Oseltamivir for Influenza

The most recent issue of The Medical Letter (January 20, 2014) reviews Antiviral Drugs for Influenza 2013-2014. A news article in the June 28, 2013 issue of Science titled “Dueling Reviews for Controversial Flu Drug” described an ongoing controversy about the value of the neuraminidase inhibitor oseltamivir (Tamiflu) for treatment of influenza virus infection. The negative reviews, which have come mainly from the Cochrane Collaboration and the British Journal of Medicine, have contended that there is no acceptable evidence that the drug prevents complications or hospitalizations and questioned the completeness of the data from controlled trials conducted by the manufacturer (Roche). In particular, the Cochrane/BMJ researchers believe that government stockpiling of oseltamivir for a possible pandemic, as recommended by the World Health Organization, is a waste of money.

The Medical Letter comes down squarely on the side of the WHO, the CDC, and the other organizations that support the use of oseltamivir and of zanamivir, another neuraminidase inhibitor. When used for chemoprophylaxis after exposure to susceptible strains of seasonal influenza A or B viruses, they have generally been 70-90% effective. In mild illness, started within 48 hours they can decrease the duration of fever and symptoms and may reduce the risk of complications such as pneumonia. In hospitalized and critically ill patients, they may decrease the risk of death and shorten the duration of hospitalization. We recommend treatment as soon as possible for patients at high risk of complications and for those who show signs of clinical deterioration, develop symptoms of lower respiratory infection, or require hospitalization.

In reviewing the controversy about oseltamivir (zanamivir is usually given by inhalation, and no one has recommended stockpiling it), a few things jump out at me. The drug is active against the virus in vitro and has been effective in reducing the duration of mild illness, which is relatively easy to study. Whether it prevents pneumonia, hospitalizations, and death is more difficult to prove, because these are uncommon events, but it stands to reason that it would prevent some of these events, and in a pandemic that could mean saving many lives. The literature on oseltamivir is dominated by articles deeply concerned with the possibility of resistance to the drug, because there is nothing else. Stockpiling it certainly could turn out to be a waste of money, but in my view, that would be money wasted well.

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Comments

  1. Since we’re in the midst of a full-fledged epidemic of influenza in Texas now, and I see a lot of Tamiflu dispensed, perhaps some additional research findings will surface on the subject. Thanks for a timely post.

  2. Herb Kleinman says:

    I was pretty underwhelmed with the references cited to support your position. I think we need to be very careful about trusting any guidelines, as they are often created by folks with inappropriate ties to the pharmaceutical industry. Even in your blog, you are using the word “may” quite a bit. I remain unconvinced of Tamiflu’s general utility.

  3. Steven Vidrine MD says:

    Something else about the controversy should have jumped out at you. All the points you made about Tamiflu were based on the studies provided to the FDA by the manufacturer, however they were other studies at that time that were not submitted. These eventually were analyzed in Australia and found to have no benefit over placebo. When all studies are combined there is no benefit. Sorry do not remember the reference but is in the Primary Care Medical Abstract’s database. The FDA remains curiously quite about this study.

  4. Ken Grauer, MD says:

    I believe the articles Steven Vidrine is referring to are the following:
    i) Effectiveness of Oseltamivir in Adults: A Meta-Analysis of Published and Unpublished Clinical Trials (Ebell MH et al – Fam Pract 30(2):125, April 2013).
    ii) Tamiflu: The Battle for Secret Drug Data (Payne D – Br Med J 345:e7303, October 29, 2012).
    Benefit (if any) seems to be minimal with use of Tamiflu. Roche was extremely reluctant/resistant to releasing data obtained from unpublished trials (which greatly outnumber data from the published trials). These articles are concerning given all the hype in favor of this drug ….

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