Denosumab

Indications

Denosumab is used for: Postmenopausal Osteoporosis

Adult Dose

Recommended Dose: 60 mg single SC injection administered once every 6 months. Patients should receive calcium and vitamin D supplements whilst undergoing treatment. 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.

Child Dose

Renal Dose

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.

Administration

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

Contra Indications

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

Precautions

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

Pregnancy-Lactation

Interactions

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.

Adverse Effects

Side effects of Denosumab : >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%)

Mechanism of Action

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.