Drug Treatment of Influenza

The next issue of The Medical Letter will include an article on antiviral drugs for influenza. Oseltamivir (Tamiflu), which is taken orally, and zanamivir (Relenza), which is inhaled, are now the only drugs recommended, at least in North America, for either prevention or treatment of flu. Both are neuraminidase inhibitors that block replication of the virus. For treatment, the usual recommendation is that they need to be started within 48 hours of the onset of symptoms to be effective, but one recent study found evidence of effectiveness when they were started up to 5 days after the onset of symptoms.

For most people, the effect of antiviral treatment of influenza is relatively trivial – perhaps one day less of flu symptoms. For those at high risk, however, the effect could be life-saving, and the most recent definition of high risk offered by public health authorities is fairly expansive, including all children less than 2, all senior citizens (65 or older), pregnant women, everyone who is immunosuppressed or has a chronic disease, such as diabetes, and all native American/Inuit residents of Alaska. That’s a lot of people, and the recommendation that they all be treated puts some pressure on primary care providers to document the diagnosis, which many of them may not be accustomed to doing.

It’s pretty clear from controlled trials that oseltamivir and zanamivir shorten the duration of influenza symptoms. Whether they prevent pneumonia complications, hospitalizations and death has been more difficult to document, but one observational study examined the experience of nursing homes in Ontario during a flu outbreak in 1999-2000 and found that residents who received oseltamivir treatment for flu symptoms were less likely to be treated with antibiotics (presumably for pneumonia), to be hospitalized, or to die, compared to those who were not treated. All of these differences were statistically significant and were not affected by immunization status.

The British Journal of Medicine has recently accused Roche, the manufacturer of Tamiflu, of withholding negative data on the safety and efficacy of the drug. Of course there is no such thing as being too cynical about the lengths pharmaceutical manufacturers will go to in order to promote use of their products, but virtually all of the experts we consulted in preparing our article seem to be convinced that the drug is safe, and that it could save lives in patients at high risk. There is no question that influenza can be deadly, that immunization is our most important weapon against the disease, or that when immunization fails, these drugs are all we have to offer our patients.

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