Denosumab is a human IgG2 monoclonal antibody with high affinity and specificity for human RANKL. It binds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts—the cells responsible for bone resorption. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. By inhibiting the RANKL/RANK interaction, Denosumab suppresses osteoclast formation, function, and survival, thereby reducing bone resorption and increasing bone mass and strength in both cortical and trabecular bone.
Denosumab is a RANK ligand (RANKL) inhibitor indicated for:
Treatment of Postmenopausal Osteoporosis at High Risk for Fracture: Denosumab is indicated for postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture or multiple risk factors for fracture, or for patients who have failed or are intolerant to other available osteoporosis therapies. In these women, Denosumab reduces the incidence of vertebral, nonvertebral, and hip fractures.
Treatment to Increase Bone Mass in Men with Osteoporosis: Denosumab is indicated for increasing bone mass in men with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture or multiple risk factors for fracture, or for patients who have failed or are intolerant to other available osteoporosis therapies.
Treatment of Glucocorticoid-Induced Osteoporosis: Denosumab is indicated for the treatment of glucocorticoid-induced osteoporosis in men and women at high risk of fracture who are either initiating or continuing systemic glucocorticoid therapy at a daily dosage equivalent to 7.5 mg or greater of prednisone and are expected to remain on glucocorticoids for at least six months. High risk of fracture is defined as a history of osteoporotic fracture, multiple risk factors for fracture, or failure/intolerance to other available osteoporosis therapies.
Treatment of Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer: Denosumab is indicated to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer. In these patients, Denosumab also reduces the incidence of vertebral fractures.
Treatment of Bone Loss in Women Receiving Adjuvant Aromatase Inhibitor Therapy for Breast Cancer: Denosumab is indicated to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.
Treatment of Multiple Myeloma and Bone Metastases from Solid Tumors: Denosumab is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.
Treatment of Giant Cell Tumor of Bone: Denosumab is indicated for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.
Treatment of Hypercalcemia of Malignancy: Denosumab is indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.
Administration: Denosumab should be administered by a healthcare professional. It is intended for subcutaneous injection only and should not be administered intravenously, intramuscularly, or intradermally.
Dosage:
Osteoporosis and Bone Loss: Administer 60 mg every six months as a subcutaneous injection in the upper arm, upper thigh, or abdomen.
Patients should take calcium (1,000 mg daily) and at least 400 IU of vitamin D daily.
If a dose is missed, administer the injection as soon as possible, then schedule subsequent injections every six months from the last injection date.
Multiple Myeloma and Bone Metastases from Solid Tumors: Administer 120 mg every four weeks as a subcutaneous injection.
Giant Cell Tumor of Bone: Administer 120 mg every four weeks, with additional 120 mg doses on Days 8 and 15 of the first month of therapy.
Hypercalcemia of Malignancy: Administer 120 mg every four weeks, with additional 120 mg doses on Days 8 and 15 of the first month of therapy.
Calcium and Vitamin D: Administer calcium and vitamin D as necessary to prevent or treat hypocalcemia.
Denosumab is contraindicated in:
Hypocalcemia: Pre-existing hypocalcemia must be corrected before initiating Denosumab.
Pregnancy: Denosumab may cause fetal harm if administered to pregnant women. Women of reproductive potential should undergo pregnancy testing before starting treatment.
Hypersensitivity: Denosumab is contraindicated in patients with a history of systemic hypersensitivity to any component of the product, including anaphylaxis, facial swelling, and urticaria.
Hypersensitivity Reactions: Anaphylactic reactions may occur. Discontinue permanently if a clinically significant reaction occurs.
Hypocalcemia: Severe symptomatic hypocalcemia has been reported, including fatal cases. Patients with renal impairment are at higher risk. Monitor calcium levels, especially during the first few weeks of therapy, and ensure adequate calcium and vitamin D intake.
Osteonecrosis of the Jaw: Perform an oral examination before initiating therapy. Avoid invasive dental procedures during treatment.
Atypical Femoral Fractures: Evaluate patients with thigh or groin pain for femoral fractures.
Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation: Patients discontinuing Denosumab should be transitioned to another antiresorptive agent to reduce the risk of fractures.
Serious Infections: Skin infections, including cellulitis requiring hospitalization, may occur.
Dermatologic Reactions: Severe dermatitis, rashes, and eczema have been reported. Discontinue Denosumab if severe symptoms develop.
Severe Bone, Joint, and Muscle Pain: Discontinue use if severe symptoms occur.
Suppression of Bone Turnover: Monitor for consequences of excessive bone suppression.
Hypercalcemia Following Treatment Discontinuation: Monitor patients for signs and symptoms, particularly those with growing skeletons or giant cell tumor of bone.
Embryo-Fetal Toxicity: Denosumab can cause fetal harm. Advise females of reproductive potential to use effective contraception.
Store Denosumab in a refrigerator at 2°C to 8°C (36°F to 46°F) in its original carton.
Do not freeze.
Once removed from the refrigerator, do not expose Denosumab to temperatures above 25°C (77°F) or direct light. Use within 14 days.
Protect from direct light and heat. Avoid vigorous shaking.
Medicine: Keep out of reach of children.
