Is High-Dose Tamiflu Necessary to Treat Severe Flu?

Around 28,000 influenza infections are severe enough to warrant intensive care unit (ICU) admissions each year.

The current standard of care in these situations is a high-dose neuraminidase inhibitor such as oseltamivir (Tamiflu) and supportive care.

The World Health Organization recommends higher doses, such as oseltamivir 150 mg twice daily, for longer durations than for less severely ill patients. However, the quality of evidence for this finding is low.

Clinical shortages of oseltamivir have been reported for the past 4 consecutive years, and high-dose oseltamivir's unproven clinical benefit must be weighed against its limited supply.

A new study published in the March 2016 issue of Journal of Intensive Care Medicine suggests that high-dose oseltamivir use exacerbates the limited drug supply without clinical advantage compared with standard dosing. This retrospective study enrolled patients at an academic medical center admitted to the ICU between January 1, 2007, and March 31, 2014.

The researchers excluded patients if they were admitted to the ICU for a non-influenza indication, were treated with a neuraminidase inhibitor other than oseltamivir, or were treated at an outside facility for more than 72 hours.

They found that high-dose oseltamivir was not superior to standard dosing when measured by duration of mechanical ventilation, oxygenation, ICU length of stay, and overall length of stay. Two previous studies also found that high-dose oseltamivir did not produce superior clinical or virologic outcomes in non-critically ill patients.

However, one retrospective analysis found that neuraminidase inhibitors effectively improve survival in critically ill patients. A pharmacokinetic study in critically ill patients found that 75 mg of oseltamivir taken twice daily achieved serum concentration in excess of the MIC90 value.

The researchers concluded that oseltamivir given in normal doses is appropriate in the ICU. Standard dosing conserves the limited supply of oseltamivir without affecting patient outcomes.