Stoboclo

Package leaflet: Information for the patient

Stoboclo 60 mg injectable solution 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 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 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 Stoboclo.

Contents of this leaflet

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

1. What Stoboclo is and what it is used for

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

For what type of treatment is Stoboclo used
Stoboclo is used for the treatment of:

• osteoporosis in postmenopausal women (postmenopausal osteoporosis) 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 resulting from reduced hormone levels (testosterone) due to surgery or medical therapy in patients with prostate cancer.
• bone loss due to long-term treatment with glucocorticoids in patients at increased risk of fracture.

2. What you need to know before using Stoboclo

Do not use Stoboclo

• 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 Stoboclo.
While being treated with Stoboclo, you may develop a skin infection with symptoms such as swelling, redness, most commonly in the lower leg, with a feeling of warmth and pain (cellulitis), possibly accompanied by fever. Inform your doctor immediately if you experience any of these symptoms.
While being treated with Stoboclo, you must also take calcium and vitamin D supplements. Your doctor will discuss this with you.
While being treated with Stoboclo, you may have low levels of calcium in your blood. Inform your doctor immediately if you notice any of the following symptoms: muscle spasms, twitching or cramps, and/or numbness or tingling in the fingers, toes or around the mouth, and/or seizures, confusion or loss of consciousness.
In rare cases, severely low levels of calcium in the blood have 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 in patients at risk of developing hypocalcemia, within two weeks after the initial dose.
Inform your doctor if you currently have or have ever had severe kidney problems, impaired kidney function, if you are on dialysis, or if you are taking medicines called glucocorticoids (such as prednisolone or dexamethasone), as these may increase your risk of low blood calcium levels if you do not take calcium supplements.

Problems with mouth, teeth or jaw
A rare side effect (may occur in up to 1 in 1,000 patients) called osteonecrosis of the jaw/mandible (severe deterioration of the jaw/mandible bone tissue) has been reported in patients receiving denosumab for osteoporosis. 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 starting treatment, inform your doctor or nurse (healthcare professional) if you:

• have any mouth or dental problems, such as poor dental hygiene, gum disorders, 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 disorders);
• 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 Stoboclo.
During treatment, it is necessary to maintain good oral hygiene and to have regular dental check-ups. If you wear dentures, make sure they fit properly. If you are currently undergoing dental treatment or are scheduled for dental surgery (e.g. tooth extractions), inform your doctor about the dental treatment and inform your dentist that you are being treated with Stoboclo.
Contact your doctor and dentist immediately if you notice any new problems with your mouth or teeth, such as tooth loss, pain or swelling, or failure of mouth sores to heal, or presence of discharge, as these could be signs of a side effect called osteonecrosis of the jaw/mandible.

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

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

Other medicines and Stoboclo
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 Stoboclo together with other medicines containing denosumab.

Pregnancy and breastfeeding
Stoboclo has not been studied in pregnant women. It is important that you inform your doctor if you are pregnant, think you may be pregnant, or are planning a pregnancy. The use of Stoboclo is not recommended during pregnancy. Women of childbearing potential must use effective contraception while taking Stoboclo and for at least 5 months after stopping treatment with Stoboclo.
If you become pregnant during treatment with Stoboclo or within 5 months after stopping treatment with Stoboclo, please inform your doctor.
It is not known whether denosumab passes into 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 stop breastfeeding or stop taking Stoboclo, taking into account the benefit of breastfeeding for the child and the benefit of taking Stoboclo for the mother.
If you are breastfeeding during treatment with Stoboclo, inform your doctor.
Ask your doctor or pharmacist for advice before using this medicine.

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

Stoboclo contains sorbitol (E420)
This medicine contains 47 mg of sorbitol per mL of solution.

Stoboclo contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per 60 mg, i.e. essentially ‘sodium-free’.

Stoboclo contains polysorbate 20 (E432)
This medicine contains 0.1 mg of polysorbate 20 per syringe, equivalent to 0.1 mg/L. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Stoboclo

The recommended dose is one 60 mg pre-filled syringe administered once every 6 months, as a single injection under the skin (subcutaneous). The most suitable injection sites are the upper thighs and the abdomen. If an assistant is administering the injection, the upper outer area of the arm may also be used. Consult your doctor regarding the date of your next possible injection.
Each Stoboclo package contains a reminder card included in the box, to help you keep track of the date of your next injection.
During treatment with Stoboclo, 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 your assistant to administer the Stoboclo injection. Your doctor or nursing staff will show you or your assistant how to use Stoboclo. For instructions on how to inject Stoboclo, please refer to the section at the end of this leaflet.
Do not shake.
If you forget to use Stoboclo
If you have missed a dose of Stoboclo, the injection should be given as soon as possible.
Afterwards, injections should be given every 6 months starting from the date of the last injection.
If you stop treatment with Stoboclo
To obtain the maximum benefit from treatment in reducing the risk of fractures, it is important to use Stoboclo 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 everyone experiences them.
Uncommonly, patients treated with Stoboclo may develop skin infections (especially cellulitis). Contact your doctor immediately if any of the following symptoms occur while you are taking Stoboclo: appearance of redness and swelling of the skin, most commonly in the lower leg, with a sensation of warmth and pain, possibly accompanied by fever.
Rarely, patients treated with Stoboclo may develop pain in the mouth and/or jaw/mandible, swelling or non-healing lesions in the mouth or jaw/mandible, discharge, numbness or a feeling of heaviness in the jaw/mandible, or loose teeth. These could be signs of a serious deterioration of the jaw/mandible bone tissue (osteonecrosis). Contact your doctor and dentist immediately if you experience such symptoms during or after treatment with Stoboclo.
Rarely, patients treated with Stoboclo may have low levels of calcium in the blood (hypocalcemia); severe hypocalcemia may require hospitalization and can even be life-threatening. Symptoms include muscle spasms, contractions or cramps, 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 known as QT interval prolongation, which can be detected by electrocardiogram (ECG).
Rarely, atypical femoral fractures may occur in patients treated with Stoboclo. Contact your doctor if you develop new or unusual pain in the hip, groin, or thigh, as this could be an early sign of a possible femoral fracture.
Rarely, allergic reactions may occur in patients treated with Stoboclo. Symptoms include swelling of the face, lips, tongue, throat or other body parts; skin rash, itching, hives, wheezing or difficulty breathing. Contact your doctor if you experience any of these symptoms during treatment with Stoboclo.

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

• bone, joint and/or muscle pain, sometimes severe,
• pain in the arms or legs (extremity pain).

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

• frequent and painful urination, blood in urine, urinary incontinence,
• upper respiratory tract infections,
• 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 occur in up to 1 in 100 people):

• fever, vomiting, abdominal pain or abdominal disorders (diverticulitis),
• ear infections,
• skin rash or mouth ulcers (drug-induced lichenoid eruptions).

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

• allergic reaction that may damage blood vessels, mainly affecting the skin (e.g. purple or red-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 an ear infection. These could be signs of damage to the ear bone.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. You may also report side effects directly through 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 Stoboclo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and 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.
The pre-filled syringe 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 syringe has reached room temperature (up to 25 °C), it must be used within 1 month.
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 Stoboclo contains

• The active substance is denosumab. Each 1 mL pre-filled syringe contains 60 mg of denosumab (60 mg/mL).
• The other components are acetic acid, sodium acetate trihydrate, sorbitol (E420), polysorbate 20 (E432), and water for injections.

Description of the appearance of Stoboclo and contents of the pack
Stoboclo is a clear, colourless to pale yellow injectable solution in a ready-to-use pre-filled syringe.
Each pack contains one pre-filled syringe with safety guard.

Marketing Authorisation Holder
Celltrion Healthcare Hungary Kft.
1062 Budapest
Váci út 1-3. WestEnd Office Building B tower
Hungary

Manufacturer
Nuvisan France S.A.R.L
2400 Route des Colles,
Biot, 06410
France

Manufacturer
Midas Pharma GmbH
Rheinstrasse 49, West,
Ingelheim Am Rhein,
Rhineland-Palatinate, 55218
Germany

Manufacturer
Kymos S.L.
Ronda de Can Fatjó, 7B
Parc Tecnològic del Vallès,
Cerdanyola del Vallès,
Barcelona, 08290
Spain

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

België/Belgique/Belgien Lietuva
Celltrion Healthcare Belgium BVBA EGIS PHARMACEUTICALS PLC atstovybė
Tél/Tel: + 32 1528 7418 Tel: +370 5 231 4658
[email protected]

България Luxembourg/Luxemburg
EGIS Bulgaria EOOD Celltrion Healthcare Belgium BVBA
Tel.: + 359 2 987 6040 Tél/Tel: + 32 1528 7418
[email protected]

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

Danmark Malta
Celltrion Healthcare Denmark ApS Mint Health Ltd
Tlf.: +45 3535 2989 Tel: +356 2093 9800
[email protected]

Deutschland Nederland
Celltrion Healthcare Deutschland GmbH Celltrion Healthcare Netherlands B.V.
Tel: +49 (0)30 346494150 Tel: + 31 20 888 7300
[email protected] [email protected]

Eesti Norge
Celltrion Healthcare Hungary Kft. Celltrion Healthcare Norway AS
[email protected] [email protected]

Ελλάδα Österreich
ΒΙΑΝΕΞ Α.Ε. Astro-Pharma GmbH
Τηλ: +30 210 8009111 - 120 Tel: +43 1 97 99 860

España Polska
CELLTRION FARMACEUTICA (ESPAÑA) EGIS Polska Sp. z o.o.
S.L. Tel.: + 48 22 417 9200
Tel: +34 919 94 23 90

France Portugal
Celltrion Healthcare France SAS CELLTRION PORTUGAL, UNIPESSOAL LDA
Tél.: +33 (0)1 71 25 27 00 Tel: +351 21 936 8542

Hrvatska România
Oktal Pharma d.o.o. Egis Pharmaceuticals PLC Romania
Tel: +385 1 6595 777 Tel: + 40 21 412 0017

Ireland Slovenija
Celltrion Healthcare Ireland Limited OPH Oktal Pharma d.o.o.
Tel: +353 1 223 4026 Tel.: +386 1 519 29 22
[email protected]

Ísland Slovenská republika
Celltrion Healthcare Hungary Kft. EGIS SLOVAKIA spol. s r.o
[email protected] Tel: +421 2 3240 9422

Italia Suomi/Finland
Celltrion Healthcare Italy S.R.L. Celltrion Healthcare Finland Oy.
Tel: +39 0247927040 Puh/Tel: +358 29 170 7755
[email protected] [email protected]

Κύπρος Sverige
C.A. Papaellinas Ltd Celltrion Healthcare Hungary Kft.
Tel: +357 22741741 [email protected]

Latvija
EGIS Pharmaceuticals PLC pārstāvniecība Latvijā
Tel: +371 67613859

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

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Instructions for use:

Read and follow the instructions for use provided with the Stoboclo pre-filled syringe before
starting to use it and each time you receive a new supply. There may be new information.
Stoboclo may be administered by healthcare professionals, caregivers, or may be self-administered by
patients who have received appropriate training. Please consult your doctor if you have any questions
about self-administering an injection.

Important information

• Stoboclo is administered as an injection into the tissue just beneath the skin (subcutaneous injection).
• Do not open the sealed carton until you are ready to use the pre-filled syringe.
• Do not remove the needle cap from the pre-filled syringe until the time of injection.
• Do not attempt to activate the pre-filled syringe before injection.
• Do not attempt to remove the transparent safety shield from the pre-filled syringe.
• Do not use the pre-filled syringe if it has been dropped on a hard surface. Use a new pre-filled syringe.
• Do not shake the pre-filled syringe. Vigorous shaking may damage the medicine.
• The pre-filled syringe cannot be reused. Immediately dispose of the used pre-filled syringe in a sharps disposal container (see Step 15. Disposal of Stoboclo).

Storage of Stoboclo

• Keep the pre-filled syringe out of sight and reach of children; it contains small parts.
• Store the pre-filled syringe in a refrigerator at a temperature between 2 °C and 8 °C. Do not freeze.
• Once removed from the refrigerator, Stoboclo must not be exposed to temperatures above 25 °C. Stoboclo must be stored in its original packaging and used within 30 days. If not used within 1 month, Stoboclo must be discarded.
• Keep the pre-filled syringe sealed in its packaging to protect it from light.

Parts of the pre-filled syringe (see Figure A)

Before use After use
Figure A
Preparing the injection

1. Gather the injection materials.

1a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area.
1b. Remove the box containing the pre-filled syringe from the refrigerator.
1c. Make sure you have the following materials (see Figure B):

• Box containing the pre-filled syringe Not included in the box:
• Alcohol swab
• Cotton ball or gauze pad
• Adhesive bandage
• Sharps disposal container

Figure B

2. Check the expiry date on the carton (see Figure C).

• Do not use after the expiry date has passed. If the expiry date has been exceeded, return the entire carton to the pharmacy.
• The printed expiry date refers to the last day of the month.

Figure C

3. Remove the pre-filled syringe from the carton.

3a. Open the carton. Holding the body of the pre-filled syringe, lift it out of the carton (see Figure D).

• Do not grasp the thumb pad, plunger, safety shield, wings, or needle cap.
• Do not pull back the plunger at any time.

Figure D
Injection preparation

4. Inspect the prefilled syringe.

4a. Look at the prefilled syringe and make sure it contains the

correct medicine (Stoboclo).
4b. Look at the prefilled syringe and make sure it is not cracked or damaged.
4c. Check the expiry date on the label of the prefilled syringe (see Figure E).

• Do not use if the needle cap is missing or not securely attached.
• Do not use if the expiry date has been exceeded.
• Do not shake the prefilled syringe.

Figure E

5. Inspect the medicine.

5a. Observe the medicine and confirm that the liquid is

clear, from colorless to pale yellow, and contains no visible particles or floccules (see Figure F).

• Do not use the pre-filled syringe if the liquid has changed color, is cloudy, or contains visible particles or floccules.
• The presence of air bubbles in the liquid is normal.

Figure F

6. Wait 30 minutes.

6a. Leave the prefilled syringe outside the box for

30 minutes at room temperature (between 20 °C and 25 °C) to allow it to
30
warm up (see Figure G).
minutes

• Do not warm the prefilled syringe using heat sources such as hot water or microwave oven.
• If the syringe does not reach room temperature, the injection may be uncomfortable.

Figure G
Preparing the injection

7. Choose an appropriate injection site (see Figure H).

7a. The injection can be administered:

FOR CAREGIVERS AND
HEALTHCARE PROFESSIONALS ONLY – in the upper thighs

• in the abdomen, except within 5 cm around the navel AUTO-INJECTION
• in the outer area of the upper arms (only if and caregivers administered by a caregiver or healthcare professional).
  • Do not inject into moles, scars, bruises, or areas where the skin is tender, red, hard, or has cracks or breaks.
  • Do not inject through clothing.

7b. Select a different injection site for each new injection, at least 2.5 cm away from the area used for the previous injection.

Figure H

8. Wash your hands.

8a. Wash your hands with water and soap and dry them thoroughly

(see Figure I ).
Figure I

9. Clean the injection site.

9a. Clean the injection site using an alcohol swab,

using a circular motion (see Figure J).
9b. Allow the skin to dry before administering the injection.

• Do not blow on or touch the injection site again before administering the injection.

Figure J
Administering the injection

10. Remove the cap.

10a. Hold the pre-filled syringe body in one hand, between

thumb and index finger. With the other hand, carefully pull off the needle cap immediately (see Figure K).

• Do not grasp the plunger rod while removing the cap.
• You may notice a drop of liquid at the tip of the needle. This is normal.
  10b. Immediately dispose of the cap in a sharps disposal container (see Step 15 and Figure K).
• Do not use the pre-filled syringe if it has been dropped without the needle cap. In this case, use a new pre-filled syringe.
• Remove the needle cap only when ready for injection.
• Do not recap the pre-filled syringe.
• Do not touch the needle. This could cause a needle-stick injury.

11. Insert the pre-filled syringe at the injection site.

11a. Hold the body of the pre-filled syringe in one hand

between thumb and index finger.
11b. Use the other hand to gently pinch the clean skin
45°
between thumb and index finger. Do not squeeze tightly.
Note: It is important to keep the skin pinched when
inserting the needle to ensure injecting under the skin (into
the fatty tissue) but not deeper (into the muscle).
11c. With a quick and firm motion, insert the needle fully into the skin fold at a 45-degree angle (see Figure L).
OR

• Never pull back the plunger. 45°

Figure L
Administration of the injection

12. Administer the injection.

12a. After inserting the needle, release the skin fold.

12b. Slowly push the plunger rod all the way down
to inject the full dose of medicine and completely
empty the syringe (see Figure M).

• Do not change the position of the pre-filled syringe after starting the injection.
• If the plunger rod is not pushed all the way down, the safety shield will not extend to cover the needle upon removal.

Figure M

13. Remove the prefilled syringe from the injection site

13a. After emptying the prefilled syringe, slowly remove
the needle by lifting your thumb from the plunger until
the needle is completely covered by the safety shield
(see Figure N).

• If the needle is not covered, dispose of the syringe carefully (see Step 15, Disposal of Stoboclo).
• Do not recap the needle on the used prefilled syringe.
• Do not reuse the prefilled syringe.
• Do not rub the injection site.

Figure N
After injection

14. Care of the injection site.

14a. If bleeding occurs, treat the injection site by gently pressing a cotton ball or gauze pad over the site without rubbing, and apply an adhesive bandage if necessary.
After the injection

15. Disposal of the pre-filled syringe.

15a. Immediately after use, place the used pre-filled syringe into

a sharps disposal container (see Figure O).
15b. Do not dispose of the pre-filled syringe in household waste.

• Keep the syringe and the sharps disposal container out of sight and reach of children.
• If you do not have a sharps disposal container, you may use a puncture-resistant, sealable household container.
• For your safety and the safety of others, needles and syringes must never be reused. Unused medicine and waste material from such medicine must be disposed of in accordance with local regulations shown in Figure O.
• Do not throw any medicine into drains or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.