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No Benefit Of Double Dose Antiviral Drug For Severe Influenza

Findings have major implications for stockpiling drugs during pandemics, say experts

There are no virological or clinical benefits of giving of the antiviral drug oseltamivir (Tamiflu) to patients admitted to hospital with severe influenza, finds a large study from South East Asia published on bmj.com today.

This is the first study to examine the effectiveness of higher doses of oseltamivir in cases of hospitalized severe (seasonal, pandemic and bird flu strains). The authors say their findings have implications for global guidelines, clinical management and pandemic preparedness, including for the current H7N9 outbreak.

Human influenza is usually a self-limiting illness. Occasionally, however, it can lead to respiratory complications, admission to hospital, and death. Some studies suggest that, if given early, oseltamivir can help reduce mortality. This has led to suggestions to use double doses of the drug for severe influenza.

So researchers at the South East Asian Infectious Disease Clinical Research Network investigated whether oseltamivir improves outcomes compared with the standard dose in patients admitted to hospital with severe influenza.

The study took place between April 2007 and February 2010 and involved 326 patients (mostly children aged under 15) with severe influenza at 13 hospitals in Indonesia, Singapore, Thailand and Vietnam.

Patients received either standard dose oseltamivir (75 mg twice a day or children’s equivalent) or double dose (150 mg twice a day or children’s equivalent) for five days. Nose and throat swabs were then taken to test for virus levels.

Other outcomes including death, admission to intensive care, and help with breathing (mechanical ventilation) were also assessed.

The researchers found no differences between the treatment groups in virus levels on day five. There were also no differences in deaths or rates of adverse events between the different doses.

The investigators say that the results “do not support routine use of double dose oseltamivir to treat severe influenza.” And they conclude: “There are no virological or clinical advantages with double dose oseltamivir compared with standard dose in patients with severe influenza admitted to hospital.”

In an accompanying editorial, Ian Barr and Aeron Hurt from the WHO Collaborating Centre for Reference and Research on Influenza say, despite some study limitations, what is clear is that double dose oseltamivir “is unlikely to significantly improve the clinical outcomes of severe cases of seasonal influenza.”

These findings “could help to preserve oseltamivir stocks during a future pandemic … if clinicians were to prescribe only regular rather than double doses,” they add. However, they stress that treatment options for patients with severe influenza “still need to be expanded” and that future studies “will hopefully lead to more effective treatments or better combinations of drugs.”


Research: “Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial”,
South East Asia Infectious Disease Clinical Research Network
BMJ 2013;346:f3039 doi: 10.1136/bmj.f3039

Editorial: “Double dose oseltamivir for severe influenza – does it help?”,
Ian G Barr, Aeron C Hurt.
BMJ 2013;346:f3449 doi: 10.1136/bmj.f3449