A Tamiflu Rx question for my prescribing colleagues

[Skeptic Ginger]

And anyone else who wants to chime in.

Last week my neighbor's 14 year old was diagnosed with 2009H1N1. The boy's physician told them Tamiflu was being reserved for high risk patients only and the doc did not prescribe the drug for the boy.

I don't see it that way and I wrote him a script.

Two days later, my neighbor thanked me and said she had just read about the 14 yr old girl who died of H1N1 last Sunday after her provider also declined to write an Rx for Tamiflu.

Tests confirm that 14-year-old Benbrook girl died of swine flu

...Lindsey, an eighth-grader, had no underlying health problems. She ran track and played clarinet in the school band, he said. ...

Lindsey went home from school Wednesday evening feeling “flushed,” Osborne said. On Thursday morning, she had a fever, and her mother, Tammy Osborne, made her stay home.

By Friday, Lindsey was congested and feeling worse, so her parents took her to her pediatrician’s office, where she tested positive for flu.

However, she did not receive the antiviral medication Tamiflu because the doctors said the CDC guidelines recommend giving it only to people most at risk, he said.

Health officials announced this month that the antiviral medicines should be reserved for people most at risk, including pregnant women, children younger than 5 and those with certain chronic conditions like asthma and heart disease.

After writing the script for my neighbor, I went back to review the CDC guidelines. We all know Tamiflu works best if given in the first 48 hours and preferably the first 24. CDC guidelines say reserve the Rx for the very ill.

Well what does that mean? I say it means a moderately severe case of flu, not just a case severe enough to be hospitalized. How is any provider supposed to predict in the first 24 hours after symptom onset how ill a person is going to become? Yet if you wait longer than 48 hours, the drug is much less effective. In the case of the Texas girl, that would have been Saturday. She died Sunday. It may already have been too late at that point.

I asked myself, what if it were my son? I would give him the Tamiflu, no question. I wonder how many other providers are having a hard time with the CDC guideline saying reserve the Tamiflu for "severe disease" but yet not addressing the issue of just what that actually means?

My neighbors have another son a year or so younger. He had some mild illness in the few days before the brother became ill. It did not present exactly like influenza.

That would be the kid with mild illness I would not prescribe the Tamiflu for. But the kid with sudden onset, extreme fatigue and temp over 101F? I'm sorry but I'm calling that one severe enough to get Tamiflu until the CDC makes it clear what they mean by reserve a drug for the very ill when the drug may be too late to help on day 3.

 

[JoeTheJuggler]

Not a prescriber, but just one of those others chiming in. . .

Is the CDC concern about prescribing Tamiflu a concern about the supply of the drug or a concern about causing a Tamiflu-resistant strain of the virus to evolve?

I wonder if the answer to that question would clarify the "when to prescribe" question.

It does seem strange that they say to prescribe it early but only in severe cases. My understanding is that early in the infection, no one has a severe illness.

 

[Skeptic Ginger]

Not a prescriber, but just one of those others chiming in. . .

Is the CDC concern about prescribing Tamiflu a concern about the supply of the drug or a concern about causing a Tamiflu-resistant strain of the virus to evolve?
....

Both. And I agree with their philosophy there. I won't, for example, prescribe it for prophylaxis now. We did when the pandemic first started. But now that we've seen more of what's going on, prophy is just not needed.

It's my feeling/belief/conclusion the CDC hasn't been clear enough about the problem of needing to give a drug in the first 48 hours and at the same time trying to reserve it only for the sickest people. It's almost like they are trying to wish that little problem away or that they are in denial.

They've been searching for evidence the drug works after the first 48 hours. They've even suggested it works then if we give larger doses. And there is some evidence it does. But that still leaves us with the problem of identifying a severe case early on. And for that question, the CDC guideline is absolutely frustratingly silent.

I am angry the guideline led to the girl's death. I am glad I wrote the script for my neighbor's child. And I wonder who at the CDC involved in writing that guideline would withhold the Tamiflu from their own loved ones.

 

[JoeTheJuggler]

On the supply issue, I just did a little googling and I see that while adult doses are in ample supply, there's a shortage of children's doses. That seems like a pretty huge miscalculation. (I thought we knew from early on that younger people seemed to be at greater risk than older folks.)

So, if I understand right, prescribing Tamiflu for a sick child isn't really a problem for fear of creating resistant viruses (only using it prophylactically--I wasn't aware that that was being done at all).

So the question you're posing is really about the supply issue. That's a toughie. I'd hate to hear of even one child dying because he or she wasn't sick enough to get timely life-saving treatment. But if the epidemic really takes off, overusing it now could result in more deaths later.

Seems to me the solution is for the manufacturers to hurry up and increase the supply so that we have enough for those future cases that we don't have to be too stingy with what's available right now for current cases.

 

[Aepervius]

Well I looked it up in wiki :

Resistance mechanism

The genetic sequence for the neuraminidase enzyme is highly conserved across virus strains. This means that there are relatively few variations, and there is also evidence that variations that do occur tend to be less "fit." Thus, mutations that convey resistance to oseltamivir may also tend to cripple the virus by giving it an otherwise less-functional enzyme. The lack of variation in neuraminidase gives two advantages to oseltamivir and zanamivir, the drugs that target that enzyme. First, these drugs work on a broader spectrum of influenza strains. Second, the development of a robust, resistant virus strain appears to be less likely.[9] It is worth noting that the oseltamivir-resistant strains detected by Kiso et al. all appeared within individual children after treatment with oseltamivir – the children did not catch the resistant strains in human-to-human or bird-to-human transmission.

Sure wiki isn't pubmed, but it does sound like resistance to Oseltamivir isn't to be so feared, to my untrained eye it looks like making the virus less active is an advantage for us (the host).

That said, if really as said in wiki Oseltamivir slow the replication of the Virus down, I would indeed expect the biggest effect in the first phase of incubation.

 

[Skeptic Ginger]

Resistance to all anti-infectives is a problem. A few Tamiflu resistant strains of 2009H1N1 have occurred, none of which have spread yet. But the gene for resistance is widely circulating in seasonal flu strains, and flu readily exchanges genes between strains.

OTOH, the vaccine is beginning to be available. So there is leeway here.

As for the pediatric doses, a 14 yr old of average size takes an adult dose. Unless you weigh 88 pounds or less, you take an adult dose and since some patients are now being given even higher doses, I would not be concerned giving the 75 mg dose to a child as small as 60 pounds if there was no pediatric dose available. A 50 to 88 pound child is supposed to get 60 mg.

We had years to stock up on Tamiflu. We had months to get it distributed locally. There is no excuse for the government to use excessively strict or unclear prescribing guidelines rather than having obtained enough drug for the need.

And there is still Relenza which neither seasonal nor the new flu are resistant to. A teenager could take Relenza. Why are the docs not prescribing it? You break a capsule and inhale it (with a device) so it would not work for young kids. But it is as if the medical community isn't even aware of the Relenza option. And why has the CDC not added it to the guidelines?

I remain upset.

 

[Professor Yaffle]

In the UK there was a similar debate, but it was slightly different in that they were talking about blanket coverage for all cases, versus giving it only to high risk groups, (as opposed to severe cases as you are talking about).
http://www.guardian.co.uk/world/2009/aug/16/swine-flu-tamiflu-helpline-paracetamol

There was also some stuff about high rates of side effects in children:
http://www.telegraph.co.uk/health/s...flu-harm-outweighs-benefits-for-children.html#

 

[Skeptic Ginger]

Regarding the side effects: Kids vomit more. Gee, what a surprise.

They might get dehydrated. That is manageable. Though the need to get an IV in an ED has some risks of its own.

And the benefit the researchers used to weigh the risks against was shortening the symptoms by a day. How about the benefit of preventing death?

It amazes me how much bias there is in the medical community that influenza is a benign disease. I have a much different bias.

 

[Professor Yaffle]

But if the side effects are very common, would blanket prescription lead to more kids ending up in hospital with dehydration compared to a policy of high risk only prescription leading to some severe cases being missed?

 

[paximperium]

I would prescribe tamiflu to any of the at risk groups. Younger children, chronic illness, elderly, pregnant and maybe their caretakers. I would not have prescribe tamiflu to a healthy 14year old.

 

[Professor Yaffle]

This article talked a bit more about neuropsychiatric effects in children:

http://www.guardian.co.uk/society/2009/jul/31/tamiflu-side-effects-children

 

[Careyp74]

I would prescribe tamiflu to any of the at risk groups. Younger children, chronic illness, elderly, pregnant and maybe their caretakers. I would not have prescribe tamiflu to a healthy 14year old.

So, in regards to the 14 year old neighbor diagnosed with H1N1, would you have?

Can someone answer: Is there a threat of running out of Tamiflu? Would there be less of a possibility if people with H1N1 received the Rx and did not spread the Flu?

 

[paximperium]

So, in regards to the 14 year old neighbor diagnosed with H1N1, would you have?

No.

 

[JoeTheJuggler]

Can someone answer: Is there a threat of running out of Tamiflu? Would there be less of a possibility if people with H1N1 received the Rx and did not spread the Flu?

Supplies of adult doses, at least in the U.S. are good. Children's doses are in short supply.

As Skeptigirl points out, though, many of these children's cases are kids big enough to take an adult dose.

 

[JoeTheJuggler]

It amazes me how much bias there is in the medical community that influenza is a benign disease. I have a much different bias.

Me too.

I'd go even broader than that and say that people in general have a pretty distorted view of what is most risky and what isn't. I think few people have an awareness of how dangerous driving is, for example. I think, as with the 30,000 or so flu-related deaths that occur every year, the fact that traffic fatalities seldom make the news makes people sort of assume that that level of deaths is acceptable.

ETA: I would've thought the medical community had a better grasp of actual risks than people in general. OTOH, that isn't setting the bar very high.

 

[BenBurch]

The issue is not so much running out as it is getting a Tamiflu resistant strain.

I do believe that any pharmacist could convert adult doses into children's doses with some effort. The oral dosage form is a capsule and it can be re-dispensed in a smaller dosage in a standard gel cap...

 

[Skeptic Ginger]

But if the side effects are very common, would blanket prescription lead to more kids ending up in hospital with dehydration compared to a policy of high risk only prescription leading to some severe cases being missed?

No, and I am not talking about any "blanket prescription". In addition, the CDC guideline says to give Tamiflu to kids 5 and under who have probable flu.

What I was saying about the research is if your criteria for evaluating Tamiflu is a belief all it will do is shorten the clinical course by a day, then you are going to conclude the risk of increased vomiting outweighs the benefit.

If, OTOH, you use the criteria that a small number of cases of flu in otherwise healthy children are going to be fatal, then vomiting is manageable and the benefit of Tamiflu outweighs the risk.

 

[Skeptic Ginger]

I would prescribe tamiflu to any of the at risk groups. Younger children, chronic illness, elderly, pregnant and maybe their caretakers. I would not have prescribe tamiflu to a healthy 14year old.

And if the 14 yr old in Texas who died was your patient, would you reassess that position?

 

[Skeptic Ginger]

This article talked a bit more about neuropsychiatric effects in children:

http://www.guardian.co.uk/society/2009/jul/31/tamiflu-side-effects-children

I've followed that claim and don't see that the research supports it. It started with people in Japan believing Tamiflu was causing their children to commit suicide. The effect was not seen in any other country. But just as the Wakefield data led to the current anti-vaxer idiocy, people latched on to that hazard as if it were proved.

CONCLUSIONS: No increase in CNS-related and neuropsychiatric events was observed in adults, children, or adolescents with influenza who were prescribed oseltamivir in this study.

CONCLUSION: In this retrospective cohort study, no increase in claims-based neuropsychiatric events was detected in influenza patients who were and were not exposed to oseltamivir.

The available data do not suggest that the incidence of NPAEs in influenza patients receiving oseltamivir is higher than in those who do not, and no mechanism by which oseltamivir or oseltamivir carboxylate could cause or worsen such events could be identified.


There are more studies like these.

 

[Skeptic Ginger]

...
Can someone answer: Is there a threat of running out of Tamiflu? Would there be less of a possibility if people with H1N1 received the Rx and did not spread the Flu?

There is not a worldwide shortage of Tamiflu. There are local shortages due to lack of decisions to stockpile the drug and distribution delays.

Apparently there is a shortage of the pediatric formulation (liquid). I have not looked into this at all. 14 yr olds can mostly swallow capsules just fine.