Tamiflu Overview

Tamiflu (oseltamivir phosphate) is an antiviral drug marketed by the Swiss pharmaceutical company Roche. It belongs to a group of drugs called neuraminidase inhibitors and can shorten the duration and lessen the severity of the type A and B strains of the flu, as well as bird flu.

Each 75-milligram capsule contains the active chemical oseltamivir, as well as several inactive ingredients. Scientists synthesize oseltamivir from shikimic acid, a naturally occurring substance found in plants like Chinese star anise, ginkgo, spruce, pine and fir trees.

Roche primarily obtains shikimic acid from the Chinese star anise, a spice found in the star-shaped fruit of the Illicium verum, a small evergreen tree. Roche uses a specific type of anise that grows in four mountain provinces (Guanxi, Sichuan, Yunnan and Guizhou) of southwest China. Because these regions are high altitude and have a hot, humid, climate, they produce a higher purity and greater yield of star anise than other regions.

The manufacture of Tamiflu involves a complex, 10-step process that takes approximately 6-8 months to complete. First, a Roche supplier extracts shikimic acid from the pods (the part that wraps around the seeds) of the star anise. The remaining steps involve a series of complex chemical reactions. Thirty kilograms (66 pounds) of star anise produces only 1 kilogram (just over 2 pounds) of shikimic acid.

Although most shikimic acid comes from star anise, Roche and its partners are increasingly using fermentation to produce it. Roche uses a special strain of the E. Coli bacteria in its fermentation process. When these bacteria are overfed glucose, or sugar, they produce shikimic acid. This process could produce greater yields of shikimic acid, and scientists are working to improve the fermentation process so they can use it more readily.

Tamiflu targets a protein called neuraminidase that lives on the flu virus cells. This protein helps the flu virus break through the cell walls so it can move on to other cells and replicate itself. Tamiflu inhibits the neuraminidase protein, so that the virus can't leave the cell to infect other cells. Eventually, the virus dies.

Tamiflu can't stop the flu entirely. However, studies have shown that if you take it within 48 hours of showing symptoms, it can shorten the duration of the flu (strains A and B). Patients with the flu who took it felt better 30 percent (or 1.3 days) faster than people who didn't take it [ref]. The drug also can help protect you from getting the flu if you're exposed to someone who has it. But Tamiflu can't prevent the spread of the disease, and it won't stop illnesses (like the common cold) that resemble the flu.

Tamiflu isn't cheap, either. A 10-dose course can cost $60 to $80 in the United States. Currently there is no generic version of the drug available in the U.S.

Between 2004 and 2005, 12 children in Japan reportedly died after taking Tamiflu. However, the children also had neurological problems that could have been associated with the flu itself. In November 2005, the Pediatric Advisory Committee of the FDA ruled that the drug was safe for children [ref].

We'll find out how Tamiflu stands up to bird flu in the next section.

Viruses that normally occur in birds cause bird flu, and there are many different strains. Some of these viruses can pass from birds to other animals, and most of them are mild. However, there have been several human outbreaks of the H5N1 strain of bird flu in Asia and Europe over the last decade. Scientists are concerned that this strain will eventually mutate into a form that can pass directly from human to human. When the H5N1 strain re-emerged in Asia during the winter of 2003, it set off fears of a worldwide pandemic. (See How Bird Flu Works for more information.)

The flu vaccine that works against the A and B "regular flu" strains is not effective against bird flu. Although scientists are hard at work developing an avian flu vaccine, currently antiviral drugs are the only weapon against the disease.

Laboratory studies show that Tamiflu is effective against several strains of bird flu, including H5N1. It works the same way that it works against the "regular flu." However, it only lessens the severity of the illness -- it can't stop the virus entirely. The World Health Organization recommends Tamiflu as the drug of choice should an avian flu pandemic occur. Doctors in Asia are already using Tamiflu to treat patients who have become ill with the H5N1 strain.

The problem with any antiviral drug is that the virus can develop resistance to it. Doctors are concerned that the flu could become resistant to Tamiflu, just as the influenza A strain has become resistant to the antiviral drugs Symmetrel (amantadine) and Flumadine (rimantadine).

Some flu strains have already shown resistance to Tamiflu, including those found in a few patients with the avian flu. Health officials are concerned that during a pandemic, when infection persists for a longer period, the risk for resistance could be even higher.

In 2005, Roche donated 3 million treatment courses (30 million capsules) of Tamiflu to the World Health Organization to create an international stockpile. The company donated an additional 2 million courses (20 million capsules) to the WHO in January 2006.

Because Roche is the sole patent owner, the company has had a difficult time producing enough to go around. This is partially due to the difficulty in isolating shikimic acid from star anise in large quantities. Roche continues to increase its manufacturing capability. It claims that by 2007, it will be able to produce over 300 million treatments of Tamiflu annually, more than ten times the production in 2004.

Some countries said they would ignore the patent and manufacture generic versions of the drug, while others said they would license their own version from Roche to protect people in the event of a pandemic. In 2005, Roche granted Vietnam permission to produce a generic version of the drug. That same year, the Indian drug company Cipla announced that it would defy Roche's patent and make its own generic version of the drug without a license. Recently, Roche granted sublicenses to manufacture Tamiflu to a Chinese and an Indian drug company [ref].

With fears rising about a potential bird flu pandemic, it's not surprising that many Americans are thinking about keeping their own supply of the antiviral drug. But is it a good idea? Many health experts warn against the practice, saying that it's often difficult to know whether you have the flu or just a garden-variety cold, and taking Tamiflu too often could lead to the development of drug-resistant virus strains. The World Health Organization has recommended that governments stockpile antiviral medications in advance of a pandemic to ensure that sufficient supplies are available.

To learn more about Tamiflu, the flu and bird flu, check out the links in the next section.