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

  1. Nayer Khazeni, MD, MS;
  2. Dena M. Bravata, MD, MS;
  3. Jon-Erik C. Holty, MD, MS;
  4. Timothy M. Uyeki, MD, MPH, MPP;
  5. Christopher D. Stave, MLS; and
  6. Michael K. Gould, MD, MS
  1. From 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; Centers for Disease Control and Prevention, Atlanta, Georgia; and Veterans Affairs Palo Alto Health Care System, Palo Alto, California.

    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.

    Article and Author Information

    • Disclaimer: The views expressed are those of the authors and do not represent the policies of the Centers for Disease Control and Prevention. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality.

    • Acknowledgment: The authors thank Ms. Corinne Jeannet for her assistance with Japanese language translation.

    • Grant Support: By the Agency for Healthcare Research and Quality (1 F32 HS018003-01A1, Dr. Khazeni) and resources and the use of facilities at the Veterans Affairs Palo Alto Health Care System (Dr. Gould).

    • Potential Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Nayer Khazeni, MD, MS, Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, 300 Pasteur Drive, H3143, Stanford, CA 94305.

    • Current Author Addresses: Dr. Khazeni: Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, 300 Pasteur Drive, H3143, Stanford, CA 94305.

    • Dr. Bravata: Center for Primary Care and Outcomes Research, 117 Encina Commons, Stanford, CA 94305-6019.

    • Dr. Holty: Stanford Sleep Medicine Center, 450 Broadway Street, Pavilion C, 2nd Floor, Redwood City, CA 94063.

    • Dr. Uyeki: Epidemiology and Prevention Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Coordinating Center for Infectious Diseases, MS A-20, Centers for Disease Control and Prevention, 1600 Clifton Road Northeast, Atlanta, GA 30333.

    • Mr. Stave: Lane Medical Library and Knowledge Management Center, Stanford University Medical Center, 300 Pasteur Drive, RM L109, Stanford, CA 94305-5123.

    • Dr. Gould: Veterans Affairs Palo Alto Health Care System (111P), 3801 Miranda Avenue, Palo Alto, CA 94304.

    • Author Contributions: Conception and design: N. Khazeni, D.M. Bravata.

    • Analysis and interpretation of the data: N. Khazeni, D.M. Bravata, J.E.C. Holty, T.M. Uyeki, M.K. Gould.

    • Drafting of the article: N. Khazeni, D.M. Bravata.

    • Critical revision of the article for important intellectual content: N. Khazeni, D.M. Bravata.

    • Final approval of the article: N. Khazeni, D.M. Bravata, J.E.C. Holty, T.M. Uyeki, M.K. Gould.

    • Provision of study materials or patients: N. Khazeni, D.M. Bravata.

    • Statistical expertise: N. Khazeni, D.M. Bravata, M.K. Gould.

    • Obtaining of funding: N. Khazeni.

    • Administrative, technical, or logistic support: N. Khazeni, T.M. Uyeki.

    • Collection and assembly of data: N. Khazeni, J.E.C. Holty, C.D. Stave.

    « Previous | Next Article »Table of Contents

    This Article

    1. Ann Intern Med October 6, 2009 vol. 151 no. 7 464-473
    1. » Abstract
    2. Figures
    3. Full Text
    4. Full Text (PDF)

    Rapid Responses

    1. Submit a response
    2. No responses published

    Current Issue

    1. November 17, 2009, 151 (10)
    1. Alert me to current issues