I too come from a country where this is called paracetamol, and here too, over the counter usage is very common. I'm surprised more people are not worried about the alcohol interaction.
The safe dose I believe is around 4g in 24hrs (2g/24hrs if you have known liver dysfunction). That’s like 8 extra strength Tylenol.
Another commenter alluded to why it is the number 1 cause of acute liver failure in the US: that’s because we can buy bottles of a couple hundred pills and thus the majority arise from suicide attempts.
The British used to have a big problem with paracetamol (what Tylenol/acetaminophen is called there) and acute liver failure, so they mandated only blister packs for the medication, no ability to buy large bottles. Suicide rates due to paracetamol and acute liver failure decreased as a result. In fact, aspirin is also an issue in the UK, and this mandate also helped with that.
The judgement from my pharmacology instructor was that paracetamol, when used within the recommended doses and durations, is a very safe drug with very little side effects.
Whereas acetylsalicylic acid ("Aspirin") was the example of heirloom drugs still in prescription free use only for historical reasons. 'If you came requesting approval for ASA today they'd laugh in your face. "With that side effect profile!"'
The other big issue with Tylenol is that the active dose is very close to its lethal dose -- far closer than other common over-the-counter drugs. People assume that since it's available without approval it must be pretty safe, so people take more than recommended.
The maximum safe dose for Tylenol is 4g per day. The low end of the toxicity range is a daily dose of 7.5g-10g for an adult, ~2.5X the maximum recommended dose - or just 12 grams spread over 2 days. The effects are exacerbated by alcohol use. And worst of all, people take it for hangovers. [1]
So, the toxic dose of Tylenol is only 2.5X the active dose, whereas for ASA it's 8X, for ibuprofen it's roughly 10X, and naproxen is about the same. Tylenol is much more dangerous than Aspirin.
Tylenol leads to 50,000 ER visits per year and 25,000 hospitalizations. It would lead to way more deaths if left untreated.
> So, the toxic dose of Tylenol is only 2.5X the active dose
The effective dose starts at 500mg. Most people are likely going to be taking 1 or 2x 500mg tablets for acute issues - and I'd argue that's often enough for most cases where you want short-term analgesia. Both 500mg and 1000mg will improve SPRID6 scores (dental; https://www.cadth.ca/sites/default/files/pdf/htis/june-2016/...).
Where I've complained of medium term pain (expected duration: weeks to months) my GP has suggested NSAIDs instead. They're not without their own problems but I think I'd personally prefer their safety profile to long-term Paracetamol.
All Tylenol figures are in daily totals, and Tylenol lasts 4 hours. 500-1000mg taken 4x daily is 2-4g. That makes the therapeutic index 1.875-2.5 as I mentioned. 12g over 2 days is 1.5X. Again that’s without alcohol which folks do not seem to appreciate.
People can and do exceed these numbers hence the 50,000 ER visits per year. It is the leading cause of acute liver failure in the United States.
The bar shouldn’t be “often enough for most cases” when 1.5X the dose for 2 days can kill you. Either the safety margin is too low or the warnings aren’t nearly big enough, but the numbers don’t lie, the status quo is bad. Especially when the alternatives require way less diligence on your part and are sold as equivalent adjacent products.
The issue with it is that people unknowingly take does. You may pop a Tylenol for a fever, then take it again in your NyQuil and not realize it.
It’s a well tested and safe drug. Both aspirin and ibuprofen have significant risks if used daily. Aspirin causes stomach bleeding, and ibuprofen causes significant kidney issues over time.
For this reason I try my hardest to buy single-active-ingredient versions of everything. I can keep a list of what pill combos combine into nyquil/mucinex/whatever, and can avoid doubling up on anything unintentionally.
They way OTC medications are packaged and marketed drives me bonkers. I take a sleeping pill every once in a while. I was at the store once comparing two boxes of pills. One was marked "Sleep Aid", and was $8 or so. The allergy medication nearby was the same count, same dosage, and only $5.
They were both diphenhydramine HCL, 25mg. Both tablets. The only differences were the labels, the pill colors (blue for ZZZZ, pink for allergy), and the price.
And the other benefit to stocking single-drug medications is more flexibility. I imagine some hapless guy whose has pain in the morning, but sees only "Advil PM" in the medicine cabinet.
If I need Advil PM, I'll take a regular ibuprofen and a regular diphenhydramine.
Was in Er for an optical migraine, they gave me a dose Of diphenhydramine.
It took everything I had to not start literally climbing up the walls. My anxiety and energy level skyrocketed.
One of kids is the same way on Benadryl.
Apparently 5% have such a reaction.
I got tired of explaining the reaction to doctors and nurses, (got called a liar several times). Although I had one nurse almost in tears as she had same reaction, but no one would believe her.
So on forms I put I’m allergic to allergy medication.
Keep in mind that taking higher doses of DPH has the opposite effects, i.e. you will definitely NOT sleep from it. See "anticholinergic toxicity". When I was younger I thought taking more of it is going to help me sleep better, but I ended up with auditory hallucinations, tachycardia, and the like. I was hospitalized for it, albeit left untreated, or rather, treated as a junkie and they threw me into a detox room, but that is a different issue.
I could not edit my comment, so here it is: I forgot to include a relevant symptom I had, which is delirium. I was in a delirious state for many hours, and it left me in a disassociated state for some time afterwards.
Just to add, most nootropics are cholinergics in some way or another. Take a look at choline supplements, or racetams (from Wikipedia: "Racetams are understood to work by activating glutamate receptors that are colocalized with cholinergic receptors, thus increasing the frequency of activation of the latter."). They are supposed to help people with Alzheimer's disease, improve their memory and whatnot. There are many studies around to support this. There is also Huperzine A that has been investigated as a possible treatment for Alzheimer's disease and there was a meta-analysis that found it efficacious in improving cognitive function (see https://en.wikipedia.org/wiki/Huperzine_A for more).
But yeah, anticholinergics are known to be bad for people with Alzheimer's disease, and some cholinergics are known to be effective in improving cognition of those who have it. Of course there are other medications that are supposed to be avoided, here is more about it for the curious (it mentions DPH, too): https://www.mind.uci.edu/medications-and-patients-with-alzhe...
It drove me crazy that in Japan OTC painkillers had a minimum of 4 active ingredients and up to 6 in one case. I could not find any that did not contain caffeine, for example.
The pharmacist explained that caffeine reduces headaches. Well that's great, but I didn't have a headache, I had muscle aches, and I was trying to sleep. He looked at me like I was crazy.
My understanding is that this is also to prevent abuse / recreational use. For example OTC cough pills containing dihydrocodeine (an opiate), but with enough caffeine and others to make recreational doses of the opiate unpleasant even for those with high caffeine tolerance. Or DXM, which is only found with enough guanfecine (IIRC) to make you feel like crap if you take too much. Kind of like how industrial ethanol is mixed with things that would make you vomit.
This is something that really irks me. The reason you always get paracetamol packaged with codeine is to prevent abuse of the codeine. They'd literally rather you destroy your liver and die than risk getting addicted to codeine.
One meta-theory I had is that the caffeine has been determined to help with headaches only because studies done on it are for people who are ill and need pain management, and ill people tend to change their coffee habits.
When I'm healthy and working, I regularly drink about three espresso shots a day. If I'm sick, that plummets to zero while I'm lying in bed and feeling miserable. Invariably, I'll get a killer headache, which the paracetamol alone doesn't fix. I know this, and either I just ignore the headache or make myself some instant coffee at home.
But a badly run scientific study would not control for this quantifiable effect: Sick people get headaches, and dosing them with caffeine reduces the headaches! Ergo... caffeine reduces headaches.
However, I very much doubt that caffeine has a headache reducing effect in sick people that aren't also having caffeine withdrawal.
Imagine a world where most office workers would regularly partake in, say, Opiates to "take the edge off" their stressful jobs. In that world, researchers would confidently conclude the OTC pain relief medication should include Naloxone!
This isn't even that outlandish a scenario. There are countries where people living at high altitude habitually chew Coca leaves to counteract altitude sickness. Should OTC pain killers in those countries include Propranolol? Is it right to force tourists wanting ordinary Paracetamol to also take drugs for acute Cocaine withdrawal just because most locals feel better if they get it?
It's absurd to mix drugs like this, if you think about it a little...
I had a chat with my chemist about why a small bit of caffeine was in the more expensive brands of acetaminophen / paracetamol. I asked if it was used as a kind of pick me up to feel more awake.
He said that the dose of caffeine was very very small and not for that, but it actually helps the paracetamol work better or faster.
>For this reason I try my hardest to buy single-active-ingredient versions of everything.
Yes, but according to the post, the single-active-ingredient version of acetaminophen might make you less cautious and more risky, and lead you to buy multiple-action drugs!
I've made this mistake - I thought I was alternating between paracetamol and ibuprofen preparations, but I'd accidentally used a paracetamol-containing version of the second product. Fortunately it was a manageable acute/one-off dose for my body weight (8g/24hrs - the A and E doctor ran a blood paracetamol level test as a precaution, but they didn't expect any issues), but it's an easy mistake to make.
There is a version of Nyquil without it. Nyquil Cough, I think. Also has HFCS instead of sucralose like some of the others (tastes less gross). Seems much harder to find, though. I've only seen it in cherry, so if you want it, probably avoid anything berry.
It's often mixed with opiates that people abuse. I'm thinking of percocet (oxycodone + paracetamol). While interaction with alcohol is best avoided, the reality is that people aren't ending up in ER's because they took two 500mg's and had half a bottle of wine with dinner.
Safety margin on aspirin is huge, you tend to notice your blood is very thin before you get any worse symptoms. Massive doses of aspirin have also been used to treat various illnesses.
Which is exactly why I take it before a long haul flight. A friend of a friend died due to a blood clot likely caused sitting
cramped in economy class 14 hours
In the UK, the NHS advice for anything mildly painful is "take paracetamol or ibuprofen" (e.g. https://www.nhs.uk/conditions/common-cold/), so they must judge the risk at typical doses as very low.
In Germany they always (n=2) act surprised when I ask for more than a single box. I don't even take it myself, my girlfriend uses one dose (usually 2x0.5g before going to sleep) maybe every tenth day or so; I myself might use it once a year. But the stuff lasts for years and I don't fancy running out or not having some with me when I (or someone near me) needs it, so we just buy it in bulk and replace when empty or after the expiry has sufficiently passed. I get a lecture from the apothecary every time. Does nobody else buy ahead, especially in the pandemic?
In the UK, paracetamol and ibuprofen are sold in supermarkets, but you're limited to buying two packs of 16 pills per visit. Of course, you can easily build up a stash over time.
That’s really interesting. I have a bottle of probably 300 acetominophen caplets from Costco, it’s my go-to hangover cure. Ibuprofen and acetaminophen are incredibly common in the US.
Yeah, US bottles seem crazy to me, for drugs where overdose is lethal. I think the theory behind the UK pack size restriction is that suicide attempts are often spontaneous, so it's life-saving not to have a lethal amount in the house. Also, accidentally popping hundreds of pills out of the blister packaging (rather than a bottle) is pretty unlikely. The restrictions seem to work, with a 40% reduction in paracetamol-related deaths: https://www.nhs.uk/news/medication/smaller-paracetamol-packs...
What’s really funny is that if you go to Amsterdam, you can get paracetamol in a quick dissolving pill that works much faster than the really hard ones you get in the states, but it’s in a bubble package and fewer doses so it’s harder to commit suicide with. But in the states you only get the hard pills, which are harder to crush and use to make illicit drugs out of, but in unlimited amounts. So.. we don’t care if you kill yourselves, as long as you don’t have any fun doing it?
> we don’t care if you kill yourselves, as long as you don’t have any fun doing it?
This is actually a good summary. As mentioned in sibling threads, most pharmaceuticals that could potentially be enjoyable are formulated stateside in combination with things that will either make you feel terrible or outright kill you at high enough doses.
Are you sure it's safe? Paracetamol has high hepatotoxic effects when taken with (or soon after consumption of) alcohol. It's probably best to ask a doctor when you have a chance.
I take a standard adult dose in the morning, 6-8 hours after I stop drinking and after plenty of water. I’m not worried about it. Also, to be fair, I usually take ibuprofen. Acetaminophen hits different though, sometimes it’s what you need.
You're missing the necessary information to make that assumption. Though the temptation to judge others is an inherent human trait of sanctimony.
I bought a massive sack of kosher salt because it was a good deal. It's a stupid amount. Doesn't mean I overdose on salt with every meal, it's going to last me a long, long time. Might become a family heirloom.
To add, people respond to alcohol differently due to genetics, metabolism, etc. I can wake up the next day with a ponding headache even after a seemingly small amount of drinks to some people, especially if I’m poorly hydrated in general,
A couple glasses of water before bed works at least as well as a pill the next morning, in my experience. Hangovers are one of the main ways I feel myself getting old! Haha
Bit confused by your comment—Costco is a big box store. I paid maybe $10 for the bottle. I’m not taking it daily, nor do I take more than a standard amount. I was just commenting that it’s sold in much larger quantities here, not that I’m abusing acetaminophen or alcohol.
I don't really, and I am polite and do thank them for the info they give / the concern they express. It just surprises me a little that they don't consider this normal.
