saprepitant has not been eva luated in patients below 18 years of age.
Race
Following oral administration of a single 125-mg dose of aprepitant, the AUC0-24hr is approximately 25% and 29% higher in Hispanics as compared with Whites and Blacks, respectively. The Cmax is 22% and 31% higher in Hispanics as compared with Whites and Blacks, respectively. These differences are not considered clinically meaningful. There was no difference in AUC0-24hr or Cmax between Whites and Blacks. No dosage adjustment is necessary based on race.
Hepatic Insufficiency
Fosaprepitant is metabolized in various extrahepatic tissues; therefore hepatic insufficiency is not expected to alter the conversion of fosaprepitant to aprepitant.
Oral aprepitant was well tolerated in patients with mild to moderate hepatic insufficiency. Following administration of a single 125-mg dose of oral aprepitant on Day 1 and 80 mg once daily on Days 2 and 3 to patients with mild hepatic insufficiency (Child-Pugh score 5 to 6), the AUC0-24hr of aprepitant was 11% lower on Day 1 and 36% lower on Day 3, as compared with healthy subjects given the same regimen. In patients with moderate hepatic insufficiency (Child-Pugh score 7 to 9), the AUC0-24hr of aprepitant was 10% higher on Day 1 and 18% higher on Day 3, as compared with healthy subjects given the same regimen. These differences in AUC0-24hr are not considered clinically meaningful; therefore, no dosage adjustment is necessary in patients with mild to moderate hepatic insufficiency.
There are no clinical or pharmacokinetic data in patients with severe hepatic insufficiency (Child-Pugh score >9) (see PRECAUTIONS).
Renal Insufficiency
A single 240-mg dose of oral aprepitant was administered to patients with severe renal insufficiency (CrCl<30 mL/min) and to patients with end stage renal disease (ESRD) requiring hemodialysis.
In patients with severe renal insufficiency, the AUC0-∞ of total aprepitant (unbound and protein bound) decreased by 21% and Cmax decreased by 32%, relative to healthy subjects. In patients with ESRD undergoing hemodialysis, the AUC0-∞ of total aprepitant decreased by 42% and Cmax decreased by 32%. Due to modest decreases in protein binding of aprepitant in patients with renal disease, the AUC of pharmacologically active unbound drug was not significantly affected in patients with renal insufficiency compared with healthy subjects. Hemodialysis conducted 4 or 48 hours after dosing had no significant effect on the pharmacokinetics of aprepitant; less than 0.2% of the dose was recovered in the dialysate.
No dosage adjustment is necessary for patients with renal insufficiency or for patients with ESRD undergoing hemodialysis.
Pharmacodynamics
Cardiac Electrophysiology
In a randomized, double-blind, positive-controlled, thorough QTc study, a single 200-mg dose of fosaprepitant had no effect on the QTc interval.
Clinical Studies
Fosaprepitant, a prodrug of aprepitant, when administered intravenously is rapidly converted to aprepitant. Fosaprepitant 115 mg I.V. infused over 15 minutes can be substituted for 125 mg oral aprepitant on Day 1 (see DOSAGE AND ADMINISTRATION). Pivotal efficacy studies were conducted with oral aprepitant.
Oral administration of aprepitant in combination with ondansetron and dexamethasone (aprepitant regimen) has been shown to prevent acute and delayed nausea and vomiting associated with highly emetogenic chemotherapy including high-do |
