Pharmacokinetic evaluation of fosaprepitant dimeglumine

Abstract

Importance of the field Chemotherapy induced nausea and vomiting (CINV) is a common complication in the treatment of patients with cancer. The introduction of the first in class neurokinin-1 receptor antagonist aprepitant provided additive control on CINV in combination to existing antiemetics. Due to formulation issues, aprepitant is only available for oral administration. Fosaprepitant, a prodrug of aprepitant, was introduced to the market in 2008 as an intravenous bioequivalent to aprepitant. Areas covered in this review This review examines the chemical development of fosaprepitant, its pharmacokinetic properties, approved uses, and potential applications. What the reader will gain The reader will get up-to-date information on the pharmacology and clinical uses of fosaprepitant. Clinical studies have demonstrated pharmacokinetic bioequivalence of aprepitant 125-mg to fosaprepitant 115-mg, as well as comparable efficacy in prevention of acute and delayed emesis following the first day of chemotherapy regimens. Take home message Fosaprepitant is an IV pro-drug of aprepitant that offers a new alternative to patients with CINV. Currently, fosaprepitant can substitute oral aprepitant in the first day of a 3-day regimen. Current studies show that a single-day fosaprepitant regimen is also bioequivalent to the 3-day aprepitant regimen, this could significantly simplify the care for CINV patients in the future.

Study of rolapitant, a novel, long-acting, NK-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC)

“…Rolapitant differs from existing NK-1 receptor antagonists, as it is neither an inhibitor nor inducer of CYP P450 3A4 (CYP3A4) and, thus, is unlikely to produce clinically important drug-drug interactions [28,33,34]. The NK-1 receptor antagonist aprepitant, the prodrug fosaprepitant, and the netupitant combination with palonosetron inhibit or induce CYP3A4 [17,18].…”

Targeting tachykinin receptors in neuroblastoma

“…Fosaprepitant (Ivemend), is a water-soluble phosphoryl prodrug of aprepitant, which is intravenously administered [5]. Currently, these drugs are used in clinical practice as antiemetics for neuroblastoma patients receiving emetogenic chemotherapy agents including platinum-based chemotherapeutics [3], and no considerable side effects have been observed.…”

Benefits and Risks of Fosaprepitant in Patients Receiving Emetogenic Regimens

“…When administered via a central venous access device, it is infused over 20 minutes, and when administered via a peripheral site, it is infused over 30 minutes. Some of the common side effects of fosaprepitant are headache, weakness, constipation, diarrhea, abdominal pain, anorexia, dizziness, and hiccups (Colon-Gonzalez & Kraft, 2010). Fosaprepitant is a cost-effective antiemetic medication when compared to the three-day oral aprepitant antiemetic regimen, which costs about $705 (Lexicomp, 2016a).…”