Health

Advisory

CDC RECOMMENDS AGAINST THE USE OF AMANTADINE AND RIMANDATINE FOR THE TREATMENT OR PROPHYLAXIS OF

INFLUENZA IN THE UNITED STATES DURING THE 2005-2006 INFLUENZA SEASON

The Division of Public Health is forwarding this Health Advisory from the Centers for Disease Control and Prevention. To contact DPH

about this Health Advisory, call 1-888-295-5156. This number is answered during normal business hours, and during non-business hours for

emergencies.

This is an official

CDC Health Advisory

Distributed via Health Alert Network

January 14, 2006, 15:25 EST (03:25 PM EST)

CDCHAN-00240-06-01-14-ADV-N

CDC Recommends against the Use of Amantadine and Rimandatine for the Treatment or Prophylaxis of Influenza in the United States during

the 2005–06 Influenza Season

Recent evidence indicates that a high proportion of currently circulating Influenza A viruses in this country are resistant to these

medications

While the primary strategy for preventing complications of influenza infections is annual vaccination, antiviral medications with

activity against influenza viruses can be effective for the prophylaxis and treatment of influenza. Two classes of antivirals are

currently available–the M2 ion channel inhibitors (i.e., the two adamantanes amantadine and rimantadine) and the neuraminidase

inhibitors (i.e., oseltamivir and zanamivir). The neuraminidase inhibitors are effective for the treatment and prophylaxis of influenza A

and B, while the adamantanes are only active against influenza A viruses. This alert provides new information about the resistance of

influenza viruses currently circulating in the United States to the adamantanes, and it makes an interim recommendation that these drugs

not be used during the 2005–06 influenza season. Amantadine is also used to treat the symptoms of Parkinson’s disease, and

should continue to be used for this indication.

Viral resistance to adamantanes can emerge rapidly during treatment because a single point mutation at amino acid positions 26, 27, 30,

31, or 34 of the M2 protein can confer cross-resistance to both amantadine and rimantadine. The transmissibility of adamantane-resistant

viruses is not impaired by any of these amino acid changes. A recent report on the global prevalence of adamantane-resistant influenza

viruses showed a significant increase (from 1.9% to 12.3%) in drug resistance over the past 3 years. In the United States, the frequency

of drug resistance increased from 1.9% in 2004 to 14.5% during the first 6 months of the 2004–05 influenza season.

For the 2005–06 season, 120 influenza A (H3N2) viruses isolated from patients in 23 states have been tested at CDC through January

12, 2006; 109 of the isolates (91%) contain an amino acid change at position 31 of the M2 protein, which confers resistance to amantadine

and rimantadine. Three influenza A(H1N1) viruses have been tested and demonstrated susceptibility to these drugs. All influenza viruses

from the United States that have been screened for antiviral resistance at CDC have demonstrated susceptibility to the neuraminidase

inhibitors.

On the basis of available antiviral testing results, CDC is providing an interim recommendation that neither amantadine nor rimandatine

be used for the treatment or prophylaxis of influenza A in the United States for the remainder of the 2005–06 influenza season.

During this period, oseltamivir or zanamivir should be selected if an antiviral medication is used for the treatment and prophylaxis of

influenza. Testing of influenza isolates for resistance to antivirals will continue throughout the 2005–06 influenza season, and

recommendations will be updated as needed. Annual influenza vaccination remains the primary means of preventing morbidity and mortality

associated with influenza.

Additional information about the prevention and control of influenza is available at http://www.cdc.gov/flu/. Specific information regarding the use of the neuraminidase inhibitors is

available at http://www.cdc.gov/flu/protect/antiviral/index.htm. These

websites will be updated as new information becomes available.