Prolia 60 mg solution for injection in a pre-filled syringe

What Prolia is and how it works

Prolia contains denosumab, a protein (monoclonal antibody) that interferes with the action of another protein, in order to treat bone loss and osteoporosis. Treatment with Prolia makes bone stronger and less likely to break.

Bone is a living tissue and is renewed all the time. Oestrogen helps keep bones healthy. After the menopause, oestrogen level drops which may cause bones to become thin and fragile. This can eventually lead to a condition called osteoporosis. Many women with osteoporosis have no symptoms, but they are still at risk of breaking bones, especially in the spine, hips and wrists.

Surgery or medicines that stop the production of oestrogen or testosterone used to treat patients with breast or prostate cancer can also lead to bone loss. The bones become weaker and break more easily.

What Prolia is used for

Prolia is used to treat:

• osteoporosis in women after the menopause (postmenopausal), reducing the risk of spinal, non-spinal and hip fractures.
• bone loss that results from a reduction in hormone (testosterone) level caused by surgery or treatment with medicines in patients with prostate cancer.

Do not use Prolia

• if you have low calcium levels in the blood (hypocalcaemia).
• if you are allergic (hypersensitive) to denosumab or any of the other ingredients of Prolia.

Take special care with Prolia

Please tell your doctor immediately if you develop a swollen, red area of skin, most commonly in the lower leg, that feels hot and tender (cellulitis), and possibly with symptoms of fever while being on treatment with Prolia.

Please tell your doctor if you have an allergy to latex (the needle cover on the pre-filled syringe contains a derivative of latex).

Tell your doctor if you have or have ever had severe kidney problems, kidney failure or have needed dialysis.

You should also take calcium and vitamin D supplements while being on treatment with Prolia. Your doctor will discuss this with you.

A dental examination should be considered before you start treatment with Prolia if you have cancer, are undergoing chemotherapy or radiotherapy, are taking steroids, do not receive routine dental care or have gum disease.

If you are under dental treatment or will undergo dental surgery, tell your dentist that you are being treated with Prolia.

It is important to maintain good oral hygiene when being on treatment with Prolia.

Prolia is not recommended for anyone under 18 years of age. The use of Prolia in children and adolescents has not been studied.

Using other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

Prolia has not been tested in pregnant women. It is important to tell your doctor if you are pregnant; think you may be pregnant; or plan to get pregnant. Prolia is not recommended for use if you are pregnant.

It is not known whether Prolia is excreted in breast milk. It is important to tell your doctor if you are breast-feeding or plan to do so. Your doctor will then help you decide whether to stop breast-feeding, or whether to stop taking Prolia, considering the benefit of breast-feeding to the baby and the benefit of Prolia to the mother.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Prolia has no or negligible influence on the ability to drive and use machines

Important information about some of the ingredients of Prolia

If you have an intolerance to some sugars

If you have been told by your doctor that you have an intolerance to some sugars (sorbitol E420), contact your doctor before taking this medicinal product.

If you are on a controlled sodium diet

This medicinal product contains less than 1 mmol sodium (23 mg) per 60 mg, i.e. essentially ?sodium-free?.

The usual dose is one pre-filled syringe of 60 mg administered once every 6 months, as a single injection under the skin (subcutaneous). The best places to inject are the top of
your thighs and the abdomen. Your carer can also use the outer area of your
upper arm. Each pack of Prolia contains a reminder card with stickers that can
be removed from the carton. Use the peel-off stickers to mark the next injection
date on your personal calendar and/or the reminder card to keep a record of the
next injection date.

You should also take calcium and vitamin D supplements while being on treatment with Prolia. Your doctor will discuss this with you.

Your doctor may decide that it is best for you or a carer to inject Prolia. Your doctor or healthcare provider will show you or your carer how to use Prolia. For instructions on how to inject Prolia, please read the section at the end of this leaflet.

If you forget to use Prolia

If a dose of Prolia is missed, the injection should be administered as soon as possible. Thereafter, injections should be scheduled every 6 months from the date of the last injection.

If you stop using Prolia

To get the most benefit from your treatment, it is important to use Prolia for as long as your doctor prescribes it for you. Please talk to your doctor before you consider stopping the treatment.

Uncommonly, patients receiving Prolia may develop skin infections (predominantly cellulitis). Please tell your doctor immediately if you develop any of these symptoms while being on treatment with Prolia: swollen, red area of skin, most commonly in the lower leg, that feels hot and tender, and possibly with symptoms of fever.

Like all medicines, Prolia can cause side effects, although not everybody gets them. The frequency of possible side effects listed below is defined using the following convention: Very common (affects more than 1 user in 10)
Common (affects 1 to 10 users in 100)
Uncommon (affects 1 to 10 users in 1,000)
Rare (affects 1 to 10 users in 10,000)
Very rare (affects less than 1 user in 10,000)
Not known (frequency cannot be estimated from the available data).

Common side effects:

• painful urination, frequent urination, blood in the urine, inability to hold your urine,
• upper respiratory tract infection,
• pain, tingling or numbness that moves down your leg (sciatica),
• cloudy area in the lens of the eye (cataracts),
• constipation,
• rash,
• arm or leg pain (pain in extremity).

Uncommon side effects:

• swollen, red area of skin, most commonly in the lower leg, that feels hot and tender (cellulitis), and possibly with symptoms of fever,
• fever, vomiting and abdominal pain and discomfort (diverticulitis),
• ear infection,
• skin condition with itching, redness and/or dryness (eczema).

Rare side effects:

• Persistent pain and/or non-healing sores of the mouth or jaw.

Very rare side effects:

• low calcium levels in the blood (hypocalcaemia).

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use Prolia after the expiry date which is 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.
Store in the original carton in order to protect from light.
Do not shake excessively.

Your pre-filled syringe may be left outside the refrigerator to reach room temperature (up to 25°C) before injection. This will make the injection more comfortable. Once your syringe has been left to reach room temperature (up to 25°C), it must be used within 30 days.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Prolia contains

• The active substance is denosumab. Each 1 ml pre-filled syringe contains 60 mg of denosumab (60 mg/ml).
• The other ingredients are glacial acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 20 and water for injections.

What Prolia looks like and contents of the pack

Prolia is a clear, colourless to slightly yellow solution for injection provided in a ready to use pre-filled syringe.

Each pack contains one pre-filled syringe with a needle guard.
Each pack contains one pre-filled syringe.

Marketing Authorisation Holder and Manufacturer

Amgen Europe B.V.
Minervum 7061
NL-4817 ZK Breda
The Netherlands

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

BelgiëBelgiqueBelgien s.a. Amgen n.v. TelTél 32 02 7752711 LuxembourgLuxemburg s.a. Amgen BelgiqueBelgien TelTél 32 02 7752711

. 359 02 805 7020 Magyarország Amgen Kft. Tel. 36 1 35 44 700

eská republika Amgen s.r.o. Tel 420 2 21 773 500 Malta Amgen B.V. The Netherlands Tel 31 076 5732500

Danmark Amgen filial af Amgen AB, Sverige Tlf 45 39617500 Nederland Amgen B.V. Tel 31 076 5732500

Deutschland AMGEN GmbH Tel. 49 89 1490960 Norge Amgen AB Tlf 47 23308000

Eesti Amgen Switzerland AG Vilniaus filialas Tel 372 5125 501 Österreich Amgen GmbH Tel 43 01 50 217

Amgen . . 30 210 3447000 Polska Amgen Sp. z o.o. Tel. 48 22 581 3000

España Amgen S.A. Tel 34 93 600 19 00 Portugal AMGEN Biofarmacêutica, Lda. Tel 351 21 4220550

France Amgen S.A.S Tél 33 01 40 88 27 00 România Amgen România SRL Tel 4021 527 3000

Slovenija AMGEN zdravila d.o.o. Tel 386 1 585 1767 Ireland Amgen Limited United Kingdom Tel 44 01223 420305

Ísland Vistor hf. Sími 354 535 7000 Slovenská republika Amgen Switzerland AG Slovakia Tel 421 33 321 13 22

Italia Amgen Dompé S.p.A. Tel 39 02 6241121 SuomiFinland Amgen AB, sivuliike SuomessaAmgen AB, filial i Finland PuhTel 358 09 54900500

K Papaellinas Co Ltd 357 22741 741 Sverige Amgen AB Tel 46 08 6951100

Latvija Amgen Switzerland AG Rgas filile Tel 371 292 84807 United Kingdom Amgen Limited Tel 44 01223 420305

Lietuva

Amgen Switzerland AG Vilniaus filialas
Tel: +370 682 28282

This leaflet was last approved in

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INSTRUCTIONS FOR INJECTING WITH THE PROLIA PRE-FILLED SYRINGE WITH AN AUTOMATIC NEEDLE GUARD

This section contains information onhow to use the Prolia pre-filled syringe. It is important that you or your carer do not give the injection unless training from your doctor or healthcare provider has been received. Always wash your hands before every injection. If you have questions about how to inject, please ask your doctor or healthcare provider for assistance.

Window Plunger Needle guard Needle cover Before you begin

Read all instructions thoroughly before using the pre-filled syringe.

To reduce the risk of accidental needle sticks to users, each pre-filled syringe comes with a needle guard that is automatically activated to cover the needle after complete delivery of the pre-filled syringe content.

DO NOT attempt to activate the needle guard prior to injection.

DO NOT use the pre-filled syringe if the needle cover has been removed, or the needle guard has been activated (covering the needle).

How do you use the Prolia pre-filled syringe?

Your doctor has prescribed a Prolia pre-filled syringe for injection into the tissue just under the skin (subcutaneous). You must inject the entire content (1 ml) of the Prolia pre-filled syringe and it should be injected once every 6 months as instructed by your doctor or healthcare provider.

Equipment:

To give an injection, you will need:

1. A new Prolia pre-filled syringe; and

2. Alcohol wipes or similar.

What to do before you give a subcutaneous injection of Prolia

1. Remove the pre-filled syringe from the refrigerator. DO NOT pick up the pre-filled syringe by the plunger or needle cover. This could damage the device.

2. The pre-filled syringe may be left outside the refrigerator to reach room temperature. This will make the injection more comfortable. DO NOT warm it in any other way, for example, in a microwave or in hot water. DO NOT leave the syringe exposed to direct sunlight.

3. DO NOT shake the pre-filled syringe excessively.

4. DO NOT remove the needle cover from the pre-filled syringe until you are ready to inject.

5. Check the expiry date on the pre-filled syringe label (EXP). DO NOT use it if the date has passed the last day of the month shown.

6. Check the appearance of Prolia. It must be a clear, colourless to slightly yellow solution. The solution should not be injected if it contains particles or if it is cloudy or discoloured.

7. Find a comfortable, well-lit, clean surface and put all the equipment within reach.

8. Wash your hands thoroughly.

Where should you give the injection The best places to inject are the top of your thighs and the abdomen. Your carer can also use the outer area of your upper arms.

How do you give the injection?

1. Disinfect the skin by using an alcohol wipe. 2. To avoid bending the needle, gently pull the cover from the needle straight off without twisting, as shown. DO NOT touch the needle or push the plunger. 3. You may notice a small bubble in the pre-filled syringe. You do not have to remove the air bubble before injecting. Injecting the solution with the air bubble is harmless. 4. Pinch without squeezing the skin between your thumb and forefinger. Put the needle fully into the skin as shown by your doctor or healthcare provider.

5. Push the plunger with a slow constant pressure, always keeping the skin pinched. Push the plunger all the way down as far as it will go to inject all the solution. The needle guard will not activate unless you empty the pre-filled syringe. 6. While the plunger is still pressed all the way down, remove the needle and let go of the skin. Release the plunger and allow the syringe to move up until the entire needle is covered by the needle guard. 7. If the needle guard is not activated, an incomplete injection may have occurred. Call your doctor or healthcare provider if you think you have not received the full dose. DO NOT put the needle cover back on used syringes.

8. If you notice a spot of blood, you may gently dab it away with a cotton ball or tissue. Do not rub the injection site. If needed, you may cover the injection site with a plaster.

9. Only use each pre-filled syringe for one injection. DO NOT use any Prolia that is left in the syringe. Remember: If you have any problems, please ask your doctor or healthcare provider for help and advice.

Disposing of used syringes

• DO NOT put the needle cover back on used syringes.
• Keep used syringes out of the reach and sight of children.
• The used syringe should be disposed of in accordance with local requirements. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

INSTRUCTIONS FOR INJECTING WITH THE PROLIA PRE-FILLED SYRINGE

This section contains information onhow to use the Prolia pre-filled syringe.It is important that

you or your carer do not give the injection unless training from your doctor or healthcare

providerhas been received.Always wash your hands before every injection. If you have questions

about how to inject, please ask your doctor or healthcare provider for assistance.

Before you begin

Read all instructions thoroughly before using the pre-filled syringe.

DO NOTuse the pre-filled syringe if the needle cover has been removed.

How do you use the Prolia pre-filled syringe?

Your doctor has prescribed a Prolia pre-filled syringe for injection into the tissue just under the skin

(subcutaneous). You must inject the entire content (1 ml) of the Prolia pre-filled syringe and it should

be injected once every 6 months as instructed by your doctor.

Equipment:

To give an injection, you will need:

1. A new Prolia pre-filled syringe; and

2. Alcohol wipes or similar.

What to do before you give a subcutaneous injection of Prolia

1. Remove the pre-filled syringe from the refrigerator. DO NOTpick up the pre-filled syringe by the plunger or needle cover. This could damage thedevice.

2. The pre-filled syringe may be left outside the refrigerator to reach room temperature. This will make the injection more comfortable. DO NOTwarm it in any other way, for example, in a microwave or in hot water.DO NOTleave the syringe exposed to direct sunlight.

3. DO NOT shake the pre-filled syringe excessively.

4. DO NOT remove the needle cover from the pre-filled syringe until you are ready to inject.

5. Check the expiry date on the pre-filled syringe label (EXP). DO NOT use it if the date has passed the last day of the month shown.

6. Check the appearance of Prolia. It must be a clear, colourless to slightly yellow solution. The solution should not be injected if it contains particles or if it is discoloured or cloudy.

7. Find a comfortable, well-lit, clean surface and put all the equipment within reach.

8. Wash your hands thoroughly.

Where should you give the injection The best places to inject are the top of your thighs and the abdomen. Your carer can also use the outer area of your upper arms.

How do you give the injection 1. Disinfect the skin by using an alcohol wipe. 2. To avoid bending the needle, gently pull the cover from the needle straight off without twisting, as shown in pictures 1 and 2. DO NOT touch the needle or push the plunger. 3. You may notice a small air bubble in the pre-filled syringe. You do not have to remove the air bubble before injecting. Injecting the solution with the air bubble is harmless. 4. Pinch without squeezing the skin between your thumb and forefinger. Put the needle fully into the skin as shown by your doctor or healthcare provider.

5. Push the plunger with a slow constant pressure, always keeping the skin pinched. Push the plunger all the way down as far as it will go to injectall the solution.

6. Remove the needle and let go of the skin.

7. If you notice a spot of blood you may gently dab it away with a cotton ball or tissue. Do not rub the injection site.If needed, you may cover the injection site with a plaster.

8. Only use each pre-filled syringe for one injection. DO NOT use any Prolia that is left in the syringe.

Remember:if you have any problems, please ask your doctor or healthcare provider for help and

advice.

Disposing of used syringes

• DO NOT put the cover back on used needles.
• Keep used syringes out of the reach and sight of children.
• The used syringe should be disposed of in accordance with local requirements. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protectthe environment.