近日，美国美国食品药品监督管理局（FDA）批准首个抗体混合物Inmazeb（atoltivimab，maftivimab和odesivimab-ebgn，曾用名REGN-EB3）上市，治疗成人和儿童埃博拉病毒感染。这是FDA批准的首个治疗埃博拉病毒感染的药物。
埃博拉病毒（Ebola virus）可以导致潜在致命的人类疾病。它通过直接接触感染者或野生动物的血液、体液和组织而传播，为埃博拉病毒感染者提供护理的个人，包括未使用正确感染控制预防措施的医护人员，感染风险最高。
批准日期：2020年10月14日 公司：再生元制药
INMAZEB（阿托西单抗/阿非西单抗/奥地西单抗[atoltivimab，maftivimab和odesivimab-ebgn]）注射，静脉使用
最初的美国批准时间：2020年
作用机理
INMAZEB是三种可抑制扎伊尔埃博拉病毒的重组人IgG1κ单克隆抗体（阿托tivtivab，maftivimab和odesivimab）的抗病毒药物组合[请参见微生物学]。
适应症和用途
INMAZEB是Zaire埃博拉病毒糖蛋白定向的人类单克隆抗体（atoltivimab，maftivimab和odesivimab）的组合，适用于成人和儿科患者，包括Zaire埃博拉病毒RT-PCR阳性母亲的新生儿所治疗的Zaire埃博拉病毒引起的感染。
使用限制
•对于其他种类的埃博拉病毒和马尔堡病毒属，尚未确定INMAZEB的功效。
•扎伊尔埃博拉病毒可能随时间而变化，诸如耐药性出现或病毒毒力变化等因素可能会削弱抗病毒药物的临床益处。在决定是否使用INMAZEB时，请考虑有关循环Zaire埃博拉病毒株的药敏模式的可用信息。
剂量和给药
推荐的INMAZEB剂量为每公斤稀释并作为单次静脉输注给药的每公斤50mg阿托西单抗，50mg阿非西单抗和50mg奥地西单抗。
有关准备和管理的信息，请参阅“完整处方信息”。
剂量形式和强度
注射剂：单次剂量每14.5毫升（每毫升16.67毫克/16.67毫克/16.67毫克）241.7毫克阿托伐单抗，241.7毫克单抗和241.7毫克奥地昔单抗。
禁忌症
没有。
警告和注意事项
超敏反应，包括与输注相关的事件：
在输注INMAZEB期间和输注后已报道了包括输注相关事件在内的超敏反应。这些可能包括在输注过程中和输注后发生的严重的，危及生命的反应。监测患者，如果出现严重或威胁生命的超敏反应，应立即停止服用INMAZEB，并进行适当的紧急护理。
不良反应
最常见的不良事件（发生率≥20％）是发热，发冷，心动过速，呼吸急促和呕吐。
要报告可疑的不良反应，请联系Regeneron，电话：1-844-734-6643或FDA，电话：1-800-FDA-1088或www.fda.gov/medwatch。
药物相互作用
与活疫苗的相互作用表明可预防扎伊尔埃博拉病毒感染：尚未进行疫苗相互作用研究。INMAZEB可能会降低活疫苗的功效。开始INMAZEB治疗后的活疫苗接种间隔应符合当前的疫苗接种指南。
在特定人口中使用
哺乳期：受扎伊尔埃博拉病毒感染的患者应被告知不要母乳喂养，因为其可能传播扎伊尔埃博拉病毒。
包装供应/存储和处理方式
INMAZEB（阿托替依单抗，maftivimab和odesivimab-ebgn）注射液为澄清至微乳白色，无色至浅黄色溶液。它装在一个纸箱中，其中装有一个单剂量的小瓶，其中包括：
•每14.5毫升（每毫升16.67毫克/16.67毫克/16.67毫克）含241.7毫克的Atoltivimab，241.7毫克的maftivimab和241.7毫克的odesivimab（NDC 61755-018-01）
稀释前
将INMAZEB小瓶在2°C至8°C（36°F至46°F）的温度下冷藏在原始纸箱中，以避光。不要冻结或摇动。
稀释后
INMAZEB不包含防腐剂。始终建议在可能的情况下，在准备后立即静脉注射药物。按照下表8的规定储存稀释的INMAZEB溶液。请勿冷冻稀释溶液[请参阅剂量和
行政]。
           稀释的INMAZEB溶液储存条件
稀释剂用于配制输液溶液      稀释的INMAZEB溶液储存条件
美国药典0.9％氯化钠注射液   在室温至25°C（77°F）的温度下存放不超过8小时，
                            或在2°C至8°C（36°F到46°F）的冰箱中存放不超过24小时。
5％葡萄糖注射液（USP）或    在室温至25°C（77°F）的温度下存放不超过4小时，
乳酸林格氏注射液（USP）     或在2°C至8°C（36°F到46°F）的温度下存放不超过4小时。
完整说明资料附件：
https://www.regeneron.com/sites/default/files/Inmazeb_FPI.pdf
REGENERON'S ANTIBODY COCKTAIL REGN-EB3(INMAZEB)IS FIRST FDA-APPROVED TREATMENT FOR EBOLA (ZAIRE EBOLAVIRUS)
U.S. Food and Drug Administration (FDA) approved Inmazeb(atoltivimab, maftivimab and odesivimab-ebgn) for the treatment of infection caused by Zaire ebolavirus in adult and pediatric patients, including newborns of mothers who have tested positive for the infection.
About Inmazeb
Inmazeb, previously called REGN-EB3, was created using Regeneron’s VelocImmune® platform and associated VelociSuite® technologies. The treatment consists of three monoclonal antibodies of similar structure, atoltivimab, maftivimab and odesivimab, that bind to different, non-overlapping epitopes on Zaire ebolavirus glycoprotein. The three antibodies help neutralize the Ebola virus by blocking its ability to invade patients’ and/or enlisting other immune cells to target infected cells and remove them from the body.
Inmazeb is administered as a single, weight-based intravenous infusion(50mg atoltivimab, 50mg maftivimab and 50mg odesivimab per kg).Inmazeb was developed in collaboration and with federal funds from BARDA, part of the Office of the Assistant Secretary for Preparedness and Response at the HHS under ongoing USG Contract Nos. HHSO100201700016C and HHSO100201500013C.
IMPORTANT SAFETY INFORMATION AND INDICATION
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions Including Infusion-Associated Events: Hypersensitivity reactions including infusion-associated events have been reported during and post-infusion with INMAZEB.These may include acute, life-threatening reactions during and after the infusion.Monitor all patients for signs and symptoms including, but not limited to, hypotension, chills and elevation of fever, during and following INMAZEB infusion.In the case of severe or life-threatening hypersensitivity reactions, discontinue the administration of INMAZEB immediately and administer appropriate emergency care.
Infusion could not be completed in 1% of subjects who received INMAZEB due to infusion-associated adverse events. The rate of infusion of INMAZEB may be slowed or interrupted if the patient develops any signs of infusion-associated events or other adverse events.
ADVERSE REACTIONS:
The most common adverse events reported in at least 10% of subjects who received INMAZEB were pyrexia (or elevation in fever), chills, tachycardia, tachypnea, vomiting, hypotension, diarrhea and hypoxia.The eva luation of adverse events in subjects who received INMAZEB may have been confounded by the signs and symptoms of the underlying Zaire ebolavirus
Selected grade 3 and 4 laboratory abnormalities for INMAZEB included high sodium(≥154mmol/L), low sodium (<125 mmol/L), high potassium(≥6.5mmol/L), low potassium(< 2.5mmol/L), creatinine((mg/dL)≥1.8xULN), high alanine aminotransferase((U/L)≥ 5 x ULN)and high aspartate aminotransferase ((U/L)≥5xULN).
DRUG INTERACTIONS: INMAZEB may reduce the efficacy of live vaccine therefore, avoid the concurrent administration of a live vaccine during treatment with INMAZEB. The interval between live vaccination following initiation of INMAZEB therapy should be in accordance with current vaccination guidelines. The efficacy of INMAZEB among subjects who reported receipt of a recombinant live vaccine prior to their enrollment in the PALM clinical trial was similar to subjects who did not receive a vaccine.
INDICATION
INMAZEB is indicated for the treatment of infection caused by Zaire ebolavirus in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection.