HealthDay News — Double-dose oseltamivir has no benefit over standard-dose treatment for patients with severe influenza, study findings indicate.

“Our results and other observational reports from avian [influenza] infections do not support routine use of double dose oseltamivir to treat severe influenza,” Jeremy J. Farrar, of SEAICRN Hospital for Tropical Diseases in Ho Chi Minh City, Viet Nam and colleagues reported in BMJ. “These findings have implications for both clinical management of severe influenza and for pandemic preparedness of emerging influenza viruses including the current H7N9 epidemic.”

Oseltamivir is known to be beneficial for patients with uncomplicated influenza when it is administered within 48 hours of symptom onset — several observational studies have shown it reduces mortality and shortens hospital stays when administered early. Some health officials have also recommended administering double doses of the drug to treat patients with severe influenza, despite a lack of clinical evidence supporting this option.

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To determine whether higher doses of oseltamivir control viral replication faster and improve clinical outcomes compared with standard doses, Farrar and researchers from the South East Asia Infectious Diseases Clinical Research Network conducted a double blind randomized trial in 13 hospitals in Indonesia, Singapore, Thailand and Vietnam.

The study involved 326 patients aged 1 year or older with confirmed severe influenza, including 246 children younger than 15 years. The researchers randomly assigned 161 patients to standard-dose oseltamivir (75 mg twice a day, or pediatric equivalent) and 165 patients to double-dose oseltamivir (150 mg twice a day, or pediatric equivalent).

The primary endpoint was the proportion of patients with no detectable viral RNA by rapid antigen test (RT-PCR) in a combined nasal and throat swab on day five after oseltamivir treatment, as in a previously suggested standard. 

At this time point, similar proportions of patients in the double-dose and standard-dose groups were negative for influenza RNA (72.3% vs. 68.2%, respectively; P = 0.42), the researchers determined. Furthermore, in subgroup analyses by virus type/subtype, and patient age and illness duration, there were no differences noted in viral  clearance.

Mortality was similar in both groups (7.3% in double-dose vs. 5.6% in standard-dose recipients). No between-group differences were seen in the median days on supplemental oxygen, in intensive care or on mechanical ventilation.

In an accompanying editorial, Ian G. Barr and Aeron C. Hurt of the WHO Collaborating Centre for Reference and Research on Influenza, in North Melbourne, Victoria, Australia, said the findings were important, due to the potential for an influenza pandemic and limited current treatment options.

“These findings could help to preserve oseltamivir stocks during a future pandemic through better use of currently available drug resources if clinicians were to prescribe only regular rather than double doses,” they wrote, adding that treatment options need to be expanded, particularly with the emergence of avian A(H7N9) influenza cases.

“Future studies will hopefully lead to more effective treatments or better combinations of drugs, including those that act both on the influenza virus and detrimental host factors,” Barr and Hurt wrote.

The  study had several limitations. The majority of patients were children and were infected with seasonal or pandemic virus rather than the more serious A(H5N1) virus, and the findings are likely not generalizable to other geographical locations and populations, the researchers acknowledged.


  1. Farrar J et al. BMJ. 2013; 346: f3039.
  2. Barr IG, Hurt AC. BMJ. 2013; 346: 3449.