Repatha 140 mg solution for injection in pre-filled pen: detailed information

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

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

evolocumab

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.
This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.
The warnings and instructions contained in this document are intended for the person using the medicine. If you are a parent or caregiver responsible for administering the medicine to another person, for example, a child, you should follow this information accordingly.

Contents of the 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 Repatha is and what it is used for

What Repatha is and how it works

Repatha is a medicine that lowers levels of "bad" cholesterol, a type of fat found in the blood.

Repatha contains the active substance evolocumab, a monoclonal antibody (a type of specialized protein designed to bind to a specific substance in the 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 and reduces the level of cholesterol in the blood.

What Repatha is used for

Repatha is used as an add-on to diet to reduce cholesterol in patients:

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, when cholesterol levels are not sufficiently controlled with the maximum tolerated dose of a statin.
- alone or together with other cholesterol-lowering medicines when statins are ineffective or cannot be used.
Pediatric patients aged 10 years and older with high blood cholesterol levels due to an inherited disorder (heterozygous familial hypercholesterolemia or HeFH). It is administered alone or together with other cholesterol-lowering treatments.
Adults and pediatric patients aged 10 years and older with high blood cholesterol levels due to an inherited disorder (homozygous familial hypercholesterolemia or HoFH). It is administered together with other cholesterol-lowering medicines.
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, when cholesterol levels are not sufficiently controlled with the maximum tolerated dose of a statin.
- alone or together with other cholesterol-lowering medicines when statins are ineffective or cannot be used.

Repatha is used in patients who cannot control their cholesterol levels with diet alone. While taking this medicine, you must continue to follow the cholesterol-lowering diet prescribed for you. Repatha may help prevent heart attacks, strokes, and certain cardiac procedures performed to restore blood flow to the heart, which are caused by 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 medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Repatha if you have a liver disease.

For the purpose of improving traceability of this medicine, your doctor or pharmacist should record in your medical record the name and batch number of the medicine that has been administered to you. You are advised to also write down this information in case you are asked about it 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 need to take any other medicines.

Pregnancy and breastfeeding

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

Repatha has not been studied in pregnant women. It is unknown whether Repatha can harm the fetus.

It is unknown whether Repatha is present in human breast milk.

It is important that you inform your doctor if you are breastfeeding or intend to breastfeed. Your doctor will help you decide whether to discontinue breastfeeding or treatment with Repatha, taking into account the benefits of breastfeeding for the baby and the benefits of Repatha for the mother.

Driving and using machines

The effect of Repatha on the ability to drive and use machines is negligible or none.

Repatha contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; that is, essentially "sodium-free".

3. How to use Repatha

Follow exactly the administration instructions given by your doctor. If in doubt, consult your doctor again.

The recommended dose depends on the 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 from 10 years of age with heterozygous familial hypercholesterolemia, the dose is 140 mg every two weeks or 420 mg once a month.
for adults or children from 10 years of age with homozygous familial hypercholesterolemia, the recommended initial 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 also receive apheresis, a procedure similar to dialysis in which cholesterol and other fats are removed from the blood, your doctor may decide to start with a dose of 420 mg every two weeks to coincide with the apheresis treatment.
for adults with established atherosclerotic cardiovascular disease (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 injection under the skin (subcutaneous route).

If your doctor prescribes a dose of 420 mg, you must use three pre-filled pens, as each pre-filled pen contains only 140 mg of medication. After reaching room temperature, all injections should be administered within a 30-minute interval.

If your doctor considers that you or a caregiver can administer Repatha injections, you or your caregiver must receive training on how to properly prepare and inject Repatha. Do not attempt to inject Repatha until your doctor or nurse has shown you how to do it.

See the detailed instructions for use at the end of this leaflet for information on how to store, prepare, and administer Repatha injections at home. If you use the pre-filled pen, place the correct end (yellow end) of the pen against the skin before injection.

Before starting treatment with Repatha, you should already be following a cholesterol-lowering diet. While using Repatha, you must continue this diet.

If your doctor has prescribed Repatha together with another cholesterol-lowering medicine, follow their instructions on how to use these medicines together. In this case, also read the administration instructions 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 take Repatha

Administer the missed dose as soon as possible. Then contact your doctor to determine when to administer the next dose, and follow the new schedule exactly as instructed by your doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Frequent (may affect up to 1 in 10 people)

Influenza (fever, sore throat, nasal discharge, cough, and chills)
Common cold, such as nasal discharge, sore throat, or sinus infection (nasopharyngitis or upper respiratory tract infections)
Malaise (nausea)
Back pain
Joint pain (arthralgia)
Muscle pain
Reactions at the injection site, such as bruising, redness, bleeding, pain, or swelling
Allergic reactions, including skin rash
Headache

Uncommon (may affect up to 1 in 100 people)

Red, itchy skin welts (urticaria)
Influenza-like symptoms

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

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

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, 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 listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Repatha

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 and packaging after EXP or CAD. The expiry date refers to 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 pre-filled pen may be removed from the refrigerator and allowed to reach room temperature (up to 25 °C) before injection. This will make the injection less uncomfortable. Once removed from the refrigerator, Repatha may be stored at room temperature (up to 25 °C) in its original container and must be used within 1 month.

Do not use this medicine if you notice any change in colour or if it contains clumps, flakes, or large coloured particles.

Medicines must not be disposed of via wastewater or household waste.

Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Repatha

The active substance is evolocumab. Each SureClick pre-filled pen 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.

Appearance of the medicinal product and contents of the pack

Repatha is a solution that is transparent to opalescent, colourless to yellowish, and practically free from particles.

Each pack contains one, two, three, or six single-use SureClick pre-filled pens.

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:

Belgium/Belgium/Belgium

s.a. Amgen S.A.

Tel/Tel: +32 (0)2 7752711

Lithuania

Amgen Switzerland AG Vilnius Branch

Tel: +370 5 219 7474

Text in Cyrillic characters with the word Bulgaria, the name Amgen Bulgaria EOOD, and the telephone number +359 (0)2 424 7440

Luxembourg/Luxembourg

s.a. Amgen

Belgium/Belgium

Tel/Tel: +32 (0)2 7752711

Czech Republic

Amgen s.r.o.

Tel: +420 221 773 500

Hungary

Amgen Kft.

Tel.: +36 1 35 44 700

Denmark

Amgen, branch of Amgen AB, Sweden

Tlf: +45 39617500

Malta

Amgen B.V.

The Netherlands

Tel: +31 (0)76 5732500

Germany

AMGEN GmbH

Tel.: +49 89 1490960

Netherlands

Amgen B.V.

Tel: +31 (0)76 5732500

Estonia

Amgen Switzerland AG Vilnius Branch

Tel: +372 586 09553

Norway

Amgen AB

Tel: +47 23308000

Greece

Amgen Hellas Pharmaceuticals E.P.E.

Tel.: +30 210 3447000

Austria

Amgen GmbH

Tel: +43 (0)1 50 217

Spain

Amgen S.A.

Tel: +34 93 600 18 60

Poland

Amgen Biotechnologia Sp. z o.o.

Tel.: +48 22 581 3000

France

Amgen S.A.S.

Tel: +33 (0)9 69 363 363

Portugal

Amgen Biofarmacêutica, Lda.

Tel: +351 21 422 06 06

Croatia

Amgen d.o.o.

Tel: +385 (0)1 562 57 20

Romania

Amgen România SRL

Tel: +4021 527 3000

Ireland

Amgen Ireland Limited

Tel: +353 1 8527400

Slovenia

AMGEN zdravila d.o.o.

Tel: +386 (0)1 585 1767

Iceland

Vistor hf.

Tel: +354 535 7000

Slovakia

Amgen Slovakia s.r.o.

Tel: +421 2 321 114 49

Italy

Amgen S.r.l.

Tel: +39 02 6241121

Finland

Amgen AB, Finland Branch/Amgen AB, filial i Finland

Tel/Puh: +358 (0)9 54900500

Cyprus

C.A. Papaellinas Ltd

Tel.: +357 22741 741

Sweden

Amgen AB

Tel: +46 (0)8 6951100

Latvia

Amgen Switzerland AG Riga Branch

Tel: +371 257 25888

United Kingdom (Northern Ireland)

Amgen Limited

Tel: +44 (0)1223 420305

Date of the most recent review of this leaflet.

Other sources of information

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

_____________________________________________________________________________

Instructions for use:

Repatha single-use prefilled pen SureClick

Components guide

	Important: The needle is inside the yellow safety shield.

Important

Before using a Repatha prefilled pen, read this important information:

Do not freeze the Repatha prefilled pen or use a pen that has been frozen.
Do not remove the orange cap from the Repatha prefilled pen until you are ready for injection.
Do not use the Repatha prefilled pen if it has been dropped on a hard surface. A component of the Repatha prefilled pen may be broken even if you cannot see the break.

Step 1: Preparation

Remove a prefilled pen of Repatha from the carton.

Carefully lift the prefilled pen straight up and out of the carton.
Return the original carton containing unused prefilled pens to the refrigerator.
Allow the prefilled pen to reach room temperature naturally for at least 30 minutes before administering the injection.

Do not attempt to warm the prefilled pen using a heat source such as hot water or a microwave.
Do not expose the prefilled pen to direct sunlight.
Do not shake the prefilled pen.
Do not remove the orange cap from the prefilled pen too early.

Inspect the Repatha prefilled pen.

Diagram of an injection pen with an orange cap, yellow protective cover with inner needle, central viewing window, and medication indication

Make sure the medicine in the viewing window is clear and colorless to slightly yellow.

Check the expiration date.

Do not use the prefilled pen if the medicine is cloudy or has changed color, or contains clumps, flakes, or large particles.
Do not use the prefilled pen if any part is cracked or broken.
Do not use the prefilled pen if it has been dropped.
Do not use the prefilled pen if the orange cap is missing or loose.
Do not use the prefilled pen if the expiration date has passed.

If any of these situations apply, use a new prefilled pen.

Gather all the materials you will need for the injection.

Wash your hands thoroughly with soap and water.

On a clean, well-lit work surface, place the following:

A new pre-filled pen.
Alcohol wipes.
Cotton ball or gauze.
A bandage.
A sharps disposal container.

Blue injection pen, white pouch, two cotton swabs, skin-colored adhesive bandage, and red biohazard waste container

Prepare and clean the injection site.

Human body diagram with grey areas indicating the upper arm, abdominal area, and upper thigh

Use only these injection sites:

Thigh.
Abdominal area (abdomen), except for the area within 5 centimeters around the navel.
Outer area of the upper arm (only if someone else is administering the injection).

Clean the injection site with an alcohol wipe. Allow the skin to dry.

Do not touch this area again before the injection.
Choose a different site for each injection. If you need to use the same injection site, make sure not to inject in the exact same spot as the last time.
Do not administer injections in areas where the skin is tender, bruised, red, or hard. Avoid areas with scars or stretch marks.

Step 2: Prepare

Remove the orange cap by pulling it straight off, only when you are ready for the

injection. Do not leave the pre-filled pen without the orange cap for more than 5 minutes, as

this could dry out the medication.

Two hands removing the orange cap from a blue injection pen, with a black arrow indicating movement to the left

It is normal to see a drop of medication at the tip of the needle or yellow safety shield.

Do not twist, bend, or move the orange cap.
Do not reattach the orange cap to the pre-filled pen.
Do not insert your fingers into the yellow safety shield.

Important: Do not remove the orange cap from the pre-filled pen until you are ready to inject.

If you are unable to perform the injection, consult your healthcare professional.

Create a firm surface at the selected injection site (thigh, abdomen, or outer areas of the upper arm) using either the stretch method or the pinch method.

Stretch method

A hand pinching the skin between thumb and index finger, with two black arrows indicating lateral pulling motion

Firmly stretch the skin by moving the thumb and fingers in opposite directions to create an area about 5 centimeters wide.

Pinch method

Schematic drawing of two hands pinching the skin between thumb and index finger, with black arrows indicating the direction of pressure

Firmly pinch the skin between the thumb and fingers, covering an area about 5 centimeters wide.

Important: It is essential to keep the skin stretched or pinched during the injection.

Step 3: Inject

Keep the skin stretched or pinched. Once the orange cap has been removed, place

the yellow safety shield against your skin at a 90-degree angle. The needle

is inside the yellow safety shield.

Do not press the grey start button yet.

Medical diagram showing a hand holding a blue injection device for 90-degree use, with a close-up of the yellow needle guard

B	Push the pre-filled pen firmly against the skin until it stops moving.

Important: You must push the pen as far as it will go, but do not touch the gray start button until you are ready to inject.

C	When ready for injection, press the grey start button. You will hear a click.

D	Continue pushing on the skin. Then, remove your thumb while keeping the pre-filled pen against your skin. The injection may take about 15 seconds to complete.

	NOTE: Once you remove the pre-filled pen from the skin, the needle will be covered automatically.

Step 4: Finish

Remove the used pre-filled pen and the orange needle cap.

A hand inserting a blue injection pen into a red biohazard waste container marked with the biological hazard symbol

Dispose of the used pre-filled pen and the orange needle cap in a sharps disposal container.

Ask your healthcare professional how to properly dispose of the pens. There may be local regulations regarding this.

Keep the pre-filled pen and the sharps disposal container out of sight and reach of children.

Do not reuse the pre-filled pen.
Do not recap the pre-filled pen or place your fingers inside the yellow safety shield.
Do not recycle the pre-filled pen or the sharps disposal container, or throw them in the household trash.

B	Examine the injection site.
If you see blood, press the injection site with a cotton ball or gauze. Do not rub the injection site. Apply a bandage if necessary.