Denosumab is also available as Xgeva for prevention of skeletal-related events or treatment of hypercalcemia in patients with malignancies. The warning has not been added to the Xgeva label.

An FDA analysis of studies from the Centers for Medicare & Medicaid Services found that use of Prolia in patients with advanced CKD was associated with a significant increase in the risk of developing severe hypocalcemia, compared to use of bisphosphonates. In 2804 dialysis-dependent patients treated for osteoporosis, the incidence of severe hypocalcemia was 41.1% with denosumab, compared to 2.0% with oral bisphosphonates. Prolia is given subcutaneously once every 6 months. Severe hypocalcemia, which generally occurred 2-10 weeks after each injection of the drug, can lead to muscle spasms, seizures, cardiac arrhythmias, and death.2,3

In patients with advanced CKD, pre-existing hypocalcemia should be corrected before starting Prolia and serum calcium levels should be monitored weekly for the first month of treatment with the drug and monthly thereafter. Adequate calcium and vitamin D supplementation can decrease the risk of hypocalcemia.