6 ms·

How is this "dangerously close to toxic"? Extra strength is 500mg. Adults should not take more than 3000mg in a day. Taking 7000 more more can lead to liver p

How is this "dangerously close to toxic"? Extra strength is 500mg. Adults should not take more than 3000mg in a day. Taking 7000 more more can lead to liver problems. https://medlineplus.gov/ency/article/002598.htm 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.

thedailymail 5y ago
My understanding is that acetaminophen toxicity has been a problem particularly for children, because 1) the toxic dose is lower, 2) many common OTC products for children include some amount of acetaminophen among their active ingredients and 3) parents may give their children multiple such products (one for runny nose, one for fever reduction, one for nighttime relief, etc.) over the course of a day and end up exceeding the safe dose, leading to liver toxicity. That was the situation a few years ago at least.
- freedomben 5y ago
  acetaminophen is often put in medications because it's toxic. It's there to dissuade people from *gasp* taking too much and possibly experiencing some positive feelings or enjoyment that offends the sensibilities of decision makers. Better that we destroy a few people's livers than that those people get a buzz. (to be clear, this last sentence is not my view. I'm mocking that view)
  - caymanjim 5y ago
    This is the one and only reason that Vicodin and Percocet exist. They don't want people getting high, so they're punishing them by trying to kill them. It's barbaric. Literally evil. 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.
  - skyechurch 5y ago
    This also is silly, illegal drug users constantly take their dosages mixed with much worse things than Tylenol with no noticeable dissuasion effect that I am aware of. Acetaminophen is mixed with oxycodone etc bc it increases the pain relieving effect of the opiate drug (which for many people (e.g. me), are of limited effectiveness relative to the side effects/"buzz"), and because, unlike NSAIDs, it doesn't thin your blood so it can be taken after surgeries. 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.
    - samtho 5y ago
      I don’t think anyone reasonable is actively arguing to delist Tylenol as OTC, rather we shouldn’t be so restrictive on these medications that can actually really help people. In addition we should be giving people resources for discontinuing use when they no longer need it. 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.
      - freedomben 5y ago
        Yes absolutely. I don't want to see Tylenol go away. I want more options, not less. I think as long as companies are being honest about the product they are selling, even if it's ineffective I think it should be available.
paulmd 5y ago
5:1 ratio (a dose is "take two 325mg") between therapeutic and danger doses is really low as far as modern drugs would be concerned. Most drugs are more in the 50:1 or 100:1 range, drugs with a 5:1 ratio typically would not be approved and certainly would require very close supervision. Tylenol being OTC is complete insanity (or rather, regulatory capture and general public comfort with it). 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.
cwkoss 5y ago
Note that metabolism of drugs is roughly proportional to bodyweight. A petite 100 lb person may only need 200mg for an effective dose. An obese 400 lb person may require ~4x that dosage for the equivalent effect. 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.
- ratsmack 5y ago
  This is especially important when it comes to children. This is because kids vary in weight in relation to age more than adults do, but the vast majority of drugs are dosed by age. This is just insanity at it's finest.
  - cwkoss 5y ago
    Yep, and that's only using the rough metric of bodyweight. There are a number of other major factors like size and health of liver, whether the patient has any under/over expression of metabolic enzymes, etc that can further complicate the determination of proper dosage. 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.
  - simulate-me 5y ago
    Is there any evidence that harm is being caused from age-based dosing?
cowmoo728 5y ago
Most people don't read the label on medicines that they take. Take two extra strength acetaminophen tablets, combination liquid cold medicine, some of the sleep aids with diphenhydramine + acetaminophen, a glass of wine, repeat for 3 days, and you're easily into danger territory.
emerged 5y ago
Well I was in the ER 2 days ago and my liver enzymes were bad. I don’t drink, he said it was the acetaminophen I’ve been taking. I had been taking significantly less than the recommended amount for less than a week.
- paulmd 5y ago
  (to be clear: not a doctor) 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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913076/ Specifically this study referenced: https://jamanetwork.com/journals/jama/fullarticle/211014 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/ 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/ 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.)
LorenPechtel 5y ago
Check your labels more carefully! 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.
- hedora 5y ago
  Ah, but two every 6 hours is 4000 mg/day, and my bottle claims that's safe. When I'm anywhere near that dose, I have a > 102F fever, which means I'm in peak form to compute dosages and timings. 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.

thedailymail 5y ago

My understanding is that acetaminophen toxicity has been a problem particularly for children, because 1) the toxic dose is lower, 2) many common OTC products for children include some amount of acetaminophen among their active ingredients and 3) parents may give their children multiple such products (one for runny nose, one for fever reduction, one for nighttime relief, etc.) over the course of a day and end up exceeding the safe dose, leading to liver toxicity. That was the situation a few years ago at least.

freedomben 5y ago
acetaminophen is often put in medications because it's toxic. It's there to dissuade people from *gasp* taking too much and possibly experiencing some positive feelings or enjoyment that offends the sensibilities of decision makers. Better that we destroy a few people's livers than that those people get a buzz. (to be clear, this last sentence is not my view. I'm mocking that view)
- caymanjim 5y ago
  This is the one and only reason that Vicodin and Percocet exist. They don't want people getting high, so they're punishing them by trying to kill them. It's barbaric. Literally evil. 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.
- skyechurch 5y ago
  This also is silly, illegal drug users constantly take their dosages mixed with much worse things than Tylenol with no noticeable dissuasion effect that I am aware of. Acetaminophen is mixed with oxycodone etc bc it increases the pain relieving effect of the opiate drug (which for many people (e.g. me), are of limited effectiveness relative to the side effects/"buzz"), and because, unlike NSAIDs, it doesn't thin your blood so it can be taken after surgeries. 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.
  - samtho 5y ago
    I don’t think anyone reasonable is actively arguing to delist Tylenol as OTC, rather we shouldn’t be so restrictive on these medications that can actually really help people. In addition we should be giving people resources for discontinuing use when they no longer need it. 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.
    - freedomben 5y ago
      Yes absolutely. I don't want to see Tylenol go away. I want more options, not less. I think as long as companies are being honest about the product they are selling, even if it's ineffective I think it should be available.

paulmd 5y ago

5:1 ratio (a dose is "take two 325mg") between therapeutic and danger doses is really low as far as modern drugs would be concerned. Most drugs are more in the 50:1 or 100:1 range, drugs with a 5:1 ratio typically would not be approved and certainly would require very close supervision. Tylenol being OTC is complete insanity (or rather, regulatory capture and general public comfort with it). 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.

cwkoss 5y ago

Note that metabolism of drugs is roughly proportional to bodyweight. A petite 100 lb person may only need 200mg for an effective dose. An obese 400 lb person may require ~4x that dosage for the equivalent effect. 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.

ratsmack 5y ago
This is especially important when it comes to children. This is because kids vary in weight in relation to age more than adults do, but the vast majority of drugs are dosed by age. This is just insanity at it's finest.
- cwkoss 5y ago
  Yep, and that's only using the rough metric of bodyweight. There are a number of other major factors like size and health of liver, whether the patient has any under/over expression of metabolic enzymes, etc that can further complicate the determination of proper dosage. 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.
- simulate-me 5y ago
  Is there any evidence that harm is being caused from age-based dosing?

cowmoo728 5y ago

Most people don't read the label on medicines that they take. Take two extra strength acetaminophen tablets, combination liquid cold medicine, some of the sleep aids with diphenhydramine + acetaminophen, a glass of wine, repeat for 3 days, and you're easily into danger territory.

emerged 5y ago

Well I was in the ER 2 days ago and my liver enzymes were bad. I don’t drink, he said it was the acetaminophen I’ve been taking. I had been taking significantly less than the recommended amount for less than a week.

paulmd 5y ago
(to be clear: not a doctor) 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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913076/ Specifically this study referenced: https://jamanetwork.com/journals/jama/fullarticle/211014 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/ 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/ 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.)

LorenPechtel 5y ago

Check your labels more carefully! 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.

hedora 5y ago
Ah, but two every 6 hours is 4000 mg/day, and my bottle claims that's safe. When I'm anywhere near that dose, I have a > 102F fever, which means I'm in peak form to compute dosages and timings. 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.