• N Lee, D S C Hui, Z Zuo, K L K Ngai, G C Y Lui, S K Wo, W W S Tam, M C W Chan, B C K Wong, R Y K Wong, K W Choi, W W Y Sin, E L Y Lee, B Tomlinson, F G Hayden, and P K S Chan.
• Department of Medicine and Therapeutics.
• Clin. Infect. Dis. 2013 Dec 1;57(11):1511-9.

BackgroundIt is unclear if higher-dose oseltamivir provides benefit beyond the standard dose in influenza patients who require hospitalization.MethodsA prospective intervention study was performed in 2 acute care general hospitals in Hong Kong over 4 seasonal peaks (2010-2012). Adults (≥18 years) with laboratory-confirmed influenza (85 A/H3N2, 34 A/H1N1pdm09, 36 B) infections who presented within 96 hours were recruited. Study regimen of either 150 mg or 75 mg oseltamivir twice daily for 5 days was allocated by site, which was switched after 2 seasons. Subjects with preexisting renal impairment (creatinine clearance, 40-60 mL/minute) received 75 mg oseltamivir twice daily. Viral clearance by day 5 and clinical responses were compared between groups. Plasma steady-state trough oseltamivir carboxylate (OC) concentration was measured by high-performance liquid chromatography-tandem mass spectrometry.ResultsAltogether, 41 and 114 patients received 150 mg and 75 mg twice-daily oseltamivir, respectively; their enrollment characteristics (mean age, 61 ± 18 vs 66 ± 16 years) and illness severity were comparable. Trough OC levels were higher in the 150-mg group (501.0 ± 237.0 vs 342.6 ± 192.7 ng/mL). There were no significant differences in day 5 viral RNA (44.7% vs 40.2%) or culture negativity (100.0% vs 98.1%), RNA decline rate, and durations of fever, oxygen supplementation, and hospitalization. Results were similar when analyzed by study arm (all cases and among those without renal impairment). Subanalysis of influenza B patients showed faster RNA decline rate (analysis of variance, F = 4.14; P = .05) and clearance (day 5, 80.0% vs 57.1%) with higher-dose treatment. No oseltamivir resistance was found. Treatments were generally well tolerated.ConclusionsWe found no additional benefit of higher-dose oseltamivir treatment in adults hospitalized with influenza A, but an improved virologic response in influenza B.Clinical Trials RegistrationClinicalTrials.gov, NCT01052961.

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