What Is Denosumab (Xgeva®, Prolia®)?

Reviewed by: HU Medical Review Board | Last reviewed: July 2022 | Last updated: July 2022

Xgeva® (denosumab) is a human monoclonal antibody that is a RANK (receptor activator of nuclear factor kappa-B) ligand inhibitor. Xgeva is indicated for certain individuals with bone metastases from solid tumors (cancer that has spread to the bones) or multiple myeloma (a specific form of blood cancer). Xgeva is also indicated for the treatment of hypercalcemia of malignancy, otherwise known as excess calcium in the blood 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. 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 certain cases of osteoporosis (bone loss), as well as for increasing bone mass in some breast cancer, and non-metastatic prostate cancer, patients receiving specific treatments who are also at high risk of bone fracture.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 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 osteoclasts (the cells that destroy bone) to function, RANK-L needs to be activated. Xgeva binds to the RANK-L, blocking it from the receptor, and preventing the activation process that allows osteoclasts to work. By preventing osteoclasts from functioning normally, 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 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, nausea, shortness of breath, diarrhea, and headache. These are not all the possible side effects of Xgeva. Talk to your doctor about what to expect or if you experience any changes that concern you during treatment with Xgeva.

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 possible 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 (prescription and over-the-counter), 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.

Receiving Xgeva

Xgeva is administered via a subcutaneous (under the skin) injection into the upper arm, upper thigh, or abdomen, typically given once every 4 weeks, and may be given more frequently in the first few weeks of treatment depending on exactly which condition is being treated. 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 by your doctor, and not to stop taking Xgeva or any accompanying medications on your own. Patients should talk to their doctor if they have any questions, or if they have questions regarding their Xgeva regimen.1

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