21 ms·

> OTC medicines that by current standards would not be made OTC Acetaminophen would almost certainly be in this category, if it could even get FDA approval at

> OTC medicines that by current standards would not be made OTC Acetaminophen would almost certainly be in this category, if it could even get FDA approval at all. The effective dose is dangerously close to a toxic dose that causes liver damage, and not comfortably-far from the LD50. The only reasons acetaminophen is OTC is that it's been informally grandfathered in, makes an absolute fortune for pharmaceutical companies, and doesn't get you high.

genghisjahn 5y ago
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.
- 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.
paulmd 5y ago
> doesn't get you high. this is the big one. Phenyl-epinephrine doesn't work at all, it's consistently failed to outperform placebo, and the only reason it's on the market is because the FDA doesn't like pseudo-ephedrine (sudafed) because it can be used as a precursor for meth. Same reason they've required individual blister packs for sudafed (if only there was some illicit drug which gave you the focus and drive to perform repetitive tasks for hours on end...) Same thing for imodium. The reason all of a sudden it's in blister packs? People found a way to abuse it and the FDA is going to ruin it for the rest of us. In the case of acetaminophen, the FDA actively uses it as a poison to "discourage" addicts from taking large doses of painkillers or cough syrup. The point is explicitly that if you take too much, you'll burn out your liver, the FDA is actively inserting poison into the medicine to "discourage abuse". In all of these cases, the common factor is that it makes things much more annoying or even dangerous/lethal for average people, while addicts are completely unaffected. No opiate addict in the world is going to get clean because of individual pill blister packaging. Meth addicts will just pop some pills and churn through the sudafed blister packaging, etc. I am waiting for the other shoe to drop on imodium, now that the FDA is targeting it, it can't be too long until it's behind the counter or pulled entirely. And as someone who (TMI warning) suffers from what I'd term as moderately frequent IBS (never diagnosed but maybe I should) that's really going to suck for me. The FDA is simply an instrument of drug-war policy, they're not oriented towards patient care and outcomes at all.
- edmundsauto 5y ago
  What makes you say the FDA is actively adding poison to other drugs, are there first hand sources from them? This sounds like it could also be a case where they want to lower opiate consumption, and so adding some Tylenol increases pain relief without increasing opiate intake. I am not sure that’s wise policy, but if you don’t think Tylenol is all that bad (again, I’m not sufficiently informed to say this, but the FDA obviously thinks it’s safe), then it’s not a bad overall policy. It sounds like it could be either situation, I’m just looking for more evidence before making up my mind. (Yes, I am aware the US government poisoned people during prohibition in this exact manner, but I dispute that has any relevance as the decision makers and cultural awareness is very different now. We’ve come a long way since the 30s)
sniperjoe360 5y ago
Although perhaps true about FDA clearance, I wouldn't be alarmist and characterize the effective dose as "dangerously" close to the LD50. The highest dose that therapeutically is used is about 1000mg per dose. The fatal dose is about 15 times that amount. To put it into perspective, a patient would have to be willfully taking 45 tylenol (325mg/pill) all at once to cause lethal liver damage. Doses like that are usually not accidental.
- klodolph 5y ago
  Not accidental, but very tragic. It's the #1 cause for calls to poison control, and accounts for 26,000 hospitalizations every year, and 500 deaths. Dying from an acetaminophen overdose is not a good way to go out, you spend a couple days in the hospital suffering as your organs fail and your loved ones watch. Other OTC drugs are much safer. I don't allow acetaminophen in the house. Pseoudoephedrine? Yes. Acetaminophen also should not be taken as a hangover cure, due to interactions with alcohol (alcohol and acetaminophen compete for the same metabolic pathways in the liver, and this exacerbates the toxic effects of acetaminophen). The problem is that someone who's drinking and has a hangover is probably going to reach for one of the two most common OTC pain relievers in their medicine cabinet, and not consider that one of those two pain relievers should not be combined with alcohol.
  - sniperjoe360 5y ago
    Yes, agree with everything factual you said. I guess the problem isn't the compound itself but rather not enough information regarding its use. I personally keep tylenol in the house because it's probably the best non-narcotic non-NSAID pain medicine. We use it all the time in patients who are elderly with decreased renal function because they don't do well with opiates or NSAIDs (ibuprofen)
  - refurb 5y ago
    500 deaths (many intentional attempts at suicide) in a country of 350M where arguably every household has acetaminophen present is incredibly low.
skyechurch 5y ago
This is very silly, acetaminophen is very effective against pain, and for many people (e.g. me) is tolerated much better, especially at higher doses, than ibuprofen etc. There is already way to much panic about drugs/medicines, especially pain meds, especially especially for chronic conditions, without further hysterics about the 'threat' of useful and well tolerated chemicals. (Not a doctor, not offering medical advice.) >doesn't get you high A huge point in its favor if you can't lay in bed opiated all day.
- caymanjim 5y ago
  I'm not saying it'd be good if acetaminophen got you high, just that one of the reasons it's still OTC is that it doesn't get you high, so there's no one champing at the bit to crack down on it, the way they robbed us of the highly-effective and fairly-harmless pseudoephedrine for the one and only reason that it can be illicitly turned into a street drug.
  - skyechurch 5y ago
    That's reasonable. My concern is that during my lifetime I have had my access to useful medicines with zero abuse potential restricted because of (imo) panics that it could be turned into street drugs (pseudoephedrine), and also because of panics (imo) that it is too hard on my body (Torodol), and of course because of panics (imo) that they will turn me into a drug addict (opiates). The last class is admittedly worth being cautious about, especially with the more potent forms, but all of these drugs have legitimate medicinal uses and people suffer when they are taken away. (Also, for drugs that you have to take to get through the day, the lack of a buzz is a definite benefit, and not just because it closes off one argument for restricting them.)
- tssva 5y ago
  I find acetaminophen almost completely useless for pain. Ibuprofen is better but still not very effective. Naproxen sodium is the only OTC pain medicine which is effective for me.
  - 5y ago
refurb 5y ago
I doubt it. Ibuprofen and other NSAISDs were approved not that long ago, cause plenty of GI bleeds, have nephrotoxicity when used chronically and increase the risk of cardiovascular events. And they’re OTC. Acetaminophen is actually very safe considering the number of serious events and the facts it’s in hundreds of different OTC combinations.
- grangerg 5y ago
  Any sources on that bit about chronic ibuprofen usage? I'm aware of the GI issues (stomach lining actually), and not the others. I'm a long chronic user (daily for years now), and appear to have a reliable mitigation for the GI problems, so I'd love to know more about the other stuff you mentioned.
  - refurb 5y ago
    I think Google would help with the nephrotoxicity topic, but with regards to cardiovascular risk, the FDA has been doing a ton of work on it since the early 2000's when Vioxx and Bextra were pulled off the market. The other NSAIDs like ibuprofen, naproxen were kept on the market due to a lower, but not non-existent, risk. I take NSAID for pain, but personally I'm not too concerned as it's only a ~10-50% increase in relative risk. If I was at a higher risk for stroke or heart attack, or took them very frequently (say daily for arthritis) I'd probably look for alternatives, but there are lots of others things to worry about. This is the latest FDA update I could find, there may be more information out there: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-strengthens-warning-non-aspirin-nonsteroidal-anti-inflammatory https://www.fda.gov/drugs/drug-safety-and-availability/fda-d...
consumer451 5y ago
Here are some interesting related HN posts regarding Acetaminophen: https://hn.algolia.com/?dateEnd=1648670057&dateRange=custom&dateStart=1426118400&page=0&prefix=true&query=acetaminophen&sort=byPopularity&type=story https://hn.algolia.com/?dateEnd=1648670057&dateRange=custom&...

genghisjahn 5y ago

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.
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.

paulmd 5y ago

> doesn't get you high. this is the big one. Phenyl-epinephrine doesn't work at all, it's consistently failed to outperform placebo, and the only reason it's on the market is because the FDA doesn't like pseudo-ephedrine (sudafed) because it can be used as a precursor for meth. Same reason they've required individual blister packs for sudafed (if only there was some illicit drug which gave you the focus and drive to perform repetitive tasks for hours on end...) Same thing for imodium. The reason all of a sudden it's in blister packs? People found a way to abuse it and the FDA is going to ruin it for the rest of us. In the case of acetaminophen, the FDA actively uses it as a poison to "discourage" addicts from taking large doses of painkillers or cough syrup. The point is explicitly that if you take too much, you'll burn out your liver, the FDA is actively inserting poison into the medicine to "discourage abuse". In all of these cases, the common factor is that it makes things much more annoying or even dangerous/lethal for average people, while addicts are completely unaffected. No opiate addict in the world is going to get clean because of individual pill blister packaging. Meth addicts will just pop some pills and churn through the sudafed blister packaging, etc. I am waiting for the other shoe to drop on imodium, now that the FDA is targeting it, it can't be too long until it's behind the counter or pulled entirely. And as someone who (TMI warning) suffers from what I'd term as moderately frequent IBS (never diagnosed but maybe I should) that's really going to suck for me. The FDA is simply an instrument of drug-war policy, they're not oriented towards patient care and outcomes at all.

edmundsauto 5y ago
What makes you say the FDA is actively adding poison to other drugs, are there first hand sources from them? This sounds like it could also be a case where they want to lower opiate consumption, and so adding some Tylenol increases pain relief without increasing opiate intake. I am not sure that’s wise policy, but if you don’t think Tylenol is all that bad (again, I’m not sufficiently informed to say this, but the FDA obviously thinks it’s safe), then it’s not a bad overall policy. It sounds like it could be either situation, I’m just looking for more evidence before making up my mind. (Yes, I am aware the US government poisoned people during prohibition in this exact manner, but I dispute that has any relevance as the decision makers and cultural awareness is very different now. We’ve come a long way since the 30s)

sniperjoe360 5y ago

Although perhaps true about FDA clearance, I wouldn't be alarmist and characterize the effective dose as "dangerously" close to the LD50. The highest dose that therapeutically is used is about 1000mg per dose. The fatal dose is about 15 times that amount. To put it into perspective, a patient would have to be willfully taking 45 tylenol (325mg/pill) all at once to cause lethal liver damage. Doses like that are usually not accidental.

klodolph 5y ago
Not accidental, but very tragic. It's the #1 cause for calls to poison control, and accounts for 26,000 hospitalizations every year, and 500 deaths. Dying from an acetaminophen overdose is not a good way to go out, you spend a couple days in the hospital suffering as your organs fail and your loved ones watch. Other OTC drugs are much safer. I don't allow acetaminophen in the house. Pseoudoephedrine? Yes. Acetaminophen also should not be taken as a hangover cure, due to interactions with alcohol (alcohol and acetaminophen compete for the same metabolic pathways in the liver, and this exacerbates the toxic effects of acetaminophen). The problem is that someone who's drinking and has a hangover is probably going to reach for one of the two most common OTC pain relievers in their medicine cabinet, and not consider that one of those two pain relievers should not be combined with alcohol.
- sniperjoe360 5y ago
  Yes, agree with everything factual you said. I guess the problem isn't the compound itself but rather not enough information regarding its use. I personally keep tylenol in the house because it's probably the best non-narcotic non-NSAID pain medicine. We use it all the time in patients who are elderly with decreased renal function because they don't do well with opiates or NSAIDs (ibuprofen)
- refurb 5y ago
  500 deaths (many intentional attempts at suicide) in a country of 350M where arguably every household has acetaminophen present is incredibly low.

skyechurch 5y ago

This is very silly, acetaminophen is very effective against pain, and for many people (e.g. me) is tolerated much better, especially at higher doses, than ibuprofen etc. There is already way to much panic about drugs/medicines, especially pain meds, especially especially for chronic conditions, without further hysterics about the 'threat' of useful and well tolerated chemicals. (Not a doctor, not offering medical advice.) >doesn't get you high A huge point in its favor if you can't lay in bed opiated all day.

caymanjim 5y ago
I'm not saying it'd be good if acetaminophen got you high, just that one of the reasons it's still OTC is that it doesn't get you high, so there's no one champing at the bit to crack down on it, the way they robbed us of the highly-effective and fairly-harmless pseudoephedrine for the one and only reason that it can be illicitly turned into a street drug.
- skyechurch 5y ago
  That's reasonable. My concern is that during my lifetime I have had my access to useful medicines with zero abuse potential restricted because of (imo) panics that it could be turned into street drugs (pseudoephedrine), and also because of panics (imo) that it is too hard on my body (Torodol), and of course because of panics (imo) that they will turn me into a drug addict (opiates). The last class is admittedly worth being cautious about, especially with the more potent forms, but all of these drugs have legitimate medicinal uses and people suffer when they are taken away. (Also, for drugs that you have to take to get through the day, the lack of a buzz is a definite benefit, and not just because it closes off one argument for restricting them.)
tssva 5y ago
I find acetaminophen almost completely useless for pain. Ibuprofen is better but still not very effective. Naproxen sodium is the only OTC pain medicine which is effective for me.
- 5y ago

refurb 5y ago

I doubt it. Ibuprofen and other NSAISDs were approved not that long ago, cause plenty of GI bleeds, have nephrotoxicity when used chronically and increase the risk of cardiovascular events. And they’re OTC. Acetaminophen is actually very safe considering the number of serious events and the facts it’s in hundreds of different OTC combinations.

grangerg 5y ago
Any sources on that bit about chronic ibuprofen usage? I'm aware of the GI issues (stomach lining actually), and not the others. I'm a long chronic user (daily for years now), and appear to have a reliable mitigation for the GI problems, so I'd love to know more about the other stuff you mentioned.
- refurb 5y ago
  I think Google would help with the nephrotoxicity topic, but with regards to cardiovascular risk, the FDA has been doing a ton of work on it since the early 2000's when Vioxx and Bextra were pulled off the market. The other NSAIDs like ibuprofen, naproxen were kept on the market due to a lower, but not non-existent, risk. I take NSAID for pain, but personally I'm not too concerned as it's only a ~10-50% increase in relative risk. If I was at a higher risk for stroke or heart attack, or took them very frequently (say daily for arthritis) I'd probably look for alternatives, but there are lots of others things to worry about. This is the latest FDA update I could find, there may be more information out there: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-strengthens-warning-non-aspirin-nonsteroidal-anti-inflammatory https://www.fda.gov/drugs/drug-safety-and-availability/fda-d...

consumer451 5y ago

Here are some interesting related HN posts regarding Acetaminophen: https://hn.algolia.com/?dateEnd=1648670057&dateRange=custom&dateStart=1426118400&page=0&prefix=true&query=acetaminophen&sort=byPopularity&type=story https://hn.algolia.com/?dateEnd=1648670057&dateRange=custom&...