Important safety information on crysvita (burosumab) and the risk of severe hypercalcemia in patients with tertiary hyperparathyroidism

CRYSVITA (burosumab) may increase the risk of severe hypercalcemia in patients with underlying tertiary hyperparathyroidism and other risk factors, such as prolonged immobilization, dehydration, hypervitaminosis D, or renal impairment. Audience Healthcare professionals including pediatric and adult endocrinologists, and other specialists who are experienced in the diagnosis and management of rare metabolic bone diseases and who manage, or are likely to manage X-linked hypophosphatemia and FGF23-related hypophosphatemia in tumor-induced osteomalacia. Key messages CRYSVITA (burosumab) may increase the risk of severe hypercalcemia in patients with underlying tertiary hyperparathyroidism and other risk factors. Healthcare professionals are advised that: CRYSVITA should NOT be administered in patients with moderate to severe hypercalcemia until the condition has been adequately managed. Serum calcium and parathyroid hormone levels should be monitored before and during treatment with CRYSVITA. The Canadian Product Monograph for CRYSVITA has been updated to include this information. Background CRYSVITA is indicated for the treatment of: • X-linked hypophosphatemia in adult and pediatric patients 6 months of age and older. • FGF23-related hypophosphatemia in tumor-induced osteomalacia associated with tumors that cannot be curatively resected or localized in adult patients. Mild to moderate elevation of serum calcium levels have been reported in patients treated with CRYSVITA, including some cases occurring at treatment initiation. In several of these reports, a rise in parathyroid hormone levels after starting CRYSVITA was also noted. In the post-market setting, severe hypercalcemia has been reported in patients with underlying tertiary hyperparathyroidism in association with other risk factors for hypercalcemia, such as prolonged immobilization, dehydration, hypervitaminosis D, or renal impairment. CRYSVITA may affect calcium levels through the restoration of phosphate homeostasis. The effect on parathyroid hormone as a result of CRYSVITA inhibition of FGF23 remains unclear. Information for consumers CRYSVITA is used to treat X-linked hypophosphatemia (low levels of phosphate in the blood) in adults and children 6 months of age and older. CRYSVITA is also used to treat hypophosphatemia in adults with tumor-induced osteomalacia (soft bones caused by a type of tumor). CRYSVITA may cause hypercalcemia (high levels of calcium in the blood), especially in patients who already have a condition called tertiary hyperparathyroidism (persistently high levels of parathyroid hormone [a hormone that helps control blood calcium and phosphate levels] in the blood caused by other long-standing conditions) and other risk factors for hypercalcemia, including being immobile for a long time, not drinking enough fluids, taking too much vitamin D, or having kidney problems. CRYSVITA may also be associated with increases in parathyroid hormone. To reduce these risks, healthcare professionals should check the calcium and parathyroid hormone levels in patients’ blood before and during treatment. Mild to moderate hypercalcemia often causes few or no symptoms. When symptoms do occur, they may include constipation, nausea, vomiting, abdominal pain, loss of appetite and excessive urination. Long-term or severe hypercalcemia can result in kidney damage, abnormal heart rhythms and nervous system dysfunction. Patients should discuss any questions or concerns about this information with their healthcare professional. Patients should inform their healthcare professional if they are experiencing any side effects while receiving CRYSVITA. Information for healthcare professionals Healthcare professionals are advised that: • CRYSVITA should NOT be administered in patients with moderate to severe hypercalcemia until the condition has been adequately managed. • Serum calcium and parathyroid hormone levels should be monitored before and during treatment with CRYSVITA. Action taken by Health Canada Health Canada, in collaboration with Kyowa Kirin, Inc., has updated the Canadian Product Monograph for CRYSVITA to include this new information. Health Canada is communicating this important safety information to healthcare professionals and Canadians via the Recalls and Safety Alerts Database on the Healthy Canadians Web Site. This communication will be further distributed through the MedEffect™ e-Notice email notification system. Report health or safety concerns Managing marketed health product-related side effects depends on healthcare professionals and consumers reporting them. Any case of severe hypercalcemia or other serious or unexpected side effects in patients receiving CRYSVITA should be reported to Kyowa Kirin, Inc. Or Health Canada. Kyowa Kirin, Inc. 510 Carnegie Center Drive, Suite 600 Princeton, NJ 08540 USA Tel: 609-919-1100 To correct your mailing address or fax number, contact Kyowa Kirin, Inc. You can report any suspected adverse reactions associated with the use of health products to Health Canada by: • Calling toll-free at 1-866-234-2345; or • Visiting MedEffect Canada's Web page on Adverse Reaction Reporting (http://www.hc-sc.gc.ca/dhp-mps/medeff/report-declaration/index-eng.php) for information on how to report online, by mail or by fax. For other health product inquiries related to this communication, contact Health Canada at: Marketed Health Products Directorate Email: mhpd-dpsc@hc-sc.gc.ca Telephone: 1-613-954-6522 Fax: 1-613-952-7738 Original signed by Eslie Dennis SVP, Chief Medical Officer, Head of Medical Affairs

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Brand: Crysvita.