ose adjustment is required in patients with renal impairment.
Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] 15 to29 mL/min/1.73 m2 by MDRD equation) or receiving dialysis are at greater risk of developinghypocalcemia [see Contraindications (4), Warnings and Precautions (5.3) and Adverse Reactions (6.1)].
Monitor calcium concentrations and adequately supplement calcium and vitamin D in patients who havesevere renal impairment or are receiving dialysis.
11 DESCRIPTION
Romosozumab-aqqg is a humanized monoclonal antibody (IgG2) produced in a mammalian cell line(Chinese Hamster Ovary) by recombinant DNA technology that binds to and inhibits sclerostin.
Romosozumab-aqqg has an approximate molecular weight of 149 kDa.
EVENITY (romosozumab-aqqg) injection is supplied as a sterile, preservative-free, clear to opalescent,colorless to light yellow solution for subcutaneous injection in a single-use prefilled syringe.
Two 105 mg/1.17 mL single-use prefilled syringes are required to administer the recommended 210 mgdose of EVENITY [see Dosage and Administration (2.1)]. Each single-use prefilled syringe delivers1.17 mL of solution containing 105 mg of romosozumab-aqqg, acetate (3.8 mg), calcium (0.61 mg),polysorbate 20 (0.07 mg) and sucrose (70 mg) in Water for Injection, USP, and sodium hydroxide to a pHof 5.2.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
EVENITY inhibits the action of sclerostin, a regulatory factor in bone metabolism. EVENITY increasesbone formation and, to a lesser extent, decreases bone resorption. Animal studies showed thatromosozumab-aqqg stimulates new bone formation on trabecular and cortical bone surfaces bystimulating osteoblastic activity resulting in increases in trabecular and cortical bone mass andimprovements in bone structure and strength [see Nonclinical Toxicology (13.2) and Clinical Studies
(14.1)].
12.2 Pharmacodynamics
In postmenopausal women with osteoporosis, EVENITY increased the bone formation markerprocollagen type 1 N-telopeptide (P1NP) with a peak increase from baseline of approximately 145%compared to placebo 2 weeks after initiating treatment, followed by a return to concentrations seen withplacebo at month 9 and a decline from baseline to approximately 15% below the concentration changeseen with placebo at month 12.
EVENITY decreased the bone resorption marker type 1 collagen C-telopeptide (CTX) with a maximalreduction from baseline of approximately 55% compared to placebo 2 weeks after initiating treatment.
CTX remained below concentrations seen with placebo and was approximately 25% below theconcentration change seen with placebo at month 12.
After discontinuation of EVENITY, P1NP levels returned to baseline within 12 months; CTX increasedabove baseline levels within 3 months and returned toward baseline levels by month 12.
12.3 Pharmacokinetics
Administration of a single dose of 210 mg EVENITY in healthy volunteers resulted in a mean (standarddeviation [SD]) maximum romosozumab-aqqg serum concentration (Cmax) of 22.2 (5.8) mcg/mL and amean (SD) AUC of 389 (127) mcg*day/mL. Steady-state concentrations were achieved by month 3following the monthly administration of 210 mg to postmenopausal women. The mean trough serumromosozumab-aqqg concentrations at months 3, 6, 9, and 12 ranged from 8 to 13 mcg/mL.
Romosozumab-aqqg exhibited nonlinear pharmacokinetics with exposure incr |
