A comprehensive new meta-analysis on the controversial topic of oseltamivir's effectiveness found that the drug reduces the duration of influenza symptoms and the risk of hospitalization in adults and adolescents, while increasing the risk of nausea and vomiting.
A US-British team, with Arnold S. Monto, MD, of the University of Michigan as senior author, included in the analysis all randomized controlled trials sponsored by Roche, the drug's manufacturer, as well as other relevant trials. The study, reported yesterday in The Lancet, was funded by Roche, but the researchers worked independently.
Treatment reduces symptoms but can cause nausea
They analyzed nine trials that included 4,238 patients, and examined individual patient data rather than aggregated results. The team found that adult and adolescent patients with confirmed flu who received oseltamivir enjoyed a significant 21% reduction in symptom duration, from 122.7 hours to 97.5 hours, compared with placebo patients.
In addition, treated flu patients were significantly less likely to be hospitalized than placebo patients were (0.6% versus 1.7% of patients) and significantly less likely to have lower respiratory tract complications requiring antibiotics more than 2 days after randomization (4.9% versus 8.7%).
However, oseltamivir significantly increased the risk of nausea, which occurred in 9.9% of treated patients versus 6.2% of controls, and of vomiting (8.0% versus 3.3%). The authors found no increase in neurologic or psychiatric disorders or serious adverse events in treated patients.
In a University of Michigan press release, Monto commented that previous research has questioned the use of oseltamivir because of its gastrointestinal side effects, but he said the previous studies "combined those infected with influenza and those without, which diluted the positive effect in treatment."
Other experts weigh in
In an accompanying editorial, a pair of experts from Australia and Hong Kong, Heath Kelly, MPH, and Benjamin J. Cowling, BSc, PhD, write that the data included in the analysis are probably as complete as possible for adults and adolescents. They say this fact, along with the analysis of individual patient data, distinguishes the study from a previous meta-analysis by the Cochrane Group.
Kelly and Cowling note that the analysis showed no oseltamivir benefits in patients who did not have confirmed flu. "In view of the risk of nausea and vomiting in all patients who receive the drug, confirmation of the diagnosis of influenza before treatment is advisable" in routine practice, they write. But in a severe epidemic or pandemic the approach might be different.
By comparison, the Centers for Disease Control and Prevention (CDC) currently advises clinicians not to postpone antiviral treatment while waiting for flu test results in patients who have flu-like illness and an increased risk of serious flu complications.
"The rational use of oseltamivir is becoming clear," Kelly and Cowling sum up. "Oseltamivir might reduce symptom duration, the risk of antibiotic prescription for lower respiratory tract infection, and hospital admission for any cause in adult and adolescent patients with laboratory-confirmed influenza, but no benefit accrues to patients without influenza virus infection." They add that a review of all evidence on the effectiveness of oseltamivir in children would be welcome.
Jan 29 Lancet report abstract
Jan 29 Lancet editorial excerpt
Jan 29 University of Michigan press release
Related Jan 9 CIDRAP News story