Xgeva 120 mg solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

XGEVA 120 mg solution for injection

denosumab

Read all of this 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 must not be given to other people, even if they have the same symptoms as you, because it could 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.
• Your doctor will provide you with a patient alert card containing important safety information that you should know before and during treatment with XGEVA.

Contents of this leaflet

1. What XGEVA is and what it is used for
2. What you need to know before using XGEVA
3. How to use XGEVA
4. Possible side effects
5. How to store XGEVA
6. Contents of the pack and other information

1. What XGEVA is and what it is used for

XGEVA contains denosumab, a protein (monoclonal antibody) that slows down bone destruction caused by cancer spreading to the bones (bone metastases) or by giant cell tumor of bone.

XGEVA is used in adults with advanced cancer to prevent serious 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.

2. What you need to know before using XGEVA

Do not use XGEVA

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

Your healthcare provider will not administer XGEVA to you if you have untreated low blood calcium levels.

Your healthcare provider will not administer XGEVA if you have unhealed wounds from dental or oral surgery.

Warnings and precautions

Talk to your doctor before starting XGEVA.

Calcium and vitamin D supplements

You must 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, toes, or around your mouth and/or seizures, confusion, or loss of consciousness during treatment with XGEVA. Your blood calcium level may be low.

Renal impairment

Inform your doctor if you have or have had severe kidney problems, renal failure, or if you have required dialysis, as this may increase the risk of low blood calcium levels, especially if you are not taking calcium supplements.

Problems with mouth, teeth, and jaw

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

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

• Before receiving treatment, inform 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 unhealed wounds in your mouth due to dental procedures 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 dentures, make sure they fit properly.
• If you are undergoing dental treatment or are scheduled for 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, non-healing or oozing sores, as these could be signs of osteonecrosis of the jaw.

Patients receiving chemotherapy and/or radiotherapy, taking steroids or anti-angiogenic medicines (used to treat cancer), who have undergone dental surgery, who do not have regular dental check-ups, who have gum disease, or who smoke may have an increased 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 develop new 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 developed high blood calcium levels weeks or months after stopping treatment. Your doctor will monitor you for signs and symptoms of high 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. The use of 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 medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. This includes medicines obtained without a prescription. It is very important that you inform your doctor if you are being treated with

• another medicine containing denosumab
• a bisphosphonate

You should not take XGEVA together with other medicines containing denosumab or bisphosphonates.

Pregnancy and breastfeeding

XGEVA has not been studied in pregnant women. It is important 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 potential should use effective contraception during treatment with XGEVA and for at least 5 months after stopping treatment with XGEVA.

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

It is unknown whether XGEVA is excreted in human breast milk. It is important to inform your doctor if you are breastfeeding or plan to breastfeed. Your doctor will help you decide whether to discontinue breastfeeding or to discontinue 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.

Talk to your doctor or pharmacist before taking any other medicine.

Driving and using machines

The influence of XGEVA on the ability to drive and use machines is negligible or none.

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 dose; essentially “sodium-free”.

3. How to use XGEVA

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

The recommended dose of XGEVA is 120 mg given once every 4 weeks as a single subcutaneous injection (under the skin). 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 hypercalcemia (excess calcium in the blood). Your doctor will advise you on this matter.

If you have any further questions about how to use this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

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

Tell your doctor immediately if you experience any of the following symptoms during treatment with XGEVA (may affect more than 1 in 10 people):

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

Tell your doctor and dentist immediately if 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, swelling and/or non-healing sores in the mouth or jaw, pus discharge, numbness or a feeling of heaviness in the jaw, or loosening of a tooth. These may be signs of bone damage in the jaw (osteonecrosis).

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

• bone, joint and/or muscle pain, which may sometimes be severe,
• breathing difficulties,
• diarrhoea.

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

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

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

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

Rare adverse 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 body parts; skin rash, itching or hives). In rare cases, allergic reactions could be severe.

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

• consult 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 adverse effects

If you experience any adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse 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 stated on the carton and label 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 the vial in the outer packaging to protect it from light.

Before injection, the vial may be removed from the refrigerator and allowed to reach room temperature (up to 25 °C) to make the injection less uncomfortable. Once the vial has reached room temperature (up to 25 °C), it must be used within 30 days.

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 XGEVA

• The active substance 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), polysorbate 20, and water for injections.

Appearance of the product and contents of the pack

XGEVA is an injectable solution.

XGEVA is a clear, colourless to slightly yellowish solution, which may contain residual amounts of translucent to white protein particles.

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

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Amgen Europe B.V.

Minervum 7061,

4817 ZK Breda,

The Netherlands

Marketing Authorization 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 more information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this summary:

Detailed information on this medicine is available on the European Medicines Agency website:

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

This information is intended for healthcare professionals only:

• The XGEVA solution should be inspected visually before administration. The solution may contain residual translucent to white protein particles. Do not inject the solution if it is cloudy, discolored, or contains numerous particles or foreign material.
• Do not shake.
• To minimize discomfort at the injection site, allow the vial to reach room temperature (up to 25°C) before injection, and administer the injection slowly.
• The entire contents of the vial must be injected.
• A 27 G needle is recommended for the administration of denosumab.
• Do not reinsert the needle into the vial.

Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations.