How good is Tamiflu?
Posted by medconsumers on September 28, 2009
The antiviral drugs Tamiflu (generic name: oseltamivir) and Relenza (zanamivir) are getting renewed attention now that the flu season is upon us. Both are in the same drug class called neuraminidase inhibitors. Because Tamiflu dominates the market for antivirals, it is named throughout this article but the findings are generally applicable to both drugs.
The benefit once you get the flu: Roche Laboratories had to conduct two trials to get FDA approval for this indication. The studies showed that Tamiflu, reduced the duration of the seasonal flu by a little more than one day…but only when taken within 40 hours of the onset of flu symptoms. This benefit, however, is limited to those with influenza A or B. The two trials had a combined total of 1,355 people who were randomly assigned to take 75 mg Tamiflu or a placebo, twice daily for five days. At the start of the trials, all participants were proven to be infected with influenza A. In time, more studies were published and all were reviewed for a recent issue of Lancet Infectious Diseases. This review found Tamiflu shortened the duration of influenza by 13 hours for healthy people and by 18 hours for high-risk people. Tamiflu costs between $5 and $10 a pill, depending on where it is purchased.
Problems with the above: When flu symptoms develop, you are not likely to know whether you have influenza A or B; nor will there be much time for laboratory confirmation. (The test is highly inaccurate anyway.) Chances are high that you don’t have influenza A or B because both are relatively rare, representing less than 10% of the 200 or so circulating viruses. What’s more, the symptoms are indistinguishable from the other 90% of circulating viruses that cause what is known as influenza-like illness. H1N1, or swine flu, is an influenza A virus, which is why this drug is allowed to be marketed for seasonal as well as H1N1 influenza. (The yearly seasonal vaccines are also aimed solely at influenza A and B viruses.)
Benefit when trying to prevent the flu: In the Roche-sponsored trials for this purpose, healthy unvaccinated adults, aged 13 to 65 years, took 75 mg Tamiflu once daily for 42 days during an outbreak of influenza in their community. 5% of the people taking a placebo got the flu, compared with 1% of those taking Tamiflu. In healthy children, aged 1 to 12 years, taking 30 mg or 60 mg (depending on the child’s weight) Tamiflu once daily for ten days, 17% of those taking the placebo got the flu, compared with 3% of those taking Tamiflu. As for Tamiflu’s ability to reduce complications, see Postscript below.
Resistance: “Emergence of drug-resistant influenza viruses after treatment has been reported, particularly in children in Japan, where the dosing schedule is different [i.e., more aggressive] from that used throughout the rest of the world,” according to a report in the February 15, 2009 issue of Clinical Infectious Diseases. The authors of this report also found that resistance to Tamiflu is more likely to occur in H1N1 influenza A [swine flu] than in other influenza A or influenza B viruses.
Revised CDC recommendations: On September 22, 2009, the CDC updated its recommendations to physicians, stating that Tamiflu should be reserved for high risk populations like pregnant women and babies. “Most healthy persons who develop an illness consistent with influenza, or persons who appear to be recovering from influenza, do not need antiviral medications for treatment or prophylaxis.” In other words, now that antivirals have shown some resistance, not to mention marginal effectiveness, the CDC says these drugs should be reserved for people at high risk for flu-related complications.
History: Tamiflu was approved by the FDA in 1999 for the treatment of influenza A and B. About four years ago when the avian flu was the threat, several governments, including that of the U.S., started stockpiling Tamiflu. In the U.S. government’s case, the stockpiling was for the military. Just since the emergence of swine flu in Mexico last spring, J.P. Morgan, the investment bank, estimated that governments have placed new orders for antiviral drugs of $3billion, despite the fact that this flu season looks like it will be relatively mild. Initially, Roche was required by the FDA to state in the drug’s label that Tamiflu’s efficacy in the treatment of influenza in people with chronic cardiac disease and/or respiratory disease had not been established. This disclaimer appears again in the updated 2008 FDA-approved label for Tamiflu because Roche still has not tested its drug for this high-risk population that needs it the most. [The drug label is the package insert that comes with medications and reprinted in the Physicians’ Desk Reference. The label is written by the drug company and then negotiated and approved by the FDA.]
Unanswered questions: Why haven’t the government-customers for Tamiflu leaned on Roche to prove its drug is effective in treating people with chronic cardiac disease and/or respiratory disease? What incentive does a company have to develop a better drug when it can make a billion dollars selling a barely effective drug like Tamiflu to the U.S. government each year?
Risks: Years after Tamiflu went on the market, reports surfaced that Tamiflu-treated people with influenza had experienced delirium and abnormal behavior, leading to injury and even death. Most of the cases occurred in children and in Japan where this drug was used excessively. Influenza itself (without Tamiflu) can be associated with a variety of neurologic and behavioral symptoms such as hallucinations, delirium, and abnormal behavior. In 2008, the FDA and Roche revised the label for Tamiflu accordingly. Nausea is a common side effect of Tamiflu.
Other antiviral drugs to avoid: In 2005 the Lancet published a study showing that influenza A viruses had developed resistance to Symmetrel and Flumadine and other antiviral drugs in a class called amantadine. These drugs were widely prescribed before 2005.
Postscript, added December 8, 2009
The British Medical Journal announced the publication of an updated review of all studies related to Tamiflu effectiveness, concluding, “There is no clear evidence that the antiviral drug most commonly used against influenza – oseltamivir (Tamiflu) – prevents complications like pneumonia in healthy people [who who become ill with influenza]. …Yet such claims have been a key factor in decisions to stockpile these drugs as part of global pandemic preparedness plans.” The review is described as part of a joint investigation by the Cochrane Collaboration, the British Medical Journal, and [BBC] Channel 4 News.
And this addendum December 7, 2010: See this new website for an excellent explanation of the benefits and risks of Tamiflu.
Maryann Napoli,Center for Medical Consumers(c)