CONEXXENCE 60 mg SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE

Introduction

Package Leaflet: Information for the Patient

Conexxence 60 mg solution for injection in pre-filled syringe

denosumab

This medicine is subject to additional monitoring, which will allow quick identification of new safety information. You can help by reporting any side effects you may get. The last section of this leaflet includes information on how to report side effects.

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 further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.
• Your doctor will provide you with a patient reminder card, which contains important safety information that you should know before and during treatment with Conexxence.

Contents of the pack

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

1. What is Conexxence and what is it used for

What is Conexxence and how does it work

Conexxence contains denosumab, a protein (monoclonal antibody) that interferes with the action of another protein to treat bone loss and osteoporosis. Treatment with Conexxence strengthens bones and reduces the risk of fractures.

Bone is a living tissue that is constantly renewed. Estrogens contribute to the preservation of bone health. After menopause, estrogen levels decrease, which can cause bones to become thinner and more fragile. Over time, this can lead to a disease called osteoporosis. Osteoporosis can also occur in men due to various causes, including age and/or low levels of the male hormone, testosterone. It can also occur in patients undergoing treatment with glucocorticoids. Many patients with osteoporosis do not have symptoms, although they still have a risk of fracturing bones, especially in the spine, hip, and wrists.

Surgical interventions or medications that stop the production of estrogen or testosterone, used to treat patients with prostate or breast cancer, can also cause bone loss. This makes bones weaker and more prone to breaking.

What is Conexxence used for

Conexxence is used to treat:

• postmenopausal osteoporosis in women and men who have an increased risk of fracture (bone breakage), reducing the risk of fractures of the hip, spine, and non-vertebral sites.
• bone loss caused by reduced hormonal levels (testosterone) as a result of surgical intervention or treatment with medications in patients with prostate cancer.
• bone loss resulting from long-term treatment with glucocorticoids in patients who have a high risk of fracture.

2. What you need to know before you use Conexxence

Do not use Conexxence:

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

Warnings and precautions

Consult your doctor or pharmacist before starting treatment with Conexxence.

During treatment with Conexxence, you may develop a skin infection with symptoms such as an inflamed and reddened area on the skin, more frequently on the lower leg, which feels hot and sensitive to the touch (cellulitis), and may be accompanied by fever. Inform your doctor immediately if you experience any of these symptoms.

In addition, you should take calcium and vitamin D supplements during treatment with Conexxence. Your doctor will discuss this with you.

While receiving Conexxence, you may experience low levels of calcium in the blood. Inform your doctor immediately if you notice any of the following symptoms: muscle spasms, contractions, or cramps, and/or numbness or tingling in the fingers of the hands, feet, or around the mouth, and/or convulsions, confusion, or loss of consciousness.

Inform your doctor if you have or have had severe kidney problems, renal failure, if you have needed to undergo dialysis, or if you are taking medications called glucocorticoids (such as prednisolone or dexamethasone), as they may increase the risk of having low levels of calcium in the blood if you do not take calcium supplements.

Problems in the mouth, teeth, or jaw

In patients receiving Conexxence for osteoporosis, a rare side effect called osteonecrosis of the jaw (ONJ) (damage to the jawbone) has been reported (may affect up to 1 in 1,000 people). The risk of ONJ increases in patients treated for a long time (may affect up to 1 in 200 people if treated for 10 years). ONJ can also occur after stopping treatment. It is essential to try to prevent the development of ONJ, as it can be a painful condition that can be difficult to treat. To reduce the risk of developing ONJ, follow these precautions:

Before receiving treatment, inform your doctor or nurse (healthcare professional) if:

• you have any problems in your mouth or teeth, such as poor dental health, gum disease, or a planned tooth extraction.
• you do not receive regular dental check-ups or have not had a dental check-up for a long time.
• you are a smoker (as this may increase the risk of dental problems).
• you have been previously treated with a bisphosphonate (used to prevent or treat bone disorders).
• you are taking medications called corticosteroids (such as prednisolone or dexamethasone).
• you have cancer.

Your doctor may ask you to undergo a dental check-up before starting treatment with Conexxence.

During treatment, you should maintain good oral hygiene and undergo routine dental check-ups. If you use dental prosthetics, ensure they fit properly. If you are undergoing dental treatment or are about to undergo dental surgery (e.g., tooth extractions), inform your doctor about your dental treatment and inform your dentist that you are being treated with Conexxence.

Contact your doctor and dentist immediately if you experience any problems in your mouth or teeth, such as loose teeth, pain, or inflammation, or ulcers that do not heal or are suppurating, as these could be symptoms of ONJ.

Unusual fractures of the thigh

Some people have developed unusual fractures of the thigh while being treated with Conexxence. Consult your doctor if you experience new or unusual pain in the hip, groin, or thigh.

Children and adolescents

Conexxence should not be used in children and adolescents under 18 years of age.

Other medicines and Conexxence

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. It is especially important that you inform your doctor if you are being treated with another medicine that contains denosumab.

Do not use Conexxence with another medicine that contains denosumab.

Pregnancy and breastfeeding

Conexxence has not been tested in pregnant women. It is essential that you inform your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant. Conexxence is not recommended during pregnancy. Women of childbearing age should use effective contraceptive methods during treatment with Conexxence and for at least 5 months after stopping treatment with Conexxence.

If you become pregnant during treatment with Conexxence or less than 5 months after stopping treatment with Conexxence, inform your doctor.

It is not known whether Conexxence is excreted in breast milk. It is essential that you inform your doctor if you are breastfeeding or plan to breastfeed. Your doctor will help you decide whether to stop breastfeeding or stop using Conexxence, considering the benefit of breastfeeding for the child and the benefit of Conexxence for the mother.

If you are breastfeeding during treatment with Conexxence, please inform your doctor.

Consult your doctor or pharmacist before using any medicine.

Driving and using machines

The influence of Conexxence on the ability to drive and use machines is negligible.

Conexxence contains sorbitol

This medicine contains 47 mg of sorbitol per ml of solution.

Conexxence contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 60 mg dose; this is essentially "sodium-free".

Conexxence contains polisorbate 20

This medicine contains 0.1 mg of polisorbate 20 in each pre-filled syringe, equivalent to 0.1 mg/ml. Polysorbates can cause allergic reactions. Inform your doctor if you have any known allergies.

3. How to use Conexxence

The recommended dose is a single injection of 60 mg administered under the skin (subcutaneously) once every 6 months. The best places for injection are the top of the thighs and the abdomen. If the injection is given by a caregiver (the person taking care of you), it can also be administered in the outer aspect of the upper arm. Consult your doctor for the date of the next possible injection.

In addition, you should take calcium and vitamin D supplements during treatment with Conexxence. Your doctor will discuss this with you.

Your doctor may decide whether it is better for you or a caregiver to administer the Conexxence injection. Your doctor or healthcare professional will show you or your caregiver how to use Conexxence. If you want to obtain instructions on how to inject Conexxence, read the last section of this leaflet.

Do not shake.

If you miss a dose of Conexxence

If you miss a dose of Conexxence, the injection should be given as soon as possible. Subsequent injections should be scheduled every 6 months from the date of the last injection.

If you stop treatment with Conexxence

To get the most benefit from your treatment and reduce the risk of fractures, it is essential that you use Conexxence for the entire period prescribed by your doctor. Do not stop treatment without talking to your doctor first.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Patients treated with Conexxence may develop skin infections (mainly cellulitis) infrequently. Tell your doctor immediatelyif you experience any of these symptoms during treatment with Conexxence: a swollen and reddened area on the skin, usually on the lower leg, hot and sensitive to the touch, and may be accompanied by fever.

Rarely, patients receiving Conexxence may develop pain in the mouth and/or jaw, inflammation, or ulcers that do not heal in the mouth or jaw, suppurating, numbness, or a feeling of heaviness in the jaw, or tooth mobility. These could be symptoms of bone damage in the jaw (osteonecrosis). Tell your doctor and dentist immediatelyif you experience such symptoms while being treated with Conexxence or after stopping treatment.

Rarely, patients receiving Conexxence may experience low levels of calcium in the blood (hypocalcemia). Symptoms include muscle spasms, contractions, or cramps, and/or numbness or tingling in the fingers of the hands, feet, or around the mouth, and/or convulsions, confusion, or loss of consciousness. If you experience any of these, tell your doctor immediately. Low levels of calcium in the blood can also cause a change in heart rhythm called QT prolongation, which can be seen on an electrocardiogram (ECG).

Rarely, unusual fractures of the thigh can occur in patients receiving Conexxence. Consult your doctorif you experience new or unusual pain in the hip, groin, or thigh, as this may be an early indication of a possible fracture of the thigh.

Rarely, allergic reactions can occur in patients receiving Conexxence. Symptoms include swelling of the face, lips, tongue, throat, or other parts of the body; rash, itching, or hives on the skin; wheezing or difficulty breathing. Tell your doctorif you experience such symptoms while being treated with Conexxence.

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

• pain in bones, joints, and/or muscles, which can be intense,
• pain in legs or arms (pain in the limbs).

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

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

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

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

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

• allergic reaction that can damage blood vessels, mainly in the skin (e.g., purple or reddish-brown spots, hives, or skin ulcers) (hypersensitivity vasculitis).

Frequency not known(cannot be estimated from the available data):

• consult your doctor if you have ear pain, your ear is suppurating, and/or you are experiencing an ear infection. These could be symptoms of damage to the bones of the ear.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Conexxence

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 carton after "EXP". The expiry date refers to the last day of the month shown.

Store in a refrigerator (between 2°C and 8°C).

Do not freeze.

Keep the container in the outer carton to protect it from light.

Before injection, the pre-filled syringe can be left at room temperature (up to 25°C) for a maximum of 30 days. This will make the injection less painful.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Contents and Additional Information

Conexxence Composition

• The active ingredient 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 injectable preparations.

Appearance of Conexxence and Container Contents

Conexxence is a clear, colorless to slightly yellowish injectable solution, available in a pre-filled syringe ready for use.

Each container contains a pre-filled syringe with a needle protector.

Marketing Authorization Holder

Fresenius Kabi Deutschland GmbH

Else-Kroener-Strasse 1,

61352 Bad Homburg von der Hoehe,

Germany

Manufacturer

Fresenius Kabi Austria GmbH

Hafnerstrasse 36

8055 Graz

Austria

Date of Last Revision of this Leaflet

Other Sources of Information

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

1. Instructions for Use

Component Guide:

Read this important information before using the Conexxence pre-filled syringe with automatic needle protector:

• It is important that you do not attempt to administer the injection yourself unless you have been trained by your doctor or healthcare professional.

• Conexxence is administered by subcutaneous injection into the tissue just under the skin.

• Do notremove the gray needle cap from the pre-filled syringe until you are ready for injection.

• Do notuse the pre-filled syringe if the outer packaging is damaged or the seal is broken.

• Do notuse the pre-filled syringe if it has been dropped onto a hard surface. Use a new pre-filled syringe and contact your doctor or healthcare professional.

• Do notattempt to push the plunger rod of the pre-filled syringe before injection.

• Do notshake the pre-filled syringe.

• Important: Keep the pre-filled syringe out of sight and reach of children.

Storage of the Conexxence Pre-filled Syringe

• Store Conexxence in the refrigerator between 2 °C and 8 °C in the original packaging. Do notfreeze.

• Before injection, allow Conexxence to reach room temperature up to 25°C in the original packaging. This may take between 15 and 30 minutes. Do notheat Conexxence in any other way.

• Once Conexxence has been removed from the refrigerator, it must be used within 30 days. If not used within 30 days, Conexxence must be discarded.

• Do notuse Conexxence after the expiration date stated on the label.

• You must protect Conexxence from direct light and heat.

If you have any doubts, contact your doctor or healthcare professional.

Step 1: Preparation of Materials

1.1 Gather Materials

On a clean and well-lit work surface, gather the materials you need for your injection (see Figure A):

. alcohol wipes

. cotton or gauze

. an adhesive bandage

. a sharps disposal container (see Step 4: Dispose of Your Pre-filled Syringe)

1.2 Wait for 15 to 30 minutes until the pre-filled syringe reaches room temperature

Remove the container from the refrigerator (see Figure B) and place it on a flat surface.

Allow the container to reach room temperature between 15 and 30 minutes (see Figure C)

Do notattempt to heat the pre-filled syringe using a heat source such as hot water or a microwave.

Do notleave the pre-filled syringe exposed to direct sunlight.

Do notshake the pre-filled syringe.

Keep the pre-filled syringe out of sight and reach of children.

1.3 Wash Your Hands

Wash your hands with water and soap and dry them with a clean towel (see Figure D).

1.4 Remove the Pre-filled Syringe from the Tray

Place two fingers, one on each side, in the center of the transparent needle protector. Pull the pre-filled syringe upwards and out of the tray (see Figure E).

Do nothold it by the plunger.

Do nothold it by the needle cap.

1.5 Examine the Pre-filled Syringe and Medication

Examine the pre-filled syringe to ensure:

• The name on the label is Conexxance (see Figure F).
• The expiration date on the label has not passed.
• The pre-filled syringe is not cracked or broken.

Check the liquid for particles or discoloration (see Figure G).

Do not use the pre-filled syringe if:

• The name on the label is not Conexxance.
• The expiration date on the label has passed.
• Any of the components are cracked or broken.
• The needle cap is missing or loose.
• The medication is cloudy or contains particles. It should be a clear, colorless to slightly yellowish solution.

In all these cases, use a new pre-filled syringe and contact your doctor or healthcare professional.

Step 2: Prepare for Injection

2.1 Choose an Injection Site

You can inject the medication into (see Figure H):

• the top of the thighs
• the abdomen, except for an area of 5 cm around the navel
• the outer aspect of the upper arm (only if the injection is being administered by another person)

Do not inject the medication into areas where the skin is sensitive, bruised, red, or hardened.

Avoid injecting into areas with scars or stretch marks.

2.2 Clean the Injection Site

Clean the injection site with an alcohol swab (see Figure I).

Allow the skin to air dry.

Do not blow or touch the injection site after cleaning.

2.3 Remove the Needle Cap

Carefully pull the needle cap straight off and away from your body (see Figure J). You may need to use some force to remove the needle cap

Do notremove the needle cap from the pre-filled syringe until you are ready for injection.

Do nothold the pre-filled syringe by the plunger.

Do nottwist or bend the needle cap.

Discard the needle cap in your sharps disposal container (see Step 4: Dispose of Your Pre-filled Syringe).

Do notreplace the needle cap on the used pre-filled syringe.

Do nottouch the needle or allow it to touch any surface after removing the needle cap.

Step 3: Inject the Medication

3.1 Pinch the Skin

Pinch the injection site to create a firm surface (see Figure K).

Note: It is important to keep the skin pinched when injecting.

3.2 Insert the Needle

Quickly insert the needle directly into the pinched skin at an angle of 45 to 90 degrees (see Figure L).

Do not inject into the muscle or blood vessels

3.3 Inject

Push the plunger with slow and constant pressure (see Figure M) until it can no longer be pushed and all the liquid has been injected under the skin (subcutaneously) (see Figure N). You may hear or feel a “click”.

Do notlift the pre-filled syringe from the skin.

3.4 Release the Plunger

Slowly release the plunger and allow the needle to exit the skin at the same angle it entered. The transparent needle protector will safely cover the needle (see Figure O).

Do notreplace the needle cap on the used pre-filled syringe.

3.5 Treat the Injection Site

If there is blood or liquid at the injection site, gently press the injection site with a cotton ball or gauze (see Figure P).

If necessary, apply a bandage.

Do notrub the injection site.

Step 4: Dispose of Your Pre-filled Syringe

4.1 Dispose

Dispose of your used pre-filled syringe and needle cap in a sharps disposal container immediately after use (see Figure Q).

Medicines should be disposed of in accordance with local regulations. Ask your pharmacist how to dispose of medicines no longer needed. This will help protect the environment.

Do notreuse the pre-filled syringe.

Do notthrow away (dispose of) used syringes in your household trash.

Do notreuse your sharps disposal container.

Keep Conexxence pre-filled syringes, the sharps disposal container, and all medicines out of sight and reach of children.