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Treating the Flu with Tamiflu

The flu virus is a major concern. Unfortunately, antibiotics are of no use since they only kill bacteria and there is conflicting evidence when it comes to anti-virals like Tamiflu.

Flu season means a lot of people are going to be getting sick. The CDC estimates that there have been 29 million flu cases, a quarter million hospitalizations, and 16,000 deaths so far this season. So, any treatment that can help with that would be very welcome.

Since the flu is a virus, antibiotics won’t help because antibiotics only kill bacteria. There are however anti-virals that have shown some effect against the flu virus. People used to use drugs like amantadine to treat influenza, but it has two drawbacks. First, amantadine and similar medications were only effective against Influenza A and not Influenza B. Second, in recent years high rates of resistance have developed. As a result, these types of medications are rarely used anymore.

The medication that people would be most familiar with is Tamiflu (scientific name oseltamivir). Oseltamivir (Tamiflu) and zanamivir (Ranimivir) belong to a class of medications called neuraminidase inhibitors which block infected cells from releasing more virus particles into your body.

There is pretty much widespread agreement that Tamiflu and the neuraminidase inhibitors class of medications do work against the virus. Meta-analyses have shown that taking Tamiflu reduces symptom duration by about one day. Whether this improvement is clinically significant is debatable. You may or may not decide that speeding recovery by one day is worth the cost of the medication. We must also face the fact that if we overuse neuraminidase inhibitors like Tamiflu, then the virus will eventually become resistant like it did with amantadine and will, over time, be less effective.

But the real controversy of Tamiflu is whether it helps prevent the more serious complications of the flu. For example, does it prevent people who have the flu from developing a pneumonia? Does it prevent hospitalizations? Or death?

The problem is that multiple research groups have looked at the data and come to different conclusions. The Cochrane Collaboration published a 2014 review of Tamiflu and concluded that while it did decrease symptom duration it did not prevent complications like being hospitalized or getting pneumonia. The Cochrane researchers found that previous analyses relied mostly on unpublished data supplied by Roche, the pharmaceutical company that makes Tamiflu. After multiple attempts to get access to the data, researchers ran their analysis with the data they had available. The whole saga of researchers attempting to get access to the data is documented on the BMJ website.

Another review, this one in 2015 by another group of scientists, came to a different conclusion. They found that treating patients with Tamiflu decreased hospitalizations, albeit by a small amount (1.1%). There are multiple possible reasons why the two studies came to different conclusions. The first being that the 2015 review received funding from Roche, the maker of Tamiflu, even though the authors denied that Roche had any role in the study design or analysis. The 2015 review also had access to individual patient-level data, whereas the 2014 review only had summary data. As a general rule, using patient-level data is thought to result in more accurate analyses.

Another issue when looking at multiple studies is that analyses can come to different conclusions depending on how the flu is characterized. Some people are diagnosed with the flu because they go to their doctor or the hospital and get a nasal swab, whereas others with typical symptoms (like fever, cough, headache, muscle aches) are simply diagnosed based on these symptoms. These people have what is called an influenza-like illness (ILI) since the flu was never actually diagnosed. ILIs tend to be milder than confirmed flu cases because people usually do not need to go to the hospital and often go untreated since they get better on their own.

Using ILI instead of confirmed flu cases will affect how effective a treatment seems. Medications work best the sicker you are. So using ILI instead of confirmed flu cases will make medications seem less effective.

There is considerable controversy about how effective neuraminidase inhibitors like Tamiflu actually are. They obviously have some benefit in terms of reducing symptoms, but these benefits can be outweighed by both the cost and side effects. They are also most effective if started within 48 hours of when the symptoms begin. But given the logistical impracticalities of seeing a doctor within 48 hours, most people would not qualify for treatment.

For now, Tamiflu is generally reserved for severe cases or high-risk patients since they are the ones most likely to derive a benefit (provided it can be started within 48 hours of symptoms). It does seem to have some benefit on flu virus activity, and you likely will feel a little bit better if you take it when you get the flu. But whether it is worth the cost and whether it prevents the more severe complications of the flu, is still uncertain.

Take-home message:
- Tamiflu can reduce the length of flu symptoms by about a day if started within 48 hours of the appearance of symptoms.
- Tamiflu’s ability to reduce complications of the flu, like pneumonia or being hospitalized, is less certain and the data is conflicting.
- Tamiflu is generally reserved for severe cases and high-risk patients because widespread use could lead to the virus becoming resistant to the medication.


@DrLabos

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