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Medical Areas: Gastroenterology | Oncology
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Approval Status: Approved March 2003
Treatment Area: Chemotherapy-induced Nausea and Vomiting
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 prevention of acute and delayed
nausea and vomiting associated with initial and repeat courses of
highly emetogenic cancer chemotherapy.
Emend capsules for oral administration contains either 80 mg or
125 mg of aprepitant.
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
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.
Adverse events associated with the use of Emend may include (but
are not limited to) the following:
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.
b>Campos, D., Pereira, J.R., Reinhardt, R.R., Carracedo, C.,
Poli, S., Vogel, C., et al. (2001). Prevention of cisplatin-induced
emesis by the oral neurokinin-1 antagonist, MK-869, in combination
with granisetron and dexamethasone or with dexamethasone alone.
Journal of Clinical Oncology, 19, 1759-1767.
Herrstedt, J., Aapro, M.S., Smyth, J.F., & Del
Favero, A. (1998). Corticosteroids, dopamine antagonists,
and other drugs. Supportive Care in Cancer, 6,
Martin, A.R., Cai, B., Pearson, J., Horgan, K.,
Wittreich, J., & Gertz, B. (2001). Patient-assessed
impact of chemotherapy-induced nausea on daily life: How much is
too much? [Abstract]. Oncology Nursing Forum, 28, 338.
Navari, R.M., Reinhardt, R.R., Gralla, R.J., Kris, M.G.,
Hesketh, P.J., Khojastem, A., et al. (1999). Reduction of
cisplatin-induced emesis by a selective neurokinin-1-receptor
antagonist. New England Journal of Medicine, 340,