This is an official CDC HEALTH ADVISORY
Distributed via Health Alert Network
Friday, December 19, 2008, 11:50 EST (11:50 AM EST)
CDCHAN-00279-2008-12-19-ADV-N
CDC Issues Interim Recommendations for the Use of Influenza Antiviral
Medications in the Setting of Oseltamivir Resistance among Circulating
Influenza A (H1N1) Viruses,
2008-09 Influenza Season
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 Table below). Guidance Table):
1)
Review local or
state influenza virus surveillance data weekly during influenza season, to
determine which types (A or B) and subtypes of influenza A virus (H3N2 or H1N1)
are currently circulating in the area. 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.
a.
Patients testing
positive for influenza B may be given either oseltamivir or zanamivir (no
preference) if treatment is indicated.
b.
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.
c.
If a patient
tests negative for influenza, consider treatment options based on local
influenza activity and clinical impression of 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.
d.
If available,
confirmatory testing with a diagnostic test capable of distinguishing influenza
caused by influenza A (H1N1) virus from 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,
or persons 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, visit http://www.cdc.gov/flu/professionals/antivirals/index.htm
TABLE
Interim recommendations
for the selection of antiviral treatment using laboratory test results and
viral surveillance data, United States, 2008-09 season‡
Rapid antigen or other laboratory test
|
Predominant virus(es) in community
|
Preferred medication(s)
|
Alternative (combination antiviral treatment)
|
Not done or negative, but
clinical suspicion for influenza
|
H1N1 or unknown
|
Zanamivir
|
Oseltamivir + Rimantadine*
|
Not done or negative, but
clinical suspicion for influenza
|
H3N2 or B
|
Oseltamivir or Zanamivir
|
None
|
Positive A
|
H1N1 or unknown
|
Zanamivir
|
Oseltamivir + Rimantadine*
|
Positive A
|
H3N2 or B
|
Oseltamivir or Zanamivir
|
None
|
Positive B
|
Any
|
Oseltamivir or Zanamivir
|
None
|
Positive A+B**
|
H1N1 or unknown
|
Zanamivir
|
Oseltamivir + Rimantadine*
|
Positive A+B**
|
H3N2 or B
|
Oseltamivir or Zanamivir
|
None
|
*Amantadine can be
substituted for rimantadine but has increased risk of adverse events. Human
data are lacking to support the benefits of combination antiviral treatment of
influenza; however, these interim recommendations are intended to assist
clinicians treating patients who might be infected with oseltamivir-resistant
influenza A (H1N1) virus.
**Positive A+B indicates a
rapid antigen test that cannot distinguish between influenza and influenza B
viruses
‡ Influenza antiviral medications used for treatment are most
beneficial when initiated within the first two days of illness. Clinicians
should consult the package insert of each antiviral medication for specific
dosing information, approved indications and ages, contraindications/warnings/precautions,
and adverse effects.
|