New Antiemetic Treats Chemotherapy-Induced Nausea and Vomiting
M. Hancock, APN, MSN, RN, CS, OCN®
Nausea and vomiting are two of the most common symptoms associated
with chemotherapy. A 1993 report of survey findings documented that
patients ranked the feelings of “being sick” (vomiting)
and “feeling sick” (nausea) as the two most feared treatment-related
effects of cancer chemotherapy (Coates et al., 1993). The incidence
of nausea and vomiting depends on the chemotherapeutic regimen and
combination of agents prescribed. Chemotherapeutic agents can be classified
as low, moderate, and high regarding their emetogenic potential. Examples
of highly emetogenic chemotherapeutic agents include cisplatin, cyclophosphamide,
doxorubicin, and methotrexate (Goodman, 1997). If a patient is to
receive a combination of several highly emetogenic agents (i.e., cyclophosphamide
and doxorubicin for treatment of breast cancer), his or her risk for
experiencing nausea and vomiting is increased significantly.
Chemotherapy-induced nausea and vomiting can be characterized as acute,
delayed, persistent, and anticipatory. Cisplatin and other moderately
to highly emetogenic chemotherapy can induce nausea and vomiting that
persists for several days in almost all patients who do not receive
adequate antiemetics, and delayed or persistent nausea and vomiting
also may occur after administration of agents considered to be mildly
to moderately emetogenic (Wickham, 1999). Chemotherapy-induced nausea
and vomiting can severely impact a patient’s quality of life
as well as activities of daily living. As healthcare practitioners,
these symptoms must be recognized and treated adequately.
In March 2004, the U.S. Food and Drug Administration (FDA) approved
Emend® (aprepitant, Merck & Co., Inc., Whitehouse Station,
NJ) for the treatment of chemotherapy-induced nausea and vomiting.
Emend, 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 (Merck & Co., Inc., 2004). Emend’s
primary ingredient, aprepitant, is a selective high-affinity antagonist
of human substance P/neurokinin1 receptors. It has little or
no affinity for serotonin (5-HT3), dopamine, or corticosteroid receptors.
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 that Emend, in combination with ondansteron (Zofran®,
GlaxoSmithKline, Research Triangle Park, NC) and dexamethasone (Decadron®,
Merck & Co., Inc.), prevented acute and delayed nausea and vomiting
associated with highly emetogenic chemotherapy, including high-dose
cisplatin (Merck & Co., Inc., 2004).
More than 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, fluorouracil, gemcitabine, vinorelbine, paclitaxel,
and doxorubicin. The aprepitant-treated subjects ranged in age from
14–84, with a mean age of 56 years (Campos et al., 2001; Navari
et al., 1999).
In both studies, patients receiving the aprepitant had a complete
response to antiemetic therapy in comparison to patients receiving
standard therapy. An additional benefit is that 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 (Merck
& Co., Inc., 2004).
Dosage and Administration
The recommended dosage of Emend is 125 mg orally one hour prior to
chemotherapy treatment (day 1) and 80 mg once daily in the morning
on days 2 and 3. Emend is given as part of a regimen that includes
a corticosteroid and a 5-HT3 antagonist. Emend is supplied in 80 or
125 mg capsules in bottles of 30. Merck & Co., Inc., also offers
a “unit-of-use” trifold pack that contains one 125 mg
capsule and two 80 mg capsules.
Emend should be used in caution with patients receiving concomitant
medicinal products, including chemotherapy agents that are metabolized primarily
through CYP3A4. Inhibition of CYP3A4 by aprepitant could
result in elevated plasma concentrations of these concomitant medicinal
products. The effect of Emend on the pharmacokinetics of orally administered
CYP3A4 substrates is expected to be greater than the effect of Emend
on the pharmacokinetics of IV administered CYP3A4 substrates.
Chemotherapy agents that are known to be metabolized by CYP3A4 include
docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib,
vinorelbine, vinblastine, and vincristine. In clinical studies, Emend
was administered commonly with etoposide, vinorelbine, or paclitaxel.
The doses of these agents were not adjusted to account for potential
drug interactions (Merck & Co., Inc., 2004).
Patients taking the following medications may not take Emend because
of its ability to inhibit CYP34A: pimozide, terfanadine, astemizide,
The most frequently reported adverse effects in the therapeutic trials
of Emend were fatigue (17.8%), hiccups (10.8%), diarrhea (10.3%),
dizziness (6.6%), dehydration (5.9%), abdominal pain (4.6%), and fever
In conclusion, Emend is the first of a new class of antiemetics that
has been proven effective in the treatment of chemotherapy-induced
nausea and vomiting. It is always used concomitantly with a regimen
of other medications (e.g., corticosteroids and a 5-HT3 receptor agonist).
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.
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R.M., et al. (1993). On the receiving end: Patient perception of the
side effects of cancer chemotherapy. European Journal of Cancer
and Clinical Oncology, 29, 203–208.
Goodman, M. (1997). Risk factors and antiemetic management of chemotherapy-induced
nausea and vomiting. Oncology Nursing Forum, 24(Suppl. 7),
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Whitehouse Station, NJ: Author.
Navari, R.M., Reinhardt, R.R., Gralla, R.J., Kris, M.G., Hesketh,
P.J., Khojasteh, A., et al. (1999). Reduction of cisplatin-induced
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Wickham, R.W. (1999). Nausea and vomiting. In C.H. Yarbro, M.H. Frogge,
& M. Goodman (Eds.), Cancer symptom management (2nd ed.,
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