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Ask the Experts: Updated recommendations on use of antivirals for influenza

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ACIP recommendations provide valuable guidance on use and monitoring of antiviral agents for treatment and prevention of influenza.

Question: There are new published recommendations of the Advisory Committee on Immunization Practices (ACIP) on the use of antivirals against influenza. What changes were made in these new guidelines?

Answer: The H1N1 pandemic of 2009 increased concern about how to appropriately treat and prevent influenza outbreaks. Influenza can affect people of all ages and is seen most often in school-aged children.1 Although the incidence is greatest in these children, serious illness and death are reported most frequently in patients 65 years or older, children younger than 2 years, and those with medical conditions that put them at increased risk for complications.2,3 Illness caused by influenza also may lead to secondary bacterial infections, which were suspected in 20% to 38% of patients who died or required intensive care during the 2009 H1N1 pandemic.4 Early antiviral treatment is recommended to decrease the risk of severe illness or death related to infection with the influenza virus.5

In the United States, the four influenza antiviral agents available are amantadine, oseltamivir, rimantadine, and zanamivir. Amantadine and rimantadine are similar antiviral medications in a class of antivirals known as adamantanes that are active against influenza A viruses. The adamantanes are not, however, active against influenza B viruses. This class of medications has fallen out of favor because of adamantane resistance among the seasonal influenza A (H3N2) strains and the 2009 H1N1 influenza strains.6 Oseltamivir and zanamivir are two antiviral medications in the class known as neuraminidase inhibitors; they are active against both influenza A and B viruses. With the exception of rare strains, most influenza A and B viruses are susceptible to oseltamivir and zanamivir.7 Because of the prevalence of adamantane-resistant influenza viruses, oseltamivir and zanamivir are the antiviral agents of choice for the treatment and chemoprophylaxis of influenza.8

The following are updates from ACIP regarding the recommendations for use of antivirals for treatment and prevention of influenza:

  • “Antiviral treatment is recommended as soon as possible for patients with confirmed or suspected influenza who have severe, complicated, or progressive illness or who require hospitalization.” Studies conducted with severely ill patients proved that although most benefit is shown in patients with early antiviral treatment (<2 days after onset of illness), treatment up to 5 days after illness onset showed morbidity and mortality benefit.4,5
  • “Antiviral treatment is recommended as soon as possible for outpatients with confirmed or suspected influenza who are at higher risk for influenza complications on the basis of their age or underlying medical conditions; clinical judgment should be an important component of outpatient treatment decisions.” Studies during the 2009 H1N1 pandemic have shown that one or more underlying comorbidities were present in 50% to 80% of patients who required hospitalization.5
  • “Recommended antiviral medications include oseltamivir and zanamivir, on the basis of recent viral surveillance and resistance data indicating that less than 99% of currently circulating influenza virus strains are sensitive to these medications. Amantadine and rimantadine should not be used because of the high levels of resistance to these drugs among circulating influenza A viruses, but information about these drugs is provided for use if current recommendations change because of the reemergence of adamantane-susceptible strains.” This was evident in 2009, when H1N1 strains were resistant to adamantanes,7 and in the 2005–06 influenza season, as 92% of the strains were resistant to adamantanes.9
  • “Oseltamivir may be used for treatment or chemoprophylaxis of influenza among infants aged <1 year when indicated.” According to a large population-based study, the highest hospitalization rate was for those patients younger than 6 months.10
  • “Antiviral treatment also may be considered on the basis of clinical judgment for any outpatient with confirmed or suspected influenza who does not have known risk factors for severe illness if treatment can be initiated within 48 hours of illness onset.” Evidence supports that healthy patients who have initiated antiviral treatment within 48 hours of illness onset may reduce the duration of influenza illness by 1 day compared with placebo.11
  • “Because antiviral resistance patterns can change over time, clinicians should monitor local antiviral resistance surveillance data.”

Pharmacists should urge physicians to incorporate these guidelines when recommending antiviral agents for the treatment of influenza, as well as monitor the use of these medications.

Rachael A. Clark
Student Pharmacist

Stephan L. Foster, PharmD
Professor and Vice Chair
College of Pharmacy
University of Tennessee Health Sciences Center
Memphis
APhA Liaison Representative to the Advisory Committee on Immunization Practices (ACIP)

References

  1. Glezen PF, Cough RB. Interpandemic influenza in the Houston area, 1974-76. N Engl J Med. 1978;298:587–92.
  2. Thompson WW, Shay DK, Weintraub E, et al. Influenza-associated hospitalizations in the United States. JAMA. 2004;292:1333–40.
  3. Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289:179–86.
  4. Bautista E, Chotpitayasunondh T, Gao Z, et al. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med. 2010;362:1708–19.
  5. Jain S, Kamimoto L, Bramley AM, et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med. 2009;361:1935–44.
  6. CDC. FluView: week ending May 20, 2010. Accessed at www.cdc.gov/flu/weekly, February 19, 2010.
  7. CDC. Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009-10 season. Accessed at www.cdc.gov/H1N1flu/recommendations.htm, February 19, 2010.
  8. CDC. Antiviral agents for the treatment and chemoprophylaxis of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60:1–24.
  9. Bright RA, Shay DK, Shu B, et al. Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States. JAMA. 2006;295:891–4.
  10. Dawood FS, Fiore A, Kamimoto L, et al. Burden of seasonal influenza hospitalization in children, United States, 2003 to 2008. J Pediatr. 2010;157:808–14.
  11. Hayden FG, Osterhaus AD, Treanor JJ, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections: GG167 Influenza Study Group. N Engl J Med. 1997;337:874–80.
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