We searched the Cochrane Acute
Respiratory Infections Group Specialised Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the GlaxoSmithKline Clinical Trials Register, generally from inception through to December 2002. We also screened the references of retrieved articles and scrutinised relevant web sites. We also screened references of retrieved articles and other systematic reviews, scrutinised web sites of European and US regulatory bodies, and contacted manufacturers and authors.
SELECTION CRITERIA: Double-blind randomised controlled trials comparing
neuraminidase inhibitors with placebo or other
antiviral drugs in children less than 12 years of age. Additional safety and tolerability data from other sources were also included.
DATA COLLECTION AND ANALYSIS: We identified three randomised controlled trials reporting data from 1500 children with a clinical case definition of
influenza, of whom 798 had laboratory confirmed
influenza infection. Two were trials of
oseltamivir (in healthy children and in children with
asthma) and one was a trial of
zanamivir (in healthy children). Overall, trial quality was good.
Oseltamivir reduced the median duration of illness by 26% (36 hours) in previously healthy children with laboratory confirmed
influenza (p < 0.0001) and by 17% (21 hours) in the intention-to-treat population (p = 0.0002).
Zanamivir reduced the median duration of illness by 24% (1.25 days) in previously healthy children with laboratory confirmed
influenza (p < 0.001) and by 10% (0.5 days) in the intention-to-treat population (p = 0.011). Both drugs also significantly reduced the time to return to normal activity. Only
oseltamivir produced a significant reduction in the complications of
influenza (particularly
otitis media), although there was a trend to benefit for
zanamivir. No data on the use of
zanamivir in 'at risk' children were available. The reduction in time to resolution of illness in 'at risk' children (with
asthma) treated with
oseltamivir was not statistically significant. Although we identified three trials of
neuraminidase inhibitors in the prevention of
influenza in families (including children), Roche and GlaxoSmithKline were not willing to break-out data for paediatric populations, and so no data were eligible for inclusion in the review. The adverse events profile of
zanamivir was no worse than placebo and we found no reports of
zanamivir-induced
bronchospasm in children.
Vomiting was more common in children treated with
oseltamivir (p = 0.008), but study withdrawals were similar (<2%) between
oseltamivir and placebo.
REVIEWER'S CONCLUSIONS:
Neuraminidase inhibitors were effective in shortening illness duration and hastening return to normal activity in previously healthy children with a clinical or laboratory diagnosis of
influenza.
Oseltamivir was effective in reducing the incidence of secondary complications. Efficacy in 'at risk' children remains to be proven. The drugs are safe, but
oseltamivir can cause
vomiting.