Gravenstein S, Johnston S L, Loeschel E, Webster A
Eastern Virginia Medical School, Norfolk, Virginia, USA.
Drug Saf. 2001;24(15):1113-25. doi: 10.2165/00002018-200124150-00003.
Post-marketing experience shows zanamivir to be well tolerated in the general population for the treatment and prophylaxis of influenza type A and B infections. Individuals at high-risk of influenza have potentially more to gain from zanamivir therapy. We assessed safety and tolerability findings from treatment and prophylaxis studies in over 982 high-risk subjects. Eight treatment studies involving high-risk subjects have been conducted with zanamivir 10 mg twice daily for 5 days. The incidence and pattern of adverse events was similar in zanamivir and placebo recipients. Lower respiratory adverse events reported by recipients receiving zanamivir occurred at similar or lower frequencies to those receiving placebo. In one treatment study involving 525 patients with asthma or chronic obstructive pulmonary disease, zanamivir recipients had a small but significantly increased mean morning peak expiratory flow rate (PEFR) and evening PEFR compared with placebo during the treatment period (days 1 to 5). Eight prophylaxis studies have been conducted, five in family or community settings and three in nursing homes. Data from these studies demonstrate that zanamivir is well tolerated for prophylaxis. In nursing home studies, where 90% of participants were high risk, the pattern and incidence of adverse events were similar to that reported in otherwise healthy individuals, and similar to both placebo and rimantadine, a comparator in one study. In treatment and prophylaxis studies the incidence and pattern of adverse events in participants > or =65 years or with chronic underlying respiratory disorders was similar for zanamivir or placebo recipients. Overall, zanamivir was well tolerated and study drug discontinuations were low. A small number of deaths have been reported in studies of high-risk elderly individuals, but none were considered to be related to zanamivir. Thus clinical studies have demonstrated that zanamivir has a comparable safety profile in high-risk and otherwise healthy recipients. Approximately 1.72 million treatment courses of zanamivir were prescribed up to the end of January 2001. Many spontaneous adverse event reports received since marketing, a third of these from non-healthcare professionals, reflect the underlying condition being treated. However, a number of events have resulted in changes to the zanamivir prescribing information, including rare reports of bronchospasm, dyspnoea, rash, urticaria and allergic type reactions including facial and oropharyngeal oedema. The reported safety profile of zanamivir, for treatment and prophylaxis of high risk subjects with influenza type A and B infections supports its continued use in these individuals who are likely to benefit most.
上市后经验表明，扎那米韦在普通人群中用于治疗和预防甲型和乙型流感感染时耐受性良好。流感高危个体可能从扎那米韦治疗中获益更多。我们评估了超过982名高危受试者的治疗和预防研究中的安全性和耐受性结果。已对扎那米韦开展了八项治疗研究，涉及高危受试者，剂量为每日两次，每次10毫克，疗程5天。扎那米韦组和安慰剂组的不良事件发生率及模式相似。接受扎那米韦治疗的受试者报告的下呼吸道不良事件发生率与接受安慰剂治疗的受试者相似或更低。在一项涉及525例哮喘或慢性阻塞性肺疾病患者的治疗研究中，与安慰剂相比，接受扎那米韦治疗的受试者在治疗期间（第1至5天）早晨和晚上的平均呼气峰值流速（PEFR）虽有小幅但显著增加。已开展八项预防研究，五项在家庭或社区环境中进行，三项在疗养院进行。这些研究数据表明，扎那米韦用于预防时耐受性良好。在疗养院研究中，90%的参与者为高危人群，不良事件的模式和发生率与健康个体报告的情况相似，且与安慰剂及一项研究中的对照药物金刚烷胺相似。在治疗和预防研究中，年龄≥65岁或患有慢性基础呼吸系统疾病的参与者中，扎那米韦组和安慰剂组的不良事件发生率及模式相似。总体而言，扎那米韦耐受性良好，研究药物停药率较低。在高危老年个体的研究中报告了少数死亡病例，但均未被认为与扎那米韦有关。因此，临床研究表明，扎那米韦在高危和健康受试者中的安全性相当。截至2001年1月底，已开出约172万疗程的扎那米韦治疗处方。自上市以来收到了许多自发的不良事件报告，其中三分之一来自非医疗专业人员，这些报告反映了正在治疗的基础疾病。然而，一些事件导致扎那米韦的处方信息发生了变化，包括罕见的支气管痉挛、呼吸困难、皮疹、荨麻疹以及包括面部和口咽水肿在内的过敏样反应报告。扎那米韦用于治疗和预防甲型和乙型流感感染高危受试者的已报告安全性概况支持其继续用于这些可能最受益的个体。
