TUZEMTY

, Endocrine and Metabolism, Hypocalcemia). TUZEMTY (denosumab injection) ................................................................................................................... 6% of patients treated with denosumab. 4% of patients treated with denosumab.

Two clinical trials were conducted in subjects without cancer and with varying degrees of renal function. In one study, subjects (N = 55) with varying degrees of renal function (ranging from normal through end- stage renal disease requiring dialysis) received a single 60 mg subcutaneous dose of denosumab.

Hypocalcemia was observed in 8 subjects (15%), 1 (2%) of whom was symptomatic. Two subjects (4%) each experienced an adverse event of hypocalcemia that was classified as serious. Both subjects had severe chronic kidney disease (CKD) and were enrolled before the protocol required supplementation of calcium and vitamin D.

In a second study, patients (N = 32) with severe renal impairment (creatinine clearance less than 30 mL/minute and/or on dialysis) were given two 120 mg subcutaneous doses (Days 1 and 29) of denosumab. Two patients overall (1 in each group) had symptomatic hypocalcemia, based on clinical adverse events and concomitant symptoms.

One patient in the severe CKD group had concomitant muscle spasms and 1 patient in the CKD on dialysis group had concomitant paresthesia. 5%) in the CKD on dialysis group. Both events of symptomatic hypocalcemia were mild in severity.

Accompanying increases in parathyroid hormone (PTH) have also been observed in patients receiving denosumab with severe renal impairment or receiving dialysis. 0 pg/mL) in the severe CKD and CKD on dialysis groups, respectively. 1 pmol/mL) in the severe CKD and CKD on dialysis groups, respectively.

5% in the CKD on dialysis group. 1 pmol/L) in the CKD on dialysis group. 9%) in the CKD on dialysis group. 0 days (6 days, 115 days) in the CKD dialysis group. 0 days) in the CKD on dialysis group. In both studies, there was a greater risk of developing hypocalcemia with increasing degree of renal impairment, and in the absence of, or inadequate calcium supplementation.

3% of patients in the zoledronic acid group (see 7. Warnings and Precautions). Fifty-eight percent of subjects in the denosumab group and 65% of subjects in the zoledronic acid group had a prior or concurrent tooth extraction, 42% of subjects in the denosumab group and 27% of subjects in the zoledronic acid group had used a denture or other dental TUZEMTY (denosumab injection) ...................................................................................................................

Page 19 of 51 Unclassified / Non classifié appliance, and 31% of subjects in the denosumab group and 32% of subjects in the zoledronic acid group had poor oral hygiene. 1 Clinical Trials by Indication). 6 thereafter. 6 months (range: 4 – 53) (see 7 Warnings and Precautions).