U.S. flag An official website of the United States government

On Oct. 1, 2024, the FDA began implementing a reorganization impacting many parts of the agency. We are in the process of updating FDA.gov content to reflect these changes.

  1. Home
  2. Drugs
  3. Drug Safety and Availability
  4. FDA Drug Safety Podcasts
  5. FDA adds Boxed Warning for increased risk of severe hypocalcemia in patients with advanced chronic kidney disease taking osteoporosis medicine Prolia (denosumab)
  1. FDA Drug Safety Podcasts

FDA adds Boxed Warning for increased risk of severe hypocalcemia in patients with advanced chronic kidney disease taking osteoporosis medicine Prolia (denosumab)

FDA Drug Safety Podcast

Claim 0.5 CE credit (CME/AAPA/CNE/CPE/CPT/CPH) by listening to our podcast and responding to the questions

Listen

Welcome to the FDA Drug Safety Podcast for health care professionals from the Division of Drug Information.

Based on a completed FDA review of available information, we have concluded that the osteoporosis medicine Prolia (active ingredient denosumab) increases the risk of severe hypocalcemia, very low blood calcium levels, in patients with advanced chronic kidney disease (or CKD), particularly patients on dialysis. Severe hypocalcemia appears to be more common in patients with CKD who also have a condition known as mineral and bone disorder (or CKD-MBD). In patients with advanced CKD taking Prolia, severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death. As a result, on January 19, 2024, we are revising the Prolia prescribing information to include a new Boxed Warning, FDA’s most prominent warning, communicating this increased risk.

Severe hypocalcemia can be asymptomatic or may present with symptoms that include confusion; seizures; irregular heart rhythm; fainting; face twitching; uncontrolled muscle spasms; or weakness, tingling, or numbness in parts of the body.

We are adding a Boxed Warning to the Prolia prescribing information about the significant risk of developing severe hypocalcemia in patients with advanced CKD. This warning and new labeling contains information to help reduce this risk, including appropriate patient selection for Prolia treatment, increased monitoring of blood calcium levels, and other strategies. We are also adding this updated information to the patient Medication Guide and the Prolia Risk Evaluation and Mitigation Strategy (or REMS), a drug safety program required by FDA to help ensure that Prolia’s benefits outweigh its risks.

It is important that the appropriateness of Prolia treatment in patients with advanced CKD be determined by a health care professional with expertise in the diagnosis and management of CKD-MBD including renal osteodystrophy, a complication that weakens bone. Treating bone disease in patients with advanced and dialysis-dependent CKD is challenging because of the difficulty in diagnosing and confirming the underlying altered bone metabolism responsible for the low bone mass and increased fracture risk, and the complex benefit-risk considerations of approved osteoporosis treatments in this population.

Before prescribing Prolia, health care professionals should assess their patients’ kidney function. For patients with advanced CKD, particularly those on dialysis, health care professionals should consider the risk of severe hypocalcemia with Prolia in the context of other available treatments for osteoporosis. If Prolia is still being considered for these patients, for initial or continued use, check their calcium blood levels and assess them for evidence of CKD-MBD.

Side effects involving Prolia should be reported to FDA’s MedWatch reporting program at www.fda.gov/medwatch.

A link to the full communication detailing specific information for health care professionals and the complete Data Summary can be found at www.fda.gov/drugsafetycommunications. If you have drug questions, you can reach us at druginfo@fda.hhs.gov. And follow us on X (formerly Twitter) @FDA_Drug_Info. Thank you for listening.

Back to Top