Double-Dose Oseltamivir — No Better for Influenza

Viral shedding, morbidity, and mortality were not improved by doubling the dose of oseltamivir in patients with severe influenza, regardless of virus type.

Recent years have seen the emergence of new influenza A strains with high mortality. Oseltamivir, when given early after symptom onset, has been shown to improve survival. Some authorities believe that raising the dose might increase efficacy.
This hypothesis was tested in a double-blind trial conducted between April 2007 and February 2010 in 13 hospitals in Indonesia, Singapore, Thailand, and Vietnam. A total of 326 patients hospitalized with severe influenza were randomized to receive double- or standard-dose oseltamivir (150 or 75 mg twice daily, or the pediatric equivalent) for 5 days.

Of these patients, 80% had influenza A (A/H3N2 in 41%, A/H1N1-pdm09 in 22%, seasonal A/H1N1 in 12%, A/H5N1 in 5%), and 16% had influenza B; 4% had false-positive test results. No significant between-arm differences were seen in the proportion of patients shedding virus at day 5 — the primary endpoint — or in morbidity (need for oxygen therapy, time in intensive care or on mechanical ventilation, clinical failure rates) or mortality. In patients with A/H5N1 infection, mortality was markedly increased, regardless of the treatment regimen.

CITATION(S):

South East Asia Infectious Disease Clinical Research Network. 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. BMJ 2013 May 30; 346:f3039.