Jane S. Ricciuti, RPh, MS

Disclosures

April 22, 2003

In This Article

Antiemetics

Emend
(aprepitant)Capsules

Manufacturer: Merck & Co, Inc

Drug Approval Classification: Original New Drug Application (Approval Date: 03/26/03)

Indication: Emend (aprepitant), in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin.

Dosing: Emend is given for 3 days as part of a regimen that includes a corticosteroid and a 5-HT3 antagonist. The recommended dose of Emend is 125 mg orally 1 hour prior to chemotherapy treatment (Day 1) and 80 mg once daily in the morning on Days 2 and 3. Emend has not been studied for the treatment of established nausea and vomiting.

Clinical Summary: Aprepitant belongs to a new class of drugs called the neurokinin receptor antagonists. Aprepitant is a potent substance P receptor antagonist belonging to the neurokinin family of neuropeptides. The biological effect of aprepitant is through blocking the neurotransmitter pathway of the neurokinin-1 receptor. It is believed that by blocking the neurokinin-1 receptor, neurokinin-1 antagonist agents could regulate the pathophysiology of the vomiting reflex, depression, and anxiety.

Aprepitant was studied in 2 phase 3 multicenter, randomized, double-blind, parallel-group, active controlled trials in 1099 adult cisplatin-naive patients. Cisplatin-naive patients were treated with chemotherapy regimens that included cisplatin ≥ 70 mg/m2 administered on a single day.

Efficacy of aprepitant demonstrated that 20% fewer patients vomited or required rescue medications for established nausea or emesis. Aprepitant demonstrated efficacy in the delayed phase of chemotherapy-induced nausea and vomiting (CINV), with 30% fewer patients experiencing nausea and vomiting over the control group.

Adverse Effects: The safety of aprepitant was evaluated in approximately 3300 patients. Most adverse events were described as mild to moderate. The most serious adverse events reported in phase 3 trials were neutropenia (2.2%), dehydration (1.8%), and febrile neutropenia (1.3%) -- these adverse events were no greater than those observed in the standard therapy group.

Pharmacokinetics: The mean oral bioavailability of aprepitant is approximately 60% to 65% and the mean peak plasma concentration (Cmax) of aprepitant occurred at approximately 4 hours (Tmax). The pharmacokinetics of aprepitant are nonlinear.

Aprepitant is metabolized primarily by CYP3A4. Aprepitant may interact with some chemotherapy, birth control pills, and warfarin.

Aprepitant does not require dose adjustment in renal insufficiency. There are no clinical or pharmacokinetic studies of aprepitant in severe hepatic insufficiency.

Emend (aprepitant) Labeling

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