120 mg solution for injection ( solution for injection )
denosumab
What XGEVA is and what it is used for
XGEVA contains denosumab, a protein (monoclonal antibody ) that works by slowing the breakdown of bone caused by cancer spreading to the bone (skeletal metastases) or giant cell tumors of the bone.
XGEVA is used in adult patients with advanced cancer to prevent the serious complications that bone metastases can cause (for example, fractures, pressure on the spinal cord, or the need for radiation therapy or surgery ).
XGEVA is also used to treat giant cell tumors of the bone that cannot be operated on or when surgery is not the best treatment option in adults and adolescents whose bones have stopped growing.
What you need to know before using XGEVA
Do not use XGEVA
– if you are allergic to denosumab or any other ingredient in 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.
Healthcare professionals will not give you XGEVA if you have unhealed wounds after dental or oral surgery.
Warnings and precautions
Talk to your doctor before using XGEVA.
Supplementation of calcium and vitamin D
When you are treated with XGEVA, you must take calcium and vitamin D supplements if you do not have high levels of calcium in your blood. Your doctor will discuss this with you. If the level of calcium in your blood is low, your doctor may give you calcium supplements before you start treatment with XGEVA.
Low levels of calcium in the blood
Tell your doctor immediately if you experience spasms, twitching, or cramps in the muscles and/or numbness or tingling in the fingers, toes, or around the mouth and/or seizures, confusion, or loss of consciousness while being treated with XGEVA. It is then possible that you have low calcium levels in your blood.
Impaired kidney function
Tell your doctor if you have or have had severe kidney problems, kidney failure or need to be treated with dialysis. This can increase the risk of you suffering from low calcium levels in the blood, especially if you do not take calcium supplements.
Problems with the mouth, teeth, or jaw
A side effect called osteonecrosis of the jaw (bone damage to the jaw) has been reported commonly (may affect up to 1 in 10 people) in patients receiving XGEVA injections for cancer-related conditions. Osteonecrosis of the jaw may also occur when treatment is completed.
It is important to try to prevent osteonecrosis of the jaw from developing, as it can be a painful condition that is difficult to treat. To reduce the risk of osteonecrosis of the jaw, you should take the following precautions:
- Before the treatment, you must tell the doctor or nurse (medical staff) if you have any oral or dental problems. The doctor should postpone the start of treatment if you have unhealed wounds in the mouth due to dental or oral surgery. Your doctor may recommend a dental examination before you can start treatment with XGEVA.
- During treatment, you should maintain good oral hygiene and go for regular dental check-ups. If you use a denture, you should make sure it fits well.
- If you are receiving any type of dental care or are going to undergo dental surgery (eg, tooth extraction), inform the doctor and tell the dentist that you are being treated with XGEVA.
- Contact your doctor or dentist immediately if you experience any problems with your mouth or teeth, such as loose teeth, pain or swelling, and non-healing or oozing sores, as these may be signs of osteonecrosis of the jaw.
Patients who receive chemotherapy and radiation therapy, use steroids or angiogenesis inhibitors (used to treat cancer), undergo dental surgery, do not have regular dental checkups, have gum disease, or are smokers may have a higher risk of developing osteonecrosis in the jaw.
Unusual femur fractures
Some people have suffered unusual femur fractures when treated with XGEVA. Contact a doctor if you experience new or unusual pain in the hip, groin, or thigh.
High levels of calcium in the blood after stopping treatment with XGEVA
Some patients with giant cell tumors of the skeleton have had high levels of calcium in their blood for weeks to months after treatment has ended. Your doctor will monitor you for signs and symptoms of high calcium levels after you stop taking XGEVA.
Children and young people
XGEVA is not recommended for children and adolescents under 18 years of age, except for adolescents with giant cell tumors of the skeleton and whose bones have stopped growing. The use of XGEVA has not been studied in children and adolescents with other cancers that have spread to the bone.
Other medicines and XGEVA
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This also applies to over-the-counter medicines. You must tell the doctor if you are being treated with
• another medicine containing denosumab
• a bisphosphonate
You should not use XGEVA together with other medicines containing denosumab or bisphosphonates.
Pregnancy and breastfeeding
XGEVA has not been tested in pregnant women. You must tell the doctor if you are pregnant, think you may be pregnant, or plan to become pregnant. It is not recommended that you use XGEVA if you are pregnant. Women of childbearing potential should use an effective method of contraception while being treated with XGEVA and for at least 5 months after treatment with XGEVA has ended.
If you become pregnant during treatment with XGEVA or within 5 months of stopping treatment with XGEVA, tell your doctor.
It is not known whether XGEVA is excreted in human milk. You must tell the doctor if you are breastfeeding or plan to breastfeed. The doctor will help you decide whether to stop breastfeeding or to stop taking XGEVA, taking into account the benefit of breastfeeding to the baby and your benefit from XGEVA.
If you are breastfeeding during treatment with XGEVA, tell your doctor.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving ability and use of machinery
XGEVA has no or negligible effect on the ability to drive and use machines.
Important information about any ingredient(s) in XGEVA
XGEVA contains sorbitol
This medicine contains 78 mg of sorbitol per vial.
XGEVA contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 120 mg dose, i.e. it is almost “sodium-free”.
How to use XGEVA
XGEVA should be administered under the responsibility of the physician.
The recommended dose of XGEVA is 120 mg every 4 weeks as a single injection under the skin ( subcutaneously ). XGEVA can be injected into the thigh, abdomen, or upper arm. If you are being treated for a giant cell tumor of the skeleton, you will receive another dose 1 week and 2 weeks after the first dose.
Must not be shaken.
You should also take calcium and vitamin D supplements during treatment with XGEVA unless you have an excess of calcium in your blood. Your doctor will discuss this with you.
If you have further questions about the use of this medicine, contact your doctor, pharmacist, or nurse.
Possible side effects
This medicine can cause side effects like all medicines, although not everybody gets them.
Tell your doctor immediately if you develop any of the following symptoms while being treated with XGEVA (it may affect more than 1 in 10 people):
- spasms, twitching, muscle cramps, numbness or tingling in the fingers, toes, or around the mouth and/or seizures, confusion, or loss of consciousness. Such symptoms may be signs that you have low calcium levels in your blood. Low blood calcium levels can also lead to an altered heart rhythm known as a prolonged QT interval, which is observed using electrocardiography ( ECG ).
Tell your doctor and dentist immediately if you experience any of the following symptoms while being treated with XGEVA or after stopping treatment (may affect up to 1 in 10 people):
- persistent pain in the mouth and/or jaw, and/or swelling or unhealed sores in the mouth or jaw, blistering, numbness, or a heavy feeling in the jaw or loose teeth may be signs of bone damage in the jaw ( osteonecrosis ).
Very common side effects ( may affect more than 1 in 10 people):
- pain in the bones, joints, or muscles which can sometimes be severe
- respiratory distress
- diarrhea
Common side effects ( may affect up to 1 in 10 people):
- low levels of phosphate in the blood ( hypophosphatemia )
- tooth extraction
- profuse sweating
- for patients with advanced cancer: development of another type of cancer.
Uncommon side effects ( may affect up to 1 in 100 people):
- high levels of calcium in the blood ( hypercalcemia ) after completion of treatment in patients with giant cell tumors of the skeleton,
- new or unusual pain in the hip, groin, or thigh (these may be early signs of a possible femur fracture),
- rash that may appear on the skin or sores in the mouth (a lichenoid rash caused by medicines).
Rare side effects ( may affect up to 1 in 1,000 people):
- allergic reactions (including wheezing or difficulty breathing; swelling of the face, lips, tongue, throat, or other parts of the body; rash, itching, or hives on the skin). In rare cases, allergic reactions can be serious
Has been reported (occurring in an unknown number of users):
- Contact a doctor if you experience pain in the ears if fluid flows from the ear, and/or if you suffer from an ear infection. This may be a sign of bone damage in the ear.
How to store XGEVA
Keep this medicine out of the sight and reach of children.
Use before the expiry date which is stated on the label and carton after EXP. The expiration date is the last day of the specified month.
Store in a refrigerator (2°C– 8°C).
Do not freeze.
Store the vial in the outer carton. Light sensitive.
You can leave the vial outside the refrigerator to reach room temperature (up to 25 °C) before injection. This makes the injection more comfortable. Once the vial has been removed from the refrigerator and has reached room temperature (up to 25°C), it must be used within 30 days.
Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.
Contents of the packaging and other information
Contents declaration
- The active substance is denosumab. Each vial contains 120 mg of denosumab in 1.7 ml of solution (corresponding to 70 mg/ml).
- Other ingredients are glacial acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 20, and water for injections.
Appearance and package sizes of the medicine
XGEVA is a solution for injection ( injection ).
XGEVA is a clear, colorless slightly yellow solution. It may contain trace amounts of transparent to white particles.
Each pack contains one, three, or four single-use vials.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Amgen Europe BV
Minervum 7061,
4817 ZK Breda,
Netherlands
Manufacturer
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
Co Dublin
Ireland
Manufacturer
Amgen NV
Telecom claim 5-7
1831 Diegem
Belgium