The Medical Letter on Drugs and Therapeutics
In Brief: Severe Hypocalcemia with Denosumab (Prolia) in Chronic Kidney Disease
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Med Lett Drugs Ther. 2024 Mar 4;66(1697):40   doi:10.58347/tml.2024.1697c
Principal Faculty
  • Mark Abramowicz, M.D., President has disclosed no relevant financial relationships.
  • Jean-Marie Pflomm, Pharm.D., Editor in Chief has disclosed no relevant financial relationships.
Additional Contributor(s)
  • Brinda M. Shah, Pharm.D., Consulting Editor has disclosed no relevant financial relationships.
Upon completion of this activity, the participant will be able to:
  1. Discuss the new warning about the use of denosumab (Prolia) in patients with chronic kidney disease.
 Select a term to see related articles  bisphosphonates   calcium supplements   chronic kidney disease   denosumab   osteoporosis   osteoporosis   postmenopausal osteoporosis   postmenopausal osteoporosis   Prolia   vitamin D   Xgeva 

The FDA is requiring a boxed warning in the label of denosumab (Prolia – Amgen)1, a monoclonal antibody that inhibits osteoclasts, about an increased risk of severe hypocalcemia in patients with advanced chronic kidney disease (CKD; eGFR <30 mL/min/1.73 m2), particularly those on dialysis.2 FDA-approved indications for Prolia are listed in Table 1.

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.

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