NPR

FDA Recommends New Limits On Acetaminophen

An FDA advisory panel yesterday warned about the risk of acetaminophen, a painkiller in Tylenol, Nyquil and other drugs.

The panel also called for a ban on Vicodin and Percocet, two drugs that combine acetaminophen with narcotics.

Dr. William Lee is director of the Clinical Center for Liver Diseases at UT Southwestern Medical in Dallas. He has seen how acetaminophen can harm the liver.

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Transcript

NEAL CONAN, host:

Painkillers like Tylenol, NyQuil or Excedrin are so popular that most of us think of them as harmless. But the ingredient they share, acetaminophen, can cause serious liver damage at high doses. And because it's often combined with other medicines, it's all too easy to take more than you realize.

A panel of medical experts yesterday advised the Food and Drug Administration to lower the maximum dosages for these over-the-counter products, and to ban prescription drugs like Vicodin and Percocet which combine acetaminophen with narcotics.

If you have questions about acetaminophen, please give us a call, 800-989-8255. The email address is talk@npr.org. You can also join the conversation at our Web site; go to npr.org and click on TALK OF THE NATION.

Dr. William Lee joins us now from his office in Dallas, where he's director of the Clinical Center for Liver Diseases at the University of Texas Southwestern Medical Center. He was a guest speaker to the panel advising the FDA yesterday. Nice to have you with us on the program today.

Dr. WILLIAM LEE (Clinical Center for Liver Diseases): Thanks so much.

CONAN: So how bad is acetaminophen for the liver?

Dr. LEE: Well, in our study - which is a national study sponsored by the NIH called the acute liver failure study - we try to register cases of this very severe liver injury, the most severe liver injury, the kind that either dies or typically gets transplanted. And every year, we register 150 cases of all kinds of liver injury and 75, or roughly 50 percent of them, are acetaminophen. So over the past decade, we've got over 600 cases of either death or transplant or very severe liver injury that recovers due to this.

And there are several situations. One would be an intentional overdose because acetaminophen is a dose-related toxin. It differs from the other prescription drugs, where you have an idiosyncratic reaction that occurs in one in 30,000 people, let's say. Any of us would get toxicity if we took too much.

CONAN: Well, how much is too much?

Dr. LEE: Well, probably eight or 10 grams, which would be 20 extra- strength pills. But remember, you don't have to take them all at once. If you took, let's say, six or eight grams three days in a row.

Part of the problem is that there are so many different products that contain acetaminophen. People don't read the labels carefully. They might be taking NyQuil and Tylenol, they might be taking DayQuil and Vicodin. All of them contain acetaminophen, so you rapidly ramp up the dose that you're taking.

CONAN: I happen to have a bottle of Tylenol Arthritis Pain Caplets in front of me. And I'm just looking at it and it tells me to take no more than six caplets per day, two every eight hours. And each one contains 650 milligrams of acetaminophen. My arithmetic is not my strong suit, but I get 3,900 milligrams there.

Dr. LEE: Right. Well, that's roughly what the upper limit of packaged dosing is now. It's four grams. So it's either eight extra-strength or six of these bigger-size caplets.

But what the advisory committee said was, that's probably too much. It ought to be somewhere around 3,200 milligrams. So start with the 325-milligram pills, make the pill size smaller. And there's no clear evidence, or very little, that you need these larger doses. And if people recognize that this had potential for toxicity, and if you cut down the size of each pill, that you would probably reduce the harm that's caused.

So they said not 4,000 anymore, 3,250. And the biggest size pill available over the counter is supposed to now be 325, whereas it used to be 500, or as you say 650. So the 650s and the 500s, I think, will probably be gone. But you can get bigger pills by prescription. But prescription gives you the feeling that it's more likely to be recognized as being a serious drug rather than being over the counter.

See, if you go to a big-box store, you can get a thousand, 500-milligram caplets - a thousand, 500 milligram caplets. That's enough to kill about 25 people.

CONAN: And yet it gives you the impression that you can take them like candy.

Dr. LEE: Correct. I think the overall message from the advisory committee meeting was: This isn't candy; it causes more deaths per year in the U.S. than all other prescription drugs combined, more deaths than all other prescription drugs combined.

And in my data, we have - roughly 40 percent of the cases involve the narcotic combination. So two things happen. Either the patient is taking the narcotic combination, becomes addicted to it, increases the dose over several months. So now, instead of taking four Vicodin a day, they're taking 12 Vicodin a day. Well, if that's got 500 milligrams, that's six grams of acetaminophen every day.

And then, if they get something else and take a couple of Tylenol on top of it, that's when they kind of break through the threshold of tolerance that they've had and get the toxicity.

CONAN: The weird thing is people would think the opiate might be dangerous. In fact, at toxic levels, it's the acetaminophen.

Dr. LEE: Right.

CONAN: Let's get…

Dr. LEE: But it's because they've built up their…

CONAN: Tolerance.

Dr. LEE: …addiction - tolerance to both drugs in a way, yeah.

CONAN: Yeah. Let's get some callers in on the conversation.

Dr. LEE: Sure.

CONAN: If you have questions about acetaminophen and these recommendations, give us a call, 800-989-8255. Email is talk@npr.org. We'll start with Sean(ph) in Avondale, Pennsylvania.

SEAN (Caller): Hi, Neal. Thanks for taking my call. My question is about the risks of acetaminophen interacting with alcohol. It seems like a no-brainer, to me at least, that you don't want to take 15 ibuprofens or 15 Tylenols in one dose. But if you're like me, you might go out for a couple of beers and then you wake up the next morning and you've got a nasty headache, and you take some acetaminophen. I'm told that there's a very good likelihood that there's probably still some alcohol in my system when I wake up the next morning and I'm worried that - I'm wondering if having alcohol in my system would make an otherwise safe dosage of acetaminophen dangerous to my liver.

Dr. LEE: That's a great question. I think the answer is, we're not absolutely certain, but we think it is true that alcohol and acetaminophen together have, in some instances at least, the synergistic effect. The other thing I will say, though - about 20 percent of our cases of unintentional overdose - okay, so there are people that willfully overdose at one point in time, but what we're talking about are the people that have a pain issue and unintentionally overdose over, say, several days.

Often, they are - about 20 percent of them are alcohol abusers and - which sounds pretty high to me, which suggests that chronic alcohol use is associated. But the other thing it does is it clouds your thinking. So, did I take two pills two hours ago? I've still got this darn headache. Let me take two more. So I think it's not clear, exactly, the danger of alcohol and acetaminophen, partly because it turns out that alcohol competes for the same metabolic pathway as acetaminophen.

So when you still have the alcohol in your system, you might, in some bizarre way, be protected. But once you stop drinking, then the time that you have the hangover, the actual enzyme has been induced. So you have too much metabolic capability. And that's when you probably get a synergistic effect of the alcohol is after you stop drinking.

CONAN: Sean, thanks very much. Let's go next to - this is Anne, or Aun(ph), excuse me, in Williams, California.

AUN (Caller): Hi. Yes. Looks like a lot of this research has been done on adults and I was wondering, how safe is it still for kids and also for pregnant women - on the fetus?

Dr. LEE: Well, again, I think most people can take - even with liver disease or pregnancy or in kids can take - well, let's say adults first, can take up to, let's say, three grams a day. And virtually everyone will be totally safe at that level. So that's six extra-strength, as it's currently constituted, but it would be more like eight or so of the 325-milligram pills.

Now, in kids, there - the issue that came up at the advisory committee meeting is that there's two concentrations, and it's very confusing for parents. The more concentrated is actually the infant size, and the less concentrated is actually the bigger person size. But what happens is sometimes if you get that mixed up and you use the more concentrated in - say, instead of in a dropper, in a teaspoon, then you overdose.

And we have - there is a pediatric acute liver failure study - just like my adult study. And they have cases at all ages, usually where the parents are chronically overdosing over several days for a viral infection, and they develop liver failure. But the number one cause, actually, in the pediatric population is adolescent overdoses. It's teenagers taking too much.

CONAN: Aun, thanks very much.

AUN: Thank you. Bye-bye.

CONAN: Email from Hannah(ph) in Minneapolis. I'm a 21-year-old healthy woman. In October, I had my first ulcer. The pain was pretty severe. I know I should not take aspirin, but was told I could take acetaminophen for stomach pains, colds or headache. Is this good advice, or should I look for yet another option, given acetaminophen's apparent toxicity?

Dr. LEE: No. I think, again, in doses that are sensible, read the labels, don't overdose, don't take more than six or possibly eight tablets a day; it's very, very safe. But I think the main message, in a way, is that people were totally unaware that there was any hazard to this, that there was any possibility that they would injure themselves or they never would have done it. I mean, we have people who died taking Vicodin for bunion - after bunion surgery or dental extraction.

And, again, usually they were overdosing. They said, if four tablets a day is what the package says, maybe I'll take some Vicodins and then I'll get some Percocets from my wife's stash in the medicine cabinet. So they're always overdosing in these situations. And sometimes we know exactly how much, and sometimes we don't.

CONAN: We're talking with Dr. William Lee from the University of Texas Southwestern Medical Center in Dallas - where he's director of Clinical Center for Liver Diseases - about, well, new dangers disclosed about acetaminophen overdoses. You're listening to TALK OF THE NATION from NPR News. And let's go to Fred(ph). Fred with us from Harrisonburg, Virginia.

FRED (Caller): Hello. My question was for the doctor. Did I hear correctly when you said 600 people in a decade?

Dr. LEE: Six hundred people in a decade that we have in our registry. Now obviously, we have roughly 22 sites around the U.S., mostly adult transplant centers collecting cases. And you know, some hospitals see three of these cases a month. And again, they don't all die but a major transplant center - most liver specialists in the U.S. know and see these cases month after month, year after year. So we have 600 well-characterized cases in a decade.

And the - about 25 percent of them die; a small number, about 8percent of them; get transplanted; and then roughly two-thirds do survive.

FRED: Okay. Now, the reason I'm calling is, is I served in the military for 10 years and I absolutely do not want to cheapen life, you know, or disregard it. But it seems like to me that 600 people in a decade is a small number. But when you talk about how many people are in the U.S., or the world much less, but I mean, more people die in the back alleys of Los Angeles over something as trivial as a necklace or Reebok sneakers than they do to this.

Dr. LEE: Yeah. But this should be manageable.

FRED: I mean, how big of a deal is this?

Dr. LEE: Well, the estimates are somewhere around 200 or 300 cases a year. So obviously, we don't see - we don't see but a fraction of the cases, first of all. So 600 isn't the total number for the U.S. population. It's more like 2,000 or…

CONAN: Per year?

Dr. LEE: …or 3,000 in a decade - no, I'm saying in 200 or 300 per year. If this is manageable by better patient education and by limiting package size -nobody's taking away the product completely. And let me just say, this is what the advisory committee advised FDA to do. FDA will do what it feels is in the best interest of the American public, and I think they do it quite well. But they have to have time to figure this all out.

And whether they actually do in the end unbundle the narcotic from the acetaminophen is still unclear. But I would still argue that 200 deaths a year is not a trivial number.

CONAN: Fred, thank you.

FRED: Thank you.

CONAN: Bye-bye. Let's see if we can go next to Judith(ph), Judith with us from Virginia Beach.

JUDITH (Caller): Hello.

CONAN: Go ahead, please.

JUDITH: Thank you so much for this program. I am a chronic pain sufferer. As of 2002, I cannot function without pain medication. I am aware of this liver toxicity with acetaminophen, but it seems like the doctors are not cognizant. And when you try to tell a doctor that you want more pain meds, less acetaminophen, they look at you like you're, A, doc shopping or B, trying to get some kind of fix. I'm just looking for relief.

Dr. LEE: Sure.

JUDITH: You know, and I've been screaming what you're talking about now for 10 years. So when I heard this program, I really - I just almost feel like crying because somebody finally understands. My husband died of cirrhosis at the age of 45. He was a chronic pain sufferer and he did drink a few beers here and there. But I wish that you could publish a newsletter because it's not only the consumer that needs to be educated, it's in fact a great number of doctors.

CONAN: Would you agree with that, Dr. Lee?

Dr. LEE: Yeah. I think - one of the issues here regarding the narcotic-acetaminophen combination is this whole idea that people become addicted to it. But one of the reasons is it's because it's the only kind of narcotic that doctors can write without a triplicate special narcotic form prescription. And so, it's the only one you can phone in to a pharmacy. So often, people do become Vicodin addicts. They get multiple prescriptions.

But I think if the - and that's how they start to abuse it and eventually get a lethal dose of the acetaminophen because they're gaining tolerance to both medications initially, and then they'll break through the tolerance to the acetaminophen. But if the drugs were to be unbundled, then it would - the doctor would have to write a triplicate narcotic form. Yes, that's more work for him or her, but they need to be doing that so that they are keeping track of how much narcotic the patient is getting. And, of course, these records can now be tracked on a statewide basis.

Right now, you can get Vicodin over the internet. You can just - if you hit the Internet right now, you'll get a hundred thousand hits for Vicodin and you can get it from Bermuda or wherever you want. You don't even have to have a prescription. So something needs to be done in part to manage the addiction potential.

CONAN: Dr. Lee…

Dr. LEE: But again, the spin-off of that is the liver toxicity of acetaminophen.

CONAN: Dr. Lee, thank you very much for your time today.

Dr. LEE: Thank you.

CONAN: Dr. William Lee from the UT Southwestern Medical Center in Dallas. Tomorrow, we'll talk about how violence affects a community, plus a conversation with NPR's ombudsman. Why doesn't NPR call waterboarding torture?

This is TALK OF THE NATION from NPR News. I'm Neal Conan in Washington. Transcript provided by NPR, Copyright NPR.

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