Yaxwer

Package leaflet: Information for the patient

Yaxwer 120 mg solution for injection

denosumab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.
• Your doctor will give you a patient reminder card containing important safety information that you must know before and during treatment with Yaxwer.

Contents of this leaflet

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

1. What Yaxwer is and what it is used for

Yaxwer contains denosumab, a protein (monoclonal antibody) that acts to reduce bone destruction caused by cancer spreading to the bone (bone metastases) or by giant cell bone tumour.
Yaxwer is used in adults with advanced cancer to prevent serious complications caused by bone metastases (e.g. fracture, pressure on the spinal cord, or need for radiotherapy or surgery).
Yaxwer is also used to treat giant cell bone tumour that cannot be treated surgically or where surgery is not the best option, in adults and in adolescents whose bones have stopped growing.

2. What you should know before using Yaxwer

Do not use Yaxwer

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

The healthcare provider will not administer Yaxwer to you if you have severely low levels of calcium in your blood that have not been treated.
The healthcare provider will not administer Yaxwer if you have unhealed wounds following dental or oral surgery.

Warnings and precautions

Talk to your doctor before using Yaxwer.

Calcium and vitamin D supplementation
You must take calcium and vitamin D supplements while being treated with Yaxwer, except in cases where your blood calcium levels are high. Your doctor will discuss this with you. If your blood calcium level is low, your doctor may decide to give you calcium supplements before starting treatment with Yaxwer.

Low levels of calcium in the blood
Tell your doctor immediately if, during treatment with Yaxwer, you experience muscle spasms, twitching or cramps, and/or numbness or tingling in the fingers, toes, or around the mouth, and/or seizures, confusion, or loss of consciousness. These may be signs of low blood calcium levels.

Kidney problems
Inform your doctor if you currently have, have had in the past, or have ever had severe kidney problems, kidney failure, or if you are undergoing dialysis, as these conditions may increase the risk of low blood calcium levels, especially if you are not taking calcium supplements.

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

It is important to try to prevent the development of osteonecrosis of the jaw, as it is 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:

• Before starting treatment, inform your doctor/nurse (healthcare provider) if you have any mouth or dental problems. Your doctor should delay starting treatment if you have unhealed mouth wounds following dental procedures or oral surgery. Your doctor may ask you to have a dental examination before starting treatment with Yaxwer.
• During treatment, you must maintain good oral hygiene and have regular dental check-ups. If you wear dentures, ensure they fit properly.
• If you are currently undergoing dental treatment or are planning to have dental surgery (e.g., tooth extractions), inform your doctor about the dental treatment and inform your dentist that you are being treated with Yaxwer.
• Contact your doctor and dentist immediately if you notice any new mouth or dental problems, such as loose teeth, pain or swelling, or failure of mouth sores to heal, or discharge, as these could be signs of osteonecrosis of the jaw.

Patients who are receiving chemotherapy and/or radiation therapy, taking steroids or anti-angiogenic drugs (used to treat cancer), undergoing dental surgery, not receiving routine dental care, suffering from gum disease, or who are smokers may have a higher risk of developing osteonecrosis of the jaw.

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

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

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

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. In particular, it is important that you inform your doctor if you are taking:

• another medicine containing denosumab
• a bisphosphonate

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

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning to become pregnant, or breastfeeding, ask your doctor for advice before taking this medicine.
Yaxwer has not been studied in pregnant women. It is important that you inform your doctor if you are pregnant, think you might be pregnant, or are planning a pregnancy. The use of Yaxwer is not recommended during pregnancy. Women of childbearing potential must use effective contraception while taking Yaxwer and for at least 5 months after stopping treatment with Yaxwer.
If you become pregnant during treatment with Yaxwer or within 5 months after stopping treatment with Yaxwer, please inform your doctor.
It is not known whether Yaxwer is excreted in human breast milk. It is important that you inform your doctor if you are breastfeeding or planning to breastfeed. Your doctor will help you decide whether to discontinue breastfeeding or discontinue Yaxwer, taking into account the benefit of breastfeeding for the child and the benefit of Yaxwer for the mother.
If you are breastfeeding 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 of sorbitol per dose (1.7 mL).
This medicine contains 0.17 mg of polysorbate 20 per dose (1.7 mL). Polysorbates may cause allergic reactions. Inform your doctor if you or your child have known allergies.
This medicine contains less than 1 mmol of sodium (23 mg) per dose (1.7 mL), i.e., essentially ‘sodium-free’.

3. How to use Yaxwer

Yaxwer must be administered under the supervision of a healthcare professional.
The recommended dose of Yaxwer is 120 mg given once every 4 weeks, as a single
subcutaneous injection. Yaxwer will be injected into the thigh, abdomen, or upper arm. If you are being treated for giant cell tumor of the bone, you will receive additional doses 1 week and 2 weeks after the first dose.
Do not shake.
During treatment with Yaxwer, you must also take calcium and vitamin D supplements unless you have excess calcium in your blood. Your doctor will discuss this with you.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately if, during treatment with Yaxwer, you notice any of the following symptoms (these may affect more than 1 in 10 people):

• muscle spasms, contractions, cramps, numbness or tingling in the fingers of the hands and feet or around the mouth and/or seizures, confusion or loss of consciousness. These signs could indicate low levels of calcium in the blood. Low calcium levels in the blood may also lead to a change in heart rhythm called QT interval prolongation, which is detected by electrocardiogram (ECG).

Contact your doctor and dentist immediately if, during treatment with Yaxwer or after stopping treatment with Yaxwer, you notice any of the following symptoms (these may occur in up to 1 in 10 people):

• persistent pain in the mouth and/or jaw, and/or swelling or failure of mouth sores to heal, or discharge, numbness or a feeling of heaviness in the jaw, or loosening of a tooth, as these signs could indicate a severe deterioration of the jawbone tissue (osteonecrosis).

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

• bone, joint and/or muscle pain, sometimes severe,
• shortness of breath (dyspnoea),
• diarrhoea.

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

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

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

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

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

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

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

• inform your doctor if you experience ear pain, ear discharge, and/or ear infection. These could be signs of damage to the ear bone.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Yaxwer

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 after "Exp." and on the
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 packaging to protect the medicine from light.
The vial may be removed from the refrigerator and allowed 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 a
maximum of 30 days in the original packaging and outer packaging to protect the medicine from light.
It must be used within this 30-day period.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Yaxwer contains

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

Description of the appearance of Yaxwer and contents of the pack
Yaxwer is an injectable solution (injection).
Yaxwer is a clear, colourless to slightly yellow solution, free from visible particles.
1.7 mL solution in a single-use injection vial made of clear glass (Ph. Eur. type I glass),
sealed with a bromobutyl rubber stopper coated with a fluorinated film and an aluminium crimp cap
with a plastic flip-off cap.
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
Hungary
Gedeon Richter Plc.
Gyömrői út 19-21.
1103 Budapest
Hungary

Other sources of information
Detailed information on this product is also available by scanning with a smartphone
the QR code included below or on the outer packaging. The same information is also available
at the following address: www.yaxwerinfo.com
QR code to be included
More detailed information on this medicinal product is available on the website of the European Medicines Agency, https://www.ema.europa.eu/.

The following information is intended exclusively for healthcare professionals:

• Before administration, the Yaxwer solution should be inspected visually. Do not inject the solution if it contains visible particles, is cloudy, or shows discoloration.
• Do not shake.
• To minimize discomfort at the injection site, allow the vial to reach room temperature (up to 25°C) before injection and inject slowly.
• The entire contents of the vial must be injected.
• For denosumab administration, a 27-gauge steel needle is recommended.
• The vial must not be reused.

Any unused medicine and waste material derived from this medicine must be disposed of in accordance with
local applicable regulations.