近日,美国食品和药物管理局已批准AKYNZEO IV(netupitant/palonosetron)静脉注射与成人地塞米松联合用于预防急性和延迟性恶心和呕吐,这些恶心和呕吐与高致吐性癌症化疗的初始和重复过程相关。用于注射的AKYNZEO尚未用于预防与蒽环霉素加环磷酰胺化疗相关的恶心和呕吐。 批准日期:2018年4月 公司:Helsinn Healthcare SA AKYNZEO(奈妥吡坦/帕洛诺司琼 netupitant/palonosetron)胶囊,用于口服 美国最初批准:2014年 AKYNZEO(奈妥吡坦/帕洛诺司琼 fosnetupitant/palonosetron)用于注射,用于静脉注射 美国最初批准:2018年 最近的重大变化 适用和用法:04/2018 剂量和用法,推荐用量:04/2018 剂量和用法,准备:04/2018 剂量和用量,不相容性:04/2018 作用机制 Netupitant是人类P物质/神经激肽1(NK-1)受体的选择性拮抗剂。 帕洛诺司琼是一种5-HT3受体拮抗剂,对该受体具有很强的结合亲和力,对其他受体的亲和力很小或没有。癌症化疗可能与恶心和呕吐的高发生率相关,特别是当使用某些药剂如顺铂时。 5-HT3受体位于外周迷走神经末梢,并位于后区域的化学感受器触发区的中央。化学治疗剂通过刺激小肠的肠嗜铬细胞释放5-羟色胺而产生恶心和呕吐。5-羟色胺然后激活位于迷走神经传入的5-HT3受体以引发呕吐反射。已知急性呕吐的发展依赖于5-羟色胺,并且已经证明其5-HT3受体选择性地刺激催吐反应。 延迟性呕吐主要与物质P激活速激肽家族神经激肽1(NK-1)受体(广泛分布于中枢和外周神经系统)有关。如体外和体内研究所示,netupitant抑制物质P介导响应。 适应症和用法 AKYNZEO胶囊与成人中的地塞米松组合用于预防与癌症化学疗法的初始和重复过程相关的急性和延迟恶心和呕吐,包括但不限于高致吐性化学疗法。 用于注射的AKYNZEO与成人中的地塞米松联合用于预防与高致吐性癌症化学疗法的初始和重复过程相关的急性和延迟恶心和呕吐。 使用限制 注射用AKYNZEO尚未研究用于预防与蒽环霉素加环磷酰胺化疗相关的恶心和呕吐。 AKYNZEO是帕洛诺司琼,血清素-3(5-HT3)受体拮抗剂和netupitant或fosnetupitant,P物质/神经激肽-1(NK-1)受体拮抗剂的组合:帕洛诺司琼可预防急性期恶心呕吐和netupitant/fosnetupitant可预防癌症化疗后急性期和延迟期的恶心和呕吐。 剂量和给药 在化疗开始前约1小时施用一个AKYNZEO胶囊,有或没有食物。 一瓶AKYNZEO用于注射;在50ml 5%葡萄糖注射液,USP或0.9%氯化钠注射液,USP中重建,并在化疗开始前约30分钟开始给药30分钟。 剂量形式和强度 胶囊:300mg netupitant/0.5mg palonosetron 注射:在单剂量小瓶中用于重构的235mg fosnetupitant/0.25mg帕洛诺司琼冻干粉末用于重建。 禁忌症 没有 警告和注意事项 已经报道了接受帕洛诺司琼(AKYNZEO的一种成分)的患者的超敏反应,包括过敏反应,有或没有已知的对其他5-HT3受体拮抗剂的超敏反应。 据报道5-羟色胺综合征单独使用5-HT3受体拮抗剂,特别是同时使用5-羟色胺能药物。如果出现这种症状,停止AKYNZEO并开始支持治疗。如果AKYNZEO与其他5-羟色胺能药物同时使用是临床保证,应该让患者意识到血清素综合征可能增加的风险。 不良反应 AKYNZEO胶囊最常见的不良反应(≥3%)是头痛,乏力,消化不良,疲劳,便秘和红斑。 注射用AKYNZEO的安全性通常与AKYNZEO胶囊的安全性相似。 药物相互作用 CYP3A4底物:在单剂量给予AKYNZEO后,netupitant对CYP3A4的抑制可导致伴随药物的血浆浓度增加6天;如果可行的话,避免同时使用CYP3A4底物一周。如果不能避免,可考虑减少CYP3A4底物的剂量。 CYP3A4诱导剂(例如利福平):降低血浆的netupitant浓度;避免使用。 用于特定人群 怀孕:可能导致胎儿伤害。 肝功能损害:避免用于严重肝功能损害的患者. 肾功能损害:避免用于严重肾功能不全或终末期肾病患者。 包装提供/存储和处理 胶囊 AKYNZEO(300毫克netupitant/0.5毫克帕洛诺司琼)胶囊:硬明胶胶囊,白色身体和焦糖帽,身上印有“HE1”。 它们提供如下: NDC:69639-101-01:在一个水泡中包装一个胶囊 NDC:69639-101-04:四粒胶囊(每个水泡条两粒胶囊)。 存储 AKYNZEO胶囊应储存在20°C至25°C(68°F至77°F)的温度下; 允许从15°C到30°C(59°F到86°F)的偏移[见USP受控室温]。 用于注射 用于注射的AKYNZEO(235mg fosnetupitant/0.25mg帕洛诺司琼):在单剂量小瓶中的无菌,白色至灰白色冻干粉末,用于重建。 NDC#69639-102-01:一个小瓶的包装 存储 用于注射的AKYNZEO应储存在纸箱中,在2°至8°C(35.6°F至46.4°F)的温度下避光。 完整说明书附件:https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8e47618e-af46-4d82-94e8-1507c042252d Helsinn Group announces the FDA approval of the IV formulation of AKYNZEO® (fosnetupitant/palonosetron) in the United States INDICATION and IMPORTANT SAFETY INFORMATION AKYNZEO for injection is a combination of palonosetron an fosnetupitant, a prodrug of netupitant: palonosetron prevents nausea and vomiting during the acute phase and fosenetupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy. Limitations of Use AKYNZEO for injection has not been studied for the prevention of nausea and vomiting associated with anthracycline plus cyclophosphamide chemotherapy. IMPORTANT SAFETY INFORMATION Warnings and Precautions Hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving palonosetron, one of the components of AKYNZEO, with or without known hypersensitivity to other 5-HT3 receptor antagonists. Serotonin syndrome has been reported with 5-HT3 receptor antagonists alone but particularly with concomitant use of serotonergic drugs. Serotonin syndrome can be life threatening. Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: mental status changes, autonomic instability, neuromuscular symptoms, seizures, and gastrointestinal symptoms. Patients should be monitored for the emergence of serotonin syndrome, and if symptoms occur, discontinue AKYNZEO and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if AKYNZEO is used concomitantly with other serotonergic drugs. Adverse Reactions Most common adverse reactions for AKYNZEO capsules and injection: headache, asthenia, dyspepsia, fatigue, constipation and erythema Drug Interactions Use with caution in patients receiving concomitant medications primarily metabolized by CYP3A4. The plasma concentrations of CYP3A4 substrates can increase when co-administered with AKYNZEO. The inhibitory effect on CYP3A4 can last for multiple days Dexamethasone doses should be reduced when given with AKYNZEO. A more than two-fold increase in the systemic exposure of dexamethasone was observed 4 days after a single dose of netupitant or a single infusion of fosnetupitant Consider the potential effects of increased plasma concentrations of midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) when administering with AKYNZEO. When administered with netupitant, the systemic exposure to midazolam was significantly increased Avoid concomitant use of AKYNZEO in patients on chronic use of a strong CYP3A4 inducer such as rifampin as this may decrease the efficacy of AKYNZEO Use in Specific Populations Avoid use of AKYNZEO in patients with severe hepatic impairment, severe renal impairment, or end-stage renal disease Avoid use in pregnancy, limited data is available, may cause fetal harm |
Akynzeo injection(奈妥吡坦/帕洛诺司琼静脉冻干粉注射剂)简介:近日,美国食品和药物管理局已批准AKYNZEO IV(netupitant/palonosetron)静脉注射与成人地塞米松联合用于预防急性和延迟性恶心和呕吐,这些恶心和呕吐与高致吐性癌症化疗的初始和重复过程相关。用于注射 ... 责任编辑:p53 |
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