Conexxence: Uses, Side Effects and Dosage

What CONEXXENCE is used for:

CONEXXENCE is used for the treatment:

• of osteoporosis (thinning and weakening of the bone) in women after menopause who

  • have an increased risk for fractures or;
  • cannot use other osteoporosis medicines, or other osteoporosis medicines did not work well.
• to increase bone mass in men with osteoporosis at high risk for fracture.
• to increase bone mass and may reduce fractures that occur when medication to reduce testosterone levels are taken for the treatment of prostate cancer that has not spread to other parts of the body (nonmetastatic).
• to increase bone mass in women who are receiving certain treatments for breast cancer, which has not spread to other parts of the body (nonmetastatic) and at high risk of fracture.
• to increase bone mass to treat osteoporosis in both women and men at high risk for fracture related to the use of corticosteroid medicines, such as prednisone.
• to increase bone mass to prevent osteoporosis in both women and men at high risk for fracture related to starting corticosteroid medicines, such as prednisone.

What is osteoporosis?

Bone is constantly changing. There are special cells in the body called osteoclasts whose primary function is to remove bone. There is another type of cell called osteoblasts, which are bone-forming cells. In normal bone, there is a balance between the actions of these two cells. In people with osteoporosis, this balance no longer exists. Instead, the cells that remove bone work overtime, removing bone faster than new bone can be created. The result is bone that is thinner, weaker and more likely to break. Osteoporosis may occur without any pain or other symptoms. Sometimes the first symptom of osteoporosis is a fragility fracture, a broken bone that may be caused by a minor fall, or simple activities such as lifting groceries or getting out of bed. A fragility fracture can significantly increase the risk of future fractures. Aside from prescribing CONEXXENCE, your doctor can guide you in other ways to manage your bone health.

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

Corticosteroids, like prednisone, can also cause thinning and weakening of the bone increasing your chance of broken bones.

How CONEXXENCE works:

CONEXXENCE works differently than other osteoporosis medications. It is a RANK ligand inhibitor. RANK ligand is a protein which activates the cells that break down bone (osteoclasts). CONEXXENCE blocks RANK ligand to stop the cells that break down bone. This action strengthens your bones by increasing bone mass and lowers the chance of breaking bones of the hip, spine, and nonspinal sites.

The ingredients in CONEXXENCE are:

Medicinal ingredients: denosumab.

Non-medicinal ingredients: acetic acid, glacial, polysorbate 20, sodium acetate trihydrate, sorbitol, and water for injection.

The components of the prefilled syringe are not made with natural rubber latex.

CONEXXENCE comes in the following dosage forms:

CONEXXENCE is a liquid for injection, available in a pre-filled syringe.

CONEXXENCE is a clear, colourless to slightly yellow solution. Do not use if the solution is cloudy.

Do not use CONEXXENCE if you:

• are allergic to denosumab or any other ingredient of CONEXXENCE. Allergic reactions (e.g., rash, hives, or in rare cases, swelling of the face, lips, tongue, throat, or trouble breathing) have been reported.
• have low calcium levels in your blood (hypocalcemia).
• are less than 18 years of age (see also What CONEXXENCE is used for above and Other warnings you should know about below).

• are pregnant or breastfeeding.

• are a woman before menopause [unless you have been diagnosed with breast cancer or are taking CONEXXENCE for the treatment or prevention of osteoporosis related to the use of corticosteroid medicines (see also What is CONEXXENCE used for above and Other warnings you should know about below)].
• are currently taking denosumab.
• do not have access to a health professional or trained injector.

Other warnings you should know about:

CONEXXENCE contains the same medicine as found in other denosumab products. If you are being treated with CONEXXENCE, you should not be taking any other denosumab product or vice versa.

There is an increased risk of skin infection (cellulitis) with CONEXXENCE therapy, most commonly on the leg. See a doctor urgently if you develop swollen, red, hot or painful skin, with or without fever.

You should take calcium and vitamin D supplements as recommended by your healthcare professional.

To help avoid side effects and ensure proper use, talk to your healthcare professional before you take CONEXXENCE. Talk about any health conditions or problems you may have, including if you:

• Have low blood calcium.
• Cannot take daily calcium and vitamin D.
• Had parathyroid or thyroid surgery (glands located in your neck).
• Have been told you have trouble absorbing minerals in your stomach or intestines (malabsorption syndrome).
• Have kidney problems or are on kidney dialysis.
• Have ever had an allergic reaction to CONEXXENCE.
• Plan to have dental surgery or teeth removed.
• Have a history of cancer.
• Are pregnant or could become pregnant.

CONEXXENCE may interfere with normal bone and tooth development in fetuses, nursing babies, and children under 18 years of age. CONEXXENCE is not indicated for use in patients under 18 years of age.

Do not take CONEXXENCE if you are pregnant or could become pregnant as CONEXXENCE may harm your unborn baby. Your healthcare provider should do a pregnancy test before you start treatment with CONEXXENCE. You should use an effective method of birth control (contraception) during treatment with CONEXXENCE and for at least 5 months after your last dose of CONEXXENCE. If you become pregnant while taking CONEXXENCE, stop taking CONEXXENCE and tell your doctor right away.

Nursing mothers should not take CONEXXENCE. It may also interfere with breastfeeding.

CONEXXENCE may lower levels of calcium in the blood. If you are prone to low calcium levels, your doctor will monitor your blood, especially in the first few weeks after starting CONEXXENCE. Severe low blood calcium levels may lead to hospitalization, life-threatening events, and death. Low blood calcium should be treated before receiving CONEXXENCE. Symptoms of low blood calcium may include muscle spasms, twitches, cramps, numbness or tingling in hands, feet or around the mouth, and weakness. Some patients may not have any symptoms of low calcium. Tell your doctor if you have any of these symptoms. Tell your doctor if you have or have had severe kidney problems as this may increase your risk of getting low blood calcium.

Tell your doctor right away if you have symptoms of infection, including:

• Fever or chills
• Skin that looks red, swollen, hot or tender to touch
• Severe abdominal pain
• Frequent or urgent need to urinate or burning feeling when you urinate

Tell your doctor if you have any of the following symptoms of skin problems that do not go away or get worse:

• Redness
• Itching
• Rash
• Dry or leathery skin
• Open, crusted or peeling skin
• Blisters

After you start CONEXXENCE:

• Take good care of your teeth and gums, and see your dentist regularly.
• If you have a history of dental problems (such as poorly fitting dentures or gum disease), see your dentist before starting CONEXXENCE.
• Tell your dentist that you are taking CONEXXENCE, especially if you are having dental work.

A dental condition called osteonecrosis of the jaw (ONJ) which can cause tooth and jawbone loss has been reported in patients treated with CONEXXENCE. The risk of ONJ may increase with length of time on CONEXXENCE. Tell your doctor and dentist immediately about any dental symptoms, including pain or unusual feeling in your teeth or gums, or any dental infections.

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

After your treatment with CONEXXENCE is stopped, it is possible that broken bones in your spine may occur especially if you have a history of broken bones in the spine. Do not stop taking CONEXXENCE without first talking with your doctor. If your CONEXXENCE treatment is stopped, discuss other available treatment options with your doctor.

Tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines.

The following may interact with CONEXXENCE:

In a drug interaction study, CONEXXENCE (60 mg) did not interfere with the action of a drug called midazolam which is metabolized (broken down) by a certain liver enzyme called cytochrome P450 3A4. No drug interactions are expected with CONEXXENCE and other drugs metabolised by this enzyme in women with postmenopausal osteoporosis.

You should discuss with your doctor any medications or vitamins or herbal products you are taking before using CONEXXENCE.

How to take CONEXXENCE:

CONEXXENCE is administered as a single injection under the skin (subcutaneous) every 6 months. The injection can be in your upper arm, upper thigh, or abdomen. It can be given any time with or without food by a healthcare professional, by a trained injector, or a patient may self-inject if a healthcare professional determines that is appropriate.

Your pre-filled syringe may be left outside the refrigerator to reach room temperature (up to 25 ^oC) before injection. This will make the injection more comfortable. See instructions for injection.

Keep all medicines, including CONEXXENCE, away from children.

Do not share a CONEXXENCE product with others, even if they have a similar disease.

Usual dose:

The usual dose of CONEXXENCE is 60 mg administered once every 6 months. You should also take supplements of calcium and vitamin D.

Overdose:

If you think you, or a person you are caring for, have taken too much CONEXXENCE, contact a healthcare professional, hospital emergency department, regional poison control centre or Health Canada’s toll-free number, 1-844 POISON-X (1-844-764-7669) immediately, even if there are no symptoms.

Missed dose:

If you miss a dose you should receive your next dose as soon as convenient. Schedule your next dose 6 months from the date of your last injection.

Possible side effects from using CONEXXENCE:

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

These are not all the possible symptoms or side effects you may experience; if you are concerned about any effects you experience you should contact your healthcare professional.

Possible side effects include:

• Pain, sometimes severe, in the muscles, joints, arms, legs or back.
• Low blood calcium (hypocalcemia). Symptoms of low blood calcium may include muscle spasms, twitches, cramps, numbness or tingling in fingers, toes or around the mouth.
• Allergic reactions (e.g., rash, hives, or in rare cases, swelling of the face, lips, tongue, throat, or trouble breathing).
• Allergic reaction that can damage blood vessels mainly in the skin (e.g., purple or brownish- red spots, hives or skin sores)
• Severe allergic reaction (drug reaction with eosinophilia and systemic symptoms [DRESS] syndrome) with skin rash/blisters, fever and/or increase in a type of white blood cell (eosinophils) with possible organ damage, such as liver, kidney, or lung.
• Skin condition with itching, redness and/or dryness (eczema). Injection site reactions were uncommon.
• Rash that may occur on the skin or sores in the mouth (lichenoid drug eruption).
• Hair loss (alopecia).
• Skin infection with swollen, red area of skin, that feels hot and tender and may be accompanied by fever (cellulitis).
• Common cold (runny nose or sore throat).
• Broken bones in the spine after stopping CONEXXENCE (multiple vertebral fractures).

Serious side effects and what to do about them

If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with your daily activities, tell your healthcare professional.

Reporting Side Effects

You can report any suspected side effects associated with the use of health products to Health Canada by:

• Visiting the Web page on Adverse Reaction Reporting (canada.ca/drug-device-reporting) for information on how to report online, by mail or by fax; or
• Calling toll-free at 1-866-234-2345.

NOTE: Contact your health professional if you need information about how to manage your side effects. The Canada Vigilance Program does not provide medical advice.

Storage:

Keep out of the reach and sight of children.

When prescribed CONEXXENCE, you will likely need to fill your prescription at a pharmacy. Store CONEXXENCE in your refrigerator at 2 ^oC to 8 ^oC until your injection appointment with your health professional or trained injector. Do not freeze.

When removed from the refrigerator, CONEXXENCE must be kept at room temperature (up to 25 ^oC) in the original carton and must be used within 30 days.

Store in original carton in order to protect from light.

Do not use CONEXXENCE after the expiry date which is printed on the carton and label. The expiry date refers to the last day of that month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer required.

If you want more information about CONEXXENCE:

• Talk to your healthcare professional
• Find the full product monograph, that is prepared for health professionals and includes this Patient Medication Information by visiting the Health Canada Drug Product Database website (https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database.html); the manufacturer’s website https://www.fresenius-kabi.com, or by calling: 1-877-821-7724

Fresenius Kabi Canada Ltd.

165 Galaxy Blvd, Suite 100

Toronto, ON M9W 0C8

Date of Authorization: April 18, 2026

Instructions for Use

^PrConexxence

Denosumab injection

60 mg/mL

Subcutaneous injection

Single use pre-filled syringe

The following instructions are for preparing and giving an injection of Conexxence using a single-use pre-filled syringe with an automatic needle guard:

Guide to parts:

Before you use a Conexxence pre-filled syringe with automatic needle guard, read this important information:

• 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 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.

Storing Conexxence pre-filled syringe

• 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.

Step 1: Prepare materials

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)

Figure A

1.2. Wait 15 to 30 minutes

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

Figure B

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

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).

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.

Figure E

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.

Figure F

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

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.

Step 2: Prepare to inject

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

Figure H

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.

Figure I

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.

Figure J

Step 3: Inject medicine

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.

Figure K

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.

Figure L

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).

Figure M

Figure N

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).

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.

Figure P

Do not rub the injection site.

Step 4: Throw away your pre-filled syringe

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.

Figure Q

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