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What Is Denosumab (Xgeva®, Prolia®)?


Xgeva® (denosumab) is a human monoclonal antibody that is a RANK (receptor activator of nuclear factor kappa-B) ligand inhibitor. Xgeva is indicated for individuals with bone metastases from solid tumors (cancer that has spread to the bones). Xgeva is also indicated for the treatment of hypercalcemia of malignancy, otherwise known as excess calcium in the body as a result of cancer that has spread to the bones. Xgeva helps prevent skeletal-related events, such as bone fractures, that are a result of cancer spreading to the bones. It is also indicated for adults and skeletally mature adolescents with inoperable giant cell tumor of bone.

Xgeva is administered as a subcutaneous (under the skin) injection in the upper thigh, upper arm, or abdomen once a month. Xgeva is also often co-administered with oral calcium and vitamin D supplements. Individuals taking Xgeva should be monitored for changes to the jaw bone and hypocalcemia (too little calcium in the blood). Denosumab is also on the market under the brand name Prolia, which is used for osteoporosis (bone loss).1,2

What are the ingredients in Xgeva?

The active ingredient in Xgeva is denosumab, the human monoclonal antibody that acts as a RANK ligand inhibitor.

How does Xgeva work?

Xgeva’s active ingredient is a human monoclonal antibody that inhibits the creation of osteoclast cells. Our bodies are continuously building and destroying our bones in a balanced process that keeps us healthy and strong. Cells in our body called osteoclasts regularly break down bone to release minerals, like calcium into our blood stream. Our body also builds bone using cells called osteoblasts, and takes these nutrients out of the blood and puts them back into our bones when needed. This process is critical to our skeletal stability and maintaining our nutrient balance.

When cancer metastasizes, it can destroy bones, and add to the normal, healthy bone destruction process. At this point, bone destruction can outweigh bone growth. When bones are broken down too quickly, excess calcium is released into the blood and our bones get weaker. This can lead to hypercalcemia, or too much calcium in the blood, as well as to bone pain and fractures. In order for new osteoclasts (the cells that destroy bone) to be made, RANK-L needs to be activated. Xgeva binds to the RANK-L, blocking it from the receptor, and preventing the activation process needed to make mature osteoclasts. By preventing new osteoclasts from being made, the bone building process can catch up. When our body builds bone, it utilizes calcium in the blood stream, keeping our nutrients in balance, as well as increases our skeletal stability. This can help reduce bone pain and decrease the risk of fractures.

What are the possible side effects of Xgeva?

Multiple clinical trials evaluated the safety and efficacy of Xgeva across many different conditions. The most common side effects of Xgeva include fatigue, low levels of phosphate in the blood, nausea, joint pain, back pain, pain in the hands and feet, shortness of breath, diarrhea, and headache. This is not an exhaustive list of all potential side effects of Xgeva. Talk to your healthcare provider or pharmacist for further information.

Things to note about Xgeva

Several more serious side effects can accompany Xgeva including developing hypocalcemia, or too little calcium in the blood. Alert your provider immediately if you notice any of the following symptoms:

  • Burning or prickling feeling in the hands and feet
  • Muscle stiffness, twitching, spasms or cramps

Additionally, there is a risk of developing destruction of the jaw bone while on Xgeva. Alert your provider immediately if you notice pain, numbness, swelling, or drainage from the jaw, mouth, or teeth, as well as persistent pain in the mouth or jaw after any dental procedures. If possible, it is best to avoid any invasive dental procedures while taking Xgeva. Also, individuals taking Xgeva should be monitored for skin reactions and infections.

Before starting Xgeva talk to your provider if you:

  • Have had any major dental conditions or have a major dental procedure scheduled
  • Are taking any other medication that contains denosumab, including Prolia
  • Are allergic to Xgeva or any of its ingredients, or have any other allergies
  • Have any other medical conditions
  • Are currently taking any other medications, vitamins, or herbal supplements

You should also contact your provider if you notice any signs of an allergic reaction to the medication, including chest pain, fever, flu-like symptoms, or difficulty breathing. It is also important to consult the prescribing information for any other medications prescribed with Xgeva.

Dosing information

Xgeva is administered via a subcutaneous (under the skin) injection into the upper arm, upper thigh, or abdomen once every 4 weeks. A typical dose of Xgeva is 120mg, but may need to be adjusted depending on if it is being used to treat solid tumors, hypercalcemia, or giant cell tumors of the bone. Your provider will determine the appropriate dosage and administration schedule for you. They will also determine the appropriate dosage and administration schedule of any other medications taken with Xgeva, such as calcium supplements. It is important to follow your provided schedule exactly as instructed, and not to stop taking Xgeva or any accompanying medications on your own. The dose of your Xgeva can be adjusted as needed by your doctor.1

Written by: Casey Hribar | Last reviewed: July 2019
  1. Xgeva Prescribing Information. June 2013. Available from: Accessed September 1, 2017.
  2. Prolia Prescribing Information. June 2010. Available from: Accessed September 1, 2017.