Double dose of Tamiflu offers no added benefit in severe flu

Giving double doses of the antiviral drug Tamiflu to patients admitted to hospital with severe flu offers no clinical advantage over the standard dose, according to a randomised trial involving Oxford University researchers based in South East Asia.

This is the first study to look at the effectiveness of higher doses of Tamiflu, or oseltamivir, in cases of severe influenza infection.

The findings have implications for global guidelines on clinical management of severe flu, and also the stockpiling of drugs by national governments for pandemic preparedness, including in the current outbreak of the H7N9 bird flu virus in China.

Professor Jeremy Farrar, head of the Oxford University Clinical Research Unit in Vietnam and director of the South East Asia Infectious Disease Clinical Research Network, led the research. He said: 'The recommendation to give higher doses of oseltamivir to severe cases of flu infection has major implications for clinical management, public health, and planning for antiviral stockpiles but has not been grounded in evidence. Our findings do not support routine use of double doses to treat severe flu infections, which could help to conserve drug stocks in the event of a pandemic.'

The study is published in the medical journal BMJ and was funded by the Wellcome Trust, US National Institute of Allergy and Infectious Diseases and the Singapore National Medical Research Council.

Most people who are infected with flu will recover in a few days or up to two weeks. But some people will develop complications, such as difficulty with breathing, that result in hospital admission and can be life-threatening.

Studies have found that early treatment with Tamiflu is beneficial for patients with uncomplicated flu infection and improves survival in hospitalised patients with severe infection. This has led some authorities to recommend double doses of the drug for treatment of patients with severe flu infections.

The new study was conducted by researchers from the South East Asia Infectious Diseases Clinical Research Network, including scientists from Oxford University clinical research units in Indonesia, Thailand and Vietnam.

The trial involved 326 patients with severe flu infection at 13 hospitals in Indonesia, Singapore, Thailand and Vietnam. Most of the patients were children under the age of 15.

Patients were given either a standard dose or double dose of Tamiflu for five days. Their virus levels were monitored for the duration of the treatment along with other outcomes, such as admission to intensive care, the need for mechanical ventilation to assist with breathing and death.

The findings reveal no difference in virus levels at day five between the different doses. There were also no clinical differences in the outcomes for patients, including need for ventilation, time in hospital, deaths, or rates of adverse events.