Sunday, November 11, 2007

How Much Tamiflu Is Enough?





Today's story out of the UK indicates that their Pandemic Influenza Scientific Advisory Group is urging the government to triple their stockpile of Tamiflu (oseltamavir).   


They believe that coverage for 75% of their population is essential if they are to "exert reasonable control over the scale and severity of the national ­outbreak"


First the story, then a discussion.




'Too few jabs' to fight flu epidemic


Last Updated: 2:44am GMT 11/11/2007


Stockpiles of drugs to fight a flu pandemic must be increased if the death toll from an outbreak of the virus is to be minimised, senior government advisers have warned


The latest research by the Pandemic Influenza Scientific Advisory Group claims that the number of antiviral doses held by the Government must be tripled if a flu pandemic is to be effectively controlled.


The current stockpile of 14.6 million courses of the antiviral drug Tamiflu covers 25 per cent of the population.


However, the group warned that "under no circumstances" would it be possible to limit effectively the number of cases and deaths with the existing stocks.


It said there were not enough doses available to give drugs to family members of an infected patient, making it hard to stop an outbreak spreading once it gained hold.


Instead, the scientists recommend boosting the stockpile to cover more than 75 per cent of the population.


Such a move would allow doctors to "exert reasonable control over the scale and severity of the national ­outbreak".



Last month, in a blog called How (not) To Break Bad News I recounted the hoary story of the English gentleman calling home to his butler, to find that his dog had died.   I equated that slow motion dispensing of bad news to the way information about a pandemic is released. 


By drips and drabs.


Here we have another drip.  Although, not an  unexpected one.


Conventional wisdom over the past couple of years has stated that 25% coverage of the population with Tamiflu would be sufficient.  We are also told that a 10-pill course of Tamiflu is all that is required.    Both of these assumptions have come under fire in the past, and are likely to continue to do so.


I suspect these original estimates were based more on what officials thought they could `sell' to their respective governments, more than on logic and science.  Budgets are tight, and spending money to thwart a pandemic that might not happen anytime soon is politically risky.


Two years ago, the 10-pill course for 25% of the population may have been seen as about as much as pandemic planners could hope for.  Better to get that, than ask for 3 times that much, and get turned down flat.


But we now know that the 10 pill course of Tamiflu is probably insufficient.   And estimates of the attack rate, the percentage of people who are sickened in a pandemic, have escalated over the past couple of years, going from a conservative 25% to speculation that 50% or more of the population may be susceptible.



Right now patients are routinely given more than the 2 pills a day for 5 days (10 pill course) of Tamiflu, and still, many of them die.  There are trials underway looking at whether a `double the dose for double the duration' will improve survival.  


In other words, instead of 10 pills, a course would require 40 pills.


In a country like Britain, one that already has enough tamiflu at the lower dose to treat 25% of their population, an increase in the dose to 40 pills would reduce their coverage to roughly 6%. 


The United States, which currently only has enough Tamiflu on hand to treat about 15% of the nation (at the lower dose), would be down to only enough for 4% at the higher dose.


Of course, we don't know if the higher doses will improve patient outcomes.  Early data suggests that it might, but no controlled studies have been completed.


And this only figures treating people already infected. It provides nothing for prophylaxis. 


But let's use the 10 pill course for now, even if it may prove woefully inadequate in the future.   The United States, which after two years is still a year away from achieving a 25% stockpile,  would need another 160 million courses of the medicine under these guidelines.  The UK, another 30 million Courses. 


Even at the heavily discounted price governments pay for the stuff, this is hardly chump change.   We are talking billions of dollars to purchase, and it has a limited shelf life.  Then there are storage costs, distribution costs during a crisis, and some real problems with the dosing being purchased.


Almost all of the Tamiflu purchased by the United States  has been in the form of 75mg capsules, used for the Adult dose.  Out of 50 million courses, reportedly only 100,000 are in the pediatric liquid form.   Since we are stockpiling for a disease that strikes the young, buying 99% of our Tamiflu in adult formulation doesn't make a lot of sense.


And for children  under the age of 1 year old, Tamiflu is an unapproved drug.


There are concerns that Tamiflu may cross the immature blood brain barrier in infants, and cause brain damage.  Additionally there are reports that children and teenagers, mostly in japan, have on rare occasions experienced neuro-psychiatric side effects while on Tamiflu, resulting in a small number of patients attempting suicide.


There are studies ongoing, and expected to run into 2009, testing the safety of Tamiflu for infants.  Roche labs is said to be investigating the reports of side effects in teenagers.


So, Tamiflu isn't a panacea.   And there is a risk that once it is put into play combating a pandemic, overuse could drive the virus to become resistant, rendering the remainder of the stockpile pretty much useless.


Buying more Tamiflu is, admittedly, a risk.


But right now, it is the only game in town.    Without a vaccine, antivirals are our best weapon against influenza.  We either have them, or we are reduced to NPI's (Non-pharmaceutical Interventions) to limit the spread of the disease. 


The government obviously needs to stockpile more pediatric doses of Tamiflu. The idea that we only have enough for 100,000 children is ludicrous. There are 40 million children under the age of 10 in the United States.  If only 25% are sickened (a low estimate), then we'd need 2.5 million courses.


Governments, I'm sure, are going to be reluctant to spend billions of dollars to stockpile more Tamiflu.  And by looking at the facts, tripling the number of doses may not be enough.  A 75% coverage with an inadequate dose is better than a 25% coverage, but it doesn't get the job done.   If the 40 pill course is eventually adopted, that 75% coverage drops to 19%.


While more stockpiling is needed, at the same time we should enable our citizens to buy Tamiflu, at a discount and without a Rx, to keep on  hand in their homes.  


Right now, the price of Tamiflu is ridiculously high.  A 10-pill course, retail, runs as much as $100.    The government buys that same course for a fraction of that cost.   Roche could probably lower the price to the public by 70% and still make a profit.


Doctors have been reluctant to write scripts to patients who want to have tamiflu on hand because the government has warned them not to. They wanted first dibs on the existing supply.    We should remove that restriction, or better yet, make Tamiflu available over-the-counter.


Millions of American families would probably buy enough tamiflu for themselves if the price were reasonable, and the government was recommending it.  That would move the burden of buying much of the tamiflu from the government to individuals, and it would also mean that the medicine would be in the hands of the public when a pandemic began.


Worries that the public isn't responsible enough to keep some Tamiflu in their sock drawer for a rainy day are misplaced.   PSA's urging people not to use it unless a pandemic has erupted could be run on radio and TV stations, and would likely be very effective.  



People aren't as dumb as their governments like to believe.



Could it all be for naught?   Could Tamiflu end up being useless in the face of a pandemic?


I suppose so.  It's a gamble. 


But right now, we don't have a lot of options.  We either fight using the tools we have, or we accept whatever a pandemic throws at us.


Scott McPherson said...

The solution is probenecid, my good man!

npro said...

Dear Fla_Medic,

Have you bought Tamiflu - in what strength? Did you buy it for your children? For you ex-? For your favorite teachers? Did you buy it online?

speak up

FLA_MEDIC said...

Scott, probenecid is the solution my doctor and I have chosen. ;)


I've relayed before in this blog that I purchased Tamiflu for my personal use.

I discussed it with my physician, and we talked about the fact that both of us would be exposed caring for patients during a pandemic. He wrote an Rx for my ex-wife, and for myself. 75 mg capsules. Along with a Rx for probenecid.

I made my purchases from a local pharmacy.

What you should have on hand, and what is appropriate for you based on you own personal health, is something best determined in consult with your doctor.

All prescription (and most over-the counter) medicines have risks. None are 100% safe. Each person needs to make an informed decision based on the risks and benefits of each drug, or combination.

There are some people for whom probencid would not be a good solution. It can react with a variety of medications. In some European countries, I've heard it isn't even available.