Neuraminidase inhibitors are effective and safe in reducing influenza complications: meta-analysis of randomized controlled trials.

  • Sofía Tejada
    Corresponding author at: Vall d'Hebron Institut de Recerca, Ps Vall d'Hebron 119 AMI-14th floor. 08035 Barcelona, Spain.
    CIBER de Enfermedades Respiratorias (CIBERES), Instituto Salud Carlos III, Barcelona, Spain

    Clinical Research/Epidemiology in Pneumonia & Sepsis (CRIPS), Vall d'Hebron Institut of Research (VHIR), Barcelona, Spain
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  • Miia Jansson
    University of Oulu, Oulu University Hospital, Oulu, Finland
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  • Candela Solé-Lleonart
    Intensive Care Unit, Hospital Universitari de Vic, Barcelona, Spain
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  • Jordi Rello
    CIBER de Enfermedades Respiratorias (CIBERES), Instituto Salud Carlos III, Barcelona, Spain

    Clinical Research/Epidemiology in Pneumonia & Sepsis (CRIPS), Vall d'Hebron Institut of Research (VHIR), Barcelona, Spain

    Clinical Research, CHU Nimes, Université de Nîmes-Montpellier, France
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Published:December 21, 2020DOI:


      • NAIs comparing to placebo therapy did demonstrate to be effective in reducing time to clinical resolution, total influenza-related complications, otitis media, and antibiotic use.
      • NAIs increased the risk of nausea and vomiting, but reduced occurrence of diarrhea.
      • Reductions on mortality, pneumonia, bronchiolitis, asthma or hospitalization rates required further research.



      There is scarce evidence verifying the impact of neuraminidase inhibitors (NAIs) in reducing influenza complications. The aim was to evaluate the available evidence from randomized-controlled trials (RCT) regarding the efficacy and safety of NAIs in reducing influenza complications.


      A systematic search of the literature was performed in the Cochrane Library, PubMed and Web of Science databases (2006–2019). Eligibility criteria were RCT that enrolled patients of any age or clinical severity with seasonal influenza (H1N1, H3N2, or B) or influenza-like syndrome and receiving NAIs comparing to placebo therapy.


      Eighteen RCTs (9004 patients) were included: nine focused on oral oseltamivir, six on inhaled zanamivir, and three on intravenous peramivir. Administration of NAIs therapy significantly decreased the time to clinical resolution (median difference: -17.7 hours; and total influenza-related complications (OR: 0.64, 95%CI: 0.51–0.82). In addition, NAIs significantly decreased acute otitis media complication (OR: 0.50, 95%CI: 0.31–0.82) and need for antibiotic treatment (OR: 0.64, 95%CI: 0.46–0.90); and showed a trend towards a reduced occurrence of pneumonia (OR: 0.44, 95%CI: 0.10–2.00), bronchitis (OR: 0.80, 95%CI: 0.43–1.48), sinusitis (OR: 0.73, 95%CI: 0.40–1.32), asthma exacerbations (OR: 0.57, 95%CI: 0.28–1.16), and hospitalizations (OR: 0.57, 95%CI: 0.24–1.38). The overall proportion of AEs tend to increase with NAIs treatment (OR: 1.16, 95%CI: 0.92–1.47). Use of NAIs was associated with a significant increase of nausea and vomiting (OR: 1.61, 95%CI: 1.04–2.50) and a decrease on diarrhea (OR: 0.81, 95%CI: 0.65–1.00).


      NAIs are effective in reducing time to clinical resolution, total influenza-related complications, otitis media, and need of antibiotic administration. Reductions on mortality, pneumonia, asthma exacerbations or hospitalization rates only did demonstrate a trend benefit in favor of NAIs. The only significant AE is the increased occurrence of nausea and vomiting.



      AE (Adverse Events), NAI (Neuraminidase Inhibitors), OR (Odd Ratio), RCT (Randomized Controlled Trials), SR (Systematic Review)
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