重点关注流感中的扎那米韦。

Susan M Cheer, Antona J Wagstaff
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引用次数: 11

摘要

扎那米韦是一种有效的竞争性神经氨酸酶糖蛋白抑制剂,在甲型和乙型流感病毒的感染周期中至关重要。与安慰剂相比,Zanamivir(通过Diskhaler吸入10mg,每日两次,或吸入10mg加鼻内6.4 mg,每日2或4次,持续5天)使主要流感症状缓解的中位时间缩短了2.5天。在涉及健康成人、高风险患者或5至12岁儿童的III期试验中,吸入扎那米韦与安慰剂相比可显著减少1至2.5天。还观察到扎那米韦加速恢复正常活动,减少对睡眠的干扰,减轻药物的消耗和导致抗菌药物使用的并发症发生率。当用于预防时,吸入扎那米韦10至20mg /天,持续10天至4周(在一项试验中增加6.4 mg/天鼻内),在大学社区67%的接受者中预防了甲型流感,与安慰剂相比,显著减少了新流感病例的家庭数量,或预防了长期护理机构的新流感病例。在健康成人、高危和老年患者以及儿童中,吸入或鼻内扎那米韦的耐受性与安慰剂相似。在一项对照良好的试验中,推荐剂量的扎那米韦对呼吸系统疾病患者的肺功能没有不良影响,尽管有罕见的支气管痉挛和/或呼吸功能下降的报道。总之,扎那米韦(在症状出现后48小时内使用)可缩短有症状疾病的持续时间,加速恢复正常活动,或减少成人、高危人群和流感患儿需要使用抗菌药物的并发症。在某些人群中,预防接种仍然是首选的干预措施。然而,扎那米韦的疗效、良好的耐受性和缺乏耐药性使其成为一个有用的选择,特别是那些没有接种疫苗或接种疫苗保护不充分的人,他们能够使用吸入装置。扎那米韦在呼吸系统疾病患者中的应用尚不清楚,因为担心其可能导致支气管痉挛。需要对预防流感严重并发症,特别是高危患者的严重并发症的有效性进行前瞻性成本效益分析和调查。扎那米韦在疫苗接种禁忌症或无效人群、长期护理机构中的老年人或高危患者以及家庭中显示出预防潜力。
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Spotlight on zanamivir in influenza.

Zanamivir is a potent competitive inhibitor of the neuraminidase glycoprotein, which is essential in the infective cycle of influenza A and B viruses. Zanamivir (10 mg by inhalation via the Diskhaler twice daily, or 10 mg inhaled plus 6.4 mg intranasally 2 or 4 times daily, for 5 days) reduced the median time to alleviation of major influenza symptoms by up to 2.5 days compared with placebo. Significant reductions of 1 to 2.5 days versus placebo were observed with inhaled zanamivir in phase III trials involving otherwise healthy adults, high-risk patients or children aged 5 to 12 years. Accelerated return to normal activities, and reduced interference with sleep, consumption of relief medication and incidence of complications leading to antibacterial use were also observed with zanamivir. When used for prophylaxis, inhaled zanamivir 10 to 20 mg/day for 10 days to 4 weeks (plus 6.4 mg/day intranasally in one trial) prevented influenza A in 67% of recipients in a university community, significantly reduced the number of families with new cases of influenza compared with placebo or prevented new cases of influenza in long-term care facilities. The tolerability of inhaled or intranasal zanamivir was similar to that of placebo in otherwise healthy adults, high-risk and elderly patients, and children. Recommended dosages of zanamivir did not adversely affect pulmonary function in patients with respiratory disorders in a well-controlled trial, although there have been rare reports of bronchospasm and/or a decline in respiratory function. In conclusion, zanamivir (used within 48 hours of symptom development) reduces the duration of symptomatic illness, causes accelerated return to normal activities or reduces complications requiring antibacterial use in adults, high-risk individuals and children with influenza. Vaccination remains the intervention of choice for prophylaxis in selected populations. However, the efficacy, good tolerability profile and lack of resistance with zanamivir make it a useful option, particularly in those not covered or inadequately protected by vaccination, who are able to use the inhalation device. The use of zanamivir in patients with respiratory disorders remains unclear because of concerns regarding its potential for bronchospasm. Prospective cost-effectiveness analyses and investigations of efficacy in preventing serious complications of influenza, particularly in high-risk patients, are required. Zanamivir shows potential for prophylaxis in persons for whom vaccination is contraindicated or ineffective, in elderly or high-risk patients in long-term care facilities and in households.

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