Please ... don't take Tylenol. Ever.

[BroncoBuff]

Always puzzled me how the dangers of acetominophen flew so quietly under the radar, but it looks like that's finally changing. FDA capping per-dose quantities. It's so strange ... when you're prescribed Percocet, Vicodan or T3-Codeine, it's the acetaminophen suspension that gets all the label warnings. And we're talking hard-core opiates here. Plus there's always been liver problems, and the Tylenol with Coca-Cola stuff.

Just Think Aspirin ... the wonder drug of all wonder drugs.

FDA Limits Tylenol in Prescription Combination Products Due to Liver Damage
by Marilisa Kinney Sachteleben – Sun Jan 16, 12:54 pm ET

The FDA announced it is restricting the amount of Tylenol (acetaminophen) allowed in combination prescription drugs to 325 mgs. The move is prompted by warnings that acetaminophen can cause liver damage. OTC products are not affected. The FDA has set 325 mg per capsule or tablet as the safe level for prescription combination products. The FDA is causing labels to be placed on combination prescription pain relievers, warning of liver damage caused from high levels of acetaminophen.

http://news.yahoo.com/s/ac/20110116/...o_liver_damage

[Los Broncos]

Dam, I'm taking these now for my kidney stone pain.

[BroncoBuff]

Originally Posted by Ramblin' Bronco

Dam, I'm taking these now for my kidney stone pain.

Seems like you should get an Rx for that kind of pain ... always heard it's comparable to childbirth. It's not of course, but point taken. If you can, get PercoDAN (oxycodone in an aspirin suspension) instead of PercoCET (an acetaminophen base).

This FDA action restricts acetominophen in combination with other drugs, but even by itself I stay far away. Aspirin is truly the wonder drug of all wonder drugs ... great for pain and systemically therapeutic too. Naproxyn and Ibuprofen for soft tissue. There's nothing Tylenol can do that these can't do better.




Now this is just sad ... from Wikipedia, an FDA advisory panel recommended BANNING these acetaminophen drugs nearly three years ago!! And now finally this week the FDA got around to it. Not BANNING of course, why listen to the experts?! Just slap a warning label on, done and done.

Well, the Wiki article says just 400 deaths a year, so that's just maybe 1100 dead since they ignored their own expert panel's advice. That might sound like a lot of bodies, but it's actually a very small number in relation to the population as a whole

This country is halfway down the tubes, I don' think there's any turning back at this point.

Implicated in deaths

On June 30, 2009, an FDA advisory panel recommended that Percocet, Vicodin, and every other combination of acetaminophen with narcotic analgesics[4] be removed from the market because of their contributions to an alleged 400 acetaminophen related deaths in the United States each year, that were attributed to acetaminophen overdose and associated liver damage.

In December 2009, the Canadian Medical Association Journal reported a study finding a five-fold increase in oxycodone-related deaths in Ontario (mostly accidental) between 1991 and 2007 that led to a doubling of all opioid-related Ontario deaths over the same period.

http://en.wikipedia.org/wiki/Percocet

[Dr. Broncenstein]

Tylenol is much safer than any NSAID including asprin. You have to really, really try to hurt your liver with acetaminophen. What's happening with prescription analgesic combinations is not limited to acetaminophen -- people are abusing them, diverting them, and taking them in every fashion except as prescribed. Taken as prescribed, there is almost no chance of hepatotoxicity with these medications.

For every legit acetaminophen hepatotoxiciy case I've seen, there have been 100 complications from NSAIDS -- namely peptic ulcers and kidney failure -- but sometimes life threatening bleeding complications following surgical procedures due to platelet inactivation. Every medication has a good and bad effect. Aspirin and Ibuprofen can have seriously deleterious side effects, even when taken in the proper dosages.

[BroncoBuff]

Originally Posted by Dr. Broncenstein

Tylenol is much safer than any NSAID including asprin. You have to really, really try to hurt your liver with acetaminophen.

For every legit acetaminophen hepatotoxiciy case I've seen, there have been 100 complications from NSAIDS -- namely peptic ulcers and kidney failure -- but sometimes life threatening bleeding complications following surgical procedures due to platelet inactivation. Every medication has a good and bad effect. Aspirin and Ibuprofen can have seriously deleterious side effects, even when taken in the proper dosages.

Not a doctor, but I can't imagine where you get this stuff. Sounds like you're relying on anecdotal experiences instead of published results? (you cited the cases "I've seen," a very un-doctorly phrase).

You must know aspirin is a wonder drug, how can you compare it to Tylenol? Aspirin is universally known as a blood thinner, not suitable for surgery of any kind, and no provider would do so. But I can't find anything on the hepatic complications you mention, so the one remaining dubious side effect is stomach upset (and of course Reyes).

Show me nsaid horrors even close to this:

Acetaminophen causes three times as many cases of liver failure as all other drugs combined, and is the most common cause of acute liver failure in the United States, accounting for 39% of cases.

While it occurs through overdosing, even recommended doses especially combined with even small amounts of alcohol, have caused irreversible liver failure.

Acetaminophen is metabolized in the liver, resulting in a by-product, N-acetyl-p-benzoquinone imine (NAPQI), that can damage liver cells, but is typically converted into a harmless substance by an antioxidant glutathione. However, large doses of acetaminophen overwhelms the body's supply of glutathione, resulting in destruction of the liver cells.

In infants and small children, studies have indicated that the toxic dose is less than twice the recommended dose.

A study published by the Journal of the American Medical Association in 2006 suggests problems even in healthy people taking the pain reliever as directed. Healthy adults taking maximum doses of Tylenol for two weeks had abnormal liver test results. According to a preliminary study mixing acetaminophen and caffeine may cause liver damage.

http://en.wikipedia.org/wiki/Tylenol


Less than double the prescribed dosage can cause death in children?! Better keep it under the sink with the drain cleaner.

Tylenol is the #1 cause of liver failure ... and the FDA is more worried about the Tylenol in Percocet, Vicodin, than it is the narcotic opiate content. Isn't that enough?

[Dr. Broncenstein]

First and foremost you haven't the slightest idea what you are talking about. Your thread states "Please don't take tylenol ever," and then go on to explain your reason with the most unsound and uninformed reasoning. You topped that off with "just take asprin and ibuprofen." Seriously, this is quite possibly the dumbest if not most dangerous thing I've read on this site. NSAIDs include the "wonder drug" asprin. While they have their purpose, they certainly have serious consequences. Here is a link for starters.

Here is an excerpt from the "Morbidity and Mortality" section:

Both acute and chronic poisoning with NSAIDs results in significant morbidity and mortality. The Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) system has estimated that more than 100,000 hospitalizations and more than 16,000 deaths in the United States each year are due to NSAID-related complications with costs greater than $2 billion. Gastrointestinal (GI), renal, central nervous system (CNS), hematologic, and dermatologic symptoms may ensue

Then take a look at this article about acute liver failure.

From the "Frequency" section of the article:

The incidence of fulminant hepatic failure appears to be low, with approximately 2000 cases annually occurring in the United States. Drug-related hepatotoxicity comprises more than 50% of acute liver failure cases, including acetaminophen toxicity (42%) and idiosyncratic drug reactions (12%). Nearly 15% of cases remain of indeterminate etiology. Other causes seen in the United States are hepatitis B disease, autoimmune hepatitis, Wilson disease, fatty liver of pregnancy, and HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome.

From the "Morbidity / Mortality" section:

Acetaminophen toxicity: Fulminant hepatic failure due to acetaminophen toxicity generally has a relatively favorable outcome

From the "Causes" section:

Drug toxicity – Acetaminophen (also known as paracetamol and APAP)
Intentional or accidental overdose. In the US Acute Liver Failure (ALF) study, unintentional acetaminophen use accounted for 48% of cases, whereas 44% of cases were due to intentional use; in 8% of cases, the intention was unknown.
Dose-related toxicity
May have greatly increased susceptibility to hepatotoxicity with depleted glutathione stores in the setting of chronic alcohol use (consider increased susceptibility due to chronic alcohol use)

Then you retort by attacking my experience as "anecdotal," while you cite literature from topics that you haven't the slightest bit of knowledge. Let me qualify my anecdotal experience: I'm a board certified general surgeon and a fellow of my specialty's college. I'm an associate professor of surgery for the university at which I trained. I perform over 900 surgical cases per year at a federal tertiary referral center in the Indian Health System, in addition to training surgical residents and medical students. The scope of my practice involves minimally invasive abdominal / thoracic, plastic / reconstructive, peripheral vascular, breast, basic ENT, trauma, surgical critical care, wound care, and endoscopy. I operate on neonates, geriatrics, and all those in between.

The oral analgesic of choice that I use unless contraindicated is percocet, which is a combination of oxycodone and acetaminophen. I have prescribed this medication literally thousands of times without a single documented case of hepatotoxicity related to acetaminophen, let alone fulminant hepatic failure. Not one single case. Zero.

I have operated hundreds of cases directly related to NSAID toxicity, namely from gastrointestinal bleeding and/or renal failure. Hundreds.

[ghwk]

I never thought his thread was going to end well for Broncobuff. That having been said I could use a couple of percocet for my back about now.

[Gnomeflinger]

Long live Vicodin!

[kappys]

Thanks for pointing this thread out to me.

We had an interesting discussion at the Poison Center here after the recent panel recommendations came out - we went through them point by point. Suffice it to say that among our group there was agreement with several points and significant disagreement with some other. I have to go to work in about 30 minutes so this will be from memory but happy to offer up some literature afterwards.

1) Tylenol infant suspensions - this probably has the most widespread agreement - infant drops are highly concentrated and thus very prone to dosing errors. These have been voluntarily withdrawn by some manufacturer's switching to children's suspensions which are more dilute and thus harder to make a serious inadvertent dosing error - good move

2) Acetaminophen taken at a maximum of 4 grams daily or 2 grams daily for those with some preexisting liver conditions - some studies have shown a statistically significant number of people taking these doses chronically develop liver function tests(LFT's) abnormalities typically with LFT"S < 1.5 X the upper limit of normal. The significance of such low level rises in liver functions is unclear but does suggest some liver inflammation - whether this would ever be significant enough to cause cirrhosis is a matter of debate - probably not.

3) Acetaminophen + pain products - here is where the real killer lies. Most cases of fulminant hepatic failure are related to tylenol toxicity - though this is still a very rare disease. However the combination of products does play significantly into the DEA classification of drugs which classifies most combo products as schedule III drugs rather than schedule II - this alters physician prescribing patterns and requirements for complicated triplicate prescriptions for these meds. I think the move to 325 mg was an attempt to reduce the risk of tylenol toxicity while still allowing these drugs to be sold under current regulations.

for some perspective - a healthy adult

- takes about 10 grams of tylenol in a single dose to potentially cause liver injury - of those who develop liver injury very few die and most make a full recovery - if you receive the antidote within 10 hours there is almost a 100% chance of recovery(some very rare reports of truly massive ingestion have died despite this)

- Chronically taking over 100 mg/kg a day(about 7 grams a day) can put someone at risk for liver failure. This is where most of the deaths come from - from patients taking these medications at higher than prescribed doses or combining their pain pills with OTC tylenol and not recognizing the dangers

- Chronic alcoholism increased the chance of liver injury with tylenol overdose - though 4 grams a day remains very safe unless someone has already developed cirrhosis

- Acute alcohol consumption along with your tylenol overdose actually inhibits tylenol metabolism and is therefore safer(for your liver at least)

- Data on tylenol related deaths need to be interpreted right - there are 2 groups of people - those who die from liver toxicity and the much higher number of people who die from the combined sedative effects of the pain pills/alcohol that are consumed - tylenol usually has little influence in these deaths

Dr. bronc is right when it comes to NSAID's versus tylenol when taken at appropriate doses - NSAIDS cause far more side effects principally being GI bleeding which can be fatal though in most patients has a benign outcome with good management - NSAIDS can also cause a significant percentage to develop renal disease. Contrasting that with the use of normal doses of tylenol which cause some mild liver testing abnormalities of unclear significance is difficult - none of the patients in those studies developed any sort of over liver disease but over decades of use it remains a theoretical concern. Actual human data in the form of cohorts(retrospectively looking at people taking 4 grams a day) does not show evidence of liver injury.

- In overdose NSAIDs are much safer than tylenol - rarely leading to any severe problems other than those mentioned above which are not usually life threatening

Aspirin for what its worth is highly toxic in overdose - and quite unpleasant. Although the overall case fatality of aspirin toxicity remains fairly low do a quick search on what happens when people ingest a whole bunch - there are a number of deaths per year from this - much lower than tylenol but that also reflects less use of aspirin by most folks. In addition whereas tylenol overdose is initially asymptomatic aspirin overdose may be very unpleasant(lots of nausea, vomiting, tinnitus, dizziness, etc.) Aspirin also carries the risks of GI bleeding and kidney injury that NSAID's do due to their shared mechanisms of action.

[kappys]

One of the gurus of liver disease here who specializes in liver failure mentions that if ibuprofen, aspirin, or tylenol were new drugs that applied for FDA permission to be marketed likely all 3 would be rejected due to their toxicities either in overdose or in normal dosing. I think that he is right.

[theAPAOps5]

Ok so I just need to know. Can I live like Charlie Sheen if I don't take that horrid drug Tylenol?

[Gnomeflinger]

You can also die from drinking too much water. Are they going to put warning labels on water, too? Articles like these take the anxieties of few and exploit them causing panic for everyone.

[BroncoBuff]

Originally Posted by Dr. Broncenstein

First and foremost you haven't the slightest idea what you are talking about. Your thread states "Please don't take tylenol ever," and then go on to explain your reason with the most unsound and uninformed reasoning.

I cited the FDA, two of their advisory boards (experts), and an article sourcing the Canadian Medical Journal. To the extent I don't know what I'm talking about, these guys do. Surprised you disagree. If you choose to disregard these sources, go ahead ... but don't yell at me.

Your quarrel can only be with the thread's title. It might sound hyperbolic, but it's not. It's my opinion, and it's well supported.

Originally Posted by Doc

You topped that off with "just take asprin and ibuprofen." Seriously, this is quite possibly the dumbest if not most dangerous thing I've read on this site.

Dumbest most dangerous thing ever? That's way over the top, and way too angry. Methinks milady doth protesteth too much. Doc I like you a lot, always have, but you flamed and insulted me pretty good in here, despite my impeccable sourcing, so I've gotta say ... it's been mentioned a time or two elsewhere, and I think I'm also doubting you're a doctor. Not an MD anyway. You support your conclusions in an odd manner, "I have prescribed this medication literally thousands of times without a single case of hepatotoxicity" and "in all the cases I've seen," and "Not one single case. Zero." Health professionals don't talk like that. You're not Lewis and Clark blazing a new western passage. As a doctor you'd be part of a well-oiled global network of information. So over and over citing your own experiences as "definitive proof!" - and that is definitely what you've done here - just misses the point. Anybody who watches House knows that.

And I can assure you you'll be more believable as a doctor if you STOP QUOTING WebMD!!

Originally Posted by Doc

NSAIDs include the "wonder drug" asprin. While they have their purpose, they certainly have serious consequences. Here is a link for starters.

Still with the WebMD?

[BroncoBuff]

Originally Posted by theAPAOps5

Ok so I just need to know. Can I live like Charlie Sheen if I don't take that horrid drug Tylenol?

Anything for you Birthday Boy

Did you see the picture where Charlie has no teeth? Gross. I wonder what kind of pain killer his dentist prescribed.

[theAPAOps5]

Originally Posted by BroncoBuff

Anything for you Birthday Boy

Did you see the picture where Charlie has no teeth? Gross. I wonder what kind of pain killer his dentist prescribed.

Actually that is the only reason I posted that. I had just seen that picture. So I thought I would use it in a funny! Man he looks like chit.

[Dr. Broncenstein]

Buff, you'll argue that the sky is purple if it suits your point. For the record your argument includes the following:

1. Tylenol should never be ingested and should be locked under the sink
2. NSAIDS are perfectly safe
3. Wikipedia is an impeccable source
4. Medscape is not
5. I'm not a physician
6. Even if I am a physician, my experience with thousands of patients has no validity against your conclusions drawn from the internet.

Never mind the fact that another physician in this thread who practices emergency medicine has contradicted your opinion as well. Your opinion on tylenol (as stated in the thread title) is silly and without perspective. Your opinion on NSAIDs is outright dangerous. Honestly I don't care if you believe me or not. Take whatever you feel like. The purpose of my involvement in this thread was to point out to other posters how incorrect you are on this matter.

[Dr. Broncenstein]

DIAGNOSIS AND TREATMENT OF NONSTEROIDAL ANTI-INFLAMMATORY DRUG-ASSOCIATED UPPER GASTROINTESTINAL TOXICITY

Gastroenterologists and other clinicians need to be informed and vigilant regarding nonsteroidal anti-inflammatory drug (NSAID)–induced gastrotoxicity. NSAID-associated gastropathy is the commonest and most frequently lethal medication toxicity in the United States.46 NSAID toxicity results in more than 100,000 hospitalizations and 10,000 to 20,000 deaths in the United States each year.137 To place these statistics in perspective, more Americans die annually from NSAID toxicity than from esophageal, gastric, or hepatic cancer.92 Gastrotoxicity substantially raises the cost of NSAID therapy: In one study, for every $100 spent on arthritis therapy, approximately $50 was spent on treating adverse gastrointestinal drug reactions.13 In this study, the total annual cost of treating gastrointestinal side effects from NSAIDs was estimated at about $4 billion.13 Despite the widespread use of NSAIDs, NSAID-associated peptic ulcer disease (PUD) is frequently overlooked and underdiagnosed because of the asymptomatic presentation of early disease and the underreporting of nonprescription NSAID use.38


Page 138 from Current Diagnosis and Treatment: Nephrology and Hypertesion.

"Estimated 5-7% of all hospital admissions occur due to toxicity due to NSAIDS"

"Anywhere from 1-5% of patients who ingest NSAIDS will develop nephrotoxicity"

[BroncoBuff]

Again, you seem over-invested yo me, Doc. Now more of your dubious "support" for this aspirin argument I haven't yet joined: Now there are TWO doctors who "contradict my opinion." Sorry, but kappys thoughtful post appears to avoid taking sides.

Okay, NOW I'm ready to join the aspirin argument... my conclusion: You guys are waaaay off.

Quoted here is an analysis of recent articles in the British Medical Journal and the Lancet. Not WebMD, not Wikipedia, LANCET. Please read closely: please:

Originally Posted by Analysis of Lancet article

In 2010 papers in the British Medical Journal (BMJ) and the Lancet showed long-term aspirin use to be the most protective cancer drug yet found.

Gastrointestinal bleeding is clearly an important side-effect of aspirin. But whatever the frequency of bleeding its seriousness does not match that of the diseases aspirin can prevent. In addition a bleed is not associated with other long-term conditions which often accompany vascular disease or cancer which make a sufferer’s life difficult. The bleeds caused by aspirin are not serious bleeds and there is no evidence that aspirin has lead to a greater number of deaths from bleeding. Furthermore there are drugs which could also be taken in conjunction with aspirin to reduce the risk of bleeding.

http://www.significancemagazine.org/...nder-drug.html


"The most protective cancer drug yet found." Wow. Bet you regret your quotation marks around "wonder drug." And that seems funny too ... there is broad if not universal consensus aspirin qualifies as such. There's even a book or two on the topic.

ghwk, you gave up on me too soon pad'nuh!

I'd give me about an 80 percentile rank on this thread. The title and broad, somewhat overstated opinion/advice "just stick with aspirin and ibuprofen" are all that stand in way of 100

[Hogan11]

I'll just take Aleve and side step the issue entirely

[Dr. Broncenstein]

Originally Posted by Hogan11

I'll just take Aleve and side step the issue entirely

NSAID

[Hogan11]

Originally Posted by Dr. Broncenstein

NSAID

Whoops...that's what I get for just glancing at the thread.

Headed back to the shadows......

[Dr. Broncenstein]

Originally Posted by BroncoBuff

Again, you seem over-invested yo me, Doc. Now more of your dubious "support" for this aspirin argument I haven't yet joined: Now there are TWO doctors who "contradict my opinion." Sorry, but kappys thoughtful post appears to avoid taking sides.

So you must have entirely skipped the section that said "Dr. Bronc is right when it comes to NSAID's versus tylenol when taken at appropriate doses." You know, the entire point of my first post: when taken at appropriate doses, tylenol is safer than any NSAID. Tylenol becomes toxic in overdose situations, either accidentally or intentionally ingested. As Kappys pointed out, it takes a very large dose of tylenol to cause hepatotoxicity in a healthy adult. NSAIDS are frequently toxic at recommended doses. Gee, that sounds familiar.

[kappys]

Originally Posted by Dr. Broncenstein

So you must have entirely skipped the section that said "Dr. Bronc is right when it comes to NSAID's versus tylenol when taken at appropriate doses." You know, the entire point of my first post: when taken at appropriate doses, tylenol is safer than any NSAID. Tylenol becomes toxic in overdose situations, either accidentally or intentionally ingested. As Kappys pointed out, it takes a very large dose of tylenol to cause hepatotoxicity in a healthy adult. NSAIDS are frequently toxic at recommended doses. Gee, that sounds familiar.

FWIW I also did a 2 year toxicology fellowship - so this fits into my area of expertise. I know some of the members of the drug safety advisory board for the FDA - but I don't recall exactly who was on the acetaminophen panel.

At any rate its worth remembering that these are vote based findings from a panel that are then put forth to the general voting body of the FDA - somewhat of a parlimentary procedure.

To summarize:

- In a single large overdose tylenol is more dangerous than NSAIDs which tend to be pretty safe. Aspirin is also quite dangerous in such an overdose

- In a chronic overdose - i.e. taking too much pain medicine for some time - both tylenol and NSAIDs can be quite dangerous. Fewer people develop severe liver toxicity from chronic overuse of tylenol than patients who develop serious GI bleeding or kidney injury from NSAIDs, but the latter group tends to do better once identified and treated appropriately. Reducing the tylenol dosing from 500 mg to 325 mg will likely reduce the number of people who develop tylenol toxicity from overuse of pain medications by reducing the total tylenol ingested.

- In appropriate doses - i.e. 4 g of tylenol daily it is much, much safer than appropriate doses of NSAIDS which still carry significant GI bleeding risk. There does appear to be a population which develops mild liver function test abnormalities at these doses but again the consequences are not really clear - no one seems to develop overt liver disease or cirrhosis.

[Dr. Broncenstein]

Originally Posted by kappys

FWIW I also did a 2 year toxicology fellowship - so this fits into my area of expertise. I know some of the members of the drug safety advisory board for the FDA - but I don't recall exactly who was on the acetaminophen panel.

At any rate its worth remembering that these are vote based findings from a panel that are then put forth to the general voting body of the FDA - somewhat of a parlimentary procedure.

To summarize:

- In a single large overdose tylenol is more dangerous than NSAIDs which tend to be pretty safe. Aspirin is also quite dangerous in such an overdose

- In a chronic overdose - i.e. taking too much pain medicine for some time - both tylenol and NSAIDs can be quite dangerous. Fewer people develop severe liver toxicity from chronic overuse of tylenol than patients who develop serious GI bleeding or kidney injury from NSAIDs, but the latter group tends to do better once identified and treated appropriately. Reducing the tylenol dosing from 500 mg to 325 mg will likely reduce the number of people who develop tylenol toxicity from overuse of pain medications by reducing the total tylenol ingested.

- In appropriate doses - i.e. 4 g of tylenol daily it is much, much safer than appropriate doses of NSAIDS which still carry significant GI bleeding risk. There does appear to be a population which develops mild liver function test abnormalities at these doses but again the consequences are not really clear - no one seems to develop overt liver disease or cirrhosis.

I sat through the mandatory biennial proper prescribing CME lecture last year. I was stunned by the OBNDD's statistics regarding diversion, especially the mortality attributable to diversion of prescription opiates and benzodiazipines. We had approximately 600 overdose deaths last year in this setting, which is just about even with MVC related mortality. Prescription diversion is rampant here, and I would imagine similar trends nationally.

As we have both stated, there is almost no chance for hepatic injury with the proper dose of acetaminophen. Do you think that the diversion trends played any role in the FDA's recommendation to reduce the acetaminophen dose in combined opiate analgesics? More to the point, do you think that knowing the sheer number of people illegally obtaining and abusing these medications had anything to do with the FDA's recommendations?

[bombay]

The Doc Abides.