Netupitant/palonosetron Disease Interactions

Limited data are available with fosnetupitant (only available in combination with palonosetron in the US) in patients with severe hepatic impairment (Child-Pugh score greater than 9), therefore, its use should be avoided in these patients. No dosage adjustment is necessary for patients with mild to moderate hepatic impairment (Child-Pugh score 5 to 8).

No dosage adjustment for netupitant/fosnetupitant (only available in combination with palonosetron in the US), is necessary in patients with mild to moderate renal impairment (creatinine clearance of 30 to 60 mL/min). The pharmacokinetics and safety of netupitant/fosnetupitant have not been studied in patients with severe renal impairment. Severe renal impairment (creatinine clearance < 30 mL/min) did not substantially affect pharmacokinetics of palonosetron. The pharmacokinetics for netupitant and palonosetron were not studied in patients with end-stage renal disease requiring hemodialysis, therefore, avoid the use of this drug in patients with severe renal impairment or end-stage renal disease.

Netupitant is extensively metabolized to form three major metabolites: desmethyl derivative, M1; N-oxide derivative, M2; and OH-methyl derivative, M3. Metabolism is mediated primarily by CYP450 3A4 and to a lesser extent by CYP450 2C9 and CYP450 2D6. Care should be exercised when using this agent in patients with hepatic impairment. In patients with mild or moderate hepatic impairment, the mean AUC from zero to infinity (AUCinf) of netupitant was 67% and 86% higher, respectively, than in healthy subjects and the mean Cmax for netupitant was about 40% and 41% higher, respectively, than in healthy subjects. Avoid use in patients with severe hepatic impairment.

Population pharmacokinetic analysis showed that mild and moderate renal impairment (creatinine clearance 30 to 60 mL/min) did not significantly affect the pharmacokinetics of netupitant. The pharmacokinetics and safety of netupitant have not been studied in patients with severe renal impairment. Avoid use in patients with severe renal impairment or end-stage renal disease.

Mild to moderate renal impairment does not significantly affect palonosetron pharmacokinetic parameters. However, total systemic exposure increased approximately 28% in patients with severe renal impairment. Additionally, the pharmacokinetics of palonosetron have not been studied in patients with end-stage renal disease. Caution is advised.

No dosage adjustment for palonosetron is necessary for patients with mild to moderate hepatic impairment (Child-Pugh score 5 to 8). Limited data are available in patients with severe hepatic impairment (Child-Pugh score greater than 9). It is recommended to avoid use of palonosetron in patients with severe hepatic impairment.