The level of evidence is downgraded by study quality (selective reporting)
A Cochrane review [Abstract] 1 included 46 studies, 20 oseltamivir (9 623 participants) and 26 zanamivir trials (14 628 participants). All clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments were reviewed.
A systematic review 2 included all published and unpublished randomised placebo-controlled, double-blind trials of 75 mg twice a day oseltamivir in adults. Data were included from nine trials with 4328 participants.
Treatment trialsT1. In the Cochrane review 1 for the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours. There was no effect in asthmatic children, but in otherwise healthy children there was (reduction by a mean difference of 29 hours). Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days. The effect in children was not significant. In the other systematic review 2, in the intention-to-treat (ITT) population with laboratory confirmed infection, a 21% shorter time to alleviation of all symptoms for oseltamivir versus placebo recipients (time ratio 0.79, 95% CI 0.74 to 0.85) was noted. The median times to alleviation were 97.5 h for oseltamivir and 122.7 h for placebo (difference -25.2 h, 95% CI -36.2 to -16.0). For the intention-to-treat population, the estimated treatment effect was attenuated (time ratio 0.85) but remained highly significant (median difference -17.8 h).
| Outcome | No. of participants(studies) | Corresponding risk: treatment |
| Oseltamivir: time to first alleviation of symptoms in adult ITT treatment 1 | 3954 (8) | The mean time (hours) was 16.76 lower(25.1 to 8.42 lower) (equating from 7 to 6.3 days) |
| Oseltamivir: time to first alleviation of symptoms in adult ITT treatment 2 | 4264 (9) | The mean time (hours) was 17.8 lower(27.1 to 9.3 lower) |
| Oseltamivir: time to first alleviation of symptoms in adult with confirmed infection treatment 2 | 2860 (9) | The mean time (hours) was 25.2 lower(36.2 to 16.0 lower) (equating from 122.7 to 97.5 hours or from 5.1 to to 4.1 days) |
| Oseltamivir: time to first alleviation of symptoms the treatment of children without asthma 1 | 669 (1) | The mean time (hours) was 29.40 lower(47.04 to 11.76 lower) |
| Oseltamivir: time to first alleviation of symptoms the treatment of children with asthma 1 | 660 (2) | The mean time (hours) was 5.18 higher(21.41 higher to 11.06 lower)(n.s.) |
| Zanamivir: time to first alleviation of symptoms in adult treatment 1 | 5411 (13) | The mean time (days) was 0.60 lower(0.81 to 0.39 lower) (equating from 6.6 to 6.0 days) |
| Zanamivir: time to first alleviation of symptoms in child treatment 1 | 723 (2) | The mean time (days) was 1.08 lower(2.32 lower to 0.15 higher) (n.s.) |
Treatment trials - complications. In 1, treatment of adults or children with oseltamivir had no significant effect on hospitalisations or serious complications. 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. There was no significant effect of zanamivir on either self reported or radiologically confirmed pneumonia in the treated population.In 2, in the intention-to-treat population with laboratory confirmed infection, fewer lower respiratory tract complications requiring antibiotics were noted more than 48 h after randomisation (RR 0.56, 95% CI 0.42 to 0.75; 4.9% oseltamivir vs 8.7% placebo and also fewer admittances to hospital for any cause (RR 0.37, 95% CI 0.17 to 0·81; 0.6% oseltamivir, 1.7% placebo).
Prophylaxis trialsT2. In 1, oseltamivir and zanamivir reduced the risk of symptomatic influenza in adult individuals. 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.
| Outcome | Relative effect(95% CI) | No. of participants(studies) | Assumed risk: control | Corresponding risk: treatment |
| Oseltamivir: prophylaxis of symptomatic influenza in adults | RR 0.45 (0.30 to 0.67) | 2479 (3) | 55 per 1000 | 25 per 1000(17 to 37) |
| Zanamivir: prophylaxis of symptomatic influenza in adults | RR 0.39 (0.22 to 0.70) | 5275 (4) | 33 per 1000 | 13 per 1000(7 to 23) |
Side effects. In both studies, neuraminidase inhibitor treatment was associated with increased (2 to 4-fold) risk of nausea and vomiting.
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.
Date of latest search: 2013-12-31
Primary/Secondary Keywords