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Important safety information

Hypocalcemia: Pre-existing hypocalcemia must be corrected before initiating Ospomyv. May worsen, especially in patients with renal impairment. Adequately supplement all patients with calcium and vitamin D. Concomitant use of calcimimetic drugs may also worsen hypocalcemia risk. Evaluate for presence of chronic kidney disease mineral-bone disorder. Monitor serum calcium. ( 5.1 ) Same Active Ingredient: Patients receiving Ospomyv should not receive other denosumab products concomitantly. ( 5.2 ) Hypersensitivity including anaphylactic reactions may occur. Discontinue permanently if a clinically significant reaction occurs. ( 5.3 ) Osteonecrosis of the jaw: Has been reported with denosumab products. Monitor for symptoms. ( 5.4 ) Atypical femoral fractures: Have been reported. Evaluate patients with thigh or groin pain to rule out a femoral fracture. ( 5.5 ) Multiple vertebral fractures have been reported following treatment discontinuation. Patients should be transitioned to another antiresorptive agent if Ospomyv is discontinued. ( 5.6 ) Serious infections including skin infections: May occur, including those leading to hospitalization. Advise patients to seek prompt medical attention if they develop signs or symptoms of infection, including cellulitis. ( 5.7 ) Dermatologic reactions: Dermatitis, rashes, and eczema have been reported. Consider discontinuing Ospomyv if severe symptoms develop. ( 5.8 ) Severe bone, joint, muscle pain may occur. Discontinue use if severe symptoms develop. ( 5.9 ) Suppression of bone turnover: Significant suppression has been demonstrated. Monitor for consequences of bone over-suppression. ( 5.10 ) 5.1 Severe Hypocalcemia and Mineral Metabolism Changes Denosumab products can cause severe hypocalcemia and fatal cases have been reported. Pre-existing hypocalcemia must be corrected prior to initiating therapy with Ospomyv. Adequately supplement all patients with calcium and vitamin D [see Dosage and Administration (2.1) , Contraindications (4) , and Adverse Reactions (6.1) ] . In patients without advanced chronic kidney disease who are predisposed to hypocalcemia and disturbances of mineral metabolism (e.g. history of hypoparathyroidism, thyroid surgery, parathyroid surgery, malabsorption syndromes, excision of small intestine, treatment with other calcium-lowering drugs), assess serum calcium and mineral levels (phosphorus and magnesium) 10 to 14 days after Ospomyv injection. In some postmarketing cases, hypocalcemia persisted for weeks or months and required frequent monitoring and intravenous and/or oral calcium replacement, with or without vitamin D. Patients with Advanced Chronic Kidney Disease Patients with advanced chronic kidney disease [i.e., eGFR <30 mL/min/1.73 m 2 ] including dialysis-dependent patients are at greater risk for severe hypocalcemia following denosumab products administration. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported. The presence of underlying chronic kidney disease-mineral bone disorder (CKD-MBD, renal osteodystrophy) markedly increases the risk of hypocalcemia. Concomitant use of calcimimetic drugs may also worsen hypocalcemia risk. To minimize the risk of hypocalcemia in patients with advanced chronic kidney disease, evaluate for the presence of chronic kidney disease mineral and bone disorder with intact parathyroid hormone (iPTH), serum calcium, 25(OH) vitamin D, and 1,25(OH) 2 vitamin D prior to decisions regarding Ospomyv treatment. Consider also assessing bone turnover status (serum markers of bone turnover or bone biopsy) to evaluate the underlying bone disease that may be present. Monitor serum calcium weekly for the first month after Ospomyv administration and monthly thereafter. Instruct all patients with advanced chronic kidney disease, including those who are dialysis-dependent, about the symptoms of hypocalcemia and the importance of maintaining serum calcium levels with adequate calcium and activated vitamin D supplementation. Treatment with Ospomyv in these patients should be supervised by a healthcare provider who is experienced in diagnosis and management of CKD-MBD. 5.2 Drug Products with Same Active Ingredient Patients receiving Ospomyv should not receive other denosumab products concomitantly. 5.3 Hypersensitivity Clinically significant hypersensitivity including anaphylaxis has been reported with denosumab products. Symptoms have included hypotension, dyspnea, throat tightness, facial and upper airway edema, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of Ospomyv [see Contraindications (4) , Adverse Reactions (6.2) ] . 5.4 Osteonecrosis of the Jaw Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing. ONJ has been reported in patients receiving denosumab products [see Adverse Reactions (6.1) ] . A routine oral exam should be performed by the prescriber prior to initiation of Ospomyv treatment. A dental examination with appropriate preventive dentistry is recommended prior to treatment with Ospomyv in patients with risk factors for ONJ such as invasive dental procedures (e.g. tooth extraction, dental implants, oral surgery), diagnosis of cancer, concomitant therapies (e.g. chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and comorbid disorders (e.g. periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, ill-fitting dentures). Good oral hygiene practices should be maintained during treatment with Ospomyv. Concomitant administration of drugs associated with ONJ may increase the risk of developing ONJ. The risk of ONJ may increase with duration of exposure to denosumab products. For patients requiring invasive dental procedures, clinical judgment of the treating physician and/or oral surgeon should guide the management plan of each patient based on individual benefit-risk assessment. Patients who are suspected of having or who develop ONJ while on Ospomyv should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition. Discontinuation of Ospomyv therapy should be considered based on individual benefit-risk assessment. 5.5 Atypical Subtrochanteric and Diaphyseal Femoral Fractures Atypical low energy or low trauma fractures of the shaft have been reported in patients receiving denosumab products [see Adverse Reactions (6.1) ] . These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with antiresorptive agents. Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral, and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. During Ospomyv treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patients presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of Ospomyv therapy should be considered, pending a benefit-risk assessment, on an individual basis. 5.6 Multiple Vertebral Fractures (MVF) Following Discontinuation of Treatment…