The Trouble With Tamiflu

If avian flu starts to spread easily among humans, the preventive drug Tamiflu has been hailed as a possible way to stem the epidemic.

But will it work? A report in the New England Journal of Medicine today points to no. It details the cases of two Vietnamese patients who both died from a form of avian flu that was apparently resistant to Tamiflu, casting some doubt over the potential effectiveness of the drug.

One of the patients, a 13-year-old girl, died even though treatment was begun at the ideal time -- just hours after her symptoms had appeared.

The deaths mean that public-health experts and individuals should consider broader strategies to combat the spread of avian flu, wrote Dr. Anne Moscona in an accompanying editorial.

"Improper use of personal stockpiles of oseltamivir [the medical name for Tamiflu] may promote resistance, thereby lessening the usefulness of our frontline defense against influenza, and should be strongly discouraged," wrote Moscona, a medical professor at Weill Medical College of Cornell University in New York who specializes in pediatrics, microbiology and immunology.

Tamiflu, which inhibits an enzyme necessary for the flu virus to spread internally, has been in such high demand here that its manufacturer, Roche, stopped shipping it to the United States in late October.

Another editorial in the same issue of the Journal urges family doctors not to write Tamiflu prescriptions for patients who demand it for the sole purpose of staving off avian flu.

Earlier today, Roche held a news briefing to respond to the findings on Tamiflu-resistant avian flu. Dr. David Reddy, influenza pandemic task force leader for Roche, said the case reports confirmed that Tamiflu is effective against the virus, because four of the eight treated patients experienced a drop in their viral levels in response to Tamiflu, and they survived. The virus progressed in the other four patients who received Tamiflu, and they later died.

Reddy also stressed the need for more study. So far, 30 out of 138 avian flu patients are known to have been treated with Tamiflu, so doctors do not yet know the ideal dose and length of treatment.

A joint study by the National Institutes of Health and the World Health Organization is planned for early 2006 to investigate whether doubling the dose of Tamiflu and lengthening the course of treatment would increase survival rates.

"We are not yet dealing with a pandemic strain," said Reddy. He characterized the avian flu virus as a "moving target" that may become less aggressive if it shifts to a pandemic strain. Whether this shift would increase or decrease the effectiveness of Tamiflu remains unknown.

Roche expects to manufacture enough Tamiflu to treat 150 million people in 2006 and 300 million people in 2007.

"The current supply of oseltamivir [Tamiflu] is inadequate to meet the demand that would arise in the event of an avian influenza pandemic. Moreover, personal stockpiling of oseltamivir [Tamiflu] depletes the supply available for patients who could benefit from the drug during the usual human influenza season: A person who is assertive enough to ask for a prescription does not necessarily need the drug more than unassertive people do," wrote Drs. Allan Brett and Abigail Zuger.

Dr. Marvin Bittner agreed, and said the current focus on Tamiflu misses the point.

"We need to work on a variety of countermeasures -- not just Tamiflu -- in the hope that some, and ideally many, will indeed be effective," said Bittner, chief of infectious diseases at the VA Medical Center in Omaha, Neb.

For a broader approach, he suggested widespread dispensing of pneumonia vaccines to prevent a common complication of the flu; urging smokers to quit to help them have the healthiest possible lungs and hearts; developing new ways to manufacture the flu vaccine; testing new theories to slow the spread of infection; and formulating plans to keep essential services, such as emergency medical care, running.

The Journal reports indicated that a similar drug, Relenza, might not be prone to the same problems, although there is little evidence to confirm that at this point.