Denosumab

Prolia is a RANK ligand (RANKL) inhibitor indicated for treatment: of postmenopausal women with osteoporosis at high risk for fracture to increase bone mass in men with osteoporosis at high risk for fracture of glucocorticoid-induced osteoporosis in men and women at high risk for fracture to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

Prolia binds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption. Prolia prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone.

Pregnancy must be ruled out prior to administration of Prolia. Before initiating Prolia in patients with advanced chronic kidney disease, including dialysis patients, evaluate for the presence of chronic kidney disease mineral and bone disorder with intact parathyroid hormone, serum calcium, 25(OH) vitamin D, and 1,25(OH) 2 vitamin D. Prolia should be administered by a healthcare provider. Administer 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen. Instruct patients to take calcium 1000 mg daily and at least 400 IU vitamin D daily.

Prolia is contraindicated in: Patients with hypocalcemia: Pre-existing hypocalcemia must be corrected prior to initiating therapy with Prolia. Pregnant women: Prolia may cause fetal harm when administered to a pregnant woman. In women of reproductive potential, pregnancy testing should be performed prior to initiating treatment with Prolia. Patients with hypersensitivity to Prolia: Prolia is contraindicated in patients with a history of systemic hypersensitivity to any component of the product. Reactions have included anaphylaxis, facial swelling, and urticaria. Hypocalcemia. Pregnancy. Known hypersensitivity to Prolia

Boxed warning (severe hypocalcemia in patients with advanced kidney disease): Patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m 2 ), including dialysis-dependent patients, are at greater risk of severe hypocalcemia following Prolia administration. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported. Hypocalcemia: Pre-existing hypocalcemia must be corrected before initiating Prolia. 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. Same Active Ingredient: Patients receiving Prolia should not receive other denosumab products concomitantly.

The following serious adverse reactions are discussed below and also elsewhere in the labeling: Severe Hypocalcemia and Mineral Metabolism Changes Hypersensitivity Osteonecrosis of the Jaw Atypical Subtrochanteric and Diaphyseal Femoral Fractures Multiple Vertebral Fractures (MVF) Following Discontinuation of Prolia Treatment Serious Infections Dermatologic Adverse Reactions The most common adverse reactions reported with Prolia in patients with postmenopausal osteoporosis are back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis. The most common adverse reactions reported with Prolia in men with osteoporosis are back pain, arthralgia, and nasopharyngitis. The most common adverse reactions reported with Prolia in patients with glucocorticoid-induced osteoporosis are back pain, hypertension, bronchitis, and headache.

Store Prolia refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Prior to administration, Prolia may be allowed to reach room temperature up to 25°C (77°F) in the original container. Once removed from the refrigerator, Prolia must not be exposed to temperatures above 25°C (77°F) and must be used within 30 days.