ST LOUIS (MD Consult) - On October 23, 2009, the US Food and Drug Administration (FDA) announced that it has issued an emergency use authorization (EUA) for the investigational antiviral drug peramivir. The authorization specifies that peramivir, a neuraminidase inhibitor, may be administered intravenously (IV) to certain adult and pediatric patients with confirmed or suspected 2009 H1N1 influenza who are admitted to a hospital. The FDA authorization was granted in response to a request from the US Centers for Disease Control and Prevention.
Intravenous peramivir is authorized for use only in hospitalized patients for whom therapy with an IV drug is deemed clinically appropriate. Per the FDA, the criteria determining clinical appropriateness are the following:
- a patient's condition is not responding to either oral or inhaled antiviral therapy;
- drug delivery by a route other than an IV route is not expected to be dependable or feasible; and
- as a result of other circumstances, IV therapy–for adult patients only–is indicated, as per clinical judgment.
At least 1 of the aforementioned 3 criteria must be satisfied before IV peramivir may be administered under the EUA.
Results from phase 2 and 3 trials that employed IV and intramuscular (IM) administration of peramivir include a statistically significant effect with a single 300-mg IV or 600-mg IV dose of peramivir (compared with placebo) in adult patients with acute uncomplicated influenza. Additionally, results of 3 phase 2 trials and 1 phase 3 trial, including 1 trial of peramivir in hospitalized patients, did not show statistically significant treatment differences between peramivir and placebo or oseltamivir.
Approximately 1,891 patients in clinical trials have received peramivir IV or IM, including 478 patients who received a single 600-mg IV dose. Data on multidose administration are limited to that from 33 adults who received approximately 600 mg (or higher) IV doses of peramivir once daily for 5 or more days.
The FDA warns that a number of limitations exist in regard to the safety and efficacy data available at this stage of peramivir's development. Furthermore, the data that have been reported are preliminary in nature. However, on the basis of the totality of scientific evidence available, the FDA believes that it is reasonable to assume that IV peramivir may be effective in certain patients.
Commonly reported adverse events in peramivir IV clinical trials were diarrhea, nausea, vomiting, and neutropenia. Additional adverse events associated with the drug, some of which may be serious, may become apparent with more widespread use. As part of the conditions of the EUA, health care providers must report adverse events and all medication errors associated with peramivir to the FDA's MedWatch program within 7 calendar days from the onset of the adverse event.
The standard adult dose of peramivir is 600 mg IV once daily for 5 to 10 days. Patients with critical illness (eg, persons with respiratory failure or persons requiring intensive care unit admission) might benefit from a longer treatment course, though no available data exist demonstrating that longer treatment courses are more effective.
Peramivir is available in 200-mg/20mL (10-mg/mL) vials. Peramivir injection must be diluted in a preparation of 0.9% or 0.45% sodium chloride for injection that does not contain dextrose or other electrolytes. Infusion rates should not exceed 40 mg/min.
Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
圣路易斯(MD Consult)——2009年10月23日，美国食品药品管理局(FDA)宣布，研发中的抗病毒药帕拉米韦已获得紧急使用授权(EUA)。该授权特别指出，2009年度H1N1流感确诊病例或疑似病例(包括某些成人及儿科患者)住院后可接受神经氨酸酶抑制剂帕拉米韦静脉用药治疗。FDA应美国疾病预防控制中心(CDC)的要求而做出此项授权。
仅授权帕拉米韦静脉注射用于认为静脉注射用药有”临床合理性”的住院患者。根据FDA的要求，临床合理性的判定标准如下：
- 口服或吸入性抗病毒疗法对患者病情无效；
- 除静脉途径用药外，医生认为使用其他任何用药途径均不可靠或不可行；以及
- 鉴于其他情况，根据临床判断，适宜静脉用药治疗——仅针对成人患者。
在帕拉米韦静脉用药之前，必须至少满足上述3项标准之一方可在紧急使用授权下用药。
采用静脉和肌肉内(IM)给予帕拉米韦的2期及3期试验结果显示，成人急性单纯性流感患者在单剂300 mg或600 mg帕拉米韦静脉用药后获得了有统计学意义(与安慰剂对照相比)的疗效。此外，3项2期试验和1项3期试验的结果显示，帕拉米韦与安慰剂对照或奥司他韦(达菲)之间在疗效上的差异无统计学意义，这几项试验还包括1项帕拉米韦用于住院患者的试验。
在临床试验中，有大约1,891例患者接受了帕拉米韦静脉用药或肌肉内注射治疗，其中有478例接受单剂600 mg 静脉用药治疗。多剂给药的数据仅限于33例接受大约600 mg(或更高剂量) 帕拉米韦1日1次静脉用药、持续至少5日的成人患者。
FDA警告，在帕拉米韦研发的现阶段所获得的安全性和有效性数据存在许多局限性。另外，已报告的数据属于初期数据。然而，根据现有的整体科学证据，FDA认为帕拉米韦静脉用药对某些患者有效这一观点是合理的。
帕拉米韦静脉用药临床试验中常报告的不良事件有腹泻、恶心、呕吐以及嗜中性粒细胞减少症。随着应用的普及，可能会出现其他与本药相关的不良事件，其中可能会有一些严重的不良事件。医护人员必须将不良事件和各种与帕拉米韦关联的用药失误在出现不良反应的7历日内报告至FDA的医学监视系统(MedWatch program)，这也是紧急使用授权的一部分内容。
成人帕拉米韦的标准剂量为600 mg，静脉用药，1日1次，持续5至10日。尽管尚无数据证实较长疗程更有效，但较长的疗程可能对病情严重的患者(如呼吸衰竭者或需要入住重症监护病房者)有益。
帕拉米韦现有的剂型为200 mg/20ml(10mg/ml)瓶装液。在注射帕拉米韦注射液前，必须以0.9% 或 0.45%不含左旋糖或其他电解质的氯化钠溶液进行稀释。输注速率不应超过40 mg/min。
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