> But if acetaminophen is safer, then why don’t official sources tell you that?
Guess it depends on country. Here in Norway official sources[1][2] do say acetaminophen (paracetamol here) should be the default for treating fever and pain in kids, adults, pregnant women and elderly, and have for some time. Ibuprofen they say should be used with caution.
I feel like this is one of those things where Europe and the US are very different, culturally speaking - I've lived in the Netherlands, Germany and now Sweden, and the amount of painkillers used and prescribed here seems much lower than what Americans tell me is normal in the US.
Pain a warning signal from the body. It's something one should listen to, not just try to ignore and overrule. If I sprain my ankle it only hurts when I lean on it. Because it's healing. So I don't. Why would headaches or other "inconvenient" pains be different?
In my case headaches are usually caused by sleep deprivation causing high sensitivity to external stimuli, muscle tension, dehydration, or some combination of that. So I'll first try to take a nap and/or stick to low-stimuli environments, have a good stretch and/or heated up massage pillow for the neck, and make a quick home-made oral rehydration solution with some salt and sugar. That usually alleviates most if not all of the pain.
And I'm not saying painkillers should always be avoided. If I have insomnia-induced headaches in the morning and a long day ahead with many social interactions, then I know that headaches will make me a grumpy asshole, so I'll obviously will take a painkiller for everyone's sake. And sometimes I can only fall asleep if I take a painkiller to get rid of the headache first, so I need it to break the vicious cycle. I'm not saying people should "walk it off" here, just to focus on trying to figure out the actual cause first before medicating the symptom way. That's also healthier in the long run, no?
AIUI one of the many quirks of the US health insurance system is that a lot of people have only minimal cover which doesn't include things like physiotherapy and rehabilitation treatment. That means that they often can't treat a painful condition at source so their only option is to mask the pain with painkillers.
This is so absurd to me. The expression "prevention is better than cure" isn't just folk wisdom, in just about any country with nationalized healthcare the studies also confirm that this costs less money. The only exception I ever heard was a Dutch study in the 2000s suggesting that people growing older due to smoking less was going to increase healthcare costs, because people were getting older putting pressure on the pension system, but let's not peer further into that can of worms.
So by all accounts it should be cheaper for for-profit insurance companies too, unless they have ways to externalize the costs onto the rest of society. Which I guess is more circumstantial evidence for how messed up the system must be.
Long-winding tangential anecdote (which is why I'm replying to myself in a separate comment), but I have pretty extreme example of this: I managed to avoid nearly all suffering after getting a tonsillectomy in my mid-thirties, while using almost no painkillers.
My ENT surgeons warned that me "I'd hate him for about a month, then I'd love him for never having to deal with [serious medical condition that justified the removal of tonsils] again". He prescribed all kinds of stuff to alleviate the expected suffering, and advised me to try to take the weakest options I was comfortable with, because the heavier ones might have some unpleasant side effects. It's the only time in my life I've been prescribed painkillers at all, actually (this was in Sweden, btw).
I got codeine/paracetamol as a coughing suppressor and mild painkiller, a couple of heavier painkillers for if it got worse (I forgot the name but some kind of heavy-duty variation of diclophenac that you can only get with a prescription), and some kind of nasty solution to gargle with that supposedly would numb my throat if it got really bad. I've been told this is nothing compared to what you can expect in the US.
Then in the evening after the surgery, when I was trying to eat a soup with my mom, I realized soup didn't hurt as much as drinking plain tap water. And then I thought: isn't it odd that drinking plain water feels like a thousand paper-cuts in the open wound in my throat, but whenever the coughing made the wounds open and bleed, the blood doesn't hurt at all? Blood is mostly water, so what is the difference? Could it be the salt? Is this similar to why drinking demineralized water is bad for you? What's the opposite of demineralized water? Oral rehydration solution. Ok, trivial to make, let's try that. I'll drink it luke-warm to be close to body temperature too.
Turns out that that works. Oral rehydration solution is almost painless to drink after a tonsillectomy. I know this is anecdata, but sample size three: I've since shared this information with two friends who got a tonsillectomy, and they've been extremely grateful for this tip.
It even seemed to speed up my recovery, probably due to a lack of irritation triggering inflammation. I was eating solid food within days. DAYS. My mom, a retired family physician herself, couldn't believe her eyes.
I ended up only needing the codeine/paracemtal in the evening to suppress coughing in my sleep, and brought back all the other pain-killers without opening them.
Since we're talking about acetaminophen and ibuprofen, in France you're liable to end up with a medicine cabinet full of acetaminophen, because almost anytime you go to the doctor with any type of pain, they add it to the prescription.
> Pain a warning signal from the body. It's something one should listen to, not just try to ignore and overrule. If I sprain my ankle it only hurts when I lean on it. Because it's healing. So I don't. Why would headaches or other "inconvenient" pains be different?
Pain is also suffering, and there is no virtue in suffering needlessly.
Even more importantly, there's also chronic pain, which can severely affect quality of file permanently and is essentially an illness all of its own. Research supports the concept of "pain memory", where chronic pain develops as the result of leaving the pain from a temporary condition untreated.
> Pain a warning signal from the body. It's something one should listen to, not just try to ignore and overrule.
This is vastly overstating the rationality of the human body. It's no more rational than the human mind, which is often quite irrational. Your body isn't the product of medical school, nor intelligent design, but rather random natural selection, which is decent but demonstrably far from perfect.
Especially if a new one, pain is undoubtedly a 'warning signal from the body' which is a succinct metaphor we all understand and has a clear meaning. If you don't know why or from whence the pain, check it out. It may be one of those things or perhaps not.
Perdue Pharma/The Sacklers went on a huge campaign in the 90s convincing doctors and the general public that pain was bad and worth stopping at any cost and even though they were pushing opioids, I can imagine this also increased the cultural tendency to use NSAIDs as well.
I agree that Purdue Pharma was probably the most significant factor, maybe enhanced by the relative ease of granular lobbying of private doctors as compared to the challenges it may face in universal healthcare systems. However, I do suspect that the limited rights of most US workers to take sick leave served as one more cultural advantage in favour of Purdue's campaign.
In many countries if a doctor believes you're too sick to work you have a right to take leave until you recover, without risking your job and without expending limited "sick days". In those circumstances the doctor will of course prescribe something for your pain, but as a patient you have no incentive to insist the painkiller is strong enough to allow you to continue working.
Yup - in the UK, paracetamol is usually recommended for general pain relief before Ibuprofen. Additionally, Ibuprofen and NSAIDs have a lot of interactions which can make them unsafe - SSRIs or blood thinners for example.
aspirin is an NSAID, taking it modifies the prostaglandine levels (through its COX inhibition) and this influences the mucosa of your stomach. ibuprofen can still have the same side effects, because its belonging to the same class of drugs.
Ibuprofen is better are reducing fever and managing headaches.
Paracetamol is the safer version Phenacetin. You used to be able to buy aspirin, phenacetin and caffeine..but phenacetin with withdrawn. APC when it was marketed was very popular but soon you were told to never give children aspirin for a fever so we used Paracetamol. Then Phenacetin was withdrawn and paracetamol became part of APC (like Alka selzta XS , or just the popular caffeine paracetamol combos)
Paracetamol came in as safer but similar, yet no where near effective. It captured bith the market feeling of its pros and cons. So we interpreted it as safer than alternatives (especially aspirin for children due to Reye syndrome). But also dangerous which might be why OPs view was that ibuprofen is safer.
The NNT (number of people you'd need to take it) to be headache free after 2 hours is about 12-20 for paracetamol. But only 7-10 for ibuprofen.
It's quite surprising that paracetamol became the defacto analgesic given it performs so poorly but it was historical inertia. And plenty of people argue that if we were to start over we would not make paracetamol OTC.
Here is a summary of COCHRANE evidence on Paracetamol "widely used and ineffective"[0].
It's a paradox no?
Paracetamol is only the presumed only active metabolite, and that is why paracetamol rapidly replaced phenacetin.
There is a quirk though, phenacetin actually delivers paracetamol to your brain and spine (where it primarily reduces pain) faster than an oral dose of paracetamol.
Similarly IV paracetamol is far more effective that oral paracetamol.
Phenacetin was also considered mildly addictive, and induced a gentle euphoria and then sedation.(We still see sedation after paracetamol in children and the elderly).
But general use we don't see these effects in paracetamol, why did phenacetin do this more effectively? Probably the higher peak levels around nerve endings.
These effects are both wanting of an explanation of phenacetin is just paracetamol and directly analegisic.
I guess it tracks with personal experience. I find Paracetamol is OK for fevers/generic cold symptoms but absolutely useless for a headache, Ibuprofen is the only thing that shifts them.
Well it's the only thing that shifts them now I'm in a country where I can't buy soluble aspirin and codeine OTC.
I once got it to make a small difference for pain - but I was in the hospital (surgery recovery) where the doctors were giving me more than the daily maximum.
"I took it and it didn't work so it's a fake placebo drug" - wow, your scientific method is flawless, have you considered a career at the US Department of Health?
I have a counter-study with size n=1: I did all my recovery from tonsilectomy on paracetamol and definitely noticed it working. That was however on the maximum safe dose.
(one of the major problems with paracetamol is that the effective dose is only a few multiples away from the dose which starts to cause liver damage! It is by a long way the most dangerous OTC drug)
You're partially right compared to placebo only about 5% of people are painfree over the effect of a placebo when taking paracetamol.
Paracetamol got it's start as replacing the more effective but much more dangerous and withdrawn drug Phenacetin.
Why don't people notice that it's such a small benefit over nothing? Well because placebo effect is quite good for pain and pain is usually transitory anywhere..if you have a tension headache you're probably going to aim to relax. Turn away from the screen or even have some caffeine and those are more effective than paracetamol!
Where did you pull this 5% from? There are gazillions of studies showing higher or lower efficacies for different kinds of pain. Along with the inaccuracies about Phenacetin (whose MOA is metabolising into paracetamol).
You will indeed find various figures for various pain types all are far worse than ibuprofen.
Here is an example from the Cochrane library
> For the IHS preferred outcome of being pain free at two hours the NNT for paracetamol 1000 mg compared with placebo was 22 (95% confidence interval (CI) 15 to 40) in eight studies (5890 participants; high quality evidence), with no significant difference from placebo at one hour.
A NNT of 22 means that in absolute terms 1/22 people met the positive endpoint criteria more than placebo. This figure is usually quoted as 20% for placebo and 25% for paracetamol giving NNT of 20.
"pain free" is a long way from the pain is manageable. Pain is an understudied subject, where we have too little knowledge. Just using the word manageable is an indication of this.
That's very true, but the metric is applied to all medications you compare against that's what's important. You also just get a baseline idea of what's good by guessing what you'd accept.
Episodic tension type headache tested with ibuprofen Vs placebo NNT is 14. (Btw that's not great itself) But it's better than paracetamols often quoted figure 20.
Here's why I say it's not great. Why don't you guess some reasonable NNTs for say moderate depression treated with SSRIs, or no relapse in schizophrenia treated with an antipsychotic.
Now guess the NNT for a statin to prevent a first heart attack.
SSRI for moderate depression about 10, antipsychotics to prevent schizophrenia relapse over 2 years NNT= 3 (excellent )Statin to prevent a first heart attack 200! (This one always shocks me). Statins have a clear role of course.
I take both. 500-1000mg acetaminophen, 200-400mg ibuprofen. Usually helps for headaches which I get frequently. I only take them for the worst headaches though, so probably once every couple of weeks on average.
Yeah if I need to I take both also. In addition I be sure to have a caffeinated drink also as caffeine has been shown to both speed the absorption and boost the efficacy (5-10%) of paracetemol over a multi hour period. https://pubmed.ncbi.nlm.nih.gov/17442681/
That is interesting. In the UK they're both available pretty much everywhere, and they're some of the cheapest drug prices I've seen anywhere in the world... ~20p for 16 tablets or something.
Neither paracetamol nor ibuprofen work by blocking pain. Depending on the type of pain and your physiology it can range from really effective to not at all.
I only take paracetamol, it works better than both ibuprofen and opioids for me. I know other people who have the exact opposite experience. There’s no absolute here.
Same here. Paracetamol also gives me pretty strong stomach aches whereas ibuprofen rarely has a gastric effect and when it does it's mild at best. I've been told by many people that the opposite should be true but oh well.
I wish they dipyrone was sold here, but alas I can only get it when I travel abroad.
With medicine both can be true, the response depends on so many factors in your body. Same way that for some people, particularly those with ADHD, taking stimulants can make them sleepy.
Many years ago I had 4 surgical procedures done around my nose/throat at the same time - straightening a deviated septum, turbinectomy, enlarging the openings into my sinuses and removing my tonsils. This meant I couldn't breath through my nose for about a month - and breathing through your mouth when you've just had tonsils removed is quite painful.
Soluble paracetamol literally turned the pain off like a switch - of course I was limited as to how much I could take, which I was careful to stick to but I was almost in tears waiting for the time to come where I could take more paracetamol.
So in some situations paracetamol can be an extremely effective painkiller.
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.
> Apparently for some people it also helps with lessening tolerance for their ADHD meds, but I'm not so sure about that.
I'd believe it. I first heard of NAC on the nootropic subreddit in a past lifetime. The benefits vary, but generally it's a safe thing with a low chance of making anything worse, but a possibility to improve things. Many neurodivergent folk have written about how they benefit.
I'd give more info on the exact benefits they found (iirc OCD and rumination loops could be broken more easily), but unfortunately my memory is failing me.
How is nac (acetylcysteine) delivered there? I can buy dissolvable tablets here in Europe but from what I see that’s less helpful for mucous, things like mucomyst require inhalation, which isn’t in otc products I know of.
The dissolvable tablets completely fix a runny nose for me. Much better than any nose spray, which tend to irritate the nose and lead to chronic runny nose if taken for too long.
In the Philippines it's available as an effervescent tablet to be dissolved in water. They still tend to work better than the western remedies (guaifenesin etc) even in this form IME.
Usually here in Canada it's available in capsule form which I find less effective.
Same here actually, I find it slightly helpful but the effect’s useful time is limited. I’ve wondered if I could capture the gas released while bubbling and inhale that…
I randomly bought NAC just to try it. I dont know about the chemical interactions, but going out with collegues at that time taught me that it's basically impossible to get drunk. Usually a pint of beer is enough to make le feel at least a little dizzy, but when taking NAC, it was all like drinking water
When I go out drinking with my pharmacist buddy, we take NAC before going out. He swears it makes hangovers less likely. I can't say I've noticed that particular effect, but I do seem to sleep a bit better on those nights.
Certain esters have been found to be much safer (in mice, at least):
> The glutathione hepatic values in mice obtained by intraperitoneal injection of the ester are superimposable on controls and the oral LD50 was found to be greater than 2000 mg kg^-1 and the intraperitoneal LD50 was 1900 mg kg^-1 ...
and more general analogs apparently can also be designed to not produce NAPQI:
> Thus, in 2020, N-sulpharyl-APAP prodrugs 39–40
(Fig. 11) were developed. [...] They are not hepatotoxic because they do not generate toxic metabolite NAPQI, even in concentrations equal to a toxic dose of APAP (600 mg kg^−1 in mice).
I am blessed with living in one of the most polluted areas in the world (PM2.5 going into thousands of µg/m³ in winter; summers are not much better due to dense chemical smog). Can you say more about how you're using it to combat that? Thanks!
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've been prescribed slightly more than 5g per day (2 x 650mg tablets every 6 hours) for pain after an operation jointly with ibuprofen, which is scarily close to the limits.
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.
> I guess it is much better than the situation before that, where you paid $5000+ and they also gave you an opioid addiction.
Having a condition that actually warrants strong opioids and not being able to get them at any price is definitely not an improvement.
The problem is fundamentally that we want to pretend doctors can always distinguish two people describing the same symptoms when one person actually has them and the other is trying to get drugs. The often can't, so you can either make it hard for people to get pain medications even if they need them, or you can make it easy for people to get them even if they don't. And between these the second one is unambiguously better, because the first one is the government screwing innocent people and the second one is guilty people screwing themselves.
> And between these the second one is unambiguously better, because the first one is the government screwing innocent people and the second one is guilty people screwing themselves.
Could not agree more. Depriving people with legitimate pain of opioids is IMHO legitimate torture. It's a bit of a variance on the trolley problem in that the doctor/government isn't causing the pain, but their inaction is prolonging it.
Whenever people here mention to my critique of US healthcare how its now mostly solved problem now, its 'good' to see the other side and reality. It certainly doesn't seem solved unless you have a million or two just laying around on the account, while mortgages and kids tuitions are paid. And I can easily imagine a long term condition or 10 which, if unlucky in terms of treatment cost coverage can wipe out that sum in a decade or two, for a single person.
Seriously, how can you guys consider this acceptable. I am not of faith but doesn't bible teach to be kind to your fellow men above all? One would expect more adherence to such basic moral rules in such conservative christian society.
The problem with the US system is that it doesn't know what it's trying to be.
If you did a socialist system then everything is "free" but possibly slow and expensive on the back end when the government isn't efficient.
If you did a libertarian system then everything is cheap but it's caveat emptor because nobody is stopping you from buying morphine for $10 from Amazon.
The US system isn't either one. It pretends to be a market sometimes but then has a bunch of rules to thwart competition. Doctors are required by law to do residency but the government limits the number of residency slots in response to lobbying from the AMA so there aren't enough doctors. "Certificate of need" laws explicitly prohibit new competitors for various services. Insurance is tied to employment to make it hard for individuals to shop around. Laws encourage, require or have the government provide "prescription drug coverage" to make patients price insensitive so drug companies can charge a huge premium for patenting a minor improvement or simple combination of existing drugs and have the patient will something which is marginally if at all better even if it's dramatically more expensive because they don't see the cost when the insurance/government is required to pay for it.
It's a big pile of corruption, because all that money is going to places. But then if you try to fix it, half the population insists on doing the first one and the other half is only willing to do the second one, and the industry capitalizes on this to prevent either one.
Maybe instead we should do both rather than neither. Have the government provide a threshold level of services, like emergency rooms and free clinics and anything more than that the local government wants to fund, and then have a minimally regulated private system that anyone can use if the government system doesn't satisfy them.
I don’t know a single person in my life who thinks US healthcare is good, so that’s weird. And many my peers a have good jobs with good health insurance. Everyone I know has at least one bad story about insurance, if you’ve ever had more than really basic checkups.
As an American this is such a weird question to me. I purchase my ibuprofen and benadryl in bottles of anywhere from 400 to 1000 pills every few years.
Apparently a common source of problems is taking two different medications without realizing they both contain acetaminophen.
Suppose your arthritis is acting up, so you start taking Tylenol 8hr Arthritis Pain[1]. That's 2 tablets every 8 hours. They're extended-release with 650mg per tablet. A total of 3900 mg in 24 hours.
A few days later you get the flu, so you decide to add what seems like a completely different medication: Theraflu Flu Relief Max Strength[2]. It has a cough suppressant and an antihistamine. But each caplet also contains 500 mg of acetaminophen. It says to take 2 caplets every 6 hours, so you take 8 of them in 24 hours[3]. That's another 4000 mg.
Between the two, you're at 7900 mg.
Then you wake up in the morning and take both medications, but 30 minutes later you've forgotten you took them. You're not thinking straight because you're sick. So you accidentally take a second dose. That additional 2300 mg brings your total to 10200 mg.
[3] You weren't supposed to take 8 of them, though. If you'd read the label very carefully, you'd have seen it also says not to exceed 6 in a 24-hour period.
My personal rule is to only purchase over-the-counter meds with a single active ingredient. I'd rather separately take an antihistamine, expectorant and painkiller than a concoction where I have to read the whole label and do math while sick to separate the doses and timings.
There are some that are very hard to find as a single ingredient. Recently I was purchasing a medication for back pain, I had a choice as to which other ingredient I wanted, but I didn't have the choice of none. I picked the combined ingredient I don't like to take, because I wouldn't be adding it on top.
I did toss on the other option, stand alone, at one point so I could get some sleep.
It left the medication I was more comfortable taking as an add-on option if things got bad enough. (This particular medication has much lower risk of overdose, so if I got stupid and took it again there would be no significant additional risk.)
It's ironic, but taking the combined medication with a known higher risk of its own was better than taking the lower risk medication.
One was controlled, higher risk, taken at specific times, while the other was taken in addition, on demand, as required.
Specifically this is one reason they’ll sell you cocodemol or Vicodin but not codeine or hydrocodone directly — if you take enough to get a codeine high, you’ll have taken a toxic amount of paracetamol/acetaminophen, so they assume you won’t.
I didn't until I had a bulging lower back disc pressing on my sciatic nerve. My leg felt like it was constantly on fire no matter what position I put myself in. In the past I've torn my ACL and had surgery to reconstruct and that pain was like stubbing my toe compared to the back pain. I understood how people become addicted to pain meds after my back situation.
Totally get it, I too only understood it "theoretically" till I had a (fairly minor!) dental operation.
... Suddenly I'm maintaining a continuous note of when I'm taking which medicine to avoid crossing safe limits (which I anyway was crossing most days).
I was only told to take 2 paracetamols a day (bullshit dose, I'd be waking up from the pain even with more pain meds).
"Diclofenac for rare use" - well, if nothing else is touching the pain, is it an emergency?
Eventually after forever I was able to transition to Ibuprofen + paracetamol. And I already have a health condition which is heavy on my kidneys... pain management can be absolutely crazy.
Pain management can be crazy but in your case it sounds like they didn't prescribe the appropriate medication presumably due to the anti opiate hysteria that has taken hold.
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.
Just in case, ibuprophen does not work well for pain relief [at lest for some kind of pain]. Paracetamol [acetaminophen] usually is much better against pain.
And paracetamol + ibuprophen can help with strong pain for which neither paracetamol or ibuprophen work at normal doses.
Not really. Both address different sources of pain, and do so using different processes.
Ibuprofen is a Nonsteroidal Anti-inflammatory Drug (NSAID) that reduces pain and inflammation, while acetaminophen does not. (Acetaminophen is believed to act mainly in the brain rather than at the site of injury).
Ibuprofen- Fundamentally, if the pain is caused by inflammation, reducing the immune systems response to it can reduce pain, but if the pain is more acute it won't make a dent.
With acetaminophen, taking more isn't a solution in most cases, you need another method to reduce the pain further if it doesn't achieve its goal.
(That's why it's combined with things like codeine, which affects the brain in a different way for an additive effect)
> you need another method to reduce the pain further
I don’t know about “most cases” but often you don’t want to reduce the pain _further_, you want to reduce the pain _again_. (Having an alternative definitely helps in the meantime.)
The .nl indicates the netherlands. Many people in the netherlands vent/joke about how the doctors here only ever tell you to take paracetamol and come back in two weeks if it's still a problem (recursive solution).
However the last time I went to my GP she scoffed at me taking the maximum and suggested I take literally double the maximum recommended dose 4-5 times a day which totaled I think 2.5x the daily maximum on the package. I am very much a "believer" in science and reasonable medical authority but this experience sowed the seeds of doubt, because from what I have always heard, that can actually kill you or cause permanent liver issues. I was also taking diclofenac simultaenously, and when I told her how many mg, she asked "where can you even buy such small doses, that's what I would give a small child" =/
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).
Buy a pack of 20x500mg (just checked, common size in Germany), take 2-3 every half hour for a while.
Sure, that's extreme. But if you're unaware of the risks, you feel sick, and you believe it's helping you.
I mean, people aren't killing themselves in masses with it, but it happens every now and then. Easily imaginable that one in a few million people will have enough tendency to take more pills and is unaware of the overdose danger.
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.
I've heard it suggested that acetaminophen just come with a small dose of NAC alongside it to make it safer. I guess this would require a lot of regulatory work to approve, but given that 500 people a year OD, it seems like a thing we should at least consider.
Meanwhile, it's funny that it seems like acetaminophen should safer in more scenarios, but the other has a lot of overdoses with typical use, I guess that's why there's a gap between the two, because ODs are apparently a lot more common or at least more legible than problems caused by the other drug.
You can still buy 100 packs, they are just behind the counter at chemists. TBH it's a rather stupid restriction - do they think people only ever own 1 packet of paracetamol at a time? In my household we have at least half a dozen, including a 100-pack from Oz and a 500-pack from America.
Oh right - that's probably what we did, buy a big pack from behind the counter.
I don't think you can even do that in the UK.
Yeah we usually have a few packs hanging around, and I get the 'it seems stupid' thing, but sometimes just adding a tiny bit of friction when someone's trying to kill themselves might save a life. I dunno, I hope that's shown in the evidence anyway. Otherwise it's just pointless like the whole pseudoephedrine song and dance, which has inconvenienced anyone looking for a decongestant while doing sweet FA to the availability of meth.
> Oh right - that's probably what we did, buy a big pack from behind the counter.
No, when you visited they were still on the shelf. They only put them behind the counter in 2025.
> sometimes just adding a tiny bit of friction when someone's trying to kill themselves might save a life
I'm philosophically not for making suicide harder. If someone wants to die, that's their right. And practically, while you might be able to show a stat-sig decrease in paracetamol poisoning, I'd expect the suicides to largely just move to other methods.
Paraphrasing from [0], after September 1998 when the restriction was introduced, "The annual number of deaths from paracetamol poisoning decreased by 21% [...] the number from salicylates decreased by 48% [...] Liver transplant rates after paracetamol poisoning decreased by 66% [...] The rate of non-fatal self poisoning with paracetamol in any form decreased by 11%"
See also [1]: "in the 11 years following the legislation there were an estimated 765 fewer suicide and open verdict deaths from paracetamol poisoning, which represented a reduction of 43% [...] This reduction was largely unaltered after controlling for a downward trend in deaths involving other methods of poisoning and also suicides by all methods."
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.
Alcohol and Acetominophen/paracetamol should not be mixed.
When alcohol enters the picture, it increases the activity of CYP2E1, so the body produces more of the NAPQI toxin. Alcohol also decreases glutathione production, the body’s natural defense mechanism, meaning NAPQI is more likely to build up in the liver in dangerous concentrations.
There is a danger in chronic abuse resulting in upregulation. Mixing the two at once is no problem for the liver, which is also why patient information leaflets for paracetamol do not contain a warning to avoid alcohol, only about chronic alcohol abuse.
Your crappy source is vague in what consumption pattern constitutes a risk and actually cites a better source that supports the idea that acute alcohol consumption reduces paracetamol toxicity. https://www.biorxiv.org/content/10.1101/2020.07.07.191916v1....
That's a mathematical model, but this relationship between the two is what I was taught in medical school and it is still supported by the science. There's plenty of other sources, I just picked that one because your article cites it. Just search for "paracetamol ethanol" on Google Scholar.
My US doctors almost never recommended Ibuprofen over Acetaminophen for mild pain. In fact, I don't remember them ever recommending Ibuprofen for anything while I hear about Tylenol pretty often.
I've had doctors prescribing short runs of opioids (2 weeks for surgery recovery) but they always said "try Tylenol first and if the pain is too much you can fill the prescription". I liked having the option but never really used it up to this point.
Only twice have I ever used Acetaminophen close to the max daily limit, and those were both when I was experiencing a raging tooth infection. I'd pop 2x500 mg paracetamol 4 times a day, which helped just enough to get through the day. The tooth infections were so severe that the dentist had to put anesthesia directly into the root / nerve, multiple times - felt like a lightning strike each time. One of these times I'd put the pain level at a 9 out of 10. I'm just going to assume that 10 out of 10 pain is when you basically consider ending it all, purely in the heat of the moment.
Having gout, I've also had some pretty severe bouts where the pain level has been in the 8/10 range. Unfortunately nether paracet or ibuprofen worked.
In any case, when I see regular people eating these painkillers as candy, I'm starting to wonder what pain levels they are experiencing. I'm generally very cautious of using this stuff.
Pain is weird. It's extremely subjective, not only between people but also within your own body. Paraphrasing something Paul Rozin mentioned in a paper on so-called benign masochism: people can learn to enjoy eating the most extremely spicy food, but even those people will still scream out in pain you rub the ghost pepper they're eating in their eyes. Pain sensation is localized and contextual.
As far as 10/10 pain goes, I've heard cluster headaches can get so bad it has driven people to suicide during an episode.
I lived with an ICU nurse for years and one of the things he emphasized was the risk of acetaminophen overdose. He's more than once treated the liver failure (and death) from it and by his words, it's one of the worse ways to go.
The positive of it is it got me in the habit of logging whenever I take it, either in a note on my phone or just a sheet of paper I place on my dresser under the bottle. This helps make sure I stay under the 3-4g/d limit.
Last year I was diagnosed with a rare headache disease (NDPH). We thought it completely came out of nowhere, but I had logs in my phone recording headaches and acetaminophen use intermittently from a few weeks prior. This proved useful in the diagnosis.
Moral of the story: log when you take it to avoid overdosing. Combine that with some basic symptom logging (like 1 line, 10 words or less). You never know when that might be useful for your doctors later on.
In my wilderness first responder class they emphasized taking a cocktail of ibuprofen and acetaminophen - both are effective pain relievers, each with different dangerous side effects.
The benefits stack, the side effects don't.
So if you are going to be loading up on higher doses of pain relief, take half acetaminophen and half ibuprofen.
P.S. like someone mentioned in a comment below happened to them, be careful with NSAIDs over the long term. Until recently I took them daily for better part of 3 years. I was recently diagnosed with chronic kidney disease. Can't definitively say causation, but they definitely contributed. They're fine for short term use but can really f$%# you up with long term, daily use.
It is absolutely valid to warn about long term use, and NSAIDs in particular (I was lucky and had a gastroscopy before they'd done any serious damage, but they found significant erosion of my stomach lining due to NSAIDs), but acetaminophen/paracetamol isn't an NSAID (ibuprofen and aspirin, for example, are)
In mozambique i was committed to the hospital with my liver failing after spending two weeks taking acetaminophen daily because everyone at work got sick and someone had to keep the business up (it was a bank, our IT department was very specific and only 6 people knew that job and everyone got extremely hill).
After two weeks, i finally went to the hospital and I couldn't leave; spent the next two weeks fighting for my life and at some point I was told I was not going to make it.
All due a simple over the counter medicine... crazy. This was 2016.
To this day I still get extremely tired if I take it, so I have to choose it carefully when to take it.
You are running a high fever or have a massive headache, so know you are going to max out at 4g/day. At that point, it's kind of hard to keep track of the clock.
"My head is pounding. Shit...did I take this at 3PM or 5PM? I know I took it and then fell asleep, but I can't remember when. It is now 9PM, can I take more or not?"
It often happens when people take the max dose of straight paracetamol, and then also take another drug that has paracetamol in it without knowing that (e.g. a codeine/paracetamol or ibuprofen/paracetamol combination).
People who are in a lot of pain and don’t know the risks.
Rationalizations like “they probably put the limit way lower than the real limit so idiots don’t OD themselves, so I can safely take a bit more” become very attractive when you’re in a lot of pain.
To be fair, the "real" limit depends on how lucky you are with your body's makeup. The safe limit is below that limit.
I know people with permanent pain due to medical conditions who have been given a doctor's approval to exceed the limits printed on the packaging (after having previously been monitored). You can exceed the limit on the packaging by one or two pills.
A bit more is often not deadly, but it's very easy to take more than a bit. When I had a messed up mouth for several days, I took the maximum doses and set timers to help me regulate the dosage throughout the day, but I sure wished I could've taken more at that time.
Okay that's right, if you just keep upping the dose because you're still in pain it might be easy to just slam a few every 4 hours
From personal experience if i have a headache I'll take 1000 mg all at once; it either works right away or it doesnt and I stop bothering until I've had a good nights rest...
Imagine if that rest will do nothing for that headache and its there morning day and night. Or some injury-related pain which simply can't be downtuned. Plus when old, half of the body aches, all old injuries and general deterioration.
I had only very brief experiences with longer intense pain but it made my mind into pudding and desperate knot of how-to-stop-this-at-all-costs. Normal life is not possible and sanity is not granted.
Yah...I've been there for 6 months now with a constant headache. The first month or so, I was taking 3.5g/day consistently. At hour 4.5 - 5, it would wear off. If it wasn't for my tracking, I probably would have ODed.
If you take 2 on average every 4 hours, you're at 12. If you're feverish or otherwise feeling ill enough and sleep deprived enough, forgetting when you took them last is easy. Personally I write down the time I took the last one.
In the article it is mentioned but it is worth stressing that N-acetylcysteine is a trivially available antidote for paracetamol overdose (and you may have it at home without knowing, Fluimucil, Mucomyst, NAC or alike).
Also: in Europe everybody normally takes paracetamol and not FANS as a first reach to minimize adverse effects. So this article looks like very US centric. AFAIK liver failure because of paracetamol in Europe is very rare. So here there could be cultural issues at play (medical culture of what is prescribed, and the fact that Europeans in general take lower dosages of everything).
EDIT: trick, if you very rarely take paracetamol and other pain medications, the next time try to take just 250mg. It works for most people, no need to take 750 or even 1 gram of paracetamol. 500 works for almost everybody, 250 for many folks.
The right tool for the right job. When it comes to medication, in the right dosage.
I'm aware of acetaminophen's down sides, and yet recently I was taking it combined with 2 other medications at the time.
Why? Because all three medications are recommended for dealing with the issue I had. (Alone and in combination)
The moment it wasn't helping further? Done.
There is this broken idea, particularly apparent in North America, but in western society that more is better for many things. It's not.
More pain killers don't do anything if they max out the relief they can give you, overloading their mechanism doesn't reduce anything, but taxing your liver or your kidneys.
All medications are potentially toxic, your body wants to dispose of them. In appropriate dosages they will benefit you, but more isn't inherently better.
Even water can kill you in sufficient quantity.
We do the same with diet; where someone declares one ingredient in a meal healthier than another; it isn't. A single ingredient isn't better or worse for you in a meal. Your diet however can be good or bad; over time that matters.
Yeah can confirm. I try to keep it low but then pain lingers for days and cumulatively over the days most probably I took as much as I should have taken in stating few days already.
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.
> largely because I had no expectation that it would provide additional benefit..
An interesting thing with ibuprofen is that at the regular dose of 400mg it inhibits pain but if you take 1600mg it doesn't inhibit much more pain than the 400mg dose, but the inflammatory effect does increase significantly. A lot of people don't know that and take too much thinking it scales linearly.
If your doctor recommends to take a specific dose, take the specific dose. Don't half it. Taking half of stuff can also cause further damage. Like with antibiotics, where it can lead to bacteria becoming resistant.
So don't be the "smarter" person. Do as your doctor says and if you have doubts, consult another doctor before just doing what you think is safe, but actually isn't.
Is this not the case for OTC drugs? Specifically, the two mentioned in the article. I rarely take either of them, but if my doctor tells me to take 1 ibuprofen every 6 hours or so, if I halve that am I actually doing more damage?
In general, taking a lower dose than recommended can cause problems, but aside from antibiotics, the problems are probably going to be from insufficiently treating the underlying condition, rather than the medication itself. Most OTC drugs give a single recommended dosage for all adults, so some people will necessarily get a lower "effective" dose than others (eg. a 200 lb man compared to a 90 lb woman).
> Specifically, the two mentioned in the article. [...] but if my doctor tells me to take 1 ibuprofen every 6 hours or so, if I halve that am I actually doing more damage?
With the caveat that I'm not a doctor, you should be fine: the only effect of acetaminophen is pain suppression, so if the pain is tolerable, then you should be fine. Ibuprofen has some anti-inflammatory effects that could be important here, but realistically, if the anti-inflammatory effects are the primary reason for the prescription, then your doctor is more likely to prescribe naproxen or celecoxib.
But if this ever comes up for you again, probably the best solution would be to tell your doctor/pharmacist "I have a high pain tolerance, would it be okay if I take less?", since in my experience, medical practitioners are generally pretty happy to hear when you want to take less drugs.
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.
It's a very strange cultural thing too, Australians (and I presume other Commonwealth countries) default to paracetamol (acetaminophen) before ibuprofen
Paracetemol has always been seen as first thing you'd take for pain relief, and you'd "step up" ibuprofen as an escalation, but that might more to do with marketing of Panadol (paracetemol) vs Nurofen (ibuprofen).
We'd look on at the US where you were taking Advil like candy in confusion.
One great thing you learn as a parent, you can alternate acetaminophen and ibuprofen. Both of them are recommended every four hours, but you can stagger one by two hours to maintain consistency of pain-relief taking ibuprofen then paracetemol two hours later
It is a damn shame bordering conspiracy that metamizole (https://en.wikipedia.org/wiki/Metamizole, known as Analgin in eastern Europe and the Balkans, apparently also India) is not more widely available in the west. It's literally a wonder drug, the only non-narcotic (hence non-addictive) that actually relieves serious pain (including post-op) pain in my experience.
Since I've had a fair share of it in my life so far (more than 1kg of it so far, in total), and I investigated the disparaging studies and they are definitely not convincing at all; more recent ones somewhat absolve it (check the Wikipedia page).
I've never had any side effects from it, and I don't know anyone who did, unlike for any other painkiller (diclofenac, ketoprofen, ibuprofen, acetaminophen / paracetamol).
It is a medicine where I'm almost 100% sure the studies against it are intentional sabotage by pharma companies, and the vigor and persistence this is done with is really telling (lots of doctors and pharmacists in my extended family, including in regulatory bodies). The campaign against it never ends.
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.
Still take it with a huge grain of salt. Even official advice usually has severe limitations due to its broadness or straight politics, so medical analysis from random blogs truely isn't the best.
Acetoaminophen also has issues for people with weaker stomachs (I can attest), and will come with additional medication to cover these effects as needed. The whole "Is it safe yes/no" table has many asterixes and might be outright false depending on the how you look at it.
Never take anything that written on the medications with a grain of salt. Disregard everything that you have read online. The medicine instructions are your single source of truth
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.
Whenever its prescribed here, its paired with some sort of intestine protection medicine to stop it burning holes in your stomach/intenstines
Ibuprofen is much safer, so long as you eat with it.
Paracetamol is also safer, so long as you don't OD.
BUT! so long as you stay below 4 grams a day, you'll be safe. (yes yes, in some situations you can take double, but unless you are under supervision, thats asking for liver pain.)
I had to use naproxen for some time as most effective way to control inflammation. Actually the only way, ibuprofen had some effect only in horse dozes. After visiting doctor, analyses, checking available sources was able to eliminate the reason of inflammation. Apparently it was a well known problem/solution. So far so good. Not sure about the long lasting effects of naproxen use.
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 there's one thing I'm hopeful for regarding all this AI hype, it's that some day we might actually get the Expert Systems we were promised decades ago. Then, finally, we can stop expecting human doctors to know everything. There's just so much going on inside our bodies and it's unrealistic.
I had a relative with a different story in the same theme. It sucks and I want to see this technology do something truly beneficial for a change....
The expert system relies on training data, and most of the medical data on the internet is either outdated or outright wrong. AI is not going to solve what the existence of Google hasn't solved already.
Acetaminophen (paracetamol) is the drug of first choice for addressing pain and fever, in India at least. To the extent that it's regularly abused, and I know people who have been hospitalized because of abuse.
Even then, doctors are usually disapproving of ibuprofen (or some combination of it with paracetamol) unless paracetamol is contraindicated for some reason, and I had always wondered why.
I did listen to this 99% Invisible story about the use of NSAIDs in India once[1]
What you describe in an interesting contrast to the situation in The Netherlands.
Here, virtually no one is prescribing ibuprofen _without_ also prescribing a baseline of paracetamol.
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!
My mom fell (88 yo) X-rayed, nothing broken but ignored her history of ulcerative colitis (tough to do, given the colostomy bag she’s worn for 50 years). Sent her home with Motrin. Ended up in the hospital for two weeks with bleeding ulcers.
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.
> I feel dumb saying this, but when I saw those labels in the past, I thought of them as a bunch of random information thrown together for legal reasons. But after spending a lot of time trying to understand these drugs myself, I now realize that these labels are... really good? (...) these labels are a triumph. This isn’t random information — every word is a synthesis of a mountain of research, carefully optimized to save lives.
Two disclaimers:
First, having grown up in the Netherlands rather than the US, I should probably not speak for the expectations one might have for the latter's drug labels.
Second, both of my parents were family physicians who also had a small pharmacy (not-uncommon in towns too small to sustain an independent pharmacist). I hold them both in high regard, so I am obviously quite biased to be defensive of them.
Which I'm sharing so you'll understand the context within which this sentence made me want to scream YES OF COURSE THEY ARE, YOU ARROGANT IDIOT! ALMOST ALL HEALTHCARE WORKERS WORK THEIR ASS OFF TO MAKE UNINFORMED PEOPLE LESS UNINFORMED SO THEY DON'T END UP DOING STUPID SHIT THAT GETS THEM KILLED! AND AS MUCH AS IT PAINS ME TO ADMIT THIS, THIS EVEN INCLUDES PHARMACISTS! IT'S THE PATIENTS WHO DON'T LISTEN OR BOTHER TO READ AAAAARGH!!!
Anyway, with that out of my system... I actually enjoyed the article as a whole!
Also, funny thing about the COX inhibitors part: apparently there's two COX enzymes: cyclooxygenase-1 and cyclooxygenase-2. COX-2 is the one that also triggers inflammation, COX-1 is the one that does most of the beneficial things. COX-inhibiting drugs target both. Targeting only COX-2 would be nice. Ginger apparently does that[0].
Ginger doesn't work as acute pain-relief but taking it regularly does seem to have positive effects like a faster recovery and reduced muscle pain after training. And it's anti-inflammatory in general, which is nice. (I also wonder if anyone tested if it synergizes with painkillers to let them work better at lower doses).
I created this open-source application (https://alexcpn-faers-signal-detection.hf.space/) to analyse the FDA FAERS data set a few weeks back, just to do some good work and use Claude Code completely. I got roasted on Reddit for attempting this. But this is meant for specialists to use, as most platforms that analyse this data charge a lot from what I read.
FDA FAERS is the official dataset for reporting Adverse events from taking a drug. FDA adverse event reports about 2 million cases and 4,067 unique drugs
I agree the results are not easy for non medical professionals to interpret correctly. For example DEATH is very strong with Parecetemol and so is DEPENDECE. The latter because from AI it is a confounding factor. Acetaminophen/parecetemol is frequently co-formulated with opioids (like Hydrocodone or Codeine). The "Dependence" signal is likely attributed to the opioid, not the Acetaminophen itself...
Cool, throughout this entire read I was thinking "I'm gonna save this, it reads a lot like dynomight". And then at the end it turns out it was dynomight all along. I guess I should read headers more carefully.
I had intestinal bleeding after double ibuprofen dosage over several weeks for back pain. Definitely watch out for any prolonged and heavy use of NSAIDs.
I’ve alternated these for fever, especially for kids, especially when it’s high and hard to control. That way you keep below the daily limit of each and don’t overdose on either.
Have gotten into a habit of keeping a note of which med when on the fridge.
I feel like this article leaves out the latest research pointing to acetaminophen having a negative effect on fertility, hindering embrionic development and potentially also also follicular development in baby girls. It's a trade-off for sure, but if you're trying to have a baby, you may want to swing back to ibuprofen.
I went from introvert only-child to married with kids. As they hit daycare, I was perpetually riddled with disease for about 15 months. I still had to take care of the kids though, so I was liberally taking Ibuprofen. At some point, I started to get horrible heartburn. I tried all kinds of dietary restrictions until I realized it was probably the Ibuprofen. Now, if I take even one pill, the heartburn comes back. I switched to Acetaminophen and found it was much more effective at reducing fever with no apparent side effects.
Yeah our son became eligible for creche just when covid came. All at home but we couldn't take full time care for him forever so eventually he started going in (they can start at 6 months here in Switzerland if you are lucky and get the spot, we did it gradually since 9 months). Then daughter came and same cycle.
Needless to say we had covid at least 12 times at this point, all with positive tests so no mistake there. Plus few other questionable cases without tests. Some were brutal, like first and second one, that was before vaccines, and then a recent one when we seem to have lost most of immunity. Back then I lost taste for few weeks completely and smell didn't fully come back till 6 months after (sniffing bottle of vodka did smell like forest air, even later my perfume smelled rotten). Weird times, eating nice looking gunk and trying to imagine how it tasted before.
I don't think I had flu that many times over my whole life, hate that shit with fiery passion and having small kids in creche/school is just a 24/7 virus importing service. None of our peers had it as bad as we did, no idea why the 'luck'.
"since 2019, on the advice of the National Agency for the Safety of Medicines and Health Products, French health workers have been told not to treat fever or infections with ibuprofen." [1]
But yet in some countries pediatricians will libreally prescribe it to toddlers
Also
from [2] "In this systematic review of NSAID use during acute lower respiratory tract infections in adults, we found that the existing evidence for mortality, pleuro-pulmonary complications and rates of mechanical ventilation or organ failure is of extremely poor quality, very low certainty and should be interpreted with caution."
One of the problems is that if you give it to kids with chicken pox it can cause complications. There was also some hints early in the pandemic that ibuprofen had a similar effect on covid-19. However as you link to, the data doesn't really support that view anymore.
No, even if morphine were metabolically safer (I don't know), its addictive potential would outweigh the potential safety benefit.
On the other hand, if in the early 2000s you were to share those concerns with certain doctors, they would propose a more effective and non addictive alternative to morphine instead. Only the first part of what they would tell you was true.
In my personal experience, paracetamol hardly does anything when it comes to alleviating fever symptoms. Like I'm not sure whether I'd be able to distinguish it from placebo. I always default to ibuprofen and the difference it makes is like night and day. I only take it like a handful of times a year and usually no more than 1000mg a day so I'm hoping I'll be fine.
To the author, my guy, you are clearly not an endocrinologist stop pretending you are, and trust the people that study these things for a living.
Not only you can't take more than 4 grams of paracetamol per day, you must not take it for more than 3 days straight, it says so on the leaflet.
Biochemistry and medicine are hard and complex, all the quacks out there that preach snake oil treatments went down the path of thinking their domain specific knowledge in random domains somehow transfers to medicine it does not.
I keep reading about this lately but what doesn't make sense then is how few deaths/injuries there are relative to how much acetaminophen is consumed. If tens of millions take it every day, that's billions of doses a year of acetaminophen. Why don't we see MORE injuries/deaths?
"Acetaminophen toxicity is the second most common reason for liver transplantation worldwide and the most common cause of acute liver failure in the United States. Responsible for 56,000 emergency department visits and 2600 hospitalizations, acetaminophen poisoning causes 500 deaths annually in the United States."
56,000 emergency room visits is the key here, because "the mortality associated with acetaminophen overdose is low if recognized and treated within the first 8 hours after an acute ingestion."
So I guess it depends on if you think 56,000 is low or not.
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.
If acetaminophen was invented today it would almost certainly be available by prescription only because of the safety concerns. There are far more benign medications that are Rx only.
The article doesn't touch on it, but from what I've read NSAIDs like ibuprofen also slow healing. I have also read, but am unsure how reliable this is, that they can harm the remodeling process during healing and lead to chronic pain.
That said, I've found great relief at times taking a moderately large dose of ibuprofen for several days to break what seems to be a cycle of persistent inflammation. YMMV I guess.
Why are COX-2 drugs like Celebrex still prescription only ? Seems like it would theoretically be a lot safer to offer a medium low dose of it over the counter vs other NSAIDs
That being said I weirdly find Naproxen the most effective of all of these. Everyone is different though
For migraines, I take two CVS Migraine about every week to ten days. It's a cocktail of acetaminophen, aspirin and caffeine which tallies to 500 mg of acetaminophen, well under then 4g limit. It's good for four hours but you can only take two per day.
I didn't know about this acetaminophen risk. So I'll be looking for alternatives. Ibuprofen is for inflammation and not headaches. Naproxen is a candidate.
Ibuprofen is very well supported as a treatment for migraines. Not necessarily headaches generally, but definitely migraines.
But there are multiple classes of abort drugs now that a doctor might be able to prescribe you, like triptans and CGRP inhibitors, that work much better than either NSAIDs or acetaminophen.
High dose aspirin (1000mg) + caffeine worked much better for me for migraines than paracetamol/ibuprofen/naproxen which did nothing. There're some studies supporting this too...
I once read that if acetaminophen were introduced today it 100% would require a prescription because of how dangerous an overdose is.
Unrelated, but it feels like an oversight that this article said nothing about how both acetaminophen and ibuprofen reduce fevers. They aren't used solely for reducing pain.
I kind of doubt that, to be honest, given how much more effective and less directly damaging it is during normal use compared to NSAIDs.
I find it interesting that people take these as fever reduction mechanisms. Fevers are a defence mechanism, not just an inconvenience. Maybe it makes more sense in places without decent workers' rights (like having a limited amount of sick days you need to manage), but it feels weird for me to actively harm your body's defence mechanisms unless you're in "you should see a doctor" territory already.
Plus caffeine, for those who don't drink coffee. Quite standard combo for people suffering from migraine. I stick to 500mg+200mg and I find it suspicious adverts for painkillers somehow always show 2 pills while dosage recommend in leaflet is just one.
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.
and my own editorializing -- this is not just a problem for little kids. As various articles explain, if you've had flu-like symptoms (from whatever cause) you should be wary of aspirin. Will one standard dosage kill you? Unlikely. But if you've got better options, particularly pre-loading NAC before Tylenol, why not consider them first?
"Good for fever"? Only ignorant consumers would attempt to counteract the body's very own defenses against infection and disease.
A fever is not dangerous within normal parameters, except for being dangerous to the virus and bacteria that threaten the body. Your body runs a fever because it engages in a battle to the death with these microbes.
If you defeat the body's own defenses by lowering the fever, for example if you are a nervous mother who hates her baby's fussing, or if you're hospitalized and the nurses are laser-focused on "number go down" treatments, then you can expect to be ravaged by the contagion for much longer than expected.
The priorities have drifted. In the middle of night I don't care about getting healthy, I need to get rid of fever, so I can fall asleep and able to got to work/school in the morning. And somehow there is never right time to be sick and everyone just want to supress syndromes here and now.
Someone with a basic understanding of evolution and biology understands that evolution will take any free lunch it can get.
The vast majority of the time medicine can only ever help with (acute) symptoms and rarely the underlying cause unless it is something like vaccines or antibiotics.
Medicine has side effects because if there was a free lunch to be obtained from medicine, the human body would have synthesized the medicine directly. Hence medicine is always about making tradeoffs.
When it comes to general health, there is always a causal chain of cause -> primary symptom -> secondary symptom -> tertiary symptom -> ... and a lot of medicine tends to work on the secondary or tertiary symptom.
Pain evolved to be an accurate indicator of damage to encourage you to stop ruining your body and not a punishment.
This is a good argument, but it has a flaw here, which is that a systemic fever during illness may still be an evolutionarily beneficial adaption on average if there are a some situations where it can be the difference between life and death, e.g. bacterial pneumonia or sepsis, but that doesn't mean it's equally useful for all types of illness.
I did a fevered research dive last time I had the flu and came to the conclusion that there wasn't really any good evidence that fever is helpful for flu, and I should have few compunctions about suppressing it. (And that most of the situations where fever is really valuable for are ones where in the modern world you should go to a hospital and in the case of a bacterial infection be given antibiotics)
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.
For non-habitual pain relief, combinations outperform either in isolation. Studies show a significant effect, and anecdotally for me it's often the difference between dampening and outright curing a headache. Combo pills are widely available in most countries (branded as Advil Dual Action and Motrin Dual Action in the US), but they're pretty new so consumer awareness isn't yet super high.
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.
Interesting! In the UK the common wisdom is paracetamol is the safest. Ibuprofen is available but not the first choice. Aspirin is considered bad.
I wish people would stop saying "drinking" to mean alcohol consumption. I genuinely thought it meant after drinking any fluid until I read the description and realised it meant alcohol. I also don't like how alcohol is singled out as a "special" drug. What about other drugs? Is alcohol special in this regard?
To me it's obvious that acetaminophen and ibuprofen do not target the same kind of problems. I am not a woman, but my wife says acetaminophen does not work on menstrual pain for instance.
I take acetaminophen for fever, and those kind of full-body diffuse ill-feeling.
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.
The article is not signed, we don't even know if the person writing it has any sort of medical background, take it with a grain of salt, the about page lists people and none of them has a medical background
Honestly this article is mixing a lot of different factors
> Acetaminophen has a scarily narrow therapeutic window. The instructions on the package say it's okay to take up to four grams per day. If you take eight grams, your liver could fail and you could die.
Gee I don't know, I think this is a wide enough window to not miss it. That difference is 8 500mg pills
> that for most people in most circumstances, acetaminophen is safer than ibuprofen, provided you use it as directed. I think most doctors agree with this.
Could be but I think a lot of doctors underestimate the dangers of paracetamol as well
All of the factors the author mentions about IBP are true. But it's all about the details. Safer? Safer in which condition?
"Dehydrated" ok take a glass of water. Active bleeding? Most NSAIDs interfere with that, and no you won't become a hemophiliac by taking one Ibuprofen
An as a conclusion, I find it "funny" that nobody considers how healty/safe it is to take paracetamol and have mild analgesia (translation - you're still in pain) and taking ibp and having better analgesia
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”.
8g is not an insignificant amount. That's 16 500mg pills. You really need to mess up to take 16 pills and not realise you're doing something wrong. If a patient is not lucid than we have bigger issues.
And from what I see in pharmacies, you would rarely see a "cough syrup" called just like that if it contains paracetamol. It would usually be marketed as a flu-relief all-around symptom relief.
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.
As pointed out in the article, naproxen is an NSAID like Ibuprofen, though slightly more COX1 selective. It likely has a somewhat lower risk of serious renal and cardiovascular events, but higher risk of GI bleeds. There are some studies that show little to no increase cardiovascular risk, but most do show some or even comparable to ibuprofen.
Convenience vs ibuprofen is a thing given the longer half life, but it still generally comes with similar risks. If you are taking anything for more than just an occasional headache, definitely discuss with a doctor, COX2 selectives like celecoxib may be a better risk profile and even more convenient.
(COX1 and COX2 selectivity loosely separate which systems get the brunt of the side effects)
The higher risk of GI bleeds is could be somewhat balanced by not having to take as many.
There are also slow release forms of naproxen. (Which make sense given its long action: lets people fade in the next one while the previous dose slowly fades out). That could also help make it easier on the GI tract.
> The higher risk of GI bleeds is somewhat balanced by not having to take as many!
Unless I am missing something, the data really doesn't back that up. naproxen is much more longer lasting and has a higher chance of causing ulcers. Hence why its not over the counter in the UK and is prescribed with omeprazole to reduce the risk of issues.
I'm reading about this in more detail. Indeed, it's not the contact between the medication and the digestive tract that is the problem, but simply its presence in the blood stream. By inhibiting those certain enzymes, it reduces the production of prostaglandings, causes problems for the lining.
Naproxen will be around longer due to its long half-life, so it creates more opportunity for this problem.
I weirdly always found Naproxen much more effective than ibuprofen but also find Celebrex great which seems to further confuse the whole COX 1 vs 2 situation
> But if acetaminophen is safer, then why don’t official sources tell you that?
Guess it depends on country. Here in Norway official sources[1][2] do say acetaminophen (paracetamol here) should be the default for treating fever and pain in kids, adults, pregnant women and elderly, and have for some time. Ibuprofen they say should be used with caution.
[1]: https://www.dmp.no/nyheter/behov-for-smertestillende-slik-ve...
[2]: https://nhi.no/for-helsepersonell/nytt-om-legemidler/arkiv-2...
I feel like this is one of those things where Europe and the US are very different, culturally speaking - I've lived in the Netherlands, Germany and now Sweden, and the amount of painkillers used and prescribed here seems much lower than what Americans tell me is normal in the US.
Pain a warning signal from the body. It's something one should listen to, not just try to ignore and overrule. If I sprain my ankle it only hurts when I lean on it. Because it's healing. So I don't. Why would headaches or other "inconvenient" pains be different?
In my case headaches are usually caused by sleep deprivation causing high sensitivity to external stimuli, muscle tension, dehydration, or some combination of that. So I'll first try to take a nap and/or stick to low-stimuli environments, have a good stretch and/or heated up massage pillow for the neck, and make a quick home-made oral rehydration solution with some salt and sugar. That usually alleviates most if not all of the pain.
And I'm not saying painkillers should always be avoided. If I have insomnia-induced headaches in the morning and a long day ahead with many social interactions, then I know that headaches will make me a grumpy asshole, so I'll obviously will take a painkiller for everyone's sake. And sometimes I can only fall asleep if I take a painkiller to get rid of the headache first, so I need it to break the vicious cycle. I'm not saying people should "walk it off" here, just to focus on trying to figure out the actual cause first before medicating the symptom way. That's also healthier in the long run, no?
AIUI one of the many quirks of the US health insurance system is that a lot of people have only minimal cover which doesn't include things like physiotherapy and rehabilitation treatment. That means that they often can't treat a painful condition at source so their only option is to mask the pain with painkillers.
This is so absurd to me. The expression "prevention is better than cure" isn't just folk wisdom, in just about any country with nationalized healthcare the studies also confirm that this costs less money. The only exception I ever heard was a Dutch study in the 2000s suggesting that people growing older due to smoking less was going to increase healthcare costs, because people were getting older putting pressure on the pension system, but let's not peer further into that can of worms.
So by all accounts it should be cheaper for for-profit insurance companies too, unless they have ways to externalize the costs onto the rest of society. Which I guess is more circumstantial evidence for how messed up the system must be.
> That's also healthier in the long run, no?
Long-winding tangential anecdote (which is why I'm replying to myself in a separate comment), but I have pretty extreme example of this: I managed to avoid nearly all suffering after getting a tonsillectomy in my mid-thirties, while using almost no painkillers.
My ENT surgeons warned that me "I'd hate him for about a month, then I'd love him for never having to deal with [serious medical condition that justified the removal of tonsils] again". He prescribed all kinds of stuff to alleviate the expected suffering, and advised me to try to take the weakest options I was comfortable with, because the heavier ones might have some unpleasant side effects. It's the only time in my life I've been prescribed painkillers at all, actually (this was in Sweden, btw).
I got codeine/paracetamol as a coughing suppressor and mild painkiller, a couple of heavier painkillers for if it got worse (I forgot the name but some kind of heavy-duty variation of diclophenac that you can only get with a prescription), and some kind of nasty solution to gargle with that supposedly would numb my throat if it got really bad. I've been told this is nothing compared to what you can expect in the US.
Then in the evening after the surgery, when I was trying to eat a soup with my mom, I realized soup didn't hurt as much as drinking plain tap water. And then I thought: isn't it odd that drinking plain water feels like a thousand paper-cuts in the open wound in my throat, but whenever the coughing made the wounds open and bleed, the blood doesn't hurt at all? Blood is mostly water, so what is the difference? Could it be the salt? Is this similar to why drinking demineralized water is bad for you? What's the opposite of demineralized water? Oral rehydration solution. Ok, trivial to make, let's try that. I'll drink it luke-warm to be close to body temperature too.
Turns out that that works. Oral rehydration solution is almost painless to drink after a tonsillectomy. I know this is anecdata, but sample size three: I've since shared this information with two friends who got a tonsillectomy, and they've been extremely grateful for this tip.
It even seemed to speed up my recovery, probably due to a lack of irritation triggering inflammation. I was eating solid food within days. DAYS. My mom, a retired family physician herself, couldn't believe her eyes.
I ended up only needing the codeine/paracemtal in the evening to suppress coughing in my sleep, and brought back all the other pain-killers without opening them.
Since we're talking about acetaminophen and ibuprofen, in France you're liable to end up with a medicine cabinet full of acetaminophen, because almost anytime you go to the doctor with any type of pain, they add it to the prescription.
> the amount of painkillers used and prescribed here seems much lower than what Americans tell me is normal in the US.
Americans' relationship with painkillers is absolutely unhinged.
> Pain a warning signal from the body. It's something one should listen to, not just try to ignore and overrule. If I sprain my ankle it only hurts when I lean on it. Because it's healing. So I don't. Why would headaches or other "inconvenient" pains be different?
Pain is also suffering, and there is no virtue in suffering needlessly.
Even more importantly, there's also chronic pain, which can severely affect quality of file permanently and is essentially an illness all of its own. Research supports the concept of "pain memory", where chronic pain develops as the result of leaving the pain from a temporary condition untreated.
> home-made oral rehydration solution
water?
EDIT: I see it's a thing. Salt, water and sugar.
> Pain a warning signal from the body. It's something one should listen to, not just try to ignore and overrule.
This is vastly overstating the rationality of the human body. It's no more rational than the human mind, which is often quite irrational. Your body isn't the product of medical school, nor intelligent design, but rather random natural selection, which is decent but demonstrably far from perfect.
Especially if a new one, pain is undoubtedly a 'warning signal from the body' which is a succinct metaphor we all understand and has a clear meaning. If you don't know why or from whence the pain, check it out. It may be one of those things or perhaps not.
Perdue Pharma/The Sacklers went on a huge campaign in the 90s convincing doctors and the general public that pain was bad and worth stopping at any cost and even though they were pushing opioids, I can imagine this also increased the cultural tendency to use NSAIDs as well.
I agree that Purdue Pharma was probably the most significant factor, maybe enhanced by the relative ease of granular lobbying of private doctors as compared to the challenges it may face in universal healthcare systems. However, I do suspect that the limited rights of most US workers to take sick leave served as one more cultural advantage in favour of Purdue's campaign.
In many countries if a doctor believes you're too sick to work you have a right to take leave until you recover, without risking your job and without expending limited "sick days". In those circumstances the doctor will of course prescribe something for your pain, but as a patient you have no incentive to insist the painkiller is strong enough to allow you to continue working.
Yup - in the UK, paracetamol is usually recommended for general pain relief before Ibuprofen. Additionally, Ibuprofen and NSAIDs have a lot of interactions which can make them unsafe - SSRIs or blood thinners for example.
Where does Aspirin fit into this? I only use paracetemol and ibuprofen. The one time I tried asprin I got a stomach pain.
aspirin is an NSAID, taking it modifies the prostaglandine levels (through its COX inhibition) and this influences the mucosa of your stomach. ibuprofen can still have the same side effects, because its belonging to the same class of drugs.
It’s the same in the UK - paracetamol is the default. Ibuprofen is better for reducing swelling, inflammation etc.
Ibuprofen is better are reducing fever and managing headaches.
Paracetamol is the safer version Phenacetin. You used to be able to buy aspirin, phenacetin and caffeine..but phenacetin with withdrawn. APC when it was marketed was very popular but soon you were told to never give children aspirin for a fever so we used Paracetamol. Then Phenacetin was withdrawn and paracetamol became part of APC (like Alka selzta XS , or just the popular caffeine paracetamol combos)
Paracetamol came in as safer but similar, yet no where near effective. It captured bith the market feeling of its pros and cons. So we interpreted it as safer than alternatives (especially aspirin for children due to Reye syndrome). But also dangerous which might be why OPs view was that ibuprofen is safer.
The NNT (number of people you'd need to take it) to be headache free after 2 hours is about 12-20 for paracetamol. But only 7-10 for ibuprofen.
It's quite surprising that paracetamol became the defacto analgesic given it performs so poorly but it was historical inertia. And plenty of people argue that if we were to start over we would not make paracetamol OTC.
Wiki for phenacetin says it's mechanism of action is being metabolized into paracetamol. IDK about your "nowhere as effective".
It was withdrawn for sometimes being metabolized into another, toxic and carcenogenic, molecule.
Here is a summary of COCHRANE evidence on Paracetamol "widely used and ineffective"[0].
It's a paradox no?
Paracetamol is only the presumed only active metabolite, and that is why paracetamol rapidly replaced phenacetin.
There is a quirk though, phenacetin actually delivers paracetamol to your brain and spine (where it primarily reduces pain) faster than an oral dose of paracetamol.
Similarly IV paracetamol is far more effective that oral paracetamol.
Phenacetin was also considered mildly addictive, and induced a gentle euphoria and then sedation.(We still see sedation after paracetamol in children and the elderly). But general use we don't see these effects in paracetamol, why did phenacetin do this more effectively? Probably the higher peak levels around nerve endings.
These effects are both wanting of an explanation of phenacetin is just paracetamol and directly analegisic.
[0] https://web.archive.org/web/20240721144157/http://www.eviden...
Interesting.
I guess it tracks with personal experience. I find Paracetamol is OK for fevers/generic cold symptoms but absolutely useless for a headache, Ibuprofen is the only thing that shifts them.
Well it's the only thing that shifts them now I'm in a country where I can't buy soluble aspirin and codeine OTC.
I end up using paracetamol often for pain because it's what's to hand.
What annoys me is that so many people have your experience and are effectively gaslit about the fact it seems to often perform so poorly.
Reminder: don't take medical advice from someone who can't write correctly.
Very interesting though that the original article makes no comment on efficacy. It's all about metabolic safety which is not contentious.
Same in Portugal.
Here in my body, it tells me acetaminophen does absolutely nothing for pain where as ibuprofen does. I wouldn't take ibuprofen for fever
I once got it to make a small difference for pain - but I was in the hospital (surgery recovery) where the doctors were giving me more than the daily maximum.
In Western Europe too.
> but it does absolutely nothing with actual pain. It is placebo at best.
This is simply false.
you responded to the wrong comment. I assume this want mean for https://news.ycombinator.com/item?id=47860061
It is not false. It does nothing. Head hurts, you take paracetamol ... head still hurts. The belly hurts, you take paracetamol ... nothing change.
When I took ibuprofen it did actually made an actual real change.
"I took it and it didn't work so it's a fake placebo drug" - wow, your scientific method is flawless, have you considered a career at the US Department of Health?
That might be a good fit considering who's in charge today.
Guideline #1 for comments-
Be kind. Don't be snarky. Converse curiously; don't cross-examine. Edit out swipes.
Maybe you had an inflammation-induced pain. That would explain why ibuprofen helped, and paracetamol did not.
I have a counter-study with size n=1: I did all my recovery from tonsilectomy on paracetamol and definitely noticed it working. That was however on the maximum safe dose.
(one of the major problems with paracetamol is that the effective dose is only a few multiples away from the dose which starts to cause liver damage! It is by a long way the most dangerous OTC drug)
You're partially right compared to placebo only about 5% of people are painfree over the effect of a placebo when taking paracetamol.
Paracetamol got it's start as replacing the more effective but much more dangerous and withdrawn drug Phenacetin.
Why don't people notice that it's such a small benefit over nothing? Well because placebo effect is quite good for pain and pain is usually transitory anywhere..if you have a tension headache you're probably going to aim to relax. Turn away from the screen or even have some caffeine and those are more effective than paracetamol!
Where did you pull this 5% from? There are gazillions of studies showing higher or lower efficacies for different kinds of pain. Along with the inaccuracies about Phenacetin (whose MOA is metabolising into paracetamol).
You will indeed find various figures for various pain types all are far worse than ibuprofen.
Here is an example from the Cochrane library
> For the IHS preferred outcome of being pain free at two hours the NNT for paracetamol 1000 mg compared with placebo was 22 (95% confidence interval (CI) 15 to 40) in eight studies (5890 participants; high quality evidence), with no significant difference from placebo at one hour.
A NNT of 22 means that in absolute terms 1/22 people met the positive endpoint criteria more than placebo. This figure is usually quoted as 20% for placebo and 25% for paracetamol giving NNT of 20.
The NNT of 22 gives 1/22= 4.5%.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD...
"pain free" is a long way from the pain is manageable. Pain is an understudied subject, where we have too little knowledge. Just using the word manageable is an indication of this.
That's very true, but the metric is applied to all medications you compare against that's what's important. You also just get a baseline idea of what's good by guessing what you'd accept.
Episodic tension type headache tested with ibuprofen Vs placebo NNT is 14. (Btw that's not great itself) But it's better than paracetamols often quoted figure 20.
Here's why I say it's not great. Why don't you guess some reasonable NNTs for say moderate depression treated with SSRIs, or no relapse in schizophrenia treated with an antipsychotic. Now guess the NNT for a statin to prevent a first heart attack.
SSRI for moderate depression about 10, antipsychotics to prevent schizophrenia relapse over 2 years NNT= 3 (excellent )Statin to prevent a first heart attack 200! (This one always shocks me). Statins have a clear role of course.
[0] https://thennt.com/nnt/ibuprofen-treatment-episodic-tension-...
Really? I get headaches semi-frequently and my first line of defense is ibuprofen, I use acetaminophen sporadically as a last resort
Why? Does ibuprofen work better? It's bad for your stomach walls.
I take both. 500-1000mg acetaminophen, 200-400mg ibuprofen. Usually helps for headaches which I get frequently. I only take them for the worst headaches though, so probably once every couple of weeks on average.
Yeah if I need to I take both also. In addition I be sure to have a caffeinated drink also as caffeine has been shown to both speed the absorption and boost the efficacy (5-10%) of paracetemol over a multi hour period. https://pubmed.ncbi.nlm.nih.gov/17442681/
In Ireland you can buy acetaminophen in stores, gas stations etc.
For ibuprofen you need to go to a pharmacy.
I couldn't get over this after moving here from the UK where you can pick up a pack for 10p in a supermarket.
That is interesting. In the UK they're both available pretty much everywhere, and they're some of the cheapest drug prices I've seen anywhere in the world... ~20p for 16 tablets or something.
Same in France
The only issue with treating pain with paracetamol is that it does not work at all against the pain.
It works against fewer or maybe mild inflammation and what not ... but it does absolutely nothing with actual pain. It is placebo at best.
> but it does absolutely nothing with actual pain
Neither paracetamol nor ibuprofen work by blocking pain. Depending on the type of pain and your physiology it can range from really effective to not at all.
I only take paracetamol, it works better than both ibuprofen and opioids for me. I know other people who have the exact opposite experience. There’s no absolute here.
Yeah paracetamol does absolutely nothing to me with pain. I thought its mainly fever medicine.
Same here. Paracetamol also gives me pretty strong stomach aches whereas ibuprofen rarely has a gastric effect and when it does it's mild at best. I've been told by many people that the opposite should be true but oh well.
I wish they dipyrone was sold here, but alas I can only get it when I travel abroad.
With medicine both can be true, the response depends on so many factors in your body. Same way that for some people, particularly those with ADHD, taking stimulants can make them sleepy.
Yeah, for me paracetamol is worse in everything - fever, pain, etc.
For mild stuff I use ibuprofen, if it gets worse, diclofenac works every time.
Many years ago I had 4 surgical procedures done around my nose/throat at the same time - straightening a deviated septum, turbinectomy, enlarging the openings into my sinuses and removing my tonsils. This meant I couldn't breath through my nose for about a month - and breathing through your mouth when you've just had tonsils removed is quite painful.
Soluble paracetamol literally turned the pain off like a switch - of course I was limited as to how much I could take, which I was careful to stick to but I was almost in tears waiting for the time to come where I could take more paracetamol.
So in some situations paracetamol can be an extremely effective painkiller.
It may not work for you, I don't know. But it absolutely does work in general!
What is actual pain?
When it hurts. Like, when your head hurts for example.
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.
> Apparently for some people it also helps with lessening tolerance for their ADHD meds, but I'm not so sure about that.
I'd believe it. I first heard of NAC on the nootropic subreddit in a past lifetime. The benefits vary, but generally it's a safe thing with a low chance of making anything worse, but a possibility to improve things. Many neurodivergent folk have written about how they benefit.
I'd give more info on the exact benefits they found (iirc OCD and rumination loops could be broken more easily), but unfortunately my memory is failing me.
You'll find a detailed description oft potential effects and uses here: https://en.wikipedia.org/wiki/Acetylcysteine (aka NAC)
How is nac (acetylcysteine) delivered there? I can buy dissolvable tablets here in Europe but from what I see that’s less helpful for mucous, things like mucomyst require inhalation, which isn’t in otc products I know of.
Dissolvable tablets & powders are still useful for getting rid of mucus. Maybe inhaling is better, but anecdotally the tablets seem to work.
The dissolvable tablets completely fix a runny nose for me. Much better than any nose spray, which tend to irritate the nose and lead to chronic runny nose if taken for too long.
Have you tried a neti pot or similar?
In the Philippines it's available as an effervescent tablet to be dissolved in water. They still tend to work better than the western remedies (guaifenesin etc) even in this form IME.
Usually here in Canada it's available in capsule form which I find less effective.
Same here actually, I find it slightly helpful but the effect’s useful time is limited. I’ve wondered if I could capture the gas released while bubbling and inhale that…
Same where I'm from, it's in pill / capsule form
I randomly bought NAC just to try it. I dont know about the chemical interactions, but going out with collegues at that time taught me that it's basically impossible to get drunk. Usually a pint of beer is enough to make le feel at least a little dizzy, but when taking NAC, it was all like drinking water
Just a note: “research about the safety of taking NAC every day for the long term is limited.” cf. a concerning 2019 animal study regarding higher risks of cancer https://doi.org/10.1172/jci.insight.127647 also discussed at https://www.science.org/content/blog-post/n-acetyl-cysteine-...
NAC taken before consuming alcohol has a positive effect apparently, but taken afterwards it's detrimental as mentioned here: https://en.wikipedia.org/wiki/Acetylcysteine
On mice.
Vaccine Ordering https://xkcd.com/2422/
Took me a while, because i pronounce "Pfizer" as "pfee-tseh-r" in my head
That's the original pronunciation
When I go out drinking with my pharmacist buddy, we take NAC before going out. He swears it makes hangovers less likely. I can't say I've noticed that particular effect, but I do seem to sleep a bit better on those nights.
Could somebody package Tylenol with a sufficient amount of NAC to de-risk it? I suspect such a formulation would not require trials?
Certain esters have been found to be much safer (in mice, at least):
> The glutathione hepatic values in mice obtained by intraperitoneal injection of the ester are superimposable on controls and the oral LD50 was found to be greater than 2000 mg kg^-1 and the intraperitoneal LD50 was 1900 mg kg^-1 ...
That's for pyroglutamic and glutamic acid esters of paracetamol: https://pubmed.ncbi.nlm.nih.gov/8799871/
and more general analogs apparently can also be designed to not produce NAPQI:
> Thus, in 2020, N-sulpharyl-APAP prodrugs 39–40 (Fig. 11) were developed. [...] They are not hepatotoxic because they do not generate toxic metabolite NAPQI, even in concentrations equal to a toxic dose of APAP (600 mg kg^−1 in mice).
https://pubs.rsc.org/zh-tw/content/articlepdf/2024/ra/d4ra00... p. 9702.
These would probably require trials, though.
See superscript 6 on the article. Apparently NAC might has side effects of its own.
One of the side effects in a study in mice was inducing lung cancer: https://doi.org/10.1172/jci.insight.127647
Similar rules in Europe, or at least, Portugal.
NAC is so amazing for us in terribly polluted areas. Also great before drinking
I am blessed with living in one of the most polluted areas in the world (PM2.5 going into thousands of µg/m³ in winter; summers are not much better due to dense chemical smog). Can you say more about how you're using it to combat that? Thanks!
Glycine + NAC even better, both precursors for Glutathione, Glycine also great for sleeping.
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've been prescribed slightly more than 5g per day (2 x 650mg tablets every 6 hours) for pain after an operation jointly with ibuprofen, which is scarily close to the limits.
I managed to overdose by accident with severe dental pain. Wasn't thinking straight, took about 8g - which is even more scarily close to the limits.
I'm fairly sure that caused some liver damage. I wasn't aware of anything apart from feeling a bit weird.
At the time, I had no idea it was potentially deadly.
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.
It is mind boggling how statements like that are possible in the US.
I guess it is much better than the situation before that, where you paid $5000+ and they also gave you an opioid addiction.
> I guess it is much better than the situation before that, where you paid $5000+ and they also gave you an opioid addiction.
Having a condition that actually warrants strong opioids and not being able to get them at any price is definitely not an improvement.
The problem is fundamentally that we want to pretend doctors can always distinguish two people describing the same symptoms when one person actually has them and the other is trying to get drugs. The often can't, so you can either make it hard for people to get pain medications even if they need them, or you can make it easy for people to get them even if they don't. And between these the second one is unambiguously better, because the first one is the government screwing innocent people and the second one is guilty people screwing themselves.
> And between these the second one is unambiguously better, because the first one is the government screwing innocent people and the second one is guilty people screwing themselves.
Could not agree more. Depriving people with legitimate pain of opioids is IMHO legitimate torture. It's a bit of a variance on the trolley problem in that the doctor/government isn't causing the pain, but their inaction is prolonging it.
Whenever people here mention to my critique of US healthcare how its now mostly solved problem now, its 'good' to see the other side and reality. It certainly doesn't seem solved unless you have a million or two just laying around on the account, while mortgages and kids tuitions are paid. And I can easily imagine a long term condition or 10 which, if unlucky in terms of treatment cost coverage can wipe out that sum in a decade or two, for a single person.
Seriously, how can you guys consider this acceptable. I am not of faith but doesn't bible teach to be kind to your fellow men above all? One would expect more adherence to such basic moral rules in such conservative christian society.
> Whenever people here mention to my critique of US healthcare how its now mostly solved problem now
Who says that? I don't think anyone sane can believe that US healthcare is "solved".
The problem with the US system is that it doesn't know what it's trying to be.
If you did a socialist system then everything is "free" but possibly slow and expensive on the back end when the government isn't efficient.
If you did a libertarian system then everything is cheap but it's caveat emptor because nobody is stopping you from buying morphine for $10 from Amazon.
The US system isn't either one. It pretends to be a market sometimes but then has a bunch of rules to thwart competition. Doctors are required by law to do residency but the government limits the number of residency slots in response to lobbying from the AMA so there aren't enough doctors. "Certificate of need" laws explicitly prohibit new competitors for various services. Insurance is tied to employment to make it hard for individuals to shop around. Laws encourage, require or have the government provide "prescription drug coverage" to make patients price insensitive so drug companies can charge a huge premium for patenting a minor improvement or simple combination of existing drugs and have the patient will something which is marginally if at all better even if it's dramatically more expensive because they don't see the cost when the insurance/government is required to pay for it.
It's a big pile of corruption, because all that money is going to places. But then if you try to fix it, half the population insists on doing the first one and the other half is only willing to do the second one, and the industry capitalizes on this to prevent either one.
Maybe instead we should do both rather than neither. Have the government provide a threshold level of services, like emergency rooms and free clinics and anything more than that the local government wants to fund, and then have a minimally regulated private system that anyone can use if the government system doesn't satisfy them.
I don’t know a single person in my life who thinks US healthcare is good, so that’s weird. And many my peers a have good jobs with good health insurance. Everyone I know has at least one bad story about insurance, if you’ve ever had more than really basic checkups.
> What does ingesting 10g of acetaminophen even look like?
20 not-especially-large tablets
As an American this is such a weird question to me. I purchase my ibuprofen and benadryl in bottles of anywhere from 400 to 1000 pills every few years.
Is this not suicidal behavior?
Apparently a common source of problems is taking two different medications without realizing they both contain acetaminophen.
Suppose your arthritis is acting up, so you start taking Tylenol 8hr Arthritis Pain[1]. That's 2 tablets every 8 hours. They're extended-release with 650mg per tablet. A total of 3900 mg in 24 hours.
A few days later you get the flu, so you decide to add what seems like a completely different medication: Theraflu Flu Relief Max Strength[2]. It has a cough suppressant and an antihistamine. But each caplet also contains 500 mg of acetaminophen. It says to take 2 caplets every 6 hours, so you take 8 of them in 24 hours[3]. That's another 4000 mg.
Between the two, you're at 7900 mg.
Then you wake up in the morning and take both medications, but 30 minutes later you've forgotten you took them. You're not thinking straight because you're sick. So you accidentally take a second dose. That additional 2300 mg brings your total to 10200 mg.
---
[1] https://www.tylenol.com/products/arthritis/tylenol-8hr-arthr...
[2] https://www.theraflu.com/products/day-night-flu-relief-max-s...
[3] You weren't supposed to take 8 of them, though. If you'd read the label very carefully, you'd have seen it also says not to exceed 6 in a 24-hour period.
My personal rule is to only purchase over-the-counter meds with a single active ingredient. I'd rather separately take an antihistamine, expectorant and painkiller than a concoction where I have to read the whole label and do math while sick to separate the doses and timings.
There are some that are very hard to find as a single ingredient. Recently I was purchasing a medication for back pain, I had a choice as to which other ingredient I wanted, but I didn't have the choice of none. I picked the combined ingredient I don't like to take, because I wouldn't be adding it on top.
I did toss on the other option, stand alone, at one point so I could get some sleep.
It left the medication I was more comfortable taking as an add-on option if things got bad enough. (This particular medication has much lower risk of overdose, so if I got stupid and took it again there would be no significant additional risk.)
It's ironic, but taking the combined medication with a known higher risk of its own was better than taking the lower risk medication.
One was controlled, higher risk, taken at specific times, while the other was taken in addition, on demand, as required.
Specifically this is one reason they’ll sell you cocodemol or Vicodin but not codeine or hydrocodone directly — if you take enough to get a codeine high, you’ll have taken a toxic amount of paracetamol/acetaminophen, so they assume you won’t.
Doin' the Lord's Work here, sir.
Also, loved your TV show back in the day. :-)
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.
> Apparently i don't understand pain
I didn't until I had a bulging lower back disc pressing on my sciatic nerve. My leg felt like it was constantly on fire no matter what position I put myself in. In the past I've torn my ACL and had surgery to reconstruct and that pain was like stubbing my toe compared to the back pain. I understood how people become addicted to pain meds after my back situation.
Totally get it, I too only understood it "theoretically" till I had a (fairly minor!) dental operation.
... Suddenly I'm maintaining a continuous note of when I'm taking which medicine to avoid crossing safe limits (which I anyway was crossing most days).
I was only told to take 2 paracetamols a day (bullshit dose, I'd be waking up from the pain even with more pain meds).
"Diclofenac for rare use" - well, if nothing else is touching the pain, is it an emergency?
Eventually after forever I was able to transition to Ibuprofen + paracetamol. And I already have a health condition which is heavy on my kidneys... pain management can be absolutely crazy.
Pain management can be crazy but in your case it sounds like they didn't prescribe the appropriate medication presumably due to the anti opiate hysteria that has taken hold.
> Apparently i don't understand pain...
Speaking as someone who is not-infrequently in significant pain, I sincerely hope that you never have to.
Did you suffer any liver function damage as a result?
I presume your protein intake was adequate and diverse prior to this misadventure....
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.
Just in case, ibuprophen does not work well for pain relief [at lest for some kind of pain]. Paracetamol [acetaminophen] usually is much better against pain. And paracetamol + ibuprophen can help with strong pain for which neither paracetamol or ibuprophen work at normal doses.
Not really. Both address different sources of pain, and do so using different processes.
Ibuprofen is a Nonsteroidal Anti-inflammatory Drug (NSAID) that reduces pain and inflammation, while acetaminophen does not. (Acetaminophen is believed to act mainly in the brain rather than at the site of injury).
Ibuprofen- Fundamentally, if the pain is caused by inflammation, reducing the immune systems response to it can reduce pain, but if the pain is more acute it won't make a dent.
With acetaminophen, taking more isn't a solution in most cases, you need another method to reduce the pain further if it doesn't achieve its goal.
(That's why it's combined with things like codeine, which affects the brain in a different way for an additive effect)
> you need another method to reduce the pain further
I don’t know about “most cases” but often you don’t want to reduce the pain _further_, you want to reduce the pain _again_. (Having an alternative definitely helps in the meantime.)
Only if you take them all at once.
Also dementia
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?
The .nl indicates the netherlands. Many people in the netherlands vent/joke about how the doctors here only ever tell you to take paracetamol and come back in two weeks if it's still a problem (recursive solution).
However the last time I went to my GP she scoffed at me taking the maximum and suggested I take literally double the maximum recommended dose 4-5 times a day which totaled I think 2.5x the daily maximum on the package. I am very much a "believer" in science and reasonable medical authority but this experience sowed the seeds of doubt, because from what I have always heard, that can actually kill you or cause permanent liver issues. I was also taking diclofenac simultaenously, and when I told her how many mg, she asked "where can you even buy such small doses, that's what I would give a small child" =/
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).
The linked size is also quite common in Belgium.
In Europe for sure they're also sold in 1g dosing. I think the packages don't contain lots of pills, though. Definitely not US style buckets of pills.
Buy a pack of 20x500mg (just checked, common size in Germany), take 2-3 every half hour for a while.
Sure, that's extreme. But if you're unaware of the risks, you feel sick, and you believe it's helping you.
I mean, people aren't killing themselves in masses with it, but it happens every now and then. Easily imaginable that one in a few million people will have enough tendency to take more pills and is unaware of the overdose danger.
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.
I've heard it suggested that acetaminophen just come with a small dose of NAC alongside it to make it safer. I guess this would require a lot of regulatory work to approve, but given that 500 people a year OD, it seems like a thing we should at least consider.
Meanwhile, it's funny that it seems like acetaminophen should safer in more scenarios, but the other has a lot of overdoses with typical use, I guess that's why there's a gap between the two, because ODs are apparently a lot more common or at least more legible than problems caused by the other drug.
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 buy 100 packs, they are just behind the counter at chemists. TBH it's a rather stupid restriction - do they think people only ever own 1 packet of paracetamol at a time? In my household we have at least half a dozen, including a 100-pack from Oz and a 500-pack from America.
Oh right - that's probably what we did, buy a big pack from behind the counter.
I don't think you can even do that in the UK.
Yeah we usually have a few packs hanging around, and I get the 'it seems stupid' thing, but sometimes just adding a tiny bit of friction when someone's trying to kill themselves might save a life. I dunno, I hope that's shown in the evidence anyway. Otherwise it's just pointless like the whole pseudoephedrine song and dance, which has inconvenienced anyone looking for a decongestant while doing sweet FA to the availability of meth.
> Oh right - that's probably what we did, buy a big pack from behind the counter.
No, when you visited they were still on the shelf. They only put them behind the counter in 2025.
> sometimes just adding a tiny bit of friction when someone's trying to kill themselves might save a life
I'm philosophically not for making suicide harder. If someone wants to die, that's their right. And practically, while you might be able to show a stat-sig decrease in paracetamol poisoning, I'd expect the suicides to largely just move to other methods.
> I hope that's shown in the evidence anyway
tl;dr: Yes
Paraphrasing from [0], after September 1998 when the restriction was introduced, "The annual number of deaths from paracetamol poisoning decreased by 21% [...] the number from salicylates decreased by 48% [...] Liver transplant rates after paracetamol poisoning decreased by 66% [...] The rate of non-fatal self poisoning with paracetamol in any form decreased by 11%"
See also [1]: "in the 11 years following the legislation there were an estimated 765 fewer suicide and open verdict deaths from paracetamol poisoning, which represented a reduction of 43% [...] This reduction was largely unaltered after controlling for a downward trend in deaths involving other methods of poisoning and also suicides by all methods."
[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC31616/
[1] https://www.psych.ox.ac.uk/research/research-groups/csr/rese...
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/
s/idiot-proof/idiot-resistant/g
Also applies to most similar phrases ending in -proof. Should be eye-opening.
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.
No.
Alcohol and Acetominophen/paracetamol should not be mixed.
https://www.medicalnewstoday.com/articles/322813Sorry, crappy link. If you don't like it, it is easy to search for a better one.
There is a danger in chronic abuse resulting in upregulation. Mixing the two at once is no problem for the liver, which is also why patient information leaflets for paracetamol do not contain a warning to avoid alcohol, only about chronic alcohol abuse.
Your crappy source is vague in what consumption pattern constitutes a risk and actually cites a better source that supports the idea that acute alcohol consumption reduces paracetamol toxicity. https://www.biorxiv.org/content/10.1101/2020.07.07.191916v1....
That's a mathematical model, but this relationship between the two is what I was taught in medical school and it is still supported by the science. There's plenty of other sources, I just picked that one because your article cites it. Just search for "paracetamol ethanol" on Google Scholar.
This is correct.
My US doctors almost never recommended Ibuprofen over Acetaminophen for mild pain. In fact, I don't remember them ever recommending Ibuprofen for anything while I hear about Tylenol pretty often.
I've had doctors prescribing short runs of opioids (2 weeks for surgery recovery) but they always said "try Tylenol first and if the pain is too much you can fill the prescription". I liked having the option but never really used it up to this point.
Only twice have I ever used Acetaminophen close to the max daily limit, and those were both when I was experiencing a raging tooth infection. I'd pop 2x500 mg paracetamol 4 times a day, which helped just enough to get through the day. The tooth infections were so severe that the dentist had to put anesthesia directly into the root / nerve, multiple times - felt like a lightning strike each time. One of these times I'd put the pain level at a 9 out of 10. I'm just going to assume that 10 out of 10 pain is when you basically consider ending it all, purely in the heat of the moment.
Having gout, I've also had some pretty severe bouts where the pain level has been in the 8/10 range. Unfortunately nether paracet or ibuprofen worked.
In any case, when I see regular people eating these painkillers as candy, I'm starting to wonder what pain levels they are experiencing. I'm generally very cautious of using this stuff.
Pain is weird. It's extremely subjective, not only between people but also within your own body. Paraphrasing something Paul Rozin mentioned in a paper on so-called benign masochism: people can learn to enjoy eating the most extremely spicy food, but even those people will still scream out in pain you rub the ghost pepper they're eating in their eyes. Pain sensation is localized and contextual.
As far as 10/10 pain goes, I've heard cluster headaches can get so bad it has driven people to suicide during an episode.
I lived with an ICU nurse for years and one of the things he emphasized was the risk of acetaminophen overdose. He's more than once treated the liver failure (and death) from it and by his words, it's one of the worse ways to go.
The positive of it is it got me in the habit of logging whenever I take it, either in a note on my phone or just a sheet of paper I place on my dresser under the bottle. This helps make sure I stay under the 3-4g/d limit.
Last year I was diagnosed with a rare headache disease (NDPH). We thought it completely came out of nowhere, but I had logs in my phone recording headaches and acetaminophen use intermittently from a few weeks prior. This proved useful in the diagnosis.
Moral of the story: log when you take it to avoid overdosing. Combine that with some basic symptom logging (like 1 line, 10 words or less). You never know when that might be useful for your doctors later on.
In my wilderness first responder class they emphasized taking a cocktail of ibuprofen and acetaminophen - both are effective pain relievers, each with different dangerous side effects.
The benefits stack, the side effects don't.
So if you are going to be loading up on higher doses of pain relief, take half acetaminophen and half ibuprofen.
P.S. like someone mentioned in a comment below happened to them, be careful with NSAIDs over the long term. Until recently I took them daily for better part of 3 years. I was recently diagnosed with chronic kidney disease. Can't definitively say causation, but they definitely contributed. They're fine for short term use but can really f$%# you up with long term, daily use.
It is absolutely valid to warn about long term use, and NSAIDs in particular (I was lucky and had a gastroscopy before they'd done any serious damage, but they found significant erosion of my stomach lining due to NSAIDs), but acetaminophen/paracetamol isn't an NSAID (ibuprofen and aspirin, for example, are)
To be clear, it was nabumetone, celecoxib or meloxicam (at various times, not overlapping) for me.
In mozambique i was committed to the hospital with my liver failing after spending two weeks taking acetaminophen daily because everyone at work got sick and someone had to keep the business up (it was a bank, our IT department was very specific and only 6 people knew that job and everyone got extremely hill). After two weeks, i finally went to the hospital and I couldn't leave; spent the next two weeks fighting for my life and at some point I was told I was not going to make it. All due a simple over the counter medicine... crazy. This was 2016. To this day I still get extremely tired if I take it, so I have to choose it carefully when to take it.
That sounds terrible! Glad you made it out alive and hopefully recovered well! Out of curiosity: how much did you take per day?
Agreed!! Here’s my trick: take 1g and set an alarm for +6 hours. If I don’t need it, fine. If I do, repeat.
I'm not disagreeing with you or trying to be disagreeable, but how do people accidentally exceed 3-4 grams daily? That's 6-8 pills!
You are running a high fever or have a massive headache, so know you are going to max out at 4g/day. At that point, it's kind of hard to keep track of the clock.
"My head is pounding. Shit...did I take this at 3PM or 5PM? I know I took it and then fell asleep, but I can't remember when. It is now 9PM, can I take more or not?"
It often happens when people take the max dose of straight paracetamol, and then also take another drug that has paracetamol in it without knowing that (e.g. a codeine/paracetamol or ibuprofen/paracetamol combination).
People who are in a lot of pain and don’t know the risks.
Rationalizations like “they probably put the limit way lower than the real limit so idiots don’t OD themselves, so I can safely take a bit more” become very attractive when you’re in a lot of pain.
To be fair, the "real" limit depends on how lucky you are with your body's makeup. The safe limit is below that limit.
I know people with permanent pain due to medical conditions who have been given a doctor's approval to exceed the limits printed on the packaging (after having previously been monitored). You can exceed the limit on the packaging by one or two pills.
A bit more is often not deadly, but it's very easy to take more than a bit. When I had a messed up mouth for several days, I took the maximum doses and set timers to help me regulate the dosage throughout the day, but I sure wished I could've taken more at that time.
Okay that's right, if you just keep upping the dose because you're still in pain it might be easy to just slam a few every 4 hours
From personal experience if i have a headache I'll take 1000 mg all at once; it either works right away or it doesnt and I stop bothering until I've had a good nights rest...
Imagine if that rest will do nothing for that headache and its there morning day and night. Or some injury-related pain which simply can't be downtuned. Plus when old, half of the body aches, all old injuries and general deterioration.
I had only very brief experiences with longer intense pain but it made my mind into pudding and desperate knot of how-to-stop-this-at-all-costs. Normal life is not possible and sanity is not granted.
Yah...I've been there for 6 months now with a constant headache. The first month or so, I was taking 3.5g/day consistently. At hour 4.5 - 5, it would wear off. If it wasn't for my tracking, I probably would have ODed.
If you take 2 on average every 4 hours, you're at 12. If you're feverish or otherwise feeling ill enough and sleep deprived enough, forgetting when you took them last is easy. Personally I write down the time I took the last one.
It can also happen if the person has some disease that affects the liver, which in turns lowers how much of the drug they can take.
Hot Coldrex (Tylenol) + Pills. People don't read.
In the article it is mentioned but it is worth stressing that N-acetylcysteine is a trivially available antidote for paracetamol overdose (and you may have it at home without knowing, Fluimucil, Mucomyst, NAC or alike).
Also: in Europe everybody normally takes paracetamol and not FANS as a first reach to minimize adverse effects. So this article looks like very US centric. AFAIK liver failure because of paracetamol in Europe is very rare. So here there could be cultural issues at play (medical culture of what is prescribed, and the fact that Europeans in general take lower dosages of everything).
EDIT: trick, if you very rarely take paracetamol and other pain medications, the next time try to take just 250mg. It works for most people, no need to take 750 or even 1 gram of paracetamol. 500 works for almost everybody, 250 for many folks.
The right tool for the right job. When it comes to medication, in the right dosage.
I'm aware of acetaminophen's down sides, and yet recently I was taking it combined with 2 other medications at the time.
Why? Because all three medications are recommended for dealing with the issue I had. (Alone and in combination)
The moment it wasn't helping further? Done.
There is this broken idea, particularly apparent in North America, but in western society that more is better for many things. It's not.
More pain killers don't do anything if they max out the relief they can give you, overloading their mechanism doesn't reduce anything, but taxing your liver or your kidneys.
All medications are potentially toxic, your body wants to dispose of them. In appropriate dosages they will benefit you, but more isn't inherently better.
Even water can kill you in sufficient quantity.
We do the same with diet; where someone declares one ingredient in a meal healthier than another; it isn't. A single ingredient isn't better or worse for you in a meal. Your diet however can be good or bad; over time that matters.
Try dealing with a herniated disc, more ibu is definitely better. Too little wont do anything, proper dose and you feel healed
Yeah can confirm. I try to keep it low but then pain lingers for days and cumulatively over the days most probably I took as much as I should have taken in stating few days already.
yeah tried to reserve ibu for sleep and during the day walking as much as possible. I know not everyone feels better while walking, luckily I did.
Spine issues are the single thing that pish me to ibuprofen or naproxen over acetaminophen. The latter does nothing for my issues.
yeah, its the inflammation going down that reliefs the nerve.
Took me 3 months, out of 2 i wasn't able to sit. Luckily I could walk and that give me great relief. So walked for hours.
Keeping the habit, will mostly being coding from my phone & walking from now on.
Really nice you found a workaround. I am constantly trying different ways to alleviate my pain without drugs.
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.
> largely because I had no expectation that it would provide additional benefit..
An interesting thing with ibuprofen is that at the regular dose of 400mg it inhibits pain but if you take 1600mg it doesn't inhibit much more pain than the 400mg dose, but the inflammatory effect does increase significantly. A lot of people don't know that and take too much thinking it scales linearly.
Some know that you can combine ibuprofen with paracetamol to get extra pain suppression.
And when you want to be gentle, you alternate between them.
If your doctor recommends to take a specific dose, take the specific dose. Don't half it. Taking half of stuff can also cause further damage. Like with antibiotics, where it can lead to bacteria becoming resistant.
So don't be the "smarter" person. Do as your doctor says and if you have doubts, consult another doctor before just doing what you think is safe, but actually isn't.
Is this not the case for OTC drugs? Specifically, the two mentioned in the article. I rarely take either of them, but if my doctor tells me to take 1 ibuprofen every 6 hours or so, if I halve that am I actually doing more damage?
> Is this not the case for OTC drugs?
In general, taking a lower dose than recommended can cause problems, but aside from antibiotics, the problems are probably going to be from insufficiently treating the underlying condition, rather than the medication itself. Most OTC drugs give a single recommended dosage for all adults, so some people will necessarily get a lower "effective" dose than others (eg. a 200 lb man compared to a 90 lb woman).
> Specifically, the two mentioned in the article. [...] but if my doctor tells me to take 1 ibuprofen every 6 hours or so, if I halve that am I actually doing more damage?
With the caveat that I'm not a doctor, you should be fine: the only effect of acetaminophen is pain suppression, so if the pain is tolerable, then you should be fine. Ibuprofen has some anti-inflammatory effects that could be important here, but realistically, if the anti-inflammatory effects are the primary reason for the prescription, then your doctor is more likely to prescribe naproxen or celecoxib.
But if this ever comes up for you again, probably the best solution would be to tell your doctor/pharmacist "I have a high pain tolerance, would it be okay if I take less?", since in my experience, medical practitioners are generally pretty happy to hear when you want to take less drugs.
This. But also don't trust doctors and always remember Richard Feynman's Wife. Science is hard.
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.
It’s also easy to imagine that you may be in a state of confusion and lose track of time and/or the count of doses.
It's a very strange cultural thing too, Australians (and I presume other Commonwealth countries) default to paracetamol (acetaminophen) before ibuprofen
Paracetemol has always been seen as first thing you'd take for pain relief, and you'd "step up" ibuprofen as an escalation, but that might more to do with marketing of Panadol (paracetemol) vs Nurofen (ibuprofen).
We'd look on at the US where you were taking Advil like candy in confusion.
One great thing you learn as a parent, you can alternate acetaminophen and ibuprofen. Both of them are recommended every four hours, but you can stagger one by two hours to maintain consistency of pain-relief taking ibuprofen then paracetemol two hours later
> I presume other Commonwealth countries) default to paracetamol (acetaminophen) before ibuprofen
Can confirm this is true in India.
Paracetamol is widely used. Paracetamol + Ibuprofen is more common than Ibuprofen by itself.
> Australians (and I presume other Commonwealth countries) default to paracetamol
The same is the case in the Netherlands.
It is a damn shame bordering conspiracy that metamizole (https://en.wikipedia.org/wiki/Metamizole, known as Analgin in eastern Europe and the Balkans, apparently also India) is not more widely available in the west. It's literally a wonder drug, the only non-narcotic (hence non-addictive) that actually relieves serious pain (including post-op) pain in my experience.
Since I've had a fair share of it in my life so far (more than 1kg of it so far, in total), and I investigated the disparaging studies and they are definitely not convincing at all; more recent ones somewhat absolve it (check the Wikipedia page).
I've never had any side effects from it, and I don't know anyone who did, unlike for any other painkiller (diclofenac, ketoprofen, ibuprofen, acetaminophen / paracetamol).
It is a medicine where I'm almost 100% sure the studies against it are intentional sabotage by pharma companies, and the vigor and persistence this is done with is really telling (lots of doctors and pharmacists in my extended family, including in regulatory bodies). The campaign against it never ends.
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.
Still take it with a huge grain of salt. Even official advice usually has severe limitations due to its broadness or straight politics, so medical analysis from random blogs truely isn't the best.
Acetoaminophen also has issues for people with weaker stomachs (I can attest), and will come with additional medication to cover these effects as needed. The whole "Is it safe yes/no" table has many asterixes and might be outright false depending on the how you look at it.
As usual, it's just complicated.
Never take anything that written on the medications with a grain of salt. Disregard everything that you have read online. The medicine instructions are your single source of truth
Is the salt supposed to offset hyponatremia or something?
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.
Naproxen sodium has much higher risk of GI damage especially with long term use.
Looking at the Wikipedia article, it seems naproxen is a NSAID like ibuprofen and can cause all the same gastrointestinal issues.
wait, how are you getting naproxen?
Whenever its prescribed here, its paired with some sort of intestine protection medicine to stop it burning holes in your stomach/intenstines
Ibuprofen is much safer, so long as you eat with it.
Paracetamol is also safer, so long as you don't OD.
BUT! so long as you stay below 4 grams a day, you'll be safe. (yes yes, in some situations you can take double, but unless you are under supervision, thats asking for liver pain.)
I had to use naproxen for some time as most effective way to control inflammation. Actually the only way, ibuprofen had some effect only in horse dozes. After visiting doctor, analyses, checking available sources was able to eliminate the reason of inflammation. Apparently it was a well known problem/solution. So far so good. Not sure about the long lasting effects of naproxen use.
All the over the counter NSAIDs have a similar safety profile.
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 there's one thing I'm hopeful for regarding all this AI hype, it's that some day we might actually get the Expert Systems we were promised decades ago. Then, finally, we can stop expecting human doctors to know everything. There's just so much going on inside our bodies and it's unrealistic.
I had a relative with a different story in the same theme. It sucks and I want to see this technology do something truly beneficial for a change....
The expert system relies on training data, and most of the medical data on the internet is either outdated or outright wrong. AI is not going to solve what the existence of Google hasn't solved already.
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Acetaminophen (paracetamol) is the drug of first choice for addressing pain and fever, in India at least. To the extent that it's regularly abused, and I know people who have been hospitalized because of abuse.
Even then, doctors are usually disapproving of ibuprofen (or some combination of it with paracetamol) unless paracetamol is contraindicated for some reason, and I had always wondered why.
I did listen to this 99% Invisible story about the use of NSAIDs in India once[1]
What you describe in an interesting contrast to the situation in The Netherlands. Here, virtually no one is prescribing ibuprofen _without_ also prescribing a baseline of paracetamol.
[1]: https://99percentinvisible.org/episode/579-towers-of-silence...
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!
My mom fell (88 yo) X-rayed, nothing broken but ignored her history of ulcerative colitis (tough to do, given the colostomy bag she’s worn for 50 years). Sent her home with Motrin. Ended up in the hospital for two weeks with bleeding ulcers.
How the hell did the attending physician not see a colostomy bag during the exam?!
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
> 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.
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 expect us to know those acronyms?
I thought they were cheat codes.
--DRESS means your clothes with fall off.
> I feel dumb saying this, but when I saw those labels in the past, I thought of them as a bunch of random information thrown together for legal reasons. But after spending a lot of time trying to understand these drugs myself, I now realize that these labels are... really good? (...) these labels are a triumph. This isn’t random information — every word is a synthesis of a mountain of research, carefully optimized to save lives.
Two disclaimers:
First, having grown up in the Netherlands rather than the US, I should probably not speak for the expectations one might have for the latter's drug labels.
Second, both of my parents were family physicians who also had a small pharmacy (not-uncommon in towns too small to sustain an independent pharmacist). I hold them both in high regard, so I am obviously quite biased to be defensive of them.
Which I'm sharing so you'll understand the context within which this sentence made me want to scream YES OF COURSE THEY ARE, YOU ARROGANT IDIOT! ALMOST ALL HEALTHCARE WORKERS WORK THEIR ASS OFF TO MAKE UNINFORMED PEOPLE LESS UNINFORMED SO THEY DON'T END UP DOING STUPID SHIT THAT GETS THEM KILLED! AND AS MUCH AS IT PAINS ME TO ADMIT THIS, THIS EVEN INCLUDES PHARMACISTS! IT'S THE PATIENTS WHO DON'T LISTEN OR BOTHER TO READ AAAAARGH!!!
Anyway, with that out of my system... I actually enjoyed the article as a whole!
Also, funny thing about the COX inhibitors part: apparently there's two COX enzymes: cyclooxygenase-1 and cyclooxygenase-2. COX-2 is the one that also triggers inflammation, COX-1 is the one that does most of the beneficial things. COX-inhibiting drugs target both. Targeting only COX-2 would be nice. Ginger apparently does that[0].
Ginger doesn't work as acute pain-relief but taking it regularly does seem to have positive effects like a faster recovery and reduced muscle pain after training. And it's anti-inflammatory in general, which is nice. (I also wonder if anyone tested if it synergizes with painkillers to let them work better at lower doses).
[0] https://nutritionfacts.org/blog/ginger-powder-as-a-pain-kill... (has links to lots of pubmed research about this subject)
I created this open-source application (https://alexcpn-faers-signal-detection.hf.space/) to analyse the FDA FAERS data set a few weeks back, just to do some good work and use Claude Code completely. I got roasted on Reddit for attempting this. But this is meant for specialists to use, as most platforms that analyse this data charge a lot from what I read.
FDA FAERS is the official dataset for reporting Adverse events from taking a drug. FDA adverse event reports about 2 million cases and 4,067 unique drugs
I agree the results are not easy for non medical professionals to interpret correctly. For example DEATH is very strong with Parecetemol and so is DEPENDECE. The latter because from AI it is a confounding factor. Acetaminophen/parecetemol is frequently co-formulated with opioids (like Hydrocodone or Codeine). The "Dependence" signal is likely attributed to the opioid, not the Acetaminophen itself...
Adverse Event Acetaminophen PRR (95% CI) Acetaminophen n ibuprofen PRR (95% CI) ibuprofen n ACUTE KIDNEY INJURY 0.87 (0.80-0.96) 498 4.27 (3.91-4.67) * 483 ANAPHYLACTIC REACTION 0.61 (0.51-0.72) 122 9.85 (8.90-10.90) * 382 ANGIOEDEMA 1.31 (1.13-1.53) 170 15.26 (13.77-16.92) * 378 DEATH 1.44 (1.40-1.49) 3958 0.07 (0.06-0.10) 42 DEPENDENCE 237.12 (231.51-242.88) * 39679 0.02 (0.01-0.05) 4 DEPRESSION 2.18 (2.05-2.31) * 1157 0.39 (0.29-0.52) 43 DRUG EFFECTIVE FOR UNAPPROVED INDICATION 16.77 (16.11-17.46) * 3180 44.17 (42.18-46.25) * 1921 DRUG HYPERSENSITIVITY 0.57 (0.51-0.64) 327 3.30 (2.98-3.65) * 372
For the rest of the world:
Acetaminophen = Paracetamol
Cool, throughout this entire read I was thinking "I'm gonna save this, it reads a lot like dynomight". And then at the end it turns out it was dynomight all along. I guess I should read headers more carefully.
I had intestinal bleeding after double ibuprofen dosage over several weeks for back pain. Definitely watch out for any prolonged and heavy use of NSAIDs.
I’ve alternated these for fever, especially for kids, especially when it’s high and hard to control. That way you keep below the daily limit of each and don’t overdose on either.
Have gotten into a habit of keeping a note of which med when on the fridge.
I feel like this article leaves out the latest research pointing to acetaminophen having a negative effect on fertility, hindering embrionic development and potentially also also follicular development in baby girls. It's a trade-off for sure, but if you're trying to have a baby, you may want to swing back to ibuprofen.
[1] https://pubmed.ncbi.nlm.nih.gov/40819833/
[2] https://ddeacademy.dk/ddea/what-new-research-reveals-about-p...
I went from introvert only-child to married with kids. As they hit daycare, I was perpetually riddled with disease for about 15 months. I still had to take care of the kids though, so I was liberally taking Ibuprofen. At some point, I started to get horrible heartburn. I tried all kinds of dietary restrictions until I realized it was probably the Ibuprofen. Now, if I take even one pill, the heartburn comes back. I switched to Acetaminophen and found it was much more effective at reducing fever with no apparent side effects.
Yeah our son became eligible for creche just when covid came. All at home but we couldn't take full time care for him forever so eventually he started going in (they can start at 6 months here in Switzerland if you are lucky and get the spot, we did it gradually since 9 months). Then daughter came and same cycle.
Needless to say we had covid at least 12 times at this point, all with positive tests so no mistake there. Plus few other questionable cases without tests. Some were brutal, like first and second one, that was before vaccines, and then a recent one when we seem to have lost most of immunity. Back then I lost taste for few weeks completely and smell didn't fully come back till 6 months after (sniffing bottle of vodka did smell like forest air, even later my perfume smelled rotten). Weird times, eating nice looking gunk and trying to imagine how it tasted before.
I don't think I had flu that many times over my whole life, hate that shit with fiery passion and having small kids in creche/school is just a 24/7 virus importing service. None of our peers had it as bad as we did, no idea why the 'luck'.
"since 2019, on the advice of the National Agency for the Safety of Medicines and Health Products, French health workers have been told not to treat fever or infections with ibuprofen." [1]
But yet in some countries pediatricians will libreally prescribe it to toddlers
[1] https://www.bmj.com/content/368/bmj.m1086
Also from [2] "In this systematic review of NSAID use during acute lower respiratory tract infections in adults, we found that the existing evidence for mortality, pleuro-pulmonary complications and rates of mechanical ventilation or organ failure is of extremely poor quality, very low certainty and should be interpreted with caution."
https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.1451...
One of the problems is that if you give it to kids with chicken pox it can cause complications. There was also some hints early in the pandemic that ibuprofen had a similar effect on covid-19. However as you link to, the data doesn't really support that view anymore.
After reading this, I wonder whether maybe low doses of morphine over a short period are safer than either.
No, even if morphine were metabolically safer (I don't know), its addictive potential would outweigh the potential safety benefit.
On the other hand, if in the early 2000s you were to share those concerns with certain doctors, they would propose a more effective and non addictive alternative to morphine instead. Only the first part of what they would tell you was true.
In my personal experience, paracetamol hardly does anything when it comes to alleviating fever symptoms. Like I'm not sure whether I'd be able to distinguish it from placebo. I always default to ibuprofen and the difference it makes is like night and day. I only take it like a handful of times a year and usually no more than 1000mg a day so I'm hoping I'll be fine.
If you take either of these medications regularly talk to your doctor.
To the author, my guy, you are clearly not an endocrinologist stop pretending you are, and trust the people that study these things for a living.
Not only you can't take more than 4 grams of paracetamol per day, you must not take it for more than 3 days straight, it says so on the leaflet.
Biochemistry and medicine are hard and complex, all the quacks out there that preach snake oil treatments went down the path of thinking their domain specific knowledge in random domains somehow transfers to medicine it does not.
I keep reading about this lately but what doesn't make sense then is how few deaths/injuries there are relative to how much acetaminophen is consumed. If tens of millions take it every day, that's billions of doses a year of acetaminophen. Why don't we see MORE injuries/deaths?
"Acetaminophen toxicity is the second most common reason for liver transplantation worldwide and the most common cause of acute liver failure in the United States. Responsible for 56,000 emergency department visits and 2600 hospitalizations, acetaminophen poisoning causes 500 deaths annually in the United States."
56,000 emergency room visits is the key here, because "the mortality associated with acetaminophen overdose is low if recognized and treated within the first 8 hours after an acute ingestion."
So I guess it depends on if you think 56,000 is low or not.
Source: "Acetaminophen Toxicity", David H. Schaffer; Brian P. Murray; Babak Khazaeni. 2026/02/19. https://www.ncbi.nlm.nih.gov/books/NBK441917/
About 50% of overdoses are intentional (especially suicidal teenagers), with the other 50% accidental.
So when pondering the issue of numbers, it matters what path people took to overdose.
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.
If acetaminophen was invented today it would almost certainly be available by prescription only because of the safety concerns. There are far more benign medications that are Rx only.
The article doesn't touch on it, but from what I've read NSAIDs like ibuprofen also slow healing. I have also read, but am unsure how reliable this is, that they can harm the remodeling process during healing and lead to chronic pain.
That said, I've found great relief at times taking a moderately large dose of ibuprofen for several days to break what seems to be a cycle of persistent inflammation. YMMV I guess.
Why are COX-2 drugs like Celebrex still prescription only ? Seems like it would theoretically be a lot safer to offer a medium low dose of it over the counter vs other NSAIDs
That being said I weirdly find Naproxen the most effective of all of these. Everyone is different though
For migraines, I take two CVS Migraine about every week to ten days. It's a cocktail of acetaminophen, aspirin and caffeine which tallies to 500 mg of acetaminophen, well under then 4g limit. It's good for four hours but you can only take two per day.
I didn't know about this acetaminophen risk. So I'll be looking for alternatives. Ibuprofen is for inflammation and not headaches. Naproxen is a candidate.
> Ibuprofen is for inflammation and not headaches
Ibuprofen is very well supported as a treatment for migraines. Not necessarily headaches generally, but definitely migraines.
But there are multiple classes of abort drugs now that a doctor might be able to prescribe you, like triptans and CGRP inhibitors, that work much better than either NSAIDs or acetaminophen.
High dose aspirin (1000mg) + caffeine worked much better for me for migraines than paracetamol/ibuprofen/naproxen which did nothing. There're some studies supporting this too...
I once read that if acetaminophen were introduced today it 100% would require a prescription because of how dangerous an overdose is.
Unrelated, but it feels like an oversight that this article said nothing about how both acetaminophen and ibuprofen reduce fevers. They aren't used solely for reducing pain.
I kind of doubt that, to be honest, given how much more effective and less directly damaging it is during normal use compared to NSAIDs.
I find it interesting that people take these as fever reduction mechanisms. Fevers are a defence mechanism, not just an inconvenience. Maybe it makes more sense in places without decent workers' rights (like having a limited amount of sick days you need to manage), but it feels weird for me to actively harm your body's defence mechanisms unless you're in "you should see a doctor" territory already.
You can combine the two for better effect.
1g of Paracetamol with 400mg of Ibuprofen gives similar pain relief as 2mg of IV morphine.[1]
[1] https://pubmed.ncbi.nlm.nih.gov/29017585/
Plus caffeine, for those who don't drink coffee. Quite standard combo for people suffering from migraine. I stick to 500mg+200mg and I find it suspicious adverts for painkillers somehow always show 2 pills while dosage recommend in leaflet is just one.
https://www.eurekalert.org/news-releases/1086746
This is semi recent research on how it might be blocking pain
Could they safer and/or higher dose acetaminophen pills if they included NAC?
Don’t anyone mentioning this, but alternating acetaminophen and ibuprofen every 6 hours as needed works well
This is a repost from an article that was posted last week: https://news.ycombinator.com/item?id=47799088
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.
OMG! I have been taking Dayquill/Nyquill in syrup form when having cold/cough and often without formally measuring! Will be careful from now on.
> You should not switch medications based on the uninformed ramblings of [crazy] people.
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?).
Should definitely hold up in whatever court they’re trying to avoid being in, lol
Don't forget ye olde aspirin. It has a cheat mechanic: https://en.wikipedia.org/wiki/Salicylate_poisoning
You take too much and it can give you a fever, which might entice you to take more aspirin. Nasty.
Obligatory Reye's mention:
https://www.uspharmacist.com/article/reyes-syndrome-a-rare-b...
and my own editorializing -- this is not just a problem for little kids. As various articles explain, if you've had flu-like symptoms (from whatever cause) you should be wary of aspirin. Will one standard dosage kill you? Unlikely. But if you've got better options, particularly pre-loading NAC before Tylenol, why not consider them first?
Further reading:
https://www.nhs.uk/medicines/low-dose-aspirin/who-can-and-ca...
And for those of you with kids: https://www.nhs.uk/conditions/kawasaki-disease/
Of course it's not all bad. There's even some discussion of anti-cancer potential. How might this work? One hypothesis: https://www.nature.com/articles/srep45184
This topic is a bit personal for me and I'm glad it's getting some attention here. Bravo, hackers.
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?
> If you don't make a habit of taking either, what actually performs better?
Tylenol/acetaminophen is good for fever which NSAIDs won't help. Otherwise, take both and alternate their dosing times for better pain coverage.
"Good for fever"? Only ignorant consumers would attempt to counteract the body's very own defenses against infection and disease.
A fever is not dangerous within normal parameters, except for being dangerous to the virus and bacteria that threaten the body. Your body runs a fever because it engages in a battle to the death with these microbes.
If you defeat the body's own defenses by lowering the fever, for example if you are a nervous mother who hates her baby's fussing, or if you're hospitalized and the nurses are laser-focused on "number go down" treatments, then you can expect to be ravaged by the contagion for much longer than expected.
The priorities have drifted. In the middle of night I don't care about getting healthy, I need to get rid of fever, so I can fall asleep and able to got to work/school in the morning. And somehow there is never right time to be sick and everyone just want to supress syndromes here and now.
> "Good for fever"? Only ignorant consumers would attempt to counteract the body's very own defenses against infection and disease.
Yes, ignorant consumers and physicians across the world.
You can't just 'vibe medicine' or 'vibe biology' - please don't comment if you don't know what you're talking about.
Someone with a basic understanding of evolution and biology understands that evolution will take any free lunch it can get.
The vast majority of the time medicine can only ever help with (acute) symptoms and rarely the underlying cause unless it is something like vaccines or antibiotics.
Medicine has side effects because if there was a free lunch to be obtained from medicine, the human body would have synthesized the medicine directly. Hence medicine is always about making tradeoffs.
When it comes to general health, there is always a causal chain of cause -> primary symptom -> secondary symptom -> tertiary symptom -> ... and a lot of medicine tends to work on the secondary or tertiary symptom.
Pain evolved to be an accurate indicator of damage to encourage you to stop ruining your body and not a punishment.
This is a good argument, but it has a flaw here, which is that a systemic fever during illness may still be an evolutionarily beneficial adaption on average if there are a some situations where it can be the difference between life and death, e.g. bacterial pneumonia or sepsis, but that doesn't mean it's equally useful for all types of illness.
I did a fevered research dive last time I had the flu and came to the conclusion that there wasn't really any good evidence that fever is helpful for flu, and I should have few compunctions about suppressing it. (And that most of the situations where fever is really valuable for are ones where in the modern world you should go to a hospital and in the case of a bacterial infection be given antibiotics)
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.
For non-habitual pain relief, combinations outperform either in isolation. Studies show a significant effect, and anecdotally for me it's often the difference between dampening and outright curing a headache. Combo pills are widely available in most countries (branded as Advil Dual Action and Motrin Dual Action in the US), but they're pretty new so consumer awareness isn't yet super high.
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.
Most human medicines would be dangerous to dogs, what is your point?
Interesting! In the UK the common wisdom is paracetamol is the safest. Ibuprofen is available but not the first choice. Aspirin is considered bad.
I wish people would stop saying "drinking" to mean alcohol consumption. I genuinely thought it meant after drinking any fluid until I read the description and realised it meant alcohol. I also don't like how alcohol is singled out as a "special" drug. What about other drugs? Is alcohol special in this regard?
there is an antidote for paracetamol: ACC (Acetylcysteine)
> Acetylcysteine
That's NAC (N-acetylcysteine, C5H9NO3S), mentioned in the article many times.
my bad
why they don't make pills with ibuprofen + nac?
To me it's obvious that acetaminophen and ibuprofen do not target the same kind of problems. I am not a woman, but my wife says acetaminophen does not work on menstrual pain for instance.
I take acetaminophen for fever, and those kind of full-body diffuse ill-feeling.
I take ibuprofen for localized intense pain.
I take aspirin for headaches and sore muscles.
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.
The article is not signed, we don't even know if the person writing it has any sort of medical background, take it with a grain of salt, the about page lists people and none of them has a medical background
Nice, now do Acetminophen vs Dexibuprofen.
Honestly this article is mixing a lot of different factors
> Acetaminophen has a scarily narrow therapeutic window. The instructions on the package say it's okay to take up to four grams per day. If you take eight grams, your liver could fail and you could die.
Gee I don't know, I think this is a wide enough window to not miss it. That difference is 8 500mg pills
> that for most people in most circumstances, acetaminophen is safer than ibuprofen, provided you use it as directed. I think most doctors agree with this.
Could be but I think a lot of doctors underestimate the dangers of paracetamol as well
All of the factors the author mentions about IBP are true. But it's all about the details. Safer? Safer in which condition?
"Dehydrated" ok take a glass of water. Active bleeding? Most NSAIDs interfere with that, and no you won't become a hemophiliac by taking one Ibuprofen
Also, some countries do add a notice for kidney problems for Paracetamol as well (e.g.) https://www.medicines.org.uk/emc/product/5164/pil
An as a conclusion, I find it "funny" that nobody considers how healty/safe it is to take paracetamol and have mild analgesia (translation - you're still in pain) and taking ibp and having better analgesia
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”.
8g is not an insignificant amount. That's 16 500mg pills. You really need to mess up to take 16 pills and not realise you're doing something wrong. If a patient is not lucid than we have bigger issues.
And from what I see in pharmacies, you would rarely see a "cough syrup" called just like that if it contains paracetamol. It would usually be marketed as a flu-relief all-around symptom relief.
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.
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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.
As pointed out in the article, naproxen is an NSAID like Ibuprofen, though slightly more COX1 selective. It likely has a somewhat lower risk of serious renal and cardiovascular events, but higher risk of GI bleeds. There are some studies that show little to no increase cardiovascular risk, but most do show some or even comparable to ibuprofen.
Convenience vs ibuprofen is a thing given the longer half life, but it still generally comes with similar risks. If you are taking anything for more than just an occasional headache, definitely discuss with a doctor, COX2 selectives like celecoxib may be a better risk profile and even more convenient.
(COX1 and COX2 selectivity loosely separate which systems get the brunt of the side effects)
The higher risk of GI bleeds is could be somewhat balanced by not having to take as many.
There are also slow release forms of naproxen. (Which make sense given its long action: lets people fade in the next one while the previous dose slowly fades out). That could also help make it easier on the GI tract.
> The higher risk of GI bleeds is somewhat balanced by not having to take as many!
Unless I am missing something, the data really doesn't back that up. naproxen is much more longer lasting and has a higher chance of causing ulcers. Hence why its not over the counter in the UK and is prescribed with omeprazole to reduce the risk of issues.
I'm reading about this in more detail. Indeed, it's not the contact between the medication and the digestive tract that is the problem, but simply its presence in the blood stream. By inhibiting those certain enzymes, it reduces the production of prostaglandings, causes problems for the lining.
Naproxen will be around longer due to its long half-life, so it creates more opportunity for this problem.
I weirdly always found Naproxen much more effective than ibuprofen but also find Celebrex great which seems to further confuse the whole COX 1 vs 2 situation