BOMYNTRA

Following subcutaneous administration, bioavailability was 62%. Denosumab displayed nonlinear pharmacokinetics at doses below 60 mg, but approximately dose-proportional increases in exposure at higher doses. With multiple subcutaneous doses of 120 mg once every 4 weeks, up to 2.8-fold accumulation in serum denosumab concentrations was observed and steady-state was achieved by 6 months. A mean (± standard deviation) serum steady-state trough concentration of 20.5 (± 13.5) mcg/mL was achieved by 6...

14 CLINICAL TRIALS 14.1 Bone Metastasis from Solid Tumors The safety and efficacy of denosumab for the prevention of skeletal-related events in patients with bone metastases from solid tumors was demonstrated in three international, randomized (1:1), double-blind, active-controlled, noninferiority trials comparing denosumab with zoledronic acid. In all three trials, patients were randomized to receive 120 mg denosumab subcutaneously every 4 weeks or 4 mg zoledronic acid intravenously (IV) every 4 weeks (dose adjusted for reduced renal function). Patients with creatinine clearance less than 30 ...

The following adverse reactions are discussed below and elsewhere in the labeling: Hypersensitivity [see Warnings and Precautions ( 5.2 )] Hypocalcemia [see Warnings and Precautions ( 5.3 ) and Use in Specific Populations ( 8.6 )] Osteonecrosis of the Jaw [see Warnings and Precautions ( 5.4 )] Atypical Subtrochanteric and Diaphyseal Femoral Fracture [see Warnings and Precautions ( 5.5 )] Hypercalcemia following treatment discontinuation in patients with giant cell tumor of bone and in patients w...

Hypocalcemia ( 4.1 ) Known clinically significant hypersensitivity to denosumab products ( 4.2 ) 4.1 Hypocalcemia Pre-existing hypocalcemia must be corrected prior to initiating therapy with Bomyntra [see Warnings and Precautions ( 5.3 )] . 4.2 Hypersensitivity Bomyntra is contraindicated in patients with known clinically significant hypersensitivity to denosumab products [see Warnings and Precaut...

Drug Products with Same Active Ingredient: Patients receiving Bomyntra should not receive other denosumab products concomitantly ( 5.1 ) Hypersensitivity reactions including anaphylaxis may occur. Discontinue permanently if a clinically significant reaction occurs. ( 5.2 ) Hypocalcemia: Denosumab products can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Correct hypocalcemia prior to initiating Bomyntra. Monitor calcium levels during therapy, especially in the first ...