Conexxence 60 mg Solution for injection

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, or 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 give you a patient reminder card, which contains important safety information you need to be aware of before and during your treatment with Conexxence.

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

Conexxence contains denosumab, a protein (monoclonal antibody) that interferes with the action of another protein, in order to treat bone loss and osteoporosis. Treatment with Conexxence makes bone stronger and less likely to break.

Bone is a living tissue and is renewed all the time. Oestrogen helps keep bones healthy. After the menopause, oestrogen level drops which may cause bones to become thin and fragile. This can eventually lead to a condition called osteoporosis. Osteoporosis can also occur in men due to a number of causes including ageing and/or a low level of the male hormone, testosterone. It can also occur in patients receiving glucocorticoids. Many patients with osteoporosis have no symptoms, but they are still at risk of breaking bones, especially in the spine, hips and wrists.

Surgery or medicines that stop the production of oestrogen or testosterone used to treat patients with breast or prostate cancer can also lead to bone loss. The bones become weaker and break more easily.

Conexxence is used to treat:

• osteoporosis in women after the menopause (postmenopausal) and men who have an increased risk of fracture (broken bones), reducing the risk of spinal, non-spinal and hip fractures.
• bone loss that results from a reduction in hormone (testosterone) level caused by surgery or treatment with medicines in patients with prostate cancer.
• bone loss that results from long-term treatment with glucocorticoids in patients who have an increased risk of fracture.

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

Talk to your doctor or pharmacist before using Conexxence.

Whilst being treated with Conexxence you may develop a skin infection with symptoms such as a swollen, red area of skin, most commonly in the lower leg, that feels hot and tender (cellulitis), and possibly with symptoms of fever. Please tell your doctor immediately if you develop any of these symptoms.

You should also take calcium and vitamin D supplements while being on treatment with Conexxence. Your doctor will discuss this with you.

You may have low levels of calcium in your blood while receiving Conexxence. Please tell your doctor immediately if you notice any of the following symptoms: spasms, twitches, or cramps in your muscle, and/or numbness or tingling in your fingers, toes or around your mouth, and/or seizures (fits), confusion, or loss of consciousness.

Severe low blood calcium levels leading to hospitalisation and even life-threatening reactions have been reported in rare cases. Before each dose and in patients predisposed to hypocalcaemia within two weeks after initial dose, the calcium levels in your blood will therefore be checked (via blood test).

Tell your doctor if you have or have ever had severe kidney problems, kidney failure or have needed dialysis or are taking medicines called glucocorticoids (such as prednisolone or dexamethasone), which may increase your risk of getting low blood calcium if you do not take calcium supplements.

A side effect called osteonecrosis of the jaw (ONJ) (bone damage in the jaw) has been reported rarely (may affect up to 1 in 1 000 people) in patients receiving Conexxence for osteoporosis. 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 important to try to prevent ONJ developing as it may be a painful condition that can be difficult to treat. In order to reduce the risk of developing ONJ, take the following precautions:

Before receiving treatment, tell your doctor or nurse (health care professional) if you:

• have any problems with your mouth or teeth such as poor dental health, gum disease, or a planned tooth extraction.
• don’t receive routine 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 undergo a dental examination before you start treatment with Conexxence.

While being treated, you should maintain good oral hygiene and receive routine dental check-ups. If you wear dentures you should make sure these fit properly. If you are under dental treatment or will undergo dental surgery (e.g. tooth extractions), inform your doctor about your dental treatment and tell your dentist that you are being treated with Conexxence.

Contact your doctor and dentist immediately if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling, or non-healing of sores or discharge, as these could be signs of ONJ.

Unusual thigh bone fractures

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

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

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

You should not use Conexxence together with another medicine containing denosumab.

Conexxence has not been tested in pregnant women. It is important to tell your doctor if you are pregnant, think you may be pregnant; or plan to get pregnant. Conexxence is not recommended for use if you are pregnant. Women of child-bearing potential should use effective methods of contraception while being treated 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, please inform your doctor.

It is not known whether Conexxence is excreted in breast milk. It is important to tell your doctor if you are breast-feeding or plan to do so. Your doctor will then help you decide whether to stop breast-feeding, or whether to stop using Conexxence, considering the benefit of breast-feeding to the baby and the benefit of Conexxence to the mother.

If you are breast-feeding during Conexxence treatment, please inform your doctor.

Ask your doctor or pharmacist for advice before taking any medicine.

Conexxence has no or negligible influence on the ability to drive and use machines.

This medicine contains 47 mg sorbitol in each ml of solution.

This medicine contains less than 1 mmol sodium (23 mg) per 60 mg, that is to say essentially ‘sodium-free’.

This medicine contains 0.1 mg of polysorbate 20 in each pre-filled syringe which is equivalent to 0.1 mg/mL. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.

If a dose of Conexxence is missed, the injection should be administered as soon as possible. Thereafter, injections should be scheduled every 6 months from the date of the last injection.

To get the most benefit from your treatment in reducing the risk of fractures, it is important to use Conexxence for as long as your doctor prescribes it for you. Do not stop your treatment without contacting your doctor.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

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

Conexxence is a clear, colourless to slightly yellow solution for injection provided in a ready to use pre-filled syringe.

Each pack contains one pre-filled syringe with a needle guard.

• It is important that you do not try to give yourself the injection unless you have received training from your doctor or healthcare provider.
• Conexxence is given as an injection into the tissue just under the skin (subcutaneous injection).
• Do not remove the grey needle cap from the pre-filled syringe until you are ready to inject.
• Do not use the pre-filled syringe if the carton 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 call your doctor or healthcare provider.
• Do not try to push the plunger rod of the pre-filled syringe before the injection.
• Do not shake the pre-filled syringe.
• Important: Keep the pre-filled syringe out of the sight and reach of children.

• Store Conexxence in a refrigerator between 2 °C to 8 °C in the original carton. Do not freeze.
• Before giving the injection, Conexxence may be allowed to reach room temperature up to 25 °C in the original container. This takes 15 to 30 minutes. Do not warm Conexxence in any other way.
• After Conexxence is removed from the refrigerator, it must be used within 30 days. If not used in 30 days, it should be thrown away (discarded).
• Do not use Conexxence after the expiration date printed on the label.
• Protect Conexxence from direct light and heat.

Call your doctor or healthcare provider if you have any questions.

1.1. Gather supplies

On a clean, well-lit work surface, gather the supplies needed for your injection (see Figure A):

• alcohol wipes
• cotton ball or gauze pad
• adhesive bandage
• sharps disposal container (see Step 4 Throw away your pre-filled syringe)

1.2. Wait 15 to 30 minutes for the pre-filled syringe to reach room temperature

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

Let it warm at room temperature for 15 to 30 minutes (see Figure C)

Do not try to warm the pre-filled syringe by 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 sight and reach of children.

1.3. Wash your hands

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

1.4. Remove pre-filled syringe from tray

Place two fingers on either side, in the middle of the clear needle guard. Pull the pre-filled syringe straight up and out of the tray (see Figure E).

Do not grasp the plunger.

Do not grasp the needle cap.

1.5. Inspect pre-filled syringe and medicine

Check the pre-filled syringe to make sure that:

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

Check the liquid to see if there are any particles or discoloration (see Figure G).

Do not use the pre-filled syringe if:

• The name on the label is not Conexxence.
• The expiration 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 there are particles in it. It must be a clear, colourless to slightly yellow solution.

In all cases, use a new pre-filled syringe and call your doctor or healthcare provider.

2.1. Choose an injection site

You can inject into (see Figure H):

• upper thighs
• belly, except for a 5 cm area around the belly button
• outer area of upper arm (if you are injecting into someone else)

Do not inject into areas where the skin is tender, bruised, red, or hard.

Avoid injecting into areas with scars or stretch marks

2.2. Clean the injection site

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

Let your skin air dry.

Do not blow on or touch the injection site after cleaning.

2.3. Remove needle cap

Carefully pull the needle cap straight off and away from your body (see Figure J). It may take some force 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 rod.

Do not twist or bend the needle cap.

Throw away (dispose of) the needle cap in your sharps disposal container (see Step 4 Throw away your pre-filled syringe).

Do not put the needle cap back onto the pre-filled syringe.

Do not touch the needle or let it touch any surface after removal of the needle cap.

3.1. Pinch the skin

Pinch your 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 straight into the pinched skin at a 45 to 90-degree angle (see Figure L).

Do not inject into muscle or blood vessel.

3.3. Inject

Push the plunger with slow and constant pressure (see Figure M) until you cannot press anymore and have injected all of the liquid under the skin (subcutaneously) (see Figure N). You may hear or feel a “click”.

Do not lift the pre-filled syringe off the skin.

3.4. Release plunger

Slowly release the plunger and allow the needle to come out of the skin at the same angle it was inserted. The clear needle guard will safely cover the needle (see Figure O).

Do not put the needle cap back on the needle.

3.5. Treat injection site

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

You may use an adhesive bandage if needed.

Do not rub the injection site.

4.1. Dispose

Put your used pre-filled syringe and needle cap in a sharps disposal container right away after use (see Figure Q).

Medicines should be disposed of in accordance with local requirements. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Do not reuse the pre-filled syringe.

Do not throw away (dispose of) used syringes in your household trash.

Do not recycle your used sharps disposal container.

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