Denoza: Uses, Side Effects and Dosage

What DENOZA is used for:

DENOZA 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 osteoporosis is:

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 DENOZA, 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 DENOZA works:

DENOZA 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). DENOZA 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 DENOZA are:

Medicinal ingredient: denosumab

Non-medicinal ingredients: sorbitol, acetic acid, polysorbate 20, water for injection and sodium hydroxide. The prefilled syringe is not made with natural rubber latex.

DENOZA comes in the following dosage forms:

DENOZA is a liquid for injection, available in a prefilled syringe.

DENOZA is a colourless to yellowish solution. Do not use if the solution is cloudy.

Do not use DENOZA if:

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

• you are pregnant or breastfeeding.

• you are a woman before menopause [unless you have been diagnosed with breast cancer or are taking DENOZA for the treatment or prevention of osteoporosis related

  • to the use of corticosteroid medicines (see also What DENOZA is used for above and Other warnings you should know about below)].
• you are currently taking denosumab-containing medicinal products.
• you do not have access to a healthcare professional or trained injector.

To help avoid side effects and ensure proper use, talk to your healthcare professional before you take DENOZA. 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 DENOZA.
• Plan to have dental surgery or teeth removed.
• Have a history of cancer.
• Are pregnant or could become pregnant.

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

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

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

DENOZA 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 DENOZA. Severe low blood calcium levels may lead to hospitalization, life-threatening events, and death. Low blood calcium should be treated before receiving DENOZA. 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 DENOZA:

• 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 DENOZA.
• Tell your dentist that you are taking DENOZA, 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 denosumab. The risk of ONJ may increase with length of time on DENOZA. 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 DENOZA 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 DENOZA without first talking with your doctor. If your DENOZA treatment is stopped, discuss other available treatment options with your doctor.

Other warnings you should know about:

If you are being treated with DENOZA, you should not be taking other denosumab-containing medicinal products.

There is an increased risk of skin infection (cellulitis) with DENOZA 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.

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 DENOZA:

In a drug interaction study, denosumab (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 DENOZA 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 DENOZA.

How to take DENOZA:

DENOZA 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 prefilled syringe may be left outside the refrigerator for about 30 minutes to reach room temperature (up to 25°C) before injection. This will make the injection more comfortable. Keep the prefilled syringe in the original carton until ready to use in order to protect from light. See instructions for injection.

Keep all medicines, including DENOZA, away from children.

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

Usual dose:

The usual dose of DENOZA 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 DENOZA, 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 signs or 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.

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

Guide to parts

Important:

Before you use an DENOZA prefilled syringe, read this important information:

Using the prefilled syringe

• Administration should be performed by an individual who has been trained in injection techniques. This includes patients who have been deemed appropriate by their healthcare professional to administer DENOZA.

  If your doctor decides that you or your caregiver may be able to give your injections of DENOZA at home, ensure that your doctor or nurse shows you or your caregiver how to prepare and inject with the DENOZA prefilled syringe before you use it for the first time.

  Be sure that you read and understand these Instructions for Use before injecting with the DENOZA prefilled syringe. Talk to your doctor if you have any questions

• Make sure the name DENOZA appears on the carton and prefilled syringe label.
• Check the carton and prefilled syringe label to make sure the dose strength is 60 mg.
• Do NOT use a syringe after the expiration date on the label.
• Do NOT shake the syringe.
• Do NOT open the outer box until you are ready to use this medicine.
• Do NOT remove needle cap from the syringe until you are ready to inject.
• Do NOT use the syringe if the carton is open or damaged.
• Do NOT use a syringe if it has been dropped on a hard surface. Part of the syringe may be broken even if you cannot see the break. Use a new syringe.
• Do NOT attempt to activate the pre-filled syringe prior to injection
• Do NOT attempt to remove the needle guard from the pre-filled syringe.
• The prefilled syringe is not made with natural rubber latex.

Call your healthcare provider if you have any questions.

Prepare

1. A. Remove the prefilled syringe carton from the refrigerator.

Leave the carton with pre-filled syringe inside at room temperature for about 30 minutes before injecting

• Do NOT use the prefilled syringe if the carton is damaged.
• Do NOT try to warm the prefilled syringe by using a heat source such as hot water or microwave.
• Do NOT leave the prefilled syringe in direct sunlight.
• Do NOT shake the prefilled syringe.

• Wash your hands thoroughly with soap and water.

• Open the carton.
• Grab the pre-filled syringe by the body.
• Lift the syringe straight out of the carton
• Put the syringe on a clean and flat work surface

For safety reasons:

• Do NOT grab the plunger rod.
• Do NOT grab the needle cap.
• Inspect the medicine and prefilled syringe.

Always hold the syringe by the syringe barrel.

Make sure the medicine in the prefilled syringe is colourless to slightly yellow.

Do NOT use the prefilled syringe if:

• The medicine is cloudy or discoloured.
• Any part appears cracked or broken.
• The prefilled syringe has been dropped.
• The needle cap is missing or not securely attached.
• The expiration date printed on the label has passed.

In all cases, use a new prefilled syringe and call your healthcare professional or Apotex Inc. at 1-800-667-4708.

1. C. Gather all materials needed for the injection.

Wash your hands thoroughly with soap and water.

On a clean, well-lit work surface, place the:

• Prefilled syringe
• Alcohol wipe
• Cotton ball or gauze pad
• Adhesive bandage
• Sharps disposal container

Get ready

1. D. Prepare and clean the injection site

You can use:

• Upper thigh
• Stomach area (abdomen), except for a 5 cm (2-inch) area right around the navel (belly button)
• Outer area of upper arm (only if someone else is giving you the injection).

Clean the injection site with an alcohol wipe. Let the skin dry.

• Do NOT touch this area again before injecting.

• Do NOT inject into areas where the skin is tender, bruised, red, or hard. Avoid injecting

  • into areas with scars or stretch marks.
• Hold the prefilled syringe by the syringe barrel. Carefully pull the needle cap straight off and away from the body.

• Do NOT remove the needle cap from the prefilled syringe until you are ready to inject.
• Do NOT twist or bend the needle cap.
• Do NOT hold the prefilled syringe by the plunger rod.
• Do NOT put the needle cap back onto the prefilled syringe. Important: Throw the needle cap into the sharps disposal container.

Subcutaneous (under the skin) injection.

1. F. Pinch the injection site to create a firm surface.

Important: Keep skin pinched while injecting.

1. G. Hold the pinch. Insert the needle into the skin at 45 to 90 degrees.

1. H. Use slow and constant pressure to push the plunger all the way in until all the liquid is injected, and the syringe is empty

Note: The plunger must be pushed all the way down to be sure the full dose has been injected and the needle guard will activate

Release your thumb

• Take your thumb off the plunger to allow the needle guard to cover the needle.

• Then lift the syringe off the skin.

• Release the pinched skin.

Important: Call your healthcare professional right away if:

• You remove the syringe and it looks like the medicine is still in the syringe barrel, this means that you did not inject the full dose

Or

• The needle guard does not activate after injecting.

Finish

1. I. Discard (throw away) the used prefilled syringe.

• Put the used prefilled syringe in a sharps disposal container right away after use. Do NOT throw away (dispose of) the syringe in the household trash.

• If you do not have a sharps disposal container, you may use a household container that is:

  • made of a heavy-duty plastic,
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
  • upright and stable during use,
  • leak-resistant, and
  • properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes.
• Do NOT reuse the prefilled syringe.
• Do NOT recycle the prefilled syringe or sharps disposal container or throw them into household trash.

Important: Always keep the sharps disposal container out of the reach of children.

1. J. Examine the injection site.

If there is blood, press a cotton ball or gauze pad on the injection site. Do NOT rub the injection site. Apply an adhesive bandage if needed.

1. K. Record date of next injection
2. •

   Record the date of your next injection on the sticker included on the card, in the

   • carton and place on your calendar. Your next injection will be 6 months from the date of injection.

Possible side effects from using DENOZA:

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

These are not all the possible side effects you may have when taking DENOZA. If you experience any side effects not listed here, tell 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 (eg, 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 (eg, 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 DENOZA (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 healthcare 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 DENOZA, you will likely need to fill your prescription at a pharmacy. Store DENOZA in your refrigerator at 2°C to 8°C until your injection appointment with your healthcare professional or trained injector. Do not freeze or shake.

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

Store in original carton in order to protect from light.

Do not use DENOZA 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 DENOZA:

• Talk to your healthcare professional
• Find the full product monograph, that is prepared for healthcare professionals and includes this Patient Medication Information by visiting the Health Canada Drug Product Database website (Drug Product Database: Access the database); the manufacturer’s website (http://www.apotex.ca/products); or by calling 1-800-667-4708.

Date of Authorization: March 11, 2026