Neuraminadase inhibitors not always beneficial to patients with influenza

A recent Cochrane review recommends that the guidance on using neuraminidase inhibitors be reviewed to take into account the small benefit compared with the risk of harm, according to data published in the British Medical Journal and The Cochrane Library.

“We now have the most robust, comprehensive review on ‘neuraminidase inhibitors’ that exists,” David Tovey, MD, editor-in-chief of the Cochrane Library, said in a press release. “Initially thought to reduce hospitalizations and serious complications from influenza, the review highlights that Tamiflu is not proven to do this, and it also seems to lead to harmful effects that were not fully reported in the original publications. This shows the importance of ensuring that trial data are transparent and accessible.”

On behalf of the Cochrane Collaboration and the BMJ, several experts recently released a statement that called on government and health policy decision makers to review guidance on the use of oseltamivir based on the evidence that the antiviral appears ineffective.

Previous clinical trials of oseltamivir (Tamiflu, Genentech) used to treat influenza indicated the drug increased the risk of nausea and vomiting by about 4% in adults and 5% in children. In prevention trials, oseltamivir increased the risk of headaches, psychiatric disturbances, and renal events. Oseltamivir also did not prevention influenza transmission, according to results of the systematic review published in BMJ.

Quicker alleviation of influenza-like symptoms was evident in adults taking oseltamivir, however the effect is more uncertain in children, according to the statement from Tovey and BMJ Editor-in-Chief Fiona Godlee, MD. No evidence was found either for decreased hospitalizations of serious influenza complications including: confirmed pneumonia, bronchitis, sinusitis or otitis media in adults or children. The ability to produce antibodies to fight infection was also prevented in some patients treated with oseltamivir, according to study evidence.

Fiona Godlee

BMJ reported similar findings were for zanamivir (Relenza, GlaxoSmithKline), which led to alleviation of symptoms in adults but not children. However, the risk of pneumonia was not reduced and the effect on pneumonia in children was not significant. No significant effects on otitis media or sinusitis were found among adults and children. However, there was a small effect on bronchitis among adults but not children. Reduction in the risk of complications of influenza, hospital admission or death were not evident with zanamivir use, according to the authors of the systematic review also published in BMJ.

“This (Cochrane) review is the result of many years of struggles to access and use trial data, which was previously unpublished and even hidden from view,” Godlee said in the release. “It highlights with certainty that future decisions to purchase and use drugs, particularly when on a mass scale, must be based on a complete picture of the evidence, both published and unpublished. We need the full data from clinical trials made available for all drugs in current use. With the new European Clinical Trials Directive brining in rules for future drugs, it highlights the enormous challenge we face. We need the commitment of organizations and drug companies to make all data available, even if it means going back 20 years. Otherwise we risk another knee-jerk reaction to a potential pandemic. And can we really afford it?”

For more information:

Jefferson T. BMJ. 2014;doi:10.1136/bmj.g2545.

Jefferson T. Cochrane Libr. 2014;doi:10.1002/14651858.CD002965.pub4.

Heneghan CJ. BMJ. 2014;doi:10.1136/bmj.g2547.

Disclosure: See the studies for the full list of disclosures.