Stoboclo: Uses, Side Effects and Dosage

What STOBOCLO is used for:

STOBOCLO 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 STOBOCLO, 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 STOBOCLO works:

STOBOCLO 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). STOBOCLO 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 STOBOCLO are:

Medicinal ingredient: denosumab.

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

STOBOCLO comes in the following dosage forms:

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

STOBOCLO is a clear, colourless to pale yellow solution. Do not use if the solution is cloudy.

Do not use STOBOCLO if you:

• are allergic to denosumab or any other ingredient of STOBOCLO. Allergic reactions (eg, 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 is STOBOCLO 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 STOBOCLO for the treatment or prevention of osteoporosis related to the use of corticosteroid medicines (see also What is STOBOCLO used for above and Other warnings you should know about below)].
• are currently taking denosumab, under the brand name OSENVELT.
• do not have access to a health professional or trained injector.

Other warnings you should know about:

Patients being treated with STOBOCLO should not be treated concomitantly with other denosumab-containing medicinal products.

There is an increased risk of skin infection (cellulitis) with STOBOCLO 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 STOBOCLO. 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 STOBOCLO.
• Plan to have dental surgery or teeth removed.
• Have a history of cancer.
• Are pregnant or could become pregnant.

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

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

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

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

• 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 STOBOCLO.
• Tell your dentist that you are taking STOBOCLO, 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 denosumab. 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 STOBOCLO 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 STOBOCLO without first talking with your doctor. If your STOBOCLO 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 STOBOCLO:

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 STOBOCLO 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 STOBOCLO.

How to take STOBOCLO:

STOBOCLO 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 to reach room temperature (up to 30°C) before injection. Keep the prefilled syringe in in the original carton until ready to use in order to protect from light. This will make the injection more comfortable. See instructions for injection.

Keep all medicines, including STOBOCLO, away from children.

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

Usual dose:

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

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.

Overdose:

If you think you, or a person you are caring for, have taken too much STOBOCLO, contact your healthcare professional, hospital emergency department or regional poison control centre immediately, even if there are no symptoms.

Instructions for use:

Read and follow the Instructions for use that come with your Stoboclo prefilled syringe before you start using it and each time you get a refill. There may be new information. Stoboclo may be administered by healthcare professionals (HCPs), caregivers or may be self-administered by the patients if they have received training. Talk to your doctor if you have any questions about giving yourself an injection.

Guide to Parts

Figure A

Important Information

• Stoboclo is given as an injection into the tissue just under the skin (subcutaneous injection).
• Do not open the sealed carton until you are ready to use the prefilled syringe.
• Do not remove the needle cap from the prefilled syringe until just before you give the injection.
• Do not attempt to activate the prefilled syringe prior to injection.
• Do not attempt to remove the clear safety guard from the prefilled syringe.
• Do not use the prefilled syringe if it has been dropped on a hard surface. Use a new prefilled syringe.
• Do not shake the prefilled syringe. Strong shaking may damage the medicine.
• The prefilled syringe cannot be re-used. Dispose of the used prefilled syringe immediately after use in a sharps disposal container (see Step 15. Dispose of STOBOCLO).

Storing Stoboclo

• Keep the prefilled syringe out of the sight and reach of children. Contains small parts.
• Store the prefilled syringe in a refrigerator between 2 ^oC and 8 ^oC. Do not freeze.

• Once removed from the refrigerator, Stoboclo may be stored at temperatures up to a maximum of 30°C

  Before Use

  After Use

  Plunger Rod

  Medicine

  Finger Flange

  Viewing Window

  Safety

  Guard

  Needle

  Needle

  Cap

  • for a single period of up to 63 days but not exceeding the original expiry date. If necessary, the product may be returned to the refrigerator once within 63 days and provided this does not exceed the original expiry date. It must be used after subsequent removal from refrigeration. Discard Stoboclo if not used by the original expiry date.
• Store the prefilled syringe sealed inside its carton to protect it from light.

Preparing for the Injection

1. 1. Gather the supplies for the injection.

1a. Prepare a clean, flat surface, such as a table or counter top, in a well-lit area.

1b. Take the carton containing the prefilled syringe out of the refrigerator.

1c. Make sure you have the following supplies (see Figure B):

• Carton containing prefilled syringe

Not included in the carton:

• Alcohol swab
• Cotton ball or gauze
• Adhesive bandage

• Sharps disposal container

  Figure B

1. 2. Check the expiration date on the carton (see Figure C).

Do not use it if the expiration date has passed. If the expiration date has passed, return the entire carton to the pharmacy.

Figure C

1. 3. Wait 15 - 30 minutes.

3a. Leave the unopened carton at room temperature (up to 30 °C) for 15 - 30 minutes to allow it to warm up (see Figure D).

• Do not warm the prefilled syringe using heat sources such as hot water or a microwave.

• If the syringe does not reach room temperature, this could cause the injection to feel uncomfortable and make it hard to push the plunger rod.

  Figure D

1. 4. Remove the prefilled syringe from the carton.

4a. Open the carton. Gripping the syringe body, lift the prefilled syringe from the carton (see Figure E).

• Do not hold by the head of the plunger rod, plunger rod, safety guard, or needle cap.

• Do not pull back on the plunger rod at any time.

  Figure E

1. 5. Inspect the prefilled syringe.

5a. Look at the prefilled syringe and make sure you have the correct medicine (STOBOCLO).

5b. Look at the prefilled syringe and make sure it is not cracked or damaged.

5c. Check the expiration date on the label of the prefilled syringe (see Figure F).

• Do not use if the needle cap is missing or not securely attached.
• Do not use if the expiration date has passed.

• Do not shake the prefilled syringe.

  Figure F

1. 6. Inspect the medicine.

6a. Look at the medicine and confirm that the liquid is clear, colourless to pale yellow, and does not contain any particles or flakes in it (see Figure G).

• Do not use the prefilled syringe if the liquid is discoloured, cloudy, or has particles or flakes in it.

• You may see air bubbles in the liquid. This is normal.

  Figure G

1. 7. Choose an appropriate injection site (see Figure H).

7a. You may inject into:

• The upper thighs.
• The abdomen, except for the 5 cm around the belly button (navel).
• The outer area of the upper arm (only if you are a caregiver or HCP).
• Do not inject into moles, scars, bruises, or areas where the skin is tender, red, hard, or if there are cracks in the skin.
• Do not inject through clothing.

7b. Choose a different injection site for each new injection at least 2.5 cm away from the area used for the last injection.

Figure H

1. 8. Wash your hands.

8a. Wash your hands with soap and water and dry them thoroughly (see Figure I).

Figure I

1. 9. Clean the injection site.

9a. Clean the injection site with an alcohol swab using a circular motion (see Figure J).

9b. Let the skin dry before injecting.

• Do not blow on or touch the injection site again before giving the injection.

  Figure J

Administering the Injection

1. 10. Remove the cap.

10a. Hold the body of the prefilled syringe in one hand between the thumb and index fingers. Carefully pull the needle cap straight out and away from your body (see Figure K).

• Do not hold the plunger rod while removing the cap.
• You may notice a few drops of liquid at the tip of the needle. This is normal.

10b. Dispose of the cap right away in a sharps disposal container (see Step 15 and Figure K).

• Do not use the prefilled syringe if it is dropped without the needle cap in place. If this happens, please contact your healthcare provider or pharmacist.
• Inject the dose promptly after removing the needle cap.
• Do not re-cap the prefilled syringe.

• Do not touch the needle. Doing so may result in a needle stick injury.

  Figure K

1. 11. Insert the prefilled syringe into the injection site.

11a. Hold the body of the prefilled syringe in one hand between the thumb and index fingers.

11b. Use the other hand to gently pinch the cleaned skin between your thumb and index finger. Do not squeeze it tightly.

Note: It is important to keep the skin pinched when injecting to make sure that you inject under the skin (into the fatty area) but not any deeper (into muscle).

11c. With a quick and dart-like motion, insert the needle completely into the fold of skin at a 45-degree angle (see Figure L).

• Do not pull back on the plunger rod at any time.

  Figure L

1. 12. Give the injection.

12a. After the needle is inserted, release the pinch.

12b. Slowly push the plunger rod all the way down until the full dose of medicine gets injected, and the syringe is empty (see Figure M).

• Do not change the position of the prefilled syringe after the injection has started.

• If the plunger rod is not fully pressed, the safety guard will not extend to cover the needle when it is removed.

  Figure M

1. 13. Remove the prefilled syringe from the injection site.

13a. After the prefilled syringe is empty, as the needle is being taken out, slowly remove the needle by lifting your thumb from the plunger rod until the needle is completely covered by the safety guard (see Figure N).

• If the needle is not covered, proceed to carefully dispose of the syringe (see step 15. Dispose of STOBOCLO).
• Do not put the needle cap back on used prefilled syringes.
• Do not reuse the prefilled syringe.

• Do not rub the injection site.

  Figure N

After the Injection

1. 14. Care for the injection site.

14a. If some bleeding occurs, treat the injection site by gently pressing, not rubbing, a cotton ball or gauze to the site and apply an adhesive bandage if needed.

1. 15. Dispose of STOBOCLO.

15a. Put the used prefilled syringe and other supplies in sharps disposal container right away after use (see Figure O).

15b. Do not throw away (dispose of) the prefilled syringe in your household trash.

• Keep the syringe and sharps disposal container out of sight and reach of children.
• If you do not have a sharps disposal container, you may use a household container that is closable and puncture resistant.
• For the safety and health of you and others, needles and used syringes must never be reused. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

  Figure O

What are possible side effects from using STOBOCLO?

Like all medicines, STOBOCLO 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 (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 STOBOCLO (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.

If you want more information about STOBOCLO:

• Talk to your healthcare professional
• Find the full product monograph that is prepared for healthcare professionals and includes the Patient Medication Information by visiting the Health Canada Drug Product Database website (Drug Product Database: Access the database)

Celltrion, Inc.

23, Academy-ro,

Yeonsu-gu, Incheon (22014),

Republic of Korea

Date of Authorization:

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.