Jubbonti

Package leaflet: Information for the patient

Jubbonti 60 mg solution for injection in pre-filled syringe

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 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 or pharmacist.
• 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 or pharmacist. See section 4.
• Your doctor will provide you with a patient reminder card containing important safety information that you must know before and during treatment with Jubbonti.

Contents of this leaflet

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

1. What Jubbonti is and what it is used for

What Jubbonti is and how it works
Jubbonti contains denosumab, a protein (monoclonal antibody) that interferes with the action of another protein, for the treatment of bone loss and osteoporosis. Treatment with Jubbonti makes bones stronger and less prone to fractures.
Bone is a living tissue that is constantly being renewed. Oestrogens help maintain healthy bones. After menopause, reduced oestrogen levels can make bones thin and fragile, which may lead to the development of a condition called osteoporosis. Osteoporosis can also occur in men for various reasons, including ageing and/or low levels of the male hormone testosterone. It can also occur in patients receiving glucocorticoids. Many patients with osteoporosis do not have symptoms, but are still at risk of bone fractures, especially in the spine, hip, and wrists.
Surgical procedures or medications that stop the production of oestrogen or testosterone, used in the treatment of patients with breast or prostate cancer, can also cause bone loss. As a result, bones become more fragile and more likely to fracture.

What Jubbonti is used for
Jubbonti is used to treat:

• osteoporosis in postmenopausal women and in men who have an increased risk of fractures (broken bones), to reduce the risk of vertebral, non-vertebral, and hip fractures.
• bone loss in men with prostate cancer resulting from reduced hormone levels (testosterone) due to surgery or drug therapy.
• bone loss in patients at increased risk of fracture due to long-term treatment with glucocorticoids.

2. What you need to know before using Jubbonti

Do not use Jubbonti

• if you have low levels of calcium in your blood (hypocalcemia).
• if you are allergic to denosumab or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor or pharmacist before using Jubbonti.
During treatment with Jubbonti, you may develop a skin infection with symptoms such as swelling, redness of the skin, most commonly in the lower leg, with a feeling of warmth and pain (cellulitis), and possibly fever. Inform your doctor immediately if you experience any of these symptoms.
During treatment with Jubbonti, you must also take calcium and vitamin D supplements. Your doctor will discuss this with you.
During treatment with Jubbonti, you may have low levels of calcium in your blood. Inform your doctor immediately if you notice any of the following symptoms: muscle spasms, stiffness or cramps, and/or numbness or tingling in your fingers, toes or around your mouth, and/or seizures, confusion or loss of consciousness.
In rare cases, severe hypocalcemia has been reported, leading to hospitalization and even life-threatening reactions. Therefore, your blood calcium levels will be monitored (through blood tests) before each dose and within two weeks after the initial dose in patients at risk of developing hypocalcemia.
Inform your doctor if you have or have ever had severe kidney problems, renal failure, or if you are undergoing dialysis, or if you are taking medicines called glucocorticoids (such as prednisolone or dexamethasone), which could increase your risk of low blood calcium levels if you are not taking calcium supplements.

Problems with mouth, teeth or jaw
In patients receiving denosumab for osteoporosis, a rare adverse effect called osteonecrosis of the jaw/mandible (severe deterioration of the jaw/mandible bone tissue) has been reported (may occur in up to 1 in 1,000 patients). The risk of osteonecrosis of the jaw/mandible increases in patients treated for a long period (may occur in up to 1 in 200 patients treated for 10 years). 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 can be difficult to treat. To reduce the risk of developing osteonecrosis of the jaw/mandible, take the following precautions:
Before receiving treatment, inform your doctor or nurse (healthcare provider) if you:

• have any problems with your mouth or teeth, such as poor dental hygiene, gum disease, or if you are scheduled for a tooth extraction;
• do not regularly receive dental care or have not had a dental check-up for a long time;
• are a smoker (as this may increase the risk of dental problems);
• have previously been treated with a bisphosphonate (used to treat or prevent bone diseases);
• are taking medicines called corticosteroids (such as prednisolone or dexamethasone);
• have cancer.

Your doctor may ask you to have a dental examination (by a dentist) before starting treatment with Jubbonti.
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 plan 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 Jubbonti.
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 ulcers to heal or presence of discharge, as these could be signs of an adverse reaction called osteonecrosis of the jaw/mandible (ONJ).

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

Children and adolescents
Jubbonti must not be used in children and adolescents under 18 years of age.

Other medicines and Jubbonti
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. It is particularly important that you inform your doctor if you are taking other medicines containing denosumab.
You must not take Jubbonti together with other medicines containing denosumab.

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 Jubbonti is not recommended during pregnancy. Women of childbearing potential must use effective contraception during treatment with Jubbonti and for at least 5 months after stopping treatment.
If you become pregnant during treatment with Jubbonti, or within 5 months after stopping treatment with Jubbonti, 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 help you decide whether to discontinue breastfeeding or the use of Jubbonti, taking into account the benefits of breastfeeding for the child and the benefits of Jubbonti for the mother.

If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.

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

Jubbonti contains sorbitol
This medicine contains 47 mg of sorbitol per mL of solution.

Jubbonti contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per mL of solution, i.e. essentially 'sodium-free'.

3. How to use Jubbonti

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
The recommended dose is one pre-filled syringe containing 60 mg administered once every 6 months as a single subcutaneous (under the skin) injection. The most suitable injection sites are the upper thighs and the abdomen. If you have someone assisting you with the injection, the outer upper arm may also be used. Consult your doctor regarding the timing of your next possible injection. Each Jubbonti package contains a calendar card with a sticker that can be used to keep track of the date of your next injection.
During treatment with Jubbonti, you must also take calcium and vitamin D supplements. Your doctor will discuss this with you.
Your doctor will decide whether it is better for you or for the person assisting you to administer the Jubbonti injection. Your doctor or nursing staff will show you or the person assisting you how to use Jubbonti.
For instructions on how to inject Jubbonti, refer to section 7 “Instructions for use” at the end of this leaflet.
Do not shake.
If you forget to use Jubbonti
If you have missed a dose of Jubbonti, the injection should be given as soon as possible.
Afterwards, injections should be given every 6 months from the date of the last injection.
If you stop using Jubbonti
To obtain the maximum benefit from treatment in reducing fracture risk, it is important to use Jubbonti for the entire duration prescribed by your doctor. Do not stop treatment without consulting your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Patients being treated with denosumab may uncommonly develop skin infections (especially cellulitis). Contact your doctor immediately if, while taking Jubbonti, you experience any of the following symptoms: swelling, redness of the skin, most commonly in the lower leg, with a feeling of warmth and pain, and possibly fever.
Patients being treated with denosumab may rarely develop pain in the mouth and/or jaw, swelling or ulcers in the mouth or jaw that do not heal, discharge, numbness or a feeling of heaviness in the jaw, or loose teeth. These could be signs of a serious deterioration of the jawbone (osteonecrosis). Contact your doctor and dentist immediately if you experience any of these symptoms during treatment with Jubbonti or after stopping treatment.
Patients being treated with Jubbonti may rarely develop low levels of calcium in the blood (hypocalcaemia); severely low calcium levels can lead to hospitalisation and may even be life-threatening. Symptoms include muscle spasms, cramps or twitching, and/or numbness or tingling in the fingers, toes or around the mouth, and/or seizures, confusion, or loss of consciousness. Contact your doctor immediately if any of these symptoms occur. Low calcium levels in the blood may also lead to a change in heart rhythm called QT prolongation, which can be detected by an electrocardiogram (ECG).
In patients being treated with Jubbonti, atypical fractures of the femur may rarely occur. Contact your doctor if you experience new or unusual pain in the hip, groin or thigh, as this could be an early sign of a possible femur fracture.
In patients being treated with denosumab, allergic reactions may rarely occur. Symptoms include swelling of the face, lips, tongue, throat or other parts of the body; skin rash, itching, hives, wheezing or difficulty breathing. Contact your doctor if you experience any of these symptoms during treatment with Jubbonti.

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

• pain in bones, joints and/or muscles, sometimes severe,
• pain in arms or legs (limb pain).

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

• frequent and painful urination, blood in urine, urinary incontinence,
• upper respiratory tract infection,
• pain, tingling or numbness radiating to the lower limbs (sciatica),
• constipation,
• abdominal discomfort,
• skin rash,
• itching, redness and/or dryness of the skin (eczema),
• hair loss (alopecia).

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

• fever, vomiting and abdominal pain or abdominal disorders (diverticulitis),
• ear infection,
• rash which may appear on the skin or ulcers in the mouth (drug-induced lichenoid eruptions).

Very rare side effects (may affect up to 1 in 10,000 people):

• allergic reaction which may damage blood vessels, mainly at the skin level (e.g., purple or reddish-brown spots, hives or skin ulcers) (hypersensitivity vasculitis).

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

5. How to store Jubbonti

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 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 pre-filled syringe in the outer packaging to protect the medicine from light.
Before injection, the pre-filled syringe may be removed from the refrigerator and allowed to reach room temperature (up to 25 °C) to make the injection more comfortable. Once the syringe has reached room temperature (up to 25 °C), it must be used within 30 days. More detailed information is provided in section 7 “Instructions for use” at the end of this leaflet.
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 Jubbonti contains

• The active substance is denosumab. Each pre-filled syringe with safety guard contains 60 mg of denosumab (60 mg/mL).
• The other components are glacial acetic acid, sorbitol (E 420), polysorbate 20, sodium hydroxide, hydrochloric acid and water for injections.

Description of the appearance of Jubbonti and contents of the pack
Jubbonti is an injectable solution that is clear to slightly opalescent and colourless to slightly yellowish or slightly brownish. Jubbonti is supplied in a ready-to-use, transparent type I glass pre-filled syringe with a 29-gauge stainless steel needle with safety guard, needle cap made of rubber (thermoplastic elastomer), plunger stopper made of rubber (bromobutyl rubber) and plunger rod made of plastic.
Each pack contains one pre-filled syringe with safety guard.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestr. 10
6336 Langkampfen
Austria

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

België/Belgique/Belgien Lietuva
Sandoz nv/sa Sandoz Pharmaceuticals d.d filialas
Tél/Tel: +32 2 722 97 97 Tel: +370 5 2636 037

България Luxembourg/Luxemburg
Сандоз България КЧТ Sandoz nv/sa (Belgique/Belgien)
Тел.: +359 2 970 47 47 Tél/Tel: +32 2 722 97 97

Česká republika Magyarország
Sandoz s.r.o. Sandoz Hungária Kft.
Tel: +420 234 142 222 Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige Malta
Sandoz A/S Sandoz Pharmaceuticals d.d.
Tlf/Sími/Tel: +45 63 95 10 00 Tel: +35699644126

Deutschland Nederland
Hexal AG Sandoz B.V.
Tel: +49 8024 908 0 Tel: +31 36 52 41 600

Eesti Österreich
Sandoz d.d. Eesti filiaal Sandoz GmbH
Tel: +372 665 2400 Tel: +43 5338 2000

Ελλάδα Polska
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz Polska Sp. z o.o.
Τηλ: +30 216 600 5000 Tel.: +48 22 209 70 00

España Portugal
Sandoz Farmacéutica, S.A. Sandoz Farmacêutica Lda.
Tel: +34 900 456 856 Tel: +351 21 000 86 00

France România
Sandoz SAS Sandoz Pharmaceuticals SRL
Tél: +33 1 49 64 48 00 Tel: +40 21 407 51 60

Hrvatska Slovenija
Sandoz d.o.o. Sandoz farmacevtska družba d.d.
Tel: +385 1 23 53 111 Tel: +386 1 580 29 02

Ireland Slovenská republika
Rowex Ltd. Sandoz d.d. - organizačná zložka
Tel: +353 27 50077 Tel: +421 2 48 200 600

Italia Suomi/Finland
Sandoz S.p.A. Sandoz A/S
Tel: +39 02 96541 Puh/Tel: +358 10 6133 400

Κύπρος United Kingdom (Northern Ireland)
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz GmbH (Austria)
Τηλ: +30 216 600 5000 Tel: +43 5338 2000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

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

7. Instructions for Use

These “Instructions for Use” contain information on how to administer a Jubbonti injection.
If your doctor decides that you or your caregiver may administer Jubbonti injections at home,
before using it for the first time, ensure that your doctor or nurse demonstrates to you or your caregiver how to prepare and administer the injection using the Jubbonti pre-filled syringe.
Make sure you have read and understood these Instructions for Use before administering an injection with the Jubbonti pre-filled syringe. If you have any doubts, consult your doctor.

Important information you should know before administering the Jubbonti injection

• Jubbonti must be administered only via subcutaneous injection (injected directly into the fatty layer beneath the skin).
• Do not use the pre-filled syringe if either the safety seal on the outer packaging or the seal on the plastic pouch is broken.
• Never shake the pre-filled syringe.
• Do not use the pre-filled syringe if it has fallen onto a hard surface or if it has been dropped after removal of the needle cap.
• The pre-filled syringe is equipped with a safety shield that automatically covers the needle after injection. The safety shield helps prevent needlestick injuries for anyone handling the pre-filled syringe after use.
• Be careful not to touch the wings of the safety shield before use. Touching them may cause the safety shield to activate prematurely.
• Do not attempt to reuse or disassemble the pre-filled syringe.
• Do not pull back the plunger.

How to store Jubbonti

• Store in the refrigerator at a temperature between 2 °C and 8 °C.
• Do not freeze.
• If necessary, the pre-filled syringe may be stored at room temperature up to 25 °C for a maximum of 30 days.
• After 30 days, discard any pre-filled syringe stored at room temperature.
• Keep the pre-filled syringe in its original packaging until ready to use to protect the medicine from light.
• Keep out of the sight and reach of children.

Preparing for the Jubbonti injection

Step 1. Bring to room temperature
Remove the package containing the pre-filled syringe from the refrigerator without opening it, and leave it for approximately 15–30 minutes to reach room temperature.
Step 2. Prepare necessary materials

Ensure you have the following items ready
(not included in the package):

• Alcohol wipe
• Cotton ball or gauze pad
• Sharps disposal container
• Adhesive bandage

Step 3. Open the package

Open the plastic tray by tearing off the cover. Remove the pre-filled syringe by holding it in the middle, as shown.
Do not remove the needle cap until you are ready to administer the injection.
Step 4. Perform safety checks

Look through the viewing window of the pre-filled syringe. The liquid inside should be a clear to slightly opalescent solution, colorless to slightly yellowish or slightly brownish. Small air bubbles in the liquid are normal.
Do not attempt to remove the air.

• Do not use the pre-filled syringe if the liquid is cloudy or contains visible particles.
• Do not use the pre-filled syringe if it appears damaged or if liquid has leaked out.
• Do not use the pre-filled syringe after the expiry date (Exp./EXP) printed on the label of the pre-filled syringe and on the packaging.

In any of these cases, consult your doctor, nurse, or pharmacist.
Step 5. Choose the injection site

The injection should be administered in the front of the thighs or the lower part of the abdomen, except for an area within 5 cm around the navel.
Do not inject where the skin is tender, bruised, red, scaly, hardened, or in areas with scars or stretch marks.
If the injection is administered by your caregiver, doctor, or nurse, the upper arm may also be used.
Administering the Jubbonti injection

Step 6. Clean the injection site
Wash your hands with soap and water.
Clean the chosen injection site with an alcohol wipe. Allow it to dry before administering the injection.
Do not touch or blow on the cleaned area before injecting.
Step 7. Remove the needle cap

Firmly pull to remove the needle cap from the pre-filled syringe. Slight leakage of a drop of liquid from the tip of the needle is normal.
Do not replace the needle cap; discard it.
Step 8. Insert the needle

Gently pinch the skin at the injection site and keep it pinched throughout the injection. With the other hand, insert the needle into the skin at an angle of approximately 45 degrees, as shown.
Do not press the plunger while inserting the needle.
Step 9. Begin the injection

While continuing to hold the skin pinched, slowly press the plunger until it stops.
This ensures the full dose is delivered.
Step 10. Complete the injection

Check that the plunger head is positioned between the wings of the safety shield, as shown. This confirms that the safety shield has been activated and will cover the needle after injection.
Step 11. Release the plunger

While holding the pre-filled syringe in place at the injection site, slowly release the plunger until the needle is fully covered by the safety shield.
Remove the pre-filled syringe from the injection site and release the skin.
A small amount of blood at the injection site may occur. You may press a cotton ball or gauze pad on the site until bleeding stops.
Do not rub the injection site. If needed, cover the injection site with a small adhesive bandage.
After the injection

Step 12. Dispose of the pre-filled syringe
Immediately after use, place the pre-filled syringe in a sharps disposal container. Do not dispose of the pre-filled syringe in household waste.
Ask your doctor or pharmacist how to properly dispose of the sharps disposal container. Local regulations may apply.
ANNEX IV
SCIENTIFIC CONCLUSIONS AND REASONS FOR THE VARIATION OF THE TERMS OF THE MARKETING AUTHORISATION
Scientific conclusions
Taking into account the assessment by the Pharmacovigilance and Risk Assessment Committee (PRAC) of the Periodic Safety Update Reports (PSURs) for denosumab, the scientific conclusions of the PRAC are as follows:
In light of available data from clinical studies and recent published literature on the reduction of bone mineral density following discontinuation of denosumab, the PRAC concluded that the product information for medicinal products containing denosumab (indicated for osteoporosis and for bone loss associated with androgen deprivation in prostate cancer) should be updated accordingly.
Having reviewed the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the general conclusions and rationale of the recommendation.
Reasons for the variation of the terms of the marketing authorisation
Based on the scientific conclusions regarding denosumab (indicated for osteoporosis and for bone loss associated with androgen deprivation in prostate cancer), the CHMP considers that the benefit-risk balance of the medicinal product containing denosumab (indicated for osteoporosis and for bone loss associated with androgen deprivation in prostate cancer) remains unchanged, subject to the proposed amendments to the product information.
The CHMP recommends a variation to the terms of the marketing authorisation.