Yaxwer 120 mg

Yaxwer contains denosumab, a protein (monoclonal antibody) that works to slow down bone destruction caused by cancer spreading to the bone (bone metastasis) or by giant cell tumour of bone.

Yaxwer is used in adults with advanced cancer to prevent serious complications caused by bone metastasis (e.g., fracture, pressure on the spinal cord or the need to receive radiation therapy or surgery).

Yaxwer is also used to treat giant cell tumour of bone, which cannot be treated by surgery or where surgery is not the best option, in adults and adolescents whose bones have stopped growing.

Do not use Yaxwer

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

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

Your healthcare professional will not administer Yaxwer to you if you have unhealed wounds from dental or oral surgery.

Warnings and precautions

Talk to your doctor before receiving Yaxwer.

Calcium and vitamin D supplementation
You should take calcium and vitamin D supplements while being treated with Yaxwer unless your blood calcium is high. Your doctor will discuss this with you. If the level of calcium in your blood is low, your doctor may decide to give you calcium supplements before you start treatment with Yaxwer.

Low calcium levels in the blood
Please tell your doctor immediately if you have spasms, twitches, or cramps in your muscles, and/or numbness or tingling in your fingers, toes or around your mouth and/or seizures, confusion or loss of consciousness while being treated with Yaxwer. You may have low levels of calcium in your blood.

Renal impairment
Tell your doctor if you have or have had severe kidney problems, kidney failure or have needed dialysis, which may increase your risk of getting low blood calcium, especially if you do not take calcium supplements.

Problems with your mouth, teeth or jaw
A side effect called osteonecrosis of the jaw (bone damage in the jaw) has been reported commonly (may affect up to 1 in 10 people) in patients receiving denosumab injections for cancer-related conditions. Osteonecrosis of the jaw can also occur after stopping treatment.

It is important to try to prevent osteonecrosis of the jaw developing as it may be a painful condition that can be difficult to treat. In order to reduce the risk of developing osteonecrosis of the jaw, there are some precautions you should take:

• Before receiving treatment, tell your doctor/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 from dental procedures or oral surgery. Your doctor may recommend a dental examination before you start treatment with Yaxwer.
• While being treated, you should maintain good oral hygiene and receive routine dental check- ups. If you wear dentures, you should make sure these fit properly.
• If you are under dental treatment or will undergo dental surgery (e.g., tooth extractions), inform your doctor about your dental treatment and tell your dentist that you are being treated with Yaxwer.
• 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 of sores or discharge, as these could be signs of osteonecrosis of the jaw.

Patients undergoing chemotherapy and/or radiotherapy, taking steroids or anti-angiogenic medicines (used to treat cancer), undergoing dental surgery, who do not receive routine dental care, have gum disease or who are smokers, may have a higher risk of developing osteonecrosis of the jaw.

Unusual thigh bone fractures
Some people have developed unusual fractures in their thigh bone while being treated with denosumab. Contact your doctor if you experience new or unusual pain in your hip, groin, or thigh.

High calcium levels in the blood after stopping treatment with Yaxwer
Some patients with giant cell tumour of the bone have developed high calcium levels in the blood weeks to months after stopping treatment. Your doctor will monitor you for signs and symptoms of high levels of calcium, after you stop receiving Yaxwer.

Children and adolescents

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

Other medicines and Yaxwer

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 especially important that you tell your doctor if you are being treated with:

• another medicine containing denosumab
• a bisphosphonate.

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

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Yaxwer has not been tested in pregnant women. It is important to tell your doctor if you are pregnant, think you may be pregnant, or plan to get pregnant. Yaxwer is not recommended for use if you are pregnant. Women of child-bearing potential should use effective methods of contraception while being treated with Yaxwer and for at least 5 months after stopping treatment with Yaxwer.

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

It is not known whether Yaxwer is excreted in breast milk. It is important to tell your doctor if you are breast-feeding or plan to do so. Your doctor will then help you decide whether to stop breast-feeding or whether to stop taking Yaxwer, considering the benefit of breast-feeding to the baby and the benefit of Yaxwer to the mother.

If you are nursing during treatment with Yaxwer, please inform your doctor.

Driving and using machines

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

Yaxwer contains sorbitol, polysorbate 20 and sodium

This medicine contains 78 mg sorbitol in each dosage (1.7 mL).

This medicine contains 0.17 mg of polysorbate 20 in each dosage (1.7 mL). Polysorbates may cause allergic reactions. Tell your doctor if you have or your child has any known allergies. This medicine contains less than 1 mmol sodium (23 mg) per dosage (1.7 mL), that is to say essentially ‘sodium-free’.

Yaxwer should be administered under the responsibility of a healthcare professional.

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

Do not shake.

You should also take calcium and vitamin D supplements while being treated with Yaxwer unless you have an excess of calcium in the blood. Your doctor will discuss this with you. If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

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

Please tell your doctor immediatelyif you develop any of these symptoms while being treated with Yaxwer (may affect more than 1 in 10 people):

• spasms, twitches, cramps in your muscles, numbness or tingling in your fingers, toes or around your mouth and/or seizures, confusion or loss of consciousness. These could be signs that you have low calcium levels in the blood. Low calcium in the blood may also lead to a change in heart rhythm called QT prolongation, which is seen by electrocardiogram (ECG).

Please tell your doctor and dentist immediatelyif you experience any of these symptoms while being treated with Yaxwer or after stopping treatment (may affect up to 1 in 10 people):

• persistent pain in the mouth and/or jaw, and/or swelling or non-healing of sores in the mouth or jaw, discharge, numbness or feeling of heaviness in the jaw, or loosening of a tooth could 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, which is sometimes severe,
• shortness of breath,
• diarrhoea.

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

• low phosphate levels in the blood (hypophosphataemia),
• removal of a tooth,
• excessive sweating,
• in patients with advanced cancer: development of another form of cancer.

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

• high calcium levels in the blood (hypercalcaemia) after stopping treatment in patients with giant cell tumour of the bone,
• new or unusual pain in your hip, groin or thigh (this may be an early indication of a possible fracture of the thigh bone),
• rash that may occur on the skin or sores in the mouth (lichenoid drug 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; rash, itching or hives on the skin). In rare cases allergic reactions may be severe.

Not known(frequency cannot be estimated from the available data):

• Talk to your doctor if you have ear pain, discharge from the ear, and/or an ear infection. These could be signs of bone damage in the ear.

Reporting of side effects

If you get 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.

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 label and carton after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2 °C – 8 °C).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.

The vial may be left outside the refrigerator to reach room temperature (up to 25 °C) before injection. This will make the injection more comfortable. Once removed from the refrigerator, Yaxwer may be stored at room temperature (up to 25 °C) for up to 30 days in the original container and outer packaging in order to protect from light. It must be used within this 30-days period.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Yaxwer contains

• The active substance is denosumab. Each vial contains 120 mg of denosumab in 1.7 mL of solution (corresponding to 70 mg/mL).
• The other ingredients are acetic acid, glacial, sodium hydroxide, sorbitol (E420), polysorbate 20 (E432) and water for injections.

What Yaxwer looks like and contents of the pack
Yaxwer is a solution for injection (injection).

Yaxwer is a clear, colourless to slightly yellow solution, free from visible particles.

1.7 mL solution is presented in a clear glass injection vial (Ph. Eur. Type I glass) sealed with bromobutyl rubber stopper covered with a fluorinated coating and a plastic flip cap with aluminium sealing.

Each pack contains one, three or four single use vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Gedeon Richter Plc.
Gyömrői út 19-21.
1103 Budapest
Hungary

Manufacturers
Chemical Works of Gedeon Richter Plc.
(Gedeon Richter Plc.)
Richter Gedeon utca 20.
4031 Debrecen
4031
Hungary

Gedeon Richter Plc.
Gyömrői út 19-21.
1103 Budapest
Hungary

This leaflet was last revised in .

Other sources of information

Detailed information on this product is also available by scanning the QR code included below or the outer carton with a smartphone. The same information is also available on the following URL: www.yaxwerinfo.com

QR code to be included

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu , and on the website of {name of Member State Agency (link)}.

The following information is intended for healthcare professionals only:

Before administration, Yaxwer solution should be inspected visually. Do not inject the solution if it contains visible particles, is cloudy or discoloured.

• Do not shake.
• To avoid discomfort at the site of injection, allow the vial to reach room temperature (up to 25 ºC) before injecting and inject slowly.
• The entire contents of the vial should be injected.
• A 27-gauge needle is recommended for the administration of denosumab.
• The vial should not be re-entered.

Any unused product or waste material should be disposed of in accordance with local requirements.