Influenza Antiviral Medications: Summary for Clinicians
Content source: https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm Page 8
higher dosing may not provide additional clinical benefit (Abdel-Ghafar, 2008; Ariano, 2010; Kumar,
2010; Lee, 2013; South East Asia Infectious Disease Clinical Research Network, 2013). Studies
indicate that the exposure to oseltamivir carboxylate (the active metabolite of oseltamivir) is similar
between obese and non-obese subjects for both 75 mg and 150 mg doses given twice daily (Ariano,
2010; Jittamala, 2014; Pai, 2011; Thorne-Humphrey, 2011).
Limited data suggest that oseltamivir administered orally or by oro/naso gastric tube is well absorbed in
critically ill influenza patients, including those in the intensive care unit, on continuous renal replacement
therapy, and/or on extracorporeal membrane oxygenation (Ariano, 2010; Eyler, 2012a; Eyler, 2012b; Giraud,
2011; Kromdijk, 2013; Lemaitre, 2012; Mulla, 2013; Taylor, 2008).
However, for patients who cannot tolerate or absorb oral or enterically-administered oseltamivir because of
suspected or known gastric stasis, malabsorption, or gastrointestinal bleeding, the use of intravenous
peramivir or investigational intravenous zanamivir should be considered.
o In a randomized trial of treatment of influenza in hospitalized patients aged >6 years, a significant
clinical benefit was not demonstrated for intravenous peramivir at a dosage of 600 mg once daily (10
mg/kg once daily in children) for five days plus standard of care compared with placebo plus
standard of care; however, peramivir was generally safe and well tolerated (de Jong, 2014).
o Intravenous zanamivir is an investigational parenterally administered neuraminidase inhibitor
product available only under an emergency investigational new drug (EIND) request to the
manufacturer for compassionate use in hospitalized adult and pediatric patients with severe
influenza. (See Intravenous Influenza Antiviral Medications and CDC Considerations Related to
Investigational Use of Intravenous Zanamivir for 2016-2017 Influenza Season.)
It is possible that some influenza viruses may become resistant to oseltamivir and peramivir during antiviral
treatment with one of these agents and remain susceptible to zanamivir; this has been reported most often
for influenza A H1N1 viruses (Graitcer, 2011; Lackenby, 2011; Memoli, 2010; Nguyen, 2010; Nguyen, 2012).
Resistance of influenza viruses to antiviral drugs can also occur spontaneously, with no known exposure to
antiviral medications (Hurt, 2011; Takashita, 2013; Takashita, 2014).
If a hospitalized patient treated with oseltamivir and/or peramivir manifests progressive lower respiratory
symptoms, resistant virus should be considered. In view of the limited alternatives, CDC recommends that
investigational use of intravenous zanamivir should be considered for treatment of severely ill patients with
oseltamivir-resistant virus infection (Dulek, 2010; Gaur, 2010; Committee of the WHO Consultation on Clinical
Aspects of Pandemic (H1N1) 2009 Influenza, 2010). Oseltamivir or peramivir should not be stopped until
intravenous zanamivir can be initiated. However, clinicians should note that failure to improve or clinical
deterioration during oseltamivir or peramivir treatment is more likely to be related to the natural history of