Resistance develops to certain flu antivirals

Washington -- Physicians are being asked by the Centers for Disease Control and Prevention not to prescribe two of the four antiviral drugs available to treat or prevent annual influenza, because the circulating virus has become resistant to the drugs.

The CDC found that 91% of the 120 influenza A (H3N2) viruses isolated from patients in 23 states were resistant to amantadine, or Symmetrel, and rimantadine, or Flumadine, which are M2 ion channel inhibitors. This represented a sharp increase from last year, when only 11% were resistant. Fewer than 2% had been resistant the year before.

Amantadine also is used to treat the symptoms of Parkinson's disease, and it should continue to be used for this purpose, according to the CDC.

The antivirals oseltamivir, or Tamiflu, and zanamivir, or Relenza, which are neuraminidase inhibitors, are still effective against the flu and may be prescribed for treatment or prevention, according to the CDC.

"This is certainly unexpected news, as we now have to remove a few tools from our tool box that we use to combat influenza," said CDC Director Julie Gerberding, MD, MPH, in announcing the recommendation Jan. 14. "Thankfully, we still have antivirals available that work, but this new development serves as a reminder of the importance of getting people vaccinated to prevent them from getting influenza in the first place."

Flu activity may be starting to pick up across the country, according to the agency, with 18 states reporting either widespread or regional activity. People who have not yet had a flu shot are still urged to get vaccinated, as the virus is expected to circulate for the next several months. More than 80 million doses of vaccine have been distributed, and supplies vary from region to region. The CDC has 3.5 million additional doses available from its stockpile to sell through manufacturers. Plus, manufacturers also still have some available.

The CDC will continue to test influenza isolates for resistance throughout the current flu season.

Flu review

Meanwhile, a review of 50 clinical trials on the two classes of antivirals published Jan. 19 in The Lancet concluded that amantadine and rimantadine should not be used for seasonal or pandemic influenza control because they are ineffective and can cause adverse side effects.

The researchers from the Cochrane Vaccines Field agreed with the CDC that the use of amantadine quickly led to resistant viral strains.

But they also concluded that zanamivir and oseltamivir should not be routinely used for seasonal flu control but only in a serious epidemic with other public health measures, such as gloves and masks.

They found that the neuraminidase inhibitors did not stop virus shedding from the nose, an important means of influenza spread, although they did diminish the effect.

Nonetheless, a look at their findings reveals some surprisingly strong benefits to the neuraminidase inhibitors. Oseltamivir reduced an individual's chances of infection when exposed to the flu by someone in their home by more than 58% as long as the medication was given within 48 hours of exposure. Its overall efficacy rate post-exposure was 61%.

David Fedson, MD, a member of the Infectious Diseases Society of America's Task Force on Influenza, was surprised by the authors' conclusions that the neuraminidase inhibitors not be used for seasonal influenza control.

"In my opinion, the measure of effectiveness they document against a condition which is extremely common and has a great impact on society means that these agents have a societal effect which is substantial and that their use should be encouraged," he said.

He also noted that the review provides a useful summary of experience thus far with antivirals. "For the neuraminidase inhibitors, the evidence that these agents effectively shorten the duration of symptoms and reduce viral shedding and, most importantly, reduce the occurrence of lower respiratory complications in patients with influenza is very encouraging."

The World Health Organization is also banking on the effectiveness of oseltamivir against avian influenza, which had infected 148 people and caused 79 deaths as of mid-January.

The drug's manufacturer, Roche, has now donated five million doses of the antiviral to WHO, which is stockpiling it for use in developing countries that are most likely to be affected by the lethal virus.