Denosis 120

Osteoporosis, treatment of men and postmenopausal women with osteoporosis who are at high risk for fracture; treatment to increase bone mass in men at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer; treatment to increase bone mass in women at high risk for fracture who are receiving adjuvant aromatase inhibitor therapy for breast cancer. Prevention of skeletal-related events (eg, pathological fracture, bone radiation, spinal cord compression or bone surgery) in adults w/ bone metastases from solid tumours. Adults & skeletally mature adolescents w/ giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.

Administer SC in upper arm, upper thigh, or abdomen; do NOT administer intradermally, IM, or IV Administer calcium and vitamin D as needed to treat or prevent hypocalcemia Avoid vigorous shaking of vial/syringe

Denosumab 60mg Subcutaneous Osteoporosis 60 mg SC every 6 months Supplement with calcium 1000 mg/day and vitamin D 400 IU/day Aromatase Inhibitor Induced Bone Loss Women with breast cancer: 60 mg SC every 6 months Androgen Deprivation Induced Bone Loss Men with prostate cancer: 60 mg SC every 6 months Denosumab 120mg Subcutaneous Skeletal-Related Events Prevention of skeletal-related events (SREs; eg, bone fractures and pain) in patients with bone metastases from solid tumors 120 mg (1.7 mL) SC every 4 weeks Giant Cell Tumor Treatment of adults and skeletally mature adolescents with giant cell tumor of bone in whom surgical resection is impossible or is likely to result in severe morbidity 120 mg SC every 4 weeks with additional 120 mg on days 8 and 15 during first month of therapy Hypercalcemia of Malignancy Indicated for treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy 120 mg SC q4wk Give 2 additional 120 mg doses during the first month of therapy on Days 8 and 15 Elderly: Based on the available safety and efficacy data in the elderly, no dosage adjustment is required. Hepatic Impairment: The safety and efficacy have not been studied in patients with hepatic impairment.

Renal Impairment: Based on the available safety and efficacy data in the elderly, no dosage adjustment is required in patients with renal impairment. Patients with severe renal impairment [creatinine clearance (CrCl) <30 mL/min] or receiving dialysis are at greater risk of developing hypocalcemia. Adequate intake of calcium and vitamin D is important in patients with severe renal impairment or receiving dialysis.

Clinically significant hypersensitivity to denosumab or to any of the components. Hypocalcemia.

Denosumab is a human monoclonal antibody (IgG2) that targets and binds with high affinity and specificity to receptor activator of nuclear factor kappa-B ligand (RANKL) preventing RANKL from activating its only receptor, RANK, on the surface of osteoclasts and their precursors, independent of bone surface. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function and survival. Denosumab therefore reduces bone resorption and increases bone mass and strength in both cortical and trabecular bone.

Correct hypocalcemia prior to initiation of therapy. Patients should receive Ca & vit D supplements during treatment (unless hypercalcemia is present). Skin infections predominantly cellulitis may develop. Osteonecrosis of the jaw in patients w/ advanced cancer. Atypical femoral fracture. Severe renal impairment or undergoing dialysis. Pregnancy & lactation. Childn. Lactation: Unknown whether drug is distributed in breast milk; caution is advised

>10% Back pain (34.7%),Extremity pain (11.7%) 1-10% Musculoskeletal pain (7.6%),Hypercholesterolemia (7.2%),Cystitis (5.9%),Upper respiratory tract infection (4.9%),New malignancies (4.8%, compared with 4.3% in placebo group),Sciatica (4.6%),Nonfatal serious infection (4%),Bone pain (3.7%),Anemia (3.3%),Upper abdominal pain (3.3%),Rash (2.5%),Flatulence (2.2%),Osteonecrosis of jaw (2.2%),Pruritus (2.2%),Hypocalcemia (1.7%) <1% Serious infection of abdomen resulting in hospitalization (0.9%),Serious infection of urinary tract resulting in hospitalization (0.7%),Serious infection resulting in death (0.2%),Pancreatitis (0.2%),Serious infection of ear resulting in hospitalization (0.1%)

Pregnancy Contraindicated Based on findings in animals and its mechanism of action, denosumab can cause fetal harm when administered to a pregnant woman In utero exposure in cynomolgus monkeys dosed monthly with denosumab throughout pregnancy at a dose 50-fold higher than the recommended human dose based on body weight resulted in increased fetal loss, stillbirths, and postnatal mortality, and absent lymph nodes, abnormal bone growth, and decreased neonatal growth Present at low concentrations (~2% of serum exposure) in seminal fluid of male subjects receiving therapy; following vaginal intercourse, maximum amount of denosumab delivered to a female partner would result in exposures ~11,000 times lower than the prescribed 60 mg subcutaneous dose; male condom use not necessary as it is unlikely that a female partner or fetus would be exposed to pharmacologically relevant concentrations of denosumab via seminal fluid Contraception Females: Advise females of reproductive potential to use effective contraception during therapy, and for at least 5 months after the last dose of denosumab Males: Denosumab was present at low concentrations (~2% of serum exposure) in the seminal fluid of male subjects; condom use would not be necessary as it is unlikely that a female partner or fetus would be exposed to pharmacologically relevant concentrations of denosumab via seminal fluid Lactation There is no information regarding presence of denosumab in human milk, effects on breastfed infant, or effects on milk production;

Increased risk of serious infections w/ immunosuppressive agents.Denosumab did not affect the pharmacokinetics of midazolam, a drug metabolised by cytochrome P450 3A4 (CYP3A4). Incompatibilities:Denosumab must not be mixed with other medicinal products.