| Click on "►" to expand:|
 BRAND NAMES
- Europe: Prolia EPAR summary for the public, Prescribing Information, Xgeva EPAR summary for the public, Prescribing Information
- U.S.: Prolia PI, Xgeva PI
 MECHANISM OF ACTION
Denosumab, is a human monoclonal antibody (IgG2). A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen) in the body. Denosumab targets and binds with high affinity to an antigen called RANKL, preventing activation of its receptor, RANK, on the surface of osteoclast precursors and osteoclasts (cells that are involved in breaking down the bone tissue).
Prevention of the RANKL/RANK interaction reduces the formation (the number), function and survival of the osteoclasts. This reduces the loss of bone and maintains bone strength, making fractures less likely to happen.
Increased osteoclast activity, stimulated by RANKL, is a key mediator of bone destruction in metastatic bone disease and multiple myeloma. Denosumab decreases cancer-induced bone destruction.
- Prevention of bone complications (pathological fracture, radiation to bone, spinal cord compression or surgery to bone) in patients with a solid tumour that has spread to the bone.
- 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 postmenopausal women with osteoporosis at high risk for fracture
- Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer
- Treatment to increase bone mass in men with osteoporosis at high risk for fracture
- Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
Supplementation of at least 500-1000 mg calcium and 400 IU vitamin D is required in all patients unless hypercalcemia is present
- Bone Metastasis from Solid Tumors: Administer 120 mg every 4 weeks as a subcutaneous injection in the upper arm, upper thigh, or abdomen
- Giant Cell Tumor of Bone: Administer 120 mg every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy.
- Treatment of postmenopausal women with osteoporosis at high risk for fracture, To increase bone mass in men with osteoporosis at high risk for fracture, To increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer, Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer: 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen
 DOSAGE FORMS AND STRENGTHS
- Xgeva: 120 mg/1.7 mL single-use vial (3)
- Prolia: Single-use prefilled syringe containing 60 mg in a 1 mL solution or Single-use vial containing 60 mg in a 1 mL solution
- Known hypersensitivity to Denosumab
 WARNINGS AND PRECAUTIONS
- Hypocalcemia: Denosumab can cause severe symptomatic hypocalcemia. Correct hypocalcemia prior to initiating therapy.
- Patients should be adequately supplemented with calcium and vitamin D
- Osteonecrosis of the jaw can occur in patients receiving Denosumab. Perform an oral examination prior to starting therapy. Monitor for symptoms. Avoid invasive dental procedures during treatment.
- 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 (Prolia)
- Dermatologic reactions: Dermatitis, rashes, and eczema have been reported. Consider discontinuing therapy if severe symptoms develop (Prolia)
- Hypersensitivity including anaphylactic reactions may occur. Discontinue permanently if a clinically significant reaction occurs (Prolia)
- Atypical femoral fracture: Has been reported. Evaluate patients with thigh or groin pain to rule out a femoral fracture (Xgeva)
 PREGNANCY AND LACTATION
- Denosumab can cause fetal harm when administered to a pregnant woman based on findings in animals.
There are no adequate and well-controlled studies with Denosumab in pregnant women. Women should be advised not to become pregnant when taking Denosumab.
- Nursing mothers: a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
 SIDE EFFECTS
- Postmenopausal osteoporosis: Most common adverse reactions (> 5% and more common than placebo) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, cystitis and upper respiratory tract infection. Pancreatitis has been reported in clinical trials
- Male Osteoporosis: Most common adverse reactions (> 5% and more common than placebo) were: back pain, arthralgia, and nasopharyngitis
- Bone loss due to hormone ablation for cancer: Most common adverse reactions (≥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials. Cataracts were seen in men receiving treatment for prostate cancer.
- Bone Metastasis from Solid Tumors: Most common adverse reactions were fatigue/asthenia, hypophosphatemia, nausea, dyspnea and diarrhea
- Giant Cell Tumor of Bone: Most common adverse reactions (per-patient incidence greater than or equal to 10%) were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity
 RELATED LINKS