Watch for Severe Hypocalcemia in Dialysis Patients on Prolia, FDA Warns

The FDA said it's looking into the risk of severe hypocalcemia among patients on dialysis receiving denosumab (Prolia), citing the potential for severe outcomes, including hospitalization and death.

In a safety alert issued on Tuesday, the agency referred to interim results from maker Amgen's ongoing safety study of denosumab, which suggested an increased risk of hypocalcemia in patients with advanced kidney disease. The safety study, required upon denosumab's initial approval, was conducted in men and postmenopausal women with osteoporosis.

Separately, preliminary results from an internal FDA study to look more closely into the possible link identified a "substantial risk for severe and symptomatic hypocalcemia" among patients on dialysis treated with denosumab.

The announcement is intended to alert healthcare professionals and patients to the potential risk, and the FDA urged patients to not stop denosumab treatment without consulting their clinician first. The safety alert also instructed patients to watch out for symptoms of low blood calcium, which can include unusual tingling or numbness in the hands, arms, legs, or feet; painful muscle spasms or cramps; voice box or lung spasms that may cause difficulty breathing; along with vomiting, seizures, or irregular heart rhythm.

As for clinicians, the FDA recommended they weigh the pros and cons of denosumab treatment for patients on dialysis. In the event this treatment is used, denosumab should be paired with sufficient calcium and vitamin D supplementation plus frequent blood calcium monitoring -- maybe even more than is already being done. The FDA also said to tell patients to watch out for any signs of hypocalcemia and to seek immediate medical attention in this event.

First approved in 2010 for postmenopausal women with osteoporosis at high risk for bone fracture, denosumab later picked up indications to treat men with osteoporosis, glucocorticoid-induced osteoporosis, and bone loss in men receiving androgen deprivation therapy for prostate cancer and in women receiving aromatase inhibitor therapy for breast cancer. Administered via injection every 6 months, the treatment works by blocking the protein receptor activator of nuclear factor kappa beta (RANK) and prevents osteoclasts from breaking down bone in the body. Denosumab is also approved under the trade name Xgeva to reduce the risk of bone-related events in certain cancer patients.

The FDA said it will continue to monitor these safety concerns for all patients with advanced kidney disease on denosumab, but particularly those on dialysis, and will communicate its "final conclusions and recommendations when we have completed our review or have more information to share."

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