Antivirals for influenza in healthy adults: systematic review

Jefferson, T., Demicheli, V., Rivetti, D., Jones, M., Di Piettrantonj, C. and Rivetti, A. (2006) Antivirals for influenza in healthy adults: systematic review. The Lancet, 367 9507: 303-313. doi:10.1016/S0140-6736(06)67970-1

Author Jefferson, T.
Demicheli, V.
Rivetti, D.
Jones, M.
Di Piettrantonj, C.
Rivetti, A.
Title Antivirals for influenza in healthy adults: systematic review
Journal name The Lancet   Check publisher's open access policy
ISSN 0099-5355
Publication date 2006-01-28
Sub-type Article (original research)
DOI 10.1016/S0140-6736(06)67970-1
Open Access Status
Volume 367
Issue 9507
Start page 303
End page 313
Total pages 11
Place of publication London
Publisher The Lancet Publishing Group
Language eng
Subject 320000 Medical and Health Sciences
321027 Respiratory Diseases
730110 Respiratory system and diseases (incl. asthma)
Abstract Background Use of antivirals is recommended for the control of seasonal and pandemic influenza. Our aim was to review the evidence of efficacy, effectiveness, and safety of registered antivirals against naturally occurring influenza in healthy adults. Methods We searched various Databases to October, 2005, and contacted manufacturers and corresponding authors. We included randomised controlled trials comparing prophylactic (n=27) or treatment (n=27) efficacy against symptomatic or asymptomatic influenza. We did a meta-analysis and expressed prophylactic efficacy as a proportion (1-relative risk [RR]). For treatment trials, because of inconsistent and non-standardised reporting, we expressed continuous outcomes either as means or as hazard ratios. Findings We included 51 reports of 52 randomised controlled trials. Amantadine prevented 61% (95% Cl 35-76) of influenza A cases and 25% (13-36) of cases of influenza-like illness, but caused nausea (OR 2.56, 1.37-4.79), insomnia and hallucinations (2.54,1.50-4.31), and withdrawals because of adverse events (2.54,1.60-4.06). There was no effect on symptomatic cases (RR 0.85, 0.40-1.80). In treatment, amantadine significantly shortened duration of fever compared with placebo (by 0.99 days, - 1.26 to - 0.71), but had no effect on nasal shedding of influenza A viruses (0 - 93, 0.71-1.21). The fewer data for rimantadine showed comparable effects. in prophylaxis, compared with placebo, neuraminidase inhibitors have no effect against influenza-like illness (1.28, 0.45-3.66 for oral oseltamivir 75 mg daily, 1.51, 0.77-2.95 for inhaled zanamivir 10 mg daily). Higher doses appear to make no difference. The efficacy of oral oseltamivir 75 mg daily against symptomatic influenza is 61% (15-82), or 73% (33-89) at 150 mg daily. Inhaled zanamivir 10 mg daily is 62% efficacious (15-83). Neither neuraminidase inhibitor appeared effective against asymptomatic influenza. Oseltamivir induces nausea (OR 1 - 79, 1.10-2.93), especially at higher prophylactic doses (2.29, 1.34-.3.92). Oseltamivir in a post-exposure prophylaxis role has a protective efficacy of 58.5% (15.6-79.6) for households and from 68% (34.9-84.2) to 89% (67-97) in contacts of index cases. in influenza cases, compared with placebo the hazard ratios for time to alleviation of symptoms were 1.33, 1.29-1.37 for zanamivir; 1.30, 1.13-1.50 for oseltamivir provided medication was started within 48 h of symptom onset. Viral nasal titres were significantly diminished by both drugs (weighted mean difference -0.62, -0.82 to -0.41). Oseltamivir at 150 mg daily was effective in preventing lower respiratory tract complications in influenza cases (OR 0.32, 0.18-0.57). We could find no credible data on the effects of oseltamivir on avian influenza. Interpretation The use of amantadine and rimantadine should be discouraged. Because of their low effectiveness, neuraminidase inhibitors should not be used in seasonal influenza control and should only be used in a serious epidemic or pandemic alongside other public-health measures.
Keyword Medicine, General & Internal
Neuraminidase Inhibitor Zanamivir
Randomized Controlled-trial
Hong-kong Influenza
Controlled Field Trial
B Virus-infections
A H5n1 Infection
Amantadine Hydrochloride
Rimantadine Hydrochloride
Oseltamivir Treatment
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2007 Higher Education Research Data Collection
School of Public Health Publications
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Created: Wed, 02 Jan 2008, 21:20:53 EST by Thelma Whitbourne on behalf of School of Public Health