OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Aprepitant – Generic, Emend®

Fosaprepitant – Emend®

DRUG CLASS

Gastrointestinal Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Aprepitant	170729-80-3	C23-H21-F7-N4-O3

ANNOTATED BIBLIOGRAPHY

References updated: 28 February 2024

• Zimmerman HJ. Antiemetic and prokinetic compounds. Miscellaneous drugs and diagnostic chemicals. In, Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999: pp. 721.

  (Expert review of hepatotoxicity published in 1999 before the availability of NK1 antagonists such as aprepitant).
• Sharkey KA, McNaughton WK. Gastrointestinal motility and water flux, emesis, and biliary and pancreatic disease. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 921-44.

  (Textbook of pharmacology and therapeutics).
• Navari RM. Aprepitant: a neurokinin-1 receptor antagonist for the treatment of chemotherapy-induced nausea and vomiting. Expert Rev Anticancer Ther. 2004;4:715–724. [PubMed: 15485308]

  (Review of the structure, pharmacokinetics, metabolism, mechanism of action, efficacy and safety of aprepitant mentions that adverse events may include fatigue, anorexia, constipation, diarrhea, nausea, and hiccups, but the rate of adverse events is not increased by adding aprepitant to standard preventive regimens).
• Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Julie Ma G, Eldridge K, Hipple A, Evans JK, et al; Aprepitant Protocol 054 Study Group. Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer. 2003;97:3090–3098. [PubMed: 12784346]

  (Among 523 patients with cancer treated with ondansetron and dexamethasone with or without aprepitant to prevent nausea and vomiting after chemotherapy, nausea and vomiting was less with aprepitant, but side effects were similar in the two groups including rates of ALT and AST elevations above 5 times ULN [actual rates not provided]).
• Gralla RJ, de Wit R, Herrstedt J, Carides AD, Ianus J, Guoguang-Ma J, Evans JK, et al. Antiemetic efficacy of the neurokinin-1 antagonist, aprepitant, plus a 5HT3 antagonist and a corticosteroid in patients receiving anthracyclines or cyclophosphamide in addition to high-dose cisplatin: analysis of combined data from two Phase III randomized clinical trials. Cancer. 2005;104:864–868. [PubMed: 15973669]

  (Analysis of results from two large studies in more than 1000 cancer patients who received aprepitant vs placebo in addition to ondansetron and dexamethasone during chemotherapy; both early and delayed nausea and vomiting were decreased in those receiving aprepitant in comparison to controls; no mention of side effects, hepatotoxicity or ALT levels).
• Jordan K, Kinitz I, Voigt W, Behlendorf T, Wolf HH, Schmoll HJ. Safety and efficacy of a triple antiemetic combination with the NK-1 antagonist aprepitant in highly and moderately emetogenic multiple-day chemotherapy. Eur J Cancer. 2009;45:1184–1187. [PubMed: 19135359]

  (Among 78 patients with cancer treated with aprepitant, granisetron and dexamethasone to prevent the nausea and vomiting of cancer chemotherapy, side effects were largely attributed to the antineoplastic agents; no mention of ALT elevations or hepatotoxicity).
• Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52:2065–2076. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, but none were attributed to an antiemetic agent).
• Ferrajolo C, Capuano A, Verhamme KM, Schuemie M, Rossi F, Stricker BH, Sturkenboom MC. Drug-induced hepatic injury in children: a case/non-case study of suspected adverse drug reactions in VigiBase. Br J Clin Pharmacol. 2010;70:721–728. [PMC free article: PMC2997312] [PubMed: 21039766]

  (Among 624,673 adverse event reports in children between 2000 and 2006 in the WHO VigiBase, 1% were hepatic but no antiemetic was listed among the 41 most commonly implicated agents).
• Jordan K, Jahn F, Jahn P, Behlendorf T, Stein A, Ruessel J, Kegel T, et al. The NK-1 receptor-antagonist aprepitant in high-dose chemotherapy (high-dose melphalan and high-dose T-ICE: paclitaxel, ifosfamide, carboplatin, etoposide): efficacy and safety of a triple antiemetic combination. Bone Marrow Transplant. 2011;46:784–789. [PubMed: 20838387]

  (Among 64 patients with cancer treated with aprepitant, dexamethasone and granisetron to prevent chemotherapy induced nausea and vomiting, side effects were largely due to the antineoplastic agents; no mention of ALT elevations or hepatotoxicity).
• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144:1419–1425. [PubMed: 23419359]

  (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, but none were attributed to antiemetics).
• Saito H, Yoshizawa H, Yoshimori K, Katakami N, Katsumata N, Kawahara M, Eguchi K. Efficacy and safety of single-dose fosaprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving high-dose cisplatin: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial. Ann Oncol. 2013;24:1067–1073. [PMC free article: PMC3603438] [PubMed: 23117073]

  (Among 347 patients with cancer treated with granisetron and dexamethasone with or without fosaprepitant to prevent nausea and vomiting after cisplatin based chemotherapy, side effects were similar between the two groups; no mention of ALT elevations or hepatotoxicity).
• Stiff PJ, Fox-Geiman MP, Kiley K, Rychlik K, Parthasarathy M, Fletcher-Gonzalez D, Porter N, et al. Prevention of nausea and vomiting associated with stem cell transplant: results of a prospective, randomized trial of aprepitant used with highly emetogenic preparative regimens. Biol Blood Marrow Transplant. 2013;19:49–55.e1. [PubMed: 22863840]

  (Among 181 patients undergoing hematopoietic cell transplantation for malignant disease who received ondansetron and dexamethasone with either aprepitant or placebo to prevent chemotherapy induced nausea and vomiting, nausea was less with aprepitant, but other side effects were similar in the two groups, although 5 died in the aprepitant arm [one from toxic epidermal necrolysis and one from sinusoidal obstruction syndrome] compared to only 2 in the control group).
• Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata RA, Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America. An analysis of published reports. Ann Hepatol. 2014;13:231–239. [PubMed: 24552865]

  (Systematic review of literature of drug induced liver injury in Latin American countries published from 1996 to 2012 identified 176 cases, the most common implicated agents being nimesulide [n=53: 30%], cyproterone [n=18], nitrofurantoin [n=17], antituberculosis drugs [n=13] and flutamide [n=12: 7%]; no antiemetic was listed).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology. 2015;148:1340–52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, none were attributed to aprepitant or other antiemetic agents).
• IV aprepitant (Cinvanti) for chemotherapy-induced nausea and vomiting. Med Lett Drugs Ther. 2018;60:e200–e201. [PubMed: 30653479]

  (Concise review of the mechanism of action, clinical efficacy, safety, and costs of aprepitant, the first substance P inhibitor approved for prevention of nausea and vomiting after highly emetogenic chemotherapy; in discussion of adverse events, no mention of ALT elevations or hepatotoxicity).
• Aapro M, Navari RM, Roeland E, Zhang L, Schwartzberg L. Efficacy of intravenous NEPA, a fixed NK/5-HT receptor antagonist combination, for the prevention of chemotherapy-induced nausea and vomiting (CINV) during cisplatin- and anthracycline cyclophosphamide (AC)-based chemotherapy: a review of phase 3 studies. Crit Rev Oncol Hematol. 2021;157:103143. [PubMed: 33260048]

  (Analysis of 15 studies of NK-1 receptor inhibitors compared to 5-HT3 receptor inhibitors, including 2077 patients treated with both fosnetupitant and palonosetron [NEPA], 403 orally and 1674 intravenously [iv], the overall complete response with cisplatin regimens was 77% for iv NEPA, which was similar for oral NEPA [75-90%], and was higher than that with other NK-1/5-HT3 combinations [66-78%], mentions that NK-1 inhibitors were “safe and well tolerated”; no discussion of ALT elevations or hepatotoxicity).
• Hata A, Okamoto I, Inui N, Okada M, Morise M, Akiyoshi K, Takeda M, et al. Randomized, double-blind, phase III study of fosnetupitant versus fosaprepitant for prevention of highly emetogenic chemotherapy-induced nausea and vomiting: CONSOLE. J Clin Oncol. 2022;40:180–188. [PMC free article: PMC8718175] [PubMed: 34793245]

  (Among 795 patients treated with iv fosnetupitant or fosaprepitant combined with iv palonosetron and 4 days of oral dexamethasone, the complete response rates were 75% vs 71% and treatment related adverse event rates 22% vs 25%, while injection site reactions were less with NEPA [11% vs 21%]).
• Zhang Z, Yang Y, Lu P, Li X, Chang J, Zheng R, Zhou L. Cet al. Fosaprepitant versus aprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based chemotherapy: a multicenter, randomized, double-blind, double-simulated, positive-controlled phase III trial. Ann Transl Med. 2020;8:234. [PMC free article: PMC7154406] [PubMed: 32309381]

  (Among 644 Chinese adults receiving cisplatin based chemotherapy who were treated with palonosetron and dexamethasone with either fosaprepitant [single 150 mg iv dose] or aprepitant [orally for 3 days as 125 , 80, and 80 mg], rates of complete response were similar [72% vs 67%] as were total adverse events [85% vs 84%] and serious adverse events [1.9% vs 2.5%, all considered “unrelated”], and side effects were similar in the two groups; no mention of ALT elevations or hepatotoxicity).
• Wang DS, Hu MT, Wang ZQ, Ren C, Qiu MZ, Luo HY, Jin Y, et al. Effect of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in women: a randomized clinical trial. JAMA Netw Open. 2021;4:e215250. [PMC free article: PMC8035650] [PubMed: 33835174]

  (Among 248 women receiving cancer chemotherapy treated with palonosetron and dexamethasone with either oral aprepitant for 3 days [125, 80 and 80 mg] or placebo, complete response [no emesis or rescue therapy] rates were 87% vs 67% and adverse event rates were similar with no serious adverse events attributable to the antiemetics; no mention of ALT elevations or hepatotoxicity).
• Matsuura K, Tsurutani J, Inoue K, Tanabe Y, Taira T, Kubota K, Tamura T, et al. A phase 3 safety study of fosnetupitant as an antiemetic in patients receiving anthracycline and cyclophosphamide: CONSOLE-BC. Cancer. 2022;128:1692–1698. [PMC free article: PMC9306508] [PubMed: 35045185]

  (Among 102 patients treated with iv fosnetupitant or fosaprepitant in combination with palonosetron before receiving cancer chemotherapy, the complete response rate was 46% vs 51% and treatment related adverse event rates were similar [21% vs 22%], although injection site reactions were less frequent with fosnetupitant [6% vs 26%]).
• Dranitsaris G, Moezi M, Dobson K, Phelan R, Blau S. A real-world study to evaluate the safety and efficacy of three injectable neurokinin-1 receptor antagonist formulations for the prevention of chemotherapy-induced nausea and vomiting in cancer patients. Support Care Cancer. 2022;30:6649–6658. [PMC free article: PMC9213362] [PubMed: 35499619]

  (Among 294 adults receiving prophylaxis for nausea and vomiting for cancer chemotherapy in 17 community hospitals, those receiving fosaprepitant had slightly lower rates of control of nausea and vomiting and higher rates of infusion reactions compared to those receiving fosnetupitant, while most other adverse event rates were similar; no mention of ALT elevations or hepatotoxicity).
• Yu LT, Wang Z, Han YL, Zhou F, Wagner LM, Zhang SG, Li ZL, et al. Comparison of oral aprepitant and intravenous fosaprepitant for prevention of chemotherapy-induced nausea and vomiting in pediatric oncology patients: a randomized phase III trial. Transl Pediatr. 2024;13:110–118. [PMC free article: PMC10839286] [PubMed: 38323173]

  (Among 108 Chinese children receiving cancer chemotherapy treated with ondansetron and dexamethasone with either a single infusion of fosaprepitant or 3 days of oral aprepitant, the control of early nausea and vomiting [day 1] was higher with fosaprepitant [95% vs 79%] but not for combined early and late [days 1-5] symptoms [71% vs 67%], and adverse event rates were similar and largely due to the chemotherapy; no mention of ALT elevations or hepatotoxicity).