Source
Stanford University Medical Center, Center for Health Policy and Center for Primary Care and Outcomes Research, Stanford Sleep Disorders Center, and Lane Medical Library, Stanford, California 94305, USA.
Abstract
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.