Pro-netupitant/palonosetron (IV) for the treatment of radio-and-chemotherapy-induced nausea and vomiting

Abstract

Prevention of nausea and vomiting is of paramount importance for ensuring that patients undergoing anticancer treatments have optimal quality of life. The oral fixed-dose combination of netupitant/palonosetron (NEPA) was developed to improve dual-targeted anti-emetic prophylaxis administration. Areas covered: This article summarizes the available evidence for the pharmacology, safety, and efficacy of the new intravenous formulation of NEPA (IV NEPA). The clinical role of NEPA and future perspectives for anti-emetic research are also discussed. Expert opinion: Each patient undergoing emetogenic anticancer treatments should receive guideline-consistent prophylaxis from the beginning of therapy. However, physicians may be nonadherent to guidelines in prescribing prophylaxis, while patients may be nonadherent in taking their medication as prescribed. Therefore, simplification of anti-emetic regimens with agents that are administered once per treatment cycle may contribute to improve guideline adherence by physicians and compliance with regimens by patients. IV NEPA may also help overcome potential logistical issues surrounding the oral administration of NEPA. While short-term olanzapine can improve control of nausea, it also causes transient but significantly increased sedation. This side effect as well as new evidence support further efforts to explore the overall potential of NEPA against nausea caused by either chemotherapy or concurrent chemo-radiotherapy.

Fosnetupitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Short Review and Clinical Perspective

“…Fosnetupitant is a novel NK 1 receptor antagonist for intravenous administration, which has high selectivity and affinity for NK 1 receptors [ 20 , 21 ].…”

“…After administration, fosnetupitant is rapidly converted to its active form, netupitant, by phosphatases distributed widely through the body [ 21 , 22 ], giving fosnetupitant a half-life of 0.6 h [ 23 ]. Netupitant is eliminated slowly, with a half-life of approximately 70 h [ 23 ], and is primarily metabolized in the liver by cytochrome P450 (CYP) 3A to three active metabolites [ 24 , 25 ], with little contribution from renal excretion [ 26 ].…”