XGEVA® (denosumab) pharmacokinetics
Following administration, XGEVA® bioavailability is 62%. Since XGEVA® consists of only amino acids and carbohydrates as native immunoglobulin, it is unlikely to be eliminated via hepatic metabolism. Metabolism and elimination of XGEVA® are expected to follow immunoglobulin clearance pathways, with small peptides and amino acids as final products of metabolism. After 6 months of treatment with multiple doses of 120 mg every four weeks an approximately 2-fold accumulation in serum XGEVA® concentration was observed. In patients who discontinued this dosing, the mean half-life was 28 days (range 14–55 days). No clinically significant changes in systemic exposure of XGEVA® at steady state have been observed related to differences in age, ethnicity, gender or solid tumour type. Body weight has been shown to be inversely related to systemic exposure, but differences were not clinically relevant. XGEVA® has displayed non-linear pharmacokinetics over a wide dose range.[SmPC, p. 13]
Renal impairment
XGEVA® has been assessed in patients with varying degrees of renal function, including patients on dialysis, and the degree of renal impairment has no effect on the pharmacokinetics of XGEVA®. No dose adjustment or renal monitoring is required in patients with renal impairment receiving XGEVA® therapy.[SmPC, p. 13]
Hepatic impairment
No specific studies have been conducted in patients with impaired hepatic function, but since monoclonal antibodies are generally not eliminated by hepatic metabolism mechanisms, hepatic impairment is not expected to affect XGEVA® pharmacokinetics.[SmPC, p. 13]
Paediatric population
XGEVA® pharmacokinetics have not been assessed in paediatric patients.[SmPC, p. 14]