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U.S. Department of Health and Human Services
National Pharmacy & Therapeutics Committee

Pharmacovigilance Drug Safety Communication

Based on a completed U.S. Food and Drug Administration (FDA) review of available information, the FDA has concluded that the osteoporosis medicine denosumab (Prolia®) increases the risk of severe hypocalcemia in patients with advanced chronic kidney disease (CKD), particularly patients on dialysis. In patients with advanced CKD taking denosumab, severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death. As a result, the FDA is revising the denosumab prescribing information to include a new Boxed Warning communicating this increased risk. FDA is adding this updated information to the patient Medication Guide Exit Disclaimer: You Are Leaving www.ihs.gov  and the denosumab Risk Evaluation and Mitigation Strategy (REMS Exit Disclaimer: You Are Leaving www.ihs.gov ).

Denosumab is a monoclonal antibody that is used to increase bone mass and reduce the risk for fractures. Denosumab blocks a protein called RANK (receptor activator of nuclear factor kappa beta). Blocking RANK reduces osteoclast function which is believe to result in decreased bone resorption.

Recommendations for Patients

  • Do not stop taking denosumab without first consulting your health care professional.
  • Read the patient Medication Guide Exit Disclaimer: You Are Leaving www.ihs.gov  every time you receive your injection of denosumab because there may be new or important additional information about this medicine.
  • Tell your health care professional if you experience any symptoms of low blood calcium levels such as confusion, unusual tingling or numbness in the hands, arms, legs, or feet; painful or uncontrolled muscle spasms or cramps; face twitching, voice box or lung spasms causing difficulty breathing; vomiting; seizures; or irregular heart rhythm.

Recommendations for Health Care Providers

  • Inform patients about the risk of severe hypocalcemia when prescribing denosumab.
  • Be aware that most of the severe hypocalcemia events occur 2 to 10 weeks following denosumab injection, with the greatest risk for hypocalcemia occurring during Weeks 2 to 5.
  • Explain the signs and symptoms of severe hypocalcemia to patients and tell them to seek medical attention if they experience symptoms.
  • Involving a health care professional with expertise in the diagnosis and management of CKD-MBD (mineral and bone disorder), such as a nephrologist, when determining the appropriateness of initiating and continuing denosumab in patients with advanced CKD.
  • Assess the risks in patients with advanced CKD based on patient selection and risk factors for hypocalcemia: assess kidney function, identify evidence of CKD-MBD, and check blood calcium levels.
  • Correcting hypocalcemia, and supplementing with calcium and activated vitamin D prior to and during denosumab treatment may decrease the risk of severe hypocalcemia and any associated complications.
  • Following denosumab administration, close monitoring of serum calcium levels and prompt management of severe hypocalcemia is critical to reduce the risk of complications such as seizures and arrhythmias.
Report suspected adverse events with denosumab and other medications to the MedWatch program Exit Disclaimer: You Are Leaving www.ihs.gov  as recommended in the Indian Health Manual. Please include “IHS” in the Reporter Section (section G) of the form. Instructions for reporting can be found online at the NPTC Pharmacovigilance website.

The complete Drug Safety Communication can be viewed on the FDA website Exit Disclaimer: You Are Leaving www.ihs.gov .