FDA Adds Boxed Warning to Denosumab for Increased Risk of Severe Hypocalcemia in Patients With Advanced Chronic Kidney Disease

January 19, 2024

On January 19, 2024, the U.S. Food and Drug Administration (FDA) announced (https://www.fda.gov/safety/medical-product-safety-information/prolia-denosumab-drug-safety-communication-fda-adds-boxed-warning-increased-risk-severe-hypocalcemia) that it is adding a boxed warning to the denosumab (Prolia®prescribing information (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process&utm_medium=email&utm_source=govdelivery) about the significant risk of developing severe hypocalcemia in patients with advanced chronic kidney disease (CKD). The warning and new labeling contain information to help reduce that risk, including appropriately selecting patients for denosumab treatment, increased monitoring of blood calcium levels, and other strategies.

FDA update

After reviewing available information, FDA said that it concluded that denosumab increases the risk of severe hypocalcemia in patients with advanced CKD, particularly those on dialysis or who also have mineral and bone disorder (CKD-MBD). In patients with advanced CKD taking denosumab, severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death.

Severe hypocalcemia can be asymptomatic or may present with symptoms such as confusion, seizures, irregular heart rhythm, fainting, face twitching, uncontrolled muscle spasms, or weakness, tingling, or numbness.

Patient Education

FDA advised (https://www.fda.gov/safety/medical-product-safety-information/prolia-denosumab-drug-safety-communication-fda-adds-boxed-warning-increased-risk-severe-hypocalcemia) the following for patients:

Guidance for Healthcare Professionals

Treating bone disease in patients with advanced and dialysis-dependent CKD is challenging because diagnosing and confirming the underlying altered bone metabolism responsible for the low bone mass and increased fracture risk is difficult and the benefit-risk considerations of approved osteoporosis treatments in this population are complex. FDA advised (https://www.fda.gov/safety/medical-product-safety-information/prolia-denosumab-drug-safety-communication-fda-adds-boxed-warning-increased-risk-severe-hypocalcemia):

Healthcare professionals and patients should report adverse events or side effects related to the use of this product to FDA’s MedWatch Safety Information and Adverse Event Reporting Program (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm?utm_medium=email&utm_source=govdelivery).

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