Nayer Khazeni, MD, MS; Dena M. Bravata, MD, MS; Jon-Erik C. Holty, MD, MS; Timothy M. Uyeki, MD, MPH, MPP; Christopher D. Stave, MLS; Michael K. Gould, MD, MS
Neuraminidase inhibitors (NAIs) are stockpiled internationally for extended use in an influenza pandemic.
To evaluate the safety and efficacy of extended-duration (>4 weeks) NAI chemoprophylaxis against influenza.
Studies published in any language through 11 June 2009 identified by searching 10 electronic databases and 3 trial registries.
Randomized, placebo-controlled, double-blind human trials of extended-duration NAI chemoprophylaxis that reported outcomes of laboratory-confirmed influenza or adverse events.
2 reviewers independently assessed study quality and abstracted information from eligible studies.
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], âˆ’3.9 percentage points [CI, âˆ’5.8 to âˆ’1.9 percentage points]) but not asymptomatic influenza (RR, 1.03 [CI, 0.81 to 1.30]; RD, âˆ’0.4 percentage point [CI, âˆ’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, âˆ’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.
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.
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.
Neuraminidase inhibitors are a key element of public health strategies to prevent and treat pandemic influenza.
This review of 7 trials assessing the efficacy and safety of extended-duration (>4 weeks) treatment with oseltamivir and zanamivir suggests that the drugs prevent symptomatic but not asymptomatic seasonal influenza. The drugs seem to be safe, but oseltamivir causes nausea and vomiting.
All 7 trials were industry-sponsored. There was strong evidence of publication bias. No trial included children, minorities, or vaccinated populations.
Extended-duration treatment with oseltamivir and zanamivir seems to be safe and efficacious for preventing symptomatic influenza in immunocompetent white and Japanese adults.
Appendix Table 1.
FDA = U.S. Food and Drug Administration; NAI = neuraminidase inhibitor; RCT = randomized, controlled trial.
Appendix Table 2.
NAI = neuraminidase inhibitor; RD = risk difference; RR = relative risk.
* Once daily.
† Twice daily.
Top. Random-effects analysis of RD and RR for influenza confirmed by serology or positive culture in participants with at least 1 of the following: temperature 37.2 °C or higher, myalgia, fatigue, headache, cough, sore throat, or nasal congestion. Middle. Random-effects analysis of RD and RR for influenza confirmed by serology or positive culture in participants without symptoms. Bottom. Random-effects analysis of RD and RR for severe adverse events.
Abd = abdominal; NAI = neuraminidase inhibitor; RI = respiratory infection; RR = relative risk; UTI = urinary tract infection.
* Once daily.
† Twice daily.
Appendix Table 3.
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Khazeni N, Bravata DM, Holty JC, Uyeki TM, Stave CD, Gould MK. Systematic Review: Safety and Efficacy of Extended-Duration Antiviral Chemoprophylaxis Against Pandemic and Seasonal Influenza. Ann Intern Med. 2009;151:464-473. doi: 10.7326/0003-4819-151-7-200910060-00143
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Published: Ann Intern Med. 2009;151(7):464-473.
Infectious Disease, Influenza, Prevention/Screening, Pulmonary/Critical Care.
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