Oseltamivir Dosing in Critically Ill Patients With Severe Influenza

Objective: To evaluate the literature for published reports regarding the efficacy of standard versus higher dosing of oseltamivir in critically ill patients with severe influenza. Data Sources: An English-language literature search was conducted using MEDLINE (1966-February 2014) using the terms oseltamivir and influenza limited to humans and adults older than 19 years. Additional articles were identified through a manual search of the references obtained from the MEDLINE search. Study Selection and Data Extraction: Articles were manually screened for inclusion related to pharmacokinetic or clinical studies comparing varying doses of oseltamivir, particularly in the critically ill patient population. Studies investigating the pharmacokinetics of oseltamivir in continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) were also included. Data Synthesis: During the 2009 H1N1 influenza pandemic, the World Health Organization suggested 150 mg twice daily as a consideration in critically ill patients with severe influenza. The basis for the recommendation can be traced back to animal studies investigating the H5N1 virus. Three different studies in humans investigating higher doses in severe influenza have found no differences in clinical outcomes between standard and higher dosing. Pharmacokinetic studies suggest adequate absorption in critically ill patients. Although no dosage adjustment appears to be needed for ECMO patients, reduction may berequired for CRRT. Conclusions:. Although additional data are needed for a definitive conclusion, the small body of literature available in humans does not support routine use of high-dose oseltamivir in critically ill patients.