What You Should Know About Tamiflu

We’ve all probably heard about prescription drugs that were recalled and taken off the market due to health concerns.  Think Vioxx, Avandia, Budeprion or Meridia.  All are drugs that were either proven to be ineffective, or to actually do more harm than good.  Well, as Yogi Berra said, “it’s Déjà vu all over again”.  This season’s target is Tamiflu, a prescription drug for the treatment of the influenza.  We’ve all probably heard of it, but do we know enough about it?  Based on researchers who have thoroughly reviewed the data, Tamiflu may not be the wonder drug it is touted to be.

What the research says:

The US National Library of Medicine website states the following about Tamiflu (using Oseltamivir which is the pharmaceutical name for Tamiflu).

Oseltamivir is used to treat some types of influenza infection ('flu') in adults and children (older than 1 year of age) who have had symptoms of the flu for no longer than 2 days. This medication is also used to prevent some types of flu in adults and children (older than 1 year of age) when they have spent time with someone who has the flu or when there is a flu outbreak. Oseltamivir is in a class of medications called neuraminidase inhibitors. It works by stopping the spread of the flu virus in the body. Oseltamivir helps shorten the time you have flu symptoms such as a stuffy or runny nose, sore throat, cough, muscle or joint aches, tiredness, headache, fever, and chills. Oseltamivir will not prevent bacterial infections, which may occur as a complication of the flu.

This information was provided by The American Society of Health-System Pharmacists (a professional organization of pharmacists and pharmaceutical professionals), and is based upon clinical data collected and summarized by Roche (the manufacturer of Tamiflu).  However, this information is based on the manufacturer’s interpretation of the clinical studies, not on unbiased reviews of those results.  Why does that matter?  Because non-transparent reviews of data may not accurately reflect the entirety of the results. Why should that worry us?  Well, I’ll remind you again of Vioxx and Avandia.   One should always be skeptical of data or results that are summarized but not provided. Based on recent publications, Tamiflu’s results may not be all they’re touted to be.

How widely used is Tamiflu?

Tamiflu has generated more than $5 billion dollars for Roche internationally.  The drug has been stockpiled by dozens of governments worldwide in case of a global flu outbreak and was widely used during the 2009 swine flu pandemic.  In fact, the Centers for Disease Control and Prevention recommend Tamiflu as one of two medications for treating regular flu [4] and the WHO has added Tamiflu to its List of Essential Medicines.  In the US alone, more than 16 million Tamiflu prescriptions have been dispensed between the years 2007 and 2011.

What do the clinical results show?

Several research groups have attempted to perform unbiased reviews of the clinical data related to Tamiflu.  However, their efforts have been impeded by Roche’s lack of transparency and forthright-ness.  It has been widely reported that the clinical studies used to get regulatory approval for Tamiflu are unavailable and unpublished.  In fact, “eight of the 10 randomized controlled trials on which regulatory claims were based were never published” [5].  In addition, the “two that had been published were funded by Roche and authored by Roche employees and external experts paid by Roche”.  So concerns of transparency abound.    

A research group at the Cochrane Collaboration published a report pressing Roche to release its clinical results so that they could be reviewed openly [3].  The Cochrane Collaboration is an international consortium of more than 28,000 professionals focused on providing information about the effectiveness of health care.   In response to that pressure, Roche announced it would release full reports for those clinical studies.  However, full clinical study reports were never released, and Roche has only released portions of certain reports.

One researcher used documents generated by national and regional regulatory bodies during licensing processes in the UK, USA, continental Europe and Japan, partial trial reports from the manufacturers of oseltamivir and from the European regulator European Medicines Agency (EMA) to independently review the results [1].  When those results were reviewed, he found that many of the claims made were not supported by the data.  In fact, he found the following [3].

  • Duration of symptoms.  People taking Tamiflu have flu-like symptoms for approximately 21 fewer hours, so the duration of their illness decreased from approximately 7 days to approximately 6 days.  
  • Rate of hospitalizations. They found no evidence of a difference between treatment groups in the incidence of hospitalizations throughout the entire treatment period.
  •  Incidence of flu-related complications.  The results obtained were not conclusive on this matter.  However it should be noted that the FDA has required Roche’s marketing materials to state, “TAMIFLU has not been shown to prevent such complications”. 
  • Prevention of flu.  Evidence was insufficient to support or refute the effect of Tamiflu on prophylaxis of influenza-like illness. 
  • Side Effects.  Tamiflu has been associated with several side effects, including vomiting, nausea, skin reactions and neuropsychiatric events.  Yes, I said neuropsychiatric events.

What does that all mean?

In essence, Tamiflu “has modest effectiveness against the symptoms of influenza in otherwise healthy adults” [2]. It has been shown to decrease the duration of flu symptoms by less than a day.  But Roche’s claims that Tamiflu prevents the incidence of acquiring the flu, decreases the incidence of complications, and decreases the length of hospital stays are dubious and unconfirmed.  In addition, Tamiflu was found to have several side effects, including nausea, vomiting and even neuropsychiatric events. It should also be noted that the FDA assessment of the performance of oseltamivir was “modest”[1].  So keep this in mind when you’re feeling sick or someone you love is sick and your doctor prescribes Tamiflu.  It may decrease how long you’re feeling sick, but don’t expect it to do much more than that.  And let’s hope that’s all it does.

References:

1.     Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children.  Jefferson T, Jones MA, Doshi P, Del Mar CB, Heneghan CJ, Hama R, Thompson MJ.  Cochrane Database Syst Rev. 2012 Jan 18;1:CD008965. Review.

2.     Drug Data Shouldn’t Be Secret, by PETER DOSHI and TOM JEFFERSON. New York Times Op-Ed published April 10, 2012.

3.     Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis.  Jefferson T, Jones M, Doshi P, Del Mar C.  BMJ. 2009 Dec 8;339:b5106. doi: 10.1136/bmj.b5106. Review.

4.     http://www.dailymail.co.uk/health/article-2232118/Essential-medicine-Tamiflu-accused-useless-fighting-flu-experts-legal-action-Roche.html

5.     Open letter to Roche about oseltamivir trial data.  Godlee F. BMJ. 2012 Oct 29;345:e7305.

6.   Tamiflu (oseltamivir phosphate) Pediatric Safety Update: Background Summary and Review of Clinical Review Team Activities, 2007 to Present.  Written by the DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH SERVICE FOOD AND DRUG ADMINISTRATION CENTER FOR DRUG