Comparison of double-dose vs standard-dose oseltamivir in the treatment of influenza: A systematic review and meta-analysis.

Abstract

The effect of double-dose oseltamivir on mortality in patients with influenza remains controversial. We systematically reviewed the literature to investigate whether double-dose oseltamivir influences mortality in patients with influenza. PubMed, Excerpta Medica Database (Embase) and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized controlled trials (RCTs) and observational studies regarding the effect of double-dose oseltamivir on mortality in patients with influenza. The primary outcome was all-cause mortality. The Mantel-Haenszel method with random effects model was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Ten studies (four RCTs and six observational studies), involving 20947 patients, were included. Pooled analysis suggested that double-dose oseltamivir was not associated with decreased mortality in patients with influenza, both in RCTs (OR, 1.29; 95% CI, 0.52-3.15; P=.58) and observational studies (OR, 1.59; 95% CI, 0.79-3.19; P=.20; I2 =51%). Double-dose oseltamivir did not show statistical benefit on the virologic clearance rate (OR, 1.26; 95% CI, 0.85-1.88; P=.25; I2 =0%) or the incidence of adverse events (AEs) (OR, 1.52; 95% CI, 0.85-2.72; P=.15; I2 =59%). Current evidence indicates that double-dose oseltamivir does not decrease mortality or have advantages on the outcome of virologic clearance rate and incidence of AEs. However, the finding largely relied on the data from observational studies, which may potentially have led to selection bias. Therefore, high-quality and adequately powered RCTs are warranted.