Hacker Newsnew | past | comments | ask | show | jobs | submitlogin

> OTC medicines that by current standards would not be made OTC

Acetaminophen would almost certainly be in this category, if it could even get FDA approval at all. The effective dose is dangerously close to a toxic dose that causes liver damage, and not comfortably-far from the LD50. The only reasons acetaminophen is OTC is that it's been informally grandfathered in, makes an absolute fortune for pharmaceutical companies, and doesn't get you high.



> doesn't get you high.

this is the big one. Phenyl-epinephrine doesn't work at all, it's consistently failed to outperform placebo, and the only reason it's on the market is because the FDA doesn't like pseudo-ephedrine (sudafed) because it can be used as a precursor for meth. Same reason they've required individual blister packs for sudafed (if only there was some illicit drug which gave you the focus and drive to perform repetitive tasks for hours on end...)

Same thing for imodium. The reason all of a sudden it's in blister packs? People found a way to abuse it and the FDA is going to ruin it for the rest of us.

In the case of acetaminophen, the FDA actively uses it as a poison to "discourage" addicts from taking large doses of painkillers or cough syrup. The point is explicitly that if you take too much, you'll burn out your liver, the FDA is actively inserting poison into the medicine to "discourage abuse".

In all of these cases, the common factor is that it makes things much more annoying or even dangerous/lethal for average people, while addicts are completely unaffected. No opiate addict in the world is going to get clean because of individual pill blister packaging. Meth addicts will just pop some pills and churn through the sudafed blister packaging, etc.

I am waiting for the other shoe to drop on imodium, now that the FDA is targeting it, it can't be too long until it's behind the counter or pulled entirely. And as someone who (TMI warning) suffers from what I'd term as moderately frequent IBS (never diagnosed but maybe I should) that's really going to suck for me.

The FDA is simply an instrument of drug-war policy, they're not oriented towards patient care and outcomes at all.


What makes you say the FDA is actively adding poison to other drugs, are there first hand sources from them? This sounds like it could also be a case where they want to lower opiate consumption, and so adding some Tylenol increases pain relief without increasing opiate intake.

I am not sure that’s wise policy, but if you don’t think Tylenol is all that bad (again, I’m not sufficiently informed to say this, but the FDA obviously thinks it’s safe), then it’s not a bad overall policy.

It sounds like it could be either situation, I’m just looking for more evidence before making up my mind. (Yes, I am aware the US government poisoned people during prohibition in this exact manner, but I dispute that has any relevance as the decision makers and cultural awareness is very different now. We’ve come a long way since the 30s)


Why can you go to the store and buy rubbing alcohol to drink? It’s primary ingredient is just ethanol. The FDA literally mandates that the ethanol is not able to be safely consumed and is cut with poison that is not easily separated from ethanol.

Similarly, cutting opioids with Tylenol is not actually intended to be a deterrent to someone who gets their hands on the pills rather it deters people involved with illicit drug manufacture and distribution from using it as a base to grind up and sell.

Tylenol is really not super safe, at least by todays approval standards. Most official sources, which unsurprisingly have a huge bias towards Tylenol’s safety, state that allergic reactions are very uncommon, but recent meta-analysis’ are beginning to uncover that mild to moderate allergic reactions to acetaminophen is more common that originally thought. It does not get reported because if you’re already feeling like crap when you take it, some mild itchiness, redness, and discomfort would not be out of the ordinary without the Tylenol. As mentioned before, the toxic dose is much too close to the effective dose, I’ve heard from medical professionals that doubling a single recommended dose on extra strength Tylenol is enough to cause long-term damage to your liver. On top of all that, the fact that it is a weak pain reliever at best would solidly put this as a drug that’s not super useful.

I have a very low opinion of how we go about drug policy in the US. I am on a very controlled medication due to a sleep disorder (that causes hypersomnia) which I cannot go off for safety reasons. I also cannot get it filled more than 24 in advance without complicated authorization procedures that must be completed in the correct order. It’s a goddamn mess and serves only as a punishment to law-abiding patients for needing this medication. It also does nothing to curb illicit use because synthesis of a more potent product is so trivial.

This is an example of poorly targeted legislation, which was put into place because it’s the only thing they could exert control over. It does not further the stated goals of drug enforcement because it’s so easy to manufacture this stuff and the resulting product is so easy to move, bad actors can simply avoid this system. While I’m spending 3 hours every month orchestrating the complicated dance of my prescription between my providers, the pharmacy, and my insurance, someone is making a batch of shake-and-bake meth in about 3 minutes.


> Why can you go to the store and buy rubbing alcohol to drink? It’s primary ingredient is just ethanol.

AFAIK most/all rubbing alcohol (at least that which is sold in the US) is isopropanol, not ethanol. You can buy ethanol in not-for-consumption form, as denatured alcohol.


And it’s chemistry that forces the additional benzene in denatured alcohol. Water- ethanol forms an Azeotrope at 95% ethanol. Benzene is added to break the azeotrope and get to 99.99% ethanol. Chemistry not a conspiracy


No one is selling 99.99% grade alcohol as an antiseptic in the US. Its usually 70%.

There are additives in ethanol sold as an antiseptic to discourage drinking (various bitterants, not benzene).


No one is selling 70% ethanol as an antiseptic, it's isopropyl alcohol. Those additives in ethanol not intended for consumption are 8 parts acetone and 1.5 parts methyl isobutyl ketone to 100 parts ethanol. There are some rare ethanol based rubbing alcohols sold but the vast majority is isopropyl because it's not just denatured with bitterants, they add toxic substances as well.

Here's the actual formula they have to use that's enshrined in the law. https://www.law.cornell.edu/cfr/text/27/21.49


Ethanol as an antiseptic is less common, but its definitely a thing: https://www.amazon.com/Amazon-Brand-Rubbing-Alcohol-Antisept...

Its general sold as "ethyl alcohol" not ethanol, but its the same thing.


California apparently banned denatured alcohol because of the VOC content.

I accidentally found a gray market source before discovering it is banned. Makes me wonder why they still bother denaturing it.


The ethanol with methanol additive ("Denatured Alcohol") is a tax issue as well. Government wants to tax consumed ethanol.


Rubbing alcohol where I am is isopropyl alcohol (which is highly toxic -- your body metabolizes it into acetone), not ethanol. A kid in my high school class ended up getting his stomach pumped when drinking it to try to get drunk.


What makes you say the FDA is actively adding poison to other drugs, are there first hand sources from them?

"Not everyone thought it was a good idea to make alcohol deadly, when making it illegal hadn’t stopped drinkers, and New Jersey Senator Edward I. Edwards called it “legalized murder.” However, the Anti-Saloon League persisted, arguing that legal alcohol had killed many more in its day than denatured alcohol would kill during the transition to a teetotaling world. “The Government is under no obligation to furnish the people with alcohol that is drinkable when the Constitution prohibits it,” said advocate Wayne B. Wheeler. “The person who drinks this industrial alcohol is a deliberate suicide… To root out a bad habit costs many lives and long years of effort…”"

https://time.com/3665643/deadly-drinking/


This makes me wonder if it would have been possible to, instead of using something that causes significant harms to health, instead something which just causes a rather unpleasant experience.

But, I guess one important thing is whether such an additive is compatible with the altered substance still being usable for the purpose for which it is being made available.

Now, presumably something as simple as “dissolve large amounts of capsaicin in it” wouldn’t work (I’m not even sure if capsaicin can be dissolved in alcohol), but, what about something along those lines? Or something that just causes headaches, or vomiting?


During prohibition, the government tried things along those lines, as well as basically any poisonous or unpleasant chemical they could get their hands on. However, the problem was that anything not sufficiently alcohol-like could be pretty easily distilled out by bootleggers. What was much harder to distill out was large quantities of exceptionally-poisonous methanol.

Nowadays, of course, alcohol is cheap and plentiful enough that there's no incentive to re-nature it, and we can get away with much less extreme measures. In many cases, the alcohol won't contain any methanol at all, and may even be drinkable.

A good article on the government's arms race against bootlegging: https://slate.com/technology/2010/02/the-little-told-story-o... (also, the author's book "The Poisoner's Handbook")


They already add a bittering agent to ethanol when it's sold as a disinfectant. It's not toxic, just very unpleasant


Not true, they add a bitterant but if it's in the US they're still required to add acetone and methyl isobutyl ketone as well.

https://www.law.cornell.edu/cfr/text/27/21.49

That formula clearly spells out rubbing alcohol and disinfectants under the authorized uses. It's toxic and unpleasant.


Woah! I think it's different here in canada then.


I think that's what they ended up doing, post-Prohibition. A bottle of rubbing alcohol from the drugstore is either isopropyl alcohol, which is toxic by itself but not intentionally so, or ethanol mixed with a denaturing agent that's more benign than methanol or whatever they were using back in the day.


Different denaturants for different purposes.

Choose your poison:

27 CFR § 21.151 - List of denaturants authorized for denatured spirits. https://www.law.cornell.edu/cfr/text/27/21.151


Look up DXM.

You will never find it without either Gualfenisin or acetaminophen.

Does DXM need either of those to do what it does?

No.

Would it simplify dosing to be sold alone so that laymen didn't have to worry about potentially overdosing on three drugs at once instead of just one?

Yes.

However, from the war on drugs perspective, that makes it "easier to abuse" to achieve it's hallucinogenic side effect. Bundled with acetaminophen or gualfenisin however, you'd have to be a chemist intimately familiar with how to seperate the other two components to distill DXM in any amount with abuse potential, and the naive non-chemist trying to get high will either end up puking their guts out (Gualfenisin OD) or burning out their liver (Tylenol OD, which is exacerbated by alcohol consumption as well).

The Tylenol one is particularly problematic, because acetaminophen is also commonly prescribed with other common multi-drug formulations that people may not realize are additive.

When you take the route of adding a substance that does harm to discourage a pattern of behavior, you are poisoning. Poisoning being the act of artificially and with intent increasing the toxicity of an imbibed substance to disincent some pattern of behavior.

This is actually based on a natural pattern of behavior by the way. There is a mushroom that is generally completely harmless... Until you drink alcohol. Metabolizing the mushroom depletes the supply of the same enzymes that detoxify alcohol (and Tylenol).

https://en.m.wikipedia.org/wiki/Coprinopsis_atramentaria

So to be clear... If you call this mushroom poisonous, and it targets the same enzyme that alcohol does, then adding something like tylenol to something that doesn't need it to do it's job, you are poisoning.

It just happens to be handwaved because in the establishment's mind, those damn druggies aren't worth caring about anyway.

Not a partaker of DXM, but very concerned with the ethical implications, and the adverse contribution to trust in public health measures that this practice entails.



Interesting.

First off: Amazon is NOT my first choice for a source of pharmaceutical. Period.

Second, spin through the comments. Quoted below is an example of exactly what I'm talking about:

>Active ingredient is dextromethorphan. This blocks cough receptors in the brain. Got a cough? Get this!

>2. No extra ingredients. It’s so hard to find pure medicines just for cough. Store shelves are littered with bundled products for all sorts of symptoms. I don’t like taking a bunch of unnecessary meds, so I buy single symptom products like this.

8<---

>Finally, these gels are only sold in some stores. Shelf space is limited, so they rather carry heavily advertised, bundled meds that pay bigger margins. But they are here at Amazon for a great price!

8<---

Point there being, you've got a system where being able to acquire unadulterated formulations of a substance is the exception rather than the norm.

If you look through drug applications or filings with FDA, you will find that many pharmaceutical companies favor highlighting "abuse-resistant" formulations of combo drugs, while downplaying potential harms and that marketshare of the pure drug decreases after an approval of a combo drug is achieved.

I have started to pay more attention to this sort of thing since they started toying with doing the same thing on stuff I take. I can see a blatant flex of incentive shaping when I see it, and frankly, I disagree with it.

Very vocally.


You can also pick it up at your local Walgreens (https://www.walgreens.com/store/c/walgreens-wal-tussin-cough...) or CVS (https://www.cvs.com/shop/cvs-health-tussin-cough-liquid-gels...) if you prefer. Maybe your area has some regulations restricting access, but it's not a nationwide thing. It's just sitting on the shelf next to all the other cough medicines in mine.


I agree with you Amazon is not the best place to get pharmaceutical products and "abuse-resistant" formulations are effectively murder targeted at the most vulnerable. They are practically eugenicist in nature.

When I was much younger I had a bit of an adventurous spirit and never had problems finding pure DXM on the shelf. The issue I ran into most often was it was a frequent target for shoplifters so the name brand gel caps would often be out of stock. Usually you could find the generic store brand version though. Delsym was almost always available. The extended release may or may not be desirable depending on how long you want to trip, but IIRC you could just mix it with something acidic like orange juice to dissolve it and make it instant release. Just anecdotal I know, but that was my experience.


Dextromethorphan HBr? It's definitely sold on its own in the US.


I also wonder where the idea that the FDA 'denatures' hydrocodone with acetaminophen comes from. AFAICT, if you overdose on vicodin it's more likely the hydrocodone will kill you before the acetaminophen.


This is entirely false.

You can overdose from ~4 grams of APAP which you can ingest by taking 6 7.5/750 hydrocodone/APAP tablets

That's not nearly enough hydrocodone to kill you


That seems low -- 4 grams is the max daily dose for OTC acetaminophen.

According to this [1] the minimum single dose toxicity for APAP is more like 7.5 to 12 grams. Finding a value for a lethal hydrocodone dose is more difficult, but I did see 90 mg mentioned.

For the dose of Vicodin you specified, 90mg of hydrocodone would correspond to 9 grams of APAP. So it's a race that it looks like either one could win.

[1] https://www.uspharmacist.com/article/acetaminophen-intoxicat...


>The United States FDA clearly states “severe liver damage may occur if you take more than 4000 mg of acetaminophen in 24 hours.”

>There is no question that the upper threshold on the maximum daily allowed dose of APAP has been the subject of controversy.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913076/


The difference is you can build a tolerance to opioids, so the LD of hydrocodone in an addict (or even just someone using for an extended period medically) will be FAR higher than in an opiod-naive person.

Opioids kill via respiratory depression, not by destroying your organs.


Not sure I understand what you're saying about blister packaging? Are there drugs that don't come in blister packaging in the US?

Here all I can think about are the paracetamol/acetaminophen effervescent tablets that come in tubes of 8 x 1g (or 16 x 500mg).


There are drugs that come just in bottles: the typical OTC pain relievers (acetaminophen/paracetamol, ibuprofen, etc.) are all offered this way and you can easily buy bottles containing hundreds of pills. And of course there are others.

Prescription drugs are pretty routinely dispensed in just pill bottles also, though I'm sure there are some for which this isn't allowed.


I'm pretty sure there are also "degrees" of blister packaging too. You've got the ones that are just foil, you've got ones with a paper backing, and then you've got ones where I'm pretty sure the paper is glued to the foil so it's basically impossible to get it to separate and you have to cut it out with a knife.

The first doesn't really bother me. The last one is absolutely obnoxious. I'm guessing the FDA is pushing the last type for "drugs of concern" like sudafed or imodium.


oxy doesn't even come in blister packs here. at least not as of a few years ago, when i got it for spraining my ankle


You keep mentioning blister packs: I wish they were on all OTC drugs and many prescription drugs. On OTC drugs, I also support package size limits. These keep folks safer, lowering both accidental and intentional overdoses. I suspect that it taking longer to open and having a handy way to estimate what youve taken helps.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC31616/

There is plenty of cough syrup without acetaminophen sold in the US, by the way. People like all-in-one products, though, hence there being many with it in it. I'm gonna need some evidence for the "FDA actively uses it as a poison", though. I'm not so convinced a lot of folks think about side effects of tylenol but instead, see it as rather safe.

And it really doesn't matter if a few folks will find ways around an intervention. An improvement doesn't need to be perfect to be implemented nonetheless - because, it is an improvement and as such, better than before.


Umm... As you get older, you'll simultaneously need more pills and lose your ability to easily open blister packs.

A much better solution would be to have a robot pill dispenser that's hooked to the doctor's office, a pharmacy, and an alarm clock.


"Umm... As you get older, you'll simultaneously need more pills and lose your ability to easily open blister packs."

That isn't really a feature of old age. Some folks have some issues, sure, and sure - it is more likely when you are older, but by no means is it a given nor is it necessarily tied to old age. There are simple solutions for that, like ordering easy-to-open packaging from the pharmacist (here, they would literally put it in plastic bags). Some pharmacies already help folks organize medicines and I don't see where this would be a real issue.

I'll also state that most folks shouldn't need to buy a robot to take simple medicines plus it is going to add an expense that a lot of folks couldn't afford. It doesn't seem to be a huge issue in countries with blister packs that are fairly standard - again, pharmacies are generally helpful.


How is this "dangerously close to toxic"? Extra strength is 500mg. Adults should not take more than 3000mg in a day. Taking 7000 more more can lead to liver problems.

https://medlineplus.gov/ency/article/002598.htm

Common dosage forms and strengths:

Suppository: 120 mg, 125 mg, 325 mg, 650 mg Chewable tablets: 80 mg Junior tablets: 160 mg Regular strength: 325 mg Extra strength: 500 mg Liquid: 160 mg/teaspoon (5 milliliters) Drops: 100 mg/mL, 120 mg/2.5 mL Adults should not take more than 3,000 mg of single-ingredient acetaminophen a day. You should take less if you are over 65 years old. Taking more, especially 7,000 mg or more, can lead to a severe overdose problems. If you have liver or kidney disease, you should discuss the use of this drug with your health care provider.


Note that metabolism of drugs is roughly proportional to bodyweight. A petite 100 lb person may only need 200mg for an effective dose. An obese 400 lb person may require ~4x that dosage for the equivalent effect.

The one-size-fits-all drug dosing we do in this country seems crazy to me.

"Research Chemical" drug users have developed techniques to calibrate doses of substances with unknown potency - start with ~100th of what you expect to be an active dose and then gradually double it until proper effects are achieved.

I'd imagine it would be more expensive for pharmacies to distribute drugs in this way, but allowing patients to titrate their doses could significantly reduce/avoid negative side effects from just throwing the same standardized dose at every person with a prescription regardless of bodyweight.


This is especially important when it comes to children. This is because kids vary in weight in relation to age more than adults do, but the vast majority of drugs are dosed by age. This is just insanity at it's finest.


Yep, and that's only using the rough metric of bodyweight. There are a number of other major factors like size and health of liver, whether the patient has any under/over expression of metabolic enzymes, etc that can further complicate the determination of proper dosage.

Would be super cool if we had an objective measure of proper dosage - such as blood concentration or excreted metabolites - to give us more insight into how the drug is being metabolized by the individual.


Is there any evidence that harm is being caused from age-based dosing?


My understanding is that acetaminophen toxicity has been a problem particularly for children, because 1) the toxic dose is lower, 2) many common OTC products for children include some amount of acetaminophen among their active ingredients and 3) parents may give their children multiple such products (one for runny nose, one for fever reduction, one for nighttime relief, etc.) over the course of a day and end up exceeding the safe dose, leading to liver toxicity. That was the situation a few years ago at least.


acetaminophen is often put in medications because it's toxic. It's there to dissuade people from *gasp* taking too much and possibly experiencing some positive feelings or enjoyment that offends the sensibilities of decision makers. Better that we destroy a few people's livers than that those people get a buzz. (to be clear, this last sentence is not my view. I'm mocking that view)


This is the one and only reason that Vicodin and Percocet exist. They don't want people getting high, so they're punishing them by trying to kill them. It's barbaric. Literally evil.

Edit: just to be clear, there are times when it might make sense to take oxycodone or hydrocodone alongside acetaminophen, but they should be prescribed separately and with caution. The reason they're combination drugs is because the toxicity is a "desirable" side-effect meant to discourage abuse. It's that reasoning that is evil.


This also is silly, illegal drug users constantly take their dosages mixed with much worse things than Tylenol with no noticeable dissuasion effect that I am aware of. Acetaminophen is mixed with oxycodone etc bc it increases the pain relieving effect of the opiate drug (which for many people (e.g. me), are of limited effectiveness relative to the side effects/"buzz"), and because, unlike NSAIDs, it doesn't thin your blood so it can be taken after surgeries.

Having chronic pain sucks, having something that you can take for it, especially something boring like Tylenol that can't be snatched away from you by doctors/police/etc, is a huge quality of life issue.


I don’t think anyone reasonable is actively arguing to delist Tylenol as OTC, rather we shouldn’t be so restrictive on these medications that can actually really help people. In addition we should be giving people resources for discontinuing use when they no longer need it.

Also, we need to really research the NSAIDS after surgery thing, afaik, there has been nothing super rigorous on it and is only going off of the common knowledge that they do thin blood. I do not like Tylenol and my partner is allergic, we’ve both broken the rule about nsaids post surgery.


Yes absolutely. I don't want to see Tylenol go away. I want more options, not less. I think as long as companies are being honest about the product they are selling, even if it's ineffective I think it should be available.


Well I was in the ER 2 days ago and my liver enzymes were bad. I don’t drink, he said it was the acetaminophen I’ve been taking. I had been taking significantly less than the recommended amount for less than a week.


(to be clear: not a doctor)

the "daily" recommended doses are for a single day. If you are taking it daily you need to at least halve the recommended dose. I wouldn't have said a week was a problem but... yeah. Tylenol is dangerous.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913076/

Specifically this study referenced: https://jamanetwork.com/journals/jama/fullarticle/211014

> One study reported that ingestion of the recommended maximum amount of 4000 mg of APAP for 2 weeks resulted in the asymptomatic elevation of alanine transaminase, up to three times normal, in 40% of patients.19 These transaminase elevations did not amount to any clinical significance, and after the APAP was discontinued the transaminase levels returned to normal.19 Yet, while asymptomatic, chronically elevated aminotransferases may be of concern to healthcare providers, leading to further costly diagnostic studies or changes/restrictions in necessary medications

If anything the summary in that review is underselling it. Average was 2.78x baseline (3x is considered clinically significant) and 20% of the population was over 5x the peak (so, 20% had clinically significant elevations from the study). By peak levels, around 27% of the population saw peak levels of 8x baseline. So basically, even the "average" participant was almost to the threshold of clinical significance just from this study (at the recommended daily dose) and a cohort of around 20-25% will see clinically-significant warning signs at the recommended dosage, even among healthy patients. And risk factors significantly increase that.

That's basically a "liver stressor" enzyme, even if it's not killing the patients over the course of the study, it's not a good thing. That's your body's warning signal that it's stressed. And generally that's an uncontroversial finding I think, everyone agrees tylenol is a liver stressor, but they just have various thresholds of the acceptable risk. Would I do it daily? No.

And in med-speak, that's what they're saying here too. Use with caution, don't go above the recommended dosage in acute situations and use caution with chronic dosing. https://pubmed.ncbi.nlm.nih.gov/11847957/

Anyway, the rule of thumb I always heard is that half of the "daily" dose appears to be more appropriate for chronic daily usage. I am not a doctor and you can do whatever you want, but that is personally what I would hold to. Going less, or picking a different FDA-approved alternative like ibuprofen or aspirin, is always a perfectly acceptable choice.

That number appears to be reasonably supportable too. Instead of "half of our patients were over triple their baseline ALT level" this study found that 50% of the daily doage, chronically over 12 weeks, gets you to a 20% average increase in ALT levels. It's never not going to be a liver stressor and if you have other risk factors then you should probably stay away entirely (I think that's just good advice in general) but 20% increase in ALT after 12 weeks is a hell of a lot better than tripling your ALT in 2 weeks. But even then, during a 12-week study of 94 healthy adult patients, at half the recommended dose, they still had to withdraw one participant due to hepatotoxicity. https://pubmed.ncbi.nlm.nih.gov/25899926/

(as far as risk factors, see the first link above for a good review, aggravating factors for hepatoxicity can include things like non-alcoholic fatty liver or nutritional deficiency. Which basically describes an overweight computer-toucher with a poor diet to a tee.)


> the "daily" recommended doses are for a single day.

No. We've got thousands of people living more or less permanently on the maximum daily dose, including some children and vulnerable populations. Yes, some of those people have elevated liver enzymes. Yes, Tylenol is dangerous, but certainly not more than the alternatives. NSAIDs are certainly not any less dangerous, especially in populations with high prevalence of diabetes and kidney failure.

Tylenol overdose is one of the most frequent suicide plans in teens, with lethal doses usually starting from 8g. This is one of the reasons Tylenol has such a bad reputation.


The intervention-based study (giving patients a controlled dose and measuring the enzyme response) found that over half of study participants will have clinically-significant elevation of ALT at the recommended dose, and 20-30% will have numbers as bad as 5x sustained. Short study aside, that's not what I would personally choose.

Remember, there were never Phase trials showing 4g is the right maximum either. It’s just grandfathered in Uber the “well I guess if it were dangerous we’d have noticed by now” standard. But did a statistically large enough segment take exactly 4g over a course of years such that we can definitively say that’s safe? Most people are taking lower doses and shorter doses. At least on paper.

It's "there's no double-blind study that shows masks can prevent the spread of covid!" redux. And actually it's worse because there already is a standard for what clinically-significant elevated levels of that enzyme are, and healthy study participants are blasting right by it. That's not relevant .... because?

It's not just a random number going up from some un-related mechanism, it's liver stress, they even think they know what the mechanism is. It’s a reaction that is well-known for this drug, as a warning sign for this problem. Claiming that it suddenly doesn’t mean the same thing it’d mean if you took 0.001mg more is just pedantic. It was never formally studied and approved, it would be completely unsurprising if they got the number a little wrong.

And again - that's study participants who are chosen to be healthy. If you're fat, or aren't getting your macronutrients, your risk is much higher.

Using a lower dose or using something else is always a valid option. "The dose makes the poison" and using the lowest effective dose is absolutely standard practice and any doctor is going to tell you that's a baseline they always operate under.

Anyway, do whatever you want personally, but I would personally think strongly about staying at half the recommended dose or less for chronic usage, or looking for an alternative option. 20% of the healthy population, plus the unhealthy population, is a decent chunk of people.


I personally prescribe loads of painkillers, including the whole range of the WHO ladder, and many of those patients have liver tests. It rarely happens that we have to discontinue Tylenol due to hepatitis. I see people on NSAIDs with kidney failure every week. So again yes, Tylenol is toxic. But from personal experience, it's rarely a clinically relevant problem.


Frankly, I'm not sure why NSAIDs are considered the safer option. There was a period of time when I was young, where I had tried various painkillers for treatment of headaches. Every time I had tried an NSAID, my chest felt like it was going to explode, and it became difficult to breathe. Later learned that they may increase the risk of heart attacks and strokes (of which I have a family history). For these reasons, I've sworn to never take them, and only take acetaminophen on rare occasions when pain is bad enough.


Most people don't read the label on medicines that they take. Take two extra strength acetaminophen tablets, combination liquid cold medicine, some of the sleep aids with diphenhydramine + acetaminophen, a glass of wine, repeat for 3 days, and you're easily into danger territory.


5:1 ratio (a dose is "take two 325mg") between therapeutic and danger doses is really low as far as modern drugs would be concerned. Most drugs are more in the 50:1 or 100:1 range, drugs with a 5:1 ratio typically would not be approved and certainly would require very close supervision. Tylenol being OTC is complete insanity (or rather, regulatory capture and general public comfort with it).

Also note that those dosages are only for single usages! Tylenol also has a fun thing where daily/chronic usage within the "safe" dose can still cause liver damage. Chronic usage, you need to halve those doses.

The causal mechanism is believed to be basically low-level liver damage. Drinking a sixpack of beer once every couple weeks is fine - it's still not healthy, it damages your body, but your liver will repair itself in the meantime - but do it every day and your body cumulatively cannot repair the damage, while drinking a ton could cause acute failure. Tylenol actually works the same way - every dose is damaging your liver a bit, but if you don't do it every day it's fine, your body will repair it. But if you do take it daily, your body doesn't get a chance to repair the liver damage that tylenol causes, and the actual "safe" dosage becomes lower.

That puts the actual "safe" dose at closer to 1500mg per day for an adult. Having a 2.5:1 theraputic ratio on an over-the-counter drug is absolute fucking insanity.

And worse, those numbers are for men - they're lower for women. Yes, so is the theraputic dose, but they don't make special pills for women. Taking a standard dose (two 325mg pills) twice a day can cause liver damage to women, that's above the safe threshold for daily/chronic use. And that's not something people really consider when they pop a couple tylenol.

And then you've got combination products. OK, so you get sick, you take a couple tylenol and a dose of cough syrup. The dose of cough syrup likely is another 500mg or so of tylenol. So you actually took a 1125mg dose. And then you do it again before you go to bed. That's edging into dangerous territory with tylenol.

Obviously "don't do that", read the label and don't double up on an active ingredient that's already there in combination, but combination products are implicitly dangerous, they are fishing for that to happen, encouraging it. But the FDA wants it because it "discourages abuse". That's literally more important than burning out your liver.

The rest of the world uses tylenol in very niche situations. Usually it's behind the counter at a minimum (not always, but usually) and you probably will be told to take some ibuprofen instead. Ibuprofen and Aspirin are not perfect but they are much, much, much safer than tylenol is.

Tylenol is absolutely, completely, absurdly dangerous and should not be anywhere near as common as it is in the US, but drug war + legacy product sales rule the day.

To echo another sibling commenter here, I don't allow acetaminophen in the house period. It is an accident waiting to happen. I certainly don't allow combination products, and I will actively go out of my way to buy anything that doesn't include it. This is overkill as a single childless person who is aware of the danger, but you never know when something could go wrong and the cat knocks the bottle off the counter and the dog gets it, etc. You just should not keep dangerous things around unless you absolutely need to. Some things you can't avoid, but it's not hard to just buy ibuprofen instead of tylenol.


Actually every country is different in that regard. In many parts of Asia (e.g. Singapore, Hong Kong) good luck even finding ibuprofen or aspirin. It's usually behind the counter rather than in open display.

Instead there's dozens and dozens of GSK's Panadol paracetamol (acetaminophen), some of which even next to a cash register as a throw in.


Are you actually an MD?

I actually only ever hear about acetaminophen/paracetamol being dangerous from Americans - in other Anglo countries everyone will happily suggest you take it all the time, it is available OTC, and it comes as something kids will mistake for lemonade.

https://www.amazon.co.uk/Lemsip-Cold-Blackcurrant-Flavour-Sa...

> Ibuprofen and Aspirin are not perfect but they are much, much, much safer than tylenol is.

Only short term. Ibuprofen is less safe taken chronically, it'll destroy your stomach lining.


> For the average healthy adult, the generally recommended maximum daily dose is no more than 4,000 milligrams (mg) from all sources. But in some people, doses close to the 4,000 mg daily limit for adults could still be toxic to the liver.

https://www.health.harvard.edu/pain/acetaminophen-safety-be-...

4,000 mgs is easy to hit for people who don't realize that it can be dangerous. I know lots of people who would say "Well, my pain is bad, let me take double"... which for extra strength would be 4 x 500 MG, which is 2000 MGs in a single dose... which then if you do it twice in a day is right there at the 4000 MG mark. Most people are fine with that, but some people can get really sick.

If the person then does it 3 times a day, they are close to the danger zone for most people and over the danger zone for some people. Then multiply that by a few days....

You can easily say, "Well, they are taking more than they are supposed to!", but it is really common to take a bit extra if you feel really bad without realizing how dangerous it is, because Tylenol is `safe`


No, I am not. It's a dune reference.

Ulcers ("destroying your stomach lining") is less bad than "destroying your liver", and typically you will have to screw up harder before other NSAIDs reach that level. Tylenol literally is dangerous following the directions on the bottle, because those directions aren't calibrated for chronic usage, when they say "daily max" they don't mean you take it daily, that dose is even lower.


This is wrong. Kidney failure from NSAIDs is very common, and also very dangerous. And can develop at recommended dosage.


hey, thanks for the correction from a real doctor, I will be much more perceptive of that risk in the future.

again, I don't do analgesics daily but I will be sure to adhere to the doage schedule on that. Pain medication is such an unfortunate area of medicine.


I had a roommate who nearly died (his words) from taking a chronic regular dose of ibuprofen for a month or two when he was sofa-ridden after tearing his ACL.


Check your labels more carefully!

I just looked at a bottle of it here. Yes, 500mg. Adult dose: 2. That's 1,000mg. Every 6 hours to a maximum of 6 per day. That's 3,000mg/day. Danger at 7,000mg/day means a therapeutic ratio of less than three--nothing like that should be OTC and it's use should be carefully considered.


Ah, but two every 6 hours is 4000 mg/day, and my bottle claims that's safe. When I'm anywhere near that dose, I have a > 102F fever, which means I'm in peak form to compute dosages and timings.

Of course that's over the counter. Prescription strength also exists.

I'm a fan of switching between two pain killers / fever reducers (and only one liver killer), overlapping the effective time window by a few hours, but keeping both at ~50% the recommended max daily dose (a doctor recommended this to me a few years ago).

Of course, that makes the dose schedule more complicated, getting back to the problem it is trying to solve.


This is very silly, acetaminophen is very effective against pain, and for many people (e.g. me) is tolerated much better, especially at higher doses, than ibuprofen etc. There is already way to much panic about drugs/medicines, especially pain meds, especially especially for chronic conditions, without further hysterics about the 'threat' of useful and well tolerated chemicals. (Not a doctor, not offering medical advice.)

>doesn't get you high

A huge point in its favor if you can't lay in bed opiated all day.


I find acetaminophen almost completely useless for pain. Ibuprofen is better but still not very effective. Naproxen sodium is the only OTC pain medicine which is effective for me.


After going nearly a year without taking painkillers of any kind (not an aspirin, ibuprofen, or acetaminophen dose), I took some Tylenol for a bad headache, and it worked far better than it had ever worked for me before.

Granted, I've had to learn to put up with a lot more constant low-level pain in my day-to-day life. But I think that's a reasonable trade off for choosing between cooking my kidneys (aspirin, ibuprofen) or blowing out my liver (acetaminophen).

I had a really weird 1-in-ten-million side-effect with Naproxen sodium. It caused hard insomnia (confirmed under a doctor's care, this was before it was OTC).


>After going nearly a year without taking painkillers

I find this pretty shocking. Is this how people normally take painkillers, would you say? Speaking for myself, I normally go for years without taking anything.


Throughout my life I've suffered from significant allergies, so I've taken antihistamines for many decades (by prescription in my youth to OTC now). The allergies frequently cause sinus infections, which can include anything from minor pain around the ears and jaw, to heavy duty headaches.

It used to be the doctors would have me bomb my system with antibiotics, decongestants, and, yes, painkillers. Forty years on, we know a bit more, or at least I do, and I avoid as many medications (and the side-effects which increase with aging) as I can. I also suffered from tendonitis in the knees, so all of this put together meant I was regularly taking Tylenol or Advil for one or the other.

Then I stopped. I stopped using Tylenol unless I had a fever, or a really bad headache. When I got a sinus headache the first thing I'd reach for was a netty pot or sinus rinse instead of decongestants and painkillers. Physical therapy helped rehabilitate the knees, and when it rains, I just suck it up and limp for a day or two.

Those things and a few other medical issues add up to a steady catalog of pain that I just ignore for most of the day. In some cases, I stretch or exercise. I consider myself doing OK if I'm taking Tylenol or Aspirin once a quarter.

I'm happy you need no painkillers whatsoever for years on end. I think that's how it's supposed to be. For some people, it doesn't work out that way.


You probably don't have a chronic pain condition, but a fair number of people do, especially as they get older.


Many migraine sufferers will take pain killers multiple times in a month


People with chronic pain do what they have to do to get through the day.


accordind to the American Dental Association, 500mg of acetaminophen in combination with 200mg of ibuprofen is more effective than naproxen for pain relief.

https://jada.ada.org/article/S0002-8177(18)30117-X/fulltext (the result are in table 1)


Don't really care what the ADA has to say. I have conducted my own study on myself, my comment was regarding which is most effective for me, and naproxen sodium is by far more effective for my pain relief than other OTC pain relievers including combinations which I have in fact tried.


I'm not saying it'd be good if acetaminophen got you high, just that one of the reasons it's still OTC is that it doesn't get you high, so there's no one champing at the bit to crack down on it, the way they robbed us of the highly-effective and fairly-harmless pseudoephedrine for the one and only reason that it can be illicitly turned into a street drug.


That's reasonable. My concern is that during my lifetime I have had my access to useful medicines with zero abuse potential restricted because of (imo) panics that it could be turned into street drugs (pseudoephedrine), and also because of panics (imo) that it is too hard on my body (Torodol), and of course because of panics (imo) that they will turn me into a drug addict (opiates). The last class is admittedly worth being cautious about, especially with the more potent forms, but all of these drugs have legitimate medicinal uses and people suffer when they are taken away.

(Also, for drugs that you have to take to get through the day, the lack of a buzz is a definite benefit, and not just because it closes off one argument for restricting them.)


I doubt it.

Ibuprofen and other NSAISDs were approved not that long ago, cause plenty of GI bleeds, have nephrotoxicity when used chronically and increase the risk of cardiovascular events.

And they’re OTC.

Acetaminophen is actually very safe considering the number of serious events and the facts it’s in hundreds of different OTC combinations.


Any sources on that bit about chronic ibuprofen usage? I'm aware of the GI issues (stomach lining actually), and not the others. I'm a long chronic user (daily for years now), and appear to have a reliable mitigation for the GI problems, so I'd love to know more about the other stuff you mentioned.


I think Google would help with the nephrotoxicity topic, but with regards to cardiovascular risk, the FDA has been doing a ton of work on it since the early 2000's when Vioxx and Bextra were pulled off the market. The other NSAIDs like ibuprofen, naproxen were kept on the market due to a lower, but not non-existent, risk.

I take NSAID for pain, but personally I'm not too concerned as it's only a ~10-50% increase in relative risk. If I was at a higher risk for stroke or heart attack, or took them very frequently (say daily for arthritis) I'd probably look for alternatives, but there are lots of others things to worry about.

This is the latest FDA update I could find, there may be more information out there:

https://www.fda.gov/drugs/drug-safety-and-availability/fda-d...


Here are some interesting related HN posts regarding Acetaminophen:

https://hn.algolia.com/?dateEnd=1648670057&dateRange=custom&...


Although perhaps true about FDA clearance, I wouldn't be alarmist and characterize the effective dose as "dangerously" close to the LD50.

The highest dose that therapeutically is used is about 1000mg per dose. The fatal dose is about 15 times that amount.

To put it into perspective, a patient would have to be willfully taking 45 tylenol (325mg/pill) all at once to cause lethal liver damage. Doses like that are usually not accidental.


Not accidental, but very tragic. It's the #1 cause for calls to poison control, and accounts for 26,000 hospitalizations every year, and 500 deaths. Dying from an acetaminophen overdose is not a good way to go out, you spend a couple days in the hospital suffering as your organs fail and your loved ones watch.

Other OTC drugs are much safer. I don't allow acetaminophen in the house. Pseoudoephedrine? Yes.

Acetaminophen also should not be taken as a hangover cure, due to interactions with alcohol (alcohol and acetaminophen compete for the same metabolic pathways in the liver, and this exacerbates the toxic effects of acetaminophen). The problem is that someone who's drinking and has a hangover is probably going to reach for one of the two most common OTC pain relievers in their medicine cabinet, and not consider that one of those two pain relievers should not be combined with alcohol.


500 deaths (many intentional attempts at suicide) in a country of 350M where arguably every household has acetaminophen present is incredibly low.


By comparison, the number of accidental firearm deaths is around 430 per year, and somewhere around 40% of US households have a firearm. So we can say that having acetaminophen in the house is roughly as dangerous as having a firearm in the house. Obviously this is not some kind of direct comparison between firearms and acetaminophen.

I included the statistic in the first place because I thought it didn’t make sense to cherry pick the scariest statistics. I’m not fearmongering here, just trying to illustrate that acetaminophen should be treated with more care than we currently do. I think we could be making better health policy decisions about which medications are OTC and which aren’t, although this topic is incredibly complicated and doesn’t just come down to simple facts like toxicity.


I wouldn’t use accidental gun deaths when acetaminophen is often used in suicides. There are 25,000 of those with guns each year in the US.

But yes, acetaminophen is a drug, can be dangerous and shouldn’t be treated as benign.


Do you have numbers for how often acetaminophen are used in suicides?


Yes, agree with everything factual you said. I guess the problem isn't the compound itself but rather not enough information regarding its use.

I personally keep tylenol in the house because it's probably the best non-narcotic non-NSAID pain medicine.

We use it all the time in patients who are elderly with decreased renal function because they don't do well with opiates or NSAIDs (ibuprofen)




Consider applying for YC's Summer 2026 batch! Applications are open till May 4

Guidelines | FAQ | Lists | API | Security | Legal | Apply to YC | Contact

Search: