Pharmacological Class:
Substance P/neurokinin 1 (NK1) receptor antagonist + serotonin-3 (5-HT3) receptor antagonist.

Active Ingredient(s):
Netupitant, palonosetron (as HCl) 300mg/0.5mg; hard gelatin capsules.

Company
Eisai Pharmaceuticals
Indication(s):
Prevention of acute and delayed nausea and vomiting due to initial and repeat courses of chemotherapy, including highly emetogenic chemotherapy.

Pharmacology:
Netupitant is a selective antagonist of human substance P/neurokinin 1 (NK1) receptors. Palonosetron is a 5-HT3 receptor antagonist with a strong binding affinity for this receptor and little or no affinity for other receptors. Delayed emesis has been largely associated with the activation of tachykinin family NK1 receptors (broadly distributed in the central and peripheral nervous systems) by substance P.

Clinical Trials:
In a multicenter, randomized, parallel, double-blind controlled trial of 694 patients, the efficacy and safety of a single dose of oral netupitant in combination with oral palonosetron was compared to a single oral dose of palonosetron in cancer patients receiving chemotherapy that included cisplatin. Efficacy was assessed in 135 patients who received Akynzeo (netupitant 300mg + palonosetron 0.5mg) and 136 patients who received oral palonosetron 0.5mg.

The key efficacy endpoints were complete response (CR), defined as no emetic episode and no use of rescue medication for the 25–120 hour interval (delayed phase); CR for the 0–24 hour interval (acute phase); and CR within 120 hours (overall phase) after the start of chemotherapy.

Results demonstrated that in the netupitant + palonosetron group, 90.4% of patients achieved CR in the delayed phase, 98.5% in the acute phase, and 89.6% in the overall phase vs. 80.1% (P=0.032), 89.7% (P=0.002), and 76.5% (P=0.003) of patients in the oral palonosetron group, respectively.

In another multicenter, randomized, parallel, double-blind, active controlled, superiority trial (N=1,455), a single oral dose of netupitant + palonosetron was compared with a single oral dose of palonosetron 0.5mg in cancer patients scheduled to receive the first cycle of an anthracycline/cyclophosphamide regimen. All patients received a single oral dose of dexamethasone. Results demonstrated that in the netupitant + palonosetron group, 76.9% of patients achieved CR in the delayed phase vs. 69.5% in the palonosetron group (P=0.001).

For more clinical trial data, see full labeling.

Legal Classification:
Rx

Adults:
≥18 years: Highly emetogenic chemotherapy (including cisplatin-based): 1 capsule approximately 1 hour prior to chemotherapy with oral dexamethasone 12mg given 30 minutes before chemotherapy on Day 1, then 8mg orally once daily on Days 2–4. Anthracyclines and cyclophosphamide-based chemotherapy, or non-highly emetogenic chemotherapy: 1 capsule approximately 1 hour prior to chemotherapy with oral dexamethasone 12mg given 30 minutes prior to chemotherapy on Day 1.

Children:
<18 years: not established.

Warnings/Precautions:
Monitor for symptoms of serotonin syndrome; discontinue and treat if occurs. Severe hepatic or renal impairment, ESRD: avoid. Elderly. Pregnancy (Category C). Nursing mothers: not recommended.

Interaction(s)
Increased risk of serotonin syndrome with concomitant other serotonergic drugs (eg, SSRIs, SNRIs, MAOIs, mirtazapine, fentanyl, lithium, tramadol, IV methylene blue). May potentiate CYP3A4 substrates (eg, dexamethasone [use reduced dose], midazolam, alprazolam, triazolam, docetaxel, paclitaxel, etoposide, irinotecan, cyclophosphamide, ifosfamide, imatinib, vinorelbine, vinblastine, vincristine); caution and monitor. Avoid concomitant strong CYP3A4 inducers (eg, rifampin). Potentiated by strong CYP3A4 inhibitors (eg, ketoconazole).

Adverse Reaction(s)
Headache, asthenia, dyspepsia, fatigue, constipation, erythema; hypersensitivity reactions.

How Supplied:
Blister—1

LAST UPDATED:
2/20/2015

AKYNZEO奈妥吡坦和帕洛诺司琼胶囊  (palonosetron+Netupitant)

复方化疗止吐药-Akynzeo获准上市

    最新消息报道称，由卫材研制的复方止吐药物——Akynzeo获美国FDA 批准上市，用于治疗与癌症化疗相关的恶心和呕吐。

    Akynzeo为帕洛诺司琼和奈妥吡坦组成的复方药物。帕洛诺司琼于2008年获批用于预防癌症化疗急性期（启动化疗24小时内）产生的恶心和呕吐，奈妥吡坦则是一种新药，能够有效预防癌症化疗急性期和延迟期（启动化疗25-120小时内）产生的恶心和呕吐。

    2项临床试验的数据证实了Akynzeo的疗效，究表明，在急性期（24小时内），Akynzeo治疗组有98.5%的患者未经历任何呕吐或需要额外的药物支持，而单药帕洛诺司琼治疗组患者比例为89.7%。

    此外，关于两种药物在延迟期和化疗全程预防呕吐和治疗恶心的作用对比显示。在延迟期和化疗全程，Akynzeo治疗组分别有90.4%和80.6%的患者未经历任何呕吐，帕洛诺司琼治疗组比例分别为80.1%和76.5%。

    研究过程中，Akynzeo的副作用包括头痛、乏力、消化不良和便秘。

    目前，"Akynzeo"及其成分"奈妥吡坦"尚未在我国获准上市，而帕洛诺司琼早我国上市的产品为盐酸帕洛诺司琼注射液