
Despite concerns, FDA approves new opioid 10x more powerful than Fentanyl - anigbrowl
https://www.statnews.com/pharmalot/2018/11/02/fda-dsuvia-fentanyl-approval/
======
sweetcherrypie
Naloxone is the drug used to block the effects of opioids. LE carry them, but
at the cost of $4500 for two injectors. The Narcan spray is slightly lest
costly iirc. I'm a uni student working on designing an auto-injector that
could be used instead (the medicine itself is very cheap) and potentially to
administer epinepherine too (also a case of cheap medicine - expensive
administration device).

I've made some progress but have no mechanical design experience. I'm not
optimistic about the time period needed for FDA approval so I'm really doing
it for the learning experience. I'd love some help!

~~~
mv
It is absolutely criminal that a <$20 drug can be sold for $4500... Auto-
injectors have been a solved problem for decades, and there is nothing special
about naloxone vs any other drug. Treating auto-injecting tech as different
for each drug only helps drive up prices and keep out competition by making
FDA approval very expensive.

I hope you are successful getting a generic auto-injector approved, but I
don't think your biggest hurdle will be design or engineering.

[https://www.nejm.org/doi/full/10.1056/NEJMp1609578](https://www.nejm.org/doi/full/10.1056/NEJMp1609578)

~~~
DanBC
> Auto-injectors have been a solved problem for decades,

And yet we still have stuff like this:
[https://www.judiciary.uk/publications/natasha-ednan-
laperous...](https://www.judiciary.uk/publications/natasha-ednan-laperouse/)

>(3) In the Emergency treatment of anaphylactic reactions Guidelines for
healthcare providers the preferred needle length is 25 mm for adrenaline
injectors to access muscle in most people. I heard during expert evidence that
Epipen needle length was 16mm - suitable according to the UK Resuscitation
Council for “pre-term or very small infants”. The use of needles which access
only subcutaneous tissue and not muscle is in my view inherently unsafe. An
alternative autoinjector, Emerade has a 24 mm needle.

>(4) The dose of adrenaline in Epipen is 300mcg. The UK Resuscitation Council
recommends a standard emergency dose of 500mcg. Emerade contains a dose
including 500mcg. The combination of what my expert told me was an inadequate
dose of adrenaline for anaphylaxis and an inadequate length needle raises
serious safety concerns.

~~~
mv
The Auto-injector's themselves are a solved problem and the device itself did
not fail. However,

-For over 10 years, It well documented in literature that even in normal BMI women the needle is not long enough to reach muscle. [https://www.ncbi.nlm.nih.gov/pubmed?term=15945556](https://www.ncbi.nlm.nih.gov/pubmed?term=15945556)

\- Prior to around 2003 IM and subcutaneous routes were both listed as valid
treatments for anaphylaxis. (See
[https://www.aafp.org/afp/2003/1001/p1325.html](https://www.aafp.org/afp/2003/1001/p1325.html))

-Depending on her weight 300mcg may be an appropriate dose for US guidelines (listed at 0.01mg/kg).

The listed issues may be from a company taking a 'one-size-fits-most'
approach. They also do not update their product with respect to new guidelines
and recommendations (new doses, new needle lengths, etc) Possibly to avoid
further FDA approval processes? With such large profits and so little
competition there is no incentive to innovate/update.

------
etrevino
It's worth noting here that not every opioid is metabolized the same. I can't
speak for this medicine, but different metabolic pathways are used to process
opioids.[1] Having more tools in your toolkit means that you are more likely
to be able to treat a patient's pain.

That being said, I think that one of the major uses for this drug will be to
treat acute pain in chronic pain patients. Those patients aren't opioid naive
and may need something that will "override" the tolerance these patients have
developed. I'm guessing that they'd also work for patients on the opioid
agonist/antagonist Buprenorphine, which is used for chronic pain, but tends to
block other opiates.

Lastly, while potent, this drug appears to wear off very quickly. That's going
to be key here, because it's simply not useful unless you're able to
administer a high quantity of the medicine.

 __To boot, I believe that the manufacturer claims that this drug has less
cognitive side effects than other opioids. [2]

[1]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704133/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704133/)
[2]
[http://www.acelrx.com/technology/publications/arx-04/MHSRS%2...](http://www.acelrx.com/technology/publications/arx-04/MHSRS%20ProjTeamPresentation%202016%20FINAL%2008_10_16%20MRC-0076.pdf)

~~~
jplayer01
The last time these companies promised it wouldn't be as addictive as previous
opioids, they were pulling numbers out of their ass and straight _lying_ about
it. I think we should all be alarmed if they're releasing a new drug that's
even more potent.

~~~
etrevino
It's definitely concerning, but that doesn't mean that it shouldn't be
released. It's the sort of drug that will find an appropriate use, though
pretty much only in edge cases.

~~~
jplayer01
> It's the sort of drug that will find an appropriate use, though pretty much
> only in edge cases.

You're way too trusting. While I do think drugs like this should exist for
those who really need it (particularly terminally ill patients), I'm
incredibly worried about how these drug companies intend to profit from the
drug (by selling these drugs to doctors in a way that encourages their use in
circumstances that in no way warrant it). Their profit motive and the
incredible expense of developing a new drug directly contradicts the need for
restrictive and sparing use of the drug to appropriate contexts.

------
esotericn
This article seems pretty low on detail. Almost all of it seems to be talking
about, well, not the drug in question.

What, exactly, does "10x more powerful" mean?

Potency? Presumably it'd then be prescribed in lower doses?

~~~
dogma1138
It’s the the binding strength which has direct impact on addiction and
withdrawal which is a bit scary since Fentanyl is 100 times stronger than
morphine already, heroine is only 5 times as strong for comparison.

~~~
skellera
No way that’s true. Buprenorphine has a much higher binding affinity than all
the worst opiates yet you don’t see people trying to do that over heroin and
all the others.

The strengths you’re speaking of are potency. And even then, most addicts I
know would rather have an unlimited supply of oxymorphone than fentanyl or any
of the others. At a certain point, cost outweighs all of that.

There’s so much misinformation out there about these drugs.

~~~
dogma1138
Buprenorphine is a partial agonist of the Mu receptor (the one which causes
the most physical dependency) and is antagonist for the rest, it’s also has a
very high affinity which displaces other opioids which is why it’s used in
addiction treatment.

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581407/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581407/)

Yes is more to this than just affinity the type and level of the binding to
each receptor is also important but on the grand scheme of things in this
context it’s not because all the opioids which are primarily used for pain
relief are full Mu receptor agonists which is when the simple affinity
strength estimate is pretty much sufficient to estimate potency and potential
harm.

Also last time I checked the potency is derived directly from the Ki value of
the Mu receptor which represents the affinity (regardless of agonism) of the
opioid, so these are essentially interchangeable.

------
post_break
All the negativity aside, my mom had a very aggressive cancer. Found in
October, she passed in May. She was getting doses of fentanyl and it was the
only thing numbing the chronic pain. I'm pretty sure it was a patch like a
bandaid. That said I'm glad it was available because she would have suffered
even more without it.

~~~
josephv
For those of us that have had to use opioids for cancer treatment to the point
of being addicted, then kicked the habit after treatment, all of the asinine
demonization of opioids is absolutely infuriating. I used ate percs like candy
during treatment and rehab, then used fentanyl patches to wean off. It was
hard, like really hard, but life is hard.

It's not worth it to try and convince anyone that hasn't knocked on deaths
door that sometimes you need palliative care in the form of narcotics to make
it to your destination, recovery or otherwise.

I'm sorry about your mother, she wasn't bad for using fentanyl or anything
else. She did great things with her life, you're proof. Don't let the stupid
media or internet SJWs try influence you. After my ordeal I haven't watched TV
or the news in years and am much happier for it. Family, work, and video games
(or hobby of choice) is all a person needs IMO.

~~~
erulabs
> Family, work, and video games (or hobby of choice) is all a person needs
> IMO.

I hate listing credentials in online forums, but as someone who lost two
grandparents to painful cancer, yes opioids are useful medicine. Additionally
as someone who lost 2 cousins, a best friend and more than a couple
acquaintances, there is a very real issue with opioids, and "a hobby of
choice" is _NOT_ all a person needs. I'm extremely glad you kicked it, but
please don't anecdotally shrug off an issue that is currently killing young
people at an unprecedented rate. My home town looks like it had a draft for a
war that was lost terribly - there are no young people left, we either fled or
died.

~~~
lj3
> "a hobby of choice" is _NOT_ all a person needs.

That's why he said family, work AND a hobby. He missed one, too: a close
relationship with God goes a long way. Family, community and faith are the
most effective ways of dealing with addiction.

[https://www.youtube.com/watch?v=ao8L-0nSYzg](https://www.youtube.com/watch?v=ao8L-0nSYzg)

~~~
coleifer
That's been my experience as well.

------
valarauca1
If you are interested in learning more the general name for this drug (outside
of the US) is ARX-04.

The maker has some data that compares it to Fentanyl [1]. Their numbering
states that is closer to 100x, and crosses the blood brain barrier in around 6
minutes.

[1]
[http://www.acelrx.com/technology/publications/arx-04/MHSRS%2...](http://www.acelrx.com/technology/publications/arx-04/MHSRS%20ProjTeamPresentation%202016%20FINAL%2008_10_16%20MRC-0076.pdf)
here

~~~
vilhelm_s
Interesting. I'm a bit confused about slide 6, which says that it has a
theraputic index which is 100 times better than fentanyl. It cites the
reference [1], which indeed has those numbers in it, but the full table there
is:

    
    
                   ED50   LD50  Theaputic Index
        Fentanyl   0.01    3.1     277
        Sufentanil 0.007  18     26716
        
        The therapeutic index is the ratio of LD50:ED50.
    

This clearly makes no sense, someone must have moved a decimal point, and got
a number which is wrong by a factor 10.

EDIT: Ok, it seems that it is indeed an error in the cited paper, but the typo
is for the ED50 number. In the original source[2] it's given as 0.00071, which
agrees with the "10 times stronger than fentanyl" claim in the original
article, and gives the correct theraputic index.

[1]
[https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1440-1681....](https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1440-1681.1995.tb01945.x)
[2]
[https://twitter.com/davidjuurlink/status/859227636400349184?...](https://twitter.com/davidjuurlink/status/859227636400349184?lang=en)

------
cperciva
The supply of Fentanyl on the streets is not coming from FDA licensed
manufacturers anyway.

~~~
onemoresoop
Yes but the doctor prescribes it first. When addicted, and the doctor doesn't
want to prescribe it anymore, the street becomes the supplier. Most likely
some politician or lobbyist out there is gaining on this whole chain of supply
and demand, how else would a stronger drug get approved in the light of the
opioid crisis we already can't handle.

~~~
leetcrew
> Yes but the doctor prescribes it first.

fentanyl sold on the street is generally not diverted from prescriptions.
fentanyl that you can actually take home tends to come in something like a
patch where the drug is suspended at very low concentrations in a gel. illicit
fentanyl sold at scale usually comes from illicit labs overseas.

> how else would a stronger drug get approved in the light of the opioid
> crisis we already can't handle

in this context, "stronger" simply means more potent by weight. you shouldn't
assume that more potent opiates are more addictive; fentanyl is not the drug
of choice for most opiate addicts.

------
olliej
What could go wrong?

I think a solution to a lot of this would simply be to make the manufacturers
of such be responsible for the costs of getting people off them. And the
cleanup costs for cities that have to deal with the results.

------
rscho
For the record, a large part of anesthesia worldwide is done with that
molecule. Potency is not everything, and using sufentanyl in hospital contexts
is very much justified. The tablet formula of course makes it far more prone
to misuse, though... I can also add that iv remifentanyl is on the market in
the US, prescribed routinely, and is much more powerful than even sufentanyl.
In fact, so powerful that getting high on it would most certainly kill you,
making it pretty much useless to drug users. So again, potency is not
everything.

~~~
DanBC
> In fact, so powerful that getting high on it would most certainly kill you

To be fair, this is what we used to say about fentanyl until recently.

~~~
rscho
The problem is that with high potency, you also get more side effects for the
same "painkiller" effect (also depending on absorption velocity). Therefore,
using something such as remifentanyl in the mix would almost certainly be
counterproductive if you are looking for the "high". It would displace
fentanyl, and be more risky. And first of all, it is far more expensive than
fentanyl.

------
fromthestart
I just want to point out that the words "10x more powerful" serve no purpose
other than to sensationalize the headline.

Potency doesn't matter; pills are mixed with fillers to adjust dosage.

Now, if street drugs start being cut with this new drug, that's another story,
if the mixing is poor.

------
whoisjuan
This dissipates any doubt I had about the influence of lobbying.

FDA, a federal agency that is fully aware of the harmful and addictive nature
of opioids (and its impact on the public health system) approves one of the
most powerful opioids ever, disregarding the fact that its unique advantage is
the fact that this is a non-intravenous administered opioid...

Ohh, and the argument for approving is basically that they believe is good to
have more alternatives to existing opioids. Really? Like is not fentanyl
strong enough to address every possible medical use case for a powerful
opioid?

~~~
chimeracoder
> This dissipates any doubt I had about the influence of lobbying.

Who are you accusing of lobbying here? It's pretty clear from the article that
the primary advocate for this drug is the military (DoD).

> Like is not fentanyl strong enough to address every possible medical use
> case for a powerful opioid?

Strength is not something that's assessed along a one-dimensional axis, much
as popular reporting on opiates and pharmaceuticals would have you believe.

~~~
whoisjuan
> Who are you accusing of lobbying here?

AcelRx, the pharmaceutical company that produces and distributes DSUVIA. You
understand how lobbying works right? Even if the Department of Defense is
advocating for the use of a drug, they don't have any input on the safety of
whatever they are advocating for. This is the role of the FDA. AcelRx happens
to have something that the DoD wants so they lobby for its approval. In this
case, DoD, FDA, and AcelRX are all different parties but is clear that AcelRX
is the only party that will benefit financially from this.

Just from an anectodical perspective, so you can understand how this works,
check ACRX stock closing price today. It closed 16% up today.

Just because the DoD is advocating for this drug, that doesn't mean that
there's no pharmaceutical lobbying behind this. By that logic then all defense
contractors and weapon manufacturers wouldn't have to lobby as much as they
do.

~~~
chimeracoder
> You understand how lobbying works right?

Yes, I do. There's no need to be condescending.

> clear that AcelRX is the only party that will benefit financially from this

The DoD benefits as well.

> Just because the DoD is advocating for this drug, that doesn't mean that
> there's no pharmaceutical lobbying behind this.

Thr converse applies too. Just because FDA approved a drug that the military
wanted, that doesn't mean that the approval was the result of their lobbying.

------
Zelphyr
Is the FDA stacked with industry insiders like the FCC? Is that what's going
on here? Or does the DoD have that much influence?

~~~
chelmzy
Why would the DoD have a hand in this?

~~~
0d311
In the article, they discuss a few times how a consideration for this drug is
servicemen in the field.

------
d--b
I don't understand, the article states the distribution is very controlled and
geared towards the military. The problem with Fentanyl is its widespread
prescription by family doctors.

If the US doesn't allow its distribution through mainstream channels, it's no
big deal. I'm pretty sure that stuff is weaker than morphine, yet morphine is
quite available in hospitals...

EDIT: ah, apparently it's quite stronger than morphine. The argument still
holds. Hospitals do have stronger stuff :)

~~~
arebop
Fentanyl is much stronger the morphine, so if this is 10x stronger than
Fentanyl then it is also much stronger than morphine.

~~~
PhasmaFelis
Yeah, but what does "strong" mean in this context? If it means you can get the
same effect with 1/10th the dose, then you just put 1/10th as much active
ingredient in each pill and nothing effectively changes.

There's some discussion at the top of the thread that suggests it's more
complicated than that, and may make it either more or less dangerous,
depending.

------
gammateam
The FDA approves things based on the purpose they were presented to the
FDA/market for.

It isn't based on danger, it is based on evidence backed disclosure of the
danger.

In the specific use the company told the FDA about, it passed, and that will
usually happen with some objections or outright denial. The denial didn't
happen and that isn't article worthy.

------
microcolonel
Before you rage against this; fentanyl has been an immense asset to medicine,
and when dosed correctly it offers much more manageable side effects (and
greater control) than many other opioids. Just because the drug is more potent
per microgram, that doesn't mean there's some sort of moral failing involved
in bringing it to market.

When you're in immense pain, and the only safe way to relieve that for you is
some potent opioid, I guarantee you will thank people for bringing these
things to market.

------
droithomme
What could possibly go wrong?

