JAC Advance Access published online on November 28, 2002
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg007
© 2002 by The British Society for Antimicrobial Chemotherapy
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Original Paper
1 University of Manitoba,
Room 510-730 William Avenue, Winnipeg, Canada
* Corresponding author. E-mail: nelsonak{at}ms.umanitoba.ca.
Received 4 January 2002
; revised 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
Early administration of oral oseltamivir increases
the benefits of influenza treatment
2 Aldershot Health Centre, Aldershot, UK
3 Cardiothoracic Department,
Cisanello Hospital, Pisa, Italy
4 Dossenheim,
Germany
5 Euraxi, Saint Martin
d'Heres, France
6 Roche Global Development, Welwyn,
UK
7 F.
Hoffmann-La Roche, Basel, Switzerland
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