Healthcare professionals in the European Union will now be issued advice about the risk of severe hypercalcemia in people treated with Crysvita (burosumab). Increases in serum calcium, including severe hypercalcemia, and elevated parathyroid hormone levels have been reported in patients receiving the drug. The risk is particularly pronounced in people with tertiary hyperparathyroidism.

Burosumab is approved for the treatment of X-linked hypophosphatemia, a hereditary disorder of phosphate metabolism, and for osteomalacia due to phosphaturic mesenchymal tumors, which overproduce fibroblast growth factor 23, leading to phosphate loss.

At its September meeting, the European Medicines Agency's Pharmacovigilance Risk Assessment Committee discussed a direct healthcare professional communication to alert clinicians to the risk.

Clinical Recommendations

Patients presenting with moderate-to-severe hypercalcemia exceeding 3.0 mmol/L should not receive burosumab until calcium levels are appropriately managed and normalized. The regulatory update emphasizes the importance of addressing underlying calcium imbalances before initiating therapy.

Patients with moderate-to-severe hypercalcemia (more than 3.0 mmol/L) should not be treated with burosumab until calcium levels are normalized. 

Blood calcium levels should be measured before starting therapy, 1-2 weeks after initiation or any dose adjustment, and every 6 months during treatment. For children aged 1-2 years, testing is recommended every 3 months. Parathyroid hormone levels should also be monitored on the same schedule. 

Clinicians should be aware that additional factors such as hyperparathyroidism, prolonged immobility, dehydration, vitamin D toxicity, or renal impairment may further increase the risk of hypercalcemia.

Product Updates

Crysvita’s product information will be revised to incorporate these monitoring recommendations and include additional adverse effects: hyperparathyroidism, hypercalcemia, hypercalciuria, and increased parathyroid hormone concentrations. 

The new guidance underscores the importance of careful monitoring in patients receiving burosumab to mitigate the risk of severe metabolic complications while allowing clinicians to continue offering this targeted therapy for rare phosphate-wasting disorders.