Risk of severe hypocalcemia in patients on dialysis receiving denosumab
FDA is investigating the risk of severe hypocalcemia with serious outcomes, including hospitalization and death, in patients with advanced kidney disease on dialysis treated with the osteoporosis medicine denosumab (Prolia®).
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. Denosumab is known to increase the risk of hypocalcemia especially in patients predisposed to hypocalcemia and disturbances of mineral metabolism or severe renal impairment [creatinine clearance <30 mL/min] or receiving dialysis).
Interim results from ongoing safety studies suggests an increased risk of hypocalcemia with denosumabb in patients with advanced kidney disease. Adverse event reports submitted to the FDA MedWatch program show severe and symptomatic hypocalcemia, including hospitalization and death in patients with advanced kidney disease treated with denosumab. Preliminary results from a separate internal FDA study investigating the risk of hypocalcemia suggest that patients on dialysis treated with denosumab are at substantial risk for severe and symptomatic hypocalcemia, including hospitalization and death.
The FDA continues to investigate the safety of denosumab in patients with advanced kidney disease on dialysis.
Recommendations for Patients
- Do not stop taking denosumab without first consulting your health care professional.
- Tell your health care professional if you experience any symptoms of low blood calcium levels such as unusual tingling or numbness in the hands, arms, legs, or feet; painful muscle spasms or cramps; voice box or lung spasms causing difficulty breathing, vomiting, seizures, or irregular heart rhythm.
Recommendations for Health Care Providers
- Consider the risks of hypocalcemia with the use of denosumab in patients on dialysis.
- Provide adequate calcium and vitamin D supplementation and frequent blood calcium monitoring, possibly more often than is already being conducted, to help decrease the likelihood or severity of adverse events. Advise patients on dialysis to immediately seek help if they experience symptoms of hypocalcemia.
- Report suspected adverse events with denosumab and other medications to the MedWatch program as recommended in the Indian Health Manual. Instructions for reporting can be found online at the NPTC Pharmacovigilance website.
The complete Drug Safety Communication can be viewed on the FDA website.