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Is Tylenol Safe?

Tylenol (acetaminophen, also known as paracetamol outside the US) has been in the news recently. Most of the stories I’ve seen have been accurate, but I’ve run across a couple of people who misunderstood what they read. I thought I’d try to put the record straight.

An FDA advisory panel has recommended reducing the maximum allowed single dose from 1000 mg to 650 mg in over-the-counter acetaminophen products. The 1000 mg dose would be available by prescription only. They also recommended eliminating painkillers like Percocet and Vicodin that contain a combination of a narcotic and acetaminophen. They did not recommend removing acetaminophen from over-the-counter cold remedies, cough medicines and similar products that combine acetaminophen with other drugs. Advisory panel recommendations are not binding, but the FDA usually follows them.

Some people got the impression that the FDA had just discovered that acetaminophen can be dangerous. No, we always knew that. The danger is when you take too much: it can damage the liver. The “new” information is just that acetaminophen overdose is now the leading cause of liver damage, causing an estimated 1600 cases of liver failure each year.

When used appropriately in recommended doses, acetaminophen is one of the safest drugs we have. It rarely causes any side effects. It is the drug of choice during pregnancy. We even use it for pain and fever in babies. The alternatives are more dangerous: aspirin can lead to Reye’s syndrome; nonsteroidal anti-inflammatory drugs (NSAIDS) like ibuprofen can cause GI bleeding and kidney damage.

The maximum recommended dosage is 1000 mg four times a day, or 4000 mg total per day. There are exceptions: people who have liver disease, who drink significant amounts of alcohol, or who take Coumadin should take less than that. Some other medications interact with acetaminophen by increasing its metabolism and making the standard dose less effective.

The problem that led to all those cases of liver damage was that patients did not follow the recommended dosage. Either they didn’t take the label seriously and took too many pills, or they inadvertently got a higher dosage by taking combinations of acetaminophen-containing medications, often not realizing what they contained.

Patients who take maximum doses for arthritis have complained that it would be inconvenient and cost them more money to get the prescription-only 1000 mg pills. But there would be no need for them to do that: they could simply make up that dose from whatever size pills are available. Three 325mg tablets add up to 975 mg.

People have been concerned that drugs like Vicodin will no longer be available. You could conceivably get the same thing by taking a hydrocodone pill plus an acetaminophen pill. Unfortunately, plain hydrocodone is not currently available in the US, and it may require new drug applications and new clinical studies to demonstrate efficacy before such a product can be approved. Hydrocodone mixed with acetaminophen is a Schedule III drug, but hydrocodone alone falls under the more restrictive Schedule II of drugs that have more abuse potential.

Why did they recommend removing acetaminophen from Vicodin but not from Nyquil? Apparently because they thought the actual incidence of liver failure was lower from the over-the-counter products. Possibly because of other considerations. It certainly seems inconsistent – perhaps even backwards. Vicodin must be prescribed by a doctor who can take some responsibility for educating the patient, but Nyquil is sold without any supervision.

The new recommendations are intended to protect the consumer. They may protect some people who don’t read labels and who don’t take responsibility to avoid combining medications inappropriately. On the other hand, a few people will still manage to take overdoses by taking too many of the smaller-dose pills or combining them with cough and cold medicines. And eliminating the hepatotoxic component of Vicodin might free patients to take more of the narcotic and might lead to more addiction. It seems to me that a better approach would be to educate the public and put stronger warnings on the products.

Posted in: Pharmaceuticals, Politics and Regulation

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27 thoughts on “Is Tylenol Safe?

  1. Draal says:

    Some additional fun facts:
    The Food and Drug Administration assembled 37 experts to recommend ways to reduce deadly overdoses with acetaminophen, which is the leading cause of liver failure in the U.S. and sends 56,000 people to the emergency room annually. About 200 die each year.
    They cited FDA data indicating that 60 percent of acetaminophen-related deaths are related to prescription products (like Vicodin and Percocet).
    Prescription acetaminophen combination drugs were prescribed 200 million times last year, according to the FDA.
    NyQuil and other over-the-counter cold and cough medicines that combine acetaminophen with other drugs can be dangerous when taken with Tylenol or other drugs containing acetaminophen, according to the FDA, but cause only 10 percent of acetaminophen-related deaths.
    Many drugs interact with each other, and you are warned against these interactions by warning labels and your pharmacist/doctor. If you are too inept to understand this you are simply polluting our gene pool.

  2. nokomarie says:

    I’m somewhat troubled by this ban in that pharmacy recommendations are changing but doctor’s orders are not. So, I am actually receiving punch cards full of Percocet with orders for “1-2 tabs Q 4-6 hours PRN moderate to severe pain (do not give more than five tablets in a 24 hour period)” printed on the label. The MD order is the first part and the thing in parentheses is the moronic recommendation from the pharmacy in compliance with the FDA. Look, cut me a break, all of the teaching regarding pain in the past few years has been medicate when requested as you cannot possibly understand the patient’s pain level and then all of a sudden, the powers that be peach on to the fact that they have been poisoning people.

    Frankly, you try being the one to tell your severely addicted to Percocet client that they cannot have their six doses of two Percocet every four hours because it is unsafe for their liver. I will be on the sidelines eating popcorn watching the meltdown.

    Besides, isn’t this the same FDA who placed a ban on the further production of liquid Morphine sulfate 20 mg/1 ml over some labeling issues and then had to lift it in a hurry when they discovered “gasp” that the drug was in high demand by Hospice patients?

  3. lolife says:

    How credible is this “FDA advisory panel”? This looks like the war on drugs in disguise. Abuse of Percocet and Vicodin is on the rise and they don’t like people using drugs to feel better. I had to beg my dentist for Vicodin when I was in intense, fetal-position-inducing pain from a bad tooth. He was apparently much more worried about the potential for abuse than treating my pain. It’s insane and these hacks on this advisory panel are not helping.

    The drugs administered by doctors are not the drugs that need regulating.

  4. David Gorski says:

    When used appropriately in recommended doses, acetaminophen is one of the safest drugs we have.

    Well, yes and no. The problem is that acetaminophen has arguably the narrowest therapeutic window of any drug that is sold over the counter, and, worse, its hepatotoxicity is not apparent right away. Usually toxicity exhibits no symptoms for 24-48 hours, and by the time symptoms arise, the liver is fried beyond repair. The factoid that you cited, namely that acetaminophen toxicity is the leading cause of liver failure, tells us that there is a problem.

  5. trrll says:

    Nyquil does not contain acetaminophen in combination with an active ingredient that produces tolerance (tempting people with severe chronic pain to escalate the dose), and that is also a drug of abuse.

    The notion in classifying Vicodin as Schedule III rather than II is that people won’t abuse it because of the risk of Tylenol toxicity. This is like supposing that the threat of infection from dirty needles will deter heroin addicts from injecting. The reality is quite different. Vicodin is an extremely popular drug of abuse. It a particularly popular among adolescents, who filch it from their parents’ medicine cabinets or get it from friends who have had injuries. Most of them have not the faintest notion of the risks of acetaminophen. I’ve spoken to adolescents who have quite unknowingly consumed enormous doses of acetaminophen. If it had to be one way or the other, we’d be better off making Vicodin Schedule I and heroin Schedule III.

  6. Todd W. says:

    For those of you criticizing FDA, keep in mind that their decisions would only affect the labeling and marketing of the drugs. Physicians can still prescribe the drugs however they want, it would just be off-label, which is nothing new.

    The way I see this is that it will bring more awareness to physicians about what they are prescribing and what drugs their patients are taking. It might even get patients to examine what they are consuming and how it might affect their health.

  7. LovleAnjel says:

    Taking the OTC acetaminophen issue, I think a reduction in pill strength and relabeling are in order. Most people assume that OTC drugs are safer than prescription, and don’t realize that the difference is just dosage. People see no problem with doubling or even tripling their OTC doses if the pills didn’t at first work. With Tylenol (if I’m correct) two pills are proscribed, six pills are toxic and ten will be lethal. It’s fairly easy to have an even minor toxic effect with “normal” usage. Lower the dosage allowed per pill, and most people will stick to the “take two, maybe four” and be less likely to be hurt.

  8. robertoscunha says:

    I think that as far as drugs go, Tylenol is safe. But is Tylenol safer than Dipyrone?

  9. The Blind Watchmaker says:

    For a long time, I wondered why Tylenol with Codeine was a schedule 3 drug while codeine alone was a schedule 2. After-all, I thought, it is more serious if someone o.d.’ed on Tylenol with Codeine because of the acetaminophen. I never really bothered to ask why.

    I assume it is because plain codeine is easier use in underground drug labs. I doubt that druggies would want their coke mixed with Tylenol. I’dunno.

  10. mamapadawan says:

    If I may, this is all just a crock of sh!t. The real problem here is people do not follow the directions. Fried livers are because people are taking 4, 5, 6 Tylenol at a time and justifying it with “I’m in a lot of pain” and then they want the FDA to “do something!” when they’re suddenly in the ICU. We saw it a couple of years ago when combination cold remedies for children were taken off the market because parents were overdosing their children because they weren’t following the directions. The toxicity of the medication didn’t change – our disregard for following the recommendations did.
    I feel very sorry for doctors and nurses who have to follow these ridiculous rules and put their patients in pain because some loser didn’t read the directions before he took his Tylenol like they were skittles.

  11. nwtk2007 says:

    mamapadawan,

    you don’t really think that most people are educated enough to read and follow directions do you?

    When was the last time you were in the ghetto or in an average high school?

    Instructions are the last thing, if even that, that half the American population is going to look at.

    And if, as in Texas, a sizable portion of the population doesn’t read english, or even read AT ALL, then you can imagine what is going to happen.

  12. Tsuken says:

    Either they didn’t take the label seriously and took too many pills, or they inadvertently got a higher dosage by taking combinations of acetaminophen-containing medications, often not realizing what they contained.

    … or they took an intentional overdose (the intent behind which can vary from person to person).

    As a psychiatrist I’m interested to note that intentional paracetamol overdose is (either omitted or) not a major contributor to liver failure; it certainly results in a significant amount of treatment with N-acetylcysteine in hospital wards/emergency departments – perhaps with sufficient success that intentional overdose really isn’t an especially significant cause of liver failure.

    However, given the ready availability of paracetamol over the counter, and the general perception that it is safe, people who take overdoses without suicidal intent not infrequently take paracetamol – sometimes in very large amounts – thinking they will be ok. (Conversely, I’ve seen many patients intent on suicide who have taken overdoses of benzodiazepines, believing they will be lethal.) That has been a factor in New Zealand at least, in the reduction of the number of tablets per packet, and a similar argument could be made around reducing the dosage of each tablet.

    Not a cut and dried issue though, and educating the poublic is always a good thing.

  13. TheMadPersian says:

    The ED Doc Perspective.

    I view Tylenol as Very safe. Category B. okay in pregnancy as Dr Hall stated. Not much can touch it. Can it damage you? Sure. But really an adult dose it 325mg (500mg for extra strength). with a 4g max dose a day, but a known toxic dose of 7g per day (150mg/kg) (same as the N-Ac loading dose). When does it have to click that maybe taking 21 or 15 of the same pill in one day is too much. Dose tylenol have to go the same route as Cigarettes box with the surgeon general warning, really? Oh yeah that doesn’t stop people either.

    It seems this issues is about the FDA legislating basic intelligence?

    It always surprises me when I go abroad (Greece and India to site specific examples) and need a medication (tetanus in Santoria, got bit by a stray cat or cardizem for my father in india) I just walk into the store ask for what I want and they give it to you. It is up to me to know that I should take it and how much I should take.

    And despite this freedom to buy whatever prescription medication you want they don’t seem to be dropping like flies, or even considering this to be an issue. I appreciate the confounder of quality of life in these places, but with that one would suspect lower education leading to more restriction. But it is not the case.

  14. jsjohnson says:

    Isn’t there also a contraindication for fasting? I’d heard that for people who are fasting, the current recommended dose can actually be toxic. People taking OTC acetaminophen are often suffering from flu or other conditions that make them nauseous or unable to eat, so this has to be taken into account.

  15. Jules says:

    @ David Gorski:

    Pharmacologically, a drug with a lethal dose 5 times that of the effective dose–that is indeed one of the larger therapeutic windows, especially if compared to, say, nutmeg (which isn’t actually a drug per se, but in large quantities it is a potent hallucinogenic agent)

    I really don’t like this ruling. By banning Vicodin it validates the idea that preventing dependency–something which, if you really needed the pain relief, you wouldn’t be in danger of–is more important than treating pain. And the idea that pain isn’t something that’s worth treating. BTW: Vicodin is not hydrocodone + acetominophen. It’s codeine + acetominophen. Hydrocodone is not in the least addictive–it’s a cough suppressant.

    The FDA is also hopelessly muddled in terms of how it schedules drugs. I’ll start having faith in the FDA when it puts marijuana where it belongs.

  16. Jules says:

    The FDA: protecting people too stupid to live, while everybody else must do without….

  17. TheMadPersian says:

    @ Jules

    “BTW: Vicodin is not hydrocodone + acetominophen.”

    —- Vicodin Absolutely is hydrocodone and Tylenol. And it is addictive. Depending on the amount of hydrocodone to acetaminophen ration there are 3 forms I know. Norco, Lortab and Vicodin.

    http://www.rxlist.com/vicodin-drug.htm
    http://www.rxlist.com/norco-drug.htm
    http://www.rxlist.com/lortab-25-drug.htm

    – In regards to the pain relief versus dependency issue. That is complex. And in the ED when I don’t know the patient they get the initial benefit of the doubt. Usually the abusers identify themselves pretty soon.

    – In case anyone hasn’t seen this website, This is what your patients know about their drugs. It is Sad, yet very informative.

    http://forum.opiophile.org/index.php?

    http://forum.opiophile.org/showthread.php?t=23995

  18. brfoot says:

    JULES – You are 3 for 3 all wrong. The idea of narrow therapeutic index has do to with the small margin between drugs levels which are therapeutic and those which are toxic. Vicodin is most definitely hydrocodone and acetaminophen and hydrocodone has one of the highest abuse potentials. And the FDA has nothing to do with scheduling drugs that is done by the DEA. The 1 thing you got right was that hydrocodone is also part of a cough suppresant.

    As for the rest of this discussion the FDA is reacting(overly) perhaps to the fact that far to many people take OTC drugs without reading the ingredients. There are approximatly 100 different products listed in Fact & Comparisons, the book we Pharmacists look things up in, that have acetaminophin listed as an ingredient. This does not account for the “store brand” generics either. Plus most people have the general idea that if 1 pill is good 2 must be better. As with most issues in our world right now if people would only or could only take responsilility for themselves then the government would not feel compelled to regulate EVERYTHING.

  19. Pharmacologically, a drug with a lethal dose 5 times that of the effective dose–that is indeed one of the larger therapeutic windows, especially if compared to, say, nutmeg (which isn’t actually a drug per se, but in large quantities it is a potent hallucinogenic agent)

    Infact, you’ll find that this is a very small theraputic window, when we’re talking about LD50 (lethality) rather than just side effects. LD50 for most drugs is alot higher than acetominophen.

    Vicodin is not hydrocodone + acetominophen. It’s codeine + acetominophen

    *bzzz*, vicodin is absolutely addictive, absolutely hydrocodone and acetominophen. hydrocodone is ALSO used in cough syrup, and in countries where this cough syrup is available OTC, it is one of the leading ways for addicts to acquire hydrocodone to abuse.

    I’ve seen a few people with acetominophen toxicity, and my statistically insignificant sample included 3 suicide attempts, 2 people who were using other substances (alcohol or marijuana), who ingested “whatever pills they were handed”, 1 vicodin addict who had too much, and 1 teenager who took percocet for postop pain, acetominophen pills for a headache and nyquil, and hurt, but did not fry the hell out of, her liver.

    Make of this what you will.

  20. Jules says:

    Gah–my mistake about Vicodin. I was probably reading about the wrong thing…

    I had not known that hydrocodone was addictive, though. I’d always thought that it was too modified to make it onto the opioid receptors in the CNS.

    I’m not doubting the addictiveness of Vicodin. I just think that people make too much of it when nothing else works for the pain.

  21. trrll says:

    By banning Vicodin it validates the idea that preventing dependency–something which, if you really needed the pain relief, you wouldn’t be in danger of–is more important than treating pain.

    Actually, it is the other way around. The main rationale for making Vicodin more readily available than straight hydrocodone is that the acetaminophen will deter abuse. Anybody in pain could simply take hydrocodone (dose adjusted appropriately for their level of pain and degree of tolerance) along with over-the-counter acetaminophen for the synergistic effect. The irony is that the acetaminophen does not deter abuse–it just causes lots of liver damage.

    Yes, it would be nice if everybody understood the risks and benefits of the drugs that they are taking, but the fact is that there is a common presumption that OTC drugs have a wide safety margin, and that overdose hazards are minor. On one occasion, I remember almost forcibly taking a bottle of acetaminophen away from a student who had developed a headache after consuming quite a bit of alcohol (I gave him some ibuprofen to mollify him)–and he was a PhD student in Pharmacology. Reducing the maximum dose of OTC acetaminophen is a pretty small imposition, and could save a lot of livers.

  22. cloudskimmer says:

    Question: What is the basis for maximum dose? Should the maximum dose be adjusted for body weight? What about for the elderly? Can someone who is of low body weight experience liver failure at dosages below the maximum recommended? Does the slowing metabolism as one ages make it more likely that a smaller dose could cause liver failure? And are blood tests to monitor and warn of liver problems good enough to warn patients in time; how often should such tests be performed?

    I’m disappointed at the crude comments. When people are in pain, frail, elderly, and the medical profession cannot relieve their pain, it is easy to take too high a dose. It is difficult to read the tiny type on the box or bottle of pills. And if you are taking one of the drugs that contains acetaminophen, it is difficult to determine the amount and adjust your separate dose of straight acetaminophen. So please try to have some understanding for those who experience severe, chronic pain, and realize how difficult it can be to manage multiple medications.

    Chronic pain is experienced by many people, and the medical profession does not have an effective treatment. Pain medications have unfortunate side effects, which can be severe. This is one of the reasons people seek help from quacks, and is also why many doctors–such as anesthesiologists–become involved in quackery when attempting to treat this problem, such as practicing or recommending acupuncture.

  23. gwen says:

    When I worked in a PICU, at least half of our patients were unintentional overdoses. The largest number occurred when parents had a child who was running a non-specific temperature, and gave the child tylenol for a couple of weeks for an intractible fever. Taking the child to the pediatrician did not occur to them because the child was not ‘really sick’. The child would start having secondary symptoms from the tylenol injestion and in a mild liver failure. They would improve after a course of Mucomyst. I can’t remember a death from this though. We’ve had a couple of 3 and 4 year olds that got into the tylenol elixer and injested the entire bottle, they were better after treatment as well since the parents usually were aware of the injestion a short time later. I’ve seen a couple of tragic unintentional poisonings by teens who had a ‘bad headache’ that was not relieved by a ‘normal dose’, so they took 3, 4 or 5 times the recommended dosage, not wanting to bother their parents because they were old enough to “take care of it themselves”, the injestion usually occurred over several days and by the time of admission, their livers were unsalvagable and they almost always died before they could be transplanted.

  24. It’s stupid to let DEA make decisions about scheduling based on abuse potential. They are cops, not doctors, not epidemiologists. As the name suggests DEA is a law enforcement agency. They can hire doctors to make scheduling decisions, but at the end of the day the agency exists to fight the drug war, so its decisions are going to be colored by that ideology.

    Let real experts in medicine, pharmacology, and public health make scheduling decisions and let DEA handle the implementation.

  25. davidp says:

    The problem seems to be mainly when people are taking Tylenol plus another medicine that contains it. Why not combine the acetaminophen with the antidote (Methionine or some other glutathione precursor) in these other medicines ?

    I presume there is resistance to including the antidote in Tylenol because of the added cost, but the combination medicines already cost substantially more than plain Tylenol, and adding Methionine to them would minimize the risks from combining them with each other or with plain Tylenol.

    From Wikipedia Paracetamol toxicity:

    Paradote is a combination tablet containing 100 mg methionine and 500 mg paracetamol. Methionine is included in order to ensure that sufficient levels of glutathione in the liver are maintained in order to minimize the liver damage caused if a paracetamol overdose is taken

  26. weing says:

    One issue not raised is the risk of renal papillary necrosis with a cumulative acetaminophen dose of about 4Kg.

  27. @David Gorski

    “The problem is that acetaminophen has arguably the narrowest therapeutic window of any drug that is sold over the counter, and, worse, its hepatotoxicity is not apparent right away”.

    I was in a pharmacy recently and they had a special price of $4 on packets of 100 x 500mg acetaminophen tablets. That’s less than $1 per potentially hepatoxic dose.

    It reminded me of a couple of things that were said to me when I accompanied a disturbed teenager to the ER one night. The waiting room was quite full, but the words “paracetamol overdose” caused the triage nurse to say with some urgency “Go through that door there and someone will see you immediately”. The other words I remember were spoken by a doctor as the nurses cleaned up charcoal that was spattered about the place: “I think we got it all in time and saved her liver”.

    I don’t want it taken off the market, but I would like it taken out of the supermarkets and restricted to pharmacies, with limitations on how many tablets can be purchased at one time. There are far less dangerous drugs which are a lot harder to get.

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