IMPORTANT SAFETY INFORMATION

Drug Products with Same Active Ingredient

• Patients receiving Wyost should not receive other denosumab products concomitantly.

Hypersensitivity

• Clinically significant hypersensitivity including anaphylaxis has been reported with use of denosumab products. Reactions may include hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue Wyost therapy permanently.

Hypocalcemia

• Denosumab products can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Correct pre-existing hypocalcemia prior to Wyost treatment. Monitor calcium levels, throughout Wyost therapy, especially in the first weeks of initiating therapy, and administer calcium, magnesium, and vitamin D as necessary. Concomitant use of calcimimetics and other drugs that can lower calcium levels may worsen hypocalcemia risk and serum calcium should be closely monitored. Advise patients to contact a healthcare provider for symptoms of hypocalcemia.
• An increased risk of hypocalcemia has been observed in clinical trials of patients with increasing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/min and/or on dialysis), and with inadequate/no calcium supplementation. Monitor calcium levels and calcium and vitamin D intake.

Osteonecrosis of the Jaw (ONJ)

• ONJ has been reported in patients receiving denosumab products, manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials in patients with cancer, the incidence of ONJ was higher with longer duration of exposure. Risk factors include a history of tooth extraction, poor oral hygiene, or use of a dental appliance. Other risk factors include immunosuppressive therapy, treatment with angiogenesis inhibitors, systemic corticosteroids, diabetes, and gingival infections, and a history of invasive dental procedures for denosumab-treated patients with multiple myeloma.
• Perform an oral examination and appropriate preventive dentistry prior to the initiation of Wyost and periodically during Wyost therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with Wyost. Consider temporary discontinuation of Wyost therapy if an invasive dental procedure must be performed.
• Patients who are suspected of having or who develop ONJ while on Wyost should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery may exacerbate the condition.

Atypical Subtrochanteric and Diaphyseal Femoral Fracture

• Atypical femoral fracture has been reported with denosumab products. 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.
• 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 Wyost 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 evaluated to rule out an incomplete femur fracture. Patient presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of Wyost therapy should be considered, pending a risk/benefit assessment, on an individual basis.

Hypercalcemia Following Treatment Discontinuation in Patients with Giant Cell Tumor of Bone (GCTB) and in Patients with Growing Skeletons

• Clinically significant hypercalcemia requiring hospitalization and complicated by acute renal injury has been reported in denosumab product-treated patients with GCTB and patients with growing skeletons within the first year after treatment discontinuation. After treatment is discontinued, monitor patients for signs and symptoms of hypercalcemia and manage patients as clinically appropriate.

Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation

• MVF have been reported following discontinuation of treatment with denosumab products. Patients at higher risk for MVF include those with risk factors for or a history of osteoporosis or prior fractures. When Wyost treatment is discontinued, evaluate the individual patient’s risk for vertebral fractures.

Embryo-Fetal Toxicity

• Based on data from animal studies and its mechanism of action, denosumab products can cause fetal harm when administered to a pregnant woman.
• Advise females of reproductive potential to use effective contraception during therapy and for at least 5 months after the last dose of Wyost. Advise pregnant women and females of reproductive potential that exposure to Wyost during pregnancy or within 5 months prior to conception can result in fetal harm.