FDA Investigates Prolia’s Association with Severe Hypocalcemia

In a Drug Safety Communication issued on November 22, 2022, the FDA announced that it is investigating Prolia and its associations with severe hypocalcemia — low blood calcium levels — in patients on dialysis. This investigation is based on interim results from a safety study on the medication.

Prolia, also known as denosumab, was approved in June 2010 to treat osteoporosis in postmenopausal women and minimize the risk of bone fracture. The drug was also approved to treat women receiving aromatase inhibitor therapy and men with osteoporosis, glucocorticoid-induced osteoporosis, and bone loss due to androgen deprivation therapy. The medication blocks the receptor activator of nuclear factor kappa beta to prevent osteoclasts from breaking down bone. It is currently administered by injection every six months.

According to the FDA statement, approval of this medication was contingent on the manufacturer conducting a long-term study on the drug’s safety profile. Interim results of the study brought about concerns as many patients had severe symptomatic hypocalcemia. The patients experiencing this adverse side effect were patients with advanced kidney disease.

The FDA communication states, “Because of the frequency and seriousness of these risks, we are alerting healthcare professionals and patients about them and that we are continuing to evaluate this potential safety issue with Prolia use in patients with advanced kidney disease, particularly those on dialysis. We will communicate our final conclusions and recommendations when we have completed our review or have more information to share.”

The organization advises patients on Prolia to discuss their risks with a licensed healthcare professional who has detailed information on the patient's medical history and background. Additionally, patients are advised to inform their healthcare provider if they experience tingling or numbness in their limbs and extremities, muscle spasms or cramps, voice box spasms causing difficulty breathing, vomiting, seizures, or irregular heart rhythm, as these symptoms are typically associated with hypocalcemia.

Beyond patient vigilance, the FDA advises all providers to assess the risk of hypocalcemia in patients on dialysis taking Prolia. Should the patient continue on the medication, providers are urged to closely monitor calcium levels and supplementation and provide educational information on the signs of hypocalcemia.