Akynzeo for Injection(复方奈妥吡坦/帕洛诺司琼冻干粉注射剂...

来自 : www.120ty.net/bencan...php?fid 发布时间：2021-03-26

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受体位于迷走神经的外围，并位于后期区域的化学感受器触发区的中心。化学治疗剂产生并刺激小肠的肠嗜铬细胞释放5-羟色胺。 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。 延迟呕吐已与速激肽族的神经激肽1的激活在很大程度上相关联（NK-1）受体的物质P.（广泛分布于中枢和外周神经系统）如在体外和体内研究中显示，netupitant抑制P物质介导的响应。 适应症和用法 AKYNZEO胶囊表示与成人的预防急性和延迟性恶心和与癌症化疗，包括初始和重复过程相关的呕吐地塞米松组合，但不限于，高致吐化疗。 AKYNZEO注射在成人与高致吐癌症化疗的初次和重复的课程相关的预防急性和延迟恶心和呕吐的地塞米松组合表示。 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是帕洛诺司琼的组合，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：帕洛诺司琼，在急性期和netupitant防止恶心和呕吐/fosnetupitant预防癌症化疗后急性期和延迟期的恶心和呕吐。 剂量和用量 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;重构于50ml 5％葡萄糖注射液，USP或0.9％氯化钠注射液，USP和给药30分钟的输注开始前化疗开始大约30分钟。 剂量形式和强度 胶囊：300mg netupitant/0.5mg帕洛诺司琼 注射剂：235mg fosnetupitant /帕洛诺司琼为0.25mg冻干粉末在单一剂量小瓶用于重构。 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。 AKYNZEO注射AKYNZEO胶囊的安全性。 要报告疑似不良反应，请致电1-844-357-4668或致电1-800-FDA-1088或www.fda.gov/medwatch联系HELSINN。 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。 如何提供/存储和处理 AKYNZEO（300mg netupitant/0.5mg palonosetron）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）。 AKYNZEO胶囊应储存在20 C至25 C（68 F至77 F）的温度下; 15 C至30 C（59 F至86 F）[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＃69639-102-01：一包小瓶 AKYNZEO应储存在2 至8 C（35.6 F至46.4 F）的纸箱中。 完整资料附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8e47618e-af46-4d82-94e8-1507c042252d AKYNZEO(fosnetupitant and palonosetron) for injection, for intravenous use NDC: 69639-102-01 Drug Name: Akynzeo for Injection Common name: fosnetupitant and palonosetron Active substance: FOSNETUPITANT; PALONOSETRON HYDROCHLORIDE Dose: 235mg; 0.25mg Dosage form / dosage: Injectable; Injection Indications: Nausea/Vomiting, Chemotherapy Induced Licensee: Helsinn Healthcare SA c/o August Consulting, Inc. Licensee Address: 515 Capital of Texas Highway, Suite 150 Austin, TX 78746 Manufacturer: Helsinn Healthcare SA c/o August Consulting, Inc. Manufacturer Address: 515 Capital of Texas Highway, Suite 150 Austin, TX 78746 Market Status: Prescription TE code: None RLD: TBD RS: No Approved application number: NDA210493 Whether it is an orphan drug: No Approval time: 2011.04.19 Approval of the instrument:PDF Instructions:PDF ---------------------------------------------------- Helsinn Group announces the FDA approval of the IV formulation of AKYNZEO (fosnetupitant/palonosetron) in the United States U.S. Food and Drug Administration (FDA) has approved the intravenous formulation of AKYNZEO (NEPA, a fixed antiemetic combination of fosnetupitant, 235mg, and palonosetron, 0.25mg) as an alternative treatment option for patients experiencing CINV. The FDA has approved AKYNZEO IV in combination with dexamethasone in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. AKYNZEO for injection has not been studied for the prevention of nausea and vomiting associated with anthracycline plus cyclophosphamide chemotherapy. Oral AKYNZEO was previously approved by the FDA as a fixed combination oral agent in 2014 for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. AKYNZEO is an oral fixed combination of palonosetron and netupitant: palonosetron prevents nausea and vomiting during the acute phase and netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy. The bioequivalence of the IV with the oral formulation of netupitant was demonstrated and the safety of IV NEPA was established through a repeated dose safety study in cancer patients to potentially uncover adverse drug reactions that may appear during subsequent clinical practice. No anaphylactic and injection site reactions related to IV NEPA were reported in this study. Currently a repeated dose safety study is ongoing in patients receiving anthracycline plus cyclophosphamide to further establish the safety profile in this setting. The prevention of CINV has been refined in treatment guidelines over the past several decades. Currently the combination treatment of antiemetic medicines with different mechanisms of actions are recommended for the prevention of CINV. The approval of AKYNZEO in IV formulation will offer to US patients and healthcare providers an alternative route of administration of the only fixed antiemetic combination targeting two distinct CINV pathways in a single dose. Riccardo Braglia, Helsinn Group Vice Chairman and CEO, commented: The approval of the intravenous formulation of AKYNZEO paves the way to bring this important therapeutic option to more patients in a new formulation, and we are delighted that we are now able to push ahead with launching this product in the United States in May 2018 About Akynzeo INDICATION AKYNZEO (netupitant 300mg/palonosetron 0.5mg) capsules was approved in October 2014 in the United States and is indicated in combination with dexamethasone in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. AKYNZEO (fosnetupitant 235mg/palonosetron 0.25) for injection was approved in April 2018 in the United States and is indicated in combination with dexamethasone in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Limitations of Us AKYNZEO for injection has not been studied for the prevention of nausea and vomiting associated with anthracycline plus cyclophosphamide chemotherapy. AKYNZEO is a combination of palonosetron, a serotonin-3 (5-HT3) receptor antagonist, and netupitant or fosnetupitant, substance P/neurokinin-1 (NK-1) receptor antagonists: palonosetron prevents nausea and vomiting during the acute phase and netupitant/fosnetupitant prevents nausea and vomiting during both the acute and delayed phase after cancer 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.