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 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.

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.

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 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.

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.

Also, possible blood clotting or stomach issues sound scary, but Aspirin has similar (opposite) issues. Pharmacists regularly push its combinations with Acetominophen (which has, of course, synergetic bonuses, but is not the reason) under multitude of brands with a hefty premium when people ask for either one. So in many situations you need to consider the added risks from Aspirin too.

Ideally, I'd like to have an optimized strategies of using all three of the aforementioned substances for common situations. Like, is rotating ibuprofen/acetominophen during the day safer than consuming just one?

I've never once thought about taking more than the recommended dosage of acetaminophen, largely because I had no expectation that it would provide additional benefit..

In reality, I try to consume 1/2 doses of anything or nothing at all, unless it's a serious medical treatment being administered by a professional.

I'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.

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'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).

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.

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

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.

Acetaminophen = Paracetamol

Have gotten into a habit of keeping a note of which med when on the fridge.

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...

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.

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.

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.

[1] https://pubmed.ncbi.nlm.nih.gov/40819833/

[2] https://ddeacademy.dk/ddea/what-new-research-reveals-about-p...

That being said I weirdly find Naproxen the most effective of all of these. Everyone is different though

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.

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.

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/

This is semi recent research on how it might be blocking pain

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/

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.

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.

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?

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

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.

> 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

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.