Nuceiva

Package leaflet: Information for the user

NUCEIVA 50 units powder for injectable solution

botulinum toxin type A
Please read this leaflet carefully before 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.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What NUCEIVA is and what it is used for

NUCEIVA contains the active substance botulinum toxin type A.
It prevents muscles from contracting, leading to temporary paralysis. It works by blocking nerve impulses
to the muscles into which it is injected.
NUCEIVA is used for the temporary improvement of moderate to severe frown lines between the eyebrows.
It is used in adults under 65 years of age in whom these facial lines have a significant psychological impact.

2. What you need to know before using NUCEIVA

Do not use NUCEIVA

• 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 myasthenia gravis or Eaton-Lambert syndrome (chronic diseases affecting the muscles);
• if you have an infection or inflammation at the proposed injection sites between the eyebrows and above the eyebrows (as shown in Figure 1).

Warnings and precautions
Adverse reactions possibly related to the spread of botulinum toxin from the injection site (e.g. muscle weakness, difficulty swallowing, or aspiration of food or liquids into the airways) may very rarely occur. Patients receiving the recommended doses may experience excessive muscle weakness.
Injection has been associated with localized pain, inflammation/swelling, altered sensation (paresthesia), reduced sensation (hypoesthesia), tenderness, skin rash (erythema), localized infection, bleeding and/or bruising. Needle-related pain and/or anxiety may cause vasovagal reactions such as pallor, nausea, sweating, blurred vision, rapid heartbeat, mental confusion and/or a temporary drop in blood pressure causing dizziness or fainting.
Contact your doctor immediately if, after treatment, you experience difficulty swallowing, speaking, or breathing.

• This medicine is not recommended for patients who have recently or previously experienced swallowing (dysphagia) or breathing problems, which, in the physician’s opinion, would preclude safe administration of the product.
• Too frequent or excessive dosing may lead to antibody formation, which could prevent botulinum toxin type A from working, even for other uses.
• Very rarely, an allergic reaction may occur following botulinum toxin injection. Symptoms may include skin reactions such as hives and itching, red or pale skin, swelling of the eyes, lips, mouth or throat, weak and rapid pulse, dizziness, and wheezing or labored breathing.
• After treatment, drooping of the eyelid may occur.

Inform your doctor if:

• you have had problems with previous botulinum toxin injections;
• you do not observe any significant improvement in wrinkles one month after the first treatment cycle;
• you suffer from certain neurological disorders (such as amyotrophic lateral sclerosis or motor neuropathy);
• there is inflammation at the proposed injection site(s);
• the muscles to be injected are weak or atrophied;
• you have a bleeding disorder, as injection may cause bruising.

Children and adolescents
The use of this medicine is not recommended in individuals under 18 years of age.
Other medicines and NUCEIVA
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The use of botulinum toxin is not recommended in combination with aminoglycoside antibiotics, spectinomycin, or other medicines that interfere with nerve impulses to the muscle.
Inform your doctor if you have recently been injected with a medicine containing botulinum toxin (the active substance in NUCEIVA), as this may excessively increase the effect of this medicine.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
The use of this medicine is not recommended during pregnancy and in women of childbearing age who are not using contraceptive measures.
This medicine is not recommended during breastfeeding.
Driving and using machines
Muscle weakness, dizziness, and visual disturbances caused by this medicine may impair your ability to drive or operate machinery. Do not drive or use machinery until these effects have resolved.
NUCEIVA contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially "sodium-free".

3. How to use NUCEIVA

The unit doses of NUCEIVA are not interchangeable with those used for other botulinum toxin-containing preparations.
This medicine must be administered only by physicians with adequate qualifications and experience in the treatment of glabellar lines at the highest level of forehead wrinkling.
The usual dose of NUCEIVA is 20 units. A recommended volume of 0.1 millilitres (mL) (4 units) of this medicine will be injected into each of the 5 injection sites.
Improvement in the severity of frown lines between the eyebrows generally occurs within a few days after treatment.
The interval between treatments will be determined by the physician.

How NUCEIVA is injected
This medicine is injected into the muscles (intramuscularly), directly into the affected area above and between the eyebrows.
Once reconstituted, NUCEIVA must be used exclusively for the treatment of a single patient during one single session.
If you have any doubts about how to use 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.
In general, side effects occur in the first few days after the injection and are temporary. Most side effects are mild to moderate in severity.
If you experience difficulty breathing, swallowing or speaking after administration of this medicine, contact your doctor immediately.
If you develop hives, swelling (including of the face or throat), wheezing, feeling faint, or shortness of breath, contact your doctor immediately, as these may be symptoms of an allergic reaction.
The likelihood of experiencing a side effect is described using the following categories:

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. You may also report adverse reactions directly through the national reporting system listed in Annex V. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. How to store NUCEIVA

Store in the refrigerator (2 °C – 8 °C).
Keep this medicine out of the sight and reach of children.
Intact vial
Do not use this medicine after the expiry date stated on the vial and the outer carton following
Exp.

6. Package contents and other information

What NUCEIVA contains

• The active substance is: 50 units of botulinum toxin type A.
• The excipients are human albumin and sodium chloride.

Description of the appearance of NUCEIVA and contents of the pack
NUCEIVA is a white powder for injectable solution in a clear glass vial.
Each pack contains 1 vial or 4 vials (4 x 1) or 10 vials (10 x 1).
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder and Manufacturer
Evolus Pharma B.V.
Apollolaan 151
1077 AR Amsterdam
The Netherlands

For further information on this medicinal product, please contact the Marketing Authorisation Holder.

THE FOLLOWING INFORMATION IS INTENDED FOR HEALTHCARE PROFESSIONALS ONLY:
Botulinum toxin units are not interchangeable between products. The recommended doses in units differ from those of other botulinum toxin-containing preparations.
Reconstitution must be carried out according to good clinical practice, particularly with regard to aseptic technique. NUCEIVA should be reconstituted with 9 mg/mL (0.9%) sodium chloride injectable solution. Withdraw 1.25 mL of 9 mg/mL (0.9%) sodium chloride injectable solution into a syringe to obtain a reconstituted injectable solution at a concentration of 4 units/0.1 mL.

The central part of the rubber stopper should be cleaned with alcohol. Slowly inject the diluent into the vial through the rubber stopper using a needle, and gently rotate the vial, avoiding the formation of bubbles. The vial must be discarded if the vacuum fails to draw the diluent into the vial. Once reconstituted, the injectable solution should be visually inspected prior to use to ensure it is clear, colorless, and free of particulate matter.

Reconstituted NUCEIVA (50 units/1.25 mL) is injected using a sterile 30-gauge needle. Four units (4 U/0.1 mL) are administered at each of five injection sites (see Figure 1): two injections in each corrugator muscle (lower medial and upper medial profiles) and one injection in the procerus muscle, for a total dose of 20 units.

To reduce the risk of eyelid ptosis complications, the following measures should be taken:

• Avoid injection near the levator palpebrae superioris muscle, especially in patients with broader depressor supercilii complexes;
• Perform injections in the lateral corrugator muscle at least 1 cm above the supraorbital bony ridge;
• Ensure the injected volume/dose is accurate and, where possible, kept to a minimum.

Procedure for the safe disposal of vials, syringes, and used materials
Immediately after use, any unused reconstituted NUCEIVA injectable solution remaining in the vial and/or syringe must be inactivated prior to disposal by adding 2 mL of diluted sodium hypochlorite solution (0.5% or 1%). After inactivation, dispose of in accordance with applicable local regulations.
Used vials, syringes, and materials must not be emptied and should be discarded in designated containers and disposed of in accordance with applicable local regulations.

Recommendations in case of an accident during handling of botulinum toxin
In the event of an accident during handling of the product, whether in the dried, vacuum state or reconstituted, appropriate immediate measures as described below must be taken.

• The toxin is highly sensitive to heat and certain chemical agents.
• Any spills must be cleaned up immediately: use an absorbent material soaked in sodium hypochlorite solution (bleach solution) for dried, vacuum-stored product, or dry absorbent material for reconstituted product.
• Contaminated surfaces must be cleaned with absorbent material soaked in sodium hypochlorite solution (bleach solution), then dried.
• In case of vial breakage, carefully collect glass fragments and dry up the product as indicated above, avoiding skin cuts.
• In case of splashes, wash with sodium hypochlorite solution and rinse thoroughly with abundant water.
• In case of eye splashes, rinse eyes thoroughly with abundant water or with an ophthalmic irrigation solution.
• If the person administering the injection sustains an injury (cut or needlestick), proceed as described above and take appropriate medical measures based on the injected dose.

These instructions for use, handling, and disposal must be strictly followed.

Package leaflet: information for the user

NUCEIVA 100 units powder for injectable solution

Botulinum toxin type A
Read this leaflet carefully before 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.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What NUCEIVA is and what it is used for

NUCEIVA contains the active substance botulinum toxin type A.
It prevents muscles from contracting, resulting in temporary paralysis. It works by blocking nerve impulses
to the muscles into which it has been injected.
NUCEIVA is used for the temporary improvement of vertical frown lines between the eyebrows.
It is used in adults under 65 years of age in whom these facial lines have a significant psychological impact.

2. What you should know before using NUCEIVA

Do not use NUCEIVA

• 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 myasthenia gravis or Eaton-Lambert syndrome (chronic diseases affecting the muscles);
• if there is infection or inflammation at the proposed injection sites between and above the eyebrows (as shown in Figure 1).

Warnings and precautions
Adverse reactions possibly related to the spread of botulinum toxin from the injection site (e.g. muscle weakness, difficulty swallowing, or aspiration of food or liquids into the airways) may very rarely occur. Patients receiving the recommended doses may experience excessive muscle weakness.
Injection has been associated with local pain, inflammation/swelling, altered sensation (paresthesia), reduced sensation (hypoesthesia), tenderness, skin rash (erythema), localized infection, bleeding and/or bruising. Pain and/or anxiety related to needle insertion may cause vasovagal responses such as paleness, nausea, sweating, blurred vision, rapid heartbeat, mental confusion and/or a temporary drop in blood pressure causing dizziness or fainting.
Seek immediate medical advice if, after treatment, you experience difficulty swallowing, speaking, or breathing.

• This medicine is not recommended for patients who have recently or in the past experienced swallowing (dysphagia) or breathing problems that, in the physician’s opinion, would preclude safe administration of the product.
• Too frequent or excessive administration may lead to the formation of antibodies, which could prevent botulinum toxin type A from working, even for other uses. To avoid this, at least three months should elapse between doses.
• Very rarely, an allergic reaction may occur following botulinum toxin injection. Symptoms may include skin reactions such as hives and itching, flushed or pale skin, swelling of the eyes, lips, mouth or throat, weak and rapid pulse, dizziness, and wheezing or labored breathing.
• After treatment, drooping of the eyelid may occur.

Inform your doctor if:

• you have had problems with previous botulinum toxin injections;
• you do not notice any significant improvement in wrinkles one month after the first treatment cycle;
• you suffer from certain neurological disorders (such as amyotrophic lateral sclerosis or motor neuropathy);
• there is inflammation at the proposed injection site(s);
• the muscles to be injected are weak or atrophied;
• you have a bleeding disorder, as injection may cause bruising.

Children and adolescents
The use of this medicine is not recommended in individuals under 18 years of age.
Other medicines and NUCEIVA
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The use of botulinum toxin is not recommended in combination with aminoglycoside antibiotics, spectinomycin, or other medicines that interfere with nerve impulses to the muscle.
Inform your doctor if you have recently received an injection of a medicine containing botulinum toxin (the active substance in NUCEIVA), as this may excessively increase the effect of this medicine.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
The use of this medicine is not recommended during pregnancy and in women of childbearing potential who are not using contraceptive measures.
This medicine is not recommended during breastfeeding.
Driving and using machines
Muscle weakness, dizziness, and visual disturbances caused by this medicine may make driving and operating machinery dangerous. Do not drive or operate machinery until these effects have subsided.
NUCEIVA contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially "sodium-free".

3. How to use NUCEIVA

The unit doses of NUCEIVA are not interchangeable with those used for other botulinum toxin preparations.
This medicine must be injected only by physicians with appropriate qualifications and experience in the treatment of glabellar forehead lines at maximum wrinkle severity.
The usual dose of NUCEIVA is 20 units. A recommended volume of 0.1 millilitres (mL) (4 units) of this medicine will be injected into each of the 5 injection sites.
Improvement in the severity of frown lines between the eyebrows generally occurs within a few days after treatment.
The interval between treatments will be determined by the physician.

How NUCEIVA is injected
This medicine is injected into the muscles (intramuscularly), directly into the affected area above and between the eyebrows.
Once reconstituted, NUCEIVA must be used exclusively for a single patient during one single session.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
In general, side effects occur in the first few days after the injection and are temporary. Most side effects are mild to moderate in severity.
If you experience difficulty breathing, swallowing, or speaking after receiving this medicine, contact your doctor immediately.
If you develop hives, swelling (including of the face or throat), wheezing, feeling faint, or shortness of breath, contact your doctor immediately, as these may be symptoms of an allergic reaction.
The likelihood of experiencing a side effect is described using the following categories:

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist.
You can also report adverse reactions directly through the national reporting system listed in Annex V.
By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. How to store NUCEIVA

Store in the refrigerator (2 °C – 8 °C).
Keep this medicine out of the sight and reach of children.
Intact vial
Do not use this medicine after the expiry date stated on the vial and the carton after
Exp.

6. Package contents and other information

What NUCEIVA contains

• The active substance is: 100 units of botulinum toxin type A.
• The excipients are human albumin and sodium chloride.

Description of the appearance of NUCEIVA and contents of the pack
NUCEIVA is a white powder for solution for injection, presented in a clear glass vial.
Each pack contains 1 vial.

Marketing Authorisation Holder and Manufacturer
Evolus Pharma B.V.
Apollolaan 151
1077 AR Amsterdam
The Netherlands

For further information about this medicinal product, please contact the Marketing Authorisation Holder.

THE FOLLOWING INFORMATION IS INTENDED EXCLUSIVELY FOR HEALTHCARE PROFESSIONALS:

Botulinum toxin units are not interchangeable between different products. Recommended doses in units differ from those of other botulinum toxin-containing preparations.

Reconstitution must be performed in accordance with good clinical practice, particularly with regard to aseptic technique. NUCEIVA is reconstituted with 9 mg/mL (0.9%) injectable sodium chloride solution. Withdraw 2.5 mL of 9 mg/mL (0.9%) injectable sodium chloride solution into a syringe to obtain a reconstituted injectable solution at a concentration of 4 units/0.1 mL.

| Volume of solvent added to a 100-unit vial [9 mg/mL (0.9%) sodium chloride solution for injection] | Resulting dose (units per 0.1 mL) | |---|---| | 2.5 mL | 4.0 U |

The central portion of the rubber stopper should be cleaned with alcohol. Slowly inject the diluent into the vial through the rubber stopper using a needle, and gently rotate the vial, avoiding formation of bubbles. The vial should be discarded if the vacuum does not draw the diluent into the vial. After reconstitution, the injectable solution should be visually inspected prior to use to ensure it is clear, colourless, and free of particulate matter.

Reconstituted NUCEIVA (100 units/2.5 mL) is injected using a sterile 30-gauge needle. Four units (4 U/0.1 mL) are administered at each of five injection sites (see Figure 1): two injections in each corrugator muscle (lower medial and upper medial profile), and one injection in the procerus muscle, for a total dose of 20 units.

To reduce the risk of eyelid ptosis complications, the following measures should be taken:

• Avoid injection near the levator palpebrae superioris muscle, particularly in patients with broader depressor supercilii complexes;
• Perform injections into the corrugator muscle at least 1 cm above the supraorbital bony ridge;
• Ensure injected volume/dose is accurate and, whenever possible, kept to a minimum.

Procedure for safe disposal of vials, syringes, and used materials
Immediately after use, any unused reconstituted NUCEIVA injectable solution remaining in the vial and/or syringe must be inactivated prior to disposal by adding 2 mL of diluted sodium hypochlorite solution (0.5% or 1%). After inactivation, dispose of in accordance with applicable local regulations.
Used vials, syringes, and materials must not be emptied and should be discarded in designated containers and disposed of in accordance with applicable local regulations.

Recommendations in case of an accident during handling of botulinum toxin
In the event of an accident during handling of the product, whether in the lyophilized vacuum-dried form or reconstituted form, appropriate measures as described below must be taken immediately.

• The toxin is highly sensitive to heat and certain chemical agents.
• Any spills must be cleaned up immediately: use an absorbent material soaked in sodium hypochlorite solution (bleach solution) for the vacuum-dried product, or dry absorbent material for the reconstituted product.
• Contaminated surfaces must be cleaned with absorbent material soaked in sodium hypochlorite solution (bleach solution), then dried.
• In case of broken vial, carefully collect glass fragments and dry up the product as indicated above, avoiding skin cuts.
• In case of splashes, wash with sodium hypochlorite solution and rinse thoroughly with abundant water.
• In case of eye splashes, thoroughly rinse eyes with abundant water or ocular irrigation solution.
• If the person administering the injection sustains a skin injury (cut or needlestick), proceed as described above and implement appropriate medical measures based on the injected dose.

These instructions for use, handling, and disposal must be strictly followed.