Sunday, December 10, 2006

The Antiviral Debate

# 241

Beyond the actual debate over the probability of a pandemic, the biggest squabble in the flu world appears to be over Tamiflu. Is it any good? Is it dangerous to take? How much should governments stockpile? And should individual citizens have their own supply on hand, just in case?

Like just about everything else surrounding a potential pandemic, there are no easy answers.

First, a little background, then I’ll address each of these questions in turn.

The H5N1, or bird flu virus, is a novel influenza type-A virus that has produced an extraordinarily high mortality rate in the limited number of humans infected. To date, more than 60% of those infected have died. Should this avian flu become a pandemic, and retain its current lethality, the death toll could be enormous.

Beyond palliative care, and the use of antibiotics to combat secondary bacterial pneumonias, the only real treatment has been the use of antivirals. While there are several available, Tamiflu has been the one most commonly in the spotlight. Others include Relenza and (maybe) Amantadine.

Is it any good?

While Tamiflu is certainly no cure, it has so far apparently been useful in reducing the viruses rate of replication in the human body, reducing the symptoms and longevity of the infection.

In patients who receive the drug early enough, and in sufficient quantity, it appears to improve the survivability rate. In Turkey, where Tamiflu was dispensed rapidly, the mortality rate last spring was half that of Indonesia. There are other factors involved, however. Different strains of the virus, presumably faster diagnosis, and better medical infrastructure, and so no one really can say with certainty how effective the Tamiflu really was.

For now, Tamiflu does appear to give an infected patient a much better chance of recovery. But it should be noted that no controlled studies have been done on Tamiflu and the H5N1 virus. There are questions, as yet unanswered, as to how well it works, and if it works across all age groups.

There is a deep concern that as this virus evolves, it may become resistant to Tamiflu, and hence the recent calls for the stockpiling of Relenza. For now, despite these concerns, these antivirals remain our best hope for treating avian influenza.

Is it dangerous to take?

Over the past year there have been a small number of reports of adverse reactions to Tamiflu; a few hundred out of millions of prescriptions filled. While no direct link between the Tamiflu and the side effects has been established, this is worrisome. Some of these side effects have reportedly included psychiatric disturbances, and suicides, particularly in teenagers.

There is, of course, no such thing as a truly innocuous therapeutic medicine. All drugs carry some risk of adverse reactions, even those purchased over the counter. Doctor, and their patients, must make a value judgment as to whether the benefits outweigh the risks.

As long as the H5N1 virus remains sensitive to Tamiflu, and the CFR (Case fatality ratio) of the virus remains high, the benefits of taking Tamiflu appear to far outweigh the risks.

How much should governments stockpile?

The obvious answer is: As much as they can.

And governments are attempting to do so, with varying results. The worldwide production of Tamiflu isn’t enough to cover even 10% of the population, and so it would take years, and increases in our production capability, to have enough for everyone.

The Canadian government announced yesterday that their target was to have 55 million doses of Tamiflu stockpiled. That sounds pretty good, until you realize they are speaking in terms of individual pills. The absolute minimum course of treatment is 10 pills, and many researchers believe that 20, 30, or even 40 pills per patient might be required.

So, at best Canada has (or will have) enough Tamiflu to treat 5.5 million citizens. Roughly 18% of their country. If it requires 20 pills per patient, that percentage drops to only 9%.

The United States has more pills, but a larger population to cover. Right now, we have about 20 million 10-pill courses, enough to cover 6% of the nation at the minimum dose.

Some countries are stockpiled with enough to cover 25% to 30% of their citizens. Kuwait reportedly has enough to cover 100% of their country.

The assumption is that a pandemic would strike 30% of the worlds population. While there are reasons to believe that number is optimistically low, government-stockpiling targets have been devised based on that number.

Given the limited production of the drug, the cost, and the real possibility that by the time the virus evolves into a pandemic strain, that our current antivirals may no longer be effective, governments are faced with a terrible dilemma.

Should individual citizens have their own supply on hand, just in case?

Ideally, I’d say `yes’.

I know this goes against government recommendations, and given the scarcity of the drug, and the difficulty in getting an Rx, is probably a moot point. But I’ll state my case, anyway.

Early indications are that to be effective, Tamiflu must be administered within hours of the first signs of infection. Wait 24-48 hours after fever, body aches, and respiratory symptoms appear, and the efficacy of the drug drops markedly.

While the governments of the world claim that their strategic stockpiles will be quickly distributed, and they are working on elaborate plans to get the drug into the hands of infected patients, it requires a hefty leap of faith to believe that most patients will get the drugs in a timely fashion.

Add to this the fact that the United States government stockpile, right now, only has enough to cover 6% of the nation, and the odds that you or I would actually see the drug grow slimmer. By the end of 2008, two years from now, the U.S. hopes to have enough for 25% of the country. But once again, that assumes the minimum 10-pill course.

The government has done all it can to discourage personal stockpiling. It has issued strong advisories to doctors, telling them not to prescribe the drug unless a patient is actually suffering from influenza. Most, but not all, doctors are complying.

The government, and many health authorities worry that individual stockpiling will result in many people who don’t need the drug having them go unused, while others who desperately need it won’t have it. They are also concerned that people might take antivirals for a cold, or common seasonal flu, instead of for pandemic flu.

Both are compelling arguments.

But the government has told us; time and again, we are on our own should a pandemic strike. That we should not expect FEMA, or the federal government to come to our rescue. They will have their hands full, just keeping things running at the federal level.

I take them at their word.

And so, given the meager national stockpile, and the likelihood that should my family need it, antivirals will not be available in time, I think it is prudent to have them if you can get them.

Of course, getting them is the catch.

It requires a sympathetic family physician, and fairly deep pockets to stock up on Tamiflu. Roughly $200 per person. Amantadine, while far less expensive, is less likely to be effective (some H5N1 strains are already resistant), but may be better than nothing. Relenza, which must be inhaled, is also expensive, and difficult to obtain.

And none of these are guaranteed to work during a pandemic.

My strictly non-professional advice is to talk to your family physician, and try to obtain a legal supply from a reputable local pharmacy. Ordering off of the Internet, or through offshore pharmacies, exposes you to the risk of receiving counterfeit, and worthless drugs. Fake Tamiflu is a big business these days.

For those who cannot afford enough of these drugs to treat their entire family, it might be worth considering having just enough on hand to start an infected family member on them until you can get access to the strategic reserves. A single 10-pack would provide 5 days worth of slack, which would allow 5 family members 24 hours each to receive the meds from the government. The peace of mind that would provide, and the safety margin, would be worth the expense to many.

In the end, it is a personal choice, of course. Tamiflu is expensive, difficult to get, and may or may not be useful when the time comes.

But it is one you should consider now, while there is still a choice to be made.

1 comment:

cathydonna said...

My greatest fear is getting Tamiflu for my three grandchildren. I asked my daughter-in-law in the winter of 2005 to ask the kid's doctor for a prescription for it and she was told, "If the bird flu does arrive, there will be enough antiviral to go around." I tried, as diplomatically as I could, to explain to her that there's a good chance they're wrong. But she's not the type that wants to confront her doctor without a very real problem present.
Of course, it is difficult to prescribe a medication that goes by weight. If my daughter-in-law were to obtain a prescription and got it filled, it might well be out of date by the time the flu arrived. Meaning that each child may of gained enough weight to make the prescription worthless and she would need to obtain another one.
I'm still of the opinion that if you can get a child's prescription for Tamiflu it's still worth it as you may be able to alter it to conform to a child's current
weight at the time of an outbreak, i.e. give twice the original dose. There's no use asking my daughter-in-law to ask her doctor again as it's getting just too difficult now to get a prescription
and her request has already been refused once.