Fosaprepitant is a prodrug of aprepitant and accordingly, its antiemetic effects are attributable to aprepitant. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CINV). Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with aprepitant have shown that it crosses the blood brain barrier and occupies brain NK1 receptors. Animal and human studies have shown that aprepitant augments the antiemetic activity of the 5-HT3-receptor antagonist ondansetron and the corticosteroid dexamethasone and inhibits both the acute and delayed phases of cisplatin-induced emesis.

EMEND for injection is a substance P/neurokinin-1 (NK1) receptor antagonist, indicated in adults and pediatric patients 6 months of age and older, in combination with other antiemetic agents, for the prevention of :
• acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin.
• delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). Limitations of Use.
• EMEND has not been studied for the treatment of established nausea and vomiting.

• Recommended Dosage.
• Adults: 150 mg on Day 1.
• Pediatrics (6 months to 17 years): a single-day of EMEND for injection on Day 1 (for single dose chemotherapy regimens) or a 3- day EMEND regimen of EMEND for injection on Day 1 and EMEND capsules or oral suspension on Days 2 and 3 (for single or multi-day chemotherapy regimens).
• Administer EMEND for injection on Day 1 as an intravenous infusion over 20 to 30 minutes (adults), 30 minutes (12 years to 17 years) or 60 minutes (6 months to less than 12 years) completing the infusion approximately 30 minutes prior to chemotherapy.
• In pediatrics, administer EMEND through a central venous catheter.
• See Full Prescribing Information for dosages of concomitant antiemetic(s) and pediatric dosages of EMEND.

• Most common adverse reactions in adults (≥2%) are: fatigue, diarrhea, neutropenia, asthenia, anemia, peripheral neuropathy, leukopenia, dyspepsia, urinary tract infection, pain in extremity.
• Adverse reactions in pediatrics are similar to adults.

• Known hypersensitivity to any component of this drug.
• Concurrent use with pimozide.

• CYP3A4 Interactions: Fosaprepitant is a weak inhibitor of CYP3A4, and aprepitant, the active moiety, is a substrate, inhibitor, and inducer of CYP3A4; see Full Prescribing Information for recommendations regarding contraindications, risk of adverse reactions, and dosage adjustment of EMEND and concomitant drugs.
• Hypersensitivity Reactions (including anaphylaxis and anaphylactic shock): May occur during or soon after infusion. If symptoms occur, discontinue the drug. Do not reinitiate EMEND if symptoms occur with previous use.
• Infusion Site Reactions (including thrombophlebitis, necrosis, and vasculitis): Majority of reactions reported in patients receiving vesicant chemotherapy. Avoid infusion into small veins. Discontinue infusion and administer treatment if a severe reaction develops. See package insert for complete information.