Persons infected with influenza typically must restrict their activities for five to six days and miss three days of school or work. Amantadine and rimantadine are currently approved treatments for influenza, but their effectiveness is limited to treatment of early disease. Another agent, zanamivir, is effective but must be given topically (intranasally or via inhalation) or parenterally. Oseltamivir, given orally, has been shown to be effective against influenza in animal studies. Treanor and colleagues conducted a randomized controlled trial to determine the efficacy and safety of oseltamivir in the treatment of acute influenza in humans.
Adults up to 65 years of age who presented within 36 hours of the onset of influenza symptoms were included in the study. Patients had to have a documented temperature of at least 38°C (100.4°F) and report at least one respiratory symptom and one constitutional symptom. Patients who had received an influenza vaccination in the past year were excluded from the study, as were those who had significant chronic illnesses. Patients were randomly and blindly assigned to receive placebo or oseltamivir in a dosage of 75 mg twice daily or 150 mg twice daily. Each group took the medication or placebo for five days.
Patients were allowed to use acetaminophen and other medications for symptom relief. The severity of influenza symptoms was recorded twice daily for 21 days on a four-point scale. Subjects also recorded their ability to perform their normal activities and evaluated their overall health status. Nasal and pharyngeal viral culture swabs were obtained five times during the first week of the study. Type and subtype were identified, and susceptibility to oseltamivir was determined. The primary end point was time to resolution of influenza.
The study enrolled 627 patients. Of these, 59.6 percent were infected with influenza, and their data were included in the analysis. High-and low-dose oseltamivir led to significant reductions in duration and severity of illness. The duration of illness was 4.3 days in the placebo group, 3.0 days in the 75-mg group and 2.9 days in the 150-mg group. Median illness severity was reduced by about 40 percent in the oseltamivir groups compared with the placebo group. Reduction in fever also occurred in the oseltamivir groups and was evident within one day of treatment, even though these patients took less acetaminophen than those taking placebo. Complications secondary to influenza were reduced by 50 percent in the active drug groups compared with the placebo group. No serious adverse effects related to oseltamivir were reported, although there were some complaints of gastrointestinal symptoms.
The authors conclude that oseltamivir is safe and effective in the treatment of acute influenza infections. Further studies in children and high-risk patients are needed. In an accompanying editorial, Wenzel points out that neuraminidase inhibitors such as oseltamivir have costs that may limit their use. Head-to-head comparisons of zanamivir and oseltamivir are needed, as are studies of the effect of these agents on mortality rates.