Colorized transmission electron micrograph of Avian influenza A H5N1 viruses (seen in gold). Image provided by CDC/C. Goldsmith, J. Katz, and S. Zaki.

Support for a Personal Tamiflu Stockpile

By Grattan Woodson, MD, FACP

It is responsible and ethical for physicians to prescribe Tamiflu for their patients to stockpile and use later during a possible Bird Flu Pandemic. Presently the risk of an influenza pandemic is high. The severe shortage of Tamiflu, the lack of an effective H5N1 pandemic influenza vaccine, and my lack of confidence in the ability of the government to respond to an emergency on the scale of an influenza pandemic are all critical factors in my choice to support the practice of prescribing Tamiflu to patients for private stockpiles. Nationally there is a woeful lack of preparation to respond to this serious public health issue. My position differs from most government and medical bodies who have expressed an opinion. In this brief paper, I provide the rationale for why I think it is both practical and ethical for doctors to prescribe and patients to obtain Tamiflu prior to the pandemic.

The Tamiflu Shortage

The World Health Organization (WHO) has recommended that every country establish a stockpile of enough drugs to treat 20% of its citizens in preparation for a possible avian influenza pandemic.1 Most of the developed nations followed the WHO recommendations Image of the Tamiflu pill. except for the US who hesitated placing their order until recently. The CBO stated in a recent study of the macroeconomic effect of influenza pandemic on the US, that by the end of 2005, the US Strategic National Stockpile would contain enough Tamiflu for 4 million five-day treatment courses and 84,000 Relenza treatment courses.2 This is enough for about 1.4% of the US population assuming that the standard treatment regimen will be effective for Bird Flu. This dose and the length of treatment with Tamiflu for Bird Flu is currently under review by infectious disease and public health experts. There is a good chance that they will recommend that the dose and course of therapy both be doubled.3 If so, this would reduce the coverage by 75%. The US belatedly placed an order for 12 million additional treatment courses from Roche but the company has stated that they are at full manufacturing capacity now and the orders are to be filled on a first come first serve basis. Since the US was one of the last countries to order the drug, Roche has informed the US Department of Health and Human Services (US DHHS) that it will not begin to fill the US order until late 20072.

Tamiflu manufacture by both Roche and by other companies is being ramped up, but this process takes time. We cannot expect this antiviral drug to be widely available in sufficient quantities in the event of a major pandemic in the next few years.

The Lack of a Pandemic Flu Vaccine

A father and child wearing masks.

The pandemic strain of H5N1 has yet to emerge. Until it does so, only prototype vaccines, of unforeseeable efficacy, can be made using viral samples from earlier cases. When the actual pandemic virus begins to spread, there will not be any vaccine doses available for anyone for at least six months. If the pandemic lasts for 18 months, under the best conditions vaccine production will be adequate for no more that 30% of Americans. During this period, Tamiflu (and Relenza) will be the only option for effective medical treatment of pandemic flu available to most people.

 

Would Personal Stockpiles of Tamiflu Be Properly Used?

In the December 22, 2005 issue of the New England Journal of Medicine, Anne Moscona, M.D. argued “personal stockpiling of oseltamivir is likely to lead to the use of insufficient doses or inadequate courses of therapy. Shortages during a pandemic would inspire sharing of personal supplies, resulting in inadequate treatment. Such under-treatment is of particular concern in children — the main source for the dissemination of influenza within the community, since they usually have higher viral loads than adults and excrete infectious virus for longer periods. The habit of stopping treatment prematurely when symptoms resolve (a well established tendency with antibiotic therapy) could also lead to suboptimal treatment of influenza and promote the development of drug resistance.” Her conclusion is “Improper use of personal stockpiles of oseltamivir may promote resistance, thereby lessening the usefulness of our frontline defense against influenza, and should be strongly discouraged.” These sentiments are being widely supported in the public health and infectious disease community.4

I disagree. First of all, I reject the idea that people who use Tamiflu out of their private stockpile will misuse it. While there are segments of the population that may be unable to self-administer drugs properly, these are probably not the same people who are interested in obtaining a personal Tamiflu stockpile. In my experience, the people who have requested a Tamiflu prescription from me for the purpose of establishing a personal stockpile Sick child lying in bed.have researched the issue thoroughly and are very clear on the indications for use, timing of the dose, and treatment course. They probably know these things better than most doctors who rarely prescribe Tamiflu. Interestingly, this lack of experience prescribing Tamiflu is often due to the fact that by the time most patients seek treatment for the flu, it is too late in the course of the illness to start it.

For the administration of the Tamiflu in a timely manner, I can hardly think of a better place for the drug to be stored than in the house of the person coming down with the flu. With respect to being able to take the drug within 2 days of the beginning of symptoms, what could be better? It is important that the person deciding when to start the Tamiflu have a good grasp of what flu symptoms are so they don’t waste their precious drug. I provide this information to my patients and find that similar information is available in many places on the Internet today.

President Bush smiling at the dais. I advocate physicians prescribe drugs for their patients that will be useful for the management of influenza before they become scarce, an event likely to accompany the pandemic as it emerges. Specifically, I think it is prudent for patients to have Tamiflu, over-the-counter and other prescription drugs stored at home for personal use during a pandemic. As is the case any time we prescribe drugs, a key responsibility is to ensure that the patient is provided with specific advice on how to use these medications properly.

 

An influenza pandemic could begin at any time now. Under these circumstances and considering the inadequate national pandemic preparedness, I think it is both prudent and responsible for practicing physicians to give patients access to Tamiflu if they want it. This is especially so since it is well understood that once the pandemic starts, most of these people will have no chance at all of getting any.

Bird Flu resistance to Tamiflu

One of the arguments used by opponents of patient stockpiles of Tamiflu is that their misuse or even their use of the drug could result in higher rates of oseltamivir resistant H5N1 Bird Flu. Based on our experience with all other antiinfective agents, this is a true statement and will happen irrespective of how the or by who the drug is administered. A unique and truly interesting fact concerning Tamiflu resistant strains of influenza is that they are less infective and have lower virulence and lethality compared with non-resistant strains. This means that inducing Tamiflu resistance in Bird Flu could have beneficial effect. In fact, I think it might give us something we can exploit to lower the severity of Bird Flu infections. This finding has to do with the way the virus has to change itself to avoid Tamiflu. While making this change allows the flu to escape the effect of Tamiflu it also partially cripples itself by making it much harder for it to infect the cell and kill it. In other words, Bird Flu without the Tamiflu resistance mutation is much more deadly than those with it. So, this may mean that Tamiflu could be useful for treatment of Bird Flu even if there is a high prevalence of Tamiflu resistant avian influenza strains in the community. The drug would be useful by selecting out the weaker members of the viral family as the ones that got through the Tamiflu defense while screening out the stronger members.

The Tamiflu ration plan

The present ration plan announced by CDC is that the stockpiled Tamiflu and vaccine once it becomes available will be reserved for first responders, medical personnel, vaccine manufacturer employees, children aged 0-14, An elderly couple at the kitchen table.adults age 50 and older, adults age 15 – 49 with chronic disease, then healthy adults aged 15-50. If there is not enough to go around, they plan to give it to the medical and vaccine drug manufacturing personnel only. Over the 12 to 18-month course of the pandemic, the US DHSS Pandemic Influenza Plan predicts that 30% of the population will become sick3 Obviously, there will be a shortfall in the supply of antiviral drugs and specific vaccines during the pandemic if it occurs anytime over the next 2 years, a highly likely possibility in my view. Since pandemic influenza is a life and death issue, the formulation of this plan is tantamount to deciding who shall live and who shall die in advance. These are thorny issues and raise a lot of questions. Here are a few examples for you to ponder:

  1. In the typical flu season, the elderly and those with chronic diseases are at much higher risk from flu complications than young healthy adults. During a severe 1918-style pandemic, the young and healthy are at as high or greater risk as the elderly. Given these conditions, who should be given Tamiflu, the dependent population of chronically ill and elderly or independent and future population of the healthy adults and children?
  2. Whose Tamiflu is it, anyway?
  3. What is the best use of a limited resource?
  4. Who should and will decide who will get the Tamiflu? A grandmother and her granddaughter look over a recipe.
  5. Your family is allocated one course of Tamiflu. Your healthy 70 year old mother and 14 year old daughter are both ill with Bird Flu. Who are you going to give the medication to?
  6. Can the governmental agencies tasked with the management and distribution of Tamiflu be expected to carry out their responsibilities in an adequate and timely manner?

Because opinions differ about these things, it’s useful to have this discussion now.

In summary, the facts that support the establishment of a personal Tamiflu stockpiles by individuals who desire to do so include:

  1. The US Government’s failure to obtain adequate supplies of antiviral drugs even for those on its priority list.
  2. Questions about the wisdom of the current priority list rankings of different population segments.
  3. The unavailability of an efficacious pandemic vaccine for a least 6 months after the beginning of the pandemic that will be adequate for no more than 30% of the population during the course of the pandemic.
  4. The government’s failure to properly distribute emergency supplies even when they have plenty of warning and they are pre-positioned. If you doubt this, study the Katrina Hurricane disaster response.
  5. The certainty that US Government will seize all Tamiflu in warehouses at the time the Pandemic begins. Those interested in obtaining this drug for use during the pandemic must therefore purchase it before it begins
  6. That Tamiflu resistance may not be as bad a problem as it is being made out to be and in fact may improve the chances of survival for some patients.
  7. My belief that patients have a right to make this decision for themselves and that those who chose to obtain a personal supply of Tamiflu will use it responsibly.

I support the practice of prescribing drugs for the treatment of influenza for patients to stockpile in anticipation of a pandemic. Practitioners writing these prescriptions have an obligation to ensure that the patient has thorough instructions on how and when to employ these agents. Last year I wrote a pamphlet for my patients on the Bird Flu. It includes a list of drugs that will be useful for treatment of severe flu patients at home including Tamiflu. An important part of this work is a discussion of how and when to use these medications properly. I give this document to every patient to whom I write these prescriptions. In my opinion, this is an essential element required for this to be a good clinical practice for the physician.

Acknowledgment

David Jodrey, PhD assisted in the preparation and editing of this article. His sage advice and deft editorial guidance is greatly appreciated by the author.

1 WHO Global Influenza Pandemic Preparedness Plan, July 2005. Return to article.

2 A Potential Influenza Pandemic: Possible Macroeconomic Effects and Policy Issues. The Congress of the US, The Congressional Budget Office, December 8, 2005, US Government Printing Office. Return to article.

3 Moscona, A., Tamiflu Resistance Disabling Our Influenza Defenses N Engl J Med 2005: 353; 25 Return to article.

4 Joint Position Statement of the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America on Antiviral Stockpiling for Influenza Preparedness October 31, 2005; http://www.idsociety.org Return to article.