XGEVA 120 mg INJECTABLE SOLUTION

2. What you need to know before you use XGEVA

Do not use XGEVA

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

Your healthcare professional will not give you XGEVA if you have very low levels of calcium in your blood that have not been treated.

Your healthcare professional will not give you XGEVA if you have open wounds in your mouth or jaw due to dental or oral surgery.

Warnings and precautions

Talk to your doctor before you start using XGEVA.

Calcium and vitamin D supplements

You should take calcium and vitamin D supplements during treatment with XGEVA unless you have high levels of calcium in your blood. Your doctor will explain this to you. If your blood calcium levels are low, your doctor may decide to prescribe calcium supplements before starting treatment with XGEVA.

Low blood calcium levels

Contact your doctor immediately if you experience muscle spasms, twitches, or cramps, and/or numbness or tingling in your fingers and/or around your mouth and/or seizures, confusion, or loss of consciousness during treatment with XGEVA. You may have low blood calcium levels.

Kidney problems

Tell your doctor if you have or have had severe kidney problems, kidney failure, or if you have needed dialysis, as this may increase the risk of low blood calcium levels, especially if you do not take calcium supplements.

Mouth, tooth, and jaw problems

A common side effect (may affect up to 1 in 10 people) called osteonecrosis of the jaw (damage to the jawbone) has been reported in patients receiving XGEVA injection for cancer-related conditions. Osteonecrosis of the jaw can also occur after stopping treatment.

It is essential to try to prevent the development of osteonecrosis of the jaw as it can be a painful condition that can be difficult to treat. To reduce the risk of developing osteonecrosis of the jaw, you should take some precautions:

• Before treatment, tell your doctor or nurse (healthcare professional) if you have any problems with your mouth or teeth. Your doctor should delay the start of your treatment if you have open wounds in your mouth or jaw due to dental or oral surgery. Your doctor will recommend a dental examination before starting treatment with XGEVA.
• While being treated, you should maintain good oral hygiene and have regular dental check-ups. If you wear dental prostheses, you should ensure they fit properly.
• If you are undergoing dental treatment or will undergo dental surgery (e.g., tooth extractions), inform your doctor about your dental treatment and inform your dentist that you are being treated with XGEVA.
• Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth, such as loose teeth, pain, or swelling, ulcers that do not heal or are draining, as these could be signs of osteonecrosis of the jaw.

Patient undergoing chemotherapy and/or radiation therapy, taking steroids or anti-angiogenic medications (used to treat cancer), undergoing dental surgery, not undergoing regular dental check-ups, having gum disease, or being a smoker may have a higher risk of developing osteonecrosis of the jaw.

Unusual fractures of the thigh bone

Some people have developed unusual fractures of the thigh bone during treatment with XGEVA. Contact your doctor if you experience new or unusual pain in the hip, groin, or thigh.

High blood calcium levels after stopping treatment with XGEVA

Some patients with giant cell tumors of bone have developed high blood calcium levels weeks or months after stopping treatment. Your doctor will monitor you for signs and symptoms of high blood calcium levels after stopping treatment with XGEVA.

Children and adolescents

XGEVA is not recommended for children and adolescents under 18 years of age, except for adolescents with giant cell tumor of bone whose bones have stopped growing. The use of XGEVA has not been studied in children and adolescents with other types of cancer that have spread to the bone.

Using XGEVA with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines obtained without a prescription. It is particularly important that you tell your doctor if you are being treated with

• another medicine that contains denosumab
• a bisphosphonate

You should not take XGEVA with other medicines that contain denosumab or bisphosphonates.

Pregnancy and breastfeeding

XGEVA has not been tested in pregnant women. If you are pregnant, think you may be pregnant, or plan to become pregnant, tell your doctor. XGEVA should not be used during pregnancy. Women of childbearing potential should use effective contraceptive methods during treatment with XGEVA and for at least 5 months after stopping treatment with XGEVA.

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

It is not known whether XGEVA is excreted in breast milk. If you are breastfeeding or plan to breastfeed, tell your doctor. Your doctor will help you decide whether to stop breastfeeding or stop taking XGEVA, taking into account the benefits of breastfeeding for the baby and the benefits of XGEVA for the mother.

If you are breastfeeding during treatment with XGEVA, tell your doctor.

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

Driving and using machines

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

XGEVA contains sorbitol

This medicine contains 78 mg of sorbitol in each vial.

XGEVA contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 120 mg; this is essentially “sodium-free”.

3. How to use XGEVA

XGEVA should be administered under the supervision of a healthcare professional.

The recommended dose of XGEVA is 120 mg administered once every 4 weeks in a single injection under the skin (subcutaneously). XGEVA will be injected into the thigh, abdomen, or upper arm. If you are being treated for giant cell tumor of bone, you will receive an additional dose 1 and 2 weeks after the first dose.

Do not shake.

You should also take calcium and vitamin D supplements during treatment with XGEVA unless you have high levels of calcium in your blood. Your doctor will explain this to you.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor immediatelyif you experience any of these symptoms during treatment with XGEVA (may affect more than 1 in 10 people):

• muscle spasms, twitches, cramps, numbness or tingling in your fingers and/or around your mouth and/or seizures, confusion, or loss of consciousness. These symptoms may be a sign of low blood calcium levels. Low blood calcium levels can also cause a change in heart rhythm called QT prolongation, which is seen on an electrocardiogram (ECG).

Tell your doctor and dentist immediatelyif you experience any of these symptoms during treatment with XGEVA or after stopping treatment (may affect up to 1 in 10 people):

• persistent pain in the mouth and/or jaw, swelling and/or ulcers that do not heal in the mouth or jaw, draining, numbness or feeling of heaviness in the jaw or loosening of a tooth may be signs of bone damage in the jaw (osteonecrosis).

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

• bone, joint, and/or muscle pain that can be severe,
• breathing difficulties,
• diarrhea.

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

• low levels of phosphate in the blood (hypophosphatemia),
• tooth extraction,
• excessive sweating,
• in patients with advanced cancer: development of another type of cancer.

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

• high blood calcium levels (hypercalcemia) after stopping treatment in patients with giant cell tumor of bone,
• new or unusual pain in the hip, groin, or thigh (may be an early sign of a possible fracture of the thigh bone),
• skin rash or mouth ulcers (drug-induced lichenoid eruptions).

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

• allergic reactions (e.g., wheezing or difficulty breathing; swelling of the face, lips, tongue, throat, or other parts of the body; skin rash, itching, or hives). In rare cases, allergic reactions can be severe.

Frequency not known(cannot be estimated from the available data):

• tell your doctor if you have ear pain, discharge from the ear, and/or ear infection. These could be symptoms of damage to the bones of the ear.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of XGEVA

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 carton and on the label after “EXP”. The expiry date refers to the last day of the month shown.

Store in a refrigerator (2°C - 8°C).

Do not freeze.

Keep the vial in the outer packaging to protect it from light.

Before injection, the vial may be left at room temperature (up to 25°C) to allow it to reach room temperature. This will make the injection less painful. Once the vial has reached room temperature (up to 25°C), it should 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 protect the environment.

6. Contents of the pack and other information

What XGEVA contains

• The active substance is denosumab. Each vial contains 120 mg of denosumab in 1.7 ml of solution (which is equivalent to 70 mg/ml).
• The other ingredients are glacial acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 20, and water for injections.

Appearance and packaging

XGEVA is a solution for injection (injectable).

XGEVA is a clear, colorless to slightly yellowish solution that may contain residual protein particles that are translucent to white.

Each pack contains one, three, or four single-use vials.

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Amgen Europe B.V.

Minervum 7061,

4817 ZK Breda,

Netherlands

Marketing authorization 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 from the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

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

This information is intended only for healthcare professionals:

• The XGEVA solution should be inspected visually before administration. The solution may contain residual protein particles that are translucent to white. Do not inject the solution if it is cloudy, discolored, or contains many particles or foreign material.
• Do not shake.
• To avoid discomfort at the injection site, before injecting, let the vial reach room temperature (up to 25°C) and inject slowly.
• The entire contents of the vial should be injected.
• For the administration of denosumab, it is recommended to use a 27G needle.
• Do not reinsert the needle into the vial.

Disposal of unused medicine and all materials that have come into contact with it should be done according to local regulations.