These highlights do not include all the information needed to use XGEVA鈩?safely and effectively. See full prescribing information for XGEVA. Xgeva (denosumab)injection, for subcutaneous useInitial U.S. Approval: 2010
Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

Xgeva is not indicated for the prevention of skeletal-related events in patients with multiple myeloma [see Clinical Trials (14)].

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

Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia [see Warnings and Precautions (5.1)].

Visually inspect Xgeva for particulate matter and discoloration prior to administration. Xgeva is a clear, colorless to pale yellow solution that may contain trace amounts of translucent to white proteinaceous particles. Do not use if the solution is discolored or cloudy or if the solution contains many particles or foreign particulate matter.

Prior to administration, Xgeva may be removed from the refrigerator and brought to room temperature (up to 25掳C/77掳F) by standing in the original container. This generally takes 15 to 30 minutes. Do not warm Xgeva in any other way [see How Supplied/Storage and Handling (16)].

Use a 27-gauge needle to withdraw and inject the entire contents of the vial. Do not re-enter the vial. Discard vial after single-use or entry.

120 mg/1.7 mL (70 mg/mL) single-use vial.

None.

Xgeva can cause severe hypocalcemia. Correct pre-existing hypocalcemia prior to Xgeva treatment. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when Xgeva is administered with other drugs that can also lower calcium levels. Advise patients to contact a healthcare professional for symptoms of hypocalcemia [see Adverse Reactions (6.1) and Patient Counseling Information (17)].

Based on clinical trials using a lower dose of denosumab, patients with a creatinine clearance less than 30聽mL/min or receiving dialysis are at greater risk of severe hypocalcemia compared to patients with normal renal function. In a trial of 55 patients, without cancer and with varying degrees of renal impairment, who received a single dose of 60 mg denosumab, 8 of 17 patients with a creatinine clearance less than 30 mL/min or receiving dialysis experienced corrected serum calcium levels less than 8.0 mg/dL as compared to 0 of 12 patients with normal renal function. The risk of hypocalcemia at the recommended dosing schedule of 120 mg every 4 weeks has not been eva luated in patients with a creatinine clearance less than 30 mL/min or receiving dialysis.

Osteonecrosis of the jaw (ONJ) can occur in patients receiving Xgeva, manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials, 2.2% of patients receiving Xgeva developed ONJ; of these patients, 79% had a history of tooth extraction, poor oral hygiene, or use of a dental appliance [see Adverse Reactions (6.1)].

Perform an oral examination and appropriate preventive dentistry prior to the initiation of Xgeva and periodically during Xgeva therapy. Advise patients regarding oral hygiene practi