JAC Advance Access originally published online on November 28, 2002
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Journal of Antimicrobial Chemotherapy (2003) 51, 123-129
© 2003 The British Society for Antimicrobial Chemotherapy
Early administration of oral oseltamivir increases the benefits of influenza treatment
1 University of Manitoba, Room 510–730 William Avenue, Winnipeg, Canada; 2 Aldershot Health Centre, Aldershot; 6 Roche Global Development, Welwyn, UK; 3 Cardiothoracic Department, Cisanello Hospital, Pisa, Italy; 4 Dossenheim, Germany; 5 Euraxi, Saint Martin d’Heres, France; 7 F. Hoffmann-La Roche, Basel, Switzerland
Received 4 January 2002; returned 30 April 2002; revised 3 July 2002; accepted 24 September 2002
Our objective was to evaluate the benefit of early treatment of influenza illness using oral oseltamivir. This open-label, multicentre international study investigated the relationship between the interval from illness onset to first dose (time-to-treatment) and illness duration in the intent-to-treat infected population using accelerated failure time (AFT) modelling. A total of 1426 patients (12–70 years) presenting within 48 h of the onset of influenza symptoms were treated with oseltamivir 75 mg twice a day for 5 days during the 1999–2000 influenza season; 958 (67%) had laboratory-confirmed influenza virus infection. Earlier intervention was associated with shorter illness duration (P < 0.0001). Initiation of therapy within the first 12 h after fever onset reduced the total median illness duration by 74.6 h (3.1 days; 41%) more than intervention at 48 h. Intermediate interventions reduced the illness proportionately compared with 48 h. In addition, the earlier administration of oseltamivir further reduced the duration of fever, severity of symptoms and the times to return to baseline activity and health scores. Oseltamivir was well tolerated. The most common adverse events were nausea and vomiting, which were transient and generally occurred only with first dosing. When oseltamivir was taken with food, the tolerability was enhanced. The overall discontinuation rate was low (1.8%). In conclusion, the IMPACT study demonstrated that earlier initiation of oral oseltamivir therapy increased its therapeutic effects, which were seen at every time point of intervention and were progressive. Thus, early presentation, diagnosis and treatment of patients with influenza maximized the benefits of oseltamivir therapy.
Keywords: influenza, neuraminidase inhibitors, oseltamivir, treatment
* Corresponding author. Tel: +1-204-789-3625; Fax: +1-204-789-3926; E-mail: nelsonak{at}ms.umanitoba.ca
Members of the IMPACT Study Group are listed in the Acknowledgements.
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