[Source: Clinical Infectious Diseases, full page: (LINK). Abstract, edited.]

A Prospective Intervention Study on Higher-dose Oseltamivir Treatment in Adults Hospitalized with Influenza A and B infections

N. Lee 1,2, D. S. C. Hui 1,2, Z. Zuo 3, K. L. K. Ngai 4, G. C. Y. Lui 1, S. K. Wo 3, W. W. S. Tam 5, M. C. W. Chan 4, B. C. K. Wong 1, R. Y. K. Wong 1, K. W. Choi 1, W. W. Y. Sin 1, E. L. Y. Lee 1, B. Tomlinson 1, F. G. Hayden 6, and P. K. S. Chan 2,4

Author Affiliations: <SUP>1</SUP>Department of Medicine and Therapeutics <SUP>2</SUP>Stanley Ho Centre for Emerging Infectious Diseases <SUP>3</SUP>School of Pharmacy <SUP>4</SUP>Department of Microbiology <SUP>5</SUP>School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China <SUP>6</SUP>School of Medicine, University of Virginia, Charlottesville, VA, United States of America

Corresponding author: Prof. Paul KS Chan, Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong. 1/F Clinical Sciences Building, Prince of Wales Hospital, Shatin, Hong Kong SAR, PRC. Email: paulkschan@cuhk.edu.hk. Tel: 852-2632 2301

Alternate corresponding author: Prof. Nelson Lee, Department of Medicine and Therapeutics, The Chinese University of Hong Kong. 9/F Clinical Sciences Building, Prince of Wales Hospital, Shatin, Hong Kong SAR, PRC. Email: leelsn@cuhk.edu.hk. Tel: 852-26321464



It is unclear if higher-dose oseltamivir provides benefit beyond standard dose in influenza patients who require hospitalization.


A prospective, intervention study was performed in two acute general hospitals in Hong Kong over four 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 bid oseltamivir for 5 days was site-allocated, which switched after two seasons. Subjects with pre-existing renal impairment (CrCl 40-60 ml/min) received 75 mg bid oseltamivir. Viral clearance by Day 5 and clinical responses were compared between groups. Plasma steady-state trough oseltamivir carboxylate (OC) concentration was measured (HPLC-MS/MS).


Altogether, 41 and 114 patients received 150 mg and 75 mg bid oseltamivir respectively; their enrollment characteristics (mean?S.D. age: 61?18 vs. 66?16 yrs) 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 (100.0% vs. 98.1%) negativity, RNA decline rate, and durations of fever, oxygen-supplementation and hospitalization. Results were similar when analyzed by study arms (all cases and among those without renal impairment). Sub-analysis of influenza B patients showed faster RNA decline rate (ANOVA, F-value 4.14; P=0.05) and clearance (Day 5, 80.0% vs. 57.1%) with higher-dose treatment. No oseltamivir-resistance was found. Treatments were generally well tolerated.


We found no additional benefit of higher-dose oseltamivir treatment in adults hospitalized with influenza A, but an improved virologic response in influenza B.

Received May 9, 2013. Accepted August 31, 2013.

? The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

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