FDA approves new drug to treat influenza(fda.gov)
fda.gov
FDA approves new drug to treat influenza
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm624226.htm
70 comments
Just because this may not help you, doesn't mean it may not help more at-risk people who may show signs much sooner, such as the elderly, children, people with compromised immune systems, etc.
The aim isn't to have one magical drug that works for everyone, but an entire set of tools in your arsenal.
The aim isn't to have one magical drug that works for everyone, but an entire set of tools in your arsenal.
It isn't that it doesn't help me in particular. And I do understand that it can help at-risk people. I personally think the amazing part of this drug is the decrease in infectious time, and the actual healing being secondary - at least for folks like me.
Nevertheless, it will help those folks with risks more if folks like me actually use this stuff too. If people like me take this within the time frame and stop spreading, it is much better. This is what I think we should fix.
We should encourage folks like me to use things like this. Not because we are helped so much by the medicine itself, but because it cuts down on transmission. To be able to do that, the problems I mentioned in the original post needs to be addressed.
Nevertheless, it will help those folks with risks more if folks like me actually use this stuff too. If people like me take this within the time frame and stop spreading, it is much better. This is what I think we should fix.
We should encourage folks like me to use things like this. Not because we are helped so much by the medicine itself, but because it cuts down on transmission. To be able to do that, the problems I mentioned in the original post needs to be addressed.
Parents, too - if I think I'm coming down with the flu, and know there's an early timeframe treatment available, I'll absolutely make it a point to see the doctor early.
Yeah, I think this stuff is great for when you're living with someone.
A few years ago, I got the the flu while visiting home during the holidays. My family took me to the clinic to get some antibiotics to deal with some secondary infections (I also had wisdom teeth stuff going on at the same time lol). I remember the doctor offering tamiflu to my family as prophylaxis, or to come back the moment they felt symptoms for tamiflu.
A few years ago, I got the the flu while visiting home during the holidays. My family took me to the clinic to get some antibiotics to deal with some secondary infections (I also had wisdom teeth stuff going on at the same time lol). I remember the doctor offering tamiflu to my family as prophylaxis, or to come back the moment they felt symptoms for tamiflu.
Mostly agree.
But, can even a good doctor diagnose influenza at an early stage, with enough confidence to be worth the odd false positive? Or are the symptoms too much like too much else?
I think this can be solved. Seriously, we have nurse practitioners at pharmacies that can test for strep throat and treat that: I see no reason why we can't have something similar for influenza.
Ideally, I think it would work best if we had a care level that was between normal doctor and urgent care that was open 24 hours a day. It'd mostly be to treat things like this. But until then, surely we can simply do tests for everyone.
Ideally, I think it would work best if we had a care level that was between normal doctor and urgent care that was open 24 hours a day. It'd mostly be to treat things like this. But until then, surely we can simply do tests for everyone.
Additionally, compared with placebo, baloxavir treatment significantly reduced the following:
The duration of flu symptoms, by more than 1 day (median time, 53.7 hours vs 80.2 hours; P <.0001);
The duration of fever, by nearly 1 day (median time, 24.5 hours vs 42.0 hours; P <.0001);
The length of time viruses continued to be released from the body (median time of viral shedding, 24.0 hours vs 96.0 hours; P <.0001); and
The levels of virus in the nose and throat from 24 hours through 120 hours.
Relative to oseltamivir, baloxavir treatment resulted in similar median time to alleviation of symptoms (median, 53.5 hours for baloxavir vs 53.8 hours for oseltamivir; P = .7560) and similar time to resolution of fever reduction (median, 24.4 hours vs 24.0 hours; P = .9225), respectively.
However, baloxavir treatment was associated with significantly reduced viral shedding duration (24.0 hours vs 72.0 hours; P < .0001) and significantly lower levels of virus in the nose and throat at 24 hours and 72 hours.
"It is unclear why the time to alleviation of symptoms was similar in the baloxavir group and the oseltamivir group even though baloxavir showed greater antiviral activity," the authors write. "The findings suggest that the symptom benefit of antiviral agents may have a ceiling in self-limited influenza illness in adults, perhaps because viral replication levels are decreasing by the time of presentation and illness pathogenesis is linked to host proinflammatory responses."
Overall, baloxavir was well-tolerated and had a lower incidence of adverse events reported (20.7%) compared with placebo (24.6%) or oseltamivir (24.8%). The most common adverse events were diarrhea (3%), bronchitis (2.6%), nausea (1.3%), and sinusitis (1.1%).
"The antiviral effects that were observed with baloxavir in patients with uncomplicated influenza provide encouragement with respect to its potential value in treating complicated or severe influenza infections," the authors write.
The duration of flu symptoms, by more than 1 day (median time, 53.7 hours vs 80.2 hours; P <.0001);
The duration of fever, by nearly 1 day (median time, 24.5 hours vs 42.0 hours; P <.0001);
The length of time viruses continued to be released from the body (median time of viral shedding, 24.0 hours vs 96.0 hours; P <.0001); and
The levels of virus in the nose and throat from 24 hours through 120 hours.
Relative to oseltamivir, baloxavir treatment resulted in similar median time to alleviation of symptoms (median, 53.5 hours for baloxavir vs 53.8 hours for oseltamivir; P = .7560) and similar time to resolution of fever reduction (median, 24.4 hours vs 24.0 hours; P = .9225), respectively.
However, baloxavir treatment was associated with significantly reduced viral shedding duration (24.0 hours vs 72.0 hours; P < .0001) and significantly lower levels of virus in the nose and throat at 24 hours and 72 hours.
"It is unclear why the time to alleviation of symptoms was similar in the baloxavir group and the oseltamivir group even though baloxavir showed greater antiviral activity," the authors write. "The findings suggest that the symptom benefit of antiviral agents may have a ceiling in self-limited influenza illness in adults, perhaps because viral replication levels are decreasing by the time of presentation and illness pathogenesis is linked to host proinflammatory responses."
Overall, baloxavir was well-tolerated and had a lower incidence of adverse events reported (20.7%) compared with placebo (24.6%) or oseltamivir (24.8%). The most common adverse events were diarrhea (3%), bronchitis (2.6%), nausea (1.3%), and sinusitis (1.1%).
"The antiviral effects that were observed with baloxavir in patients with uncomplicated influenza provide encouragement with respect to its potential value in treating complicated or severe influenza infections," the authors write.
Although this new drug may not treat people any better, the effect on flu incidence through the population could be profound! This is a big deal. The question though, is whether people can be convinced to use it when it doesn’t alleviate symptoms any better or faster. If it’s more expensive, likely they won’t unless they have children, work in healthcare, or otherwise care highly about their infectivity.
> a lower incidence of adverse events reported (20.7%) compared with placebo (24.6%)
Isn't that an odd result? Unless the drug is treating underlying viral issues that might not have been identified prior, it should be on par with placebo, no?
Isn't that an odd result? Unless the drug is treating underlying viral issues that might not have been identified prior, it should be on par with placebo, no?
People may be attributing symptoms of a continuing cold to the drug.
> The knowledge about taking medication or the anxiety about medication effects and illness course can cause patients to monitor symptoms in more detail, resulting in an amplified perception of benign sensations and physical symptoms.
[1]: https://dx.doi.org/10.1001/archinte.166.2.155
> The knowledge about taking medication or the anxiety about medication effects and illness course can cause patients to monitor symptoms in more detail, resulting in an amplified perception of benign sensations and physical symptoms.
[1]: https://dx.doi.org/10.1001/archinte.166.2.155
> The most common adverse reactions in patients taking Xofluza included diarrhea and bronchitis.
I wish the article listed the frequency or likelihood of getting these reactions. Given the choice between flu and bronchitis, I'll take the flu.
I wish the article listed the frequency or likelihood of getting these reactions. Given the choice between flu and bronchitis, I'll take the flu.
It's in the prescribing information.[1]
Adverse event - Xofluza(%) - Placebo(%)
Diarrhea - 3% - 5% [higher in placebo]
Bronchitis - 2% - 4% [higher in placebo]
The FDA requires that the manufacturer list the most common adverse events, even if they are unrelated to the drug in question.
[1]https://www.gene.com/download/pdf/xofluza_prescribing.pdf
Adverse event - Xofluza(%) - Placebo(%)
Diarrhea - 3% - 5% [higher in placebo]
Bronchitis - 2% - 4% [higher in placebo]
The FDA requires that the manufacturer list the most common adverse events, even if they are unrelated to the drug in question.
[1]https://www.gene.com/download/pdf/xofluza_prescribing.pdf
Whoa stay away from that placebo.
Interestingly, placebos have been getting stronger and more effective over the years. It’s a real bummer for people running clinical trials.
https://www.scientificamerican.com/article/placebo-effect-gr...
https://www.scientificamerican.com/article/placebo-effect-gr...
If you're ever board and you want to watch something on placebos I highly recommend watching this lecture by Dr. Irving Kirsch. Placebos are pretty nuts and probably really undervalued. https://www.youtube.com/watch?v=ISptt3CRAqc&t=15s
I'd rather die than live a lie.
Wow, what an interesting study! Especially since the effect was only seen in the US.
The flu can also cause bronchitis. More often than not I end up with bronchitis after a severe flu or cold.
I don't even bother with the doctor anymore (unless I have a fever) because I'm not interested in the codeine and I can just buy Primatene (ephedrine + guaifenesin) over the counter. Both my doctor and a pharmacist have admitted they could do no better.
I don't even bother with the doctor anymore (unless I have a fever) because I'm not interested in the codeine and I can just buy Primatene (ephedrine + guaifenesin) over the counter. Both my doctor and a pharmacist have admitted they could do no better.
> unless I have a fever
How often do you get the flu (actual flu, not a bad cold) and not have a fever? I've only had the flu once in my life (30-something years), and it was like being hit by a bus, having said bus park on your body, and having said bus catch on fire and slowly burn.
How often do you get the flu (actual flu, not a bad cold) and not have a fever? I've only had the flu once in my life (30-something years), and it was like being hit by a bus, having said bus park on your body, and having said bus catch on fire and slowly burn.
I meant if I have a fever with persistent, unproductive coughing after the flu itself has seemingly subsided. A fever would suggest a lung infection, either causing the bronchitis or vice-versa, but which in any event might require antibiotics lest it degenerate into pneumonia.
I've had pneumonia at least twice as an adolescent, but which went untreated for awhile because it was typical for me to have prolonged coughing and lethargy after a respiratory illness. So while I'll treat my own bronchitis, I have to be mindful that the bronchitis could be secondary, or could have resulted in an infection.
I've had pneumonia at least twice as an adolescent, but which went untreated for awhile because it was typical for me to have prolonged coughing and lethargy after a respiratory illness. So while I'll treat my own bronchitis, I have to be mindful that the bronchitis could be secondary, or could have resulted in an infection.
Chances are you are going to get diarrhea and bronchitis anyway if you get flu, whether you take the cure or not.
I would be more curious about how well does it play together with something like ambroxol hydrochloride - I used to get bronchitis as a complication every time I get cold in the past but as soon as I've discovered ambroxol hydrochloride I've forgotten about ever having bronchitis as a bad dream.
I would be more curious about how well does it play together with something like ambroxol hydrochloride - I used to get bronchitis as a complication every time I get cold in the past but as soon as I've discovered ambroxol hydrochloride I've forgotten about ever having bronchitis as a bad dream.
Diarrhea is not very common in patients with influenza. Perhaps a little more in children but not so much in adults.
Then don't read the side effects for aspirin ...
Apparently the main value of this new product is that it reduces the infectious time period (“viral shedding”) from 3 days (using Tamiflu) to only 1 day.
Would be interesting to see what impact that has during flu season.
Would be interesting to see what impact that has during flu season.
Dropping the viral shedding period from 3d to 1d is amazing. Radical impact on incidence rate.
The other value add is 1 dose vs 10 doses.
Indeed. But if this drug doesn’t treat someone any better or faster, it may prove difficult to convince them to use it if it’s more expensive.
Hmm, given that Xofluza is better in this respect and the same in all other respects, could it be said that it is the superior option?
Yikes, more and more efforts to combat the flu seem to be marginal or counter-productive. Too bad we can't just stay home and quarantine ourselves when we feel like death...
I still think that something like a flu (proper) and similar infections should result in mandatory quarantine from public places. Ofc a law for employers to offer either work from home or fully-paid sick leave for the duration of this mandatory quarantine would be required.
And yes, I am advocating for jail without probabtion being possible (not long though, like a week or two should be enough for minor infractions), so that the risk of violating the quarantine is more predictable.
Indeed, it's unfortunate that some people can't even continue to work from their homes while sick.
I think it's more unfortunate that some people have to work at all while sick.
[deleted]
If you have the flu, you are not going to be working.
Not for all. I'd like to think that most people could take a few days off for it, but can't pay for rent and food without working.
Even working on the farm, I rarely could take a sick day. Cows won't milk themselves and you can't tell them to hold it for a few days either.
Even working on the farm, I rarely could take a sick day. Cows won't milk themselves and you can't tell them to hold it for a few days either.
For most people, if you actually have the flu rather than a bad cold - and there's no easy way to tell since symptoms are similar, an actual flu will have you bed-ridden for at least a day.
I don't mean that people should take a few days off, they should, but that may not be possible, I mean that you'll have a period where you're not capable of more than basic tasks.
I don't mean that people should take a few days off, they should, but that may not be possible, I mean that you'll have a period where you're not capable of more than basic tasks.
You gotta work if you want to eat. For most Americans, at least.
[deleted]
I've discovered that megadoses of Vitamin C have worked for me.
It was too late to go the doctor, and I only had Vitamin C (as Sodium Ascorbate powder) on hand, so I chugged that down, up to maybe 5 grams every half-hour in orange juice, and about 6 hours later, the worst of the flu was gone. Next morning, I was feeling like I only had a minor cold. The flu never came back, either.
Since then, that's been my go-to strategy.
It was too late to go the doctor, and I only had Vitamin C (as Sodium Ascorbate powder) on hand, so I chugged that down, up to maybe 5 grams every half-hour in orange juice, and about 6 hours later, the worst of the flu was gone. Next morning, I was feeling like I only had a minor cold. The flu never came back, either.
Since then, that's been my go-to strategy.
Tamiflu only reduces symptoms by one day when taken within 48 hours of their onset. Who knows they have the flu and not a cold at that point? Looks like this is a similar joke:
> In the second trial, there was no difference in the time to alleviation of symptoms between subjects who received Xofluza and those who received the other flu treatment.
> In the second trial, there was no difference in the time to alleviation of symptoms between subjects who received Xofluza and those who received the other flu treatment.
Can you combine this with tamiflu for super recovery?
Neither of those are especially effective. According to clinical studies they reduce duration of symptoms by one day.
So I would not expect a combination of them to do much either.
So I would not expect a combination of them to do much either.
The evidence for the efficacy of Tamiflu was faked, it doesn’t actually do much if anything.
I’d be more interested on how it combines with elderberry syrup, which ostensibly does actually work.
I’d be more interested on how it combines with elderberry syrup, which ostensibly does actually work.
Wait. Did you just call the efficacy of an FDA approved product “fake” while heaping praise on a compound that’s never gone through a clinical trial?
Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections.
https://www.ncbi.nlm.nih.gov/pubmed/15080016
Edit: Symptoms were relieved on average 4 days earlier and use of rescue medication was significantly less in those receiving elderberry extract compared with placebo.
https://www.ncbi.nlm.nih.gov/pubmed/15080016
Edit: Symptoms were relieved on average 4 days earlier and use of rescue medication was significantly less in those receiving elderberry extract compared with placebo.
All right, so it was tested in a randomized clinical trial. However it was 30 treated patients, so pretty small. And a trial not actually signed off on by the FDA.
Also, I’m surprised symptoms were alleviated 4 days (96 hours) sooner when the Tamiflu trial said total duration of symptoms were 78 hours for the placebo.
Also, I’m surprised symptoms were alleviated 4 days (96 hours) sooner when the Tamiflu trial said total duration of symptoms were 78 hours for the placebo.
> All right, so it was tested in a randomized clinical trial.
Three or four actually.
> Tamiflu trial said total duration of symptoms were 78 hours for the placebo
And again, the Tamiflu data was faked. You can read the background on this here: https://www.bmj.com/content/345/bmj.e7303
When the real data was finally FOIA'd or whatever, it became clear that it no longer had even the minimal efficacy that was originally claimed. The way that FDA trials work is that you need two phase III studies showing a drug is more effective than placebo, but you're allowed to conduct unlimited trials that don't find any advantage over placebo without being required to make the data from these other studies public. That's what happened in this case, there were one or more additional studies that showed it wasn't effective, and when you included the data from the additional studies to calculate the overall effect the advantages disappeared.
There are several books about this, but since every time I link to books people complain that I'm trying to trick them into reading, here's an Internet article about what happened instead: https://articles.mercola.com/sites/articles/archive/2015/10/...
The main caveat on elderberry, other than the lack of FDA monitored clinical trials, is just that the stuff you're likely to find in your local drug store is Sambucol, which isn't the best quality. But you can go and buy this online that's actually good quality and not that expensive:
https://www.amazon.com/Gaia-Herbs-Black-Elderberry-Syrup/dp/...
Three or four actually.
> Tamiflu trial said total duration of symptoms were 78 hours for the placebo
And again, the Tamiflu data was faked. You can read the background on this here: https://www.bmj.com/content/345/bmj.e7303
When the real data was finally FOIA'd or whatever, it became clear that it no longer had even the minimal efficacy that was originally claimed. The way that FDA trials work is that you need two phase III studies showing a drug is more effective than placebo, but you're allowed to conduct unlimited trials that don't find any advantage over placebo without being required to make the data from these other studies public. That's what happened in this case, there were one or more additional studies that showed it wasn't effective, and when you included the data from the additional studies to calculate the overall effect the advantages disappeared.
There are several books about this, but since every time I link to books people complain that I'm trying to trick them into reading, here's an Internet article about what happened instead: https://articles.mercola.com/sites/articles/archive/2015/10/...
The main caveat on elderberry, other than the lack of FDA monitored clinical trials, is just that the stuff you're likely to find in your local drug store is Sambucol, which isn't the best quality. But you can go and buy this online that's actually good quality and not that expensive:
https://www.amazon.com/Gaia-Herbs-Black-Elderberry-Syrup/dp/...
[deleted]
I don't think the FDA would sign off on this RCT since it isn't a drug trial.
My question was more song the lines - “is this rigorous enough for FDA approval”?
> “is this rigorous enough for FDA approval”
Clearly it wouldn't meet the standards for a phase III clinical trial. But that doesn't necessarily mean it's worse. Pharma studies and plant studies both have their own sets of methodological issues, so it's hard to really compare them on how likely their findings are to be accurate or whatever. E.g. because elderberry isn't patentable, that eliminates most of the incentive to basically make up results like what happened with Tamiflu. But you also don't have the money to run multi-thousand person trials. How do these really compare with one another? It's hard to say.
For me, elderberry seems like the clear winner over Tamiflu because there are no negative side effects. At worst, it just doesn't work, but it only costs ~$0.65 per dose and the evidence that it does work is actually pretty compelling even though it would obviously be better if there were multi-site trials with larger sample sizes.
Clearly it wouldn't meet the standards for a phase III clinical trial. But that doesn't necessarily mean it's worse. Pharma studies and plant studies both have their own sets of methodological issues, so it's hard to really compare them on how likely their findings are to be accurate or whatever. E.g. because elderberry isn't patentable, that eliminates most of the incentive to basically make up results like what happened with Tamiflu. But you also don't have the money to run multi-thousand person trials. How do these really compare with one another? It's hard to say.
For me, elderberry seems like the clear winner over Tamiflu because there are no negative side effects. At worst, it just doesn't work, but it only costs ~$0.65 per dose and the evidence that it does work is actually pretty compelling even though it would obviously be better if there were multi-site trials with larger sample sizes.
I'm afraid you _maybe_ just made the same mistake as those that knee-jerk down-voted you -- it would be incredible if there really were no side-effects at all; some people must be allergic? No negative interactions?
> it would be incredible if there really were no side-effects at all; some people must be allergic? No negative interactions?
Fair enough. Perhaps a more appropriate way to phrase that would be that it using it doesn't require any more precaution than trying any other new food for the first time.
Fair enough. Perhaps a more appropriate way to phrase that would be that it using it doesn't require any more precaution than trying any other new food for the first time.
How do you know 30 is small? What number is large, and how do you know that, too?
Xofluza’s phase III was almost 1,900 patients.
Generally the size of the trial scales with the potential population and the statistical power you are shooting for.
Generally the size of the trial scales with the potential population and the statistical power you are shooting for.
Just to add, it’s also a question of how many studies you can preform and not publish the results. Doing 100 different 30 person studies is vastly easier than doing the same with 2,000 people studies.
Well the efficacy of Tamiflu is very questionable, but I’ll admit the “elderberry syrup” thing threw me. Maybe a broken clock thing?
[deleted]
Wait. Did you just assume something hasn't gone through a clinical trial because of how it sounds? There have been trials done of the effectiveness of elderberry syrup.
What were the results? For that matter, do you have a reference?
as someone else pointed out above: https://www.ncbi.nlm.nih.gov/pubmed/15080016
Do you know what product and what dosage of elderberry syrup is recomeened? I just looked it up. Sounds promising.
A teaspoon of concentrated syrup is enough, you aren't likely to get any additional benefit from eating more than that. But if you did you wouldn't experience any negative side effects, people eat elderberry pies all the time. You just never see them sold commercially because they're such a pain to make that it would be like $200 for a pie, and they don't really taste any better than blueberries. And because of where they grow (edge of streams and ponds) there is a very good chance of falling and hurting yourself while trying to forage them.
Hey, the berries of some species like Sambucus Nigra are poisonous so don't go foraging them just like that.
The flowers of S.N. are OK and can be made into elderberry juice. Your local Ikea probably even carries it ("flädersaft") if you want to taste.
I don't know if the juice from the flowers has antiviral properties but certainly the taste is better than Tamiflu. It actually tastes (subjectively) delicious.
The flowers of S.N. are OK and can be made into elderberry juice. Your local Ikea probably even carries it ("flädersaft") if you want to taste.
I don't know if the juice from the flowers has antiviral properties but certainly the taste is better than Tamiflu. It actually tastes (subjectively) delicious.
> the berries of some species like Sambucus Nigra are poisonous so don't go foraging them just like that.
Well sure you obviously need a field guide to edible plants, otherwise you'd likely poison yourself regardless.
And yeah you can't just eat them because the seeds have arsenic, but since that boils off at just over room temperature all you need to do is put them through a food mill to remove the seeds and then sautee the juice for a few min with the exhaust fan on.
Well sure you obviously need a field guide to edible plants, otherwise you'd likely poison yourself regardless.
And yeah you can't just eat them because the seeds have arsenic, but since that boils off at just over room temperature all you need to do is put them through a food mill to remove the seeds and then sautee the juice for a few min with the exhaust fan on.
Hmm, we used to collect it to make wine -- I wonder if we were unknowingly taking a tonic.
Linked study synopsis says they used 15ml
This is a serious issue with these drugs. In general, I won't go to the doctor in that time frame. This is especially the case if one gets symptoms on a friday afternoon - the doctors do not open until Monday. By the time I decide I*m sick enough to visit the doctor, I've already passed the time frame (Exceptions apply, of course). And I know I'm not the only one.
To me, this is a major downfall of such remedies. This could seriously make a difference in the way the flu spreads, but for that to really happen, we need more ways to get seen by doctors or nurse practitioners. We should encourage folks to see the doctor for "little" things. We need to make sure everyone can get seen. We probably need to make sure folks in service industries get seen immediately and won't lose their jobs over such things. This is mostly because service industry workers can spread these to a wide population easily without controls.