Denbrayce

Package leaflet: Information for the patient

Denbrayce 120 mg solution for injection

denosumab
This medicinal product is subject to additional monitoring. This will allow 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 all of this leaflet carefully before you start 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 other people, even if their symptoms are the same as yours, as it may 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 give you a patient alert card containing important safety information that you need to know before and during treatment with Denbrayce.

Contents of this leaflet

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

1. What Denbrayce is and what it is used for

What Denbrayce is and how it works
Denbrayce contains denosumab, a protein (monoclonal antibody) that acts to reduce bone destruction caused by the spread of cancer to the bone (bone metastases) or by giant cell tumour of the bone.
Denbrayce 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).
Denbrayce is also used to treat giant cell tumour of the bone 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 need to know before using Denbrayce

Do not use Denbrayce

• 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 Denbrayce to you if you have severely low blood calcium levels that have not been treated.
The healthcare provider will not administer Denbrayce if you have unhealed wounds from dental or oral surgery.

Warnings and precautions

Talk to your doctor before using Denbrayce.

Calcium and vitamin D supplementation
You must take calcium and vitamin D supplements while receiving denosumab treatment, 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 Denbrayce.

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

Renal impairment
Inform your doctor if you currently 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
A side effect called osteonecrosis of the jaw 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 denosumab treatment.
• During treatment, you must maintain good oral hygiene and have regular dental check-ups. If you wear dentures, make sure 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 denosumab.
• 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 presence of discharge, as these may be signs of osteonecrosis of the jaw.

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

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

Children and adolescents
Denbrayce 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 denosumab in children and adolescents with other cancers that have spread to the bone has not been studied.

Other medicines and Denbrayce
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those 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 Denbrayce together with other medicines containing denosumab or bisphosphonates.

Pregnancy and breastfeeding
Denbrayce has not been studied in pregnant women. If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine.
The use of denosumab is not recommended during pregnancy. Women of childbearing potential must use effective contraception during treatment with denosumab and for at least 5 months after stopping treatment with denosumab.
If you become pregnant during treatment with denosumab or within 5 months after stopping treatment with denosumab, inform your doctor.
It is not known whether denosumab is excreted in human 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 discontinue denosumab, taking into account the benefits of breastfeeding for the child and the benefits of denosumab treatment for the mother.
If you are breastfeeding while receiving Denbrayce, inform your doctor.

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

Driving and using machines
Denbrayce has no effect or has a negligible effect on the ability to drive and use machines.

Denbrayce contains sorbitol
This medicine contains 78 mg of sorbitol per vial.

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

Denbrayce contains polysorbate 20 (E 432)
This medicine contains 0.17 mg of polysorbate 20 (E 432) per vial, equivalent to 0.1 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Denbrayce

Denbrayce must be administered under the supervision of a healthcare professional.
The recommended dose of Denbrayce is 120 mg given once every 4 weeks, as a single
subcutaneous injection (under the skin). Denbrayce 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 an additional dose 1 week and 2 weeks after the first dose.
Do not shake.
While receiving denosumab treatment, you should 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 you experience any of the following symptoms during treatment with Denbrayce (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 calcium levels in the blood. Low calcium levels may also lead to a change in heart rhythm called QT prolongation, which is detected by electrocardiogram (ECG).

Contact your doctor and dentist immediately if, during treatment with denosumab or after stopping treatment with denosumab, you experience 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 poor healing of sores in the mouth or jaw, discharge from the jaw, numbness or a feeling of heaviness in the jaw, or loose teeth, as these signs could indicate a serious deterioration of the jawbone (osteonecrosis).

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

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

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 could be an early sign of a possible fracture of the thigh bone),
• rash which may occur on the skin or sores in the mouth (drug-induced lichenoid eruptions).

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

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

Not known (frequency cannot be estimated from the available data):
contact 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 those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via 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 Denbrayce

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
packaging 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 the vial has reached room
temperature (up to 25°C), it must be used within 30 days.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Denbrayce contains

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

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

Marketing Authorisation Holder
Mabxience Research SL
C/ Manuel Pombo Angulo 28,
28050 Madrid
Spain

Manufacturer
GH GENHELIX S.A.
Parque Tecnológico de León
Edificio GENHELIX
C/Julia Morros, s/n
Armunia, 24009 León
Spain

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Mabxience Research SL UAB EGIS Lithuania
Tél/Tel: + 34 917 711 500 Tel: + 370 5 231 4658

България Luxembourg/Luxemburg
EGIS Bulgaria Mabxience Research SL
Teл.: + 359 2 987 60 40 Tél/Tel: + 34 917 711 500

Česká republika Magyarország
EGIS Praha, spol. s r.o Egis Gyógyszergyár Zrt.
Tel: + 420 227 129 111 Tel.: + 36 1 803 5555

Danmark Malta
Medical Valley Invest AB Mabxience Research SL
Tlf.: + 46 40 122131 Tel: + 34 917 711 500

Deutschland Nederland
Mabxience Research SL Medical Valley Invest AB
Tel: + 34 917 711 500 Tel: + 46 40 122131

Eesti Norge
Mabxience Research SL Medical Valley Invest AB
Tel: + 34 917 711 500 Tlf: + 46 40 122131

Ελλάδα Österreich
ELPEN Pharmaceutical Co. Inc Mabxience Research SL
Τηλ: + 30 210 6039326-9 Tel: + 34 917 711 500

España Polska
Mabxience Research SL Egis Polska sp. z o.o.
Tel: + 34 917 711 500 Tel.: + 48 22 417 92 00

France Portugal
Laboratoires Biogaran Mabxience Research SL
Tél: + 33 (0) 800 970 109 Tel: + 34 917 711 500

Hrvatska România
Mabxience Research SL Egis Rompharma SRL
Tel: + 34 917 711 500 Tel: + 40 21 412 00 17

Ireland Slovenija
Mabxience Research SL Mabxience Research SL
Tel: + 34 917 711 500 Tel: + 34 917 711 500

Ísland Slovenská republika
Mabxience Research SL EGIS SLOVAKIA spol. s r.o.,
Sími: + 34 917 711 500 Tel: + 421 2 3240 9422

Italia Suomi/Finland
Mabxience Research SL Medical Valley Invest AB
Tel: + 34 917 711 500 Puh/Tel: + 46 40 122131

Κύπρος Sverige
Mabxience Research SL Medical Valley Invest AB
Τηλ: + 34 917 711 500 Tel: + 46 40 122131

Latvija
Egis Latvia SIA
Tel: + 371 676 13859

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

The following information is intended for healthcare professionals only:

• Before administration, the Denbrayce solution should be inspected visually. The solution may contain traces of translucent to white protein particles. Do not inject if the solution is cloudy, discoloured, or contains numerous particles or foreign particulate matter.
• 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 administered.
• A 27-gauge steel needle is recommended for the administration of denosumab.
• The vial must not be reused.

Any unused medicinal product and waste material derived from its use must be disposed of in accordance with local regulations.