Tylenol more toxic than thought....

[Dr Mordrid]

Had this in the kiddie/Tylenol thread, but its focus is beyond kids so....

OOPS !!

In a recent trial for a new drug containing acetaminophen tests were done on 145 volunteers. Of these 106 took Extra Strength Tylenol or other meds containing acetaminophen. 39 took placebos. All were on the same diet.

Summary:

"....the over-the-counter drug (Tylenol/acetaminophen) is the leading cause of acute liver failure in the U.S., and some researchers have called for increased regulation to prevent overdoses."

Bear in mind that 3x the normal level of aminotransferase (a liver enzyme) is considered the threshold at which doctors become concerned about possible liver damage.

28% maintained aminotransferase levels within the normal range.
72% did not

39% experienced an increase to >3x normal levels
25% experienced an increase to >5x normal levels
8% experienced an increase to 8x normal levels

Of the 39 volunteers given placebos only one had a level as high as 2x normal.

Levels continued to increase for up to four days after they stopped taking acetaminophen. It took as long as 11 days to return to normal levels.

http://www.latimes.com/features/health/la-sci-tylenol5jul05,0,6571111.story?coll=la-home-health

Dr. Mordrid

[cjolley]

This does not surprise me in the slightest.

[Fluff]

What is it? Does it affect the liver in the same way that alcohol does?

[GNEP]

As far as I can work out it's what we know as paracetemol (sp?) here.

[Umfriend]

As I now know, that is correct GNEP.

[James_D]

Hmm... to be honest I think this is mostly scaremongery. To put it like this, Paracetamol is the most widely used drug in Europe besides Aspirin. Esp in hospitals, for in addition to its effect on COX1 and Cox2 (Which also most NSAIDS also have) it also have an effect on COX3 receptors in the spinal cord and brain which makes it a better pain relief than the NSAIDS. In addition the NSAIDS are much more Nephro(kidney) toxic than the paracetamol, and is causing a bigger problem for the hospitals than the paracetamol does. Besides the liver has an incredible regeneration capacity, which the kidney doesnt.
Some of the kidney problems are:
Hemodynamically induced acute renal failure
Acute interstitial nephropathy, with or without nephrotic syndrome
Papillary necrosis and chronic renal injury
Plus many leads to GI bleedings etc. etc.


JD.


Edit some typos......

[Brian Ellis]

Agree with JD

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

Interesting article

[Dr Mordrid]

The weaknesses are that it is hepatotoxic in relatively small multiples of the therapeutic dose and that it has no appreciable anti-inflammatory action. It is also more likely than NSAID's to cause rebound headaches, which if you're taking it for a headache....

More than half of OD's reported in an Oxford UK survey involved paracetamol (Tylenol etc.), up 400% since 1981. To me that trendline shows something is seriously amiss, and that FDA trial & the US numbers do nothing to allay that feeling.

I once had a conversation with a University of Michigan Hospital pharmacologist regarding Tylenol etc., brought on by a rash of OD's involving it in our ER. His opinion was that if it had gone through certification with the FDA knowing what he knew then there is no way it would be approved for over the counter use.

Dr. Mordrid

[James_D]

You seem to have missed my point. It not used for ANTI inflamatory action, its used as an analgesic. And either alone, or in more potent forms combined with codeine. Its one of the most tested drug there is, the reason was the tylenol scare from the US, where you actually withdrew it from the market for a while. And most OD's if they are so called "cries for help" suicides it sure is easier to treat early cases with paracetamol poisoning than NSAIDs, like Aspirin.

And if you also read the study that you so elegantly qouted, they also did a comparison with France where they had smaller packages, and reduced the availability for someone to take an OD. And it lead to a reduction on number of pills that you can get from 100 to 35 as max in the UK, and the follow up study in 1998 showed a sharp decrease in suicides both fatal and non fatal due to paracetamol. so keep your facts straight.

JD.

[Dr Mordrid]

The initial study showed the anamalous levels early on, so it was halted. A second trial was designed and was published in the July 5 JAMA. A third run is underway to confirm its findings.

Of course it's possible that aminotransferase elevation isn't as accurate at predicting liver damage as previously thought, but IMO we'll wait for dust to settle before it's used in our house again.

Yes, many OD's are cries for help, but here we are seeing quite a few cases where this is not the case hence the concern at the FDA and elsewhere. Many physicians are starting to think that the max OTC dose (4 grams/day) is too high by double. One such study just came out a month ago.

With all of this going on yes, packaging should be changed both in terms of adding a "black box" warning and less tablets.

Dr. Mordrid

[James_D]

http://news.bbc.co.uk/2/hi/health/5153320.stm

Since you in my eyes keep on scaremongering, I will post some positive news about the paracetamol. This study shows that using paracetamol regularly could reduce the risk of ovarian cancer by almost a third, a study says.

I dont know if its truly valid, but it as a physician should never blindly trust single studies and studies should always be done in a larger and double randomised scale if possible.

JD

[Mehen]

An argument that seems beyond the scope of my knowledge...
but I do agree that 4g/day is too high for OTC. I can understand the need to have such products available for OTC though, getting a doctor in the US, or rather being able to afford one, can be a major pain. (and then there's the cost of prescription drugs, but that is a different topic entirely)

[Umfriend]

Gees, reading the article now. So they took 4g/day for 14 days in a row.... That is not the maximum OTC recommended dosage here. 3g/day is (you get the 4g/day hint if you are in a lot of pain or on prescription or take the 1000g pills which are OTC but not standard). Moreover, it is stated that you should not use it often or for a longer period of time (ahum, 2 weeks anyone?) and that you should not take the max. daily dose at one time.

Much ado about nuttin'

[Dr Mordrid]

4 gm (4 doses of 2 500mg capsules/tablets) is the max OTC dose here, and it's often used for long periods because of its advertised 'safety'.

I quote the medical journal Hepatology: 2004 July;40(1):6-9.

Acetaminophen overdose is the leading cause for calls to Poison Control Centers (>100,000/year) and accounts for more than 56,000 emergency room visits, 2,600 hospitalizations, and an estimated 458 deaths due to acute liver failure each year.

Data from the U.S. Acute Liver Failure Study Group registry of more than 700 patients with acute liver failure across the United States implicates acetaminophen poisoning in nearly 50% of all acute liver failure in this country.

Available in many single or combination products, acetaminophen produces more than 1 billion US dollars in annual sales for Tylenol products alone. It is heavily marketed for its safety compared to nonsteroidal analgesics. By enabling self-diagnosis and treatment of minor aches and pains, its benefits are said by the Food and Drug Administration to outweigh its risks.

It still must be asked: Is this amount of injury and death really acceptable for an over-the-counter pain reliever?

[Umfriend]

But the actual manual, surely, advises not to use it for extended periods, no?

http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a681004.html

http://www.tylenol.com/product_detail.jhtml;jsessionid=HIAC5NPXSSDLECQPCAOSUYYKB2IIWNSC?id=tylenol/hdache/prod_ex.inc&prod=subpex&_requestid=135067#Top

BTW, regular strenght Tylenol dose IS 3g/day, not 4. Same warnngs. It says to stop after 10 days anyway. So what has a test that took 14 days with the absolute max dosage a day (extra strenght tablets) that should make me skip to Ibuprofen?

http://www.tylenol.com/page.jhtml?id=tylenol/hdache/subpregdir.inc

It may be that I am just very lucky (well, I am), but do any here have kids that need pain killers for two weeks in a row? If so, isn't that done under guidance from a doctor?

Edit: I'd be surprised if there has ever been an annual period where me or my kids used more than 12 regular doses. Maybe we are just prudent users that should not be concerned by these kind of things. Still, to my mind there is a difference between saying "ABC is dangerous, especially for kids, you'd better use DEF" or " Excessive use of ABS is dangerous [Yeah, that is what the word Excessive is all about, stupid], especially for kids [no, really? doh!], you'd better excessively use XYZ".