General Information

Emend (aprepitant), a P/neurokinin 1 (NK1) receptor antagonist, is an antiemetic medicine used to prevent and control nausea and vomiting caused by chemotherapy treatment. It is always used in combination with other antiemetic agents.

Emend is indicated for the following:

Emend is supplied as capsules or as an oral suspension.  

Emend for oral suspension is indicated in combination with other antiemetic agents, in patients 6 months of age and older for prevention of:

• acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin
• nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC)

Emend capsules is indicated in combination with other antiemetic agents, in patients 12 years of age and older for prevention of:

• acute and delayed nausea and vomiting associated with initial and repeat courses of HEC including high-dose cisplatin
• nausea and vomiting associated with initial and repeat courses of MEC

The recommended dose of Emend capsules in adults and pediatric patients 12 years of age and older: is 125 mg on Day 1 and 80 mg on Days 2 and 3.

The recommended dose of Emend for oral suspension in pediatric patients 6 months to less than 12 years of age or pediatric and adult patients unable to swallow capsules is as follows:

• Day 1: 3 mg/kg orally, Maximum dose 125 mg
• Day 2: 2 mg/kg orally, Maximum dose 80 mg
• Day 3: 2 mg/kg orally, Maximum dose 80 mg

Administer Emend 1 hour prior to chemotherapy on Days 1, 2, and 3. If no chemotherapy is given on Days 2 and 3, administer Emend in morning

Mechanism of Action

Emend’s main ingredient, aprepitant, is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Unlike other chemotherapy-induced side effect treatments, it has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors.

The drug has been shown in preclinical trials to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. In addition, animal and human studies using Positron Emission Tomography (PET) have shown that it crosses the blood brain barrier and occupies brain NK1 receptors. It also augments the activity of the 5-HT3-receptor antagonist ondansetron and the corticosteroid dexamethasone and inhibits both the acute and delayed phases of cisplatin-induced emesis.

Side Effects

Adverse events associated with the use of Emend in adults may include, but are not limited to, the following:

fatigue

diarrhea

asthenia

dyspepsia

abdominal pain

hiccups

white blood cell count decreased

dehydration

alanine aminotransferase increased

Adverse events associated with the use of Emend in pediatrics may include, but are not limited to, the following:

• neutropenia
• headache
• diarrhea
• decreased appetite
• cough
• fatigue
• hemoglobin decreased
• dizziness
• hiccups

Clinical Trial Results

FDA approval of Emend was based on two multicenter, randomized, parallel, double-blind, controlled clinical studies. Treatment with aprepitant was compared with standard therapy in subjects receiving a chemotherapy regimen that included cisplatin > 50 mg/m². Results showed Emend, in combination with ondansetron and dexamethasone, prevented acute and delayed nausea and vomiting associated with highly emetogenic chemotherapy including high-dose cisplatin.

In both studies, a statistically significantly higher proportion of subjects receiving aprepitant had a complete response, compared with subjects receiving standard therapy. A statistically significant difference in complete response in favor of the aprepitant regimen was also observed. In addition, the estimated time to first emesis after initiation of cisplatin treatment was longer with the Emend treatment, and the incidence of first emesis was reduced in the aprepitant regimen group compared with standard therapy group.

Over 1,000 subjects were randomized to either the aprepitant regimen or standard therapy with 95% of the subjects in the aprepitant group receiving a concomitant chemotherapeutic agent in addition to protocol-mandated cisplatin. The most common chemotherapeutic agents were etoposide, flourouracil, gemcitabine, vinorelbine, paclitaxel and doxorubicin. The aprepitant-treated subjects ranged from 14 to 84 years of age, with a mean age of 56 years. 170 subjects were 65 years or older, with 29 subjects being 75 years or older.