervals shorter than 12 weeks.
Azzalure is not indicated for patients under 18 years of age.
If you receive more Azzalure than you should
If you receive more Azzalure than required, you may begin to experience weakness in muscles other than those injected. This may not occur immediately. If this happens, contact your physician immediately.

4. Possible side effects

Like all medicines, Azzalure can cause side effects, although not everyone experiences them.
Seek urgent medical advice if:

• you experience difficulty breathing, swallowing or speaking.
• you develop facial swelling, or your skin becomes red or develops nodular erythema accompanied by itching. These may indicate an allergic reaction to Azzalure.

Contact your doctor if you notice any of the following side effects:
For glabellar lines:
Very common (occurs in more than 1 out of 10 people)

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

Common (occurs in 1 to 10 out of 100 people)

• Tired eyes or blurred vision, drooping of the upper eyelid, eyelid swelling, excessive tearing, dry eyes, muscle twitching around the eye
• Temporary facial paralysis

Uncommon (occurs in 1 to 10 out of 1,000 people)

• Vision disorders, blurred or double vision
• Dizziness
• Itching, erythema
• Allergic reactions

Rare (occurs in 1 to 10 out of 10,000 people)

• Erythema accompanied by itching and nodules
• Eye movement disorders

Not known (frequency cannot be estimated from the available data):

• Numbness
• Muscle atrophy
• Generalized weakness
• Fatigue
• Flu-like symptoms

For lateral canthal lines:
Common (occurs in 1 to 10 out of 100 people)

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

Uncommon (occurs in 1 to 10 out of 1,000 people)

• Dry eyes

Not known (frequency cannot be estimated from the available data):

• Allergic reactions
• Numbness
• Muscle atrophy
• Generalized weakness
• Fatigue
• Flu-like symptoms

These side effects usually occur during the first week after injection, are short-lived, and of mild to moderate intensity.
Very rarely, side effects have been reported in muscles other than those injected with botulinum toxin. These side effects include: excessive muscle weakness, difficulty swallowing due to coughing and choking when swallowing (if food or liquid enters the airways while swallowing, respiratory problems such as lung infections may occur). If this occurs, seek immediate medical attention.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Azzalure

Keep Azzalure out of the sight and reach of children.
The physician must not use Azzalure after the expiry date stated on the label. The expiry date refers to the last day of that month.
Store Azzalure in a refrigerator (2°C - 8°C).
Unopened vials of Azzalure may be kept at temperatures up to 25°C for a maximum of 72 hours after a single exposure. After this period, the unopened vial must be stored in the refrigerator (2°C - 8°C) for the remainder of its shelf life.
Do not freeze.
The physician will reconstitute Azzalure in a liquid injectable solution. Chemical and physical stability during use has been demonstrated for 24 hours at 2-8°C. From a microbiological standpoint, unless the reconstitution method excludes the risk of microbial contamination, the product should be used immediately.
If not used immediately, the storage times and conditions prior to use are the responsibility of the user.

6. Package contents and other information

What Azzalure contains

• The active substance is botulinum toxin type A*. One vial contains 125 Speywood units.
• The other components are human albumin 200 g/L and lactose monohydrate.
  * Toxin from Clostridium botulinum (a bacterium) type A – hemagglutinin complex.

Speywood units of Azzalure are specific to this product and are not interchangeable with units from other botulinum toxin products.

Description of the appearance of Azzalure and contents of the pack
Azzalure is a powder for solution for injection. It is available in packs containing 1 or 2 vials.
Azzalure is a white powder.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
Ipsen Pharma
70 rue Balard
75015 Paris
France

Sales Licensee:
Galderma Italia S.p.A.
Via Luciano Manara, 15
20122 Milan
Italy

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

If you require further information or would like this package leaflet in another format, please contact Galderma Italia S.p.A. at tel. +39 – 02 679740 1

The following information is intended for healthcare professionals only:

Dosage and method of administration:
Refer to section 3 of the package leaflet.
Special precautions for disposal and handling:
Instructions for use, handling, and disposal must be strictly followed.
Reconstitution of the product must be carried out in accordance with good practice standards, especially regarding aseptic technique.
Azzalure must be reconstituted with 9 mg/ml (0.9%) sodium chloride solution for injection.
The dilution table below indicates the required volume of 9 mg/ml (0.9%) sodium chloride solution for injection to be drawn into a syringe in order to obtain a clear, colourless reconstituted solution at the following concentration:

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

RECOMMENDATIONS FOR DISPOSAL OF CONTAMINATED MATERIALS
Immediately after use and prior to disposal, any unused reconstituted Azzalure solution (remaining in the vial or syringe) must be inactivated with 2 ml of diluted sodium hypochlorite solution at 0.55% or 1% (Dakin's solution).
Vials, syringes, and other materials used must not be emptied but collected in appropriate containers and disposed of in accordance with local regulations.

RECOMMENDATIONS IN CASE OF AN INCIDENT DURING HANDLING OF BOTULINUM TOXIN

• Absorb any spilled product using absorbent material soaked in sodium hypochlorite solution (bleach) if in powder form, or dry absorbent material if reconstituted.
• Contaminated surfaces must be cleaned using absorbent material soaked in sodium hypochlorite solution (bleach), then thoroughly dried.
• In case of a broken vial, follow the above procedure, carefully collecting glass fragments and absorbing the product, taking care not to injure yourself.
• 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 thoroughly with water or with an ophthalmic irrigation solution.
• If the product comes into contact with a wound, cut, or skin lesion, rinse thoroughly with water and take appropriate measures based on the dose with which contamination occurred.

These instructions for handling and disposal must be strictly followed.