What is the efficacy of oseltamivir in the treatment of influenza?

Updated: Apr 23, 2019
  • Author: Hien H Nguyen, MD, MS; Chief Editor: Michael Stuart Bronze, MD  more...
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Answer

Hayden et al documented the prophylactic efficacy of oseltamivir. [91] In this study, 1559 healthy, nonimmunized patients were treated with either placebo or oseltamivir for 6 weeks; at the end of the period, 4.8% of the placebo group had laboratory-confirmed influenza, compared with only 1.2% of the oseltamivir group.

Although oseltamivir is approved for use up to 48 hours after the onset of symptoms, one study found that earlier initiation increased the therapeutic effects of the drug: Initiation of therapy within the first 12 hours after fever onset reduced the total median illness duration by 74.6 hours (41%) more than intervention at 48 hours. [92]

Probenecid, a uricosuric agent, approximately doubles the effective dose of oseltamivir by disrupting renal excretion of the drug. It may have a role to play in a pandemic or in severe infections [93] ; however, no studies have yet been performed to confirm the appropriate dosing regimen in this situation.

A novel study documented the prophylactic and therapeutic effects of oseltamivir in experimentally induced influenza in humans. [94] In a controlled laboratory environment, volunteers were inoculated intranasally with influenza A/Texas/36/91 (H1N1). In the prophylaxis arm of the study, subjects received either oseltamivir or placebo 26 hours before virus inoculation; in the treatment arm, subjects received oseltamivir or placebo 28 hours after inoculation.

In the prophylactic group, 38% of patients developed influenza, compared with 67% of patients in the placebo group. [94] In the treatment group, oseltamivir reduced the duration of illness from 95 to 53 hours and reduced the severity by 50%, compared with placebo.

A placebo-controlled study of oseltamivir by Treanor et al demonstrated the ability of this agent to decrease the duration and severity of influenza. [95] The analysis included patients with laboratory-based diagnoses of influenza and those with clinical diagnoses based on symptoms. Compared with placebo, both standard-dose and high-dose oseltamivir reduced the mean illness duration from 103 to 70 hours and reduced symptom severity by 40%.

In a randomized, double-blind, placebo-controlled trial of children aged 1-3 years with influenza A or B, Heinonen et al found that oseltamivir decreased the incidence of acute otitis media (a common bacterial complication of influenza) by 85% when treatment began within 12 hours of symptom onset. [96] When treatment began within 24 hours of symptom onset, no significant reduction in the incidence of acute otitis media was observed.

Heinonen et al also found that when oseltamivir treatment was started within 24 hours for children with influenza A, the median time to resolution of illness was decreased by 3.5 days in all children and parental work absenteeism was reduced by 3 days. [96] Efficacy was not demonstrated against influenza B infections.

A meta-analysis of available data by Jefferson et al cited a substantial risk of publication bias with oseltamivir trials, noting that 60% of patient data from phase III treatment trials of oseltamivir have never been published and that reporting bias has been documented in the published trials. [97] This meta-analysis concluded that alleviation of influenzalike symptoms began about 21 hours sooner in patients treated with oseltamivir compared with placebo; however, oseltamivir treatment appeared to have no effect on hospitalization. [97]


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