Vevzuo

Package leaflet: Information for the patient

Vevzuo 120 mg injectable solution

Denosumab
▼Medicinal product 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 this leaflet carefully before using this medicine as 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 reminder card containing important safety information that you need to know before and during treatment with Vevzuo.

Contents of this leaflet

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

1. What Vevzuo is and what it is used for

Vevzuo 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 bone tumour.
Vevzuo 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).
Vevzuo is also used to treat giant cell tumour of the bone that cannot be surgically removed, 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

Do not use Vevzuo

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

Warnings and precautions
Talk to your doctor before using Vevzuo.

Calcium and vitamin D supplementation
You must take calcium and vitamin D supplements while being treated with Vevzuo, except in cases where 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 Vevzuo.

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

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
An adverse effect called osteonecrosis of the jaw (severe deterioration of the jawbone tissue) has been commonly reported (may occur in up to 1 in 10 people) in patients who have received denosumab for conditions related to cancer.
Osteonecrosis of the jaw may also occur after discontinuation of 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 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 mouth wounds following dental procedures or oral surgery. Your doctor may ask you to undergo a dental examination before starting treatment with Vevzuo.
• During treatment, it is necessary to maintain good oral hygiene and undergo regular dental check-ups. If you wear dentures, ensure they are properly fitted.
• If you are currently undergoing dental treatment or are planning to undergo dental surgery (e.g. tooth extractions), inform your doctor about the dental treatment and inform your dentist that you are being treated with Vevzuo.
• Contact your doctor and dentist immediately if you notice any new problems with your mouth or teeth, such as loose teeth, pain or swelling, or failure of mouth sores to heal or presence of 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, not receiving routine dental care, suffering from gum problems, 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 femoral fractures 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 treatment with Vevzuo
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 have stopped taking Vevzuo.

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

Other medicines and Vevzuo
Inform 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 Vevzuo 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 Vevzuo is not recommended during pregnancy. Women of childbearing potential must use effective contraception while taking Vevzuo and for at least 5 months after stopping treatment with Vevzuo.
If you become pregnant during treatment with Vevzuo or within less than 5 months after stopping treatment with Vevzuo, please 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 Vevzuo, taking into account the benefit of breastfeeding for the child and the benefit of Vevzuo for the mother.
If you are breastfeeding during treatment with Vevzuo, please inform your doctor.
Ask your doctor or pharmacist for advice before taking this medicine.

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

Vevzuo contains sorbitol
This medicine contains 79.9 mg of sorbitol per vial.

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

Denosumab BBL contains Polysorbate 20
This medicine contains 0.17 mg of polysorbate 20 in each 120 mg/1.7 mL vial, equivalent to 0.1 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you or your child have known allergies.

3. How to use Vevzuo

Vevzuo should be administered under the supervision of a healthcare professional.
The recommended dose of Vevzuo is 120 mg given once every 4 weeks, as a single subcutaneous injection. Vevzuo will be injected into the thigh, abdomen, or upper arm. If you are being treated for giant cell bone tumour, you will receive additional doses 1 week and 2 weeks after the first dose.
Do not shake.
While receiving treatment with Vevzuo, 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, during treatment with Vevzuo, 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 calcium levels in the blood. Low calcium levels in the blood may also lead to changes in heart rhythm called QT interval prolongation, which is detected by electrocardiogram (ECG).

Contact your doctor and dentist immediately if, during treatment with Vevzuo or after stopping treatment with Vevzuo, 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 or jaw sores to heal, 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 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 (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 treatment discontinuation 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 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 get any side effects, including any 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 Vevzuo

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
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 the vial has reached room temperature (up to 25°C), it must be used within 30 days.
Do not dispose of medicines 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 Vevzuo contains

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

Description of the appearance of Vevzuo and contents of the pack
Vevzuo is an injectable solution (injectable).
Vevzuo is a solution that is clear to slightly opalescent, colourless to pale yellow.
Each pack contains one single-use vial.

Marketing Authorisation Holder
Biosimilar Collaborations Ireland Limited
Unit 35/36, Grange Parade,
Baldoyle Industrial Estate, Dublin 13,
Dublin, Ireland, D13 R20R

Manufacturer
Biosimilar Collaborations Ireland Limited
Block B, The Crescent Building,
Santry, Demesne,
Dublin, D09 C6X, Ireland

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

België/Belgique/Belgien Lietuva
Biocon Biologics Belgium BV Biosimilar Collaborations Ireland Limited
Tél/Tel: 0080008250910 Tel: 0080008250910

България Luxembourg/Luxemburg
Biosimilar Collaborations Ireland Limited Biocon Biologics France S.A.S
Тел: 0080008250910 Tél/Tel: 0080008250910
(Belgique/Belgien)

Česká republika Magyarország
Biocon Biologics Germany GmbH Biosimilar Collaborations Ireland Limited
Tel: 0080008250910 Tel.: 0080008250910

Danmark Malta
Biocon Biologics Finland OY Biosimilar Collaborations Ireland Limited
Tlf: 0080008250910 Tel.: 0080008250910

Deutschland Nederland
Biocon Biologics Germany GmbH Biocon Biologics France S.A.S
Tel: 0080008250910 Tel: 0080008250910

Eesti Norge
Biosimilar Collaborations Ireland Limited Biocon Biologics Finland OY
Tel: 0080008250910 Tlf: +47 800 62 671

Ελλάδα Österreich
Biocon Biologics Greece ΜΟΝΟΠΡΟΣΩΠΗ Biocon Biologics Germany GmbH
Ι.Κ.Ε Tel: 0080008250910
Τηλ.: 0080008250910

España Polska
Biocon Biologics Spain S.L. Biosimilar Collaborations Ireland Limited
Tel: 0080008250910 Tel: 0080008250910

France Portugal
Biocon Biologics France S.A.S Biocon Biologics Spain S.L.
Tel: 0080008250910 Tel: 0080008250910

Hrvatska România
Biocon Biologics Germany GmbH Biosimilar Collaborations Ireland Limited
Tel: 0080008250910 Tel: 0080008250910

Ireland Slovenija
Biosimilar Collaborations Ireland Limited Biosimilar Collaborations Ireland Limited
Tel: 1800 777 794 Tel: 0080008250910

Ísland Slovenská republika
Biocon Biologics Finland OY Biocon Biologics Germany GmbH
Sími: +345 800 4316 Tel: 0080008250910

Italia Suomi/Finland
Biocon Biologics Spain S.L. Biocon Biologics Finland OY
Tel: 0080008250910 Puh/Tel: 99980008250910

Κύπρος Sverige
Biosimilar Collaborations Ireland Limited Biocon Biologics Finland OY
Τηλ: 0080008250910 Tel: 0080008250910

Latvija
Biosimilar Collaborations Ireland Limited
Tel: 0080008250910

More detailed information on this medicine 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 Vevzuo solution should be inspected visually. Do not inject the solution if it is cloudy or discoloured.
• 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.
• 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 applicable regulations.