FDA Adds Boxed Warning to Prolia in Patients with Kidney Disease

The FDA has added a boxed warning to the prescribing information for Amgen’s osteoporosis therapy Prolia (denosumab). Regulators are warning about the increased risk of severe hypocalcemia, very low blood calcium levels, in patients with advanced chronic kidney disease (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 (CKD-MBD), the agency said. In patients with advanced CKD taking Prolia, severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death.

Patients typically developed severe hypocalcemia 2 to 10 weeks following each Prolia injection, with the greatest risk occurring during Weeks 2 to 5.

The FDA also reviewed 25 cases submitted to FDA’s Adverse Event Report System (FAERS) database from July 2010 through May 2021.

"Patient safety is of the utmost importance to Amgen," a company spokesperson told Formulary Watch. "The updated label recognizes a risk of severe hypocalcemia following Prolia administration in patients identified with advanced chronic kidney disease (CKD.) Approximately 3% of treatment naïve Prolia patients with a known level of CKD are classified as having advanced CKD. We remain confident in Prolia and its overall benefit/risk profile."

Prolia was approved in June 2010 to treat postmenopausal women with osteoporosis at high risk for bone fracture. Prolia was later approved to treat men with osteoporosis, glucocorticoid induced osteoporosis, bone loss in men receiving androgen deprivation therapy for prostate cancer and in women receiving aromatase inhibitor therapy for breast cancer. The drug works by blocking a protein called RANK (receptor activator of nuclear factor kappa beta) and helps prevent bone cells called osteoclasts from breaking down bone in the body.

Prolia is administered by injection once every six months. It has a list price $1,736.63 per injection. For commercially insured patients, the Amgen SupportPlus Co-Pay Program offer Prolia for as little as $25 dose. Uninsured patients may be eligible for the Amgen Safety Net Foundation, a nonprofit patient assistance program.

Related: FDA Warns About Prolia in Patients with Kidney Disease

The FDA began investigating a possible link between severe hypocalcemia with serious outcomes, including hospitalization and death, in patients with advanced kidney disease on dialysis in November 2022. At the time, the agency said its interim review of safety study data suggested an increased risk of low calcium levels in the blood in patients with advanced kidney disease.