Tamiflu is our first line of defense in preventing and treating H5N1 human infections. It is utilized as a prophylactic, HCWs and poultry flock cullers often take it to prevent infection in a known high risk environment, it has also been used on occasion to give close contacts of confirmed or highly suspected cases. When a Tamiflu Blanket is mentioned, this is what they are referring to.
Of course, it is also the primary treatment for human infection, and while not perfect, it is, currently, the best available treatment, affording the highest chance of survival. Its success is the reason that governments around the world have or are building a Pre-Pandemic supply.
Private businesses, of all sizes have either stocked, or are trying to stock Tamiflu for their critical personnel. This would theoretically entice those workers to report to the job, keep them alive to perform it should they become infected, thus ensuring, theoretically, the continuity of the business.
While Tamiflu is currently our best defense, until we get a functional vaccine in place, ready to deploy, it is expensive, difficult to manufacture, under a patent held by one company, Roche Pharmaceuticals, and demand is far outstripping supply.
The final stressor on the limited supply is the suspected need of doubling the dosage over a longer period of time, a study spearheaded by WHO of this theory is currently getting under way. So, anything that would effectively stretch the on hand stocks, both public and private would be a monumentally good thing, or you would think so anyway.
Probenecid burst onto the Cyber Flu scene the end of October 2005 with Declan Butler's piece in Nature Wartime tactic doubles power of scarce bird-flu drug: Use of common drug could stretch world stocks of Tamiflu.
Doctors think they have hit on a way to effectively double supplies of a drug that fights bird flu. Administering Tamiflu alongside a second drug that stops it being excreted in urine means that only half doses of the treatment would be needed.
Tamiflu (oseltamivir phosphate) is the main antiflu medicine recommended by the World Health Organization (WHO). The WHO suggests that, in anticipation of a flu pandemic, countries should stockpile enough for at least a quarter of their population. But although Swiss drugmaker Roche, the sole supplier, has quadrupled its production capacity over the past two years, the current supply is thought to cover just 2% of the world population.
Last week, Joe Howton, medical director at the Adventist Medical Center in Portland, Oregon, suggested a way to double supplies, after browsing basic safety data from Roche for a talk on avian flu.
The technique was invented during the Second World War to extend precious penicillin supplies. Scientists found that a simple benzoic acid derivative called probenecid stops many drugs, including antibiotics, being removed from the blood by the kidneys. Probenecid is readily available and is still widely used alongside antibiotics to treat gonorrhoea and syphilis, and in emergency rooms, where doctors need their patients to have high, sustained levels of antibiotics in their blood.
. . . [And the article closes:]
Like many scientists, Fedson is stumped by the apparent lack of interest from Roche, and the relevant authorities. "It's stupefying," he says.
This information broke 17 months ago, beyond its repeated mention amongst the Flubies it gets no play or mention. Several physicians who are active in Flublogia (the cyber pandemic flu community) have endorsed the idea of using Probenecid in combination with Tamiflu, although it would be an "off-label" usage. Dr Grattan Woodson, perhaps one of the most well known Physician Flubies posted his comments about the concept at the original Fluwiki, the entire piece by him on Tamiflu found at the link is worth a read but I will just include the Probenecid portion here.
Using oseltamivir in combination with probenecid
While preparing a presentation on Bird Flu for his colleagues at Portland Adventist Medical Center in Oregon, Joe Howton, MD, Medical Director, Emergency Services at the hospital, ran across an obscure comment in the product information on the antiviral drug Tamiflu® used for treatment of influenza. The comment was in the section on safety and drug interactions and referred to the results of safety studies that were completed before the drug was approved for use. The finding was that when Tamiflu was given at the same time as another commonly used drug, probenecid which is used to treat gout, the blood level of Tamiflu doubled and the time it remained at effective levels in the body increased from about 8 hours to more than 20 hours.
This finding astounded Joe. He immediately realized its importance given our concerns about Bird Flu and the present severe shortage of Tamiflu. He understood that this means that if it were safe to give Tamiflu in combination with probenecid, it would increase the clinical effects of each Tamiflu tablet significantly and this would starch the available supply.
When Joe called me about this to see what I thought, at first I was a bit skeptical. Why hadn’t someone else figured this out before now? Besides gout, probenecid has been indicated for increasing penicillin blood levels and the length of time it stays in the body for years. So, it was not much of a stretch to think of it for use with Tamiflu especially since we are facing such a shortfall of this drug. So, I spent the night and much of the next on the National Library of Medicine’s web site and reading my trusty Goodman and Gilman Pharmacology Text and sure enough, Joe was right. Tamiflu levels could be increased as can the length of time it stays in the body fighting the virus by combining it with probenecid. I had used probenecid for as long as I had practiced, over 25 years now, and regarded it as a reliable old standby in my pharmaceutical armamentarium. What made this discovery all the sweeter, it is generic and relatively inexpensive at a cost of about $20 for a 10-day treatment course.
During my investigations, I discovered that infectious disease doctors worldwide were already using probenecid to increase the levels of drugs used to fight tuberculosis and HIV-AIDS, but did not find any references to using it intentionally with Tamiflu for this purpose. The way probenecid increased the effects of these drugs, including Tamiflu, is exactly the same way it increases the level and effective blood levels of penicillin. This was very reassuring. I was not too concerned that the combination of probenecid with Tamiflu was not formally approved by the any regulatory agency like the US FDA since every day, as a doctor who takes care of people, I find myself using approved drugs for “off label” indications. This is a perfectly acceptable and established practice as long as the doctor has good reason to believe that it will be of benefit to his or her patient.
In my opinion this is an important finding. We all owe Dr. Howton a debt of gratitude. While this novel combination does not solve our Bird Flu problem by any stretch of the imagination, it does mean that suddenly the world has the equivalent of two-and-a-half times more Tamiflu in the world’s stockpile now than we thought. What’s more, the Tamiflu produced from this point forward will also go two-and-a-half times further than we originally thought. Of course, this all depends on our ability to ramp up probenecid manufacture, which I believe can be accomplished rather quickly and inexpensively. On the whole, this is one of the few pieces of really good news concerning the Bird Flu pandemic that I have heard since becoming concerned about it in 2004.
Since this information hit 17 months ago it is hard for me to understand why it hasn't been "officially" looked at, but more importantly, why it isn't being loudly trumpeted. In fairness, perhaps it is being whispered about in the official circles that need the information but where does that leave the individual that is trying to prepare for themselves and their family? It leaves them out in the cold unless they just happen to stumble upon the information.
As always, I am not recommending Probenecid to anyone, I am providing a simple summary of what information is available on a promising option. What I have personally planned I did so only after researching the issues. Nothing is risk free and that includes using Probenecid. Should you decide that Probenecid holds potential benefit to your personal pandemic preparations I strongly suggest you research the issue on your own, weigh it against your individual needs and potential risk vs. benefit scale, as it does have potentially dangerous side effects. A listing of advisements and cautions can be found here.
We, as average citizens, are not helpless, even in the face of something as difficult and horrific as a severe pandemic. There are things that we can and should do for ourselves to strengthen our possibility of survival, ours and those we love and care about. But in order to take those actions we need information, good information, or what I like to term Best Available Information. This post is dedicated to the practice of that concept.