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Review
, 2014 (4), CD008965

Neuraminidase Inhibitors for Preventing and Treating Influenza in Healthy Adults and Children

Affiliations
Review

Neuraminidase Inhibitors for Preventing and Treating Influenza in Healthy Adults and Children

Tom Jefferson et al. Cochrane Database Syst Rev.

Abstract

Background: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide.

Objectives: To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments.

Search methods: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database.

Selection criteria: Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza.

Data collection and analysis: We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers.

Main results: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants). Inadequate reporting put most of the zanamivir studies and half of the oseltamivir studies at a high risk of selection bias. There were inadequate measures in place to protect 11 studies of oseltamivir from performance bias due to non-identical presentation of placebo. Attrition bias was high across the oseltamivir studies and there was also evidence of selective reporting for both the zanamivir and oseltamivir studies. The placebo interventions in both sets of trials may have contained active substances. Time to first symptom alleviation. For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P < 0.0001). This represents a reduction in the time to first alleviation of symptoms from 7 to 6.3 days. There was no effect in asthmatic children, but in otherwise healthy children there was (reduction by a mean difference of 29 hours, 95% CI 12 to 47 hours, P = 0.001). Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days, P < 0.00001), equating to a reduction in the mean duration of symptoms from 6.6 to 6.0 days. The effect in children was not significant. In subgroup analysis we found no evidence of a difference in treatment effect for zanamivir on time to first alleviation of symptoms in adults in the influenza-infected and non-influenza-infected subgroups (P = 0.53). Hospitalisations. Treatment of adults with oseltamivir had no significant effect on hospitalisations: risk difference (RD) 0.15% (95% CI -0.78 to 0.91). There was also no significant effect in children or in prophylaxis. Zanamivir hospitalisation data were unreported. Serious influenza complications or those leading to study withdrawal. In adult treatment trials, oseltamivir did not significantly reduce those complications classified as serious or those which led to study withdrawal (RD 0.07%, 95% CI -0.78 to 0.44), nor in child treatment trials; neither did zanamivir in the treatment of adults or in prophylaxis. There were insufficient events to compare this outcome for oseltamivir in prophylaxis or zanamivir in the treatment of children. Pneumonia. Oseltamivir significantly reduced self reported, investigator-mediated, unverified pneumonia (RD 1.00%, 95% CI 0.22 to 1.49); number needed to treat to benefit (NNTB) = 100 (95% CI 67 to 451) in the treated population. The effect was not significant in the five trials that used a more detailed diagnostic form for pneumonia. There were no definitions of pneumonia (or other complications) in any trial. No oseltamivir treatment studies reported effects on radiologically confirmed pneumonia. There was no significant effect on unverified pneumonia in children. There was no significant effect of zanamivir on either self reported or radiologically confirmed pneumonia. In prophylaxis, zanamivir significantly reduced the risk of self reported, investigator-mediated, unverified pneumonia in adults (RD 0.32%, 95% CI 0.09 to 0.41); NNTB = 311 (95% CI 244 to 1086), but not oseltamivir. Bronchitis, sinusitis and otitis media. Zanamivir significantly reduced the risk of bronchitis in adult treatment trials (RD 1.80%, 95% CI 0.65 to 2.80); NNTB = 56 (36 to 155), but not oseltamivir. Neither NI significantly reduced the risk of otitis media and sinusitis in both adults and children. Harms of treatment. Oseltamivir in the treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90 to 7.39); number needed to treat to harm (NNTH) = 28 (95% CI 14 to 112) and vomiting (RD 4.56%, 95% CI 2.39 to 7.58); NNTH = 22 (14 to 42). The proportion of participants with four-fold increases in antibody titre was significantly lower in the treated group compared to the control group (RR 0.92, 95% CI 0.86 to 0.97, I(2) statistic = 0%) (5% absolute difference between arms). Oseltamivir significantly decreased the risk of diarrhoea (RD 2.33%, 95% CI 0.14 to 3.81); NNTB = 43 (95% CI 27 to 709) and cardiac events (RD 0.68%, 95% CI 0.04 to 1.0); NNTB = 148 (101 to 2509) compared to placebo during the on-treatment period. There was a dose-response effect on psychiatric events in the two oseltamivir "pivotal" treatment trials, WV15670 and WV15671, at 150 mg (standard dose) and 300 mg daily (high dose) (P = 0.038). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75 to 10.29); NNTH = 19 (95% CI 10 to 57). There was a significantly lower proportion of children on oseltamivir with a four-fold increase in antibodies (RR 0.90, 95% CI 0.80 to 1.00, I(2) = 0%). Prophylaxis. In prophylaxis trials, oseltamivir and zanamivir reduced the risk of symptomatic influenza in individuals (oseltamivir: RD 3.05% (95% CI 1.83 to 3.88); NNTB = 33 (26 to 55); zanamivir: RD 1.98% (95% CI 0.98 to 2.54); NNTB = 51 (40 to 103)) and in households (oseltamivir: RD 13.6% (95% CI 9.52 to 15.47); NNTB = 7 (6 to 11); zanamivir: RD 14.84% (95% CI 12.18 to 16.55); NNTB = 7 (7 to 9)). There was no significant effect on asymptomatic influenza (oseltamivir: RR 1.14 (95% CI 0.39 to 3.33); zanamivir: RR 0.97 (95% CI 0.76 to 1.24)). Non-influenza, influenza-like illness could not be assessed due to data not being fully reported. In oseltamivir prophylaxis studies, psychiatric adverse events were increased in the combined on- and off-treatment periods (RD 1.06%, 95% CI 0.07 to 2.76); NNTH = 94 (95% CI 36 to 1538) in the study treatment population. Oseltamivir increased the risk of headaches whilst on treatment (RD 3.15%, 95% CI 0.88 to 5.78); NNTH = 32 (95% CI 18 to 115), renal events whilst on treatment (RD 0.67%, 95% CI -2.93 to 0.01); NNTH = 150 (NNTH 35 to NNTB > 1000) and nausea whilst on treatment (RD 4.15%, 95% CI 0.86 to 9.51); NNTH = 25 (95% CI 11 to 116).

Authors' conclusions: Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions. The use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults and vomiting in children. The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir. The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza. The influenza virus-specific mechanism of action proposed by the producers does not fit the clinical evidence.

Conflict of interest statement

All review authors have applied for and received competitive research grants. TJ, PD, CDM, MT, RH, MJ and CH are co‐recipients of the NIHR grant to carry out this review ( http://www.nets.nihr.ac.uk/projects/hta/108001 ). In addition:

Prof Jefferson receives royalties from his books published by Blackwell and Il Pensiero Scientifico Editore, Rome. Dr Jefferson is occasionally interviewed by market research companies for anonymous interviews about Phase 1 or 2 pharmaceutical products. In 2011‐2013 Dr Jefferson acted as an expert witness in a litigation case related to oseltamivir phosphate; Tamiflu [Roche] and in a labour case on influenza vaccines in healthcare workers in Canada. In 1997‐99 Dr Jefferson acted as consultant for Roche, in 2001‐2 for GSK and in 2003 for Sanofi‐Synthelabo for pleconaril (an anti‐rhinoviral which did not get approval from FDA). Dr Jefferson is a consultant for IMS Health.

Dr Doshi received EUR 1500 from the European Respiratory Society in support of his travel to the society's September 2012 annual congress in Vienna, where he gave an invited talk on oseltamivir.

Prof Del Mar was a Board member of two companies to commercialise research at Bond University, part of his responsibilities as Pro‐Vice Chancellor (Research) until 2010, receives fees for editorial and guideline developmental work and royalties from books, and is in receipt of institutional grants from NHMRC (Aus), NIHR (UK) and HTA (UK) and from a private donor (for support of the editorial base of the Cochrane ARI Group).

Dr Hama receives royalties from two books published in 2008 titled "Tamiflu: harmful as was afraid" and "In order to escape from drug‐induced encephalopathy". Dr Hama provided scientific opinions and expert testimony on 11 adverse reaction cases related to oseltamivir and gefitinib.

Dr Howick has received expenses and payments from Johns Hopkins and the American Society for Neurophysiological Monitoring as an EBM consultant. Dr Howick has received funding from the Wellcome Trust, the Medical Research Council of the UK, the Economics and Social Science Research Council of the UK and he is currently a National Institute for Health Research non‐clinical research fellow. He has received payment from the Canadian Medical Association Journal for writing a book review and receives royalties from the publication of his book from Blackwell/Wiley.

Dr Heneghan receives payment for running educational courses at the University of Oxford and University of Oxford ISIS consulting services for external teaching and training. He also receives royalties for books (Evidence Based Toolkit series by Blackwell BMJ Books).

Dr Onakpoya has no additional interests to disclose. Dr Thompson has no additional interests to disclose. Dr Jones has no additional interests to disclose. Dr Spencer has no additional interests to disclose. Dr Nunan has no additional interests to disclose. Dr Mahtani has no additional interests to disclose.

Figures

Figure 1
Figure 1
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies. 'Other bias' includes potentially active placebos.
Figure 2
Figure 2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study. 'Other bias' includes potentially active placebos.
Figure 3
Figure 3
Flow diagram describing the number of studies identified, inclusion, exclusion and progression from identification to stage 1 to stage 2 of the review. NB Because of the absence of trial programmes for both drugs listing all sponsored trials completed or underway, we had to rely on a variety of sources for the reconstruction of the trial programmes and retrieval of relevant clinical study reports. This complexity is reflected in the flowchart, illustrating the study selection process for this review. The two main pathways were the spontaneous release of 77 clinical full clinical study reports by Roche and the requests to regulatory authorities and GSK for all the relevant reports. There was overlap in trial reports retrieved following the different pathways
Figure 4
Figure 4
Forest plot of comparison: 1 Oseltamivir versus placebo for treatment, outcome: 1.1 Time to first alleviation of symptoms in adult treatment (ITT population) [hours].
Figure 5
Figure 5
Forest plot of comparison: 3 Zanamivir versus placebo for treatment, outcome: 3.1 Time to first alleviation of symptoms in adult treatment (days).
Figure 6
Figure 6
Forest plot of comparison: 3 Zanamivir versus placebo for treatment, outcome: 3.68 Time to first alleviation of symptoms in adults with/without relief medication [days].
Figure 7
Figure 7
Forest plot of comparison: 1 Oseltamivir versus placebo for treatment, outcome: 1.17 Complications: pneumonia in adult treatment.
Figure 8
Figure 8
Example Diary card from case‐report form for Zanamivir trial
Figure 9
Figure 9
Example Diary card from case‐report form for Zanamivir trial (cont)
Figure 10
Figure 10
Forest plot of comparison: 2 Oseltamivir versus placebo for prophylaxis, outcome: 2.19 Adverse events: headache in adult prophylaxis (on‐treatment).
Figure 11
Figure 11
Forest plot of comparison: 2 Oseltamivir versus placebo for prophylaxis, outcome: 2.54 Adverse events: psychiatric body system in adult prophylaxis (on‐ and off‐treatment).
Figure 12
Figure 12
Sample "Adverse event or intercurrent illness" form (oseltamivir study M76001)
Figure 13
Figure 13
Sample "Secondary illness" form (oseltamivir study WV15670)
Figure 14
Figure 14
Sample "Diagnosis of secondary illness" form, page 1/2 (oseltamivir study WV15978)
Figure 15
Figure 15
Sample "Diagnosis of secondary illness" form, page 2/2 (oseltamivir study WV15978)
Analysis 1.1
Analysis 1.1
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 1 Time to first alleviation of symptoms in adult treatment (ITT population).
Analysis 1.2
Analysis 1.2
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 2 Hospital admission in adult treatment (safety population).
Analysis 1.3
Analysis 1.3
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 3 Defined as influenza‐infected at baseline in adult treatment.
Analysis 1.4
Analysis 1.4
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 4 Antibody rise four‐fold or greater in adult treatment.
Analysis 1.5
Analysis 1.5
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 5 Adverse events ‐ nausea in adult treatment (on‐treatment).
Analysis 1.6
Analysis 1.6
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 6 Adverse events ‐ vomiting in adult treatment (on‐treatment).
Analysis 1.7
Analysis 1.7
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 7 Adverse events ‐ diarrhoea in adult treatment (on‐treatment).
Analysis 1.8
Analysis 1.8
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 8 Withdrawal from adult treatment trial due to adverse events.
Analysis 1.9
Analysis 1.9
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 9 All withdrawals from adult treatment.
Analysis 1.10
Analysis 1.10
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 10 Adverse events ‐ cough in adult treatment (on‐treatment).
Analysis 1.11
Analysis 1.11
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 11 Adverse events ‐ abdominal pain in adult treatment (on‐treatment).
Analysis 1.12
Analysis 1.12
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 12 Adverse events: dizziness in adult treatment (on‐treatment).
Analysis 1.13
Analysis 1.13
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 13 Adverse events: headache in adult treatment (on‐treatment).
Analysis 1.14
Analysis 1.14
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 14 Serious adverse events: overall in adult treatment (on‐treatment).
Analysis 1.15
Analysis 1.15
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 15 Serious adverse events: overall in adult treatment (off‐treatment).
Analysis 1.16
Analysis 1.16
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 16 Complications: bronchitis in adult treatment.
Analysis 1.17
Analysis 1.17
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 17 Complications: pneumonia in adult treatment.
Analysis 1.18
Analysis 1.18
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 18 Complications: sinusitis in adult treatment.
Analysis 1.19
Analysis 1.19
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 19 Complications: otitis media in adult treatment.
Analysis 1.20
Analysis 1.20
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 20 Complications in adult trials classified as serious or leading to study withdrawal.
Analysis 1.21
Analysis 1.21
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 21 Culture‐positive at baseline in adult treatment.
Analysis 1.22
Analysis 1.22
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 22 Adverse events: general body system in adult treatment (on‐treatment).
Analysis 1.23
Analysis 1.23
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 23 Adverse events: neurological body system in adult treatment (on‐treatment).
Analysis 1.24
Analysis 1.24
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 24 Adverse events: respiratory body system in adult treatment (on‐treatment).
Analysis 1.25
Analysis 1.25
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 25 Adverse events: infection body system in adult treatment (on‐treatment).
Analysis 1.26
Analysis 1.26
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 26 Adverse events: gastrointestinal body system in adult treatment (on‐treatment).
Analysis 1.27
Analysis 1.27
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 27 Adverse events: cardiac body system in adult treatment (on‐treatment).
Analysis 1.28
Analysis 1.28
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 28 Adverse events: ear body system in adult treatment (on‐treatment).
Analysis 1.29
Analysis 1.29
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 29 Adverse events: eye body system in adult treatment (on‐treatment).
Analysis 1.30
Analysis 1.30
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 30 Adverse events: metabolism body system in adult treatment (on‐treatment).
Analysis 1.31
Analysis 1.31
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 31 Adverse events: musculoskeletal body system in adult treatment (on‐treatment).
Analysis 1.32
Analysis 1.32
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 32 Adverse events: psychiatric body system in adult treatment (on‐treatment).
Analysis 1.33
Analysis 1.33
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 33 Adverse events: skin body system in adult treatment (on‐treatment).
Analysis 1.34
Analysis 1.34
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 34 Adverse events: cardiac body system in adult treatment (off‐treatment).
Analysis 1.35
Analysis 1.35
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 35 Adverse events: ear body system in adult treatment (off‐treatment).
Analysis 1.36
Analysis 1.36
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 36 Adverse events: gastrointestinal body system in adult treatment (off‐treatment).
Analysis 1.37
Analysis 1.37
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 37 Adverse events: general body system in adult treatment (off‐treatment).
Analysis 1.38
Analysis 1.38
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 38 Adverse events: infection body system in adult treatment (off‐treatment).
Analysis 1.39
Analysis 1.39
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 39 Adverse events: musculoskeletal body system in adult treatment (off‐treatment).
Analysis 1.40
Analysis 1.40
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 40 Adverse events: neurological body system in adult treatment (off‐treatment).
Analysis 1.41
Analysis 1.41
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 41 Adverse events: respiratory body system in adult treatment (off‐treatment).
Analysis 1.42
Analysis 1.42
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 42 Adverse events: skin body system in adult treatment (off‐treatment).
Analysis 1.43
Analysis 1.43
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 43 Adverse events: cough in adult treatment (off‐treatment).
Analysis 1.44
Analysis 1.44
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 44 Adverse events: headache in adult treatment (off‐treatment).
Analysis 1.45
Analysis 1.45
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 45 Adverse events: nausea in adult treatment (off‐treatment).
Analysis 1.46
Analysis 1.46
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 46 Time to first alleviation of symptoms in child treatment [hours].
Analysis 1.47
Analysis 1.47
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 47 Hospital admission in child treatment (safety population).
Analysis 1.48
Analysis 1.48
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 48 Defined as influenza‐infected at baseline in child treatment.
Analysis 1.49
Analysis 1.49
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 49 Antibody rise four‐fold or greater in child treatment.
Analysis 1.50
Analysis 1.50
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 50 Complications: bronchitis in child treatment.
Analysis 1.51
Analysis 1.51
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 51 Complications: otitis media in child treatment.
Analysis 1.52
Analysis 1.52
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 52 Complications: pneumonia in child treatment.
Analysis 1.53
Analysis 1.53
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 53 Complications: sinusitis in child treatment.
Analysis 1.54
Analysis 1.54
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 54 Complications: pneumonia in child treatment by on‐ and off‐treatment.
Analysis 1.55
Analysis 1.55
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 55 Complications in trials of children classified as serious or leading to study withdrawal.
Analysis 1.56
Analysis 1.56
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 56 Withdrawal from child treatment trial due to adverse events.
Analysis 1.57
Analysis 1.57
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 57 All withdrawals from child treatment.
Analysis 1.58
Analysis 1.58
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 58 Serious adverse events: overall in child treatment (on‐treatment).
Analysis 1.59
Analysis 1.59
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 59 Serious adverse events: overall in child treatment (off‐treatment).
Analysis 1.60
Analysis 1.60
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 60 Adverse events: abdominal pain in child treatment (on‐treatment).
Analysis 1.61
Analysis 1.61
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 61 Adverse events: diarrhoea in child treatment (on‐treatment).
Analysis 1.62
Analysis 1.62
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 62 Adverse events: nausea in child treatment (on‐treatment).
Analysis 1.63
Analysis 1.63
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 63 Adverse events: vomiting in child treatment (on‐treatment).
Analysis 1.64
Analysis 1.64
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 64 Adverse events: abdominal pain in child treatment (off‐treatment).
Analysis 1.65
Analysis 1.65
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 65 Adverse events: cough in child treatment (off‐treatment).
Analysis 1.66
Analysis 1.66
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 66 Adverse events: diarrhoea in child treatment (off‐treatment).
Analysis 1.67
Analysis 1.67
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 67 Adverse events: headache in child treatment (off‐treatment).
Analysis 1.68
Analysis 1.68
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 68 Adverse events: vomiting in child treatment (off‐treatment).
Analysis 1.69
Analysis 1.69
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 69 Adverse events: ear body system in child treatment (on‐treatment).
Analysis 1.70
Analysis 1.70
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 70 Adverse events: gastrointestinal body system in child treatment (on‐treatment).
Analysis 1.71
Analysis 1.71
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 71 Adverse events: general body system in child treatment (on‐treatment).
Analysis 1.72
Analysis 1.72
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 72 Adverse events: infection body system in child treatment (on‐treatment).
Analysis 1.73
Analysis 1.73
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 73 Adverse events: neurological body system in child treatment (on‐treatment).
Analysis 1.74
Analysis 1.74
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 74 Adverse events: respiratory body system in child treatment (on‐treatment).
Analysis 1.75
Analysis 1.75
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 75 Adverse events: skin body system in child treatment (on‐treatment).
Analysis 1.76
Analysis 1.76
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 76 Adverse events: ear body system in child treatment (off‐treatment).
Analysis 1.77
Analysis 1.77
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 77 Adverse events: gastrointestinal body system in child treatment (off‐treatment).
Analysis 1.78
Analysis 1.78
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 78 Adverse events: general body system in child treatment (off‐treatment).
Analysis 1.79
Analysis 1.79
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 79 Adverse events: infection body system in child treatment (off‐treatment).
Analysis 1.80
Analysis 1.80
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 80 Adverse events: neurological body system in child treatment (off‐treatment).
Analysis 1.81
Analysis 1.81
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 81 Adverse events: respiratory body system in child treatment (off‐treatment).
Analysis 1.82
Analysis 1.82
Comparison 1 Oseltamivir versus placebo for treatment, Outcome 82 Culture‐positive at baseline in child treatment.
Analysis 2.1
Analysis 2.1
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 1 Symptomatic influenza in adult prophylaxis of individuals.
Analysis 2.2
Analysis 2.2
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 2 Asymptomatic influenza in adult prophylaxis of individuals.
Analysis 2.3
Analysis 2.3
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 3 Symptomatic influenza in household prophylaxis.
Analysis 2.4
Analysis 2.4
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 4 Asymptomatic influenza in household prophylaxis.
Analysis 2.5
Analysis 2.5
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 5 Influenza‐like illness reported as adverse event (on‐treatment).
Analysis 2.6
Analysis 2.6
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 6 Influenza‐like illness reported as adverse event (off‐treatment).
Analysis 2.7
Analysis 2.7
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 7 Hospitalisation in adult prophylaxis (safety population).
Analysis 2.8
Analysis 2.8
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 8 Complications: bronchitis in adult prophylaxis.
Analysis 2.9
Analysis 2.9
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 9 Complications: sinusitis in adult prophylaxis.
Analysis 2.10
Analysis 2.10
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 10 Adverse events leading to study withdrawal in adult prophylaxis.
Analysis 2.11
Analysis 2.11
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 11 All withdrawals in adult prophylaxis.
Analysis 2.12
Analysis 2.12
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 12 Serious adverse events in adult prophylaxis (on‐treatment).
Analysis 2.13
Analysis 2.13
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 13 Serious adverse events in adult prophylaxis (off‐treatment).
Analysis 2.14
Analysis 2.14
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 14 Adverse events: abdominal pain in adult prophylaxis (on‐treatment).
Analysis 2.15
Analysis 2.15
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 15 Adverse events: cough in adult prophylaxis (on‐treatment).
Analysis 2.16
Analysis 2.16
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 16 Adverse events: diarrhoea in adult prophylaxis (on‐treatment).
Analysis 2.17
Analysis 2.17
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 17 Adverse events: dizziness in adult prophylaxis (on‐treatment).
Analysis 2.18
Analysis 2.18
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 18 Adverse events: fatigue in adult prophylaxis (on‐treatment).
Analysis 2.19
Analysis 2.19
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 19 Adverse events: headache in adult prophylaxis (on‐treatment).
Analysis 2.20
Analysis 2.20
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 20 Adverse events: nausea in adult prophylaxis (on‐treatment).
Analysis 2.21
Analysis 2.21
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 21 Adverse events: vomiting in adult prophylaxis (on‐treatment).
Analysis 2.22
Analysis 2.22
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 22 Adverse events: cough in adult prophylaxis (off‐treatment).
Analysis 2.23
Analysis 2.23
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 23 Adverse events: fatigue in adult prophylaxis (off‐treatment).
Analysis 2.24
Analysis 2.24
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 24 Adverse events: headache in adult prophylaxis (off‐treatment).
Analysis 2.25
Analysis 2.25
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 25 Adverse events: blood body system in adult prophylaxis (on‐treatment).
Analysis 2.26
Analysis 2.26
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 26 Adverse events: cardiac body system in adult prophylaxis (on‐treatment).
Analysis 2.27
Analysis 2.27
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 27 Adverse events: ear body system in adult prophylaxis (on treatment).
Analysis 2.28
Analysis 2.28
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 28 Adverse events: eye body system in adult prophylaxis (on‐treatment).
Analysis 2.29
Analysis 2.29
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 29 Adverse events: gastrointestinal body system in adult prophylaxis (on‐treatment).
Analysis 2.30
Analysis 2.30
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 30 Adverse events: general body system in adult prophylaxis (on‐treatment).
Analysis 2.31
Analysis 2.31
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 31 Adverse events: infection body system in adult prophylaxis (on‐treatment).
Analysis 2.32
Analysis 2.32
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 32 Adverse events: immune body system in adult prophylaxis (on‐treatment).
Analysis 2.33
Analysis 2.33
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 33 Adverse events: injury body system in adult prophylaxis (on‐treatment).
Analysis 2.34
Analysis 2.34
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 34 Adverse events: metabolism body system in adult prophylaxis (on‐treatment).
Analysis 2.35
Analysis 2.35
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 35 Adverse events: musculoskeletal body system in adult prophylaxis (on‐treatment).
Analysis 2.36
Analysis 2.36
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 36 Adverse events: neurological body system in adult prophylaxis (on‐treatment).
Analysis 2.37
Analysis 2.37
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 37 Adverse events: psychiatric body system in adult prophylaxis (on‐treatment).
Analysis 2.38
Analysis 2.38
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 38 Adverse events: renal body system in adult prophylaxis (on‐treatment).
Analysis 2.39
Analysis 2.39
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 39 Adverse events: reproductive body system in adult prophylaxis (on treatment).
Analysis 2.40
Analysis 2.40
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 40 Adverse events: respiratory body system in adult prophylaxis (on‐treatment).
Analysis 2.41
Analysis 2.41
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 41 Adverse events: skin body system in adult prophylaxis (on‐treatment).
Analysis 2.42
Analysis 2.42
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 42 Adverse events: surgical events in adult prophylaxis (on‐treatment).
Analysis 2.43
Analysis 2.43
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 43 Adverse events: vascular body system in adult prophylaxis (on‐treatment).
Analysis 2.44
Analysis 2.44
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 44 Adverse events: cardiac body system in adult prophylaxis (off‐treatment).
Analysis 2.45
Analysis 2.45
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 45 Adverse events: gastrointestinal body system in adult prophylaxis (off‐treatment).
Analysis 2.46
Analysis 2.46
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 46 Adverse events: general body system in adult prophylaxis (off‐treatment).
Analysis 2.47
Analysis 2.47
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 47 Adverse events: infection body system in adult prophylaxis (off‐treatment).
Analysis 2.48
Analysis 2.48
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 48 Adverse events: injury body system in adult prophylaxis (off‐treatment).
Analysis 2.49
Analysis 2.49
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 49 Adverse events: musculoskeletal body system in adult prophylaxis (off‐treatment).
Analysis 2.50
Analysis 2.50
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 50 Adverse events: neurological body system in adult prophylaxis (off‐treatment).
Analysis 2.51
Analysis 2.51
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 51 Adverse events: reproductive body system in adult prophylaxis (off‐treatment).
Analysis 2.52
Analysis 2.52
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 52 Adverse events: respiratory body system in adult prophylaxis (off‐treatment).
Analysis 2.53
Analysis 2.53
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 53 Adverse events: skin body system in adult prophylaxis (off‐treatment).
Analysis 2.54
Analysis 2.54
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 54 Adverse events: psychiatric body system in adult prophylaxis (on and off‐treatment).
Analysis 2.55
Analysis 2.55
Comparison 2 Oseltamivir versus placebo for prophylaxis, Outcome 55 Adverse events: renal body system in adult prophylaxis (on and off‐treatment).
Analysis 3.1
Analysis 3.1
Comparison 3 Zanamivir versus placebo for treatment, Outcome 1 Time to first alleviation of symptoms in adult treatment (days).
Analysis 3.2
Analysis 3.2
Comparison 3 Zanamivir versus placebo for treatment, Outcome 2 Complications: pneumonia in adult treatment.
Analysis 3.3
Analysis 3.3
Comparison 3 Zanamivir versus placebo for treatment, Outcome 3 Complications: pneumonia confirmed with X‐ray in adult treatment.
Analysis 3.4
Analysis 3.4
Comparison 3 Zanamivir versus placebo for treatment, Outcome 4 Complications: bronchitis in adult treatment.
Analysis 3.5
Analysis 3.5
Comparison 3 Zanamivir versus placebo for treatment, Outcome 5 Complications: sinusitis in adult treatment.
Analysis 3.6
Analysis 3.6
Comparison 3 Zanamivir versus placebo for treatment, Outcome 6 Complications: otitis media in adult treatment.
Analysis 3.7
Analysis 3.7
Comparison 3 Zanamivir versus placebo for treatment, Outcome 7 Complications in adult trials classified as serious or leading to study withdrawal.
Analysis 3.8
Analysis 3.8
Comparison 3 Zanamivir versus placebo for treatment, Outcome 8 Proportion diagnosed as influenza‐infected in adult treatment.
Analysis 3.9
Analysis 3.9
Comparison 3 Zanamivir versus placebo for treatment, Outcome 9 Proportion with four‐fold rise in antibody titre in adult treatment.
Analysis 3.10
Analysis 3.10
Comparison 3 Zanamivir versus placebo for treatment, Outcome 10 Proportion with positive culture at baseline in adult treatment.
Analysis 3.11
Analysis 3.11
Comparison 3 Zanamivir versus placebo for treatment, Outcome 11 Serious adverse events in adult treatment.
Analysis 3.12
Analysis 3.12
Comparison 3 Zanamivir versus placebo for treatment, Outcome 12 Adverse events leading to study withdrawal in adult treatment.
Analysis 3.13
Analysis 3.13
Comparison 3 Zanamivir versus placebo for treatment, Outcome 13 All withdrawals in adult treatment.
Analysis 3.14
Analysis 3.14
Comparison 3 Zanamivir versus placebo for treatment, Outcome 14 Time to first alleviation of symptoms in children (days).
Analysis 3.15
Analysis 3.15
Comparison 3 Zanamivir versus placebo for treatment, Outcome 15 Complications: pneumonia in child treatment.
Analysis 3.16
Analysis 3.16
Comparison 3 Zanamivir versus placebo for treatment, Outcome 16 Complications: bronchitis in child treatment.
Analysis 3.17
Analysis 3.17
Comparison 3 Zanamivir versus placebo for treatment, Outcome 17 Complications: sinusitis in child treatment.
Analysis 3.18
Analysis 3.18
Comparison 3 Zanamivir versus placebo for treatment, Outcome 18 Complications: otitis media in child treatment.
Analysis 3.19
Analysis 3.19
Comparison 3 Zanamivir versus placebo for treatment, Outcome 19 Proportion diagnosed as influenza‐infected in child treatment.
Analysis 3.20
Analysis 3.20
Comparison 3 Zanamivir versus placebo for treatment, Outcome 20 Proportion with four‐fold increase in antibodies in child treatment.
Analysis 3.21
Analysis 3.21
Comparison 3 Zanamivir versus placebo for treatment, Outcome 21 Proportion with positive culture at baseline in child treatment.
Analysis 3.22
Analysis 3.22
Comparison 3 Zanamivir versus placebo for treatment, Outcome 22 All withdrawals in child treatment.
Analysis 3.23
Analysis 3.23
Comparison 3 Zanamivir versus placebo for treatment, Outcome 23 Adverse events: nausea and vomiting in child treatment (on‐treatment).
Analysis 3.24
Analysis 3.24
Comparison 3 Zanamivir versus placebo for treatment, Outcome 24 Adverse events: diarrhoea in child treatment (on‐treatment).
Analysis 3.25
Analysis 3.25
Comparison 3 Zanamivir versus placebo for treatment, Outcome 25 Adverse events: gastrointestinal body system in child treatment (on‐treatment).
Analysis 3.26
Analysis 3.26
Comparison 3 Zanamivir versus placebo for treatment, Outcome 26 Adverse events: respiratory body system in child treatment (on‐treatment).
Analysis 3.27
Analysis 3.27
Comparison 3 Zanamivir versus placebo for treatment, Outcome 27 Adverse events: neurological body system in child treatment (on‐treatment).
Analysis 3.28
Analysis 3.28
Comparison 3 Zanamivir versus placebo for treatment, Outcome 28 Adverse events: ear, nose and throat body system in child treatment (on‐treatment).
Analysis 3.29
Analysis 3.29
Comparison 3 Zanamivir versus placebo for treatment, Outcome 29 Adverse events: skin body system in child treatment (on‐treatment).
Analysis 3.30
Analysis 3.30
Comparison 3 Zanamivir versus placebo for treatment, Outcome 30 Adverse events: gastrointestinal body system in child treatment (off‐treatment).
Analysis 3.31
Analysis 3.31
Comparison 3 Zanamivir versus placebo for treatment, Outcome 31 Adverse events: ear nose and throat body system in child treatment (off‐treatment).
Analysis 3.32
Analysis 3.32
Comparison 3 Zanamivir versus placebo for treatment, Outcome 32 Adverse events: nausea/vomiting in adult treatment (on‐treatment).
Analysis 3.33
Analysis 3.33
Comparison 3 Zanamivir versus placebo for treatment, Outcome 33 Adverse events: diarrhoea in adult treatment (on‐treatment).
Analysis 3.34
Analysis 3.34
Comparison 3 Zanamivir versus placebo for treatment, Outcome 34 Adverse events: dizziness in adult treatment (on‐treatment).
Analysis 3.35
Analysis 3.35
Comparison 3 Zanamivir versus placebo for treatment, Outcome 35 Adverse events: headache in adult treatment (on‐treatment).
Analysis 3.36
Analysis 3.36
Comparison 3 Zanamivir versus placebo for treatment, Outcome 36 Adverse events: cough in adult treatment (on‐treatment).
Analysis 3.37
Analysis 3.37
Comparison 3 Zanamivir versus placebo for treatment, Outcome 37 Adverse events: gastrointestinal body system in adult treatment (on‐treatment).
Analysis 3.38
Analysis 3.38
Comparison 3 Zanamivir versus placebo for treatment, Outcome 38 Adverse events: respiratory body system in adult treatment (on‐treatment).
Analysis 3.39
Analysis 3.39
Comparison 3 Zanamivir versus placebo for treatment, Outcome 39 Adverse events: neurological body system in adult treatment (on‐treatment).
Analysis 3.40
Analysis 3.40
Comparison 3 Zanamivir versus placebo for treatment, Outcome 40 Adverse events: ear, nose and throat body system in adult treatment (on‐treatment).
Analysis 3.41
Analysis 3.41
Comparison 3 Zanamivir versus placebo for treatment, Outcome 41 Adverse events: skin body system in adult treatment (on‐treatment).
Analysis 3.42
Analysis 3.42
Comparison 3 Zanamivir versus placebo for treatment, Outcome 42 Adverse events: musculoskeletal body system in adult treatment (on‐treatment).
Analysis 3.43
Analysis 3.43
Comparison 3 Zanamivir versus placebo for treatment, Outcome 43 Adverse events: eye body system in adult treatment (on‐treatment).
Analysis 3.44
Analysis 3.44
Comparison 3 Zanamivir versus placebo for treatment, Outcome 44 Adverse events: hepato body system in adult treatment (on‐treatment).
Analysis 3.45
Analysis 3.45
Comparison 3 Zanamivir versus placebo for treatment, Outcome 45 Adverse events: renal body system in adult treatment (on‐treatment).
Analysis 3.46
Analysis 3.46
Comparison 3 Zanamivir versus placebo for treatment, Outcome 46 Adverse events: cardiovascular body system in adult treatment (on‐treatment).
Analysis 3.47
Analysis 3.47
Comparison 3 Zanamivir versus placebo for treatment, Outcome 47 Adverse events: blood body system in adult treatment (on‐treatment).
Analysis 3.48
Analysis 3.48
Comparison 3 Zanamivir versus placebo for treatment, Outcome 48 Adverse events: psychiatric body system in adult treatment (on‐treatment).
Analysis 3.49
Analysis 3.49
Comparison 3 Zanamivir versus placebo for treatment, Outcome 49 Adverse events: reproduction body system in adult treatment (on‐treatment).
Analysis 3.50
Analysis 3.50
Comparison 3 Zanamivir versus placebo for treatment, Outcome 50 Adverse events: endocrine and metabolic body system in adult treatment (on‐treatment).
Analysis 3.51
Analysis 3.51
Comparison 3 Zanamivir versus placebo for treatment, Outcome 51 Adverse events: injury body system in adult treatment (on‐treatment).
Analysis 3.52
Analysis 3.52
Comparison 3 Zanamivir versus placebo for treatment, Outcome 52 Adverse events: non‐site specific events in adult treatment (on‐treatment).
Analysis 3.53
Analysis 3.53
Comparison 3 Zanamivir versus placebo for treatment, Outcome 53 Adverse events: nausea/vomiting in adult treatment (off‐treatment).
Analysis 3.54
Analysis 3.54
Comparison 3 Zanamivir versus placebo for treatment, Outcome 54 Adverse events: cough in adult treatment (off‐treatment).
Analysis 3.55
Analysis 3.55
Comparison 3 Zanamivir versus placebo for treatment, Outcome 55 Adverse events: respiratory body system in adult treatment (off‐treatment).
Analysis 3.56
Analysis 3.56
Comparison 3 Zanamivir versus placebo for treatment, Outcome 56 Adverse events: headache in adult treatment (off‐treatment).
Analysis 3.57
Analysis 3.57
Comparison 3 Zanamivir versus placebo for treatment, Outcome 57 Adverse events: diarrhoea in adult treatment (off‐treatment).
Analysis 3.58
Analysis 3.58
Comparison 3 Zanamivir versus placebo for treatment, Outcome 58 Adverse events: fatigue in adult treatment (off‐treatment).
Analysis 3.59
Analysis 3.59
Comparison 3 Zanamivir versus placebo for treatment, Outcome 59 Adverse events: gastrointestinal body system in adult treatment (off‐treatment).
Analysis 3.60
Analysis 3.60
Comparison 3 Zanamivir versus placebo for treatment, Outcome 60 Adverse events: neurological body system in adult treatment (off‐treatment).
Analysis 3.61
Analysis 3.61
Comparison 3 Zanamivir versus placebo for treatment, Outcome 61 Adverse events: ear, nose and throat in adult treatment (off‐treatment).
Analysis 3.62
Analysis 3.62
Comparison 3 Zanamivir versus placebo for treatment, Outcome 62 Adverse events: skin body system in adult treatment (off‐treatment).
Analysis 3.63
Analysis 3.63
Comparison 3 Zanamivir versus placebo for treatment, Outcome 63 Adverse events: musculoskeletal body system in adult treatment (off‐treatment).
Analysis 3.64
Analysis 3.64
Comparison 3 Zanamivir versus placebo for treatment, Outcome 64 Adverse events: non‐site specific in adult treatment (off‐treatment).
Analysis 3.65
Analysis 3.65
Comparison 3 Zanamivir versus placebo for treatment, Outcome 65 Adverse events: injury body system in adult treatment (off‐treatment).
Analysis 3.66
Analysis 3.66
Comparison 3 Zanamivir versus placebo for treatment, Outcome 66 Adverse events: endocrine and metabolic body system in adult treatment (off‐treatment).
Analysis 3.67
Analysis 3.67
Comparison 3 Zanamivir versus placebo for treatment, Outcome 67 Adverse events: eye body system in adult treatment (off‐treatment).
Analysis 3.68
Analysis 3.68
Comparison 3 Zanamivir versus placebo for treatment, Outcome 68 Time to first alleviation of symptoms in adults with/without relief medication [days].
Analysis 3.69
Analysis 3.69
Comparison 3 Zanamivir versus placebo for treatment, Outcome 69 Time to first alleviation of symptoms in adults by infection status [days].
Analysis 4.1
Analysis 4.1
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 1 Symptomatic influenza in prophylaxis of individuals.
Analysis 4.2
Analysis 4.2
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 2 Asymptomatic influenza in prophylaxis of individuals.
Analysis 4.3
Analysis 4.3
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 3 Symptomatic influenza in post‐exposure prophylaxis.
Analysis 4.4
Analysis 4.4
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 4 Asymptomatic influenza in post‐exposure prophylaxis.
Analysis 4.5
Analysis 4.5
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 5 Complications: pneumonia in adult prophylaxis.
Analysis 4.6
Analysis 4.6
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 6 Complications: bronchitis in adult prophylaxis.
Analysis 4.7
Analysis 4.7
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 7 Complications: sinusitis in adult prophylaxis.
Analysis 4.8
Analysis 4.8
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 8 Complications classified as serious or leading to study withdrawal.
Analysis 4.9
Analysis 4.9
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 9 Serious adverse events in adult prophylaxis.
Analysis 4.10
Analysis 4.10
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 10 Adverse events leading to study withdrawal in adult prophylaxis.
Analysis 4.11
Analysis 4.11
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 11 All withdrawals in adult prophylaxis.
Analysis 4.12
Analysis 4.12
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 12 Adverse events: abdominal pain in adult prophylaxis (on‐treatment).
Analysis 4.13
Analysis 4.13
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 13 Adverse events: cough in adult prophylaxis (on‐treatment).
Analysis 4.14
Analysis 4.14
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 14 Adverse events: diarrhoea in adult prophylaxis (on‐treatment).
Analysis 4.15
Analysis 4.15
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 15 Adverse events: dizziness in adult prophylaxis (on‐treatment).
Analysis 4.16
Analysis 4.16
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 16 Adverse events: fatigue in adult prophylaxis (on‐treatment).
Analysis 4.17
Analysis 4.17
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 17 Adverse events: headache in adult prophylaxis (on‐treatment).
Analysis 4.18
Analysis 4.18
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 18 Adverse events: blood body system in adult prophylaxis (on‐treatment).
Analysis 4.19
Analysis 4.19
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 19 Adverse events: nausea/vomiting in adult prophylaxis (on‐treatment).
Analysis 4.20
Analysis 4.20
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 20 Adverse events: cardiovascular body system in adult prophylaxis (on‐treatment).
Analysis 4.21
Analysis 4.21
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 21 Adverse events: ear, nose and throat body system in adult prophylaxis (on‐treatment).
Analysis 4.22
Analysis 4.22
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 22 Adverse events: endocrine and metabolic body system in adult prophylaxis (on‐treatment).
Analysis 4.23
Analysis 4.23
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 23 Adverse events: eye body system in adult prophylaxis (on‐treatment).
Analysis 4.24
Analysis 4.24
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 24 Adverse events: gastrointestinal body system in adult prophylaxis (on‐treatment).
Analysis 4.25
Analysis 4.25
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 25 Adverse events: injury body system in adult prophylaxis (on‐treatment).
Analysis 4.26
Analysis 4.26
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 26 Adverse events: musculoskeletal body system in adult prophylaxis (on‐treatment).
Analysis 4.27
Analysis 4.27
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 27 Adverse events: neurological body system in adult prophylaxis (on‐treatment).
Analysis 4.28
Analysis 4.28
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 28 Adverse events: non‐site specific in adult prophylaxis (on‐treatment).
Analysis 4.29
Analysis 4.29
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 29 Adverse events: psychiatric body system in adult prophylaxis (on‐treatment).
Analysis 4.30
Analysis 4.30
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 30 Adverse events: renal body system in adult prophylaxis (on‐treatment).
Analysis 4.31
Analysis 4.31
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 31 Adverse events: reproductive body system in adult prophylaxis (on‐treatment).
Analysis 4.32
Analysis 4.32
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 32 Adverse events: respiratory body system in adult prophylaxis (on‐treatment).
Analysis 4.33
Analysis 4.33
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 33 Adverse events: skin body system in adult prophylaxis (on‐treatment).
Analysis 4.34
Analysis 4.34
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 34 Adverse events: gastrointestinal body system in adult prophylaxis (off‐treatment).
Analysis 4.35
Analysis 4.35
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 35 Adverse events: respiratory body system in adult prophylaxis (off‐treatment).
Analysis 4.36
Analysis 4.36
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 36 Adverse events: nausea/vomiting in prophylaxis (off‐treatment).
Analysis 4.37
Analysis 4.37
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 37 Adverse events: diarrhoea in prophylaxis (off‐treatment).
Analysis 4.38
Analysis 4.38
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 38 Adverse events: headache in prophylaxis (off‐treatment).
Analysis 4.39
Analysis 4.39
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 39 Adverse events: cough in prophylaxis (off‐treatment).
Analysis 4.40
Analysis 4.40
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 40 Adverse events: fatigue in prophylaxis (off‐treatment).
Analysis 4.41
Analysis 4.41
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 41 Adverse events: neurological body system in prophylaxis (off‐treatment).
Analysis 4.42
Analysis 4.42
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 42 Adverse events: ear, nose and throat in prophylaxis (off‐treatment).
Analysis 4.43
Analysis 4.43
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 43 Adverse events: musculoskeletal body system in prophylaxis (off‐treatment).
Analysis 4.44
Analysis 4.44
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 44 Adverse events: non‐site specific in prophylaxis (off‐treatment).
Analysis 4.45
Analysis 4.45
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 45 Adverse events: injury in prophylaxis (off‐treatment).
Analysis 4.46
Analysis 4.46
Comparison 4 Zanamivir versus placebo for prophylaxis, Outcome 46 Adverse events: endocrine and metabolic in prophylaxis (off‐treatment).
Analysis 5.1
Analysis 5.1
Comparison 5 Neuraminidase inhibitor versus placebo for treatment or prophylaxis, Outcome 1 Complications: pneumonia.

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