Talk:Oseltamivir/Archive 1

Archive 1

Archive 2

Archive 3

Anti tamiflu bias

Someone has gone through this article and introduced unbalanced scepticism into every paragraph, usually at the start, this is very non nPOV and is essentially vandalism. It mostly originates with a dispute between the BMJ and Roche over the release of data, but the effectiveness of Tamiflu is not seriously in doubt beyond the obvious issues about viral resistance etc...--Hontogaichiban (talk) 06:12, 18 August 2013 (UTC)

Actually the effectiveness is in doubt. Part of science includes independent analysis and an ability to repeat previously done studies. Independent analysis is not being allowed in this case. Please note that new conversations should be added to the bottom of the talk page. Doc James (talk · contribs · email) (if I write on your page reply on mine) 03:07, 19 August 2013 (UTC)

A recently updated study showed that it "might reduce the duration of flu symptoms by half a day ... there’s no evidence that it reduces hospital admissions or complications of an infection" so perhaps the article should make this more clear that it's ineffective aside from maybe reducing symptoms by 12-24 hours when taken during the onset of the virus. 74.202.214.134 (talk) 16:51, 18 April 2014 (UTC)

I will agree that, simply skimming from the top, this article reads like an article that is biased. An article should start with fundamental baseline information, not with a lede that jumps immediately to a summary of articles saying it doesn't work. Perhaps the article isn't in fact biased. But if it's not, it should be rewritten so that it doesn't so closely mimic a biased article.Geoffrey.landis (talk) 16:30, 5 December 2014 (UTC)

Resistance

This section is in serious need of an expert rewrite. It suffers from fragmentation and a poor overview of the research on resistance to oseltamivir in general. I am not a doctor nor an epidemiologist or infectious disease specialist, so I certainly can't do it competently. — Preceding unsigned comment added by 24.242.201.62 (talk) 22:55, 7 November 2011 (UTC)

So who scrubbed all the references to Rumsfeld's stock in Tamiflu from this article?

Typical Wikipedia. This is relevant information. —Preceding unsigned comment added by 71.238.27.47 (talk) 22:46, 30 April 2009 (UTC)

use in avian influenza section: Tamiflu skeptics, annoying misquotation, the bastard John Oxford

Our Use in Avian Influenza section is tilted against tamiflu fashion. I just discovered a serious misquotation. But the web is tangled.

WIKIPEDIA:Sir Liam Donaldson, UK chief medical officer states in the British Medical Journal that oseltamivir has "lack of convincing evidence" of benefit in treating avian influenza.

The statement in the source cited? "Sir Liam Donaldson, England's chief medical officer, has noted that doctors have little idea how effective oseltamivir antiviral tablets would actually be during a pandemic." It was the journalist's opinion in the article that there is "a lack of convincing evidence that it will have any real impact on an influenza pandemic."

We need to be careful here about differentiating the efficacy of Tamiflu on treating individuals and on dealing with a global pandemic. These are different (though related) issues, and uncertainty surrounds both. If tamiful doesn't help individuals, of course it isn't going to help the pandemic from spreading. But, there's evidence that it may help individuals keep their viral loads down substantially, and thus evidence that it could help individuals survive H5N1. Lots of uncertainty, but not an utter lack of evidence. If Tamiflu helps individuals, it's a second question whether tamiflu can stem the tide of an epidemic: maybe there's not enough to go around, or maybe resistance to the drug will develop, or maybe the drug will help only a percentage of people treated, but not enough to slow down an epidemic.

HOWEVER, be careful about media stories which cite Professor John Oxford of Queen Mary College, London. The article which was miscited above is an interesting article. It's about how people funded by Roche have effectively built up Tamiflu's fame in the media. Oxford is a professor who is often cited giving strong positive assessments of Tamiflu's usefulness for treating avian flu, but he has financial ties to Roche which are rarely mentioned in the media which quote him. I was about to cite a new BBC article in support of my view that tamiflu drops viral loads and therefore helped people survive. But looky there! It's built on John Oxford quotes!

Still, stuff I've read elsewhere in the literature does indicate that tamiflu affects viral load, so the argument may be sound. It does, however, show how far the pharmaceutical corporations propaganda extends when news articles are so subtley skewed.

Recent changes have gone a little too far

Thanks very much for the efforts to clean this page. I accept that editing needed to be done, and that in some place serious cuts were warranted. However, I think some important information has been lost. For example, the dosages section had at least tried to show that there were different dosages and indications for different countries and this has been removed from the page. The adverse effects section is loses out some because there's no longer any presentation of which side-effects are more likely to occur. Finally, I accepted some edits to the probenecid section, but I restored some. My justifications were that as a reader *I* would want to know about the penecillin connection in WWII, and I would want a link not only to the 2002 article, but a good source on how it has been interpreted in 2005 (interpretation was absolutely missing from the 2002 study). I cut Techelf's sentence that "this is not in common practice". Of course it isn't in common practice, we've I don't think we've faced a local situation where Tamiflu was a functionally limiting in treatment, nor do we have a global human pandemic on our hands yet. The amount of Tamiflu that has been used so far to treat human cases of H5N1 is tiny compared to stocks on hand, or the amount currently being produced. On the other hand, I don't think that probenecid co-treatment has been certified by any governing medical bodies as the thing to do, but they're all still making this up as they go along. At any rate, the Nature news article I restored is important and gives critical perspective on the probenecid issue. Of five scientists and doctors quoted, four are strongly positive on the use of probenecid and the fifth simply points out that even in doubling the supply of tamiflu, there still would be a shortage. Neurological section I would have preserved more links here. As a rule I don't rely solely on institutional sources, such as the FDA. Clearly they are important, but they don't always convey the full picture. Pigkeeper 15:47, 21 February 2006 (UTC)

Hi Pigkeeper, thanks for your recent edits and overall contribution to the article. I'm not too sure what you mean by "different doses and indications for different countries", since the drug is new enough that these are pretty much the same across the world. The ADRs section does actually separate occurrence into "common" and "rare" (if you're interested, the AMH defines "common" as ≥1% of patients, and "rare" as <0.1%). And I agree with your points about probenecid, but I wanted to focus the mainstream information – though what is there now seems to be a good balance. I too agree that probenecid could potentially extend our limited supplies of oseltamivir, although I'm not quite famous enough to be quoted yet. =) And I don't entirely rely on the FDA either (for one thing I'm not American), but it seemed like the most comprehensive/reliable/accessible source for that particular section (it was impossible to find relevant information on the Japanese PMDA site). I removed the links about particular deaths from oseltamivir because: (i) the ones mentioned are surely not the only deaths associated with the use of oseltamivir, (ii) media outlets are not reliable reference sources, and (iii) the links were broken anyway. While unfortunate, I do not feel that it is relevant to be citing specific cases of deaths associated with oseltamivir – it is more objective simply to point out deaths have occurred. Btw, I deliberately placed less emphasis on the Tamiflu PI from Roche for similar reasons to what you said about the FDA. =) Anyway, it's great that we're able to discuss these matters. Cheers. -Techelf 09:33, 22 February 2006 (UTC)

Hi Techelf. Thanks for replying. Fair points on ADRs, thanks. I'm okay with the current neurological section, although i disagree as to whether media sources are reliable--I would say they are "differently reliable", not unreliable.  ;-) I'm glad we've got consensus on the probenecid.

Indications and dosage are NOT the same across countries. For example, at least at the time of the writing of this document [1], oseltamivir was NOT indicated for prophylaxis in the UK, and NOT approved for children under 12 (although the news article I'd had quoted (now gone) said that it had been approved in the EU for <12 in case of a pandemic). Also relevant (although maybe too detailed for this wiki article) is that dosage differences for children between the US and Japan have had relevance for resistance.

Finally,, (and this is my anal side coming through), what's up with the citation form? Citations are supposed to come BEFORE periods (wiki Harvard refs page).

anyway, thanks for all of your work on this page. it is much appreciated. Pigkeeper 17:00, 27 February 2006 (UTC)

No worries. My British National Formulary (BNF 47) does give prophylactic and childrens dosages, so I guess it might've just been omitted from that website you linked to. And no, I don't know what's with my citation form either. Probably just a habit from using Uniform Requirements for Manuscripts Submitted to Biomedical Journals style in my other writing, and which I've slowly been trying to standardise across biomedical articles on Wikipedia (though modified using author-date in body text for clarity). You're right, the reference in brackets/parentheses probably should go before the full stop/period. -Techelf 07:54, 28 February 2006 (UTC)

Quality

What still needs to be done before the quality tag can be removed? I think we're pretty much there. Sjcodysseus 19:15, 18 January 2006 (UTC)

• Remove it. Maybe the article could still use some copy-editing or whatever, but clearly the cleanup template isn't warranted. I'd remove it myself, but I think that honour belongs to one of the guys who did all the work. ;) Some possible improvements: The paragraph on chemical synthesis seems a bit overly complex/long/cluttered, I can barely read it... are all the wikilinks necessary? The quote in a box at the start of the page is fairly short for its own box. And finally, the paragraphs in the introduction are all fairly short (one or two lines depending on resolution), maybe some of them can be fused into a single paragraph. But those are minor nitpicks - great work! --Moritz 19:36, 18 January 2006 (UTC)

I was the one who put the cleanup flag on this page. Essentially, the reason I put it there originally was not because of the content per se. Rather, it needed a cleanup (and perhaps still does) because of the style of the article – a few things that come to mind are that the narrative isn't particularly consistent and that there is still some very patchy information. I'd fix it myself, but I've been too busy. I do think that the people who've contributed have done a good job with what they've brought in, and the cleanup flag was rightly removed. I'm sure the article will continue to get better with time. -Techelf 09:55, 19 January 2006 (UTC)

Pigkeeper's thoughts on quality and to-dos

I'm one of the main contributors here. Thanks for the positive feedback. My major efforts here have been to sort out this drug from the standpoint of someone who might want to use it, to understand its production and marketing, and/or to understand its place in potentially combating bird flu on a large scale. I have been focused on details, and on making judgements rather than on the article as a whole. One thing I have felt the page needed was a large-scale edit from someone who knows the drug--to tighten up arguments, spot holes, re-arrange things, and give it a general shake-down. I've avoided doing this myself because I don't have time. Maybe it's better than I thought, though? This is my only major effort on wikipedia, so I can't judge the standards. I didn't put the quality tag up, and I'm not going to be the one to take it down.
A few things which I think need to be done:

• 1) The biggest thing, I think, is a summary of the clinical trials from an efficacy standpoint. What improvements has oseltamivir shown for treatment and prophylaxis? When I read these results, it made quite an impression on me: basically, it seemed to me that--from an individual standpoint--it was perhaps good to take tamiflu for treatment, but it was even better for prevention (provided you had enough of the drug on hand). But at any rate, some reporting and assessment of clinical trials should be put up. I think at least a (simplified) version of this is in the Roche documentation ("Complete product information" (http://www.rocheusa.com/products/tamiflu/pi.pdf)).
• 2) A clean up of side effects section, esp. the Japanese part, would be good. There is some info from this talk page, below, about the japanese side effects which i don't think has been put onto the page. There's the annoying note i put in about "the authors haven't seen the actual list of japanese side effects...blah..."
• 3) I might (or might not) update the judgements made in the last page of the resistance section based upon de Jong et al and Moscona, and recent work. The question: does there seem to be a one-amino-acid substitution which conveys resistance? How well is it surviving within people? Well enough to make them sick, it seems. (Obviously, we have no data about *any* H5N1 viruses going between people, so we can't talk about changes in that rate that come from a mutation).
• 4) Production shortage/shikimic acid: BIG THING MISSING: I think I read that Roche is already synthesizing a sizeable quantity of shikimic acid--maybe 33%! Ok, wait, here's the quote:

Roche has given conflicting statements about its use of fermentation. In an e-mail message, Daniel Piller, a spokesman for Roche, said the company got about a third of its shikimic acid from fermentation and planned to increase that over time.

In a conference call with securities analysts two weeks ago, William M. Burns, the head of Roche's pharmaceutical business, said fermentation was part of the company's plan for the medium term. But for now, he said, the use of star anise was the only process approved by regulators.

Professor Frost, some industry consultants and Gilead, though, said that government manufacturing regulations did not cover the production of shikimic acid. (ANDREW POLLACK, 2005, in references)

• 5) PANDEMIC FEARS -- I feel like some more basic description about tamiflu's relation to pandemic fears would be good. This is where the stocks different countries have gotten would be good. More of an overview of the action. How tamiflu fits into, say, the WHO's plans to control H5N1. Scientists quoted in the New Scientist are really steamed that so much effort and money going into human drugs and vaccines, instead of dealing with the virus where it is now, in birds (sorry for long quote, article is not free, and a person editing may want to use this):

The H5N1 strain of the avian flu virus has still not evolved to spread from person to person. Nearly all of the 146 confirmed human cases so far, including two clusters in families in Turkey this month, resulted from close contact with infected birds. So it is on the infection in birds that efforts should focus, says Sam Jützi, head of animal production and health at the UN Food and Agriculture Organization (FAO) in Rome, Italy. The fewer birds that carry H5N1, the fewer human cases there will be and the fewer opportunities for the virus to adapt to humans.

Following the spread of H5N1 to previously unaffected countries last year, it now seems unarguable that the virus is being carried by wild birds, which can infect poultry they come into contact with. But the virus will continue to evolve as usual in the wild bird population, and this is expected to result in a virus that, like other H5 viruses in wild birds, poses no threat to people. That leaves the infection mainly in backyard poultry. "If we stamp it out there, in theory it will die out," says Jützi. "It is feasible. Why not?"

Alex Thiermann, special adviser to the head of the World Organisation for Animal Health (OIE) in Paris, France, agrees. He points out that in Thailand, which was badly affected in 2004, strict veterinary surveillance and culls of infected poultry have nearly eliminated the virus from the country's flocks. "The tools are there. What is critical is to mobilise the resources to apply them."

So far Thailand's achievement has not been repeated anywhere else. "I don't understand the lack of action in the field," Thiermann says. "It is obvious that if you reduce the viral load in birds, a pandemic becomes less likely." Yet spending on the pandemic threat by rich countries has focused on human drugs and vaccines, not on helping poor countries eliminate the threat before it evolves. "Every day the virus spreads further in poultry," Thiermann says.

That is what the World Bank would now like to remedy. "If we really move fast now and equip countries to deal with outbreaks quickly, we can keep the costs down," says John Underwood, head of operations at the World Bank and a member of its flu task force. In November its representatives met counterparts in the World Health Organization (WHO), the FAO and the OIE to devise a global strategy for H5N1, and in late December it posted a detailed analysis of what it will cost to implement it. The bill amounts to $1.4 billion. (http://www.newscientist.com/article.ns?id=dn8580)

pulling in this stuff would be good. What is on the wiki page for Pandemic Fears now is a little incomplete and out-dated. No one has gone back to look at production in India / Vietnam, etc. Roche is, i'm almost positive, shipping tamiflu to the United States again, seeing as flu season started awhile ago. This section could use some thoughtful trimming or reframing... or additions.

• 6) Is there any information about the extent of personal stockpiling? More info about the levels which individual countries have stockpiled?

• 7) References:

alphabetize. DONE
consider taking some of the most important linked citations (there are 23 now total) and putting them in the references page. NOT DONE, and some useful ones may have been lost in heavy editing
Standardize references. DONE?
"Complete Product Information" on Tamiflu from Roche should probably be a reference, rather than an "External Link." DONE

Peace y'all. Pigkeeper 22:19, 18 January 2006 (UTC)

Mechanisms of how drug works, and relation of this to resistant viruses?

Would be nice to add something on this. One place to start is the Moscona discussion in the New England Journal of Medicine (Volume 353(25), 22 December 2005, pp 2633-2636). She goes into the way the drug works, and how the known resistant strains' protein substitutions have worked to get around it. Pigkeeper 14:09, 9 January 2006 (UTC)

I have put a tiny entry about this in. I will attempt to complete it tommorrow when I have had a chance to research the mode of action more thoroughly. I'm surprised it isn't in already when so much other good information is already included. Wikipediatastic 17:01, 23 February 2006 (UTC)

Removed speculative remark

Removed straw man about differentiating Tamiflu from a counterfeit pharmaceutical. Besides the pompous language, this statement was likely false (or, at the very least, the scope of the sentence should have been limited to home users). As an example, I am certain that pharma/biotech companies have raised specific antibodies to oseltamivir; a simple ELISA could quickly confirm the presence of the drug. --chodges 02:12, 8 November 2005 (UTC)

> I meant that home users didn't have an easy way to distinguish between counterfeit drugs and the real thing. How is this a "straw man argument"? Governments wouldn't have this problem. Obviously there are expensive ways to determine the purity...Eugene Kwan 03:45, 14 November 2005 (UTC)

> Apologies for my terse words, I merely meant to correct something that seemed like an overstatement in the article. The wording (to me, at least) imparted that there was just no good way to determine if one's drug was genuine, which almost certainly is not true. I agree that this would be infeasible for home users, but simply because it's infeasible doesn't make something "impossible." Again, sorry to have caused any offense. --chodges 03:16, 18 November 2005 (UTC)

---

Looks like my words may have been justified... please see: http://www.cbc.ca/story/science/national/2005/12/23/Tamiflu-internet051223.html Eugene Kwan 01:25, 28 December 2005 (UTC)

Stockpiling of Tamiflu Nov 7 2005

Hi. E Kwan wrote:

The purported shortage of Tamiflu has prompted some individuals to stockpile Tamiflu. Several American states, including Massachusetts and Colorado have issued advisories strongly discouraging this practice. A potential problem is that the H5N1 virus can only be reliably found at proper labs; therefore, there is no way for home users to know whether to flu-like symptoms are the result of avian flu or a more benign ailment.

Thoughts on this: Do you mean diagnosed? Well, it's already the case that even when people are receiving Tamiflu under close medical supervision, the decision has to be made somewhat blindly. The drug needs to be administered within the first two days, and lab tests aren't done before then.

> Yes, what I meant was that if a private individual stockpiles Tamiflu, then he or she has no idea whether to use the drug or not, since there's no easy way for home users to determine if it's H5N1. Eugene Kwan 03:45, 14 November 2005 (UTC)

E Kwan continues: There is also no readily accessible way to distinguish Tamiflu from a counterfeit pharmaceutical. Such a test currently would require some combination of high performance liquid chromatography, mass spectrometry, and NMR.

There is a readily accessible way to distinguish counterfeits: look for convincing Roche trademarks on the packaging and pills, and get the drug from a source you trust. Of course that isn't a perfect way of distinguishing the contents of a drug. But it's the same for any drug, really. Ultimately, you're trusting someone. My aunt used to work for a generic drug manufacturing plant, and she said "there's no way i'd ever use generics." (That was years ago.) With even name brand drugs, you are trusting that the drug is going to work...but do the drug companies say in their advertisements or even in the prescription literature that most drugs work for only about half of the people who take them? No.

> Of course, but it's probably pretty hard to stockpile the drug just by going to the pharmacy. You'd have to go to some third party now, and then you have problems. Eugene Kwan 03:45, 14 November 2005 (UTC)

The issue with Tamiflu is that it is now difficult to get ahold of, and ordering from online pharmacies puts you at possibly a greater risk of being scammed. But, really, all you have to do is find an online pharmacy you trust.

> What sort of reputable pharamacy would allow someone to stockpile tamiflu now? Eugene Kwan 03:45, 14 November 2005 (UTC)

When it comes down to it, what is listed are scare tactics and incomplete arguments against stockpiling. It is similar to statements from some sectors of the US government that drugs bought from Canada are untrustworthy. Yes, yes, I might trust canadian drugs more than ones from a third world country or a fly-by-night internet pharmacy, but my point is that the argument being made has the same topology. They don't want you to stockpile, and so they are giving you arguments trying to convince you that it's not in your interest. The truth is more complicated. There *are* public-interest reasons for avoiding stockpiling. They include having drugs available for the people who need them the most, or to address outbreaks, or to avoid the inequity of rich people getting access to the drugs and poor people doing without. Still, it may be in a private individual's interests to stockpile nonetheless. Avian flu could have a very high mortality rate, and tamiflu is one of the few known preventatives. Full stop. Getting counterfeit drugs is a possible obstacle to reaching this goal of getting this protection, but it doesn't mean that it (from the POV of an individual's interests) isn't worth trying.

> I agree, personally, it might be beneficial to have Tamiflu, but it would be bad if everyone did that. Even so, I think there is no good reason to go spending lots of money buying a drug that might work for an epidemic that might happen. I mean, we could all go live underground... Eugene Kwan 03:45, 14 November 2005 (UTC)

Hoarding may be detrimental to the interests of people overall. The interests of the public at large and of individuals are at odds here. To pretend otherwise is intellectually dishonest. I can think of a number of roughly analagous scenarios to do with life boats or waiting in line for tickets.

> Yes. I think this whole thing has been blown out of proportion. I mean, there's lots of people dying of AIDS, or malaria, or TB...all these can kill young people...all these have drugs which you could stockpile...but I don't see people doing that... Eugene Kwan 03:45, 14 November 2005 (UTC)

--Pigkeeper

"therefore, there is no way for home users to know whether to flu-like symptoms are the result of avian flu or a more benign ailment." - as the drug is indicated for all forms of influenza this isn't really an issue. Tamiflu was not developed with pandemic influenza in mind, it is to treat any strain of the virus. Remember that influenza of any strain can potentially be fatal to asthmatics and the elderly.

I don't know where else to say this...

but millions will die as an indirect result of that companies greed

--

That probably isn't true. It's debatable as to whether or not Tamiflu will help in the event of a potential human-transmittable flu virus. At any rate, the chemical synthesis is so complex at this point that there really aren't that many companies around with the equipment, capital, and expertise to make Tamiflu. Would millions die if we didn't have enough of the drug? Perhaps. But that is far from clear, and it is ridiculous to say that is Roche's fault. Eugene Kwan 04:43, 27 October 2005 (UTC)

Indeed, if we actually did distribute shikimic acid to other companies, they wouldn't be able to produce nearly as much as Roche could. Star anise can be grown in many places, but in those four provinces, for some reason, the star anise produces it in a quantity that is high enough for economical extraction. I.E. It would go be wasted. I have heard from sources that Roche is ramping up the microbial shikimate synthesis that they have licenced and will be able to produce more tamiflu. Even so, the synthesis *starting* from shikimate involves several low-yielding and dangerous steps, including a few ones with highly explosive intermediates.

--I wouldn't call any of the steps "low yielding", but it's true, they aren't terrific. I read that the whole synthesis takes something like twelve months for some reason. I'm sure it would take a long time to get all the facilities setup, anyways. I don't see why people are so worked up over this avian flu deal. There's always a chance of some deadly plague coming. They come and go...you can kill all the chickens you like, but sooner or later, we'll have some sort of horrible epidemic. You're never totally protected! And it's debatable if Tamiflu will be effective against a disease *that doesn't even exist yet*. It's not like in the movies, where they discover some disease, and days later they've "found a cure". It takes forever to discover and make drugs! So if we have an epidemic, and Tamiflu doesn't work, we're on our own... --Eugene Kwan

Roche Suspension of deliveries to pharmacies Nov 2005

Removed statement that Roche was suspending [[[worldwide]]] deliveries to pharmacies. Google News search gave several stories claiming this, all in Canadian Newspapers, didn't seem like any of them had quotes from Roche. However, sources which did quote Roche only talked about suspending deliveries to the US and Canada. I cut the worldwide claim to be conservative, since it wasn't corroborrated so far as I could find. --PIGKEEPER! 2 Nov 2005

> Good call. Eugene Kwan 03:47, 14 November 2005 (UTC)

Effective? Donald Rumsfeld Conspiracy?

effective?

How effective will it be? I thought I heard that was under dispute.--Gbleem 19:45, 4 November 2005 (UTC)

> Of course it's under dispute! The so called epidemic would require a virus to mutate into a form which is easily transmissible between humans. Therefore, this virus doesn't exist yet! How can we say how effective a drug will be against a virus that doesn't exist yet? --Eugene Kwan

Doc says it's useless

Vietnamese doc's experience
Doctor says bird flu drug is ‘useless’ author: Jonathon Carr-Brown, in The Sunday Times, Ireland Dec 4, 2005

Dr Nguyen Tuong Van runs the intensive care unit at the Centre for Tropical Diseases in Hanoi and has treated 41 victims of H5N1. Van followed World Health Organisation (WHO) guidelines and gave her patients Tamiflu, but concluded it had no effect.

“We place no importance on using this drug on our patients,” she said. “Tamiflu is really only meant for treating ordinary type A flu. It was not designed to combat H5N1 . . . (Tamiflu) is useless.”

[...]

Van... said avian flu had a frightening effect on its victims and the only way to keep patients alive was to “support” all their vital organs, including the liver and kidneys, with modern technology such as ventilators and dialysis machines.

“Laboratory studies show that Tamiflu is effective against all strains of flu,” said Bill Hall, director of the National Virus Reference Laboratory, who defended Ireland’s stockpiling of Tamiflu and other flu treatments. “The only limitation is when it is not administered within the first 24 hours of onset of symptoms.”

The WHO admitted Tamiflu had not been widely successful in humans. “However, we believe in many Asian countries it hasn’t been used until late in the illness,” a spokesman said.

Take what you will from this. In person experience like this is definitely worth a lot. But the WHO may have a point: when is this stuff given? The original studies on 'regular' flu administered the drug within ~40 hours after onset of symptoms. This also isn't calling into question the phrophylactic efficacy of tamiflu. The efficacy there is actually pretty high for regular flu. Pigkeeper 22:01, 5 December 2005 (UTC)Pigkeeper

Here is a report from Canada about a test showing that tamiflu is 98% infective due to virus immunity to the medicine [2]!--86.29.254.128 (talk) 13:41, 11 May 2009 (UTC)

Not effective? Rumsfeld

On 26 Nov, 69.160.149.230 wrote:

Some scientists, however, are doubtful that oseltamivir would be at all effective in an avian flu pandemic.

1) This is a sweeping, non-specific claim. If you want to put in specific issues (e.g. the potential for Resistant viral strains, or fact that some people who take tamiflu still die, or the fact that there's a limited supply of the drug to go around), do it. But still, the "not be effective at all" statement is still too sweeping and unwarranted.

2) A very weak citation is given: the web log of a professor of physics, who himself makes a less sweeping but still unsubstantiated claim about tamiflu's efficacy. To cite "some scientists" in the wiki article gives a misleading view of the level of "expertise" behind the argument.

69.160.149.230 continues:

Some ascribe the U.S. government's unreserved endorsement of oseltamivir to Secretary of State Donald Rumsfeld's close ties to Gilead Sciences, rightsholder to the Tamiflu patent. Rumsfeld is a former chairman of Gilead and continues to own millions of dollars in stock.

I've dug into Rumsfeld's corporate connections with the FDA's dodgy approval of Aspartame (Nutrasweet)(e.g. see [3]). I neither trust the guy nor the pharma companies he has been associated with. There is also the general question of bias in clinical trials funded by the pharmaceutical industry (the pharma industry funds 80% of clinical trials). This makes me wary of tamiflu's efficacy, but if multiple studies have been done, it is less disconcerting. But it's a valid concern. And there's no way of knowing without doing our own studies, really. And that's not going to happen. Pigkeeper 20:42, 28 November 2005 (UTC)Pigkeeper

Citation for both of these was:

Park, Bob. Shamiflu: The Bush White House and the war against bird flu [Newsletter]. What's New University of Maryland Department of Physics (Accessed on November 26, 2005 at (http://bobpark.physics.umd.edu/WN05/wn112505.html).

I have removed it, and replaced it with the Fortune magazine article about Rumsfeld's link to Gilead.

Removed potential spam

removed the following external link code which referred to a site purportedly selling tamiflu and other excessivley priced prescription medication without a prescription:

*[http://www.epharma.md Buy Tamiflu]Tamiflu (oseltamivir phosphate), an oral anti-viral drug for the treatment and prevention of all common strains of influenza.Tamiflu is the first and only FDA approved neuraminidase inhibitor available in convenient pill and liquid suspension form.

--Dstroud 11:23, 7 November 2005 (UTC)

Is this drug prescription-only or over-the-counter?

I can't find a reference in the article to whether this is a prescription drug or whether it is available over-the-counter. I imagine it's prescription-only? This is probably something that everyone writing the article already knew, and didn't think about. I really think that that sort of context-setting information should be in the first sentence or paragraph of the article. -- Creidieki 00:42, 14 November 2005 (UTC)

> Prescription only. Eugene Kwan 03:47, 14 November 2005 (UTC)

> It changes from country to country. Thats why there are online stores selling brand medicines without prescription. Usually medines are cheaper in those countries in the way of producer or distributor; and it is easy to buy as the government do not require prescription.

Safety, Japanese pediatric deaths, FDA panel's review

A news.google.com search for Tamiflu today gives headlines such as "Agency insists Tamiflu is safe" (Chicago Tribune), "US clears bird flu drug Tamiflu" (BBC), "Flu Drug Cleared" (Newsday, NY), etc. These articles were based upon statements by the head of the FDA's pediatric advisory committee, and a 6-page report put out by that committee, and probably other related sources. I highly recommend reading multiple sources on news.google for stories like this, because you often find inconsistencies across reports. Another article has the title "FDA Can't Link Tamiflu to Deaths" (theStreat.com), which actually comes closer to statements made by the Advisory Committee. Not establishing a causal link is different from "insisting the drug is safe". Reading the 6-page report gives you a somewhat different view from these breathless headlines.

As quoted in that theStreet article:

The FDA notes: “Based on the information available to us, we cannot conclude that there is a causal relationship between Tamiflu and the reported paediatric deaths.” It adds that the "increased reports of neuropsychiatric events in Japanese children are most likely related to an increased awareness of influenza-associated encephalopathy", increased use of Tamiflu in Japan, and greater monitoring of adverse events.

I am not getting all paranoid that this drug is hugely dangerous. Let's do a little back-of-the-enveolope calculating:

24 million doses of it have been given in Japan. 11.6 million children under-16 have received the drug in the US and Japan combined, according to Roche [4]. In Japan we've had 32 reports of children with "neuropsychiatric events" such as hallucinations, confusion, convulsions and brain inflammation. In the U.S., there is known to be widespread under-reporting of adverse drug related events--one estimate is that 5% of adverse effects are reported; I don't know what the story is in Japan. If it were the same, we might be looking at 600 events out of several million doses given. Not high, especially since serious events are more likely to be reported (i.e. our fudge factor may not be conservative.)

Worldwide and including adults, the number of AE reports for neuropsychotic events is 130[5]. Multiplying that by 20-fold, we get 2,600, compared to a global dosing of 32million people. At any rate, this is below a 1 in 1,000 threshold.

My own conclusion is to agree with this:

“If we ever have a pandemic of avian flu, which is a debatable point, people want to know that they have a drug that will not cause more (harm) than the flu itself,” Dr Robert Nelson, chairman of the FDA’s Paediatric Advisory Committee, said. “There is no evidence that it will.”

However, I don't think the possibility a low frequency of severe neurological side-effects in children may be ruled out, and I have my suspicions that they are there. The delirium from flu is a clear confounding factor, but kids jumping out of windows and in front of trucks is beyond the pale for what you expect to hear from flu patients. Remember that members of the FDA have first defended certain antidepressants against having links to increased suicide attempts, but now they require black box warning labels. The jury is still out. Pigkeeper 21:40, 19 November 2005 (UTC)Pigkeeper

It's better to be safe than sorry, if you don't have bird flu but only run-of-the-mill influenza, then don't take it.Supersymmetry (talk) 06:38, 13 July 2009 (UTC) —Preceding unsigned comment added by Supersymmetry (talk • contribs) 06:34, 13 July 2009 (UTC)

Information from Japan: neurological effects and teen deaths

Japanese Health, Labour and Welfare Ministry added four adverse reactions for oseltamivir phosphate

Notification is listed in 2005.8 (No.141) Drug SAfety Update [6], P28 (Japanese)

oseltamivir phosphate(ja:リン酸オセルタミビル)

CLINICALLY SIGNIFICANT ADVERSE REACTIONS "Colitis haemorrhagic" added

CLINICALLY ADVERSE REACTIONS "hemorrhage beneath the skin" added "palpitatio cordis" added "anasarca" added

Rumsfeld

I'm no Rumsfeld apologist, but listing any shareholders of a company that makes a drug, is, I feel, inappropriate in the first paragraph of the drug's description. Sjcodysseus 18:50, 13 December 2005 (UTC)

Stereochemistry

At the 3-position, bearing the ether: CIP priorities, 1: etheral substituent, 2: carbon bearing amide, 3: alkene; counterclockwise with H up, clockwise with H down, therefore R. Rationale for 2 vs 3: alkene is treated as bearing C,C,H while the other carbon is treated as N,C,H. Since N is heavier than C, the carbon bearing the amide takes precedence. So the new change seems right. Eugene Kwan 01:55, 2 June 2006 (UTC)

Yep, 3R,4R,5S is correct. The original error was mine as I had misinterpreted my original structure. It's less ambiguous in the new structural image. -Techelf 10:51, 2 June 2006 (UTC)

Updated March-April 2007

I've done a major update of this article, including additions on psychological effects, a note that the supply shortage isn't so much of an issue for now (may change if epidemic actually starts), and to note that there have been transmissions resistant influenza B strains passed from person to person.

The Pandemic Fears section still needs updating. The bit about the 2005 shortage should be condensed and updated with current information (that the shortage is over for now).

Some of my suggestions above still stand. For example, it would be good to dig up the efficacy information on tamiflu when taken prophylactically. I recall that, for seasonal flu, it actually worked pretty good on this front. Pigkeeper 21:09, 11 April 2007 (UTC)

Need to combine Pandemic Fears and Production shortage

Looking at this again, I think the Pandemic Fears section should be trimmed, and combined with the Production Shortage section. Or at least sort them out better, there's a lot of overlap. Pigkeeper 17:48, 12 April 2007 (UTC)

Shikimic acid

This page states that shikimic acid cannot be produced synthetically, but Star Anise claims there is. Which is right? 124.197.13.81 21:57, 4 November 2007 (UTC)

Broken citations

A large percentage of the citations reference web pages that no longer exist. JesseHogan (talk) 02:30, 29 December 2007 (UTC)

Easier to understand article

Can someone clean this article up, by putting some things into "layman's" terms? The article reads more like an article from a medical journal than an encyclopedia. —Preceding unsigned comment added by Arob22 (talk • contribs) 01:49, 15 February 2008 (UTC)

OK, so what does this drug mean for me?

This article is thick with information, but it curiously lacks consolidated information on what Tamiflu does for patients. My guess is that by preventing reproduction, it limits severity and duration of the disease. Why is the article devoid of this info? Nova SS (talk) 03:42, 15 February 2008 (UTC)

U.S. Government policy

This section is out of date and speculative, and should be either updated or deleted. I plan to let it sit for a couple of weeks, but if no one adds anything or objects I plan to remove the section. Preston McConkie ^{(talk • contribs)} 22:31, 11 March 2008 (UTC)

I think that it is relevant. The massive stockpiling of the drug by various governments is an important part of the drugs history. It was one of the largest ever if not the largest ever stockpiling of a drug in the world's history. Financial ties to Roche or rights holder's of Tamiflu of people in gov who ordered the stock piling is very relevant as well. Whether there needs to be a reordering of the article, perhaps putting this kind of information in a "history" section or a "controversy" section might be worth considering though in my opinion.--Literaturegeek | T@1k? 12:43, 17 May 2008 (UTC)

Several Questions

I hope someone here knows further information that an interested reader (me!) might find useful: What are the normal and extended rated shelf lives of Tamiflu, and under what (home) storage conditions? If Tamiflu is taken prophylactically (prophylacticly?) how long does the protection last? What is the prophylactic dosing, e.g. for a season of protection? Jornadigan (talk) 16:54, 25 May 2009 (UTC)

Preservative

Forgive me if I've missed this information but what preservative is used in this vaccine? The NNii says that influenza vaccine is "manufactured with thimerosal as a preservative", does Tamiflu contain thimerosal? Thanks. Mimi ^(yack) 20:52, 9 August 2009 (UTC)

Oseltamivir is a drug, not a vaccine. Neither zanamivir nor oseltamivir contain thimerosal. Fvasconcellos (t·c) 00:07, 10 August 2009 (UTC)

Thank you. Mimi ^(yack) 09:16, 10 August 2009 (UTC)

First line doesn't make sense

The first line seems to be unreadable. Any suggestions?Jimjamjak (talk) 10:26, 25 September 2009 (UTC)

citation needed

"It is possible that shortages could again be encountered if a global influenza pandemic actually arose.[citation needed]"

This above sentence is in the article, but it seems obvious, and I don't believe a citation is needed. I apologize if I am not doing this with the customary protocol.

167.127.24.34 (talk) 15:13, 8 October 2009 (UTC) John Philip Johnson Oct 8 2009.

Updated H1N1 Tamiflu resistance info from CDC

The previous quotes indicating that the seasonal H1N1 virus was ~99% resistant to Tamiflu are outdated (from 2008), seem to be conjecture, and I didn't think the source looked terribly credible as it was a fluffy news article with weak language. The CDC has updated antiviral treatment guidelines as of Oct 3, 2009 and indicated that about 99% of H1N1 can be treated with Tamiflu. This is the opposite stance indicated by the current article. See [7] for details, specifically:

"As of October 3, 2009, 99% of circulating influenza viruses were 2009 H1N1 viruses susceptible to both oseltamivir and zanamivir. These treatment guidelines therefore focus on use of antiviral medications effective against 2009 H1N1 viruses. For antiviral treatment of 2009 H1N1 virus infection, either oseltamivir or zanamivir are recommended"

I'm updating this now, rather than waiting for discussion since the article is clearly outdated and incorrect. Lamber111 (talk) 15:05, 20 October 2009 (UTC)

Sorry, I didn't address the other citation in the article http://www.cdc.gov/flu/weekly/ While this citation says it's for a Flu weekly publication in September, the link updates to the most recent information available and I don't know how to pull archived weeks. However, the newest data (October 19) contains direct contradictions to the statement that H1N1 is resistant to Tamiflu. Lamber111 (talk) 15:11, 20 October 2009 (UTC)

They have not begun testing seasonal flu yet since they reset the totals like last week. As the seasonal h1n1 was 99.6 percent resistant earlier this year, it will likely be more resistant if anything this season..thats the way resistance works we have not stopped prescribing tamiflu for it.. it is not going to miraculously become less resistant when it resurfaces. leaving out the previous seasonal flu major immunity to tamiflu is dangerous.. especially as flu season is just beginning and the seasonal flu is just now resurfacing. and last year tamiflu was useless for it. Until they test more seasonal samples.. and h3n2 and B. The old data is the most accurate.. the article does need to state it is effective against 2009 pandemic h1 though. -Tracer9999 (talk) 02:47, 21 October 2009 (UTC)

Good catch. I clarified the existing comments to the 2008 seasonal strains. 199.171.86.180 (talk) 13:37, 21 October 2009 (UTC)

actually calling it 2008 seasonal strain would be incorrect also as it still is circulating in russia for instance.. and the virus has not become less resisistant. In a US centric point of view..yes, they were 2008 strains.. in a worldwide view it is currently circulating seasonal h1n1.. -Tracer9999 (talk) 13:48, 17 November 2009 (UTC)

Tamiflu has been sucessful in curing Parvo in puppies and dogs. —Preceding unsigned comment added by 75.10.140.41 (talk) 20:50, 14 July 2010 (UTC)

Secondary source needed

Do we have any secondary sources with respect to the following

===Coadministration with probenecid=== Coadministration of oseltamivir with probenecid has been suggested as a method to extend a limited supply of oseltamivir. Probenecid reduces renal excretion of the active metabolite of oseltamivir. One study showed that 500 mg of probenecid given every six hours doubled both the peak plasma concentration (C_max) and thehalf life of oseltamivir, increasing overall systemic exposure (AUC) by 150 percent. Although the evidence for this interaction comes from a study by Hoffmann–La Roche (Roche), it was publicized only in October 2005, by a doctor who had reviewed the data. Probenecid was used in similar fashion during World War II to extend limited supplies ofpenicillin. It is still used to increase penicillin concentrations in some infections.

Doc James (talk · contribs · email) (if I write on your page reply on mine) 18:13, 3 March 2013 (UTC)

Kaiser study

I see that this edit of mine was reverted, so lets discuss here. I can certainly see the point of keeping the most recent, most reliable and most up-to-date information at the top of a section entitled "Efficacy". But in the case of this article, the reported efficacy isn't an open-and-shut case. Since the disputed 2003 review by Kaiser seems to be a big part of the reason why Oseltamivir is so widely used, and since the subsequent studies mentioned in the section were mostly in response to controversy surrounding inadequacies of the 2003 study, I thought it made sense to describe it in a brief paragraph.

The sections that currently remain in the article mentions the 2003 study, which seems odd since it isn't further elaborated on at all. If we are to excise the Kaiser study from the article, I think we should leave out any mention of it entirely, rather than the present situation (which I think is a bit sketchy). Any thoughts? Gabbe (talk) 15:13, 4 March 2013 (UTC)

Sure however if we could discuss the previous study in more detail we should do so using the more recent reviews that put it into context. IMO we should list the most recent conclusions first. Feel free to change further. Doc James (talk · contribs · email) (if I write on your page reply on mine) 15:46, 4 March 2013 (UTC)

I see the point of presenting the most recent studies first, and I agree we should for clarity's sake begin the section with stating the latest consensus view. But after that, I suggest we mention the studies in chronological order.

This version of the article has a reverse chronological that makes for very peculiar reading:

1. First it says that "An updated Cochrane review, in 2012" maintains that the trials are unavailable. (This update is partly in response to the continuing inadequacies in the openness of Roche's behalf.)
2. Then it says that "Roche requested an independent reanalysis of its data in 2011." (This reanalysis was in response to the altered stance from Cochrane)
3. This is followed by "In 2009, the Cochrane Collaboration, announced it had reversed its previous findings"
4. Finally, "A previously published version of this review had included all trials mentioned in Kaiser's 2003 meta-analysis, even the unpublished ones". (But Kaiser's 2003 paper is mentioned nowhere else in the article).

Surely, a reverse chronological order is not the proper way to present these evaluations and re-evaluations?

I've rearranged the efficacy section into a chronological order, relabelled it "Studies on efficacy" to clarify that it is an overview of the available secondary sources discussing the efficacy. The lead and the "Medical use" section both already mention that the efficacy is disputed, but to be sure, I've added a brief statement at the beginning of the section saying that its efficacy is disputed. I've also added a note at the end of the paragraph on the Kaiser study to clarify that its inclusion of unpublished papers is what later cast doubts on its conclusions. Gabbe (talk) 14:35, 5 March 2013 (UTC)

I would prefer a rewording and have it from newest to oldest. The 2003 trial is really no that significant as we try to use research less than 5-7 years old for medicine per WP:MEDRS Doc James (talk · contribs · email) (if I write on your page reply on mine) 18:20, 5 March 2013 (UTC)

I agree with you that if we had to limit what the article says on efficacy to a concise, one-sentence statement then it should be something along the lines of "The efficacy of oseltamivir is in dispute". And, per WP:MEDRS, either the 2011 review by Hernán & Lipsitch or the 2012 review by the Cochrane Collaboration would be far preferable to a ten year old review. With that I am not arguing with you. I'm not saying the Kaiser study is reliable, nor am I saying it is up-to-date. I am saying that it is essential to describing the controversy surrounding the efficacy of oseltamivir. The reason I want to include it is the same as the reason for including Wakefield's 1998 study in the "MMR vaccine" article. Not because it is accurate, but because it had an enormous impact on the public's uptake of MMR jabs. Similary, as summarised in doi:10.1371/journal.pmed.1001201 or here for example, the Kaiser study is the key to the Tamiflu controversy.

Even if we limited ourselves to only presenting the latest review articles, a problem arises already with the question of Hernán & Lipsitch (2011) versus Cochrane (2012). They reach different conclusions, based primarily on whether to include the unpublished data originally mentioned in Kaiser's 2003 review. If this article should be more than a superficial glance then it necessitates describing it, if you ask me.

If the studies are to be ordered from latest-to-earlier, then I think the paragraphs should at least be rewritten to mention one another to a lesser extent. Gabbe (talk) 19:03, 5 March 2013 (UTC)

Edit

I have reverted this edit [8] as the titles are not those recommended per WP:MEDMOS. Not sure how the title "efficacy" is not NPOV? Doc James (talk · contribs · email) (if I write on your page reply on mine) 02:12, 19 August 2013 (UTC)