Fast track — ArticlesAntivirals for influenza in healthy adults: systematic review
Introduction
The M2 ion channel-blocking drugs amantadine and rimantadine and the newer generation, more expensive antiviral compounds (neuraminidase inhibitors) nebulised zanamivir (Relenza, Glaxo Wellcome, NC, USA) and oral oseltamivir (Tamiflu, Gilead Sciences, CA, USA, and Hoffman La Roche, Basel, Switzerland) have anti-influenza activity.1, 2 In 2005, WHO encouraged member countries to use antivirals in influenza interpandemic periods because “wide scale use of antivirals and vaccines during a pandemic will depend on familiarity with their effective application during the interpandemic period. The increasing use of these modalities will expand capacity and mitigate the morbidity and mortality of annual influenza epidemics”.3 The European Medicines Agency maintains that neuraminidase inhibitors (especially oseltamivir) are complementary to vaccines, and should be used in an influenza pandemic4 for treatment of index cases and for influenza prophylaxis in key personnel—namely, police officers, fire fighters, health-care workers. None of the systematic reviews done5, 6, 7 of the effects of antivirals, however, is up to date, and none has assessed their potential role in an influenza pandemic, where high viral load and high transmission seem to be the norm. In this context, trade-off between dose and adverse-event profile in prophylaxis, activity against influenza infection in those with and without symptoms, and extent of viral excretion through body fluids become important.2 Cost is also likely to be a factor when choosing a drug for use in epidemic or pandemic situations.
Our aim, was to assess the comparative studies of the efficacy (against laboratory-confirmed influenza with or without symptoms), effectiveness (against influenza-like illness), and safety of antivirals against influenza in healthy adults. This report is based on two Cochrane reviews,8, 9 which we are in the process of updating.
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Search strategy (webappendix) and selection criteria
We searched Ovid MEDLINE (to August, 2005), WebSpirs EMBASE (to June, 2005), and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2005), and checked the references of systematic reviews of the topic5, 6, 7 and of retrieved trials, for relevant published work. We wrote to manufacturers and authors of identified studies for further information.
We considered for inclusion in our systematic review randomised controlled trials that assessed the prophylactic or
Results
We identified 87 reports of studies possibly fulfilling our inclusion criteria (figure 1).14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64 We included 20 reports of 21 prophylaxis and safety trials for amantadine and rimantadine and 13 treatment trials. Two trials contained both treatment and prophylaxis data,27, 43 but only one27 had
Discussion
The evidence does not support the use of M2 ion channel inhibitors for influenza. Furthermore, it suggests that neuraminidase inhibitors should not be used routinely for seasonal influenza and only with associated public-health measures in a pandemic situation.
As for all systematic reviews, our findings and interpretation are limited by the quantity and quality of available evidence on the effects of a specific intervention for a disease (influenza) or syndrome (influenza-like illness). Because
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