Nucala 100 mg solution for injection in pre-filled pen

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Nucala 100mg solution for injection in pre-filled pen

mepolizumab

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Nucala is and what it is used for

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

Mepolizumab, the active substance in 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 reduces the number of eosinophils in the blood and lungs.

Severe eosinophilic 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 high-dose inhaled medications, but your asthma is not well controlled by these treatments, Nucala may reduce the number of asthma attacks. If you are taking medications called oral corticosteroids, Nucala may also help reduce the daily dose needed to control your asthma.

Chronic rhinosinusitis with nasal polyps (CRSwNP)

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

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

Nucala may also help reduce the need for oral corticosteroids to control your symptoms.

Chronic Obstructive Pulmonary Disease (COPD)

Some people with COPD have too many eosinophils (a type of white blood cell) in the blood and lungs, leading to inflammation and thickening of the airways. It is a chronic disease that slowly worsens over time. Symptoms include difficulty breathing, cough, chest discomfort, and production of mucus. Nucala reduces the number of eosinophils in the blood and may reduce exacerbations (flare-ups) of COPD 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, along with some form of vasculitis. This means there is inflammation of the blood vessels. This disease most commonly affects the lungs and sinuses, but often involves other organs such as the skin, heart, and kidneys.

Nucala can help control or delay flare-ups of EGPA symptoms. This medicine may also help reduce the daily dose of oral corticosteroids needed to control your symptoms.

Hypereosinophilic syndrome (HES)

Hypereosinophilic syndrome (HES) is a condition characterized by a high number of eosinophils (a type of white blood cell) in the blood. These cells can damage body 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 may also help reduce the daily dose needed to control your symptoms and HES flare-ups.

2. What you need to know before using Nucala

Do not use Nucala:

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

• Consult your doctor if you think this applies to you.

Warnings and precautions

Talk to your doctor before starting to use this medicine.

Worsening of asthma or COPD

Some people may experience adverse reactions related to asthma or COPD, or their asthma or COPD may worsen during treatment with Nucala.

• Consult your doctor or nurse if your asthma or COPD remains uncontrolled or worsens after starting treatment with Nucala.

Allergic 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 receiving Nucala.

Parasitic infections

Nucala may reduce your resistance to infections caused by parasites. If you already have a parasitic infection, it should be treated before starting treatment with Nucala. If you live in an area where such infections are common or if you are traveling to such an area:

• Consult your doctor if you think either of these situations applies to you.

Children and adolescents

Severe eosinophilic asthma

The pre-filled pen is not indicated for use in children under 12 years of age for the treatment of severe eosinophilic asthma.

For children aged 6–11 years, consult your doctor, who will prescribe the recommended dose of Nucala to be administered by a nurse or doctor.

CRSV, COPD and HES

This medicine is not indicated for use in children or adolescents under 18 years of age for the treatment of CRSV, COPD or HES.

EGPA

This medicine is not indicated for use in children under 6 years of age for the treatment of EGPA.

Other medicines and Nucala

Tell your doctor if you are taking, have recently taken, or might need to take any other medicines.

Other medicines for asthma, CRSV, COPD, EGPA or HES

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

Pregnancy and breastfeeding

If you are pregnant, think you might be pregnant, or are planning to become pregnant, consult your doctor before using this medicine.

It is unknown whether the components of Nucala can pass into breast milk. If you are breastfeeding, you must consult your doctor before using Nucala.

Driving and using machines

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

Nucala contains polysorbate

This medicine contains 0.2 mg of polysorbate in each 100 mg dose. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

Nucala contains sodium

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

3. How to use Nucala

Nucala is administered as an injection just under the skin (subcutaneous injection).

Your doctor or nurse will decide whether you or your caregiver can inject Nucala. If considered appropriate, you or your caregiver will receive training on how to use Nucala correctly.

In children aged 6 to 11 years, Nucala must be administered by a doctor, nurse, or a trained caregiver.

Severe eosinophilic asthma

Recommended dose in adults and adolescents aged 12 years and older is 100 mg. One injection will be given every four weeks.

CRScNP

Recommended dose in adults is 100 mg. One injection will be given every four weeks.

COPD

Recommended dose in adults is 100 mg. One injection will be given every four weeks.

EGPA

Recommended dose in adults and adolescents aged 12 years and older is 300 mg. Three injections will be given every four weeks.

Children aged 6 to 11 years

Children weighing 40 kg or more:

Recommended dose is 200 mg. Two injections will be given every four weeks.

Children weighing less than 40 kg:

Recommended dose is 100 mg. One injection will be given every four weeks.

Injection sites should be at least 5 cm apart.

HES

Recommended dose in adults is 300 mg. Three injections will be given every four weeks.

Injection sites should be at least 5 cm apart.

Instructions for using the pre-filled pen are provided at the end of this leaflet.

If you use more Nucala than you should

Consult your doctor if you think you may have administered too much Nucala.

If you forget a dose of Nucala

You or your caregiver may administer the next dose of Nucala as soon as you remember. If you do not realize a dose has been missed until it is time for the next scheduled dose, administer only the next dose as planned. If you are unsure what to do, ask your doctor, pharmacist, or nurse.

If you stop treatment with Nucala

Do not stop receiving Nucala injections unless your doctor tells you to. Interrupting or stopping treatment with Nucala may cause your symptoms and attacks to return.

If your symptoms worsen while you are receiving Nucala injections:

• Inform your doctor.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them. The adverse effects caused by Nucala are generally mild to moderate, although occasionally they may be severe.

Allergic reactions

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

Symptoms may include:

• chest tightness, cough, difficulty breathing

• fainting, dizziness, feeling lightheaded (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) may be having a reaction, seek immediate medical attention.

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

• Consult your doctor before you (or your child) are given Nucala.

Other adverse effects include:

Very common:

may affect more than 1 in 10 people

• headache

Common:

may affect up to 1 in 10 people

• chest infection, with symptoms such as cough and fever (high temperature)
• urinary tract infection (blood in urine, painful and frequent urination, fever, lower back pain)
• herpes zoster (shingles)
• pain in the upper abdomen (stomach pain or discomfort in the upper part of the stomach)
• fever (high temperature)
• eczema (itchy red patches on the skin)
• injection site reaction (pain, redness, swelling, itching, and burning sensation in the skin near the site where the injection was given)
• back pain
• arthralgia (joint pain)
• pharyngitis (sore throat)
• nasal congestion (stuffy nose)

Rare:

may affect up to 1 in 1,000 people

• severe allergic reactions (anaphylaxis)

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

Reporting of adverse effects

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

5. Storage of Nucala

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

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

Store in a refrigerator (between 2 °C and 8 °C).

Do not freeze.

Keep in the original packaging to protect from light.

The Nucala pre-filled pen may be removed from the refrigerator and stored in the unopened outer packaging for up to 7 days at room temperature (below 30 °C), protected from light. Discard if left outside the refrigerator for more than 7 days.

6. Contents of the pack and other information

Composition of Nucala

The active substance is mepolizumab.

Each 1 ml of the pre-filled pen contains 100 mg of mepolizumab.

The other components are: sucrose, dibasic sodium phosphate heptahydrate, monohydrate citric acid, polysorbate 80 (E 433), disodium edetate, water for injections.

Nature of the product and contents of the container

Nucala is presented in a single-use pre-filled pen as 1 ml of a solution ranging from clear to opalescent and from colourless to pale yellow to pale brown.

Nucala is available in a pack containing 1 pre-filled pen, or in a multipack containing 3 x 1 pre-filled pens or 9 x 1 pre-filled pens.

Marketing Authorisation Holder

GlaxoSmithKline Trading Services Limited
12 Riverwalk
Citywest Business Campus
Dublin 24
D24 YK11
Ireland

Manufacturer

GlaxoSmithKline Manufacturing S.P.A
Strada Provinciale Asolana, No 90
43056 San Polo di Torrile, Parma
Italy

Further information on this medicinal product is available by contacting the local representative of the Marketing Authorisation Holder:

Belgium/Belgium/Belgium GlaxoSmithKline Pharmaceuticals s.a./n.v. Tel/Tel: + 32 (0) 10 85 52 00	Lithuania UAB “BERLIN-CHEMIE MENARINI BALTIC” Tel: + 370 52 691 947 [email protected]
	Luxembourg/Luxembourg GlaxoSmithKline Pharmaceuticals s.a./n.v. Belgium/Belgium Tel/Tel: + 32 (0) 10 85 52 00
Czech Republic GlaxoSmithKline, s.r.o. Tel: + 420 222 001 111 [email protected]	Hungary Berlin-Chemie/A. Menarini Kft. Tel.: + 36 23501301 [email protected]
Denmark GlaxoSmithKline Pharma A/S Tlf.: + 45 36 35 91 00 [email protected]	Malta GlaxoSmithKline Trading Services Ltd. Tel: +356 80065004
Germany GlaxoSmithKline GmbH & Co. KG Tel.: + 49 (0)89 36044 8701 [email protected]	Netherlands GlaxoSmithKline BV Tel: + 31 (0)33 2081100
Estonia OÜ Berlin-Chemie Menarini Eesti Tel: + 372 667 5001 [email protected]	Norway GlaxoSmithKline AS Tlf: + 47 22 70 20 00
Greece GlaxoSmithKline Μονοπρόσωπη A.E.B.E. Tel: + 30 210 68 82 100	Austria GlaxoSmithKline Pharma GmbH Tel: + 43 (0)1 97075 0 [email protected]
Spain GlaxoSmithKline, S.A. Tel: + 34 900 202 700 [email protected]	Poland GSK Services Sp. z o.o. Tel.: + 48 (0)22 576 9000
France Laboratoire GlaxoSmithKline Tel: + 33 (0)1 39 17 84 44 [email protected]	Portugal GlaxoSmithKline – Produtos Farmacêuticos, Lda. Tel: + 351 21 412 95 00 [email protected]
Croatia Berlin-Chemie Menarini Hrvatska d.o.o. Tel: +385 1 4821 361 [email protected]	Romania GlaxoSmithKline Trading Services Ltd. Tel: +40 800672524
Ireland GlaxoSmithKline (Ireland) Limited Tel: + 353 (0)1 4955000	Slovenia Berlin-Chemie / A. Menarini Distribution Ljubljana d.o.o. Tel: + 386 (0)1 300 2160 [email protected]
Iceland Vistor ehf. Tel: + 354 535 7000	Slovakia Berlin-Chemie / A. Menarini Distribution Slovakia s.r.o. Tel: + 421 2 544 30 730 [email protected]
Italy GlaxoSmithKline S.p.A. Tel: + 39 (0)45 7741111	Finland GlaxoSmithKline Oy Tel: + 358 (0)10 30 30 30
Cyprus GlaxoSmithKline Trading Services Ltd. Tel: +357 80070017	Sweden GlaxoSmithKline AB Tel: + 46 (0)8 638 93 00 [email protected]
Latvia SIA Berlin-Chemie/Menarini Baltic Tel: + 371 67103210 [email protected]

Date of the most recent review of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu and on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

1. Step-by-step instructions for using the pre-filled pen

Administration once every four weeks.

Follow these instructions on how to use the pre-filled pen. Failure to follow these instructions may affect the proper functioning of the pre-filled pen. You should also receive training on how to use the pre-filled pen. The Nucala pre-filled pen is intended for subcutaneous (under the skin) use only.

How to store Nucala

• Keep refrigerated before use.
• Do not freeze.
• Store the pre-filled pen in the original packaging to protect it from light.
• Keep out of the sight and reach of children.
• If necessary, the pre-filled pen may be kept at room temperature below 30 °C for no more than 7 days, provided it is kept in the original packaging. Carefully dispose of the pen if it has been left outside the refrigerator for more than 7 days.
• Store below 30 °C.

Before using Nucala

The pre-filled pen must be used only once and then discarded.

• Do not share your pre-filled pen with another person.
• Do not shake the pen.
• Do not use the pen if it falls onto a hard surface.
• Do not use the pen if it appears damaged.
• Do not remove the needle cap until just before your injection.

Know your pre-filled pen

Preparation

1. Prepare what you need

Find a comfortable, well-lit, and clean surface. Make sure you have the following items within reach: Nucala pre-filled pen Alcohol swab (not included) Gauze or cotton ball (not included)

Remove your pre-filled pen

Take the case out of the refrigerator. Check that the security seals are intact. Remove the tray from the case. Remove the plastic cover from the tray. Holding the pen by the middle, carefully remove it from the tray. Place the pen on a clean, flat surface at room temperature, away from direct sunlight and out of the reach of children. Do not use the pen if the case’s security seal is broken. Do not remove the needle cap at this time.

Inspect and wait 30 minutes before use

Check the expiration date on the pen label. Look through the inspection window to ensure the liquid is clear (free from particles and cloudiness) and colorless to pale yellow-brown. It is normal to see one or more air bubbles. Wait 30 minutes (and no more than 8 hours) before using. Do not use after the expiration date. Do not heat the pen in a microwave, with warm water, or under direct sunlight. Do not inject the solution if it appears cloudy, discolored, or contains particles. Do not use the pen if it has been left outside its packaging for more than 8 hours. Do not remove the needle cap at this time.

Choose the injection site

You may inject Nucala into your thighs or abdomen. If someone else is administering the injection, it may be given in the upper arm. If more than one injection is needed to complete your dose, leave at least 5 cm between each injection site. Do not inject where your skin is bruised, tender, red, or hard. Do not inject within 5 cm of your navel.

Clean the injection site

Wash your hands with soap and water. Clean the injection site with an alcohol swab and allow the skin to air dry. Do not touch the injection site again until you have finished.

Injecting

Remove the clear needle cap

Remove the clear needle cap from the pen by pulling it firmly outward. Do not worry if you see a drop of liquid at the tip of the needle. This is normal. Inject immediately after removing the needle cap, and always within the next 5 minutes. Do not touch the yellow needle shield with your fingers. This could activate the pen too early and damage the needle. After removal, do not reattach the needle cap to the pen, as it may accidentally start the injection.

Begin the injection

Hold the pen with the inspection window facing you so you can see it, and with the yellow needle shield pointing downward. Place the pen directly onto the injection site with the yellow needle shield resting on the skin surface, as shown in the figure. To start the injection, press the pen firmly downward until fully seated and keep it pressed against your skin. The yellow needle shield will slide upward into the pen. You should hear a first "click" indicating that the injection has started. The yellow indicator will move downward across the inspection window as your dose is delivered. Do not lift the pen from your skin at this time, as you may not receive the full dose. Completing the injection may take up to 15 seconds. Do not use the pen if the yellow needle shield does not slide upward as described. Discard it (see step 9), and start again with a new pen.

Keep the pen in place to complete the injection

Keep pressing the pen until you hear the second "click," and the plunger and yellow indicator have stopped moving and the inspection window is fully filled. Continue holding the pen in place while counting to 5. Then lift the pen away from your skin. If you do not hear the second "click": Check whether the inspection window is completely filled by the yellow indicator. If you are unsure, press the pen for an additional 15 seconds to ensure the injection is complete. Do not remove the pen until you are certain the injection is complete. You may notice a small drop of blood at the injection site. This is normal. If needed, press the area with a cotton ball or gauze for a few moments. Do not rub the injection site.

Dispose

Dispose of the used pen

Dispose of the used pen and needle cap according to local regulations. If in doubt, consult your doctor or pharmacist. Keep used pens and used needle caps out of sight and reach of children.