Denosumab Subcutaneous

Denosumab injection is used to treat osteoporosis (thinning of the bones) in women who have an increased risk for fractures after menopause, and osteoporosis in men. It is given when other medicines cannot be used or after other medicines did not work well.

Denosumab injection is also used to treat bone loss in men with prostate cancer and women with breast cancer who are receiving cancer treatment. It is used to prevent bone problems in patients with bone metastases (cancer that has spread) from tumors. Denosumab is used to treat giant cell tumor of the bone that cannot be removed by surgery. denosumab is also used to treat hypercalcemia of malignancy that has been treated with bisphosphonates (eg, alendronate, ibandronate, risedronate, Fosamax®) but did not work well.

denosumab is to be given only by or under the supervision of your doctor.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For denosumab, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to denosumab or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Use of denosumab injection is not recommended in the pediatric population, except for teenagers with giant cell tumor of the bone. The safety and efficacy of denosumab for other conditions have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of denosumab injection in the elderly.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of denosumab. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or
• Blood clotting problems or
• Cancer or
• Dental disease, history of or
• Dental implants, history of or
• Dentures that don't fit well or
• Diabetes or
• Gum disease or
• Hypoparathyroidism (underactive parathyroid gland), history of or
• Kidney problems, severe and may require dialysis or
• Malabsorption syndrome (trouble absorbing food), history of or
• Mouth surgery, history of or
• Parathyroid surgery, history of or
• Thyroid surgery, history of or
• Tooth extraction, history of—May cause side effects to become worse.

• Ear infection or
• Eczema or
• Endocarditis (heart infection) or
• Skin infections or
• Skin rashes or
• Stomach infection or
• Urinary tract infection—Use with caution. May make these conditions worse.

• Hypocalcemia (low calcium in the blood)—Should not be given to patients with this condition.

It is important that your doctor check your progress at regular visits to make sure denosumab is working properly. Blood tests may be needed to check for unwanted effects.

Prolia® contains denosumab which can also be found in Xgeva®. Patients using Prolia® should not receive Xgeva®.

Your unborn baby could be harmed if you use denosumab while you are pregnant. Women receiving Xgeva® should use a highly effective form of birth control to keep from getting pregnant during treatment and for at least 5 months after the last dose. There is also a potential for denosumab to cause birth defects if the father is using it when his sexual partner becomes pregnant. If a pregnancy occurs while you are receiving denosumab, tell your doctor right away.

denosumab may cause serious allergic reactions, including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Tell your doctor or nurse right away if you have a rash, lightheadedness, dizziness, or fainting, itching, swelling of the face, tongue, and throat, trouble breathing, or chest pain after you get the injection.

denosumab may cause hypocalcemia (low calcium in the blood). A low blood calcium must be treated before you receive denosumab. Call your doctor right away if you have muscle spasms or twitching, or numbness or tingling in your fingers, toes, or around your mouth.

Prolia® may increase your risk of developing infections. Avoid being near people who are sick or have infections while you are using denosumab. Check with your doctor right away if you have a fever or chills, red, swollen skin, severe abdominal or stomach pain, or burning or painful urination.

Skin problems may occur after receiving Prolia®. Check with your doctor right away if you have any of the following symptoms that do not go away or get worse: blistering, crusting, irritation, itching, or reddening of the skin, cracked, dry, or scaly skin, rash, or swollen skin.

It is important that you tell all of your doctors that you are receiving denosumab injection, including your dentist. If you are having dental procedures while receiving denosumab, you may have an increased chance of having a severe problem with your jaw. Make sure you tell your doctor or dentist about any new problems, such as pain or swelling, with your teeth or jaw.

The needle cover of the prefilled Prolia® syringe contains dry natural rubber (a derivative of latex), which may cause allergic reactions in people who are sensitive to latex. Tell your doctor if you have a latex allergy before you start using denosumab.

denosumab may increase your risk of developing fractures of the thigh bone. This may be more common if you use it for a long time. Check with your doctor right away if you have a dull or aching pain in the thigh, groin, or hips.

Check with your doctor right away if you have severe muscle, bone, or joint pain after receiving Prolia®.

Do not suddenly stop using Prolia® without checking first with your doctor. Doing so may increase risk for more fractures. Talk to your doctor about other medicine that you can take.

Hypercalcemia may occur after stopping Xgeva® treatment in patients with growing bones. Tell your doctor right away if you have nausea, vomiting, headache, or decreased alertness.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Back pain
• blistering, crusting, irritation, itching, or reddening of the skin
• bloody or cloudy urine
• cracked, dry, or scaly skin
• difficult, burning, or painful urination
• frequent urge to urinate
• muscle or bone pain
• pain in the arms or legs
• rash
• skin rash, encrusted, scaly, and oozing
• swelling

• Abdominal or stomach cramps
• arm or jaw pain
• bloating or swelling of the face, arms, hands, lower legs, or feet
• body aches or pain
• chest pain or discomfort
• chest tightness or heaviness
• confusion
• congestion
• convulsions
• cough
• difficulty with breathing
• difficulty with moving
• dryness or soreness of the throat
• ear congestion
• fast or irregular heartbeat
• fever or chills
• headache
• hoarseness
• joint pain
• loss of voice
• muscle cramps in the hands, arms, feet, legs, or face
• muscle stiffness
• numbness and tingling around the mouth, fingertips, hands, or feet
• pain in the lower back, bottom, or hips
• pain in the upper leg
• painful blisters on the trunk of the body
• pale skin
• rapid weight gain
• runny or stuffy nose
• sneezing
• swollen joints
• tender, swollen glands in the neck
• tremor
• trouble swallowing
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain or loss
• voice changes

• Abdominal or stomach discomfort
• blood in the stool
• change in bowel habits
• clear or bloody discharge from the nipple
• constipation
• darkened urine
• difficulty with swallowing or eating
• dimpling of the breast skin
• indigestion
• inverted nipple
• itching, pain, redness, swelling, tenderness, or warmth on the skin
• loss of appetite
• lower back or side pain
• lump in the breast or under the arm
• lump or swelling in the abdomen or stomach
• nausea
• pains in the stomach, side, or abdomen, possibly radiating to the back
• persistent crusting or scaling of the nipple
• raised, firm, and bright red patches of the skin on the arm or leg
• redness or swelling of the breast
• sore on the skin of the breast that does not heal
• unexplained weight loss
• vomiting
• yellow eyes or skin

• Heavy feeling in the jaw
• loose teeth
• pain, swelling, or numbness in the mouth or jaw

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Dizziness or lightheadedness
• excess air or gas in the stomach or intestines
• feeling of constant movement of self or surroundings
• full feeling
• heartburn
• lack or loss of strength
• passing gas
• redness, pain, itching, burning, swelling, or a lump under your skin where the shot was given
• sensation of spinning
• trouble sleeping
• upper abdominal or stomach pain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also Precautions section.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Denosumab may cause low calcium levels, especially if you have kidney problems. Take calcium and vitamin D as directed by your doctor. (See also How to Use section.) Your doctor will order calcium blood tests before your first injection and during treatment. Tell your doctor right away if you have any symptoms of low calcium such as: muscle spasms/cramps, mental/mood changes (such as irritability or confusion), numbness/tingling (especially around lips/mouth or in fingers/toes), fast/irregular heartbeat, severe dizziness/fainting, seizures.

Denosumab can affect your immune system. You may be more likely to get a serious infection, such as a skin, ear, stomach/gut, or bladder infection. Tell your doctor right away if you develop any signs of infection, such as: fever/chills, red/swollen/tender/warm skin (with or without pus), severe abdominal pain, ear pain/discharge, trouble hearing, frequent/painful/burning urination, pink/bloody urine.

Tell your doctor right away if you have any serious side effects, including: jaw pain, new or unusual thigh/hip/groin pain, bone/joint/muscle pain.

After your treatment with denosumab is stopped, you may be at increased risk for bone fracture, including bones in your spine. Do not stop using this medication without first talking with your doctor. If your treatment is stopped, talk with your doctor about other medicines you can take.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

Denosumab can cause skin problems such as dryness, peeling, redness, itching, small bumps/patches, or blisters. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe allergic reaction. Therefore, get medical help right away if you develop any rash or if any of these symptoms persist or worsen.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.