Prescribing Information for the Patient

XGEVA 120 mg injectable solution

denosumab

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

• Keep this prescribing information, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you and should not be given 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, pharmacist, or nurse, even if they are not listed in this prescribing information. See section 4.
• 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 XGEVA.

XGEVA contains denosumab, a protein (monoclonal antibody) that inhibits bone destruction that occurs when cancer spreads to the bones (bone metastases) or giant cell tumor of bone.

XGEVA is used in adults with advanced cancer to prevent severe complications caused by bone metastases (e.g., fractures, spinal cord compression or the need for radiation therapy or surgery).

XGEVA is also used for the treatment of giant cell tumor of bone that cannot be treated with surgery or when surgery is not the best option, in adults and adolescents whose bones have stopped growing.

No use XGEVA

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

Your healthcare professional will not administer XGEVA if you have a very low level of calcium in your blood that has not been treated.

Your healthcare professional will not administer XGEVA if you have unhealed wounds produced by dental or oral surgery.

Warnings and precautions

Consult your doctor before starting to use XGEVA.

Calcium and vitamin D supplements

You should take calcium and vitamin D supplements during treatment with XGEVA unless your blood calcium levels are high. Your doctor will explain this to you. If your blood calcium level is 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 toes or around your mouth and/or convulsions, confusion, or loss of consciousness during treatment with XGEVA. It is possible that your blood calcium level is low.

Renal insufficiency

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

Problems with the mouth, teeth, and jaw

Frequent adverse effects (may affect up to 1 in 10 people) have been reported, including osteonecrosis of the jaw (bone damage in the jaw) in patients receiving XGEVA for bone-related conditions. Osteonecrosis of the jaw may 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 may be difficult to treat. To reduce the risk of developing osteonecrosis of the jaw, you should take the following precautions:

• While being treated, you should maintain good oral hygiene and receive regular dental check-ups. If you use dental prostheses, 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 inflammation, ulcers that do not heal or suppurate, as these may be signs of osteonecrosis of the jaw.

Patients undergoing chemotherapy and/or radiation therapy, taking steroids, or anti-angiogenic medications (used to treat cancer), who have undergone dental surgery, do not have regular dental check-ups, have gum disease, or are smokers, 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 recent or unusual pain in your hip, groin, or thigh.

High blood calcium levels after stopping XGEVA treatment

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

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. XGEVA has not been studied in children and adolescents with other types of cancer that have spread to the bones.

Use of XGEVA with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. This includes those obtained without a prescription. It is essential to inform your doctor if you are being treated with

• another medication containing denosumab
• a bisphosphonate

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

Pregnancy and breastfeeding

XGEVA 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. XGEVA is not recommended during pregnancy. Women of childbearing age should use effective contraceptive methods during treatment with XGEVA and at least 5 months after stopping XGEVA treatment.

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

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

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

Consult your doctor or pharmacist before taking any other medication.

Driving and operating machinery

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

XGEVA contains sorbitol

This medication contains 78 mg of sorbitol in each vial.

XGEVA contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per 120 mg; it is essentially "sodium-free".

XGEVA must be administered under the responsibility of a healthcare professional.

The recommended dose of XGEVA is 120 mg administered once every 4 weeks as a single subcutaneous injection. XGEVA will be injected in 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 agitate.

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

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

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

Inform your doctor immediatelyif any of the following symptoms occur during treatment with XGEVA (may affect more than 1 in 10 people):

• muscle spasms, tics, cramps, numbness or tingling in the fingers of the hands and feet or around the mouth and/or convulsions, confusion or loss of consciousness. These symptoms may be a sign that your blood calcium levels are low. Low blood calcium levels may also cause a change in the heart rhythm called QT prolongation, which is observed through an electrocardiogram (ECG).

Inform your doctor and dentist immediatelyif you experience any of the following 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, inflammation and/or ulcers that do not heal in the mouth or jaw, suppuration, numbness or heaviness in the jaw or loosening of a tooth may be signs of jaw bone damage (osteonecrosis).

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

• bone, joint, and/or muscle pain that is sometimes intense,
• breathing difficulties,
• diarrhea.

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

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

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

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

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

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

Unknown frequency(cannot be estimated from available data):

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

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national 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 box and on the label 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 vial in the outer packaging to protect it from light.

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

Medicines should not be thrown down the drains or in the trash. Ask your pharmacist how to dispose of the containers and medicines that you do not need. This way you will help protect the environment.

XGEVA Composition

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

Appearance of the product and contents of the pack

XGEVA is a ready-to-use solution for injection.

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

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

Only some pack sizes may be marketed.

Marketing authorization holder and manufacturer responsible for the batch release

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

For more information about this medicinal product, please consult the representative of the marketing authorization holder in your country:

Last update of this leaflet:

The detailed information on this medicinal product is available on the website of the European Medicines Agency:

http://www.ema.europa.eu/.

This information is intended for healthcare professionals only:

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

The disposal of unused medicinal product and any waste materials derived from the use of this product should be in accordance with local requirements.