Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments

Heneghan, Carl J., Onakpoya, Igho, Thompson, Matthew, Spencer, Elizabeth A., Jones, Mark and Jefferson, Tom (2014) Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ, 348 g2547.1-g2547.16. doi:10.1136/bmj.g2547

Author Heneghan, Carl J.
Onakpoya, Igho
Thompson, Matthew
Spencer, Elizabeth A.
Jones, Mark
Jefferson, Tom
Title Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments
Journal name BMJ
ISSN 1756-1833
Publication date 2014-04-10
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1136/bmj.g2547
Open Access Status DOI
Volume 348
Start page g2547.1
End page g2547.16
Total pages 16
Place of publication London, United Kingdom
Publisher B M J Group
Collection year 2015
Language eng
Formatted abstract
Objectives: To describe the potential benefits and harms of zanamivir.

Design: Systematic review of clinical study reports of randomised placebo controlled trials and regulatory information

Data sources: Clinical study reports, trial registries, electronic databases, regulatory archives, and correspondence with manufacturers.

Eligibility criteria for selecting studies: Randomised placebo controlled trials in adults and children who had confirmed or suspected exposure to natural influenza.

Main outcome measures: Time to first alleviation of symptoms, influenza outcomes and complications, admissions to hospital, and adverse events in the intention to treat (ITT) population.

Results: We included 28 trials in stage 1 (judgment of appropriate study design) and 26 in stage 2 (formal analysis). For treatment of adults, zanamivir reduced the time to first alleviation of symptoms of influenza-like illness by 0.60 days (95% confidence interval 0.39 to 0.81, P<0.001, I2=9%), which equates to an average 14.4 hours' reduction, or a 10% reduction in mean duration of symptoms from 6.6 days to 6.0 days. Time to first alleviation of symptoms was shorter in all participants when any relief drugs were allowed compared with no use. Zanamivir did not reduce the risk of self reported investigator mediated pneumonia (risk difference 0.17%, -0.73% to 0.70%) or radiologically confirmed pneumonia (-0.06%, -6.56% to 2.11%) in adults. The effect on pneumonia in children was also not significant (0.56%, -1.64% to 1.04%). There was no significant effect on otitis media or sinusitis in both adults and children, with only a small effect noted for bronchitis in adults (1.80%, 0.65% to 2.80%), but not in children. There were no data to assess effects on admissions in adults and children. Zanamivir tended to be well tolerated. In zanamivir prophylaxis studies, symptomatic influenza in individuals was significantly reduced (1.98%, (0.98% to 2.54%); reducing event rates from 3.26% to 1.27%, which means 51 people need to be treated to prevent one influenza case (95% confidence interval, 40 to 103). In contrast, the prophylaxis effect on asymptomatic influenza cases was not significant in individuals (risk difference 0.14%, -1.10% to 1.10%) or in households (1.32%, -2.20% to 3.84%). In households treated prophylactically there was an effect on symptomatic influenza (14.84%, 12.18% to 16.55%), but this was based on only two small studies including 824 participants. Prophylaxis in adults reduced unverified pneumonia (0.32%, 0.09% to 0.41%; NNTB (number needed to treat to benefit) 311, 244 to 1086) but had no effect on pneumonia in children or on bronchitis or sinusitis in adults or children (risk difference 0.32%, 0.09% to 0.41%; NNTB 311, 244 to 1086).

Conclusions: Based on a full assessment of all trials conducted, zanamivir reduces the time to symptomatic improvement in adults (but not in children) with influenza-like illness by just over half a day, although this effect might be attenuated by symptom relief medication. Zanamivir also reduces the proportion of patients with laboratory confirmed symptomatic influenza. We found no evidence that zanamivir reduces the risk of complications of influenza, particularly pneumonia, or the risk of hospital admission or death. Its harmful effects were minor (except for bronchospasm), perhaps because of low bioavailability.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2015 Collection
School of Public Health Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 20 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 28 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 02 Sep 2014, 11:02:35 EST by Nyree Divitini on behalf of School of Public Health