Product Information for the User

Prolia 60 mg pre-filled syringe injectable solution

denosumab

Read this entire product information carefully before starting to use this medication, as it contains important information for you.

• Keep this product information, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed to you alone, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this product information. See section4.
• Your doctor will provide you with a patient reminder card, which contains important safety information that you should know before and during your treatment with Prolia.

What is Prolia and how it works

Prolia contains denosumab, a protein (monoclonal antibody) that interferes with the action of another protein with the aim of treating bone loss and osteoporosis. Prolia treatment strengthens bones and reduces the likelihood of fractures.

The bone is a living tissue that is constantly renewed. Estrogens contribute to the conservation of bone health. After menopause, the level of estrogens decreases, which can cause bones to become thinner and more fragile. This can eventually lead to a disease called osteoporosis. Osteoporosis can also occur in men due to various causes including age and/or low levels of the male hormone, testosterone. It can also occur in patients undergoing glucocorticoid treatment. Many patients with osteoporosis do not present symptoms, although they still have a risk of fracturing bones, especially in the spine, hip, and wrists.

Surgical interventions or medications that stop the production of estrogen or testosterone, used to treat prostate or breast cancer patients, can also cause bone loss. As a result, bones become weaker and break more easily.

For what it is used

Prolia is used to treat:

• postmenopausal osteoporosis in women and men with an increased risk of fracture (bone breakage), reducing the risk of hip, spine, and other fractures.
• bone loss caused by reduced hormone levels (testosterone) as a result of surgical operation or medication treatment in patients with prostate cancer.

bone loss resulting from long-term treatment with glucocorticoids in patients with a high risk of fracture.

No use Prolia:

• If you have low levels of calcium in your blood (hypocalcemia).
• If you are allergic to denosumab or any of the other components of this medication (including those listed in section 6).

Advertencias y precauciones

Consult your doctor or pharmacist before starting to use Prolia.

During treatment with Prolia, you may develop a skin infection with symptoms such as a swollen and red area of skin, more frequently on the lower leg, that feels warm and sensitive to the touch (cellulitis), and may be accompanied by fever. Inform your doctor immediately if you experience any of these symptoms.

You must also take calcium and vitamin D supplements during treatment with Prolia. Your doctor will discuss this with you.

While receiving Prolia, you may experience low levels of calcium in your blood. Inform your doctor immediately if you notice any of the following symptoms: muscle spasms, contractions, or cramps, and/or numbness or tingling in the fingers of your hands, feet, or around your mouth, and/or seizures, confusion, or loss of consciousness.

In rare cases, severe low levels of calcium in the blood have been reported, requiring hospitalization and potentially life-threatening reactions. Therefore, before each dose administration and in patients with a predisposition to hypocalcemia, within two weeks after the initial dose, your blood calcium levels will be checked (through a blood test).

Inform your doctor if you have or have had severe kidney problems, kidney failure, if you have needed to undergo dialysis, or if you are taking medications called glucocorticoids (such as prednisolone or dexamethasone), as they may increase the risk of low calcium levels in the blood if you do not take calcium supplements.

Problems in the mouth, teeth, or jaw

In patients receiving Prolia for osteoporosis, rare cases (may affect up to 1 in 1,000 people) of an adverse effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) have been reported. The risk of ONJ increases in patients treated for a long time (may affect up to 1 in 200 people if treated for 10 years). ONJ may also occur after stopping treatment. It is essential to try to prevent the development of ONJ, as it can be a painful condition that may be difficult to treat. To reduce the risk of developing ONJ, follow these precautions:

Before receiving treatment, inform your doctor or nurse (healthcare professional) if:

• You have any problems in your mouth or teeth, such as poor dental health, gum disease, or a planned tooth extraction.
• You do not receive regular dental check-ups or have not had a dental check-up for a long time.
• You are a smoker (as it may increase the risk of dental problems).
• You have been previously treated with a bisphosphonate (used to prevent or treat bone disorders).
• You are taking medications called corticosteroids (such as prednisolone or dexamethasone).
• You have cancer.

Your doctor may ask you to undergo a dental check-up before starting treatment with Prolia.

During treatment with Prolia, maintain good oral hygiene and undergo regular dental check-ups. If you use dental prosthetics, ensure they fit properly. If you are undergoing dental treatment or are about to undergo dental surgery (e.g., tooth extractions), inform your doctor about your dental treatment and inform your dentist that you are receiving Prolia.

Contact your doctor and dentist immediately if you experience any problems in your mouth or teeth, such as loose teeth, pain, or inflammation, or ulcers that do not heal or suppurate, as they may be symptoms of ONJ.

Unusual fractures of the femur

Some people have developed unusual fractures in the femur while receiving Prolia. Consult your doctor if you experience new or unusual pain in the hip, groin, or thigh.

Children and adolescents

Prolia should not be used in individuals under 18 years of age.

Use of Prolia with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. It is especially important to inform your doctor if you are receiving another medication that contains denosumab.

You should not use Prolia with another medication that contains denosumab.

Pregnancy and breastfeeding

Prolia has not been tested in pregnant women. It is essential to inform your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant. Prolia is not recommended during pregnancy. Women of childbearing age should use effective contraceptive methods during treatment with Prolia and at least 5 months after stopping treatment with Prolia.

If you become pregnant during treatment with Prolia or less than 5 months after stopping treatment with Prolia, inform your doctor.

The excretion of Prolia in breast milk is unknown. It is essential to inform your doctor if you are breastfeeding or plan to breastfeed. Your doctor will help you decide whether to stop breastfeeding or whether to stop using Prolia, taking into account the benefits of breastfeeding for the baby and the benefits of Prolia for the mother.

If you are breastfeeding during treatment with Prolia, please inform your doctor.

Consult your doctor or pharmacist before using any medication.

Driving and operating machinery

The influence of Prolia on the ability to drive and operate machinery is negligible or insignificant.

Prolia contains sorbitol

This medication contains 47 mg of sorbitol per 1 ml of solution.

Prolia contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per 60 mg; this is, essentially “sodium-free”.

The recommended dose is a pre-filled syringe of 60 mg administered under the skin (subcutaneously) in a single injection every 6 months. The best places to administer the injection are the upper part of the thighs and the abdomen. If the injection is administered by a caregiver, it can also be administered in the outer area of the upper arm. Consult with your doctor for the date of the next possible injection. Each Prolia package contains a reminder card that can be detached from the carton and used to keep track of the date of the next injection.

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

Your doctor will decide whether it is better for you to administer the Prolia injection or for a caregiver to do so. Your doctor or healthcare professional will show you or your caregiver how to use Prolia. If you want to learn how to inject Prolia, read the last section of this prospectus.

Do not shake.

If you forgot to use Prolia

If you miss a dose of Prolia, the injection should be administered as soon as possible. Subsequent injections should be scheduled every 6 months from the date of the last injection.

If you interrupt treatment with Prolia

To get the most benefit from your treatment and reduce the risk of fractures, it is essential to use Prolia for the entire period prescribed by your doctor. Do not stop treatment without first talking to your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Patients treated with Prolia may develop skin infections (mainly cellulitis) infrequently.Inform your doctor immediatelyif any of these symptoms occur during treatment with Prolia: a swollen and red area on the skin, usually on the lower leg, which is warm and sensitive to the touch and may be accompanied by fever.

Rarely, patients receiving Prolia may develop jaw pain and/or mandible, inflammation or ulcers that do not heal in the mouth or mandible, suppuration, numbness or heaviness in the mandible, or tooth mobility. These could be symptoms of jaw bone damage (osteonecrosis).Inform your doctor and dentist immediatelyif you experience such symptoms while on treatment with Prolia or after stopping treatment.

Rarely, patients receiving Prolia may present low levels of calcium in the blood (hypocalcemia); very low levels of calcium in the blood may require hospitalization and, in some cases, may even be life-threatening. Symptoms include muscle spasms, contractions, or cramps, and/or numbness or tingling in the fingers of the hands, fingers of the feet, or around the mouth and/or convulsions, confusion, or loss of consciousness. If you experience any of these,inform your doctor immediately. Low levels of calcium in the blood can also cause a change in the heart rhythm called QT prolongation, which can be observed by performing an electrocardiogram (ECG).

Rarely, unusual fractures of the femur may occur in patients receiving Prolia.Consult your doctorif you experience new or unusual pain in the hip, groin, or thigh, as this may be an early indication of a possible femur fracture.

Rarely, allergic reactions may occur in patients receiving Prolia. Symptoms include swelling in the face, lips, tongue, throat, or other parts of the body; skin rash, itching, or urticaria; wheezing or difficulty breathing.Inform your doctorif you experience such symptoms while on treatment with Prolia.

Very common side effects(may affect more than 1 in 10 people):

• bone, joint, and/or muscle pain that is sometimes intense,
• leg or arm pain (pain in the extremities).

Common side effects(may affect up to 1 in 10 people):

• painful urination, frequent urination, presence of blood in the urine, urinary incontinence,
• upper respiratory tract infection,
• lower back pain, numbness, or tingling that extends to the lower leg (sciatica),
• constipation,
• abdominal discomfort,
• skin rash,
• skin condition with itching, redness, and/or dryness (eczema),
• hair loss (alopecia).

Uncommon side effects(may affect up to 1 in 100 people):

• fever, vomiting, and abdominal pain or discomfort (diverticulitis),
• ear infection,
• skin rash or ulcers in the mouth (medication-induced lichenoid eruptions).

Rare side effects(may affect up to 1 in 10,000 people):

• allergic reaction that can damage blood vessels, mainly in the skin (p.e.g.purple or reddish-brown patches, urticaria, or skin ulcers) (hypersensitivity vasculitis).

Unknown frequency(cannot be estimated from available data):

• consult your doctor if you have ear pain, the ear is discharging, and/or you have an ear infection. These may be symptoms of damage to the bones in the ear.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the label and on the box after “CAD” or “EXP”. The expiration date is the last day of the month indicated.

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

Do not freeze.

Keep the pre-filled syringe in the outer packaging to protect it from light.

Before injection, the pre-filled syringe may be left out of the refrigerator to reach room temperature (up to 25°C). This will make the injection less uncomfortable. Once the pre-filled syringe has reached room temperature (up to 25°C), it must be used before 30 days pass.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Prolia

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

Appearance of Prolia and contents of the pack

Prolia is a transparent, colourless to slightly yellowish injectable solution, available in a pre-filled syringe ready for use.

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

Each pack contains a pre-filled syringe.

Only some pack sizes may be marketed.

Marketing Authorisation Holder and Responsible Person

Amgen Europe B.V.

Minervum 7061,

4817 ZK Breda,

Netherlands

Marketing Authorisation Holder

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

Netherlands

Manufacturer

Amgen Technology (Ireland) Unlimited Company

Pottery Road

Dun Laoghaire

Co Dublin

Ireland

Manufacturer

Amgen NV

Telecomlaan 5-7

1831 Diegem

Belgium

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

Last update of this leaflet:

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu/

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Instructions for self-injecting Prolia pre-filled syringe

This section contains information on how to use the Prolia pre-filled syringe.It is essential that you or your caregiver (the person caring for you) do not administer the injection until you have received instructions from your doctor or healthcare professional.Always wash your hands before injecting. If you are unsure about how to administer the injection, consult your doctor or healthcare professional.

Before starting

Read this leaflet carefully before using the pre-filled syringe.

DO NOTuse the pre-filled syringe if it does not have a needle cap.

How to use the Prolia pre-filled syringe?

Your doctor has prescribed a Prolia pre-filled syringe for you to inject into the tissue just below the skin (subcutaneous tissue). You must inject the entire contents (1ml) of the Prolia pre-filled syringe once every 6months, as instructed by your doctor.

Material:

To administer an injection, you will need:

What to do before administering a subcutaneous injection of Prolia

DO NOThold the pre-filled syringe by the plunger or the needle cap. This could damage the device.

DO NOTwarm the pre-filled syringe in any other way, such as in a microwave or in hot water.

DO NOTexpose the pre-filled syringe to direct sunlight.

1. DO NOTshake the pre-filled syringe.

1. DO NOTremove the needle cap from the pre-filled syringe until you are ready to administer the injection.

1. Check the expiry date on the label of the pre-filled syringe (EXP).

DO NOTuse the pre-filled syringe if the expiry date has passed.

1. Check the appearance of Prolia. It should be a clear, colourless to slightly yellowish solution. Do not inject if it contains particles or is cloudy or discoloured.

1. Find a clean, comfortable, and well-lit surface and place all the necessary materials within reach.

1. Wash your hands thoroughly.

How to administer the injection?

1. Disinfect the skin with an alcohol wipe.

1. Pull the needle cap straight off in line with the syringe, as shown in figures1 and2.
2. DO NOTtouch the needle or press the plunger.

1. You may observe a small air bubble inside the pre-filled syringe. Do not remove the air bubble before the injection. Injecting the solution with the air bubble is not harmful.

1. Pinch the skin (without pinching too hard) with your thumb and index finger. Insert the needle into the skin, as instructed by your doctor or healthcare professional.

1. Push the plunger with a slow and constant pressure, without releasing the skin. Push the plunger all the way down until you have injected the entire solution.

1. Remove the needle and release the skin.

1. If you see a blood spot, gently remove it with a cotton ball or gauze. Do not rub the injection site. If necessary, apply a bandage.

1. Use each pre-filled syringe for only one injection. DO NOT use the remaining Prolia in the syringe.

Remember:if you have any problems, do not hesitate to ask for help and advice from your doctor or healthcare professional.

How to dispose of used syringes

• DO NOTreattach the needle cap to used syringes.
• Keep used syringes out of sight and reach of children.
• Used syringes must be disposed of in accordance with local regulations. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.