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 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.

Clinical 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.

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.

Literature References

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, 204-214.

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, 190-195.