Denosumab Injection

IMPORTANT WARNING:

Denosumab injection may cause serious or life-threatening low calcium levels in your blood. Tell your doctor if you have or have ever had low levels of calcium in your blood. Your doctor will probably check the level of calcium in your blood before you begin treatment and will probably tell you not to receive denosumab injection if the level is too low. Also, tell your doctor if you are receiving dialysis treatments or are taking medications to lower your calcium levels or if you have or have ever had kidney problems; hypoparathyroidism (condition in which the body does not produce enough parathyroid hormone [PTH; a natural substance needed to control the amount of calcium in the blood]); malabsorption problems (problems with your stomach or intestine that make it difficult for your body to absorb nutrients); surgery on your thyroid gland or parathyroid gland (small gland in the neck); or surgery to remove part of your small intestine. Your doctor will monitor your blood calcium levels during your treatment. If you experience any of the following symptoms during your treatment, call your doctor immediately: numbness or tingling in your fingers, toes, or around your mouth; or muscle stiffness, twitching, cramps, or spasms.

You will be given the Medication Guide when you begin receive denosumab injection. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit https://www.fda.gov/Drugs/DrugSafety/ucm085729.htm to obtain the Medication Guide.

Talk to your doctor about the risks of receiving denosumab injection.

IMPORTANT NOTICE:

Denosumab injection is available as different products that are biologic medications (medications made from living organisms). These biologic products are considered to be "biosimilar" to denosumab injection which means they work as well and are just as safe to use as denosumab injection. Denosumab injection mentioned in the monograph below refersto any of these products.

WHY is this medicine prescribed?

Denosumab injection is used

• to treat certain cases of osteoporosis (a condition in which the bones become thin and weak and break easily)
• to treat bone loss in individuals with prostate cancer or breast cancer who are being treated with certain medications that cause bone loss
• to reduce the risk of fractures caused by multiple myeloma (cancer that begins in the bone marrows and causes bone damage) or other types of cancer that has spread to the bones
• to treat a certain type of giant cell tumor of bone (GCTB; a type of bone tumor)
• to treat high calcium levels caused by cancer in people who did not respond to other medications

Denosumab injection is in a class of medications called RANK ligand inhibitors. It works to prevent bone loss by blocking a certain receptor in the body to decrease bone breakdown. It works to treat GCTB by blocking a certain receptor in the tumor cells which slows the tumor growth. It works to treat high calcium levels by decreasing bone breakdown as the breakdown of bones releases calcium.

Are there OTHER USES for this medicine?

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

HOW should this medicine be used?

Denosumab injection come as a solution (liquid) to be injected subcutaneously (under the skin) in your upper arm, upper thigh, or stomach area. It is usually injected by a doctor or nurse in a medical office or clinic. Your doctor will tell you how often you will receive denosumab injection based on your condition.

Your doctor may tell you to take supplements of calcium and vitamin D while you are being treated with denosumab injection. Take these supplements exactly as directed.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

What SPECIAL PRECAUTIONS should I follow?

Before receiving denosumab injection products,

• tell your doctor or pharmacist if you are allergic to this drug, any part of this drug, or any other drugs, foods or substances. Tell your doctor or pharmacist about the allergy and what symptoms you had.

• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.

• tell your doctor if you have or have ever had anemia (condition in which the red blood cells do not bring enough oxygen to all the parts of the body); cancer; any type of infection, especially in your mouth; problems with your mouth, teeth, gums, or dentures; dental or oral surgery (teeth removed, dental implants); any condition that stops your blood from clotting normally; any condition that decreases functioning of your immune system; polymyalgia rheumatica (disorder that causes muscle pain and weakness); high cholesterol; or diabetes.

• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you can become pregnant, you will need to take a pregnancy test before starting treatment with denosumab injection. You should not become pregnant while you are receiving denosumab injection. Use a reliable method of birth control while you are receiving denosumab injection and for at least 5 months after your final treatment. If you become pregnant while receiving denosumab injection, or within 5 months of your treatment, call your doctor immediately. Denosumab may harm the fetus.

• you should know that denosumab injection may cause osteonecrosis of the jaw (ONJ, a serious condition of the jaw bone), especially if you have dental surgery or treatment while you are receiving this medication. A dentist should examine your teeth and perform any needed treatments, including cleaning or fixing ill-fitted dentures, before you start to receive a denosumab injection product. Be sure to brush your teeth and clean your mouth properly while you are receiving denosumab injection. Talk to your doctor before having any dental treatments while you are receiving this medication.

What SPECIAL DIETARY instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

What should I do IF I FORGET to take a dose?

If you miss an appointment to receive denosumab injection, call your healthcare provider as soon as possible.

What SIDE EFFECTS can this medicine cause?

Denosumab injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• red, dry, or itchy skin; oozing or crusty blisters on the skin; or peeling skin
• muscle, joint, back, arm, or leg pain
• swelling of arms or legs
• unusual tiredness or weakness
• nausea
• diarrhea
• constipation
• abdominal pain
• headache
• runny nose

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:

• hives, rash; itching; difficulty breathing or swallowing; swelling of the face, eyes, throat, tongue or lips
• fever or chills; cough; shortness of breath; redness, tenderness, swelling or warmth of area of skin; ear drainage or severe ear pain; frequent or urgent need to urinate, burning feeling when you urinate; severe stomach pain; or other signs of infection
• frequent or urgent need to urinate, burning feeling when you urinate
• painful or swollen gums, loosening of the teeth, numbness or heavy feeling in the jaw, poor healing of the jaw
• unusual bleeding or bruising
• nausea, vomiting, headache, and decreased alertness after stopping denosumab and for up to 1 year afterwards
• new or unusual thigh, hip, or groin pain

Denosumab injection may increase the risk that you will break your thigh bone(s). You may feel pain in your hips, groin, or thighs for several weeks or months before the bone(s) break, and you may find that one or both of your thigh bones have broken even though you have not fallen or experienced other trauma. It is unusual for the thigh bone to break in healthy people, but people who have osteoporosis may break this bone even if they do not receive denosumab injection. Denosumab injection may also cause broken bones to heal slowly and may impair bone growth and prevent teeth from coming in properly in children. Denosumab injection may also increase the risk of spinal (back) fractures months to years after your treatment is discontinued. Tell your doctor if you have ever had a broken bone in your spine. Your doctor will probably tell you to take another medication to prevent fractures after you stop receiving denosumab injection. Talk to your doctor about the risks of receiving denosumab injection.

Denosumab injection may cause other side effects. Call your doctor if you have any unusual problems while receiving this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (https://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

What OTHER INFORMATION should I know?

Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests to be sure it is safe for you to receive denosumab injection and to check your body's response to denosumab injection.

Keep a written list of all of the prescription and nonprescription (over-the-counter) medicines, vitamins, minerals, and dietary supplements you are taking. Bring this list with you each time you visit a doctor or if you are admitted to the hospital. You should carry the list with you in case of emergencies.