Slideshows Images Quizzes

Copyright © 2018 by RxList Inc. RxList does not provide medical advice, diagnosis or treatment. See additional information.

Xgeva

Last reviewed on RxList: 2/25/2020
Xgeva Side Effects Center

What Is Xgeva?

Xgeva (denosumab) Injection is a human IgG2 monoclonal antibody used to treat bone problems that may occur with cancer that has spread (metastasized) to the bones.

What Are Side Effects of Xgeva?

Common side effects of Xgeva include:

Tell your doctor if you have serious side effects of Xgeva including:

Dosage for Xgeva

The recommended dose of Xgeva is 120 mg administered as a subcutaneous injection every 4 weeks in the upper arm, upper thigh, or abdomen.

What Drugs, Substances, or Supplements Interact with Xgeva?

No formal drug-drug interaction trials have been conducted with Xgeva. Tell your doctor all medications and supplements you use.

Xgeva During Pregnancy and Breastfeeding

Xgeva must not be used during pregnancy. It may harm a fetus. Discuss birth control with your doctor. If you become pregnant or think you may be pregnant, tell your doctor. It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breastfeeding while using this medication is not recommended.

Additional Information

Our Xgeva (denosumab) Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Skin Cancer Symptoms, Types, Images See Slideshow
Xgeva Consumer Information

Get emergency medical help if you have signs of an allergic reaction: itching, rash, hives; difficult breathing; feeling like you might pass out; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • new or unusual pain in your thigh, hip, or groin;
  • trouble breathing;
  • low red blood cells (anemia)--pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; o
  • low levels of calcium in your blood (hypocalcemia)--numbness or tingly feeling around your mouth or in your fingers or toes, muscle tightness or contraction, overactive reflexes.

After you stop using Xgeva, tell your doctor if you have symptoms of high calcium levels (hypercalcemia) such as nausea, vomiting, headache, confusion, lack of energy, or tiredness.

Common side effects may include:

  • feeling weak or tired;
  • nausea, vomiting, loss of appetite;
  • diarrhea, constipation;
  • headache, back pain; or
  • pain or swelling in your arms or legs.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Xgeva (Denosumab)

Xgeva Professional Information

SIDE EFFECTS

The following adverse reactions are discussed below and elsewhere in the labeling:

  • Hypersensitivity [see WARNINGS AND PRECAUTIONS]
  • Hypocalcemia [see WARNINGS AND PRECAUTIONS and Use In Specific Populations]
  • Osteonecrosis of the Jaw [see WARNINGS AND PRECAUTIONS]
  • Atypical Subtrochanteric and Diaphyseal Femoral Fracture [see WARNINGS AND PRECAUTIONS]
  • Hypercalcemia following treatment discontinuation in patients with giant cell tumor of bone and in patients with growing skeletons [see WARNINGS AND PRECAUTIONS and Use In Specific Populations]
  • Multiple vertebral fractures (MVF) following treatment discontinuation [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Bone Metastasis From Solid Tumors

The safety of Xgeva was evaluated in three randomized, double-blind, double-dummy trials [see Clinical Trials] in which a total of 2841 patients with bone metastasis from prostate cancer, breast cancer, or other solid tumors, or lytic bony lesions from multiple myeloma received at least one dose of Xgeva. In Studies 20050136, 20050244, and 20050103, patients were randomized to receive either 120 mg of Xgeva every 4 weeks as a subcutaneous injection or 4 mg (dose adjusted for reduced renal function) of zoledronic acid every 4 weeks by intravenous (IV) infusion. Entry criteria included serum calcium (corrected) from 8 to 11.5 mg/dL (2 to 2.9 mmol/L) and creatinine clearance 30 mL/min or greater. Patients who had received IV bisphosphonates were excluded, as were patients with prior history of ONJ or osteomyelitis of the jaw, an active dental or jaw condition requiring oral surgery, non-healed dental/oral surgery, or any planned invasive dental procedure. During the study, serum chemistries including calcium and phosphorus were monitored every 4 weeks. Calcium and vitamin D supplementation was recommended but not required.

The median duration of exposure to Xgeva was 12 months (range: 0.1-41) and median duration on-study was 13 months (range: 0.1-41). Of patients who received Xgeva, 46% were female. Eighty-five percent were White, 5% Hispanic/Latino, 6% Asian, and 3% Black. The median age was 63 years (range: 18-93). Seventy-five percent of patients who received Xgeva received concomitant chemotherapy.

The most common adverse reactions in patients (incidence greater than or equal to 25%) were fatigue/asthenia, hypophosphatemia, and nausea (see Table 1). The most common serious adverse reaction was dyspnea. The most common adverse reactions resulting in discontinuation of Xgeva were osteonecrosis and hypocalcemia.

Table 1: Selecteda Adverse Reactions of Any Severity (Studies 20050136, 20050244, and 20050103)

Body SystemXgeva
n = 2841 %
Zoledronic Acid
n = 2836 %
GASTROINTESTINAL
Nausea3132
Diarrhea2019
GENERAL
Fatigue/Asthenia4546
INVESTIGATIONS
Hypocalcemiab189
Hypophosphatemiab3220
NEUROLOGICAL
Headache1314
RESPIRATORY
Dyspnea2118
Cough1515
a Adverse reactions reported in at least 10% of patients receiving Xgeva in Studies 20050136, 20050244, and 20050103, and meeting one of the following criteria:
  • At least 1% greater incidence in Xgeva-treated patients, or
  • Between-group difference (either direction) of less than 1% and more than 5% greater incidence in patients treated with zoledronic acid compared to placebo (US Prescribing Information for zoledronic acid)
b Laboratory-derived and below the central laboratory lower limit of normal [8.3 -8.5 mg/dL (2.075 -2.125 mmol/L) for calcium and 2.2 -2.8 mg/dL (0.71 -0.9 mmol/L) for phosphorus]

Severe Mineral/Electrolyte Abnormalities

  • Severe hypocalcemia (corrected serum calcium less than 7 mg/dL or less than 1.75 mmol/L) occurred in 3.1% of patients treated with Xgeva and 1.3% of patients treated with zoledronic acid. Of patients who experienced severe hypocalcemia, 33% experienced 2 or more episodes of severe hypocalcemia and 16% experienced 3 or more episodes [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].
  • Severe hypophosphatemia (serum phosphorus less than 2 mg/dL or less than 0.6 mmol/L) occurred in 15.4% of patients treated with Xgeva and 7.4% of patients treated with zoledronic acid.

Osteonecrosis Of The Jaw (ONJ)

In the primary treatment phases of Studies 20050136, 20050244, and 20050103, ONJ was confirmed in 1.8% of patients in the Xgeva group (median exposure of 12.0 months; range: 0.1-40.5) and 1.3% of patients in the zoledronic acid group. The trials in patients with breast (Study 20050136) or prostate (Study 20050103) cancer included an Xgeva open-label extension treatment phase where patients were offered Xgeva 120 mg once every 4 weeks (median overall exposure of 14.9 months; range: 0.1-67.2). The patient-year adjusted incidence (number of events per 100 patient years) of confirmed ONJ was 1.1% during the first year of treatment, 3.7% in the second year, and 4.6% per year thereafter. The median time to ONJ was 20.6 months (range: 4-53) [see WARNINGS AND PRECAUTIONS].

In a placebo-controlled clinical trial with an extension treatment phase evaluating Xgeva for the prevention of bone metastases in patients with non-metastatic prostate cancer (a patient population for which Xgeva is not indicated), with longer treatment exposure of up to 7 years, the patient-year adjusted incidence (number of events per 100 patient years) of confirmed ONJ was 1.1% during the first year of treatment, 3.0% in the second year, and 7.1% per year thereafter.

Atypical Subtrochanteric And Diaphyseal Fracture

In the clinical trial program, atypical femoral fracture has been reported in patients treated with Xgeva and the risk increased with longer duration of treatment. Events have occurred during treatment and after treatment was discontinued [see WARNINGS AND PRECAUTIONS].

Multiple Myeloma

The safety of Xgeva was evaluated in an international, randomized (1:1), double-blind, active-controlled trial of patients with newly diagnosed multiple myeloma with treatment through disease progression [see Clinical Trials]. In this trial, patients received 120 mg Xgeva every 4 weeks as a subcutaneous injection (n = 850) or 4 mg (dose adjusted for renal function) of zoledronic acid intravenously (IV) every 4 weeks by IV infusion (n = 852). Entry criteria included serum calcium (corrected) from 8 to 11.5 mg/dL (2 to 2.9 mmol/L) and creatinine clearance 30 mL/min or greater. Patients who had received IV bisphosphonates were excluded, as were patients with prior history of ONJ or osteomyelitis of the jaw, an active dental or jaw condition requiring oral surgery, non-healed dental/oral surgery, or any planned invasive dental procedure. During the study, serum chemistries including calcium and phosphorus were monitored every 4 weeks. Calcium and vitamin D supplementation was recommended but not required.

The median duration of exposure to Xgeva was 16 months (range: 1-50) and median duration on-study was 17 months (range: 0-49). Of patients who received Xgeva, 46% were female, 83% percent were White, 13% Asian, 3% Black or African American, and 4% Hispanic/Latino. The median age of the patients randomized to Xgeva was 63 years (range: 29-91) and all patients who received Xgeva received concomitant anti-myeloma chemotherapy.

The adverse reaction profile of Xgeva in patients with multiple myeloma, Study 20090482, was similar to that observed in Studies 20050136, 20050244, and 20050103. The most common adverse reactions (incidence ≥ 10%) were diarrhea (34%), nausea (32%), anemia (22%), back pain (21%), thrombocytopenia (19%), peripheral edema (17%), hypocalcemia (16%), upper respiratory tract infection (15%), rash (14%), and headache (11%). The most common serious adverse reaction (incidence ≥ 5%) was pneumonia (8%). The most common adverse reaction resulting in discontinuation of Xgeva (≥ 1.0%) was osteonecrosis of the jaw.

Hypocalcemia And Hypophosphatemia

Severe hypocalcemia (corrected serum calcium less than 7 mg/dL or less than 1.75 mmol/L) and severe hypophosphatemia (serum phosphorus less than 2 mg/dL or less than 0.6 mmol/L) occurred in 2% and 21% patients treated with Xgeva, respectively.

Osteonecrosis Of The Jaw (ONJ)

In the primary treatment phase of Study 20090482, ONJ was confirmed in 4.1% of patients in the Xgeva group (median exposure of 16 months; range: 1-50) and 2.8% of patients in the zoledronic acid group (median 15 months, range: 1-45 months). At the completion of the double-blind treatment phase of Study 20090482, the patient-year adjusted incidence (number of events per 100 patient years) of confirmed ONJ in the Xgeva group (median exposure of 19.4 months; range 1-52) was 2.0% during the first year of treatment, 5.0% in the second year, and 4.5% per year thereafter. The median time to ONJ was 18.7 months (range: 1-44) [see WARNINGS AND PRECAUTIONS].

Giant Cell Tumor Of Bone

The safety of Xgeva was evaluated in two single-arm trials (Study 20062004 and Study 20040215) [see Clinical Trials] in which a total of 304 adult or skeletally mature adolescent patients with giant cell tumor of bone received at least 1 dose of Xgeva. Patients received 120 mg Xgeva subcutaneously every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Patients receiving concurrent bisphosphonate therapy were excluded from enrollment in both studies. Patients with prior history of ONJ or osteomyelitis of the jaw, an active dental or jaw condition requiring oral surgery, non-healed dental/oral surgery, or any planned invasive dental procedure were excluded from enrollment in Study 20040215. During the trial, serum chemistries including calcium and phosphorus were monitored every 4 weeks. Calcium and vitamin D supplementation was recommended but not required.

Of the 304 patients who received Xgeva, 145 patients were treated with Xgeva for ≥ 1 year, 44 patients for ≥ 2 years, and 15 patients for ≥ 3 years. The median number of doses received was 14 (range: 1-60 doses) and the median number of months on-study was 11 (range: 0-54 months). Fifty-eight percent of the enrolled patients were women and 80% were White. The median age was 33 years (range: 13-83 years); a total of 10 patients were skeletally mature adolescents (13 to 17 years of age).

The adverse reaction profile of Xgeva in patients with giant cell tumor of bone was similar to that reported in Studies 20050136, 20050244, and 20050103. The most common adverse reactions in patients (incidence ≥ 10%) were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity. The most common serious adverse reactions were osteonecrosis of the jaw and osteomyelitis (incidence of 0.7%). The most common adverse reactions resulting in discontinuation of Xgeva were osteonecrosis of the jaw (incidence of 0.7%), and tooth abscess or tooth infection (incidence of 0.7%). The adverse reaction profile appeared similar in skeletally mature adolescents and adults.

Hypocalcemia And Hypophosphatemia
  • Moderate hypocalcemia (corrected serum calcium less than 8 to 7 mg/dL or less than 2 to 1.75 mmol/L) occurred in 2.6% of patients treated with Xgeva.
  • Severe hypophosphatemia (serum phosphorus less than 2 to 1 mg/dL or less than 0.6 to 0.3 mmol/L) occurred in 29 patients (9.5%).
Osteonecrosis Of The Jaw (ONJ)

In Study 20062004 and Study 20040215, ONJ was confirmed in 4 of 304 (1.3%) patients who received Xgeva. The median time to ONJ was 16 months (range: 13-20 months) [see WARNINGS AND PRECAUTIONS].

Hypercalcemia Of Malignancy

Xgeva was evaluated in an open-label, single-arm trial (Study 20070315) in which 33 patients with hypercalcemia of malignancy (with or without bone metastases) refractory to treatment with intravenous bisphosphonate therapy were enrolled [see Clinical Trials].

The adverse reaction profile of Xgeva in patients with hypercalcemia of malignancy was similar to that reported in Studies 20050136, 20050244, 20050103, 20062004, and 20040215. Adverse reactions occurring in greater than 20% of patients were nausea (30%), dyspnea (27%), decreased appetite (24%), headache (24%), peripheral edema (24%), vomiting (24%), anemia (21%), constipation (21%), and diarrhea (21%). The following adverse reactions of Grade 3 or greater severity related to study therapy were reported on-study: fatigue (3%) and infection (6%). Grade 3 laboratory abnormalities included hypomagnesemia (3%), hypokalemia (3%), and hypophosphatemia (76%) of patients. No deaths on-study were related to Xgeva therapy.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Xgeva. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • Hypocalcemia: Severe symptomatic hypocalcemia, including fatal cases [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].
  • Hypercalcemia: Severe symptomatic hypercalcemia following treatment discontinuation can occur [see ADVERSE REACTIONS and WARNINGS AND PRECAUTIONS].
  • Hypersensitivity, including anaphylactic reactions [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].
  • Musculoskeletal pain, including severe musculoskeletal pain. Positive re-challenge has been reported.
  • Lichenoid drug eruptions (e.g., lichen planus-like reactions).
  • Alopecia.

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to denosumab in the studies described below with the incidence of antibodies to other studies or to other products may be misleading.

Using an electrochemiluminescent bridging immunoassay, less than 1% (7/2758) of patients with osseous metastases treated with denosumab doses ranging from 30-180 mg every 4 weeks or every 12 weeks for up to 3 years tested positive for binding antibodies. None of the 304 patients with giant cell tumor of bone in Study 20062004 and Study 20040215 tested positive for binding antibodies. In multiple myeloma patients in Study 20090482, 1 out of 199 patients with a post-baseline result, tested positive for binding antibodies. No patient with positive binding antibodies tested positive for neutralizing antibodies as assessed using a chemiluminescent cell-based in vitro biological assay. There was no evidence of altered pharmacokinetic profile, toxicity profile, or clinical response associated with binding antibody development.

Read the entire FDA prescribing information for Xgeva (Denosumab)

Related Resources for Xgeva

Related Health

Read the Xgeva User Reviews »

© Xgeva Patient Information is supplied by Cerner Multum, Inc. and Xgeva Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

SLIDESHOW

Skin Cancer Symptoms, Types, Images See Slideshow

Health Solutions From Our Sponsors

CONTINUE SCROLLING FOR RELATED SLIDESHOW