Neuraminidase inhibitors for preventing and treating influenza in healthy adults.
Jefferson T., Jones M., Doshi P., Del Mar C., Dooley L., Foxlee R.
BACKGROUND: Neuraminidase inhibitors (NI) are recommended for use against influenza and its complications in inter-pandemic years and during pandemics. OBJECTIVES: To assess the effects of NIs in preventing and treating influenza, its transmission, and its complications in otherwise healthy adults, and to estimate the frequency of adverse effects. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 3) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to August 2009) and EMBASE (1980 to August 2009). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-randomised placebo-controlled trials of NIs in healthy adults exposed to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: Two review authors independently applied inclusion criteria, assessed trial quality, and extracted data. We structured the comparisons into prophylaxis, treatment, and adverse events, with further subdivision by outcome and dose. MAIN RESULTS: We identified four prophylaxis, 12 treatment and four post-exposure prophylaxis trials. In prophylaxis compared to placebo, NIs had no effect against influenza-like illnesses (ILI) (risk ratio (RR) ranging from 1.28 for oral oseltamivir 75 mg daily to 0.76 for inhaled zanamivir 10 mg daily). The efficacy of oral oseltamivir against symptomatic influenza was 76% (at 75 mg daily), and 73% (at 150 mg daily). Inhaled zanamivir 10 mg daily performed similarly. Neither NI had a significant effect on asymptomatic influenza. Oseltamivir induced nausea (odds ratio (OR) 1.79, 95% CI 1.10 to 2.93). Oseltamivir for post-exposure prophylaxis had an efficacy of 58% and 84% in two trials for households. Zanamivir performed similarly. The hazard ratios for time to alleviation of symptoms were in favour of the treated group 1.20 (1.06 to 1.35) for oseltamivir and 1.24 (1.13 to 1.36) for zanamivir. Because of the exclusion of a review of mainly unpublished trials of oseltamivir, insufficient evidence remained to reach a conclusion on the prevention of complications requiring antibiotics in influenza cases (RR 0.57, 95% CI 0.23 to 1.37). Analysis of the US FDA and Japan's PMDA regulators' pharmacovigilance dataset, revealed incomplete reporting and description of harms preventing us from reaching firm conclusions on the central nervous system toxicity of neuraminidase inhibitors. AUTHORS' CONCLUSIONS: Numerous inconsistencies detected in the available evidence, followed by an inability to adequately access the data, has undermined confidence in our previous conclusions for oseltamivir. Independent RCTs to resolve these uncertainties are needed.