Letybo

Package leaflet: Information for the user

Letybo
Botulinum toxin type A
50 units, powder for solution for injection
Please read all of this leaflet carefully before the medicine is administered, as 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.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Letybo is and what it is used for
2. Important information before receiving 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 an active substance called botulinum toxin type A. It works by blocking nerve signals sent to the muscles into which it is injected. This prevents the muscles from contracting, resulting in temporary paralysis.
Letybo is used in adults under 75 years of age for the temporary improvement of the appearance of moderate or severe vertical frown lines between the eyebrows, when their presence has a significant psychological impact on the patient.

2. Important information before using Letybo

When not to use Letybo:

• if the patient is allergic to botulinum toxin type A or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has muscle function disorders such as myasthenia gravis, Lambert-Eaton syndrome or amyotrophic lateral sclerosis;
• if the patient has an acute infection or inflammatory condition at the planned injection sites.

Warnings and precautions
Before starting treatment with Letybo, consult a doctor if any of the following conditions are present:

• any disorder affecting muscles or their direct control by the nervous system;
• difficulty swallowing or breathing, currently or in the past;
• bleeding disorders.

If any of these conditions are present in the patient's history, Letybo is not recommended.
Pain associated with needle insertion or anxiety about injections may lead to fainting due to a sudden drop in blood pressure.
Very rarely, adverse reactions related to the spread of botulinum toxin to sites distant from the injection site have been reported, such as excessive muscle weakness. Swallowing and breathing difficulties are severe reactions which may lead to death.
Patients or their caregivers should be instructed to seek immediate medical help if swallowing, speech or breathing problems occur.

Children and adolescents
Letybo should not be used in children and adolescents under 18 years of age.

Letybo and other medicines
Inform the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to use.
Interactions may occur between Letybo and medicines:

• affecting nerve impulse transmission to muscles;
• used to treat bacterial infections, such as spectinomycin or aminoglycoside antibiotics;
• containing botulinum toxin available in other medicinal products.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor before using this medicine.
The use of Letybo is not recommended during pregnancy or breastfeeding, or in women of childbearing potential not using effective contraception.

Driving and operating machinery
Botulinum toxin type A may cause weakness, dizziness and visual disturbances. In such cases, due to reduced reaction ability, driving vehicles or operating machinery should be avoided.

Letybo contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. the medicine is considered "sodium-free".

3. How to use Letybo

The botulinum toxin units stated in this leaflet refer exclusively to Letybo. They cannot be interchanged with botulinum toxin units from other medicinal products.
Letybo may only be administered by a suitably qualified physician who has access to appropriate equipment for this procedure. A detailed description of solution preparation and administration instructions is provided in the section "Information intended exclusively for healthcare professionals" at the end of this leaflet.
The recommended dose is
20 units divided into five injections of 0.1 mL each (4 units). Each injection is administered into the muscles located above or between the eyebrows.
Letybo is a medicinal product for intramuscular (i.m.) injection.
After reconstitution, the vial may be used only once during a single session for one patient. Any unused solution must be discarded according to the instructions described in section 6 under "Information intended exclusively for healthcare professionals."
A minimum interval of at least three months is recommended between two treatment sessions with Letybo.
Administration of a higher than recommended dose of Letybo
Overdose may cause muscle or nerve paralysis. Symptoms of overdose may appear immediately after injection.
In case of overdose, the physician will monitor the patient for symptoms such as general weakness or muscle paralysis. Emergency medical assistance should be sought immediately or the patient should go to a hospital if symptoms of type A botulinum toxin poisoning occur, such as:

• general weakness,
• upper eyelid ptosis or double vision,
• swallowing and speech disorders,
• partial paralysis of respiratory muscles.

If you have any further doubts regarding the use of this medicinal product, consult your physician or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them.
Most side effects are mild to moderate in severity, occur during the first few days after injection, and are transient in nature.
Some side effects may be serious. If you experience any of the following side effects, contact your doctor immediately
or ask your relatives to do so and go to the nearest emergency department:
Uncommon – may affect fewer than 1 in 100 people

• drooping of the upper eyelid, eyelid spasm.

Rare – may affect fewer than 1 in 1,000 people

• sensory disturbance in the eyelid, brow ptosis,
• bleeding into the conjunctiva,
• eye pain, dry eye, reduced field of vision, loss of visual acuity,
• reduced sensation in the throat,
• constipation,
• voice quality disturbances.

Very rare – may affect fewer than 1 in 10,000 people

• muscle weakness,
• difficulty swallowing,
• infection due to aspiration of food or liquid 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; in addition to these symptoms, urticaria may occur (see section 2).

Other known side effects may occur with the following frequency. Please inform your doctor or pharmacist if these become severe:
Common – may affect fewer than 1 in 10 people

• headache,
• injection site reactions.

Uncommon – may affect fewer than 1 in 100 people

• feeling of discomfort in the head,
• local swelling, e.g. of the eyelid, face, or periorbital area,
• pain, bruising, swelling, itching, nodules, pressure at the injection site,
• bruising, e.g. around the eyes,
• infection, e.g. viral upper respiratory tract infection such as the common cold,
• "Mephistopheles effect" (elevation of the lateral parts of the eyebrows).

Rare – may affect fewer than 1 in 1,000 people

• migraine,
• folliculitis,
• dizziness,
• unusual sensations, e.g. pricking, tingling, itching,
• nausea,
• dry skin, urticaria, itching,
• facial pain,
• fever,
• oral herpes,
• increased blood potassium levels,
• influenza-like symptoms.

Reporting of side effects
If any side effects occur, including any side effects not listed in this leaflet, please inform your doctor. Side effects can be reported directly to the Department for 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
Side effects can also be reported to the marketing authorization holder.
Reporting side effects helps to 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 carton and label after:
EXP. The expiry date refers to the last day of the stated month.
Store in a refrigerator (2°C – 8°C).

Reconstituted solution
The ready-to-use solution has been shown to remain chemically and physically stable for 24 hours
at 2–8°C.
From a microbiological point of view, immediate use is recommended, unless the method of opening/reconstitution/dilution eliminates the risk of microbiological contamination. If the solution is not used immediately, the user is responsible for the duration and conditions of storage of the ready-to-use solution.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. 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 dose contains 4 units.
• The other ingredients are human albumin and sodium chloride.

What Letybo looks like and contents of the pack
Letybo is a white powder for solution for injection supplied in a 5 mL clear glass vial (Type I glass) with a chlorobutyl rubber stopper, sealed with an aluminium cap, presented in a cardboard box.
The single pack contains one or two vials.
The multipack contains 2 cardboard boxes; each cardboard box contains one vial.
The multipack contains 6 cardboard boxes; each cardboard box contains one vial.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Croma-Pharma GmbH
Industriezeile 6
2100 Leobendorf
Austria
E-mail: [email protected]
Tel.: +43 2262 684 68-0

Manufacturer Importer
Croma-Pharma GmbH
Cromazeile 2
2100 Leobendorf
Austria

Information intended exclusively for healthcare professionals:

The units of botulinum toxin in this product cannot be used interchangeably with units
of botulinum toxin in other products. Recommended doses expressed in units differ from those
of other products containing botulinum toxin.
Strict adherence to instructions regarding administration, preparation, and disposal of the medicinal product
is required.

Solution preparation
Reconstitution must be performed in accordance with good clinical practice, particularly using aseptic technique.
To reconstitute, add 1.25 mL of diluent – sodium chloride injection solution at a concentration of 9 mg/mL (0.9%) – to the Letybo medicinal product.
It is good practice to prepare the solution and syringe over a paper towel covered with a plastic-backed drape in case of spillage. The 9 mg/mL (0.9%) sodium chloride injection solution should be drawn into a syringe and gently injected into the vial to avoid foaming or air bubbles and vigorous mixing, which could cause denaturation. Discard the vial if the diluent does not get drawn into the vial under vacuum. The reconstituted Letybo solution should be clear, colorless, and free from particulate matter. The vial should be inspected visually before use to ensure the product contains no particulates.
Do not use Letybo if the reconstituted solution is not clear or contains particulate matter.

Reconstituted solution
The ready-to-use product has been shown to maintain chemical and physical stability for 24 hours at 2–8°C.
From a microbiological standpoint, immediate use is recommended unless the method of opening/reconstitution/dilution eliminates the risk of microbiological contamination. If the product is not used immediately, the user is responsible for the duration and conditions of storage of the ready-to-use solution.
Any reconstituted solution stored for longer than 24 hours should be discarded.
All unused residues of the medicinal product or waste materials must be disposed of in accordance with local regulations.

Instructions for use
Intramuscular injections should be administered using a sterile 1 mL insulin or tuberculin syringe calibrated in 0.01 mL increments and a needle sized between 30 and 31 G.
Withdraw 0.5 mL of the appropriately reconstituted Letybo solution into a sterile syringe and remove all air bubbles from the barrel. The needle used for reconstitution should be removed and replaced with a new needle for administration.
Care must be taken not to inject the Letybo medicinal product into a blood vessel.
To prevent complications such as ptosis (eyelid drooping), avoid injecting near the levator palpebrae superioris muscle, especially in patients with a larger group of brow-lowering muscles. When injecting into each corrugator muscle, the first injection should be administered directly above the medial brow margin. The second injection should be administered approximately 1 cm above the supraorbital rim (the hard bony edge palpable above the upper part of the upper eyelid), where the midlines of both brows meet.
The injection site into the nasal part of the procerus muscle is located just above the midline of the nasal bony ridge, where horizontal wrinkles form between the medial ends of the brows.
When injecting into the medial ends of the corrugator supercilii muscles and the glabellar lines, injection sites should be located at least 1 cm above the supraorbital rim (the hard bony edge palpable above the upper part of the upper eyelid).

Injections should be performed carefully to avoid injecting into blood vessels. Prior to injection, the thumb or index finger may be placed below the orbital rim and firmly pressed to prevent leakage of the medicinal product in this area. The needle should be directed upward and medially.
If treatment fails one month after the initial series of procedures, i.e., if there is no significant improvement compared to baseline, the following actions may be considered:

• Analysis of failure causes, i.e., injection into incorrect muscles, inappropriate injection technique, development of neutralizing antibodies to the toxin, or insufficient dose;
• Re-evaluation of the appropriateness of using botulinum toxin type A.

If no adverse events occur following the previous treatment session, another session may be performed, provided that at least three months elapse between sessions.

Procedure for safe disposal of used vials, syringes, and materials
For safe disposal, the unreconstituted Letybo product should be reconstituted in the vial using a small amount of water and then sterilized in an autoclave. Empty vials, vials containing residual solution, syringes, and materials contaminated with the solution should be sterilized in an autoclave. Alternatively, any residual Letybo product may be inactivated by adding diluted sodium hydroxide solution (0.1 N NaOH) or diluted sodium hypochlorite solution (0.5% or 1% NaOCl).
After inactivation, used vials, syringes, and materials must not be emptied but should be placed directly into appropriate containers and disposed of in accordance with local regulations.

Recommendations for procedures in case of unexpected events during administration of botulinum toxin

• Any spillage of the product should be cleaned up immediately: use absorbent material soaked in sodium hypochlorite solution (in case of powder) or dry absorbent material in case of reconstituted product.
• Contaminated surfaces should be wiped with absorbent material soaked in sodium hypochlorite solution and then dried.
• If a vial breaks, follow the above instructions. Carefully collect the broken glass pieces and wipe up any residual product, avoiding cuts.
• If the medicinal product comes into contact with the skin, wash the area with sodium hypochlorite solution, then rinse thoroughly with water.
• If the product gets into the eyes, rinse the eyes thoroughly with a large amount of water or eye irrigation solution.
• If the medicinal product enters a wound, cut, or skin fissure, thoroughly rinse the area with a large amount of water, then take appropriate medical actions depending on the dose to which the affected person was exposed.