Health

Advisory

CDC ISSUES INTERIM RECOMMENDATIONS FOR THE USE OF INFLUENZA ANTIVIRAL MEDICATIONS IN THE STTING OF

OSELTAMIVIR RESISTANCE AMONG CIRCULATING INFLUENZA A (H1N1) VIRUS, 2008-09 INFLUENZA SEASON

Posted: December 21, 2008

Although influenza activity is low in the United States to date, preliminary data from a limited number of states indicate that the

prevalence of influenza A (H1N1) virus strains resistant to the antiviral medication oseltamivir is high. Therefore, CDC is issuing

interim recommendations for antiviral treatment and chemoprophylaxis of influenza during the 2008-09 influenza season. When influenza A

(H1N1) virus infection or exposure is suspected, zanamivir or a combination of oseltamivir and rimantadine are more appropriate options

than oseltamivir alone. Local influenza surveillance data and laboratory testing can help with physician decision-making regarding the

choice of antiviral agents for their patients. The 2008-09 influenza vaccine is expected to be effective in preventing or reducing the

severity of illness with currently circulating influenza viruses, including oseltamivir-resistant influenza A (H1N1) virus strains. Since

influenza activity remains low and is expected to increase in the weeks and months to come, CDC recommends that influenza vaccination

efforts continue.

Background

Influenza A viruses, including two subtypes (H1N1) and (H3N2), and influenza B viruses, currently circulate worldwide, but the prevalence

of each can vary among communities and within a single community over the course of an influenza season. In the United States, four

prescription antiviral medications (oseltamivir, zanamivir, amantadine and rimantadine) are approved for treatment and chemoprophylaxis

of influenza. Since January 2006, the neuraminidase inhibitors (oseltamivir, zanamivir) have been the only recommended influenza

antiviral drugs because of widespread resistance to the adamantanes (amantadine, rimantadine) among influenza A (H3N2) virus strains. The

neuraminidase inhibitors have activity against influenza A and B viruses while the adamantanes have activity only against influenza A

viruses. In 2007-08, a significant increase in the prevalence of oseltamivir resistance was reported among influenza A (H1N1) viruses

worldwide. During the 2007-08 influenza season, 10.9% of H1N1 viruses tested in the U.S. were resistant to oseltamivir.

Influenza activity has been low thus far this season in the United States. As of December 19, 2008, a limited number of influenza viruses

isolated in the U.S. since October 1 have been available for antiviral resistance testing at CDC. Of the 50 H1N1 viruses tested to date

from 12 states, 98% were resistant to oseltamivir, and all were susceptible to zanamivir, amantadine and rimantadine. Preliminary data

indicate that oseltamivir-resistant influenza A (H1N1) viruses do not cause different or more severe symptoms compared to oseltamivir

sensitive influenza A (H1N1) viruses. Influenza A (H3N2) and B viruses remain susceptible to oseltamivir. The proportion of influenza A

(H1N1) viruses among all influenza A and B viruses that will circulate during the 2008-09 season cannot be predicted, and will likely

vary over the course of the season and among communities. Oseltamivir-resistant influenza A (H1N1) viruses are antigenically similar to

the influenza A (H1N1) virus strain represented in 2008-09 influenza vaccine, and CDC recommends that influenza vaccination efforts

continue as the primary method to prevent influenza.

Oseltamivir resistance among circulating influenza A (H1N1) virus strains presents challenges for the selection of antiviral medications

for treatment and chemoprophylaxis of influenza, and provides additional reasons for clinicians to test patients for influenza virus

infection and to consult surveillance data when evaluating persons with acute respiratory illnesses during influenza season. These

interim guidelines provide options for treatment or chemoprophylaxis of influenza in the United States if oseltamivir-resistant H1N1

viruses are circulating widely in a community or if the prevalence of oseltamivir resistant H1N1 viruses is uncertain.

Interim Recommendations

Persons providing medical care for patients with suspected influenza or persons who are candidates for chemoprophylaxis against influenza

should consider the following guidance for assessing and treating patients during the 2008-09 influenza season (see guidance table at

http://www.cdc.gov/flu/professionals/antivirals/antiviraltable.htm):

1. Review state influenza virus surveillance data weekly during influenza season, to determine which types (A or B) and subtypes ofinfluenza A virus (H3N2 or H1N1) are currently circulating in Delaware. For some communities, surveillance data might not be available or

   timely enough to provide information useful to clinicians.

2. Consider use of influenza tests that can distinguish influenza A from influenza B.
   1. Patients testing positive for influenza B may be given either oseltamivir or zanamivir (no preference) if treatment is indicated.
   2. At this time, if a patient tests positive for influenza A, use of zanamivir should be considered if treatment is indicated.Oseltamivir should be used alone only if recent local surveillance data indicate that circulating viruses are likely to be influenza

      A (H3N2) or influenza B viruses. Combination treatment with oseltamivir and rimantadine is an acceptable alternative, and might be

      necessary for patients that cannot receive zanamivir, (e.g., patient is <7 years old, has chronic underlying airways disease, or cannot use the zanamivir inhalation device), or zanamivir is unavailable. Amantadine can be substituted for rimantadine if rimantadine is unavailable.

   3. If a patient tests negative for influenza, consider treatment options based on local influenza activity and clinical impressionof the likelihood of influenza. Because rapid antigen tests may have low sensitivity, treatment should still be considered during

      periods of high influenza activity for persons with respiratory symptoms consistent with influenza who test negative and have no

      alternative diagnosis. Use of zanamivir should be considered if treatment is indicated. Combination treatment with oseltamivir and

      rimantadine (substitute amantadine if rimantadine unavailable) is an acceptable alternative. Oseltamivir should be used alone only if

      recent local surveillance data indicates that circulating viruses are likely to be influenza A(H3N2) or influenza B viruses.

   4. If available, confirmatory testing with a diagnostic test capable of distinguishing influenza caused by influenza A (H1N1) virusfrom influenza caused by influenza A (H3N2) or influenza B virus can also be used to guide treatment. When treatment is indicated,

      influenza A (H3N2) and influenza B virus infections should be treated with oseltamivir or zanamivir (no preference). Influenza A

      (H1N1) virus infections should be treated with zanamivir or combination treatment with oseltamivir and rimantadine is an acceptable

      alternative.

3. Persons who are candidates for chemoprophylaxis (e.g., residents in an assisted living facility during an influenza outbreak, orpersons who are at higher risk for influenza-related complications and have had recent household or other close contact with a person

   with laboratory confirmed influenza) should be provided with medications most likely to be effective against the influenza virus that is

   the cause of the outbreak, if known. Respiratory specimens from ill persons during institutional outbreaks should be obtained and sent

   for testing to determine the type and subtype of influenza A viruses associated with the outbreak and to guide antiviral therapy

   decisions.  Persons whose need for chemoprophylaxis is due to potential exposure to a person with laboratory-confirmed influenza A

   (H3N2) or influenza B should receive oseltamivir or zanamivir (no preference).  Zanamivir should be used when persons require

   chemoprophylaxis due to exposure to influenza A ( H1N1) virus. Rimantadine can be used if zanamivir use is contraindicated.

Enhanced surveillance for influenza antiviral resistance is ongoing at CDC in collaboration with local and state health departments.

Clinicians should remain alert for additional changes in recommendations that might occur as the 2008–09 influenza season progresses.

Oseltamivir resistant influenza A (H1N1) viruses are antigenically similar to the influenza A(H1N1) viruses represented in the vaccine,

and vaccination should continue to be considered the primary prevention strategy regardless of oseltamivir sensitivity. Information on

antiviral resistance will be updated in weekly surveillance reports (available at http://www.cdc.gov/flu/weekly/fluactivity.htm).

For more information on antiviral medications and additional considerations related to antiviral use during the 2008-09 influenza season,

call the Delaware Immunization Program at 1-800-282-8672 or visit http://www.cdc.gov/flu/professionals/antivirals/index.htm.