FDA proposes ending use of oral phenylephrine as OTC nasal decongestant

EDIT: After looking a bit more, the simple answer seems to be that it's not FDA approved for nasal congestion, and since there's not much money to be made, there's simply no incentive to go through the costly approval process..

Is ineffectiveness really a good reason to ban a substance? Why not just ban labeling it as a medicine instead?

(in case it wasn't obvious, this is broken windows fallacy)

And as OP points out: Phenylephrine is 100% useless.

A repeal won't turn back the clock on that of course, but it will make life easier for people with congestion.

https://dynomight.net/p2p-meth/

(It also gives me horrible insomnia if I take it at night so it wasn’t a huge hardship).

Guaifenesin thins the mucus instead, makes it more watery so it drains down the throat with no further complications like sore throat and coughing. And the extra volume helps flush bacteria out of the sinuses.

The restricted process around buying pseudoephedrine is imposed by state governments and not the federal government. A number of the states coordinate their policies, so it looks like nation-wide action but really isn't (in a legal sense).

FDA doesn't have the legal authority to put medications "behind the counter" like you would see in Europe or Canada. So untangled this is a weird mess of overlapping jurisdictions.

Before Sudafed was common in pills, they had the small disposable inhalers where the pseudoephedrine was not in crystal form but was dissolved in vaporous liquids like menthol. Inside the inhaler there is a cotton piece soaked with the pleasant-smelling liquid. The aroma vapors are drawn right up into the sinuses along with the active ingredient.

The inhaler itself was first marketed during World War II by the well-established 19th century Vicks company, already very successful for decades with it's earlier VapoRub aromatic topical OTC formulations. People are probably aware that this is one of the companies that is older than the US FDA. Older than the Fed & income taxes too, for those who are keeping score ;)

Natural products like ephedrine have long been the inspiration for medicinal chemists to synthesize similar compounds for potential screening as new drugs, so a number of new experimental relatives such as pseudoephedrine were produced eventually.

As the name implies, people did not always know what the real difference was between ephedrine and pseudoephedrine, since both molecules have the same molecular weight, naturally because both have the same number of carbons, hydrogens, oxygen, and nitrogen content.

Only a slight difference in chemical structure between the two, which got figured out soon enough.

Some of the less-similar new drug candidates were ordinary amphetamines. They are the ones that really got popular fast, especially in wartime :\

Now when the unique inhalers were born, it was a bit of the new synthetic ingredient along with the traditional aromatic mixture that Vicks was famous for, and the Vicks Inhaler was deemed safe & effective as recommended for OTC use. People loved it. Nobody had ever had anything as effective as that.

IIRC it was 50 milligrams per inhaler soaked into a few hundred milligrams of aromatic essential oil mixture. As expected they were a lot stronger when you first started smelling one.

That's because it was 50 mg of meth-amphetamine in the Vicks inhalers.

Parents would buy them for their kids, because they were so "safe", for self medication naturally, even at times when they would not consider dosing them up with cough syrup.

There was never any FDA-approved prescription for methamphetamine in any other form, only this one OTC product.

I would think the inhalers themselves were patent encumbered until the 1960's (remind you of an Epipen?) and by the 1970's other companies like Sudafed offered their own version, only not containing meth, give me a break.

The meth version of amphetamine became recognized as a dangerous drug in the after-war years when the negative effects became apparent with soldiers who had been given it in pill form habitually as stimulants, often when facing the most serious combat.

No other company ever was able to put meth in their inhalers, but Vicks slipped in under the wire and couldn't even be stopped for decades until some time after the DEA came into being. Everybody else was using pseudoephedrine from the start. By this time crystal meth was just beginning to emerge, which people were trying to avoid when they saw what it was like, at the same time different people started seeking meth more intently. Orders of magnitude more out-of-hand now.

The way Vicks stayed under the radar the whole time with meth in it, was hiding in plain sight.

Right there on the inhaler in fine print where it always was, active ingredient desoxyephedrine 50 mg.

Simply a less-common alternative chemical name for meth, and desoxyephedrine had become a very uncommon rapidly deprecated name quite early. Way before any amphetamines were commercialized, they were instead marketed using the well-known convention based on the Alpha-MethylPHenylEThylAMINE type nomenclature.

Anyway, back in the 1970's when it was first becoming known that shady operators were cooking meth by starting with inhalers, I looked at one of them and sure enough, 50 mg meth per Vicks inhaler. Who knew?

For a while there I figured they must be starting with way over 20 inhalers and probably would not extract nearly a gram of meth but it sounded feasible. I wasn't going to be the one to do it, my first job out of college was working for a company that was a real pharmaceutical manufacturer. So I wasn't going to tell anybody either. There was already talk among law enforcement about cracking down on this kind of thing. Suspicion of inhalers was beginning to barely arise, it was thin but widespread among anybody who had heard anything about this.

Eventually I figured out that the clandestine cookers were synthesizing their meth by using the pseudoephedrine in non-Vicks inhalers as starting material for their reactions ! Well, what do you know? Was I wrong the whole time?

I "guessed" so.

With not-so-blurry 20/20 hindsight, I would estimate that before I got around to figuring this out, a clandestine chemist had come along way before I knew a thing and had started out extracting grams of meth directly from Vicks inhalers. And the meth heads loved it, found out it was coming from inhalers and the word got around among them.

Some other chemist picks up the inexact word-of-mouth and by this time Vicks inhalers are outnumbered, sharing shelf space with numerous alternative brands, all of them containing pseudoephedrine as expected, and cheaper too. If they look at Vicks, it's the odd ball out, that doesn't look like the same kind of "ephedrine" as everything else. So they figured out how to do some home made reactions starting with Sudafed. And this is what was just starting to go through the roof.

This was before the Sudafed pills really took over, once they showed up they flew off the shelf way faster than the inhalers because there were more milligrams.

One day in the '70's I was in Walgreens and there was somebody buying over a dozen Sudafed inhalers so I knew what they were up to.

I went over to the aisle and looked at the then-current Vicks Inhaler, which I hadn't checked in a while, sure enough 50 mg of desoxyephedrine, active ingredient, same as ever.

The poor Sudafed buyer wasn't the least bit aware that real meth was right there on the shelf next to it.

And I wasn't going to say a thing :)

Most doctors and pharmacists didn't even have a clue.

Within a few years Vicks stated putting in pseudoephedrine themselves instead of meth.

Until it got way too far out of hand and the pseudoephedrine became tightly controlled, much more tightly than the meth was, as can be seen.

Edit:

"And now you know the rest of the story" - Paul Harvey

The monthly purchase limits on these tend to be ludicrously high, though. I think they're state by state, but in Texas, you can purchase up to 9 grams a month.

But it's useless as an oral decongestant.

* While there can't be any defense for the marketing of phenylephrine as a pseudoephedrine replacement, restrictions on pseudoephedrine are not irrational (that doesn't make them right, though I think they are).

* Pseudoephedrine by itself practically is methamphetamine, just in an unproductive chemical configuration. It is extraordinarily simple (though: not safe) to convert pseudoephedrine into meth.

* Pseudoephedrine is widely, practically universally available in the US without a prescription. It's a "behind the counter" drug, and, because of rampant abuse, access requires ID, like alcohol. Further, because the point of restricting pseudoephedrine is effectively a "rate limit" (to prevent people from acquiring enough Sudafed to make meth production practicable), Sudafed purchases are tracked.

* We've hashed out on HN the argument about whether that tracking results in spurious prosecutions. The one case I've seen us come up with, the arrest and prosecution of William Fousse, concerned someone who had a pseudoephedrine addiction (he was using it to come up from habitual alcohol benders).

* Restriction of pseudoephedrine does basically zero to staunch the flow of high-quality methamphetamine, which is produced at industrial scale with more sophisticated chemistry in Mexico and Asia.

* But restriction of pseudoephedrine might reduce the incidence of garage meth labs, which pose their own distinctive dangers to communities.

The argument in favor of continued pseudoephedrine restriction would be that the cost of the policy is relatively low (it inconveniences allergy sufferers, but most of those sufferers only marginally) vs. the public safety benefit (which is also probably low, but also probably nonzero).

Proculin made your eyes white white constricting the blood vessels for hours. All the stoners had it in their pockets.

Since it constricted blood vessels one could use it also to reduce the local inflammation on pimples, which was a neat off label usage.

Buy your cold medication at Walgreens. Good luck finding a non-Kroger grocer.

Xylometazoline is very effective. Sure that doesn't solve the oral/body-wide absorption of a decongestant but it's a good start.

From my personal experience phenylephrine (as a nasal spray) does work but it's one step off being useless. I've occasionally had to use it as a fallback when I haven't been able to get xylometazoline (where I am xylometazoline is only available in pharmacies whereas phenylephrine is also available in supermarkets and elsewhere).

It's interesting to note that the bans and restrictions on pseudoephedrine have had large negative consequences. Not only have ordinary users missed out on a good decongestant but it seems drug cartels have largely overcome the shortage of pseudoephedrine by substituting the precursor phenylacetone (P2P). Not only that but they've even managed to separate the chiral components of the final drugs which makes them indistinguishable from medical pharmaceuticals.

Incidentally, I prefer not to use pseudoephedrine as a decongestant, whilst I receive no mental stimulation from it, it nevertheless has stimulating properties that make me feel queasy. It's why my first choice is xylometazoline. There's also the related decongestant oxymetazoline, which I've found effective but it's not as good as xylometazoline (for me at least) but it's still vastly superior to the near-useless phenylephrine.

https://en.wikipedia.org/wiki/Methcathinone

from PE in mild conditions and aqueous solution. It has a hell of a kick and I’ve heard anecdotal accounts of people becoming seriously addicted but stimulant users as a class greatly prefer methamphetamine.

Pseudoephedrine should be easy and plentiful to obtain. I don't care if people use it to make meth. What they do in their private time doesn't concern me. Not being able to get Sudafed when I'm sick kills me. It's not like those people won't be able to get meth some other way.

We let people buy cars and cause 43,000 automobile deaths a year. People should be able to live life without stuffy noses. Maybe license people to buy meds and take it away if they abuse it? That's better than the draconian system we have now.

And don't get me started on ADHD medication and their shortages.

Edit: and there are 178,000 alcohol related deaths per year in the US. If you're going to allow that without prohibition, then please let us unstuff our noses.

I'm tired of living in a nanny state when we let people buy and own guns and swords and flamethrowers. Simply hiking on a mountain can kill you. Must we install guardrails on all the high places?

It's not that bad of a negative externality. Honestly. Not relative to all the other ones we've deemed acceptable. This is weird picking and choosing that doesn't make sense.

> Other side effects may include violent urges or, similarly, the urge to be successful in business or finance. ... > We expect that the simultaneous trends of restricting pseudoephedrine sales while N-methylamphetamine becomes less expensive and of higher purity will make the methods presented here increasingly attractive.

https://www.science.org/content/blog-post/other-methamphetam...

At least the Sudafed has acetaminophen in it ...

Always distilled water, though. It’s not worth waiting to boil the water, let it cool down, and then manage the dish used after. It’s also easy to get just the right temperature using distilled water in the microwave.

Guess I didn’t know how to properly use it, since I gave myself an awful sinus infection and was bedridden for next two weeks. To this day it’s the worst I’ve ever felt. Never touching a neti pot since then :/

It must be noted that the infection is incredibly rare and requires multiple conditions (like dysfunction of the immune system, unsafe tap water...)

- https://en.wikipedia.org/wiki/Naegleria_fowleri#Pathogenicit...

- https://charlotte.floridahealth.gov/newsroom/2023/03/DOHChar...

For example here in France tap water is disinfected with chlorine and hot water must be heated to at least 50°C which is enough to kill the microorganism.

On the other hand, depending how the distilled water is sourced (container bought in a supermarket...) & used (opened/closed daily...), it can actually create a much riskier source of infection.

I'm 58 now and I haven't had bronchitis like I used to since.

My theory is that it not only washes out stuff that might lead to infection, but also keeps your membranes from drying out and cracking, opening a vector for them.

My search was far from comprehensive, so it might merely have required looking harder. But I gave up early, on the assumption that the UK was similarly restrictive to the US.

In addition, I can't seem to find the 24 hour versions anywhere right now. I could probably buy meth more conveniently. :(

Cue: "A Simple and Convenient Synthesis of Pseudoephedrine From N-Methylamphetamine" https://improbable.com/airchives/paperair/volume19/v19i3/Pse...

Meanwhile meth making is more efficient, cheaper, and delivers purer-grade glass than ever.

I really miss being able to take pseudoephedrine. I mentioned to my doctor that it seemed to affect my blood pressure and he looked scandalized and told me I should never take it again. Apparently someone should have told me when I was diagnosed with high blood pressure. The only real information I got was a handout for a DASH diet.

My wife's a pharmacists so always laughs at it (and the decongestants) when we visit the UK.

There already is something similar - the NDA exclusivity period. You get 3-5 years where the FDA won't approve any other versions of the product.

https://www.tandfonline.com/doi/pdf/10.4155/ppa.14.30

But ambroxol isn't a decongestant - it supposed to help with phlegm.

I've used it. I thought it was going to be better than guaifenesin (equivalent available in the US). In my experience, it was not.

That entire blog post appears to be based on a second-hand report from someone who went on vacation in France and was told something by the person at the pharmacist selling them Ambroxol. I don't understand why rationalist bloggers are so keen to rely on anecdotes and hearsay when it supports a point they're trying to make.

But such suspicions became socially dangerous right around the time that Pfizer stood to make multiple billions selling a novel treatment for a recent pandemic.

(Pfizer testing drugs on Nigerian children) https://pmc.ncbi.nlm.nih.gov/articles/PMC1471980/

(Pfizer pleads guilty to criminal charges over Neurontin) https://pmc.ncbi.nlm.nih.gov/articles/PMC416587/

It would require the whole scientist communities and the sanctioning organisations to work together in order to validate a drug that is basically infective. Because you see before a drug is out on the market there are a lot of testing on animals, then humans and they have control group to measure how effective (or not) it is.

Things like that CANT happen.

Obviously I'm being sarcastic, that's the usual argument: you can't possibly have all scientist and federal organisation work together on malicious drugs.

The truth is that it happens, see that drug or the oxycontin. It just requires some shity people and the rest of scientist community to not care.

The saline wash is also known as a Neti pot here.

Compare with Dayquil - Acetaminophen 650 mg (pain reliever/fever reducer), Dextromethorphan HBr 20 mg (cough suppressant) and Phenylephrine HCI 10 mg (nasal decongestant).

> Guaifenesin, also known as glyceryl guaiacolate, is an expectorant medication taken by mouth and marketed as an aid to eliminate sputum from the respiratory tract.

> ...

> Guaifenesin is used to try to help with coughing up thick mucus, and is sometimes combined with the antitussive (cough suppressant) dextromethorphan, such as in Mucinex DM or Robitussin DM.

---

> Dextromethorphan (DXM), sold under the trade name Robitussin among others, is a cough suppressant used in many cough and cold medicines.

> ...

> The primary use of dextromethorphan is as a cough suppressant, for the temporary relief of cough caused by minor throat and bronchial irritation (such as commonly accompanies the flu and common cold), or from inhaled particle irritants, as well as chronic cough at a higher dosage.

---

The combination of the two is designed to reduce coughing and when you do cough, it is much more productive with the expectorant and cough suppression. It isn't a decongestant, but it has (personal anecdotal take) a good effect on getting rid of the secondary effects of congestion.

My lived experince with PE is it never works most of the time. But if I realise I need psuedoephedrine and I'm not somewhere or sometime where I can access it, I'll get PE and hope. Sometimes hope works, but it usually doesn't clear my sinuses very effectively. But if I have sinus congestion related to flying, I might also have soreness related to flying and take PE (because you can get it at the airport) and ibuprofen together, and maybe it works.

But also some people are more sensitive to some drugs, so it could work for you, while not being very effective in general.

The frustration largely comes from pharmacists and pharmaceutical companies selling decongestant remedies that do nothing and are known to do nothing.

Lots of versions of Alka Seltzer use aspirin instead of acetaminophen, and aspirin in combination with phenylephrine is documented to reduce congestion more than either alone.

Note - avoid the cold & flu versions (the ones with orange bottoms) and the day & night versions (orange and green bottoms), because they're not aspirin, they're acetaminophen. The traditional blue bottom "Alka Seltzer Severe Cold" is the one with aspirin and phenylephrine.

Did you pull a muscle stretching that argument into place?

People like meth. People in capitalist countries and non-capitalist countries alike.

It was in fact a hamfisted government regulation that drove this.

Nixon was the one that started the war on drugs and also enacted price controls. I would not call him a neoliberal. He also primarily interested in foreign policy and not the economy.

Also, Sudafed was only banned from being purchased easily in 2006. The bill was introduced by a random congressman from Indiana, a congressman was also easily offended by an offensive joke written on someone’s else cake.

> What else is the FDA wrong about

Too much. For one, numerous harmful additives are freely allowed. These additives may not cause immediate damage, but over the long term they really inflame the gut. They serve no good purpose in the medicines. Examples include: propylene glycol, sodium lauryl sulfate, titanium dioxide, talc, ammonium hydroxide, monoethanolamine, n-butyl alcohol.

I bet you think people should trust you even though I also bet you were wrong about something once.