3 ms·

> the "daily" recommended doses are for a single day. No. We've got thousands of people living more or less permanently on the maximum daily dose, including so

by rscho 5y ago

> the "daily" recommended doses are for a single day. 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.

paulmd 5y ago
The intervention-based study (giving patients a controlled dose and measuring the enzyme response) found that over half of study participants will have clinically-significant elevation of ALT at the recommended dose, and 20-30% will have numbers as bad as 5x sustained. Short study aside, that's not what I would personally choose. 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.
- rscho 5y ago
  I personally prescribe loads of painkillers, including the whole range of the WHO ladder, and many of those patients have liver tests. It rarely happens that we have to discontinue Tylenol due to hepatitis. I see people on NSAIDs with kidney failure every week. So again yes, Tylenol is toxic. But from personal experience, it's rarely a clinically relevant problem.
  - Rury 5y ago
    Frankly, I'm not sure why NSAIDs are considered the safer option. There was a period of time when I was young, where I had tried various painkillers for treatment of headaches. Every time I had tried an NSAID, my chest felt like it was going to explode, and it became difficult to breathe. Later learned that they may increase the risk of heart attacks and strokes (of which I have a family history). For these reasons, I've sworn to never take them, and only take acetaminophen on rare occasions when pain is bad enough.

by rscho 5y ago

paulmd 5y ago

The intervention-based study (giving patients a controlled dose and measuring the enzyme response) found that over half of study participants will have clinically-significant elevation of ALT at the recommended dose, and 20-30% will have numbers as bad as 5x sustained. Short study aside, that's not what I would personally choose. 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.

rscho 5y ago
I personally prescribe loads of painkillers, including the whole range of the WHO ladder, and many of those patients have liver tests. It rarely happens that we have to discontinue Tylenol due to hepatitis. I see people on NSAIDs with kidney failure every week. So again yes, Tylenol is toxic. But from personal experience, it's rarely a clinically relevant problem.
- Rury 5y ago
  Frankly, I'm not sure why NSAIDs are considered the safer option. There was a period of time when I was young, where I had tried various painkillers for treatment of headaches. Every time I had tried an NSAID, my chest felt like it was going to explode, and it became difficult to breathe. Later learned that they may increase the risk of heart attacks and strokes (of which I have a family history). For these reasons, I've sworn to never take them, and only take acetaminophen on rare occasions when pain is bad enough.