Rapivab注射液是第一个神经氨酸酶抑制剂被批准为静脉(IV)给药
2014年12月22日，美国FDA批准了帕拉米韦（Rapivab）用于治疗成年流感患者。帕拉米韦是第一种获批准通过静脉注射给药的神经氨酸苷酶抑制剂，也是FDA批准的第三种神经氨酸苷酶抑制剂类抗流感药物.
批准日期： 2014年12月19日；公司： BioCryst 制药公司。
RAPIVAB™(帕拉米韦 peramivir注射液)，为静脉使用
美国初次批准：[2014]
适应证和用途
RAPIVAB是一种流感病毒神经氨酸酶抑制剂适用为在18岁和以上急性无并发症流感曾有症状不超过2天患者的治疗。
使用的限制：
⑴ 疗效根据主要流感病毒类型是流感A 临床试验；纳入流感 B病毒被感染受试者数量有限。
⑵ 当决定是否使用时考虑对流感药物敏感性模式和治疗效应可得到的信息。
⑶ 有严重流感需要住院患者中的疗效未能确定。
剂量和给药方法
⑴流感症状发作2天内给予单剂量。
⑵推荐剂量是600 mg，通过最小历时14分钟静脉输注给予。
⑶肾受损：对有肌酐清除率30-49 mL/min患者推荐剂量是200 mg和对有肌酐清除率10-29 mL/min患者推荐剂量100 mg.
⑷血液透析： 透析后给予。
⑸RAPIVAB给予前必须被稀释。
⑹对药物兼容性信息见完整处方资料。
剂型和规格
注射液： 200mg在 20mL(10 mg/mL)在一次用小瓶内。
禁忌证
无。
警告和注意事项
⑴用 RAPIVAB曾发生严重皮肤/超敏性反应例如Stevens-Johnson综合征和多形性红斑。
⑵神经精神事件：有流感患者在其疾病早期可能处在幻觉，谵妄和异常行为风险增加。监视异常行为的体征。
不良反应
最常见不良反应(发生率>2%)是腹泻。
药物相互作用
活减毒流感疫苗(LAIV)，鼻内：或给予RAPIVAB前2周内或后48小时避免使用LAIV，除非医药上指示。
特殊人群中使用
⑴妊娠：如获益胜过风险使用。
⑵哺乳母亲： 当给予哺乳妇女应谨慎对待。

Rapivab (peramivir injection)
The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.
Company: Biocryst
Approval Status: Approved December 2014
Treatment Area: treatment of acute uncomplicated influenza in adults
General Information
Rapivab (peramivir injection) is an influenza virus neuraminidase inhibitor. Neuraminidase is an enzyme that releases viral particles from the plasma membrane of infected cells.
Rapivab is specifically indicated for the treatment of acute uncomplicated influenza in patients 18 years and older who have been symptomatic for no more than 2 days.
Rapivab is supplied as a solution for intravenous administration. Rapivab should be administered within 2 days of onset of symptoms of influenza. The recommended dose of Rapivab in adult patients 18 years of age or older with acute uncomplicated influenza is a single 600mg dose, administered via intravenous infusion for 15 to 30 minutes.
Clinical Results
FDA Approval
The FDA approval of Rapivab was based on a randomized, multicenter, blinded trial conducted in Japan that evaluated a single intravenous administration of Rapivab 300 mg, Rapivab 600 mg, or placebo administered over 30 minutes in subjects 18 to 65 years of age with acute uncomplicated influenza. Study treatment was started within 48 hours of onset of symptoms. Subjects participating in the trial were required to self-assess their influenza symptoms as “none’, ‘mild’, ‘moderate’, or ‘severe’ twice daily. The primary endpoint, time to alleviation of symptoms, was defined as the number of hours from initiation of study drug until the start of the 24 hour period in which all seven symptoms of influenza (cough, sore throat, nasal congestion, headache, feverishness, myalgia and fatigue) were either absent or present at a level no greater than mild for at least 21.5 hours. The overall efficacy population, consisting of subjects with confirmed influenza and administered study drug, totaled 297 subjects. Overall, subjects receiving Rapivab 600 mg experienced alleviation of their combined influenza symptoms a median of 21 hours sooner than those receiving placebo. The median time to recovery to normal temperature (less than 37°C) in the 600 mg group was approximately 12 hours sooner compared to placebo.
Limitations of Use:
•The efficacy of Rapivab was based on clinical trials of naturally occurring influenza in which the predominant influenza infections were influenza A virus; a limited number of subjects infected with influenza B virus were enrolled.
•Influenza viruses change over time. Emergence of resistance substitutions could decrease drug effectiveness. Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs.
•The efficacy of Rapivab could not be established in patients with serious influenza requiring hospitalization.
Side Effects
The most common adverse reaction associated with the use of Rapivab was diarrhea.
Mechanism of Action
Rapivab (peramivir injection) is an influenza virus neuraminidase inhibitor. Neuraminidase is an enzyme that releases viral particles from the plasma membrane of infected cells.
Additional Information
For additional information regarding the use of Rapivab or acute uncomplicated influenza in adults, please visit http://rapivab.com/
New Drugs Online Report for peramivir
Information
Generic Name: peramivir  
Trade Name: Rapivab 
Synonym: Rapivab (US) 
Entry Type: New molecular entity  
Developmental Status
UK: Phase II Clinical Trials 
EU: Phase II Clinical Trials 
US: Approved (Licensed) 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
Dec 14. FDA has approved peramivir (Rapivab®), a neuraminidase inhibitor given as a single dose (IV infusion) for the treatment of acute uncomplicated influenza. 
24/12/2014 11:03:04 
Dec 13: Filed in the US for the treatment of acute uncomplicated influenza in adults [12].
23/12/2013 09:52:07 
Jul 13: BioCryst is planning to file in the US by the end of 2013 for the treatment of acute uncomplicated influenza based on PII trials [11]. 
12/07/2013 11:49:50 
Apr 13: A preliminary comment letter from the FDA outlines a pathway by which BioCryst could file a New Drug Application (NDA). The FDA suggested the Company request a pre-NDA meeting to reach agreement on a complete NDA submission and to address review issues identified in its preliminary comment letter [10].
01/04/2013 20:52:30 
Nov 12: After an interim analysis, the independent data monitoring committee for the PIII 301 study recommended that the study be terminated. it is unlikely that peramivir development for US registration will continue [9]. 
09/11/2012 09:45:02 
Oct 10: Slow enrolment in PIII study may delay launch to 2013 [8].
18/10/2010 15:49:17 
PIII studies to start Sep 09 [6].
25/09/2009 20:18:03 
Fast tracked in US for influenza(Jan 06) (1). PIII trials expected to begin in 2008 (2). 
Trial or other data
Nov 12: Results of the planned interim analysis of the peramivir PIII ‘301’ trial in patients admitted to the hospital with serious influenza reported the difference between peramivir and control groups for the primary endpoint was small and the recalculated sample size was greater than the predefined futility boundary of 320 subjects [9]. 
09/11/2012 09:05:00
Jan 11: The ‘301’ ongoing PIII study is evaluating the efficacy and safety of 600mg peramivir once-daily for 5 days in addition to standard of care (SOC), vs SOC alone, in adults and adolescents hospitalized due to serious flu. BioCryst has requested US regulatory approval for modifications in the conduct of the study including: revision of the primary efficacy analysis, to focus on patients not treated with neuraminidase inhibitors as SOC; increasing the sample size and including more sites; adding geographical regions and extending the timeline to complete enrollment beyond the end of 2011 [8].
14/01/2011 15:26:58
Jan 11: Top-line results from the ‘303’ PIII open-label, randomized trial of IV peramivir 600mg once-daily or 300mg twice-daily reported. The study enrolled 230 subjects (aged 14-92) hospitalized with confirmed or suspected flu during the 2009-2010 H1N1 pandemic; 200 patients (85%) had symptoms for more than 48 hours. Treatment was planned for 5 days with an optional extension to 10 days. 170 patients (74%) had received prior oseltamivir. The intent to treat infected (ITTI) population consisted of 127 patients with confirmed flu. The primary endpoint was change in influenza virus titer in nasopharyngeal samples, measured by log10 tissue culture infective dose50 (TCID50). 44 patients had a positive baseline culture, 20 in the 300mg group and 24 in the 600mg group. Reductions in log10 TCID50 titre were -1.66 and -1.47, respectively, in the two groups over the first 48 hours. Overall 28 day mortality was 8.7%. In the combined ITTI population median time to resolution of fever was 25 hours; time to clinical resolution, 92 hours; time to alleviation of symptoms, 145 hours; and time to resumption of usual activities, 26.8 days [8]. 
14/01/2011 15:26:51
Oct 09: The FDA has issued an emergency use authorization (EUA) for peramivir in hospitalised adult and pediatric patients with confirmed or suspected 2009 H1N1 influenza infection for whom therapy with an IV drug is clinically appropriate, based on one or more of the following: 1] the patient is not responding to either oral or inhaled antiviral therapy, 2] when drug delivery by a route other than an intravenous route is not expected to be dependable or feasible, or 3] for adults only, when the clinician judges IV therapy is appropriate due to other circumstances [7].
26/10/2009 22:42:38
Sep 09: BioCryst has been awarded a $77.2 million contract modification by the US Department of Health & Human Services to complete PIII development of peramivir for the treatment of complicated influenza. Two PIII studies are planned. NCT00957996 is an open-label, randomised study in 300 adult and adolescent hospitalised subjects with confirmed or suspected influenza infection; they will receive peramivir 300mg twice daily or 600mg daily. The study will start Sep 09 and complete in Jun 2011. The primary outcome is reduction in influenza virus titre measured by log10 tissue culture infective dose50. NCT00958776 is a multicenter, randomised, double-blind, placebo controlled study of peramivir in addition to standard of care compared to standard of care alone in 400 adults (600mg daily) and adolescents (10mg/kg daily) hospitalised due to serious influenza. Study start is Nov 09 and completion May 2011. The primary outcome is time to clinical resolution [6].
25/09/2009 20:18:16
BioCryst is supporting the pre-emergency use authorisation review of peramivir by the FDA. In May, BioCryst said that government agencies were considering the future option of providing IV peramivir through an emergency use authorisation in the event of a severe influenza outbreak with significant hospitalisations (5). 
21/07/2009 10:29:55
Jul 09: Results reported from 2 Japanese/Korean PIII studies in patients with seasonal flu during the 2008-2009 season. In one study, 1,099 patients with uncomplicated flu were randomized a single dose of IV peramivir (300 mg or 600 mg) or oseltamivir 75 mg twice a day for 5 days. Non-inferiority was demonstrated in the peramivir groups for the primary endpoint, time to alleviation of symptoms (TTAS). The medians for TTAS were 78.0 hours, 81.0 hours and 81.8 hours, respectively. In the second study in 42 patients at high-risk of serious complications because of co-morbidity, 300 or 600mg IV permavir/day was given for up to 5 days. The median TTAS in 37 evaluable patients was 68.6 hours. BioCryst is finalising plans for PIII studies to support FDA approval [4].
17/07/2009 22:10:39
PII trial results (July 08) - 300 pts randomised to either placebo or one of two doses of peramavir (300mg or 600mg) within 48 hrs of onset of symptoms. Primary outcome of improvement in the median time to alleviation of symptoms in pts with confirmed, acute, uncomplicated influenza infection, vs. placebo alone. Peramavir was generally well tolerated. (3)
29/07/2008 09:55:43
C3 trials begun in Feb00. Developmental delays reported Nov 00, as two C3 trials in the elderly are not going ahead for logistical reasons. BioCryst continuing develop and are seeking a partner for final development and marketing. Development stopped after a phase 3 trial failed to show any significant benefit (Jun 02)
Evidence Based Evaluations
NHSC/NIHR  http://www.hsc.nihr.ac.uk/topics/peramivir-for-acute-uncomplicated-influenza-in-adu/ 
References  
Available only to registered users
 Category
BNF Category: Antiviral drugs (05.03)
Pharmacology: Neuraminidase inhibitor  
Epidemiology:  
Indication: Influenza 
Method(s) of Administration  
Intravenous 
Company Information
Name: BioCryst Pharmaceuticals 
US Name: BioCryst Pharmaceuticals 
NICE Information
Anticipated Commissioning route (England) - 
In timetable: -  
http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206426lbl.pdf