• Denosumab is a monoclonal antibody that may be used to treat osteoporosis.
• Denosumab works by binding to a protein called RANKL on osteoclasts (the cells that break down bone), inhibiting their formation, function, and survival. This decreases bone breakdown and increases bone density and strength both in the outer layer of bone and the inner spongy layer.
• Denosumab belongs to the class of medicines known as monoclonal antibodies.

• Denosumab may be used to treat postmenopausal women with osteoporosis at high risk of fracture.
• May also be used to increase bone density in men with osteoporosis.
• Denosumab may be used to increase bone mass in men who have undergone androgen deprivation therapy for prostate cancer and in women receiving aromatase inhibitor therapy for breast cancer.
• Denosumab is administered by injection under the skin of the upper thigh, abdomen, or upper arm, once every six months.
• The dosage of denosumab does not need to be reduced in people with kidney disease.
• There are two brands of denosumab, Prolia, and Xgeva.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Back pain, constipation, muscle pain, pain in the hands or feet, high cholesterol levels, nasal congestion, and bladder infections (in women) are the most common side effects reported with denosumab.
• Denosumab may exacerbate low calcium levels and has been associated with low energy or low trauma fractures of the femoral shaft. The risk of serious infections may also be increased. * Skin reactions occur frequently in people receiving denosumab, and there have been reports of severe incapacitating bone, joint, or muscle pain associated with denosumab use. Denosumab may suppress bone remodeling.
• People undergoing denosumab therapy need to receive calcium 1000mg daily and at least 400 IU of vitamin D daily.
• Denosumab has been associated with osteonecrosis of the jaw. The risk of osteonecrosis of the jaw is greater in those who have received chemotherapy, radiation, or steroids. A routine oral examination should be completed by a dentist before denosumab is started.
• Severe allergic reactions have been reported with denosumab and symptoms have included low blood pressure, shortness of breath, facial and throat tightness, and rash.
• Denosumab may not be suitable for some people including those with low calcium levels (must be corrected before administration), who are pregnant, or with allergic reactions to denosumab or its components.
• Denosumab is only available as an injection; however, people can be taught how to self-administer denosumab.
• The grey needle cap that fits onto the end of a pre-filled syringe of denosumab should not be handled by people with latex allergies because it may cause a reaction.
• Denosumab must be stored in the refrigerator until needed for use.
• The risk of fracture, including multiple vertebral fractures, increases when denosumab is discontinued, and new vertebral fractures have been reported in as little as 7 months following discontinuation. The risk decreases to pretreatment values within 24 months. Bone density returns to pretreatment values within 18 months of the last injection of denosumab. Evaluate the benefits/risks for each patient before starting denosumab. When discontinuing denosumab, consider transitioning to another osteoporosis treatment agent.
• Avoid during pregnancy because denosumab may cause fetal harm. Potential placental transfer of denosumab is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis. Denosumab should only be used by postmenopausal women. If a female is inadvertently exposed to denosumab during pregnancy enroll her in the Amgen Pregnancy Surveillance Program (1-800-772-6436).
• Denosumab is only available under the brand (trade) names of Prolia or Xgeva. No generic has been approved in the United States.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

• If you have been shown how to self-inject denosumab, administer yourself a dose once every six months, otherwise see your healthcare provider for a dose every six months. If you forget a dose, schedule it as soon as you can, then continue getting your future injections six months from that date.
• Immediately before administration take denosumab out of the refrigerator and leave it in its original container to warm up to room temperature for around 15 to 30 minutes. Do not warm in any other way. Once at room temperature, remove the grey needle cap and insert the needle under the skin of the upper thigh, abdomen, or upper arm. Push the plunger to inject the dose of denosumab under the skin. When finished, click the green safety guard into place (there is no need to replace the grey needle cap). Dispose of the used needle immediately in an approved sharps container.
• Keep denosumab in the refrigerator. Once it has been taken out of the refrigerator, use it within 14 days. Do not shake denosumab vigorously.
• Denosumab usually needs to be taken alongside calcium and vitamin D supplements. Make sure you take your supplements as directed and talk to your doctor or pharmacist if you are unsure about what supplements to take.
• Make sure you have a dental check-up before you start denosumab. Talk to both your dentist and doctor if you require dental surgery or tooth extraction and you have been administered denosumab. Keep good oral hygiene and get regular dental check-ups while you are being given denosumab. Report any oral symptoms such as tooth pain, jaw pain, loose teeth, or mouth ulcers to your doctor while you are being administered denosumab.
• Talk to your doctor or seek urgent medical attention (if severe) if you experience symptoms such as dizziness on standing or fainting, shortness of breath, facial and throat tightness, or rash. Report any signs of infection immediately to your doctor.
• Tell your doctor if you experience any thigh or groin pain, muscle cramps or twitches, severe or debilitating muscle pain, or any other adverse effects of concern while you are being administered denosumab.
• Denosumab should not be administered to women who are pregnant but if you inadvertently become pregnant while being administered denosumab, tell your doctor immediately.
• Talk to your doctor or pharmacist before taking any other medicines with denosumab. Prolia and Xgeva both contain denosumab and should not be taken at the same time.

• Maximal denosumab concentrations are reached within 10 days of an injection, and levels of denosumab decline over four to five months.
• Denosumab reduced the risk of vertebral fractures by 4.8%, hip fractures by 0.3%, and nonvertebral fractures by 1.5%.
• Bone mineral density was increased by 8.8% in the spine, 6.4% in the hip, and 5.2% in the neck after three years of treatment with denosumab.

Medicines that interact with denosumab may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with denosumab. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with denosumab include:

• calcimimetic agents such as cinacalcet
• chemotherapy agents, such as cyclophosphamide, methotrexate, or bleomycin
• corticosteroids (such as prednisone or dexamethasone)
• immunosuppressants (such as azathioprine, cyclosporine, or tacrolimus).

Note that this list is not all-inclusive and includes only common medications that may interact with denosumab. You should refer to the prescribing information for denosumab for a complete list of interactions.