NUCALA 100 mg POWDER FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Nucala 100 mg powder for solution for injection

mepolizumab

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

Contents of the pack

1. What is Nucala and what is it used for
2. What you need to know before you use Nucala
3. How to use Nucala
4. Possible side effects
5. Storing Nucala
6. Contents of the pack and further information
7. Step-by-step instructions for use

1. What is Nucala and what is it used for

Nucala contains the active substance mepolizumab, a monoclonal antibody. Mepolizumab is a type of protein designed to recognize a specific target substance in the body. It is used to treat severe asthmaand EGPA(Eosinophilic Granulomatosis with Polyangiitis) in adults, adolescents, and children from 6 years of age. It is also used to treat CRSwNP(Chronic Rhinosinusitis with Nasal Polyps) and HES(Hypereosinophilic Syndrome) in adults.

Mepolizumab, the active substance of Nucala, blocks a protein called interleukin-5. By blocking the action of this protein, it limits the production of eosinophils by the bone marrow and decreases the number of eosinophils in the blood and lungs.

Eosinophilic severe asthma

Some people with severe asthma have too many eosinophils(a type of white blood cell) in the blood and lungs. This condition is called eosinophilic asthma- the type of asthma that Nucala can treat. If you or your child are already using medications such as high-dose inhalers, but your asthma is not well-controlled by these medications, Nucala can reduce the number of asthma attacks. If you are taking medications called oral corticosteroids, Nucala can also help reduce the daily dose you need to control your asthma.

Chronic rhinosinusitis with nasal polyps (CRSwNP)

CRSwNP is a disease in which people have too many eosinophils(a type of white blood cell) in the blood, in the tissues that line the nose, and in the nasal sinuses. This can produce symptoms such as nasal congestion and loss of smell, as well as soft, gelatinous growths (called nasal polyps) that form inside the nose.

Nucala reduces the number of eosinophils in the blood and can reduce the size of your polyps, relieving nasal congestion and helping to prevent nasal polyp surgery.

Nucala can also help reduce the need for oral corticosteroidsto control your symptoms.

Eosinophilic granulomatosis with polyangiitis (EGPA)

EGPA is a disease in which people have too many eosinophils(a type of white blood cell) in the blood and tissues and also have some form of vasculitis. This means there is inflammation in the blood vessels. This disease most commonly affects the lungs and nasal sinuses, but often affects other organs such as the skin, heart, and kidneys.

Nucala can control or delay a flare-up of these EGPA symptoms. This medication can also help reduce the daily dose of oral corticosteroidsyou need to control your symptoms.

Hypereosinophilic syndrome (HES)

Hypereosinophilic syndrome (HES) is a disease in which there is a high number of eosinophils(a type of white blood cell) in the blood. These cells can damage the body's organs, particularly the heart, lungs, nerves, and skin.

Nucala helps reduce your symptoms and prevents flare-ups. If you are taking medications commonly known as oral corticosteroids, Nucala can also help reduce the daily dose of these medications you need to control your symptoms and HES flare-ups.

2. What you need to know before you use Nucala

Do not use Nucala:

• if you are allergicto mepolizumab or to any of the other ingredients of this medicine (listed in section 6).

• Consult your doctorif you think this applies to you.

Warnings and precautions

Consult your doctor before starting to use Nucala.

Asthma worsening

Some people have adverse effects related to asthma, or their asthma may worsen during treatment with Nucala.

• Consult your doctor or nurseif your asthma remains uncontrolled or worsens after starting treatment with Nucala.

Allergic reactions and injection site reactions

Medicines of this type (monoclonal antibodies)can cause severe allergic reactions when injected into the body (see section 4, “Possible side effects”).

If you have ever had a similar reaction to any injection or medicine,

• Consult your doctor before you are given Nucala.

Parasitic infections

Nucala may weaken your resistance to parasitic infections. If you already have a parasitic infection, it should be treated before starting treatment with Nucala. If you live in an area where these infections are common or if you are traveling to one of these areas:

• Consult your doctorif you think any of these circumstances apply to you.

Children

Eosinophilic severe asthma and EGPA

The use of this medicine is not indicated in children under 6 years of agefor the treatment of eosinophilic severe asthma or EGPA.

CRSwNP and HES

This medicine is not indicated for use in children or adolescents under 18 yearsfor the treatment of CRSwNP or HES.

Other medicines and Nucala

Tell your doctorif you are taking, have recently taken, or might take any other medicines.

Other medicines for asthma, CRSwNP, EGPA, or HES

• Once you have started treatment with Nucala, do not suddenly stop takingthe medicines you were taking to prevent your asthma, CRSwNP, EGPA, or HES. These medicines (especially those called oral corticosteroids) should be stopped gradually, under the direct supervision of your doctor and depending on your response to Nucala.

Pregnancy and breastfeeding

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctorbefore using this medicine.

It is not known whether the components of Nucala can pass into breast milk. If you are breastfeeding, consult your doctorbefore using Nucala.

Driving and using machines

It is unlikely that the possible side effects of Nucala will affect your ability to drive or use machines.

Nucala contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 100 mg; this is essentially “sodium-free”.

3. How to use Nucala

Nucala will be administered to you by your doctor, nurse, or healthcare professional via an injection just under your skin (subcutaneous injection).

Eosinophilic severe asthma

Adults and adolescents from 12 years

The recommended dosein adults and adolescents is 100 mg. You will be given an injection every four weeks.

Children from 6 to 11 years

The recommended doseis 40 mg. You will be given an injection every four weeks.

CRSwNP

Adults

The recommended dosein adults is 100 mg. You will be given 1 injection every four weeks.

EGPA

Adults and adolescents from 12 years

The recommended dosefor adults and adolescents is 300 mg. You will be given 3 injections every four weeks.

Children from 6 to 11 years

Children who weigh40kg or more:

The recommended doseis 200 mg. You will be given 2 injections every four weeks.

Children who weigh less than40kg:

The recommended doseis 100 mg. You will be given 1 injection every four weeks.

The injection sites should be at least 5 cm apart.

HES

Adults

The recommended dosein adults is 300 mg. You will be given 3 injections every four weeks.

The injection sites should be at least 5 cm apart.

If you miss a dose of Nucala

Contact your doctor or hospital as soon as possibleto reschedule your appointment.

If you stop treatment with Nucala

Do not stop receiving Nucala injections unless your doctor tells you to. Stopping or interrupting treatment with Nucala may cause your symptoms and attacks to come back.

If your symptoms worsen while you are receiving Nucala injections:

• Tell your doctor.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The side effects caused by Nucala are generally mild to moderate, although they can occasionally be severe.

Allergic reactions

Some people may have allergic reactions or reactions of an allergic type. These reactions can be common (may affect up to 1 in 10 people). They usually occur within minutes to hours after the injection, but sometimes the symptoms can start even several days later.

The symptoms can include:

• chest tightness, cough, difficulty breathing
• fainting, dizziness, feeling of dizziness (due to a drop in blood pressure)
• swelling of the eyelids, face, lips, tongue, or mouth
• hives
• rash

• If you think you (or your child) are having an allergic reaction, seek medical attention immediately.

If you (or your child) have ever had a similar reaction to any injection or medicine,

• Consult your doctor before you are given Nucala.

Other side effects include:

Very common:may affect more than 1 in 10 people

• headache

Common:may affect up to 1 in 10 people

• chest infection, whose symptoms may include cough and fever (high temperature)
• urinary tract infection (blood in the urine, painful and frequent urination, fever, pain in the lower back)
• upper abdominal pain (stomach pain or discomfort in the upper abdomen)
• fever (high temperature)
• eczema (red, itchy patches on the skin)
• injection site reactions (pain, redness, swelling, itching, and burning sensation in the skin near the injection site)
• back pain
• arthralgia (joint pain)
• pharyngitis (sore throat)
• nasal congestion (stuffy nose)

Uncommon:may affect up to 1 in 100 people

• herpes zoster (shingles)

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

• severe allergic reactions (anaphylaxis)

• If you get any of these symptoms, consult your doctor or nurse immediately.

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Nucala

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label or carton after EXP. The expiry date is the last day of the month shown.

Store below 25°C.

Do not freeze.

Keep the vial in the original packaging to protect it from light.

6. Container Contents and Additional Information

Nucala Composition

• The active ingredient is mepolizumab. Each vial contains 100 mg of mepolizumab.
• After reconstitution, each ml of solution contains 100 mg of mepolizumab.
• The other components are sucrose, disodium phosphate heptahydrate, and polysorbate 80.

Product Appearance and Container Contents

Nucala is a white lyophilized powder supplied in a clear, colorless glass vial with a rubber stopper.

Nucala is available in packs of 1 vial or in multipacks containing 3 individual vials.

Marketing Authorization Holder

GlaxoSmithKline Trading Services Limited

12 Riverwalk

Citywest Business Campus

Dublin 24

Ireland

Manufacturer

GlaxoSmithKline Manufacturing S.P.A

Strada Provinciale Asolana, 90

43056 San Polo di Torrile, Parma

Italy

Further information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu

You can request more information about this medication by contacting the local representative of the Marketing Authorization Holder:

Date of Last Revision of this Leaflet:

Other Sources of Information

Detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu

This information is intended only for healthcare professionals:

1. Step-by-Step Instructions for Use, Handling, Reconstitution, and Administration

Nucala is supplied as a white lyophilized powder in a single-use vial, for subcutaneous administration only.

Reconstitution should be carried out under aseptic conditions.

After reconstitution, the concentration of Nucala will be 100 mg/ml of mepolizumab. The injectable solution can be stored between 2°C and 30°C for a maximum of 8 hours. Any unused concentrate or remaining solution should be discarded after 8 hours following reconstitution.

Traceability

In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded.

Instructions for Reconstitution of Each Vial

1. Reconstitute the vial contents with 1.2 ml of sterile water for injectable preparationsusing, preferably, a 2 to 3 ml capacity syringe and a 21-gauge needle. The direction of the sterile water flow should be vertical, so that it falls into the center of the lyophilized powder. Allow the vial to stand at room temperature during reconstitution, gently rotating it in a circular motion for 10 seconds, at 15-second intervals, until the powder is dissolved.

Note: During the process, do not shakethe reconstituted solution, as this could cause foam formation or precipitation. Normally, reconstitution is complete within 5 minutes after addition of the sterile water, but may take longer.

1. If a mechanical reconstitution device (orbital shaker) is used for reconstitution of Nucala, reconstitution can be performed by orbital shaking at 450 rpm for no more than 10 minutes. Alternatively, orbital shaking can be performed at 1,000 rpm for no more than 5 minutes.

1. After reconstitution and before using Nucala, a visual inspection should be performed to determine the presence of particles and clarity. The solution should be clear to opalescent, and colorless to pale yellow or pale brown, free from visible particles. Small air bubbles are expected and are acceptable. If the solution still contains particles or is cloudy or milky, it should not be used.

1. If the reconstituted solution is not used immediately, it should be:
   • Protected from sunlight.
   • Stored below 30°C, do not freeze.
   • Discarded if not used within 8 hours after reconstitution.

Administration Instructions for 100 mg Dose

1. For subcutaneous administration, a 1 ml polypropylene syringe equipped with a 21 to 27 gauge x 0.5 inch (13 mm) disposable needle should be used preferably.
2. Before administration, withdraw 1 ml of the reconstituted Nucala solution. Do not shake the reconstituted solution during this process, as this could cause foam formation or precipitation.
3. Administer the 1 ml injection (equivalent to 100 mg of mepolizumab) subcutaneously into the upper arm, thigh, or abdomen.

If more than one vial is required for administration of the prescribed dose, repeat steps 1 to 3. It is recommended that individual injection sites be separated by at least 5 cm.

Administration Instructions for 40 mg Dose

1. For subcutaneous administration, a 1 ml polypropylene syringe equipped with a 21 to 27 gauge x 0.5 inch (13 mm) disposable needle should be used preferably.
2. Just before administration, withdraw 0.4 ml of the reconstituted Nucala solution. Do not shake the reconstituted solution during this process, as this could cause foam formation or precipitation. Discard the remaining solution.
3. Administer the 0.4 ml injection (equivalent to 40 mg of mepolizumab) subcutaneously into the upper arm, thigh, or abdomen.

Disposal

Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.