FDA Warns Prolia May Cause Severe Low Blood Calcium Levels

The U.S. Food and Drug Administration (FDA) has added a new black box label warning about the potential side effects of Prolia, indicating that the osteoporosis drug can increase the risk of severe hypocalcemia among kidney disease patients.

The new labeling requirements were announced in a Prolia drug safety communication issued on January 19, placing the information prominently in a black box at the top of the label, which is the strongest warning the agency can require a drug to carry.

Prolia (denosumab) is an osteoporosis treatment drug that was first introduced in 2010, as the first drug ever approved by the FDA specifically to treat postmenopausal women with osteoporosis, who are at high risk for bone fracture. The drug’s use was later expanded to include approval for marketing as a treatment among men with osteoporosis, as well as women receiving aromatase inhibitor therapy for breast cancer.

The drug is administered through an injection by a healthcare professional once every six months, and is advertised to work by blocking a protein called RANK (receptor activator of nuclear factor kappa beta). Prolia also is designed to help the body prevent bone cells from breaking down bone in the body.

Prolia Hypocalcemia Risks

“Based on a completed FDA review of available information, FDA has concluded that the osteoporosis medicine Prolia increases the risk of severe hypocalcemia, very low blood calcium levels, in patients with advanced chronic kidney disease (CKD), particularly patients on dialysis,” the safety communication warns. “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 FDA indicates that severe hypocalcemia can cause severe adverse health effects, including hospitalization and death. It can be asymptomatic, or include symptoms such as seizures, confusion, irregular heart rhythm, fainting, face twitching and uncontrolled muscle spasms, weakness, tingling, or numbness, the agency warns.

The Prolia safety investigation was launched by the FDA in November 2022 after determining that dialysis patients being treated with Prolia were developing hypocalcemia at alarming rates.

Prolia Boxed Warning

The “boxed warning” will be added to the Prolia prescribing information, medication guide and the Prolia Risk Evaluation and Mitigation Strategy (REMS) program. It warns that patients with advanced CKD face a significant risk of developing severe hypocalcemia.

The FDA says it will help doctors choose appropriate patients for Prolia treatment and advises doctors to perform increased monitoring of blood calcium levels in Prolia patients.

Patients considering taking Prolia are advised to talk to their health care provider about their kidney function and the risk of severe hypocalcemia. Those already taking the drug are recommended to maintain adequate calcium and vitamin D intake during the treatment. Those with advanced kidney disease taking Prolia, especially those on dialysis, should receive frequent monitoring of calcium levels in their blood, particularly during the first two to 10 weeks after each Prolia injection, the FDA recommends.

However, the FDA urges patients not to stop taking Prolia without consulting their health care professional, as stopping, delaying or skipping Prolia treatment can increase the risk of bone fracture, including fractures of the spine.

Prolia Bone Fracture Side Effects

While Prolia has been advertised for nearly 14 years as an injection that helps prevents the development of bone-removing cells and to reduce fracture risks, reports released shortly after the drugs approval found patients receiving Prolia injections faced triple the risk of hip fractures, femur fractures and other bone problems, and there were also concerns over infections and dermatologic adverse events.

In 2012, Health Canada and Amgen released a Prolia bone fracture warning letter, which was designed to alert Canadian users to an increased risk of atypical femur fractures that may occur with little or no trauma to the thigh bone; the thickest, largest, and purportedly strongest, bone in the human body.

In 2013, the prominent consumer watchdog group Public Citizen raised concerns about the Prolia fracture risks, noting that the drug has been linked to reports of bone brakes following little or no trauma. The group indicated that Prolia appears to interfere with bone metabolism and the body’s immune system, resulting in breaks that may occur in situations that would not typically result in such an injury. In 2019, Public Citizen called for a Black Box warning for Prolia fracture risks.

As a result of Amgen’s failure to adequately warn about the risk of fracture problems from Prolia, some patients have pursued Prolia lawsuits against the drug manufacturer.