Yaxwer 120 mg solution for injection

Patient Information Leaflet

Introduction

Patient Information Leaflet

Yaxwer 120 mg solution for injection

denosumab

This medicinal product is subject to additional monitoring, which will allow for quicker identification of new safety information. You can help by reporting any side effects you may experience. Section 4 at the end of this leaflet contains information on how to report side effects.

Please read all of this leaflet carefully before you start using this medicine, as 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 or pharmacist.
• This medicine has been prescribed for you only; do not pass it on to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if the side effects are not listed in this leaflet. See section 4.
• Your doctor will provide you with a patient information card containing important safety information you should 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 works to slow down bone destruction caused by cancer spreading to the bone (bone metastases) or by giant cell bone tumor.

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

Yaxwer is also used to treat giant cell bone tumor 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 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).

Your healthcare professional will not administer Yaxwer to you if you have severely low calcium levels in your blood that have 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 supplements

You must take calcium and vitamin D supplements while being treated with Yaxwer unless your blood calcium level is high. Your doctor will advise you about this. If your blood calcium level is low, your doctor may decide to give you calcium supplements before starting treatment with Yaxwer.

Low calcium levels in blood

Tell your doctor immediately if you experience muscle spasms, twitching, or cramps 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 calcium levels in your blood.

Renal impairment

Tell your doctor if you have or have had severe kidney problems, renal failure, or if you have required dialysis, as this may increase your risk of low calcium levels in blood, especially if you do not take calcium supplements.

Problems with mouth, teeth, and jaw

Osteonecrosis of the jaw (damage to the jawbone) has been frequently reported as an adverse reaction in patients receiving denosumab injections for cancer-related conditions (may affect up to 1 in 10 people). 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 may be a painful condition that can be difficult to treat. To reduce the risk of developing osteonecruise of the jaw, you should follow several precautions:

• Before receiving treatment, inform 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 due to dental procedures or oral surgery. Your doctor may recommend a dental examination before starting treatment with Yaxwer.
• While being treated, you must maintain good oral hygiene and attend regular dental check-ups. If you wear dentures, ensure they fit properly.
• If you are receiving 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 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 or draining sores, 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, not receiving regular dental care, having gum disease, or who are smokers may have an increased risk of developing osteonecrosis of the jaw.

Unusual femur bone fractures

Some people have developed unusual fractures in the femur 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 blood after stopping Yaxwer treatment

Some patients with giant cell tumor of bone have developed high calcium levels in blood weeks or months after stopping treatment. Your doctor will monitor you for signs and symptoms of high calcium levels 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 tumor of bone whose bones have stopped growing. The use of Yaxwer has not been studied in children and adolescents with other types of cancer that have spread to the bones.

Other medicines and Yaxwer

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

• 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 or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using 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 plan to become pregnant. Yaxwer is not recommended during pregnancy. Women of childbearing potential must use effective contraception during treatment with 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, inform your doctor.

It is unknown whether Yaxwer is excreted in human breast milk. It is important that you inform your doctor if you are breastfeeding or plan to breastfeed. Your doctor will help you decide whether to discontinue breastfeeding or discontinue treatment with Yaxwer, taking into account the benefit of breastfeeding for the child and the benefit of Yaxwer for you.

If you are breastfeeding during treatment with Yaxwer, 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 any 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 (under the skin) injection. Yaxwer 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 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 hypercalcemia (excess calcium in the blood). Your doctor will advise you on this.

If you have any questions 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 everyone gets them.

Tell your doctor immediately if you develop any of the following symptoms while being treated with Yaxwer (these 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 could be symptoms of low calcium levels in the blood. Low blood calcium may also lead to a change in heart rhythm called QT prolongation, which is seen on an electrocardiogram (ECG).

Tell your doctor and dentist immediately if you experience any of the following symptoms while being treated with Yaxwer or after stopping treatment (these may affect up to 1 in 10 people):

• persistent pain in the mouth and/or jaw, and/or swelling or failure of wounds in the mouth or jaw to heal, discharge, numbness or a feeling of heaviness in the jaw, or loosening of a tooth, which could be symptoms 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 may sometimes be severe,
• difficulty breathing,
• diarrhoea.

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

• low levels of phosphate in the blood (hypophosphataemia),
• tooth extraction,
• 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 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 side effects (may affect up to 1 in 1000 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.

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

• consult your doctor if you have ear pain, discharge from the ear, and/or an ear infection. These could be symptoms of damage to the bones of the ear.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Yaxwer

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the label of the carton and container after EXP. 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.

The vial may be removed from the refrigerator and kept at room temperature (up to 25 °C) prior to 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 container and outer packaging to protect it from light. It must be used within this 30-day period.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Yaxwer

• 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 excipients are glacial acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 20 (E432), and water for injections.

Nature of the product and contents of the container

Yaxwer is an injectable solution (injectable).

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

The 1.7 ml solution is supplied in a single-use injection vial made of clear glass (type I according to Ph. Eur.), sealed with a bromobutyl rubber stopper coated with a fluorinated layer and an aluminium cap with a plastic flip-off seal.

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

Marketing Authorisation Holder

Gedeon Richter Plc.

Gyömroi út 19-21.

1103 Budapest

Hungary

Manufacturer

Chemical Works of Gedeon Richter Plc.

(Gedeon Richter Plc.)

Richter Gedeon utca 20.

4031 Debrecen

Hungary

Gedeon Richter Plc.

Gyömroi út 19-21.

1103 Budapest Hungary

Date of the most recent revision of this leaflet:

Other sources of information

Detailed information about this product is also available by scanning the QR code below or on the outer packaging with your mobile phone. The same information is also available at the following URL: www.yaxwerinfo.com

QR code to be included

Detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu , and on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/.

This information is intended for healthcare professionals only:

• Before administration, the 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 injection site discomfort, 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.
• A 27-gauge needle is recommended for administration of denosumab.
• Do not insert 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.