TRIP Answers

13 May 2009

What is the evidence for using oseltamivir in influenza?

The National Public Health service for Wales (NPHS) has summarised information on the use of antivirals for influenza-like illness which is freely available at http://howis.wales.nhs.uk/sites3/page.cfm?orgid=474&pid=21310

ATTRACT found a number of secondary sources discussing the evidence for the use of oseltamivir in the treatment of and prophylaxis against influenza. NICE has produced guidance on amantadine, oseltamivir and zanamivir for the treatment of influenza (1) in 2009 and another of the same agent as prophylaxis of influenza (2) in late 2008. Section 4 of each document outlines the available evidence. The HTA evidence compilation supporting this guidance is also available (3)

There are also two Cochrane reviews of interest; one on neuraminidase inhibitors for preventing and treating influenza in healthy adults (4) the other on treatment and prophylaxis with neuraminidase inhibitors in children (5).

The Cochrane review involving adults notes:

“Main results
We identified four prophylaxis, 13 treatment and four post-exposure prophylaxis (PEP) trials. In prophylaxis compared to placebo, NIs have no effect against influenza-like illnesses (ILI) (relative risk (RR) 1.28, 95% confidence interval (CI) 0.45 to 3.66 for oral oseltamivir 75 mg daily; RR 1.51, 95% CI 0.77 to 2.95 for inhaled zanamivir 10 mg daily). The efficacy of oral oseltamivir 75 mg daily against symptomatic influenza is 61% (RR 0.39, 95% CI 0.18 to 0.85), or 73% (RR 0.27, 95% CI 0.11 to 0.67) at 150 mg daily. Inhaled zanamivir 10 mg daily is 62% efficacious (RR 0.38, 95% CI 0.17 to 0.85). Neither NI has a significant effect on asymptomatic influenza. Oseltamivir induces nausea (odds ratio (OR) 1.79, 95% CI 1.10 to 2.93). Oseltamivir for PEP has an efficacy of 58.5% (15.6% to 79.6) for households and of 68% (34.9 to 84.2%) to 89% in contacts of index cases. Zanamivir has similar performance. The hazard ratios for time to alleviation of influenza symptoms were in favour of the treated group 1.33 (1.29 to 1.37) for zanamivir and 1.30 (1.13 to 1.50) for oseltamivir. Viral nasal titres were significantly diminished by both NIs. Oseltamivir 150 mg daily prevented lower respiratory tract complications (OR 0.32, 95% CI 0.18 to 0.57). We could find no comparative data on the effects of oseltamivir on avian influenza.

Authors' conclusions

Because of their low effectiveness, NIs should not be used in routine seasonal influenza control. In a serious epidemic or pandemic, NIs should be used with other public health measures. We are unsure of the generalisability of our conclusions from seasonal to pandemic or avian influenza.”

The Cochrane review involving children states:

“Three trials involving 1500 children with a clinical case definition of influenza were included, of whom 977 had laboratory-confirmed influenza. Overall, trial quality was good. Oseltamivir reduced the median duration of illness by 26% (36 hours) in healthy children with laboratory-confirmed influenza (P value less than 0.0001). The reduction was only 7.7% (10 hours) in 'at risk' (asthmatic) children, and this did not reach statistical significance (P value = 0.54). Zanamivir reduced the median duration of illness by 24% (1.25 days) in healthy children with laboratory-confirmed influenza (P value less than 0.001). No data in 'at risk' children were available. Only oseltamivir produced a significant reduction in the complications of influenza (particularly otitis media), although there was a trend to benefit for zanamivir. We identified one randomised, controlled trial of oseltamivir for the prevention of influenza transmission in households, reporting data from 222 paediatric contacts. Where index cases had laboratory-confirmed influenza, a protective efficacy of 55% was observed, but this did not reach statistical significance (P value = 0.089). The adverse events profile of zanamivir was no worse than placebo, but vomiting was more common in children treated with oseltamivir.

Authors' conclusions

Neuraminidase inhibitors are effective in shortening illness duration in healthy children with influenza, but efficacy in 'at risk' children remains to be proven. Oseltamivir is also effective in reducing the incidence of secondary complications, and may be effective for influenza prophylaxis.”

1. http://www.nice.org.uk/nicemedia/pdf/TA168fullguidance.pdf
2. http://www.nice.org.uk/nicemedia/pdf/TA158Guidance.pdf
3. http://www.ncchta.org/execsumm/summ1311.shtml
4. http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD001265/frame.html
5. http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD002744/frame.html