Denosis

Approved Indications:

• Osteoporosis:
• Treatment of osteoporosis in postmenopausal women at high risk for fracture.
• Treatment to increase bone mass in men at high risk for fracture.
• Treatment to increase bone mass in men receiving androgen deprivation therapy for nonmetastatic prostate cancer.
• Treatment to increase bone mass in women receiving aromatase inhibitor therapy for breast cancer.
• Prevention of Skeletal-Related Events (SREs) in Cancer:
• Prevention of SREs in patients with bone metastases from solid tumors.
• Giant Cell Tumor of Bone (GCTB):
• Treatment of adults and skeletally mature adolescents with unresectable GCTB or when surgery is likely to result in severe morbidity.
• Hypercalcemia of Malignancy:
• Treatment of hypercalcemia refractory to bisphosphonates.

Off-label Uses:

• Treatment of bone loss associated with other conditions such as glucocorticoid-induced osteoporosis (limited data).
• Potential use in other bone metabolic disorders under investigation.

• Osteoporosis in Adults:
• 60 mg subcutaneously once every 6 months.
• Prevention of SREs in Cancer Patients:
• 120 mg subcutaneously every 4 weeks.
• Additional doses on days 8 and 15 during the first month of therapy.
• Giant Cell Tumor of Bone:
• 120 mg subcutaneously every 4 weeks with additional doses on days 8 and 15 during the first month.
• Hypercalcemia of Malignancy:
• 120 mg subcutaneously on days 1, 8, 15, and 29.
• Special Populations:
• No dosage adjustments are recommended for elderly patients.
• No established dosing for pediatric use except for skeletally mature adolescents with GCTB.
• Use caution in patients with renal impairment; hypocalcemia risk increases in severe renal dysfunction.
• Hepatic impairment does not require dose adjustment.
• Administration Route:
• Subcutaneous injection in the upper arm, upper thigh, or abdomen.

Denosumab is a fully human monoclonal antibody that binds with high affinity and specificity to RANKL (receptor activator of nuclear factor kappa-B ligand), a key cytokine essential for the formation, function, and survival of osteoclasts. By inhibiting RANKL, denosumab prevents osteoclast-mediated bone resorption, leading to decreased bone turnover, increased bone mass and strength, and reduced risk of fractures. In cancer, this mechanism helps prevent bone destruction caused by metastatic lesions.

• Absorption:
• Subcutaneous bioavailability is approximately 62%.
• Distribution:
• Volume of distribution is about 5-6 L, consistent with distribution mainly in vascular and interstitial spaces.
• Metabolism:
• Metabolized by the reticuloendothelial system; not processed by the liver cytochrome P450 system.
• Half-life:
• Approximately 25-28 days.
• Elimination:
• Degraded into small peptides and amino acids; no renal or hepatic excretion.

• Pregnancy:
• Category C. Animal studies have shown adverse effects on fetal bone development. Use only if benefits outweigh risks.
• Lactation:
• Unknown if excreted in human milk. Caution is advised; breastfeeding is generally not recommended during treatment.

• Primary Class: Monoclonal antibody
• Subclass: RANKL inhibitor, antiresorptive agent

• Known hypersensitivity to denosumab or any component of the formulation.
• Hypocalcemia prior to treatment (must be corrected).
• Active dental/jaw infections or planned invasive dental procedures due to risk of osteonecrosis of the jaw.

• Hypocalcemia: Monitor calcium, vitamin D, and magnesium before and during treatment; supplement as needed.
• Osteonecrosis of the jaw (ONJ): Risk increased in cancer patients; recommend dental exam before initiation.
• Atypical Femoral Fractures: Report new thigh/groin pain immediately.
• Infections: Increased risk, particularly of skin infections such as cellulitis.
• Dermatologic Reactions: Monitor for severe skin reactions (e.g., eczema, dermatitis).
• Immune Effects: May impair immune function; caution in immunocompromised patients.

Common:

• Hypocalcemia
• Musculoskeletal pain
• Dermatitis, eczema, rash
• Infections (cellulitis, urinary tract infections)
• Fatigue

Serious/Rare:

• Osteonecrosis of the jaw
• Atypical femoral fractures
• Severe hypocalcemia
• Allergic reactions including anaphylaxis
• Serious infections

• No significant cytochrome P450 interactions.
• Concomitant use with bisphosphonates not typically recommended due to additive effects on bone turnover.
• Caution with drugs affecting calcium metabolism (e.g., loop diuretics).
• No significant interaction with common medications documented.

• Updated guidelines from osteoporosis and oncology societies reinforce denosumab’s role in fracture risk reduction and prevention of skeletal-related events.
• Emphasis on monitoring for hypocalcemia and dental health prior to and during therapy.
• Recent alerts on risks of atypical fractures and ONJ with long-term use.
• Ongoing studies investigating extended dosing intervals and combination therapies.

• Store at 2°C to 8°C (36°F to 46°F); do not freeze.
• Protect from light.
• Keep in original packaging until use.
• Allow the vial or syringe to reach room temperature (up to 25°C) before administration.
• Avoid shaking the vial or syringe.