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Aprepitant: A Novel Antiemetic for Chemotherapy-Induced Nausea and Vomiting
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| OBJECTIVE: To evaluate the safety and efficacy of aprepitant in the prevention of acute and delayed chemotherapy-induced nausea
and vomiting (CINV). DATA SOURCES: MEDLINE and PubMed database searches were conducted from 1966 to May 2004 using the following search terms: aprepitant, Emend, substance P, neurokinin-1, chemotherapy, nausea, vomiting, L-754,030, and MK-869. STUDY SELECTION AND DATA EXTRACTION: Large, randomized Phase II and III clinical trials examining the use of aprepitant for CINV, as well as all published drug interaction studies with aprepitant, were included and reviewed. Data lacking in published trials were supplemented with the manufacturer product information. DATA SYNTHESIS: The pharmacokinetics of aprepitant are favorable for once-daily oral dosing. Based on the results of published clinical trials, aprepitant appears to augment the effects of corticosteroids and 5-HT3 antagonists when given prior to highly emetogenic chemotherapy, including cisplatin. Aprepitant appears to have the most benefit in the prevention of delayed CINV and in preventing emesis rather than nausea. Data in pediatric patients, patients undergoing stem-cell transplantation, and those receiving multiple-day or moderately emetogenic chemotherapy are lacking. Common adverse effects are limited to hiccups, asthenia, and diarrhea. More serious but rare adverse effects include neutropenia. Because aprepitant is a CYP3A4 substrate, a 3A4 inhibitor and inducer, and a 2C9 inducer, close monitoring for drug interactions is warranted. CONCLUSIONS: Triple antiemetic therapy with aprepitant, a corticosteroid, and a 5-HT3 antagonist appears to provide improved efficacy in the prevention of emesis in patients receiving highly emetogenic chemotherapy. Due to its novel mechanism of action and demonstrated efficacy in this combination, aprepitant should be considered for formulary addition. Key Words: aprepitant, nausea and vomiting, neurokinin-1, substance P Published Online, October 23, 2004. www.theannals.com, DOI 10.1345/aph.1E242 THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-05-002-H01 |
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