Denosumab Injection

Denosumab injection is available as several different products that are considered to be biologic medications (medications made from living organisms). These biosimilar products are highly similar to denosumab injection and work the same way as denosumab injection in the body. Therefore, the term denosumab injection products will be used to represent these medications in this discussion.

Denosumab injection products 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 a denosumab injection product 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.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with denosumab injection products. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) (or the manufacturer's website) to obtain the Medication Guide.

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

Denosumab injection products (Prolia, Jubbonti) are used

• to treat osteoporosis (a condition in which the bones become thin and weak and break easily) in women who have undergone menopause (''change of life;'' end of menstrual periods) who have an increased risk for fractures (broken bones) or who cannot take or did not respond to other medication treatments for osteoporosis.
• to treat men who have an increased risk for fractures (broken bones) or who cannot take or did not respond to other medication treatments for osteoporosis.
• treat osteoporosis that is caused by corticosteroid medications in men and women who will be taking corticosteroid medications for at least 6 months and have an increased risk for fractures or who cannot take or did not respond to other medication treatments for osteoporosis.
• to treat bone loss in men who are being treated for prostate cancer with certain medications that cause bone loss,
• to treat bone loss in women with breast cancer who are receiving certain medications that increase their risk for fractures.

Denosumab injection products (Xgeva, Wyost) are used 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.

• to reduce the risk of fractures in people who have multiple myeloma (cancer that begins in the plasma cells and causes bone damage), and in people who have certain types of cancer that began in another part of the body but has spread to the bones.
• in adults and some adolescents to treat giant cell tumor of bone (GCTB; a type of bone tumor) that cannot be treated with surgery.
• to treat high calcium levels that are caused by cancer in people who did not respond to other medications.

Denosumab injection products 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. When a denosumab injection product (Prolia, Jubbonti) is used to treat osteoporosis or bone loss, it is usually given once every 6 months. When a denosumab injection product (Wyost, Xgeva) is used to reduce the risk of fractures from multiple myeloma, or cancer that has spread to the bones, it is usually given once every 4 weeks. When a denosumab injection product (Wyost, Xgeva) is used to treat giant cell tumor of bone, or high calcium levels caused by cancer, it is usually given every 7 days for the first three doses (on day 1, day 8, and day 15) and then once every 4 weeks starting 2 weeks after the first three doses.

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

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

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

Before receiving denosumab injection products,

• tell your doctor and pharmacist if you are allergic to denosumab (Jubbonti, Prolia, Wyost, Xgeva), any other medications, or any of the ingredients in denosumab injection products. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• you should know that denosumab injection products are available under the brand names Jubbonti, Prolia, Wyost and Xgeva. You should not receive more than one product containing denosumab at the same time. Be sure to tell your doctor if you are being treated with any of these medications.
• 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. You will need to have a negative pregnancy test before starting treatment with denosumab injection products. You should not become pregnant while you are receiving denosumab injection products. You should use a reliable method of birth control to prevent pregnancy while you are receiving denosumab injection products and for at least 5 months after your final treatment. If you become pregnant while receiving denosumab injection products, or within 5 months of your treatment, call your doctor immediately. Denosumab may harm the fetus.
• you should know that denosumab injection products 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 products. Talk to your doctor before having any dental treatments while you are receiving this medication.

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

If you miss an appointment to receive an injection of a denosumab product, you should call your healthcare provider as soon as possible. The missed dose should be given as soon as it can be rescheduled. When a denosumab injection product (Jubbonti, Prolia) is used for osteoporosis or bone loss, after you receive the missed dose, your next injection should be scheduled 6 months from the date of your last injection.

Denosumab injection products 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 skin
• peeling skin
• back pain
• pain in your arms and legs
• swelling of arms or legs
• muscle or joint pain
• 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
• redness, tenderness, swelling or warmth of area of skin
• fever, cough, shortness of breath
• ear drainage or severe ear pain
• frequent or urgent need to urinate, burning feeling when you urinate
• severe abdominal pain
• 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 products 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 products. Denosumab injection products may also cause broken bones to heal slowly and may impair bone growth and prevent teeth from coming in properly in children. Denosumab injection products 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 products. Talk to your doctor about the risks of receiving denosumab injection products.

Denosumab injection products 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 (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

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.

Do not let anyone else use your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

• Jubbonti^® (denosumab-bbdz)
• Prolia^®
• Wyost^® (denosumab-bbdz)
• Xgeva^®