XBRYK

Patient Information Leaflet

Xbryk 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, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.
• Your doctor will provide you with a patient reminder card containing important safety information that you need to know before and during treatment with Xbryk.

Contents of this leaflet

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

1. What Xbryk is and what it is used for

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

2. What you need to know before using Xbryk

Do not use Xbryk

• 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 Xbryk to you if you have very low levels of calcium in your blood that have not been treated.
The healthcare provider will not administer Xbryk if you have unhealed wounds from dental or oral surgery.

Warnings and precautions
Talk to your doctor before using Xbryk.

Calcium and vitamin D supplementation
You must take calcium and vitamin D supplements while being treated with Xbryk, except if 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 Xbryk.

Low levels of calcium in the blood
Tell your doctor immediately if, during treatment with Xbryk, 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. You may have low levels of calcium in your blood.

Renal impairment
Tell your doctor if you have or have ever had severe kidney problems, kidney failure, or if you have undergone 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/mandible
An adverse effect called osteonecrosis of the jaw/mandible (severe deterioration of the jaw/mandible bone tissue) has been commonly reported (may occur in up to 1 in 10 people) in patients who have received Xbryk injections for tumour-related conditions.
Osteonecrosis of the jaw/mandible may also occur after stopping treatment.
It is important to try to prevent the development of osteonecrosis of the jaw/mandible, as it is a painful condition that may be difficult to treat. To reduce the risk of developing osteonecrosis of the jaw/mandible, you should take the following precautions:

• Before receiving treatment, inform your doctor/nurse (healthcare provider) if you have any mouth or dental problems. Your doctor should delay the start of treatment if you have unhealed wounds in your mouth following dental procedures or oral surgery. Your doctor may ask you to have a dental examination before starting treatment with Xbryk.
• During treatment, you must maintain good oral hygiene and have regular dental check-ups. If you wear dentures, ensure they are properly fitted.
• 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 Xbryk.
• 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 the presence of discharge, as these may be signs of osteonecrosis of the jaw/mandible.

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

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

High levels of calcium in the blood after stopping treatment with Xbryk
Some patients with giant cell tumour of 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 have stopped taking Xbryk.

Children and adolescents
Xbryk is not recommended for children and adolescents under 18 years of age, except for adolescents with giant cell tumour of bone whose bones have stopped growing. The use of denosumab in children and adolescents with other tumours that have invaded the bones has not been studied.

Other medicines and Xbryk
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 Xbryk together with other medicines containing denosumab or bisphosphonates.

Pregnancy and breastfeeding
Denosumab has not been studied in pregnant women. It is important that you inform your doctor if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. The use of Xbryk is not recommended during pregnancy. Women of childbearing potential must use effective contraception while taking Xbryk and for at least 5 months after stopping treatment with Xbryk.
If you become pregnant during treatment with Xbryk or within 5 months after stopping treatment with Xbryk, please inform your doctor.

It is not known whether denosumab is excreted in breast milk. It is important that you inform your doctor if you are breastfeeding or planning to breastfeed. Your doctor will then help you decide whether to discontinue breastfeeding or to discontinue/abstain from Xbryk treatment, taking into account the benefit of breastfeeding for the child and the benefit of Xbryk treatment for the mother.
If you are breastfeeding while being treated with Xbryk, please inform your doctor.

Ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines
Xbryk has no or negligible influence on the ability to drive and use machines.

Xbryk contains sorbitol (E420)
This medicine contains 74.8 mg of sorbitol (E420) per vial.

Xbryk contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 120 mg dose, i.e. essentially ‘sodium-free’.

3. How to use Xbryk

Xbryk must be administered under the supervision of a healthcare professional.
The recommended dose of Xbryk is 120 mg given once every 4 weeks, as a single
subcutaneous injection (under the skin). Xbryk 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.
During treatment with Xbryk, 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 the use of 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 Xbryk, you notice any of the following symptoms (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 known as QT prolongation, which is seen on an electrocardiogram (ECG).

Contact your doctor and dentist immediately if, during treatment with Xbryk or after stopping treatment with Xbryk, you notice any of the following symptoms (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, presence of discharge, numbness or a feeling of heaviness in the jaw, or loose teeth, 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 (dyspnea),
• diarrhoea.

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

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

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

• high levels of calcium in the blood (hypercalcemia) 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 fracture),
• rash which may occur on the skin 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 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):
inform your doctor if you experience ear pain, ear discharge, and/or an ear infection. These could be signs of damage to the ear bone.
Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Xbryk

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label after EXP and on the
pack 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 its 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 the vial has reached room temperature (up to 25°C), it may be stored at room temperature for a single period of up to 60 days, but not beyond the original expiry date. If not used within this maximum period of 60 days, Xbryk may be returned to the refrigerator for future use for up to 28 days. Do not use the vial after the expiry date stated on the label.
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. Pack contents and other information

What Xbryk 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 histidine, monohydrochloride monohydrate histidine, sorbitol (E420), polysorbate 20 and water for injections.

Description of the appearance of Xbryk and contents of the pack
Xbryk is an injectable solution (injectable).
Xbryk is a clear, colourless to slightly yellow solution. It may contain traces of
clear to white particles.
Each pack contains one or three single-use vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft
The Netherlands

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/.

The following information is intended for healthcare professionals only:

• Prior to administration, the Xbryk solution should be inspected visually. The solution may contain traces of translucent to white proteinaceous particles. Do not inject if the solution is cloudy or discolored.
• 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 content of the vial must be administered.
• A 27-gauge steel needle is recommended for denosumab administration.
• The vial must not be reused.

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