Conexxence

Package leaflet: Information for the patient

Conexxence 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. Healthcare professionals are required to report any suspected adverse reactions.
See section 4.8 for how to report adverse reactions.
Please read all of this leaflet carefully before you start taking 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, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.
• Your doctor will provide you with a patient reminder card containing important safety information that you need to know before and during treatment with Conexxence.

Contents of this leaflet

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

1. What Conexxence is and what it is used for

What Conexxence is and how it works
Conexxence contains denosumab, a protein (monoclonal antibody) that interferes with the action of another protein, for the treatment of bone loss and osteoporosis. Treatment with Conexxence 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, the reduction in 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 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 likely to fracture.

For what type of treatment is Conexxence used?
Conexxence is used for the treatment of:

• osteoporosis in postmenopausal women (postmenopausal osteoporosis) and in men who are at increased risk of fractures (broken bones), to reduce the risk of vertebral, non-vertebral, and hip fractures.
• bone loss in men due to reduced hormone levels (testosterone) caused by surgery or drug 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 should know before using Conexxence

Do not use Conexxence

• 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 Conexxence.
During treatment with Conexxence, 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.
During treatment with Conexxence, you must also take calcium and vitamin D supplements. Your doctor will discuss this with you.
During treatment with Conexxence, 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 your fingers, toes or around your mouth, and/or seizures, confusion or loss of consciousness.
Inform your doctor if you have or have ever had severe kidney problems, impaired kidney function, or if you are undergoing dialysis or taking medicines called glucocorticoids (such as prednisolone or dexamethasone), which could increase your risk of low blood calcium levels if you do not take calcium supplements.

Problems with mouth, teeth or jaw
A rare adverse effect called osteonecrosis of the jaw (severe deterioration of the jawbone tissue) has been reported (may occur in up to 1 in 1,000 patients) in patients receiving Conexxence for osteoporosis. The risk of jaw osteonecrosis increases in patients treated for a long period (may occur in up to 1 in 200 patients if treated for 10 years). Osteonecrosis of the jaw may also occur after stopping treatment. It is important to try to prevent the development of jaw osteonecrosis, as it is a painful condition that may be difficult to treat. To reduce the risk of developing jaw osteonecrosis, take the following precautions:
Before receiving 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 Conexxence.
During treatment, it is necessary to maintain good oral hygiene and undergo regular dental check-ups. If you wear dentures, ensure they fit properly. If you are 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 Conexxence.
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 if you have discharge, as these could be signs of an adverse effect called osteonecrosis of the jaw (ONJ).

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

Children and adolescents
Conexxence must 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 particularly important that you inform your doctor if you are taking other medicines containing denosumab.
You must not take Conexxence together with other medicines containing denosumab.

Pregnancy and breastfeeding
Conexxence 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 Conexxence is not recommended during pregnancy. Women of childbearing potential must use effective contraception while taking Conexxence and for at least 5 months after stopping treatment with Conexxence.
If you become pregnant during treatment with Conexxence or within 5 months after stopping treatment with Conexxence, please inform your doctor.
It is not known whether Conexxence 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 discontinue breastfeeding or Conexxence treatment, considering the benefit of breastfeeding for the child and the benefit of Conexxence for the mother.
If you are breastfeeding during treatment with Conexxence, inform your doctor.
Ask your doctor or pharmacist for advice before using this medicine.

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

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, i.e., essentially ‘sodium-free’.

Conexxence contains polysorbate 20
This medicine contains 0.1 mg of polysorbate 20 per pre-filled syringe, equivalent to 0.10 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Conexxence

The recommended dose is one 60 mg pre-filled syringe 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 an assistant administers the injection, the outer upper arm may also be used. Please consult your doctor regarding the timing of your next possible injection.
During treatment with Conexxence, you must also take calcium and vitamin D supplements. Your doctor will discuss this with you.
Your doctor will decide whether you or your assistant should administer the Conexxence injection. Your doctor or nursing staff will show you or your assistant how to administer Conexxence. For instructions on how to inject Conexxence, refer to the section at the end of this leaflet.
Do not shake.

If you forget to use Conexxence
If you have missed a dose of Conexxence, the injection should be given as soon as possible.
Afterwards, injections should continue every 6 months from the date of the last injection.

If you stop treatment with Conexxence
To achieve the maximum benefit from treatment in reducing fracture risk, it is important to use Conexxence 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.
Uncommonly, patients treated with Conexxence may develop skin infections (especially cellulitis). Contact your doctor immediately if any of the following symptoms occur while you are taking Conexxence: appearance of redness and swelling of the skin, most commonly in the lower leg, with a sensation of warmth and pain, and possibly accompanied by fever.
Rarely, patients treated with Conexxence may develop pain in the mouth and/or jaw, swelling or non-healing lesions in the mouth or jaw, discharge, numbness or 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 or after treatment with Conexxence.
Rarely, patients treated with Conexxence may have low levels of calcium in the blood (hypocalcaemia). Symptoms include 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. 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 interval prolongation, which can be detected by an electrocardiogram (ECG).
Rarely, atypical femoral fractures may occur in patients treated with Conexxence. Contact your doctor if you experience new or unusual pain in the hip, groin or thigh, as this may be an early sign of a possible femoral fracture.
Rarely, allergic reactions may occur in patients treated with Conexxence. Symptoms include swelling of the face, lips, tongue, throat or other body parts; rash, itching, hives, wheezing or difficulty breathing. Contact your doctor if you experience any of these symptoms during treatment with Conexxence.

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 the 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 discomfort (diverticulitis),
• ear infections,
• rash which may appear on the skin or ulcers in the mouth (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 in 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):

• contact 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 experience any side effect, 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 listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 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 container 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 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 Conexxence 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 Conexxence and contents of the pack
Conexxence is a clear, colourless to slightly yellow, injectable solution in a ready-to-use pre-filled syringe.
Each pack contains one pre-filled syringe with needle guard.
Marketing Authorisation 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
Further information
More detailed information on this medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu/

7 Instructions for use
Guide to components:
Needle guard

transparent plunger
Before use
Front view
Needle cap Pre-filled syringe filled with liquid
Chamber (internal)
Back view
Expiry date

transparent plunger
After use
Before using a pre-filled syringe of Conexxence with automatic needle guard,
read these important instructions:

Covered needle Spring of needle guard extended

• It is important that you do not attempt to self-administer the injection unless you have received adequate training from your doctor or healthcare professional.
• Conexxence is administered by injection into the tissue just beneath the skin (subcutaneous injection).
• Do not remove the grey needle cap from the pre-filled syringe until you are ready to administer the injection.
• Do not use the pre-filled syringe if the packaging is damaged or the seal is broken.
• Do not use the pre-filled syringe if it has been dropped on a hard surface. Use a new pre-filled syringe and contact your doctor or healthcare professional.
• Do not attempt to press the plunger of the pre-filled syringe before injection.
• Do not shake the pre-filled syringe.
• Important: Keep the pre-filled syringe out of the sight and reach of children.

Storage of the pre-filled syringe of Conexxence

• Store Conexxence in a refrigerator at 2 °C - 8 °C in the original packaging. Do not freeze.
• Before administering the injection, allow Conexxence to reach room temperature up to 25 °C while still in the original packaging. This takes 15 to 30 minutes. Do not heat Conexxence in any other way.
• Once removed from the refrigerator, Conexxence must be used within 30 days. If not used within 30 days, Conexxence must be discarded.
• Do not use Conexxence after the expiry date printed on the label.
• Protect Conexxence from direct light and heat.

For any questions, contact your doctor or healthcare professional.
Step 1: Prepare materials
1.1 Gather materials
On a clean, well-lit surface, gather the materials needed for the injection (see Figure A):

• alcohol wipes
• cotton ball or gauze
• adhesive bandage
• sharps disposal container (see Step 4: Dispose of the pre-filled syringe)

Figure A
1.2 Wait 15 to 30 minutes for the pre-filled syringe to reach room temperature
Remove the box from the refrigerator (see Figure B) and place it on a flat surface.

Figure B
Allow it to reach room temperature for 15 – 30 minutes (see Figure C)

15 - 30
minutes
Figure C
Do not try to warm the pre-filled syringe using a heat source such as hot water or
microwave.
Do not leave the pre-filled syringe in direct sunlight.
Do not shake the pre-filled syringe.
Keep the pre-filled syringe out of the sight and reach of children.
1.3 Wash your hands
Wash your hands thoroughly with soap and water and dry them with a clean towel ( Figure D ).

Figure D
1.4 Remove the pre-filled syringe from the tray
Place two fingers on both sides of the centre of the transparent needle guard. Pull the pre-filled syringe upward and out of the tray ( Figure E ).
Do not touch the plunger.
Do not touch the needle cap.

Figure E
1.5 Inspect the pre-filled syringe and medicine
Check the pre-filled syringe to ensure:

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

Conexxence
Check the liquid for particles or changes in colour (see Figure G).
Figure F

Figure G
Do not use the pre-filled syringe if:

• The name on the label is not Conexxence.
• The expiry date on the label has passed.
• Any part appears cracked or broken.
• The needle cap is missing or not firmly attached.
• The medicine is cloudy or contains particles. It must be a clear, colourless to slightly yellow solution. In any case, use a new pre-filled syringe and contact your doctor or healthcare professional.

Step 2: Prepare for injection
2.1 Choose the injection site
You may inject (see Figure H):

• in the upper thighs
• in the abdomen, except for an area within 5 cm around the navel
• in the outer area of the upper arm (if injecting another person)
  Do not inject into areas where the skin is tender, bruised, red, or thick. Try to avoid injecting into areas with scars or stretch marks.

Self-injection or assistant
Assistant only
Figure H
2.2 Clean the injection site
Clean the injection site with an alcohol wipe (see Figure I).
Allow the skin to dry in the air.
Do not blow on or touch the injection site after cleaning.

Figure I
2.3 Remove the needle cap
Carefully pull the needle cap straight off, away from the body (see Figure J). Some force may be required to remove the needle cap.
Do not remove the needle cap from the pre-filled syringe until you are ready to inject.
Do not hold the pre-filled syringe by the plunger.
Do not twist or bend the needle cap.
Dispose of the needle cap in the sharps disposal container (see Step 4: Dispose of the pre-filled syringe).
Do not replace the needle cap on the pre-filled syringe.
Do not touch or allow the needle to touch any surface after removing the needle cap.

Figure J
Step 3: Inject the medicine
3.1 Pinch the skin
Pinch the skin at the injection site to create a firm surface (see Figure K).
Note: it is important to keep the skin pinched during the injection.

Figure K
3.2 Insert the needle
Quickly insert the needle directly into the pinched skin at an angle between 45 and 90 degrees (see Figure L).
Do not inject into muscle or blood vessels.

90°
45°
Figure L
3.3 Inject
Push the plunger with slow, steady pressure (see Figure M) until no further pressure can be applied and all the liquid has been injected under the skin (subcutaneously) (see Figure N). You may hear or feel a "click".

Figure M

Figure N
Do not lift the pre-filled syringe from the skin.
3.4 Release the plunger
Slowly release the plunger and allow the needle to withdraw from the skin at the same angle as insertion. The transparent needle guard will safely cover the needle (see Figure O).

Figure O
Do not replace the cap on the needle.
3.5 Treat the injection site
If there is blood or liquid at the injection site, gently press a cotton ball or gauze pad against the skin (see Figure P).
If needed, an adhesive bandage may be used.

Figure P
Do not rub the injection site.
Step 4: Dispose of the pre-filled syringe
4.1 Dispose
Immediately after use, place the used pre-filled syringe and needle cap into a dedicated sharps disposal container (see Figure Q).
Medicines must be disposed of in accordance with local regulations. Ask your pharmacist how to dispose of unused medicines. These measures will help protect the environment.
Do not reuse the pre-filled syringe.
Do not throw (dispose of) used syringes into household waste.
Do not recycle used sharps disposal containers.

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