Denosumab (Xgeva, Prolia)

Indications

Xgeva

Prevention of Skeletal-Related Events (Pathologic Fractures, Need for XRT/Surgery to Bone, Spinal Cord Compression) in Metastatic Bone Disease Due to Solid Tumors

Prolia

Prevention of Post-Menopausal Osteoporosis

Treatment of Men Receiving Androgen Therapy in Non-Metastatic Prostate Cancer

Treatment of Women Receiving Aromatase Inhibitor Therapy in Breast Cancer


Contraindications


Pharmacology

Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Inhibitor

  • IgG2 Monoclonal Antibody which Prevents RANKL (CD254) from Activating its Receptor, RANK (CD265), on Surface of Osteoclasts (and Pre-Osteoclasts)
    • Mimics the function of osteoprotegerin -> inhibits osteoclast formation, function, and survival -> inhibits osteoclast bone resorption
    • Net effect: increased trabecular and cortical bone mass and strength
  • Other Potential Immunomodulatory Effects: related to the observations that RANKL is present on T-cells and that RANK is present on dendritic cells

Administration

  • SQ (Xgeva): 120 mg q4wks
    • Half-Life: 28 days
  • Renal Dose-Adjustment:
  • Hepatic Dose-Adjustment:

Adverse Effects

Renal Adverse Effects

  • Hypocalcemia (see Hypocalcemia, [[Hypocalcemia]]): fatal cases have been reported
  • Hypophosphatemia (see Hypophosphatemia, [[Hypophosphatemia]]):
  • Osteonecrosis of the Jaw

Other Adverse Effects

  • Atypical Femoral Fractures
  • Teratogenicity
  • xxx

References

  • xxxx