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.
The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.
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
Download citation file:
Published: Ann Intern Med. 2009;151(7):464-473.
Infectious Disease, Influenza, Prevention/Screening, Pulmonary/Critical Care.
Results provided by:
Copyright © 2018 American College of Physicians. All Rights Reserved.
Print ISSN: 0003-4819 | Online ISSN: 1539-3704
Conditions of Use