Drug Guide
Denosumab
Classification
Therapeutic: Bone Modulator / RANKL Inhibitor
Pharmacological: Monoclonal antibody
FDA Approved Indications
- Osteoporosis in postmenopausal women at high risk for fracture
- Prevention of skeletal-related events in patients with bone metastases from solid tumors
Mechanism of Action
Denosumab is a monoclonal antibody that binds to RANKL (Receptor Activator of Nuclear factor Kappa-Β Ligand), preventing RANKL from activating its receptor RANK on the surface of osteoclasts and their precursors. This inhibition decreases osteoclast formation, function, and survival, leading to decreased bone resorption.
Dosage and Administration
Adult: Prolia: 60 mg subcutaneously every 6 months. Xgeva: 120 mg subcutaneously every 4 weeks, with supplementation as needed for bone metastases.
Pediatric: Not approved for pediatric use.
Geriatric: No specific dosage adjustments, but caution in those with renal impairment or other comorbidities.
Renal Impairment: Use with caution in severe renal impairment; monitor appropriately.
Hepatic Impairment: No specific adjustments needed.
Pharmacokinetics
Absorption: Rapidly absorbed after subcutaneous injection.
Distribution: Widely distributed in the body, including bone.
Metabolism: Metabolized via proteolytic catabolism, not by hepatic enzymes.
Excretion: Excreted via the reticuloendothelial system; not via urine or feces.
Half Life: Approximately 25 days.
Contraindications
- Hypocalcemia
- Hypersensitivity to denosumab or its excipients
Precautions
- Patients with renal impairment, especially severe renal impairment or on dialysis.
- Risk of osteonecrosis of the jaw (ONJ). Monitor calcium levels. Use caution in patients with dental disease.
Adverse Reactions - Common
- Back pain (Common)
- Musculoskeletal pain (Common)
- Fatigue (Common)
- Arthralgia (Common)
- Hypercholesterolemia (Common)
Adverse Reactions - Serious
- Osteonecrosis of the jaw (ONJ) (Rare but serious)
- Hypocalcemia (Rare but serious)
- Serious infections (Rare)
- Atypical femoral fractures (Rare)
Drug-Drug Interactions
- None specifically listed; caution with other drugs affecting calcium and bone metabolism.
Drug-Food Interactions
- No specific food interactions.
Drug-Herb Interactions
- No specific herb interactions listed.
Nursing Implications
Assessment: Monitor serum calcium levels before each injection, especially in hypocalcemic patients. Evaluate dental health before initiation.
Diagnoses:
- Risk for infection, Risk for hypocalcemia, Risk for osteonecrosis of the jaw
Implementation: Administer subcutaneously as prescribed. Ensure adequate calcium and vitamin D intake. Educate patients on oral health and reporting symptoms of hypocalcemia or infection.
Evaluation: Assess patient’s calcium levels, dental health, and for signs of adverse effects during therapy.
Patient/Family Teaching
- Take calcium and vitamin D supplements as recommended.
- Report any signs of hypocalcemia (muscle cramps, tingling), infection, or jaw pain.
- Maintain good oral hygiene and dental check-ups.
- Understand the importance of adherence to dosing schedule.
Special Considerations
Black Box Warnings:
- Osteonecrosis of the jaw (ONJ)
- Atypical femoral fractures
Genetic Factors: None specific.
Lab Test Interference: None noted.
Overdose Management
Signs/Symptoms: Potential hypocalcemia, severe muscle spasms, tetany.
Treatment: Discontinue drug, administer calcium supplements and supportive care. Seek emergency medical care.
Storage and Handling
Storage: Refrigerate at 2°C to 8°C (36°F to 46°F). Do not freeze.
Stability: Stable until expiration date indicated on the label when stored properly.