*Bone complications, also known as skeletal-related events (SREs), are defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression. 22
Convenient 120 mg subcutaneous injection administered once every 4 weeks11
- Intended for subcutaneous route only and should not be administered intravenously, intramuscularly, or intradermally
- The mean elimination half-life of XGEVA® was 28 days.11
- Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®.11
- XGEVA® is contraindicated in patients with known clinically significant hypersensitivity to XGEVA®.11
With XGEVA®, there is no need to adjust dosing for patients with impaired renal function11
Dose adjustments/withholdings in head-to-head phase 3 studies of XGEVA® vs zoledronic acid33‡
Patients with creatinine clearance < 30 mL/min were excluded from XGEVA® clinical trials.33
XGEVA® (n = 2,862)33
- No dose adjustments or dose withholdings were required due to renal function.33
- Zoledronic acid (n = 2,861)33
- Studies in patients with renal impairment11
Two clinical trials were conducted in patients without cancer and with varying degrees of renal function11:
- In one study, patients (n = 55) with varying degrees of renal function (ranging from normal through end-stage renal disease requiring dialysis) received a single 60 mg subcutaneous dose of denosumab.
- In a second study, patients (n = 32) with severe renal dysfunction (creatinine clearance < 30 mL/min and/or on dialysis) were given two 120 mg subcutaneous doses of denosumab.
In both studies, greater risk of developing hypocalcemia was observed with increasing renal impairment and with inadequate/no calcium supplementation. In the second study, hypocalcemia was mild to moderate in severity in 96% of patients.11
In patients with renal impairment, monitor calcium levels and calcium and vitamin intake.11
Q4W = every 4 weeks.
†Correlation with safety and efficacy is unknown.
‡Data from a prespecified integrated analysis of 3 international, phase 3, double-blind, double-dummy, active-controlled trials comparing XGEVA® with zoledronic acid for the prevention of bone complications in patients with bone metastases from solid tumors or multiple myeloma. Patients with creatinine clearance < 30 mL/min were excluded. Per protocol, based on the zoledronic acid label, the intravenous (IV) product was dose-adjusted for baseline creatinine clearance ≤ 60 mL/min. Subsequent dose withholdings and intervals were determined by serum creatinine. Administration of the IV product was withheld for patients who experienced increased serum creatinine during therapy of an increase of ≥ 0.5 mg/dL for patients with normal baseline creatinine (1.4 mg/dL) or an increase of ≥ 1.0 mg/dL for patients with abnormal baseline creatinine (≥ 1.4 mg/dL). Re-exposure to the IV product occurred only if serum creatinine returned to within 10% of the baseline value. The IV product was reinitiated at the same dose as that prior to treatment interruption. No dose adjustments were made and no doses were withheld for increased serum creatinine for the subcutaneous product. Daily supplementation of calcium ≥ 500 mg and vitamin D ≥ 400 IU was recommended. 1,1, 9-129-12