FDA Adds Boxed Warning to Prolia Label Regarding Hypocalcemia Risk in CKD

In patients with advanced chronic kidney disease (CKD), treatment with Prolia (denosumab) increases the risk of severe hypocalcemia, according to an updated Food and Drug Administration (FDA) safety alert.

In November 2022, the FDA had issued a safety communication regarding the possibility of severe hypocalcemia with serious outcomes in patients with advanced CKD treated with the osteoporosis drug. The Agency went on to assess this risk in 2 studies using data from the Centers for Medicare & Medicaid Services.

Findings showed treatment with Prolia significantly increased the risk of developing severe hypocalcemia compared with bisphosphonates, especially in patients with advanced CKD. Severe hypocalcemia typically developed 2 to 10 weeks after each injection with Prolia; the greatest risk was observed between week 2 and 5.

The investigation also included 77 cases submitted to the FDA from July 2010 through May 2021. In these reports, patients with CKD (n=25) had experienced complications of severe hypocalcemia (eg, arrhythmias, confusion, seizures, face twitching, muscle spasms or weakness) following treatment with Prolia.

In response to these findings, the FDA has added a Boxed Warning to the prescribing information for Prolia about the increased risk of severe hypocalcemia in patients with advanced CKD, particularly in patients on dialysis or with mineral and bone disorder (MBD). This information has also been added to the patient Medication Guide and to the Prolia Risk Evaluation and Mitigation Strategy (REMS).

The FDA is recommending that health care providers assess their patients’ renal function before prescribing Prolia. The risk of severe hypocalcemia with Prolia treatment should be considered in patients with advanced CKD. If Prolia is still being considered, calcium blood levels should be obtained and these patients should be assessed for CKD-MBD.

To help reduce the risk of severe hypocalcemia, a health care professional with expertise in the diagnosis and management of CKD-MBD should be involved in the decision-making.  Managing CKD-MBD, correcting hypocalcemia and supplementing with calcium and activated vitamin D before and during Prolia treatment may decrease the risk of severe hypocalcemia. Close monitoring of serum calcium and prompt management of severe hypocalcemia is necessary to minimize the risk of complications.