Really lovely article. In paramedicine we usually treat 10g of acetaminophen in a 24-hour window as a potentially fatal overdose. That's also why the law in Australia was changed to require acetaminophen to come in blister packs (harder to get each pill out) of no more than 16. At 500 mg, that only gets you up to 8 g if you eat the whole thing, which is still hopefully non-fatal.
I always thought a simple over-the-counter supplement (NAC) being the cure for an overdose was so cool. It's a pretty cool substance in a lot of ways, and this is a great spur to myself to research it more thoroughly.
What does ingesting 10g of acetaminophen even look like? I've got to imagine the fatal dose is far, far, far lower with chronic usage. Finding out that people are ingesting grams is profoundly disturbing.
I have taken 4-5g in a day while suffering from intense pain before.
There is a limit to the amount of opioids they will prescribe you, even if you are in mind shattering pain. For instance while attempting to get your dental insurance to actually cover a treatment you may find yourself between risking organ damage or risking $5000+ in ER visit bills only to have them refuse to give you anything but Tramadol.
Taking too much acetaminophen is bad for you but 10g is 20 extra strength pills and that much isn't likely at all to kill you but damage your organs is quite possible. Reading this might make someone in a bad place think that much will do the job and it won't. Tylenol poisoning's most likely outcome is permanent organ damage and pain, don't try it.
This can easily happen over the course of 24 hours if you're in "fuck me I'll do anything to make it stop" levels of pain. I've taken more than 20 ibuprofens in a day a few times in my life, which, while not medically advised, did not kill me. I actually had no idea acetaminophen was so dangerous.
They are common in France, but not in such packages: There are restrictions that prevent you from buying more than than 8g/day (theoretically at least, I don't believe they are strictly applied in practice).
Yes, and you can still die in a car crash if you're wearing your seatbelt, and wearing a helmet on your motorcycle won't save you from a head-on with a truck, and you can still drown in a pool with a lifeguard, and you can still die in a burning building with smoke detectors.
Harm reduction is about shifting probability distributions, not guaranteeing outcomes. Kids can still get into pill bottles with childproof medication caps, but accidental ingestion of aspirin by children reduced by 40-55% after they were mandated. [0]
No. Ethanol and tylenol compete for CYP2E1 that produces toxic NAPQI, so no, acute alcohol intoxication has a protective effect at least where it comes to tylenol toxicity.
I grew up with the understanding that acetaminophen was the safe choice for fever or aches, and ibuprofen what the more potent compound for inflammation and severe pain. I recall casual anecdotes that "my doctor said 1.5x or 2x ibuprofen dose is ok when warranted" to address major incursions.
I've never once thought about taking more than the recommended dosage of acetaminophen, largely because I had no expectation that it would provide additional benefit..
In reality, I try to consume 1/2 doses of anything or nothing at all, unless it's a serious medical treatment being administered by a professional.
I think most overdoses happen as a result of someone trying to hurt themselves, but I’ve also previously been in sufficient pain (always dental) that I’m counting the minutes down to when I can take more painkillers, so it’s easy to see how you could take double the expected dosage.
This is some of the most useful information I've received in a while. Like the author, the low overdose threshold of acetaminophen made me avoid it, even though I always take low doses anyway and ibuprofen gives me acid reflux almost every time.
Both ibuprofen and naproxen sodium are NSAIDs and are bad for your kidneys especially in long term. I had kidney failure due to what was eventually diagnosed as an autoimmune disease but they first thing the ER doctor will ask is if you have been taking NSAIDs. My nephrologists told be its still safe to take acetaminophen at the proper dose.
None of us are your doctors but Naproxen has well-known gastric issues up to ulcers and stomach bleeding which is why it's advised to be taken with food and why it's also often prescribed with a PPI or H2 Antagonist. Cox-2 selectives such as Celecoxib greatly reduce this risk but seem to be associated with some small cardiovascular risk (admittedly this is a feature of all NSAIDs though less so in Naproxen apparently).
Some believe naproxen sodium is worse for you because it lasts longer. Longer duration for reduced mucous membrane coverage in your stomach and intestine. Longer duration for reduced blood flow to your kidneys.
I would definitely have a chat with a doctor about it.
I've known people who've overdosed on Tylenol and died. I'm not saying that ibuprofen won't give you acid reflux and won't damage your kidneys, but due to <reason> I tend to take a lot of ibuprofen and also for <reason> take another medication that constricts my arteries and for <reason> get a lot of blood/urine work done... and my kidney function is good and despite everything I'm generally healthy. So I would say, like many things, what medicines you take probably depend on your specific body and situation. Regardless, you won't die accidentally from an acute ibuprofen overdose. You just might die from taking tylenol if you don't realize your liver is already damaged for other reasons. So there you go!
Unless you’re in Rhabdo. If you’re in so much muscle pain and your kidneys are working overtime to clear broken down tissue and you then hit them with too much ibuprofen, then you can go into kidney failure and die accidentally.
My father, who is otherwise in very good health for a ~60 year old, has severely reduced kidney function from taking an ibuprofen+antihistamine most days of his early life to deal with allergies.
I'll second the claim that no doctor at any point in his life had told him the risks of doing that, and many encouraged the use of ibuprofen over any other alternative (including the alternative of not using OTC painkillers every single day).
After severe cramps once when I had to use a lot of ibuprofen (dental surgery / wisdom tooth) I now only use ibuprofen with a stomach protector to avoid stomach cramps, H. Pylori, and reflux.
Acetaminophen is part of ECA stack weight loss formula, while article says not OK with fasting. Either way, more safe solutions are known these days.
Depends what you’re taking it for. Generally people take NSAIDs for muscle and dental pain, or anything that’s obviously inflammation, and paracetamol for anything else, particularly headaches, and is a common adjunct treatment if you have a cold or flu.
Well, I mean, drats. I too always assumed Ibuprofen was safer than Acetaminophen; not the least because of massively oversimplificatic "reduced inflammation - GOOD!" 'Logic'. I'm 47 now and have probably preferred ibuprofen for last 27 or so.
Max dose combination (IBU/APAP FDC) can be useful as a substitute in emergency therapeutic situations compared to opiates. Not recommended ordinarily because of liver, kidney, and stomach impairment.[0]
Taking ibuprofen with questionable stomach condition may want to consider taking a famotidine adjuvant or duexis [1] or acetaminophen instead.
Overdose treatment of acetaminophen poisoning is the stinky N-acetylcysteine (NAC), so that maybe worth stocking whenever Tylenol is kept in a house with kids. Overdose of ibuprofen is palliative, requiring IV fluids and dialysis.
Both of these pills are really dangerous for dogs.
Ibuprofen damages the kidneys -- and that damage is often permanent. The little filtering devices inside the kidneys don't grow back once they're destroyed. A dog who survives the poisoning can end up with lifelong kidney disease, which means special diets, more frequent vet visits, and a shorter life than she should have had.
(I watched this happen to my own dog after a house sitter stepped on her paw and gave her ibuprofen to "help." My dog lived, but she needed a special diet for the rest of her life.)
Acetaminophen wrecks the liver, and it also can damage red blood cells so they can't carry oxygen properly. A poisoned dog may get lethargic, vomit, start to breathe heavily... This is especially dangerous for older dogs, or any dog whose red blood cells are already compromised, by conditions like IMHA.
Mischkowski’s own research has uncovered a sinister side-effect of paracetamol. For a long time, scientists have known that the drug blunts physical pain by reducing activity in certain brain areas, such as the insular cortex, which plays an important role in our emotions. These areas are involved in our experience of social pain, too – and intriguingly, paracetamol can make us feel better after a rejection.
Mischkowski wondered whether painkillers might be making it harder to experience empathy
And recent research has revealed that this patch of cerebral real-estate is more crowded than anyone previously thought, because it turns out the brain’s pain centres also share their home with empathy.
For example, fMRI (functional magnetic resonance imaging) scans have shown that the same areas of our brain become active when we’re experiencing “positive empathy” –pleasure on other people’s behalf – as when we’re experiencing pain.
Given these facts, Mischkowski wondered whether painkillers might be making it harder to experience empathy. Earlier this year, together with colleagues from Ohio University and Ohio State University, he recruited some students and spilt them into two groups. One received a standard 1,000mg dose of paracetamol, while the other was given a placebo. Then he asked them to read scenarios about uplifting experiences that had happened to other people, such as the good fortune of “Alex”, who finally plucked up the courage to ask a girl on a date (she said yes).
The results revealed that paracetamol significantly reduces our ability to feel positive empathy – a result with implications for how the drug is shaping the social relationships of millions of people every day. Though the experiment didn’t look at negative empathy – where we experience and relate to other people’s pain – Mischkowski suspects that this would also be more difficult to summon after taking the drug.
What? Read the article fully; it has to do with "negative empathy" different from "positive empathy".
Dominik Mischkowski is a Pain Researcher at Ohio University who has been studying this for a while. The word "suspects" here is statistical research-speak meaning there is a correlation (w.r.t. positive empathy) but more studies are warranted (w.r.t. negative empathy). That is all.
This is pretty misguided.A casual mistake like forgetting your cough syrup has acetaminophen can easily cause an overdose and then you fucking die. That’s not the risk profile you want for “most people in most circumstances”.
500mg from a capsule and 500 from cough syrup 4 times a day is still fine. With a 100% safety margin still.
If you’re taking more meds than that without clinical supervision Id say something is wrong in the system or your medicine practices.
Where I’m from it’s common to walk to the nearest pharmacy and get meds when needed. Even over the counter stuff like paracetamols. And talking to the pharmacist. They’ll ask what you’re already taking and tell you what else to get.
You don't want either of these; what you want is naproxen.
It works similarly, but stays a lot longer (half life is cited as being anywhere from 12 to 17 hours).
Acetaminophen and ibuprofen are just for temporary problems, like a headache that would go away on its own in a couple of hours.
They are uneconomic and inconvenient if you have something more persistent to keep at bay. Four ibuprofens or one naproxen? No brainer.
The main disadvantage of naproxen is that it's not approved for kids. So there is no naproxen syrup for infants or anything of the sort. Thus, you still need acetaminophen for that.
Really lovely article. In paramedicine we usually treat 10g of acetaminophen in a 24-hour window as a potentially fatal overdose. That's also why the law in Australia was changed to require acetaminophen to come in blister packs (harder to get each pill out) of no more than 16. At 500 mg, that only gets you up to 8 g if you eat the whole thing, which is still hopefully non-fatal.
I always thought a simple over-the-counter supplement (NAC) being the cure for an overdose was so cool. It's a pretty cool substance in a lot of ways, and this is a great spur to myself to research it more thoroughly.
Here in Singapore NAC is sold to make muckus more liquid to alleviate coughs.
Apparently for some people it also helps with lessening tolerance for their ADHD meds, but I'm not so sure about that.
Could somebody package Tylenol with a sufficient amount of NAC to de-risk it? I suspect such a formulation would not require trials?
What does ingesting 10g of acetaminophen even look like? I've got to imagine the fatal dose is far, far, far lower with chronic usage. Finding out that people are ingesting grams is profoundly disturbing.
I have taken 4-5g in a day while suffering from intense pain before.
There is a limit to the amount of opioids they will prescribe you, even if you are in mind shattering pain. For instance while attempting to get your dental insurance to actually cover a treatment you may find yourself between risking organ damage or risking $5000+ in ER visit bills only to have them refuse to give you anything but Tramadol.
Taking too much acetaminophen is bad for you but 10g is 20 extra strength pills and that much isn't likely at all to kill you but damage your organs is quite possible. Reading this might make someone in a bad place think that much will do the job and it won't. Tylenol poisoning's most likely outcome is permanent organ damage and pain, don't try it.
> What does ingesting 10g of acetaminophen even look like?
20 not-especially-large tablets
Is this not suicidal behavior?
I took 2 full packs in a day once while trying to recover from severe pain. Didnt find out until later that it was supposedly a fatal dose.
Mm. Apparently i don't understand pain and the medication it drives people towards.
This can easily happen over the course of 24 hours if you're in "fuck me I'll do anything to make it stop" levels of pain. I've taken more than 20 ibuprofens in a day a few times in my life, which, while not medically advised, did not kill me. I actually had no idea acetaminophen was so dangerous.
Or 10 slightly larger ones
edit: https://www.24pharma.nl/paracetamol-eg-1000mg-120-tabletten
I’ve pretty much only ever seen them sold at 500mg; are you regularly seeing them where you are sold in 1g form?
They are common in France, but not in such packages: There are restrictions that prevent you from buying more than than 8g/day (theoretically at least, I don't believe they are strictly applied in practice).
[delayed]
When was this changed?
I arrived in Aus in 2021 and was amazed to be able to buy a pack of 40+, coming from the UK where the limit had been in place for some years.
Jan 2025: https://www.psa.org.au/changes-to-paracetamol-scheduling-wil...
It's the usual public health balancing act of help vs harm.
You can still die if you take your idiot-proof Aussie blister packs with alcohol. So it's more an inefficient use of cabinet space.
You can overdose on water too, they haven't banned 5-gallon jugs (yet).
Yes, and you can still die in a car crash if you're wearing your seatbelt, and wearing a helmet on your motorcycle won't save you from a head-on with a truck, and you can still drown in a pool with a lifeguard, and you can still die in a burning building with smoke detectors.
Harm reduction is about shifting probability distributions, not guaranteeing outcomes. Kids can still get into pill bottles with childproof medication caps, but accidental ingestion of aspirin by children reduced by 40-55% after they were mandated. [0]
[0]: https://pubmed.ncbi.nlm.nih.gov/440889/
No. Ethanol and tylenol compete for CYP2E1 that produces toxic NAPQI, so no, acute alcohol intoxication has a protective effect at least where it comes to tylenol toxicity.
I grew up with the understanding that acetaminophen was the safe choice for fever or aches, and ibuprofen what the more potent compound for inflammation and severe pain. I recall casual anecdotes that "my doctor said 1.5x or 2x ibuprofen dose is ok when warranted" to address major incursions.
I've never once thought about taking more than the recommended dosage of acetaminophen, largely because I had no expectation that it would provide additional benefit..
In reality, I try to consume 1/2 doses of anything or nothing at all, unless it's a serious medical treatment being administered by a professional.
I think most overdoses happen as a result of someone trying to hurt themselves, but I’ve also previously been in sufficient pain (always dental) that I’m counting the minutes down to when I can take more painkillers, so it’s easy to see how you could take double the expected dosage.
This is some of the most useful information I've received in a while. Like the author, the low overdose threshold of acetaminophen made me avoid it, even though I always take low doses anyway and ibuprofen gives me acid reflux almost every time.
Same here. Great article.
I avoid both and stick with naproxen sodium. Any issues with that one? Lasts the longest too.
Both ibuprofen and naproxen sodium are NSAIDs and are bad for your kidneys especially in long term. I had kidney failure due to what was eventually diagnosed as an autoimmune disease but they first thing the ER doctor will ask is if you have been taking NSAIDs. My nephrologists told be its still safe to take acetaminophen at the proper dose.
None of us are your doctors but Naproxen has well-known gastric issues up to ulcers and stomach bleeding which is why it's advised to be taken with food and why it's also often prescribed with a PPI or H2 Antagonist. Cox-2 selectives such as Celecoxib greatly reduce this risk but seem to be associated with some small cardiovascular risk (admittedly this is a feature of all NSAIDs though less so in Naproxen apparently).
Some believe naproxen sodium is worse for you because it lasts longer. Longer duration for reduced mucous membrane coverage in your stomach and intestine. Longer duration for reduced blood flow to your kidneys.
I would definitely have a chat with a doctor about it.
Looking at the Wikipedia article, it seems naproxen is a NSAID like ibuprofen and can cause all the same gastrointestinal issues.
I've known people who've overdosed on Tylenol and died. I'm not saying that ibuprofen won't give you acid reflux and won't damage your kidneys, but due to <reason> I tend to take a lot of ibuprofen and also for <reason> take another medication that constricts my arteries and for <reason> get a lot of blood/urine work done... and my kidney function is good and despite everything I'm generally healthy. So I would say, like many things, what medicines you take probably depend on your specific body and situation. Regardless, you won't die accidentally from an acute ibuprofen overdose. You just might die from taking tylenol if you don't realize your liver is already damaged for other reasons. So there you go!
Unless you’re in Rhabdo. If you’re in so much muscle pain and your kidneys are working overtime to clear broken down tissue and you then hit them with too much ibuprofen, then you can go into kidney failure and die accidentally.
At least with the folks i hang around, liver damage from years of over-drinking is probably more likely
Just don't take it on an empty stomach.
That's ibuprofen. Which can be partially mitigated by famotidine.
IBU: -stomach -kidneys -bp+ -clotting --NERD --NECD --NEUD --SNIUAA --SNIDR --DRESS
APAP: -liver --DRESS
-- extreme, rare side-effects
> You just might die from taking tylenol if you don't realize your liver is already damaged for other reasons.
If you don’t realize your kidneys are already damaged you might die from kidney failure because of ibuprofen.
My father, who is otherwise in very good health for a ~60 year old, has severely reduced kidney function from taking an ibuprofen+antihistamine most days of his early life to deal with allergies.
I'll second the claim that no doctor at any point in his life had told him the risks of doing that, and many encouraged the use of ibuprofen over any other alternative (including the alternative of not using OTC painkillers every single day).
If you take either of these medications regularly talk to your doctor.
After severe cramps once when I had to use a lot of ibuprofen (dental surgery / wisdom tooth) I now only use ibuprofen with a stomach protector to avoid stomach cramps, H. Pylori, and reflux.
Acetaminophen is part of ECA stack weight loss formula, while article says not OK with fasting. Either way, more safe solutions are known these days.
This is why asking for medications based on the last thing you saw on social media is a really bad idea.
If you don't make a habit of taking either, what actually performs better?
Depends what you’re taking it for. Generally people take NSAIDs for muscle and dental pain, or anything that’s obviously inflammation, and paracetamol for anything else, particularly headaches, and is a common adjunct treatment if you have a cold or flu.
Well, I mean, drats. I too always assumed Ibuprofen was safer than Acetaminophen; not the least because of massively oversimplificatic "reduced inflammation - GOOD!" 'Logic'. I'm 47 now and have probably preferred ibuprofen for last 27 or so.
IANADATINMA.
Max dose combination (IBU/APAP FDC) can be useful as a substitute in emergency therapeutic situations compared to opiates. Not recommended ordinarily because of liver, kidney, and stomach impairment.[0]
Taking ibuprofen with questionable stomach condition may want to consider taking a famotidine adjuvant or duexis [1] or acetaminophen instead.
Overdose treatment of acetaminophen poisoning is the stinky N-acetylcysteine (NAC), so that maybe worth stocking whenever Tylenol is kept in a house with kids. Overdose of ibuprofen is palliative, requiring IV fluids and dialysis.
0. https://www.researchgate.net/publication/382639515_Ibuprofen...
1. https://pubmed.ncbi.nlm.nih.gov/25516006/
For those who struggled similarly to me:
I Am Not A Doctor And This Is Not Medical Advice.
(I think?).
> You should not switch medications based on the uninformed ramblings of [crazy] people.
Both of these pills are really dangerous for dogs.
Ibuprofen damages the kidneys -- and that damage is often permanent. The little filtering devices inside the kidneys don't grow back once they're destroyed. A dog who survives the poisoning can end up with lifelong kidney disease, which means special diets, more frequent vet visits, and a shorter life than she should have had.
(I watched this happen to my own dog after a house sitter stepped on her paw and gave her ibuprofen to "help." My dog lived, but she needed a special diet for the rest of her life.)
Acetaminophen wrecks the liver, and it also can damage red blood cells so they can't carry oxygen properly. A poisoned dog may get lethargic, vomit, start to breathe heavily... This is especially dangerous for older dogs, or any dog whose red blood cells are already compromised, by conditions like IMHA.
The following article showing a link between Acetaminophen/Paracetamol usage and decline in positive empathy is highly relevant here;
The medications that change who we are - https://www.bbc.com/future/article/20200108-the-medications-...
Excerpt:
Mischkowski’s own research has uncovered a sinister side-effect of paracetamol. For a long time, scientists have known that the drug blunts physical pain by reducing activity in certain brain areas, such as the insular cortex, which plays an important role in our emotions. These areas are involved in our experience of social pain, too – and intriguingly, paracetamol can make us feel better after a rejection.
Mischkowski wondered whether painkillers might be making it harder to experience empathy
And recent research has revealed that this patch of cerebral real-estate is more crowded than anyone previously thought, because it turns out the brain’s pain centres also share their home with empathy.
For example, fMRI (functional magnetic resonance imaging) scans have shown that the same areas of our brain become active when we’re experiencing “positive empathy” –pleasure on other people’s behalf – as when we’re experiencing pain.
Given these facts, Mischkowski wondered whether painkillers might be making it harder to experience empathy. Earlier this year, together with colleagues from Ohio University and Ohio State University, he recruited some students and spilt them into two groups. One received a standard 1,000mg dose of paracetamol, while the other was given a placebo. Then he asked them to read scenarios about uplifting experiences that had happened to other people, such as the good fortune of “Alex”, who finally plucked up the courage to ask a girl on a date (she said yes).
The results revealed that paracetamol significantly reduces our ability to feel positive empathy – a result with implications for how the drug is shaping the social relationships of millions of people every day. Though the experiment didn’t look at negative empathy – where we experience and relate to other people’s pain – Mischkowski suspects that this would also be more difficult to summon after taking the drug.
Also see the previous thread; A social analgesic? Acetaminophen (paracetamol) reduces positive empathy - https://news.ycombinator.com/item?id=31263305
> Mischkowski suspects that this would also be more difficult to summon after taking the drug.
Why should I trust someone who doesn’t test properly but just suspects?
What? Read the article fully; it has to do with "negative empathy" different from "positive empathy".
Dominik Mischkowski is a Pain Researcher at Ohio University who has been studying this for a while. The word "suspects" here is statistical research-speak meaning there is a correlation (w.r.t. positive empathy) but more studies are warranted (w.r.t. negative empathy). That is all.
This is pretty misguided.A casual mistake like forgetting your cough syrup has acetaminophen can easily cause an overdose and then you fucking die. That’s not the risk profile you want for “most people in most circumstances”.
500mg from a capsule and 500 from cough syrup 4 times a day is still fine. With a 100% safety margin still.
If you’re taking more meds than that without clinical supervision Id say something is wrong in the system or your medicine practices.
Where I’m from it’s common to walk to the nearest pharmacy and get meds when needed. Even over the counter stuff like paracetamols. And talking to the pharmacist. They’ll ask what you’re already taking and tell you what else to get.
Yeah this is optimizing for the good case instead of tail risks and mistakes and we see too many overdoses already.
Of course, we could press the fix this immediately button by requiring acetaminophen to be sold mixed with NAC but that would be too easy.
You don't want either of these; what you want is naproxen.
It works similarly, but stays a lot longer (half life is cited as being anywhere from 12 to 17 hours).
Acetaminophen and ibuprofen are just for temporary problems, like a headache that would go away on its own in a couple of hours.
They are uneconomic and inconvenient if you have something more persistent to keep at bay. Four ibuprofens or one naproxen? No brainer.
The main disadvantage of naproxen is that it's not approved for kids. So there is no naproxen syrup for infants or anything of the sort. Thus, you still need acetaminophen for that.