Tamiflu: The not-so-great influenza treatment

Dec 29, 2017

Over the years I've written a lot about Tamiflu because I have strong feelings about its use. Here I'll summarize what I've learned over the years because during flu season I get many requests for Tamiflu (oseltamivir). Understandably parents fear the flu once they see how miserable their kids are when it hits their house, but I don't like to use Tamiflu because I just don't think it works well and it has quite a few side effects.

The pressure's on...

In recent years I've felt coerced into writing more prescriptions for Tamiflu due to the powers of the guidelines recommending it. It's more common in my experience to hear negative feedback about side effects than it is to see patients get better faster. (Note: this is a very biased view, since those who are better would not call, but since so many call with side effects it seems fair to say I don't like the drug.)

I am not alone in my dislike of Tamiflu. I follow a listserv of pediatricians around the country and many share my views. In a discussion of influenza and antivirals, one doctor suggested watching a TED Talk by Dr. Ben Goldacre: What doctor's don't know about the drugs they prescribe. Dr. Goldacre starts talking about Tamiflu specifically about 10:10, but the entire lecture is done in an entertaining and informative manner if you have the time.

I feel deceived.

When I practice medicine, I follow standard recommendations and guidelines that are based on peer reviewed articles and data. The question is, what important data is left out? There is a movement to solve this problem of unpublished studies. You can see updates at the Tamiflu Campaign of the British Medical Journal.

The WHO has downgraded Tamiflu's status, but I haven't seen the CDC or AAP comment on that.

Back to influenza treatment...

First, current influenza treatment guidelines regarding the use of antivirals:

From the CDC's recommendations for antiviral use for influenza

Summary of Influenza Antiviral Treatment Recommendations

Clinical trials and observational data show that early antiviral treatment can shorten the duration of fever and illness symptoms, and may reduce the risk of complications from influenza (e.g., otitis media in young children, pneumonia, and respiratory failure).
Early treatment of hospitalized adult influenza patients has been reported to reduce death.
In hospitalized children, early antiviral treatment has been reported to shorten the duration of hospitalization.
Clinical benefit is greatest when antiviral treatment is administered early, especially within 48 hours of influenza illness onset.
Antiviral treatment is recommended as early as possible for any patient with confirmed or suspected influenza who:
- is hospitalized;
- has severe, complicated, or progressive illness; or
- is at higher risk for influenza complications.
Antiviral treatment also can be considered for any previously healthy, symptomatic outpatient not at high risk with confirmed or suspected influenza on the basis of clinical judgment, if treatment can be initiated within 48 hours of illness onset.

That last statement is what really gets me confused.

I know that influenza can be deadly.

And that we should try to do everything in our power to help prevent severe illness and death.

But to treat any healthy person with suspected flu with a medicine that hasn't been shown to be very effective and has side effects seems unreasonable to me.

Because it's a guideline, if a physician chooses not to give antiviral treatment and there is a bad outcome, they could be held liable.

Despite the research.

I think this option also encourages people to not get the vaccine because they think they can just treat it if they get the disease. It's not that easy...

look at what a search for "unpublished tamiflu trials" shows.

For those of you unfamiliar with the Cochrane group: They are a well respected group that reviews all the studies within certain parameters on one topic to evaluate the overall findings of several independent studies.

From the Cochrane Group:

A review of unpublished regulatory information from trials of neuraminidase inhibitors (Tamiflu - oseltamivir and Relenza - zanamivir) for influenza.

These results are from a review of published and unpublished studies that they could find.

From the abstract:

"The authors have been unable to obtain the full set of clinical study reports or obtain verification of data from the manufacturer of oseltamivir (Roche) despite five requests between June 2010 and February 2011. No substantial comments were made by Roche on the protocol of our Cochrane Review which has been publicly available since December 2010."

They found several problems with Tamiflu from the studies they were able to review:

Drug manufacturers sponsored the trials, leading to publication and reporting biases. One of the authors reported that 60% of the data was never published. This is over half of the research, and I suspect it didn't support use of the medicine (remember the company that benefits from selling the medicine was doing the trials...)
There was no decrease in hospitalization rate for influenza in people treated with Tamiflu.
There was not enough evidence of prevention of complications from influenza. Design of the trials (again by the people who make the drug) did not report the prevention of complications from influenza, such as secondary infections.
There is not evidence in the trials to support that Tamiflu reduces spread of the virus. One of the main reasons people request the medication is after exposure to prevent illness! (Note: this might have changed because the indications on the package insert now say it can be used to prevent illness in those over 1 year of age and they were previously not allowed to mention prophylaxis.)
Tamiflu reduced symptoms by 21 hours. Yep. Less than one day of fewer symptoms. For the cost of the drug and the potential side effects, is feeling sick for 1 day less really worth it?
There was a decreased rate of being diagnosed with influenza in those randomized to get Tamiflu, probably due to an altered antibody response. The authors suspect a body becomes less able to make its own antibodies against influenza when taking Tamiflu.
Side effects were not well documented. A review study done in children exclusively (Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trials) focused on treatment of disease and prevention of illness after exposure.

Findings included:

Symptom duration decreased between 0.5 and 1.5 days, but only significantly reduced symptoms in 2 of 4 trials. That means in 2 of 4 trials there was no significant reduction in symptoms.
Prophylaxis after exposure decreased incidence by 8% of symptomatic influenza. This means for every 13 people given Tamiflu to prevent disease, one case will be prevented. Not great odds.
Treatment was not associated with an overall decrease in antibiotic use, suggesting it did not alter the complication of bacterial secondary infections.
Tamiflu was associated with in increased risk of vomiting. About 1 in 20 children treated with Tamiflu had an increased risk of vomiting over the baseline vomiting due to influenza.
There was little effect on the number of asthma exacerbations or ear infections by treating influenza with Tamiflu.

Investigators have documented their discussions with the maker of Tamiflu on Tamiflu correspondence with Roche.

Recent studies have tried to compile all that is known about how oseltamivir works:

Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments.

Results from this study include:

In the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.7 hours, 29 hours in children.
There was no difference in rates of admission to hospital between treatment groups in both adults and children.
Oseltamivir relieves symptoms in otherwise healthy children but has no effect on children with asthma who have influenza-like illness.
Using oseltamivir had no significant effect on admissions to the hospital.
Oseltamivir causes gastrointestinal disturbances in both prophylaxis and treatment roles. In prophylaxis, it caused headaches, renal events (especially decreased creatinine clearance), and psychiatric effects.

So what do I recommend during the cold and flu season?

Get vaccinated! The influenza vaccines have been shown to help prevent influenza and are very well tolerated with few side effects. If you or your children are due for other vaccines, be sure to get caught up. Even if they aren't a perfect match, some protection is better than none, and if more people get the vaccine herd immunity helps!
If you get sick, stay home until you're fever free without the use of a fever reducer for at least 24 hours! Don't spread the illness to others by going to work or school. The influenza virus is spread for several days, starting the day before your symptoms start until 5-7 days after symptoms start-- kids may be contagious for even longer. You are most contagious the days you have a fever.
Wash hands well and frequently. If you can't use soap and water, use hand sanitizer.
Cover your cough and sneeze with your elbow or a tissue.
Avoid close contact with people who are sick. But remember that people spread the virus before they feel the first symptoms, so anyone is a potential culprit!
Don't share food, drinks, or towels (such as after brushing teeth to wipe your mouth) with others.
Don't touch your eyes, nose, and mouth -- these are the portals for germs to get into your body.
Keep infants away from large crowds during the sick season.
Frequently clean objects that get a lot of touches, such as keyboards, phones, doorknobs, refrigerator handle, etc.
Avoid smoke. It irritates the airway and makes it easier to get sick.
Remember that many germs make us sick during the flu season. Just because you've been sick once doesn't mean you won't catch the next bug that comes around. Use precautions all year long!
Did I mention that you should get vaccinated?

Because the guidelines recommend Tamiflu as above, I will probably be forced to prescribe it by worried parents who hope that their kids will feel better. (You've heard of defensive medicine, right?)

Key Point:

Influenza is a miserable illness. The key is prevention.

I've had my vaccine, how about you?

If you're worried about the injection, check out Vaccines Don't Have to Hurt As Much as Some Fear.

A physician's story of his sister dying of influenza despite being overall healthy and getting good medical care: Even With All Our Modern Medicine, I Watched My Sister Die From Flu

Added 1/14/18: I just saw this story about a girl with very scary hallucinations from Tamiflu. I've heard these stories before. It's not as uncommon as the story might lead you to believe.