Overview
11 DESCRIPTION Denosumab-bnht is a human IgG2 monoclonal antibody with affinity and specificity for human RANKL (receptor activator of nuclear factor kappa-B ligand). Denosumab-bnht has an approximate molecular weight of 147 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Denosumab products bind to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption. Denosumab products prevent RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone. 12.2 Pharmacodynamics In clinical studies, treatment with 60 mg of denosumab resulted in reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days, with maximal reductions occurring by 1 month.
Indications
- 1 INDICATIONS AND USAGE Conexxence is a RANK ligand (RANKL) inhibitor indicated for treatment: of postmenopausal women with osteoporosis at high risk for fracture ( 1.1 ) to increase bone mass in men with osteoporosis at high risk for fracture ( 1.2 ) of glucocorticoid-induced osteoporosis in men and women at high risk for fracture ( 1.3 ) to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer ( 1.
Common Doses
- 60 mg
- 1000 mg
- 30 mL
Dosage
2 DOSAGE AND ADMINISTRATION Pregnancy must be ruled out prior to administration of Conexxence. ( 2.1 ) Before initiating Conexxence in patients with advanced chronic kidney disease, including dialysis patients, evaluate for the presence of chronic kidney disease mineral and bone disorder with intact parathyroid hormone, serum calcium, 25(OH) vitamin D, and 1,25(OH)2 vitamin D. ( 2.2 , 5.1 , 8.6 ) Conexxence should be administered by a healthcare provider. ( 2.3 ) Administer 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen. ( 2.
Black Box Warning
WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE Patients with advanced chronic kidney disease (eGFR
Contraindications
- 4 CONTRAINDICATIONS Conexxence is contraindicated in: Patients with hypocalcemia: Pre-existing hypocalcemia must be corrected prior to initiating therapy with Conexxence [see Warnings and Precautions ( 5.1 )] . Pregnant women: Denosumab products may cause fetal harm when administered to a pregnant woman. In women of reproductive potential, pregnancy testing should be performed prior to initiating treatment with Conexxence [see Use in Specific Populations ( 8.1 )] .
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are discussed below and also elsewhere in the labeling: Severe Hypocalcemia and Mineral Metabolism Changes [see Warnings and Precautions ( 5.1 )] Hypersensitivity [see Warnings and Precautions ( 5.3 )] Osteonecrosis of the Jaw [see Warnings and Precautions ( 5.4 )] Atypical Subtrochanteric and Diaphyseal Femoral Fractures [see Warnings and Precautions ( 5.5 )] Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation of Treatment [see Warnings and Precautions ( 5.6 )] Serious Infections [see Warnings and Precautions ( 5.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.