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Neuraminidase inhibitors for preventing and treating influenza in healthy adults.

Abstract

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 Because of the exclusion of a review of mainly unpublished trials of oseltamivir, insufficient evidence remained to reach a conclusion on the prevention of complications requiring antibiotics in influenza cases (RR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.

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  • Authors+Show Affiliations

    ,

    Vaccines Field, The Cochrane Collaboration, Via Adige 28a, Anguillara Sabazia, Roma, Italy, 00061.

    , , , ,

    Source

    MeSH

    Adult
    Antiviral Agents
    Enzyme Inhibitors
    Humans
    Influenza, Human
    Neuraminidase
    Oseltamivir
    Post-Exposure Prophylaxis
    Randomized Controlled Trials as Topic
    Zanamivir

    Pub Type(s)

    Journal Article
    Meta-Analysis
    Review
    Systematic Review

    Language

    eng

    PubMed ID

    20166059

    Citation

    Jefferson, Tom, et al. "Neuraminidase Inhibitors for Preventing and Treating Influenza in Healthy Adults." The Cochrane Database of Systematic Reviews, 2010, p. CD001265.
    Jefferson T, Jones M, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults. Cochrane Database Syst Rev. 2010.
    Jefferson, T., Jones, M., Doshi, P., Del Mar, C., Dooley, L., & Foxlee, R. (2010). Neuraminidase inhibitors for preventing and treating influenza in healthy adults. The Cochrane Database of Systematic Reviews, (2), p. CD001265. doi:10.1002/14651858.CD001265.pub3.
    Jefferson T, et al. Neuraminidase Inhibitors for Preventing and Treating Influenza in Healthy Adults. Cochrane Database Syst Rev. 2010 Feb 17;(2)CD001265. PubMed PMID: 20166059.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Neuraminidase inhibitors for preventing and treating influenza in healthy adults. AU - Jefferson,Tom, AU - Jones,Mark, AU - Doshi,Peter, AU - Del Mar,Chris, AU - Dooley,Liz, AU - Foxlee,Ruth, Y1 - 2010/02/17/ PY - 2010/2/19/entrez PY - 2010/2/19/pubmed PY - 2010/4/20/medline SP - CD001265 EP - CD001265 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 2 N2 - 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. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/20166059/Neuraminidase_inhibitors_for_preventing_and_treating_influenza_in_healthy_adults_ L2 - https://doi.org/10.1002/14651858.CD001265.pub3 DB - PRIME DP - Unbound Medicine ER -