FDA Adds Boxed Warning to Prolia, Cautions Medication Could Cause Severe Hypocalcemia

Patients with mineral or bone disorders or who suffer from chronic kidney disease and take Prolia are particularly at risk for developing the illness.

The U.S. Food and Drug Administration (FDA) in White Oak, Md., on June 5, 2023. Madalina Vasiliu/The Epoch Times

Prolia (denosumab), a medication prescribed to treat osteoporosis, will now come with a boxed warning that taking it could increase a patient’s risk of developing low blood calcium levels, a condition known as hypocalcemia.

Patients with mineral or bone disorders or who suffer from chronic kidney disease and take Prolia are particularly at risk for developing the illness. According to the U.S. Food and Drug Administration (FDA), severe hypocalcemia can present with symptoms or without; common symptoms include the following:

• Confusion.
• Seizures.
• Arrhythmia.
• Fainting.
• Facial twitching.
• Uncontrolled muscle spasms.
• Weakness.
• Tingling.
• Numbness.

Some patients with advanced chronic kidney disease were hospitalized, experienced life-threatening events, or died as a result of severe hypocalcemia.

“This warning and new labeling contains information to help reduce this risk, including appropriate patient selection for Prolia treatment, increased monitoring of blood calcium levels, and other strategies,” the FDA press release noted.

Prolia is a monoclonal antibody often used by postmenopausal women at an increased risk of fracture and who have a difficult time tolerating other therapies. The drug is injected once every six months by a health care professional. Common side effects include back pain, muscle pain, and arm and leg pain. It was first approved in June 2010 for women and later approved to treat men with osteoporosis.

According to the FDA, an estimated 2.2 million pre-filled Prolia syringes were sold to U.S. health care settings in 2022. The boxed warning is the most prominent type of warning the FDA requires for medications.

The label update comes after the FDA first issued a safety alert in November 2022 about the drug’s potential risk for hypocalcemia in women on dialysis. The safety alert was issued after initial results from the drug’s manufacturer study indicated an increased risk of hypocalcemia in patients with advanced kidney disease.

Findings of the FDA’s Investigation

The new boxed warning comes after the FDA evaluated studies by the Centers for Medicare & Medicaid Services (CMS). The results showed “a significant increase in the risk of developing severe hypocalcemia with Prolia treatment compared to another class of osteoporosis medicines called bisphosphonates,” the FDA reported.

The data analyzed by the FDA showed that 41 percent of women on dialysis developed severe hypocalcemia during the first 12 weeks of treatment on Prolia, compared to 2 percent of patients taking bisphosphonates.

The condition typically developed between two to 10 weeks after each Prolia injection, with the greatest risk occurring between weeks two and five.

The evaluation also included a review of 25 cases submitted to the FDA spanning 11 years. The cases included patients with chronic kidney disease, some of whom were on dialysis and developed hypocalcemia after starting Prolia.

What Do I Do if I’m at Risk?

While all prescription drugs carry some risk, the FDA noted that “if you have advanced kidney disease, your risk of developing severe hypocalcemia when taking Prolia is increased.” Patients should take adequate calcium and activated vitamin D while taking Prolia. Additionally, patients should not stop taking Prolia without talking with their health care providers first.

The FDA suggests that chronic kidney disease patients discuss risks and benefits with their health care professionals before starting any new medication.

“Health care professionals should consider the risks of hypocalcemia with the use of Prolia in patients on dialysis,” the FDA suggested after its initial November 2022 report.

The FDA urges patients and health care professionals to report any adverse side effects experienced while taking Prolia to the FDA MedWatch program.