Package leaflet: Information for the user

Repatha 140 mg solution for injection in pre-filled syringe

evolocumab
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, pharmacist or nurse.
This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.
The warnings and instructions contained in this document are intended for the person taking the medicine. Parents or caregivers responsible for administering the medicine to others, for example to a child, should follow the information accordingly.

Contents of this leaflet

What Repatha is and what it is used for
What you need to know before using Repatha
How to use Repatha
Possible side effects
How to store Repatha
Contents of the pack and other information

1. What is Repatha and what is it used for

What Repatha is and how it works
Repatha is a medicine that lowers levels of "bad" cholesterol, a type of fat present in the blood.
Repatha contains evolocumab as the active substance, a monoclonal antibody (a type of specialized protein designed to bind to a specific target substance in the human body). Evolocumab is designed to bind to a substance called PCSK9, which affects the liver's ability to remove cholesterol from the blood. By binding to and removing PCSK9, the medicine increases the amount of cholesterol taken up by the liver, thereby lowering cholesterol levels in the blood.

What Repatha is used for
Repatha is used in addition to diet to lower cholesterol:

in adults with high blood cholesterol levels (primary hypercholesterolemia [heterozygous familial and non-familial] or mixed dyslipidemia). It is administered:
- together with a statin or another cholesterol-lowering medicine, if the maximum dose of a statin does not sufficiently reduce cholesterol levels.
- alone or together with other cholesterol-lowering medicines when statins are not effective or cannot be used.
in children aged 10 years and older with high blood cholesterol levels caused by an inherited condition (heterozygous familial hypercholesterolemia or HeFH). It is administered alone or together with other cholesterol-lowering treatments.
in adults and children aged 10 years and older with high blood cholesterol levels caused by an inherited condition (homozygous familial hypercholesterolemia or HoFH). It is administered together with other cholesterol-lowering treatments.
in adults with high blood cholesterol levels and established atherosclerotic cardiovascular disease (history of heart attack, stroke, or blood vessel problems). It is administered:
- together with a statin or another cholesterol-lowering medicine, if the maximum dose of a statin does not sufficiently reduce cholesterol levels.
- alone or together with other cholesterol-lowering medicines when statins are not effective or cannot be used.

Repatha is used in patients who cannot adequately control their cholesterol levels through a cholesterol-lowering diet alone. While being treated with this medicine, you must continue to follow your cholesterol-lowering diet. Repatha may help prevent heart attacks, strokes, and certain heart procedures to restore blood flow to the heart due to the buildup of fatty deposits in the arteries (also known as atherosclerotic cardiovascular disease).

2. What you need to know before using Repatha

Do not use Repatha if you are allergic to evolocumab or to any of the other ingredients of this
medicinal product (listed in section 6).
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Repatha if you have liver disease.
The needle cap of the pre-filled glass syringe contains dry natural rubber (a latex derivative), which may cause severe allergic reactions.
To improve traceability of this medicinal product, your doctor or pharmacist should record the
name and batch number of the product administered to you in your patient record. You may
also wish to note down these details, in case you are asked for this information in the future.
Children and adolescents
The use of Repatha has been studied in children aged 10 years and older who are being treated for
heterozygous or homozygous familial hypercholesterolemia.
The use of Repatha has not been studied in children under 10 years of age.
Other medicines and Repatha
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicines.
Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, are planning a pregnancy, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Repatha has not been studied in pregnant women. It is not known whether Repatha is harmful to the unborn child.
It is not known whether Repatha passes into breast milk.
It is important that you inform your doctor if you are breastfeeding or planning to breastfeed. Your doctor will then help you decide whether to discontinue breastfeeding or discontinue/abstain from Repatha therapy, taking into account the benefits of breastfeeding for the child and the benefits of Repatha for the mother.
Driving and using machines
Repatha has no effect or negligible effect on the ability to drive vehicles or operate machinery.
Repatha contains sodium
This medicinal product contains less than 1 mmol of sodium (23 mg) per dose, i.e. essentially ‘sodium-free’.

3. How to use Repatha

Use this medicine exactly as your doctor has told you. If you are in any doubt, consult your doctor.

The recommended dose depends on your underlying condition:

For adults with primary hypercholesterolemia and mixed dyslipidemia, the dose is 140 mg every two weeks or 420 mg once a month.
For children aged 10 years and older with heterozygous familial hypercholesterolemia, the dose is 140 mg every two weeks or 420 mg once a month.
For adults or children aged 10 years and older with homozygous familial hypercholesterolemia, the recommended starting dose is 420 mg once a month. After 12 weeks, your doctor may decide to increase the dose to 420 mg every two weeks. If you are also undergoing apheresis, a procedure similar to dialysis in which cholesterol and other fats are removed from the blood, your doctor may decide to start your treatment at a dose of 420 mg every two weeks, timed to coincide with your apheresis sessions.
For adults with established atherosclerotic cardiovascular disease (a history of heart attack, stroke, or blood vessel problems), the dose is 140 mg every two weeks or 420 mg once a month.

Repatha is administered by subcutaneous injection (injected under the skin).
If your doctor prescribes a dose of 420 mg, you must use three pre-filled syringes, as each pre-filled syringe contains only 140 mg of the medicine. After reaching room temperature, all injections must be administered within 30 minutes.
If your doctor decides that you or a caregiver may administer the Repatha injections, you must be trained on how to properly prepare and inject the medicine. Do not attempt to inject Repatha until you have received instructions from your doctor or nurse on how to do so.
For instructions on storage, preparation, and administration of Repatha injections at home, see the “Instructions for Use” at the end of this leaflet.
Before starting treatment with Repatha, you must follow a cholesterol-lowering diet. You must continue this diet throughout your treatment with Repatha.
If Repatha has been prescribed together with another cholesterol-lowering medicine, follow your doctor’s instructions regarding the combined use of these medicines. In this case, also read the dosing instructions provided in the leaflet of that specific medicine.

If you use more Repatha than you should
Contact your doctor or pharmacist immediately.

If you forget to use Repatha
After a missed dose, take Repatha as soon as possible. Then contact your doctor, who will advise you on when to schedule your next dose, and follow their new instructions exactly.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Common (may affect up to 1 in 10 people)

Influenza (high temperature, sore throat, runny nose, cough, and chills)
Common cold, characterized by runny nose and sore throat, or sinus infection (nasopharyngitis or upper respiratory tract infections)
Feeling unwell (nausea)
Back pain
Joint pain (arthralgia)
Muscle pain
Injection site reactions such as bruising, redness, bleeding, pain, or swelling
Allergic reactions including rash
Headache

Uncommon (may affect up to 1 in 100 people)

Hives, characterized by red, itchy bumps appearing on the skin
Influenza-like symptoms

Rare (may affect up to 1 in 1,000 people)

Swelling of the face, mouth, tongue, or throat (angioedema)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Repatha

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 in a refrigerator (2 °C–8 °C). Do not freeze.
Keep in the original packaging to protect the medicine from light.
Before injection, the pre-filled syringe may be removed from the refrigerator and allowed to reach room temperature (up to 25 °C). This will make the injection less uncomfortable. Once removed from the refrigerator, Repatha may be stored at room temperature (up to 25 °C) in the original carton and must be used within 1 month.
Do not use this medicine if you notice any changes in colour or the presence of large clumps, fragments, or coloured particles.
Do not dispose of medicines via wastewater or household waste.
Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Repatha contains

The active substance is evolocumab. Each pre-filled syringe contains 140 mg of evolocumab in 1 mL of solution.
The other components are proline, glacial acetic acid, polysorbate 80, sodium hydroxide, water for injections.

Description of the appearance of Repatha and contents of the pack
Repatha is a solution that ranges from clear to opalescent, colourless to slightly yellow, and is almost free from particles.
Each pack contains one single-use pre-filled syringe.

Marketing Authorisation Holder and Manufacturer
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Marketing Authorisation Holder
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Manufacturer
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
Co Dublin
Ireland

Manufacturer
Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
s.a. Amgen n.v. Amgen Switzerland AG Vilniaus filialas
Tel/Tél: +32 (0)2 7752711 Tel: +370 5 219 7474

България Luxembourg/Luxemburg
Амджен България ЕООД s.a. Amgen
Тел.: +359 (0)2 424 7440 Belgique/Belgien
Tel/Tél: +32 (0)2 7752711

Česká republika Magyarország
Amgen s.r.o. Amgen Kft.
Tel: +420 221 773 500 Tel.: +36 1 35 44 700

Danmark Malta
Amgen, filial af Amgen AB, Sverige Amgen B.V.
Tlf: +45 39617500 The Netherlands
Tel: +31 (0)76 5732500

Deutschland Nederland
AMGEN GmbH Amgen B.V.
Tel.: +49 89 1490960 Tel: +31 (0)76 5732500

Eesti Norge
Amgen Switzerland AG Vilniaus filialas Amgen AB
Tel: +372 586 09553 Tel: +47 23308000

Ελλάδα Österreich
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. Amgen GmbH
Τηλ.: +30 210 3447000 Tel: +43 (0)1 50 217

España Polska
Amgen S.A. Amgen Biotechnologia Sp. z o.o.
Tel: +34 93 600 18 60 Tel.: +48 22 581 3000

France Portugal
Amgen S.A.S. Amgen Biofarmacêutica, Lda.
Tél: +33 (0)9 69 363 363 Tel: +351 21 422 06 06

Hrvatska România
Amgen d.o.o. Amgen România SRL
Tel: +385 (0)1 562 57 20 Tel: +4021 527 3000

Ireland Slovenija
Amgen Ireland Limited AMGEN zdravila d.o.o.
Tel: +353 1 8527400 Tel: +386 (0)1 585 1767

Ísland Slovenská republika
Vistor hf. Amgen Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 321 114 49

Italia Suomi/Finland
Amgen S.r.l. Amgen AB, sivuliike Suomessa/Amgen AB, filial i Finland
Tel: +39 02 6241121 Puh/Tel: +358 (0)9 54900500

Kύπρος Sverige
C.A. Papaellinas Ltd Amgen AB
Τηλ.: +357 22741 741 Tel: +46 (0)8 6951100

Latvija United Kingdom (Northern Ireland)
Amgen Switzerland AG Rīgas filiāle Amgen Limited
Tel: +371 257 25888 Tel: +44 (0)1223 420305

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu.
__________________________________________________________________________________

Instructions for use:

Repatha, single-use pre-filled syringe

Parts Guide
Before use		After use
Plunger Medicinal Cylinder Syringe cylinder Gray needle cap inserted		Used plunger Used syringe cylinder Used needle Gray needle cap removed
	The needle is inside.

Important
Before using a single-use pre-filled Repatha syringe, read these important
information:

Do not freeze the pre-filled Repatha syringe or use a syringe that has been frozen.
Do not use the pre-filled Repatha syringe if the packaging is open or damaged.
Do not use a pre-filled Repatha syringe that has fallen onto a hard surface. Some parts of the syringe may have broken even if the damage is not visible. Use a new pre-filled Repatha syringe.
Do not remove the grey needle cap from the pre-filled Repatha syringe unless you are ready to perform the injection.

Step 1: Preparation
A	Remove the Repatha pre-filled syringe from the refrigerator and wait 30 minutes.
Before proceeding with the injection, wait at least 30 minutes to allow the pre-filled syringe to naturally reach room temperature. Check that the box label shows the name Repatha. •Do not attempt to heat the Repatha pre-filled syringe using heat sources such as hot water or a microwave oven.
Do not leave the Repatha pre-filled syringe in direct sunlight.
Do not shake the Repatha pre-filled syringe.
B	Gather all necessary materials for administering the injection.
Wash your hands thoroughly with soap and water. On a flat, clean, and well-lit surface, prepare: • One Repatha pre-filled syringe in its packaging. • Alcohol swabs. • A cotton ball or gauze pad. • A plaster (bandage). • A sharps disposal container. •Do not use the Repatha pre-filled syringe after the expiration date printed on the packaging.
C	Choose the injection site.
Upper arm Abdomen Thigh You may use:• The thigh. • The abdomen, except for the area within 5 centimeters around the navel. • The outer upper arm (only if someone else is administering the injection). •Do not select areas where the skin is tender, bruised, red, or hardened. Avoid injecting in areas with scars or stretch marks. For each injection, choose a different site. If it is necessary to use the same injection site, ensure you do not inject in the exact same spot as the previous injection.
D	Clean the injection site.
Before administering the injection, clean the site with an alcohol swab and allow it to dry. •Do not touch the disinfected area again before giving the injection.
E	Remove the pre-filled syringe from its packaging.
Invert the packaging Apply gentle pressure To remove the syringe: •Peel back the paper from the packaging. •Place the packaging in your hand. •Invert the packaging and apply gentle pressure to the center to release the syringe into your palm. •If you cannot remove the pre-filled syringe, apply gentle pressure to the back of the packaging. •Do not grasp or pull the Repatha pre-filled syringe by the plunger or the gray needle cap, as this may damage the syringe. •Do not remove the gray needle cap from the pre-filled syringe until you are ready to administer the injection. Always hold the pre-filled syringe by the barrel.
F	Inspect the medication and syringe.
Plunger Syringe barrel Label with expiration date Gray needle cap in place Medication Always hold the pre-filled syringe by the barrel. Check that:• The name Repatha appears on the label of the pre-filled syringe. • The medication inside the pre-filled syringe is clear, colorless to slightly yellow. •Do not use the pre-filled syringe if any part of it appears cracked or broken.•Do not use the pre-filled syringe if the gray needle cap is missing or not securely attached.•Do not use the pre-filled syringe if the medication has changed color or contains large clumps, fragments, or colored particles. •Do not use the pre-filled syringe if the expiration date printed on it has passed.

Step 2: Preparing for Injection
A	Carefully remove the gray needle cap by pulling it upward and away from yourself. Do not leave the pre-filled syringe without the gray cap for more than 5 minutes. This could dry out the medication.
1. It is normal to see a drop of medication at the tip of the needle.		2. Immediately dispose of the cap in a sharps disposal container.
Do not twist or bend the gray needle cap, as the needle could become damaged.•Do not re-cap the gray needle cap onto the pre-filled syringe.

B	Remove air bubbles/air pockets.
Air bubbles/air pockets may be visible in the Repatha pre-filled syringe. If air bubbles/air pockets are present: • Hold the pre-filled syringe with the needle pointing upward. • Gently tap the syringe barrel with your fingers until the bubble/air pocket rises to the top end of the syringe. • Gently and slowly push the plunger to expel the air from the pre-filled syringe. Be very careful not to expel the medicine. • Do not tap the needle end of the syringe.
C	PIECE the injection site to create a stable surface.
Firmly grasp a fold of skin with your thumb and other fingers, creating a skin fold approximately 5 centimeters wide. It is important to keep the skin lifted during the injection.
Step 3: Injection
A	Keep the skin pinched. Insert the needle into the skin at an angle of 45–90°.
Do not press on the plunger while inserting the needle.
B	PUSH the plunger with slow and steady pressure until the syringe is empty.

C	Once completed, RELEASE the thumb and gently remove the syringe from the skin.
Do not recap the gray needle cap onto the used syringe.
Step 4: Final phase
A	Immediately dispose of the used syringe in a sharps disposal container.
Ask your healthcare provider for proper disposal methods, as there may be specific local guidelines. • Do not reuse a used syringe. • Do not use any remaining medicine in a used syringe. • Do not recycle the syringe or the sharps disposal container, or throw them into household waste. Keep the used syringe and the sharps disposal container out of sight and reach of children.
B	Examine the injection site.
If bleeding occurs, apply a cotton ball or gauze pad and apply gentle pressure to the injection site. If needed, apply a bandage. • Do not rub the injection site.

Package leaflet: Information for the user

Repatha 140 mg solution for injection in a pre-filled pen

evolocumab
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, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.
The warnings and instructions in this document are intended for the person taking the medicine. Parents or caregivers responsible for administering the medicine to others, for example to a child, should follow the information accordingly.

Contents of this leaflet

What Repatha is and what it is used for
What you need to know before using Repatha
How to use Repatha
Possible side effects
How to store Repatha
Contents of the pack and other information

1. What is Repatha and what is it used for

What is Repatha and how does it work
Repatha is a medicine that lowers levels of "bad" cholesterol, a type of fat present in the blood.
Repatha contains evolocumab as the active substance, a monoclonal antibody (a type of specialised protein designed to bind to a target substance in the human body). Evolocumab is designed to bind to a substance called PCSK9, which affects the liver's ability to remove cholesterol. By binding to and removing PCSK9, the medicine increases the amount of cholesterol taken up by the liver, thereby lowering cholesterol levels in the blood.

What Repatha is used for
Repatha is used in addition to diet to lower cholesterol:

in adults with high levels of cholesterol in the blood (primary hypercholesterolaemia [heterozygous familial and non-familial] or mixed dyslipidaemia). It is administered:
- together with a statin or another cholesterol-lowering medicine, if the maximum dose of a statin does not sufficiently lower cholesterol levels.
- alone or together with other cholesterol-lowering medicines when statins are not effective or cannot be used.
in children aged 10 years and older with high levels of cholesterol in the blood caused by an inherited condition (heterozygous familial hypercholesterolaemia or HeFH). It is administered alone or together with other cholesterol-lowering treatments.
in adults and children aged 10 years and older with high levels of cholesterol in the blood caused by an inherited condition (homozygous familial hypercholesterolaemia or HoFH). It is administered together with other cholesterol-lowering treatments.
in adults with high levels of cholesterol in the blood and established atherosclerotic cardiovascular disease (history of heart attack, stroke, or blood vessel problems). It is administered:
- together with a statin or another cholesterol-lowering medicine, if the maximum dose of a statin does not sufficiently lower cholesterol levels.
- alone or together with other cholesterol-lowering medicines when statins are not effective or cannot be used.

Repatha is used in patients who cannot control their cholesterol levels through a cholesterol-lowering diet alone. During treatment with this medicine, you must continue to follow your cholesterol-lowering diet. Repatha may help prevent heart attack, stroke, and certain heart procedures to restore blood flow to the heart due to the build-up of fatty deposits in the arteries (also known as atherosclerotic cardiovascular disease).

2. What you need to know before using Repatha

Do not use Repatha if you are allergic to evolocumab or to any of the other ingredients of this
medicine (listed in section 6).
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Repatha if you have liver disease.
The needle cap of the pre-filled glass pen contains dry natural rubber (a derivative of latex), which may cause severe allergic reactions.
In order to improve traceability of this medicine, your doctor or pharmacist should record the name and batch number of the product you have been given in your patient record. You may also wish to note down these details, in case you are asked for this information in the future.
Children and adolescents
The use of Repatha has been studied in children aged 10 years and older being treated for heterozygous or homozygous familial hypercholesterolemia.
The use of Repatha has not been studied in children under 10 years of age.
Other medicines and Repatha
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Repatha has not been studied in pregnant women. It is not known whether Repatha is harmful to the unborn baby.
It is not known whether Repatha passes into breast milk.
It is important that you inform your doctor if you are breastfeeding or planning to breastfeed. Your doctor will then help you decide whether to stop breastfeeding or stop taking Repatha, taking into account the benefits of breastfeeding for the baby and the benefits of Repatha for the mother.
Driving and using machines
Repatha has no effect or negligible effect on the ability to drive vehicles or operate machinery.
Repatha contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e. essentially ‘sodium-free’.