Systematic Review: Safety and Efficacy of Extended-Duration Antiviral Chemoprophylaxis Against Pandemic and Seasonal Influenza

Background: Neuraminidase inhibitors (NAIs) are stockpiled internationally for extended use in an influenza pandemic. Purpose: To evaluate the safety and efficacy of extended-duration (>4 weeks) NAI chemoprophylaxis against influenza. Data Sources: Studies published in any language through 11 June 2009 identified by searching 10 electronic databases and 3 trial registries. Study Selection: Randomized, placebo-controlled, double-blind human trials of extended-duration NAI chemoprophylaxis that reported outcomes of laboratory-confirmed influenza or adverse events. Data Extraction: 2 reviewers independently assessed study quality and abstracted information from eligible studies. Data Synthesis: Of 1876 potentially relevant citations, 7 trials involving 7021 unique participants met inclusion criteria. Data were pooled by using random-effects models. Chemoprophylaxis with NAIs decreased the frequency of symptomatic influenza (relative risk [RR], 0.26 [95% CI, 0.18 to 0.37]; risk difference [RD], -3.9 percentage points [CI, -5.8 to -1.9 percentage points]) but not asymptomatic influenza (RR, 1.03 [CI, 0.81 to 1.30]; RD, -0.4 percentage point [CI, -1.6 to 0.9 percentage point]). Adverse effects were not increased overall among NAI recipients (RR, 1.01 [CI, 0.94 to 1.08]; RD, 0.1 percentage point [CI, -0.2 to 0.4 percentage point]), but nausea and vomiting were more common among those who took oseltamivir (RR, 1.48 [CI, 1.86 to 2.33]; RD, 1.7 percentage points [CI, 0.6 to 2.9 percentage points]). Prevention of influenza did not statistically significantly differ between zanamivir and oseltamivir. Limitations: All trials were industry-sponsored. No study was powered to detect rare adverse events, and none included diverse racial groups, children, immunocompromised patients, or individuals who received live attenuated influenza virus vaccine. Conclusion: Extended-duration zanamivir and oseltamivir chemoprophylaxis seems to be highly efficacious for preventing symptomatic influenza among immunocompetent white and Japanese adults. Extended-duration oseltamivir is associated with increased nausea and vomiting. Safety and efficacy in several subpopulations that might receive extended-duration influenza chemoprophylaxis are unknown.