Dunn C J, Goa K L
Adis International Limited, Auckland, New Zealand.
Drugs. 1999 Oct;58(4):761-84. doi: 10.2165/00003495-199958040-00016.
Zanamivir is a novel inhibitor of the enzyme neuraminidase, a surface glycoprotein essential for the replication of type A and B influenza viruses. Statistically significant reductions in median time to alleviation of major symptoms of influenza were reported in phase II and III studies of zanamivir. Benefit was seen with early treatment (within 30 or 36 hours of onset of illness) in phase II trials. Median times to alleviation of major (or 'clinically significant') symptoms were reduced by 1 to 2.5 days after treatment with zanamivir 10 mg twice daily by oral inhalation for 5 days in 3 phase III studies. Benefit of zanamivir treatment in terms of time to return to normal activities and reductions in consumption of paracetamol (acetaminophen), and reductions in the level of interference of influenza with sleep, work, leisure and recreational activities, were reported. Reductions relative to placebo of 2.5 to 3.25 days were observed in median time to alleviation of major symptoms in high-risk patients. Available data also indicate potential of zanamivir in the prophylaxis of influenza. A statistically significant reduction in the incidence of influenza A was reported with zanamivir 10 mg by oral inhalation once daily for 4 weeks in a double-blind study in 1107 persons in 2 university communities. Prophylactic benefit of zanamivir in influenza A and B outbreaks has also been suggested by data from a nursing home community. Adverse event profiles in patients receiving zanamivir therapeutically or prophylactically appear similar to those in patients receiving placebo. The most commonly reported adverse events in therapeutic trials have been nasal signs and symptoms, diarrhoea, nausea, headache, bronchitis and cough.
Prompt treatment with zanamivir in patients with naturally acquired influenza is associated with significant reductions in duration of symptomatic illness, accelerated return to normal levels of activity and reduced consumption of antibiotics for influenza-related complications. While vaccination in selected populations remains the seasonal intervention of choice for prophylaxis, the efficacy, good tolerability and lack of resistance seen with zanamivir are likely to make the drug a valuable treatment option, particularly in individuals not covered or inadequately protected by vaccination, and in those at high risk of influenza-related complications. Confirmation of the prophylactic efficacy of zanamivir would indicate a major potential role for the drug in this setting, especially in persons for whom vaccination is not suitable or fully effective, in closed communities (e.g. nursing homes) and in individuals at high risk.
扎那米韦是一种新型的神经氨酸酶抑制剂,神经氨酸酶是一种对甲型和乙型流感病毒复制至关重要的表面糖蛋白。在扎那米韦的II期和III期研究中报告了流感主要症状缓解的中位时间有统计学意义的缩短。在II期试验中,早期治疗(发病30或36小时内)可见益处。在3项III期研究中,每天两次口服吸入10 mg扎那米韦,持续5天,治疗后主要(或“临床上显著”)症状缓解的中位时间缩短了1至2.5天。报告了扎那米韦治疗在恢复正常活动时间、减少对乙酰氨基酚(扑热息痛)用量以及减少流感对睡眠、工作、休闲和娱乐活动干扰程度方面的益处。在高危患者中,主要症状缓解的中位时间相对于安慰剂缩短了2.5至3.25天。现有数据还表明扎那米韦在预防流感方面具有潜力。在一项针对两个大学社区1107人的双盲研究中,每天一次口服吸入10 mg扎那米韦,持续4周,报告甲型流感发病率有统计学意义的降低。来自一个养老院社区的数据也提示了扎那米韦在甲型和乙型流感暴发中的预防益处。接受扎那米韦治疗或预防的患者的不良事件谱与接受安慰剂的患者相似。治疗试验中最常报告的不良事件为鼻部体征和症状、腹泻、恶心、头痛、支气管炎和咳嗽。
对自然感染流感的患者及时使用扎那米韦治疗可显著缩短症状性疾病的持续时间,加速恢复正常活动水平,并减少因流感相关并发症而使用抗生素的情况。虽然在特定人群中接种疫苗仍然是季节性预防的首选干预措施,但扎那米韦的疗效、良好耐受性和无耐药性可能使其成为一种有价值的治疗选择,特别是对于未接种疫苗或接种疫苗保护不足的个体,以及那些有流感相关并发症高风险的个体。扎那米韦预防疗效的证实将表明该药物在这种情况下具有重要的潜在作用,特别是对于那些不适合接种疫苗或接种疫苗不完全有效的人群、封闭社区(如养老院)中的人群以及高风险个体。