Drug Cocktail Effective Against Tamiflu Resistant Swine Flu

allnurses Guide · Dec 9, 2009

doctors query ability of tamiflu to stop severe illness

review published in british medical journal accuses flu drug manufacturer roche of withholding evidence from trials

sarah boseley, health editor guardian.co.uk , tuesday 8 december 2009

tamiflu tablets may shorten bouts of illness by a day or two, reviewers say.

roche, the manufacturer of tamiflu, has made it impossible for scientists to assess how well the anti-flu drug stockpiled around the globe works by withholding the evidence the company has gained from trials, doctors alleged today .

a major review of what data there is in the public domain has found no evidence tamiflu can prevent healthy people with flu from suffering complications such as pneumonia.

http://www.guardian.co.uk/world/2009/dec/08/tamiflu-swine-flu-roche

indigo girl · Dec 9, 2009

doctors query ability of tamiflu to stop severe illness
review published in british medical journal accuses flu drug manufacturer roche of withholding evidence from trials
sarah boseley, health editor guardian.co.uk , tuesday 8 december 2009
tamiflu tablets may shorten bouts of illness by a day or two, reviewers say.
roche, the manufacturer of tamiflu, has made it impossible for scientists to assess how well the anti-flu drug stockpiled around the globe works by withholding the evidence the company has gained from trials, doctors alleged today .
a major review of what data there is in the public domain has found no evidence tamiflu can prevent healthy people with flu from suffering complications such as pneumonia.
http://www.guardian.co.uk/world/2009/dec/08/tamiflu-swine-flu-roche

the uk decided on a different approach than the us did. we never used the drug prophylactically here. and, we continue to see cases of people sick with flu that are being sent home without being given this drug. by the time they are finally admitted to the hospital, they are dying, and it is far too late for tamiflu.

using it for large scale prophylaxsis may not be the most effective use of the drug with a virus that is not very virulent in most cases. but,with the blessing of who, tons of this drug have been used to blanket whole villages of people in southeast asia like a finger in the dyke to try hold back the very virulent bird flu virus, and keep it from spreading to other human hosts after cases of human infection occurred, and poultry die-offs were happening. what could they do differently? there is no good answer.

the drug does work if the patient actually is infected, and if the dose is high enough though it is best given in the first 48 hours. if you get admitted to the icu with suspected swine flu or any kind of flu, this is the antiviral that is going to be given first unless your illness does not respond to it. then, they will switch to relenza or possibly to the newer peramivir as a last resort.

it did seem to make a hugh difference in brazil with pregnant women, we heard from a physician presenter at the cidrap conference that i attended in minneapolis. brazil was losing many pregnant women to the swine flu virus until they were all given scripts for tamiflu with instructions to take the drug if they began to develop flu like s/s. their death rate dropped dramatically after this. this is of course, not a clinical trial. it's just what happened in one country, but it sure was impressive, not to mention, smart.

i do agree that roche should be more forthcoming with their information. it is clear that they are making hay while the sun still shines. they know that this drug is not going to be effective against swine flu for very long. the virus has been developing resistance, and not just in people taking the drug. there have been resistant cases of swine flu infections noted in people that were never treated with tamiflu occurring fairly early on in the pandemic. just as seasonal h1n1 developed tamiflu resistance so will the swine flu. tamiflu's days are numbered. roche knows it, as does who.

i suspect that there are at least some on this board who have friends and family that were fairly ill, and tamiflu did make a big difference in their recovery. i certainly know of some. i doubt that any of these people are going to begrudge roche's profit as long as the drug saved their family members. i sure wouldn't.

so my question would be to those govts who don't want to spend the money for this drug is, what else are you going to use? the only antiviral drugs available are all neuraminidase inhibitors as is tamiflu. this is not even a new problem. if govt does not want to fund the research, then private industry will do so for profit. influenza will always be with us. pandemics will continue to occur periodically, and we will be caught offguard yet again.

indigo girl · Dec 10, 2009

See What I Mean?

http://afludiary.blogspot.com/2009/12/nejm-community-cluster-of-tamiflu.html

We are going to lose this drug, Tamiflu. It is only a matter of time. As you can clearly see in the link below, these people in Vietnam were infected with a drug resistant strain of H1N1 right from the get go. These strains do exist though WHO and Roche do tend to disregard them. These strains have been reported periodically from early on this pandemic from people not treated with the antiviral prior to being infected with a resistant strain. So far though, the drug still works for the majority of cases, and hopefully will see us through to the other side of the pandemic.

Vaccination is still the best option for all.

Seven healthy people on a train from Ho Chi Minh City to Hanoi in Vietnam caught Tamiflu-resistant H1N1 flu, researchers reported Wednesday in a prominent medical journal.
The transmission event, which occurred in July, is one of the largest clusters of cases of resistant H1N1 seen so far and the first time so many linked cases have been seen in previously healthy people who had not been on the drug.
Surveillance since the summer has only turned up three additional drug resistant viruses, the authors note in their letter to the New England Journal of Medicine. But they say they cannot rule out the possibility of ongoing transmission of resistant pandemic H1N1.
The event is a warning that resistant viruses can spread among healthy people and more such events may be in store, an antiviral expert with the World Health Organization said.
(Continue . . . )

indigo girl · Dec 10, 2009

The other day the British Medical Journal (BMJ) published a clutch of articles about whether Tamiflu was as useful a drug as some have touted. I read the main article, another one of the Cochrane Collaborative meta-analyses of the studies they deem useful about any particular subject, and it didn't seem to make much news. It confirmed what their previous review had said about the neuriminidase inhibitor antivirals for influenza (Tamiflu and Relenza): these drugs work but their effect is modest. We've been saying the same thing for years here, not because we did a fancy meta-analysis, but because that's quite clearly what the literature said. They confirmed it. Again. Not very interesting, I guess, so the BMJ, quickly becoming medical tabloid central, fastened on the one scientific aspect of the paper that might remotely have a news hook: the meta-analysis didn't have enough information to show -- according to Cochrane Collaborative standards, that is -- that healthy people who got flu and were given a neuriminidase inhibitor avoided more serious complications like pneumonia. It didn't show the antivirals didn't work for this. It just alleged there was no Cochrane-required-level-of-evidence they did. The data -- in their hands -- showed the evidence was compatible with either outcome. Yawn. But yawn was good enough. It was elevated to a different story: that one reason we didn't know is that the drug companies were hiding the data. That is a news story, I agree, but not a news story about whether the drug works or doesn't. While just an allegation (because they didn't get to see the data), the medical journal was doing this in collaboration with television channel 4 in the UK and the Cochrane Collaboration itself. Conflicts of interest?
The paper was co-authored by, among others, Dr. Thomas Jefferson and graduate student Mr. Peter Doshi, both of whom I have criticized here on one occasion or other. I'm not making any serious complaints about this paper (although why, on scientific grounds it should have been published in a high profile journal isn't clear to me since it didn't provide new evidence), but I do know enough about this kind of work to know that a great deal of judgment is used in accepting or rejecting papers (indeed that's why this follow-up was done; someone objected to a paper that was considered in the previous review). However the overwrought point-counter-point between drug maker Roche, the authors, BMJ reporters and the editors over access to the data and who was supported by whom had the effect of entangling use of an important class of drugs for influenza -- a class of drugs that everyone seems to agree works to some extent when no other does (and during a pandemic, no less) -- and the important but unrelated issue of transparency over data involving pharmaceuticals. Let me be clear that on this issue I am on the BMJ's side. I think it's a scandal that we don't have access to information used to license drugs given to the public with an official sanction of safety and efficacy. But it's an issue that would likely crop up with almost any drug they sought to examine. Doing this in tandem with a media outlet whose objectives are not science but snagging viewers and the Cochrane Collaborative itself is unseemly at best and borders on the unethical. It makes it look like the BMJ was again engaging in self-promotion (OK, I understand it's a business enterprise, but let's recognize what's involved). It didn't hurt that the self-promotion seemed to serve everyone's purpose (except for Roche's, and frankly I can't bring myself to feel sorry for them).
Well, maybe not everyone's. I don't think it served the public purpose or the public health. Tamiflu and Relenza work. They are in fact the only therapeutic modality we have other than supportive care or in critical cases heroic methods (mechanical ventilation). Vaccines are preventive, not therapeutic. So here we are in the middle of a pandemic and the Cochrane folks, aided and abetted by the BMJ and television producers, are saying, "How do you know for sure that they will prevent pneumonia in an otherwise healthy person who gets flu?" There is evidence about this, even if the Cochrane zealots don't recognize it:

More at: http://scienceblogs.com/effectmeasure/2009/12/the_tamiflu_doesnt_work_non-st.php#more

The Editors of Effect Measure are senior public health scientists and practitioners. Paul Revere was a member of the first local Board of Health in the United States (Boston, 1799). The Editors sign their posts "Revere" to recognize the public service of a professional forerunner better known for other things.

indigo girl · Dec 11, 2009

Immuno Compromised Patients and the Risk of Tamiflu Resistance

Although we have seen that resistance can also occur in people that have never been on the drug before, it is the immuno compromised patients that are most likely to develop resistance to the flu antiviral drug, Tamiflu (oseltamivir). This presents a problem. What do you treat them with? And, are others in danger of being infected with resistant strains from these patients? Here are two articles addressing these issues.

http://www.google.com/hostednews/afp/article/ALeqM5jJzZct5LIo0gwhRXTIpGH-uzUltg

In such patients with suppressed immune systems, "standard treatment doses and duration for treatment with oseltamivir (Tamiflu) are unlikely to be sufficient," the WHO said in a briefing note posted on its website.
"Though clinical judgement is important, doses may need to be increased and continued, without interruption, for the duration of acute illness," it added.
The UN health agency also recommended that the alternative drug to Tamiflu, Zanamivir, "should be considered as the treatment of choice for patients who develop prolonged influenza illness despite treatment with oseltamivir."
"Experience with seasonal influenza viruses shows that resistant viruses can quickly spread within the general population and become established, rendering one or more antiviral drugs ineffective," it cautioned.
Within the past two weeks, the number of documented cases of Tamiflu resistance in those who have contracted A(H1N1) flu has risen from 57 to 96, according to the global health watchdog.

http://www.google.com/hostednews/canadianpress/article/ALeqM5gPNZl22j9Y8jX3nZGi56N4GRo3_A

In the case of influenza, Tamiflu would help suppress replication of the virus in these patients. But the viruses that were able to evade the drug can develop resistance to it. And if a patient nearby is in the same shape, immunologically, the resistant virus could spread.
Dr. Arnold Monto, an influenza expert from the University of Michigan, said he thinks the problem seen with severely immunocompromised patients suggests clinicians may need to look to combination therapy - using two antivirals together.
That technique is used in treatment of HIV to lower the risk drug resistance will develop.
"I'm becoming a fatalist. If there's going to become a mutation that confers both resistance and transmissibility, it's going to happen a la Norway," Monto said. "But we don't have to tempt fate."
The WHO told clinicians if severely immunocompromised patients remain ill with flu for prolonged periods, switching them to the other antiviral, zanamivir (sold as Relenza) should be considered. To date there have been no reported cases of H1N1 resistance to Relenza.
And if doctors decide to put nearby patients on antivirals to prevent them from contracting flu - a measure known as prophylaxis - they should use Relenza for those patients, the WHO statement said.
It also stressed that medical staff caring for severely immunocompromised patients and family members of the patients should be vaccinated against H1N1 to minimize the risk of infection.

http://www.relenza.com/relenza-faqs.html

The problem with Relenza is, it is really not appropriate if your patient has reactive airway disease. I do know that sometimes this drug has been given IV.

Important Safety Information About RELENZA
Some patients have had bronchospasm (wheezing) or serious breathing problems when they used RELENZA. Many but not all of these patients had previous asthma or chronic obstructive pulmonary disease. RELENZA has not been shown to shorten the duration of influenza in people with these diseases. Because of the risk of side effects and because it has not been shown to help them, RELENZA is not recommended for people with chronic respiratory disease such as asthma or chronic obstructive pulmonary disease.
If you develop worsening respiratory symptoms such as wheezing or shortness of breath, stop using RELENZA and contact your healthcare provider right away.
If you have chronic respiratory disease such as asthma and chronic obstructive pulmonary disease and your healthcare provider has prescribed RELENZA, you should have a fast-acting, inhaled bronchodilator available for your use. If you are scheduled to use an inhaled bronchodilator at the same time as RELENZA, use the inhaled bronchodilator before using RELENZA.

indigo girl · Dec 24, 2009

Influenza neuraminidase inhibitors work

http://www.virology.ws/2009/12/23/influenza-neuraminidase-inhibitors-work/

One of the first human studies on the effectiveness of Tamiflu was published about ten years ago. The human subjects (117 healthy adult volunteers, 18-40 years of age, with hemagglutination-inhibition antibody titers 1:8 or lower) were infected intranasally with a seasonal H1N1 strain of influenza virus. Some subjects were given Tamiflu or placebo 26 hours before infection, while others were given the treatment 28 hours after inoculation. Frequency of infection, viral shedding in nasal washes, and clinical symptoms (such as temperature, nasal stuffiness, runny nose, sore throat, sneezing, cough, breathing difficulty, muscle aches, fatigue, headache, earache/pressure, feverishness, hoorificeness, chest discomfort, overall discomfort) were then determined.
Administration of Tamiflu 28 hours after inoculation reduced viral shedding and clinical symptoms, as shown in the following two graphs. Note that virus titers peaked in treatment and placebo groups at roughly 36 hours after inoculation. Viral titers declined more rapidly in individuals given Tamiflu, and no virus was detected by 60 hours after infection.
The authors concluded that "In these trials, prophylaxis and early treatment with oral oseltamivir were both associated with significant antiviral and clinical effects in experimental human influenza." In other words, if you know you have influenza, Tamiflu works reasonably well.