The US FDA has cautioned about the risk of severe hypocalcemia with the use of denosumab in patients with advanced kidney disease on dialysis in a drug safety communication. It has warned about serious adverse outcomes, necessitating hospitalization including death. The Agency is currently investigating the occurrence of this potentially life-threatening adverse effect in dialysis patients.¹

Clinicians should therefore consider the risks of hypocalcemia, it says, when using denosumab in patients on dialysis and ensure adequate calcium and vitamin D supplementation. These patients should be frequently monitored for serum calcium to reduce the chances of hypocalcemia or minimize the severity. They should also warn their patients about the potential risks.

The FDA has also cautioned patients on dialysis to be aware of the symptoms of hypocalcemia such as unusual tingling or numbness in the hands, arms, legs, or feet; painful muscle spasms or cramps; difficulty breathing due to spasm of the larynx or lungs; vomiting; seizures or irregular heart rhythm. It also advises patients to not discontinue the drug on their own. Instead, they should consult their physician without any delay.

Denosumab, a monoclonal antibody, was approved for treatment of osteoporosis in postmenopausal women at risk for fracture in June 2010. The approval was further extended to include men with osteoporosis, steroid-induced osteoporosis, women on aromatase inhibitors for breast cancer and men taking androgen deprivation therapy for prostate cancer. 

Reference

1. Prolia (denosumab) by Amgen: Drug Safety Communication - FDA investigating risk of severe hypocalcemia in patients on dialysis. 22.11.22. Available at: https://www.fda.gov/safety/medical-product-safety-information/prolia-denosumab-amgen-drug-safety-communication-fda-investigating-risk-severe-hypocalcemia-patients.