Letybo

Package leaflet: Information for the user

Letybo 50 units powder for solution for injection

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 or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What Letybo is and what it is used for

Letybo contains the active substance botulinum toxin type A, which works by blocking nerve impulses to the muscles into which it is injected and prevents the muscles from contracting, resulting in temporary paralysis.
Letybo is used in adults under 75 years of age to temporarily improve moderate to severe vertical lines between the eyebrows, in cases where their presence has a significant psychological impact.

2. What you need to know before using Letybo

Do not use Letybo:

• if you are allergic to botulinum toxin type A or to any of the other ingredients of this medicine (listed in section 6)
• if you have muscle activity disorders such as myasthenia gravis, Lambert-Eaton syndrome, or amyotrophic lateral sclerosis
• if you have an acute infection or inflammation at the proposed injection sites

Warnings and precautions
Consult your doctor before using Letybo if you experience:

• any disorder affecting muscles and/or their direct control by the nervous system
• difficulty swallowing or breathing, or if you have experienced these in the past
• a blood clotting disorder

If you have a history of these conditions, Letybo is not recommended for you.
Pain related to the needle and/or fear of injections may cause fainting due to a sudden drop in blood pressure.
Very rarely, adverse effects due to the spread of botulinum toxin away from the injection site and cases of botulism have been reported following the use of botulinum toxin, including double vision, blurred vision and/or drooping eyelids, difficulty breathing or speaking, excessive muscle weakness, difficulty swallowing, or unintended presence of food or liquids in the airways. Swallowing and breathing difficulties are serious and may lead to death. If you experience difficulty swallowing, speaking, or breathing, seek immediate medical attention.

Children and adolescents
The use of Letybo is not recommended in children and adolescents under 18 years of age.

Other medicines and Letybo
Inform your doctor or pharmacist if you are currently using, have recently used, or might use any other medicines.
The following medicines may affect the action of Letybo or vice versa:

• medicines that affect the transmission of nerve impulses to muscles
• certain medicines used to treat bacterial infections, such as spectinomycin or so-called aminoglycoside antibiotics
• other medicines containing botulinum toxin.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before receiving this medicine.
Letybo is not recommended during pregnancy or breastfeeding, or if you are of childbearing age and not using contraceptive measures.

Driving and using machines
Botulinum toxin type A may cause weakness, dizziness, and visual disturbances. Do not drive or operate machinery if your reaction ability is impaired.

Letybo contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially 'sodium-free'.

3. How to use Letybo

The botulinum toxin unit is specific to Letybo. This means it is different from the units of
botulinum toxin used in other botulinum toxin preparations and is not interchangeable with them.
Letybo is administered only by a qualified physician who has the appropriate equipment for this treatment.
A detailed description of the preparation of the solution and instructions for use are provided in the section “The following information is intended exclusively for healthcare professionals” at the end of this leaflet.
The recommended dose is
20 units divided into five 0.1 ml injections (4 units each). Each injection is administered into the muscles above or between the eyebrows.
Letybo is for intramuscular use (i.m. use).
Once reconstituted, the vial must be used to treat only one patient during a single session. Any unused solution must be discarded as described after paragraph 6 in the information for healthcare professionals.
It is recommended to wait at least 3 months between two treatments with Letybo.
If you have received more Letybo than you should have
Overdose may cause paralysis of muscles and/or nerves. Signs of overdose may not be immediately evident after injection.
In case of overdose, you will be monitored by your doctor for symptoms such as generalized weakness or muscle paralysis. You will be hospitalized if symptoms of botulinum toxin type A poisoning occur, such as:

• generalized weakness
• drooping of the upper eyelid or double vision
• swallowing and speech difficulties
• partial paralysis of the muscles controlling respiration.

If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Most side effects are mild to moderate in severity, occur in the first few days after injection, and are temporary.
Some side effects may be very serious. If you experience any of the following side effects, inform your
doctor immediately or ask your family to inform the doctor and go to the nearest emergency room:
Uncommon – may affect up to 1 in 100 people

• Drooping of the upper eyelid, eyelid spasm

Rare – may affect up to 1 in 1,000 people

• Eyelid sensory disturbance, eyebrow ptosis
• Bleeding in the conjunctiva
• Eye pain, dry eye, visual field defect, blurred vision
• Reduced throat sensitivity
• Constipation
• Disorders affecting speech sound production

Very rare – may affect up to 1 in 10,000 people

• Muscle weakness
• Difficulty swallowing
• Infection due to aspiration of food or liquids into the airways or lungs
• Breathing difficulties

In addition to these possible side effects, a severe allergic reaction may cause the following symptoms:

• Difficulty swallowing, breathing, or speaking due to swelling of the face, lips, mouth, or throat; hives may also occur (see section 2).

Other known side effects may occur with the following frequencies. If they worsen, inform your
doctor or pharmacist:
Common – may affect up to 1 in 10 people

• Headache
• Injection site reactions

Uncommon – may affect up to 1 in 100 people

• Head discomfort
• Local swelling, for example of the eyelid, face, or around the eyes
• Injection site: pain, bruising, swelling, itching sensation, lump, pressure
• Bruising, for example around the eyes
• Infection, such as viral upper respiratory tract infection, e.g., common cold
• Mephisto sign (elevation of the outer part of the eyebrows)

Rare – may affect up to 1 in 1,000 people

• Migraine
• Inflammation of hair follicles
• Dizziness
• Abnormal sensation, such as tingling, prickling, or itching
• Nausea
• Dry skin, hives, itching sensation
• Facial pain
• Fever
• Oral herpes
• Increased blood potassium
• Influenza-like illness

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact your doctor or pharmacist. You can also report side effects directly via the national reporting system at the following website: 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 Letybo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after
Exp. The expiry date refers to the last day of that month.
Store and transport in a refrigerator (2 °C - 8 °C).
Reconstituted solution
Chemical and physical in-use stability has been demonstrated for 24 hours at 2 - 8 °C.
From a microbiological standpoint, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the user is responsible for the storage times during use and the conditions prior to use.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Letybo contains

• The active substance is botulinum toxin type A.
• One vial contains 50 units of botulinum toxin type A produced by Clostridium botulinum.
• After reconstitution, each 0.1 ml of solution contains 4 units.
• The other excipients are human albumin, sodium chloride.

Description of the appearance of Letybo and contents of the pack
Letybo is a white powder for injectable solution supplied in a clear glass vial with a rubber stopper and an aluminium seal.
The single pack contains one vial or two vials.
The multiple pack contains 2 boxes, each box containing one vial.
The multiple pack contains 6 boxes, each box containing one vial.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder and Manufacturer
CROMA-PHARMA GmbH
Industriezeile 6
2100 Leobendorf
Austria

The following information is intended exclusively for healthcare professionals:

Botulinum toxin units are not interchangeable between different products. The recommended doses
in units differ from those of other botulinum toxin-based preparations.
Instructions regarding the use, handling, and disposal of vials must be strictly followed.

Preparation of the solution
Reconstitution must be performed in accordance with good practice standards, particularly with regard to asepsis.
To reconstitute Letybo, an injectable solution of sodium chloride 9 mg/ml (0.9%) should be used as diluent, and a volume of 1.25 ml must be added.
It is good practice to perform vial reconstitution and syringe preparation over plastic-backed absorbent paper towels to collect any spills. The injectable sodium chloride solution 9 mg/ml (0.9%) is drawn into a syringe and should be injected gently into the vial to avoid foaming/bubbles or vigorous agitation, which may cause denaturation. The vial should be discarded if the vacuum fails to draw the solvent into the vial. Reconstituted Letybo is a clear, colorless solution, practically free from particles. Before use, the vial should be visually inspected to ensure the product is free from foreign particles.
Letybo must not be used if the reconstituted solution appears cloudy or contains particles.

Reconstituted solution
Chemical and physical stability during use has been demonstrated for 24 hours at 2–8 °C.
From a microbiological standpoint, unless the method of opening/reconstitution/dilution excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the user is responsible for the storage duration and conditions prior to use.
Any injectable solution stored for more than 24 hours must be discarded.
Unused medicinal product and waste materials derived from this medicinal product must be disposed of in accordance with local regulations.

Instructions for use
Intramuscular injections should be performed using a sterile syringe, such as an insulin or tuberculin syringe with a capacity of 1 ml and graduations of 0.01 ml, and a needle with a gauge range of 30 to 31 G.
Using a sterile syringe, withdraw 0.5 ml of properly reconstituted Letybo solution and expel any air bubbles from the barrel. The needle used to reconstitute the medicine should be removed and replaced with a new one for administration.
Care must be taken to ensure that Letybo is not injected into a blood vessel.
To reduce the risk of ptosis, injections near the levator palpebrae superioris muscle should be avoided, particularly in patients with broad depressor-supercilii complexes. When injecting two sites in each corrugator supercilii muscle, the first injection should be administered just above the medial margin of the eyebrows. The second injection should be administered approximately 1 cm above the supraorbital margin (palpable rigid bony edges above the upper eyelid), where the midline of the eyebrows intersect. The injection site for the procerus muscle is just above the midline of the nasal bridge, where horizontal wrinkles form between the medial ends of the eyebrows. When injecting the medial ends of the corrugator supercilii muscles and the midline of the eyebrows, injection sites should be at least 1 cm away from the supraorbital margin (palpable rigid bony edges above the upper eyelid).

Injections should be performed cautiously to avoid intravascular injection. Before injection, the thumb or index finger should be firmly placed below the orbital rim to prevent diffusion of the medicine into this area. The needle should be oriented upward and medially.
If treatment fails one month after a previous treatment session—i.e., in the absence of significant improvement from baseline—the following approaches may be considered:

• Analysis of the causes of failure, such as incorrect selection of muscles treated, injection technique, formation of neutralizing antibodies to the toxin, or insufficient dose
• Re-evaluation of the appropriateness of treatment with botulinum toxin type A

In the absence of adverse effects related to the previous treatment session, an additional treatment session may be initiated with an interval of at least three months between treatment sessions.

Procedure for safe disposal of vials, syringes, and used materials
For safe disposal, unreconstituted Letybo should be reconstituted in the vial with a small amount of water and then autoclaved. All empty vials, vials containing residual solution, syringes, or spills must be autoclaved. Alternatively, remaining Letybo may be inactivated with diluted sodium hydroxide solution (0.1 N NaOH) or diluted sodium hypochlorite solution (0.5% or 1% NaOCl).
After inactivation, vials, syringes, and used materials must not be emptied and should be collected in designated containers and disposed of in accordance with local regulations.

Recommendations in case of an accident during handling of botulinum toxin

• Absorb any spilled product using absorbent material soaked in sodium hypochlorite solution in the case of powder, or dry absorbent material in the case of reconstituted product.
• Contaminated surfaces should be cleaned using absorbent material soaked in sodium hypochlorite solution, then thoroughly dried.
• In case of a broken vial, proceed as indicated above, carefully collecting glass fragments and absorbing the product, taking care not to cause injury.
• If the product comes into contact with the skin, wash the contaminated area with sodium hypochlorite solution, then rinse thoroughly with water.
• If the product comes into contact with the eyes, rinse thoroughly with water or an ophthalmic irrigation solution.
• If the product comes into contact with a wound, cut, or abraded skin, rinse thoroughly with water and take appropriate medical measures based on the injected dose.