The one-size-fits-all drug dosing we do in this country seems crazy to me.
"Research Chemical" drug users have developed techniques to calibrate doses of substances with unknown potency - start with ~100th of what you expect to be an active dose and then gradually double it until proper effects are achieved.
I'd imagine it would be more expensive for pharmacies to distribute drugs in this way, but allowing patients to titrate their doses could significantly reduce/avoid negative side effects from just throwing the same standardized dose at every person with a prescription regardless of bodyweight.
Would be super cool if we had an objective measure of proper dosage - such as blood concentration or excreted metabolites - to give us more insight into how the drug is being metabolized by the individual.
Edit: just to be clear, there are times when it might make sense to take oxycodone or hydrocodone alongside acetaminophen, but they should be prescribed separately and with caution. The reason they're combination drugs is because the toxicity is a "desirable" side-effect meant to discourage abuse. It's that reasoning that is evil.
Having chronic pain sucks, having something that you can take for it, especially something boring like Tylenol that can't be snatched away from you by doctors/police/etc, is a huge quality of life issue.
Also, we need to really research the NSAIDS after surgery thing, afaik, there has been nothing super rigorous on it and is only going off of the common knowledge that they do thin blood. I do not like Tylenol and my partner is allergic, we’ve both broken the rule about nsaids post surgery.
the "daily" recommended doses are for a single day. If you are taking it daily you need to at least halve the recommended dose. I wouldn't have said a week was a problem but... yeah. Tylenol is dangerous.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913076/
Specifically this study referenced: https://jamanetwork.com/journals/jama/fullarticle/211014
> One study reported that ingestion of the recommended maximum amount of 4000 mg of APAP for 2 weeks resulted in the asymptomatic elevation of alanine transaminase, up to three times normal, in 40% of patients.19 These transaminase elevations did not amount to any clinical significance, and after the APAP was discontinued the transaminase levels returned to normal.19 Yet, while asymptomatic, chronically elevated aminotransferases may be of concern to healthcare providers, leading to further costly diagnostic studies or changes/restrictions in necessary medications
If anything the summary in that review is underselling it. Average was 2.78x baseline (3x is considered clinically significant) and 20% of the population was over 5x the peak (so, 20% had clinically significant elevations from the study). By peak levels, around 27% of the population saw peak levels of 8x baseline. So basically, even the "average" participant was almost to the threshold of clinical significance just from this study (at the recommended daily dose) and a cohort of around 20-25% will see clinically-significant warning signs at the recommended dosage, even among healthy patients. And risk factors significantly increase that.
That's basically a "liver stressor" enzyme, even if it's not killing the patients over the course of the study, it's not a good thing. That's your body's warning signal that it's stressed. And generally that's an uncontroversial finding I think, everyone agrees tylenol is a liver stressor, but they just have various thresholds of the acceptable risk. Would I do it daily? No.
And in med-speak, that's what they're saying here too. Use with caution, don't go above the recommended dosage in acute situations and use caution with chronic dosing. https://pubmed.ncbi.nlm.nih.gov/11847957/
Anyway, the rule of thumb I always heard is that half of the "daily" dose appears to be more appropriate for chronic daily usage. I am not a doctor and you can do whatever you want, but that is personally what I would hold to. Going less, or picking a different FDA-approved alternative like ibuprofen or aspirin, is always a perfectly acceptable choice.
That number appears to be reasonably supportable too. Instead of "half of our patients were over triple their baseline ALT level" this study found that 50% of the daily doage, chronically over 12 weeks, gets you to a 20% average increase in ALT levels. It's never not going to be a liver stressor and if you have other risk factors then you should probably stay away entirely (I think that's just good advice in general) but 20% increase in ALT after 12 weeks is a hell of a lot better than tripling your ALT in 2 weeks. But even then, during a 12-week study of 94 healthy adult patients, at half the recommended dose, they still had to withdraw one participant due to hepatotoxicity. https://pubmed.ncbi.nlm.nih.gov/25899926/
(as far as risk factors, see the first link above for a good review, aggravating factors for hepatoxicity can include things like non-alcoholic fatty liver or nutritional deficiency. Which basically describes an overweight computer-toucher with a poor diet to a tee.)
No. We've got thousands of people living more or less permanently on the maximum daily dose, including some children and vulnerable populations. Yes, some of those people have elevated liver enzymes. Yes, Tylenol is dangerous, but certainly not more than the alternatives. NSAIDs are certainly not any less dangerous, especially in populations with high prevalence of diabetes and kidney failure.
Tylenol overdose is one of the most frequent suicide plans in teens, with lethal doses usually starting from 8g. This is one of the reasons Tylenol has such a bad reputation.
Remember, there were never Phase trials showing 4g is the right maximum either. It’s just grandfathered in Uber the “well I guess if it were dangerous we’d have noticed by now” standard. But did a statistically large enough segment take exactly 4g over a course of years such that we can definitively say that’s safe? Most people are taking lower doses and shorter doses. At least on paper.
It's "there's no double-blind study that shows masks can prevent the spread of covid!" redux. And actually it's worse because there already is a standard for what clinically-significant elevated levels of that enzyme are, and healthy study participants are blasting right by it. That's not relevant .... because?
It's not just a random number going up from some un-related mechanism, it's liver stress, they even think they know what the mechanism is. It’s a reaction that is well-known for this drug, as a warning sign for this problem. Claiming that it suddenly doesn’t mean the same thing it’d mean if you took 0.001mg more is just pedantic. It was never formally studied and approved, it would be completely unsurprising if they got the number a little wrong.
And again - that's study participants who are chosen to be healthy. If you're fat, or aren't getting your macronutrients, your risk is much higher.
Using a lower dose or using something else is always a valid option. "The dose makes the poison" and using the lowest effective dose is absolutely standard practice and any doctor is going to tell you that's a baseline they always operate under.
Anyway, do whatever you want personally, but I would personally think strongly about staying at half the recommended dose or less for chronic usage, or looking for an alternative option. 20% of the healthy population, plus the unhealthy population, is a decent chunk of people.
Also note that those dosages are only for single usages! Tylenol also has a fun thing where daily/chronic usage within the "safe" dose can still cause liver damage. Chronic usage, you need to halve those doses.
The causal mechanism is believed to be basically low-level liver damage. Drinking a sixpack of beer once every couple weeks is fine - it's still not healthy, it damages your body, but your liver will repair itself in the meantime - but do it every day and your body cumulatively cannot repair the damage, while drinking a ton could cause acute failure. Tylenol actually works the same way - every dose is damaging your liver a bit, but if you don't do it every day it's fine, your body will repair it. But if you do take it daily, your body doesn't get a chance to repair the liver damage that tylenol causes, and the actual "safe" dosage becomes lower.
That puts the actual "safe" dose at closer to 1500mg per day for an adult. Having a 2.5:1 theraputic ratio on an over-the-counter drug is absolute fucking insanity.
And worse, those numbers are for men - they're lower for women. Yes, so is the theraputic dose, but they don't make special pills for women. Taking a standard dose (two 325mg pills) twice a day can cause liver damage to women, that's above the safe threshold for daily/chronic use. And that's not something people really consider when they pop a couple tylenol.
And then you've got combination products. OK, so you get sick, you take a couple tylenol and a dose of cough syrup. The dose of cough syrup likely is another 500mg or so of tylenol. So you actually took a 1125mg dose. And then you do it again before you go to bed. That's edging into dangerous territory with tylenol.
Obviously "don't do that", read the label and don't double up on an active ingredient that's already there in combination, but combination products are implicitly dangerous, they are fishing for that to happen, encouraging it. But the FDA wants it because it "discourages abuse". That's literally more important than burning out your liver.
The rest of the world uses tylenol in very niche situations. Usually it's behind the counter at a minimum (not always, but usually) and you probably will be told to take some ibuprofen instead. Ibuprofen and Aspirin are not perfect but they are much, much, much safer than tylenol is.
Tylenol is absolutely, completely, absurdly dangerous and should not be anywhere near as common as it is in the US, but drug war + legacy product sales rule the day.
To echo another sibling commenter here, I don't allow acetaminophen in the house period. It is an accident waiting to happen. I certainly don't allow combination products, and I will actively go out of my way to buy anything that doesn't include it. This is overkill as a single childless person who is aware of the danger, but you never know when something could go wrong and the cat knocks the bottle off the counter and the dog gets it, etc. You just should not keep dangerous things around unless you absolutely need to. Some things you can't avoid, but it's not hard to just buy ibuprofen instead of tylenol.
Instead there's dozens and dozens of GSK's Panadol paracetamol (acetaminophen), some of which even next to a cash register as a throw in.
I actually only ever hear about acetaminophen/paracetamol being dangerous from Americans - in other Anglo countries everyone will happily suggest you take it all the time, it is available OTC, and it comes as something kids will mistake for lemonade.
https://www.amazon.co.uk/Lemsip-Cold-Blackcurrant-Flavour-Sa...
> Ibuprofen and Aspirin are not perfect but they are much, much, much safer than tylenol is.
Only short term. Ibuprofen is less safe taken chronically, it'll destroy your stomach lining.
https://www.health.harvard.edu/pain/acetaminophen-safety-be-...
4,000 mgs is easy to hit for people who don't realize that it can be dangerous. I know lots of people who would say "Well, my pain is bad, let me take double"... which for extra strength would be 4 x 500 MG, which is 2000 MGs in a single dose... which then if you do it twice in a day is right there at the 4000 MG mark. Most people are fine with that, but some people can get really sick.
If the person then does it 3 times a day, they are close to the danger zone for most people and over the danger zone for some people. Then multiply that by a few days....
You can easily say, "Well, they are taking more than they are supposed to!", but it is really common to take a bit extra if you feel really bad without realizing how dangerous it is, because Tylenol is `safe`
Ulcers ("destroying your stomach lining") is less bad than "destroying your liver", and typically you will have to screw up harder before other NSAIDs reach that level. Tylenol literally is dangerous following the directions on the bottle, because those directions aren't calibrated for chronic usage, when they say "daily max" they don't mean you take it daily, that dose is even lower.
again, I don't do analgesics daily but I will be sure to adhere to the doage schedule on that. Pain medication is such an unfortunate area of medicine.
I just looked at a bottle of it here. Yes, 500mg. Adult dose: 2. That's 1,000mg. Every 6 hours to a maximum of 6 per day. That's 3,000mg/day. Danger at 7,000mg/day means a therapeutic ratio of less than three--nothing like that should be OTC and it's use should be carefully considered.
Of course that's over the counter. Prescription strength also exists.
I'm a fan of switching between two pain killers / fever reducers (and only one liver killer), overlapping the effective time window by a few hours, but keeping both at ~50% the recommended max daily dose (a doctor recommended this to me a few years ago).
Of course, that makes the dose schedule more complicated, getting back to the problem it is trying to solve.
https://medlineplus.gov/ency/article/002598.htm
Common dosage forms and strengths:
Suppository: 120 mg, 125 mg, 325 mg, 650 mg Chewable tablets: 80 mg Junior tablets: 160 mg Regular strength: 325 mg Extra strength: 500 mg Liquid: 160 mg/teaspoon (5 milliliters) Drops: 100 mg/mL, 120 mg/2.5 mL Adults should not take more than 3,000 mg of single-ingredient acetaminophen a day. You should take less if you are over 65 years old. Taking more, especially 7,000 mg or more, can lead to a severe overdose problems. If you have liver or kidney disease, you should discuss the use of this drug with your health care provider.