US FDA Issues New Warning on Acetaminophen Usage

[TallGuyJohninBKK]

Acetaminophen Prescription Combination Drug Products with more than 325 mg:

FDA Statement - Recommendation to Discontinue Prescribing and Dispensing

[Posted 01/14/2014]

AUDIENCE: Consumer, Dentistry, Emergency Medicine, Internal Medicine, Pharmacy, Pain Management, Surgery

ISSUE: FDA is recommending health care professionals discontinue prescribing and dispensing prescription combination drug products that contain more than 325 milligrams (mg) of acetaminophen per tablet, capsule or other dosage unit. There are no available data to show that taking more than 325 mg of acetaminophen per dosage unit provides additional benefit that outweighs the added risks for liver injury. Further, limiting the amount of acetaminophen per dosage unit will reduce the risk of severe liver injury from inadvertent acetaminophen overdose, which can lead to liver failure, liver transplant, and death.

Cases of severe liver injury with acetaminophen have occurred in patients who:

• took more than the prescribed dose of an acetaminophen-containing product in a 24-hour period;

• took more than one acetaminophen-containing product at the same time; or

• drank alcohol while taking acetaminophen products.

BACKGROUND: In January 2011 FDA asked manufacturers of prescription combination drug products containing acetaminophen to limit the amount of acetaminophen to no more than 325 mg in each tablet or capsule by January 14, 2014. FDA requested this action to protect consumers from the risk of severe liver damage which can result from taking too much acetaminophen. This category of prescription drugs combines acetaminophen with another ingredient intended to treat pain (most often an opioid), and these products are commonly prescribed to consumers for pain, such as pain from acute injuries, post-operative pain, or pain following dental procedures.

Acetaminophen is also widely used as an over-the-counter (OTC) pain and fever medication, and is often combined with other ingredients, such as cough and cold ingredients. FDA will address OTC acetaminophen products in another regulatory action. Many consumers are often unaware that many products (both prescription and OTC) contain acetaminophen, making it easy to accidentally take too much.

More than half of manufacturers have voluntarily complied with the FDA request. However, some prescription combination drug products containing more than 325 mg of acetaminophen per dosage unit remain available. In the near future FDA intends to institute proceedings to withdraw approval of prescription combination drug products containing more than 325 mg of acetaminophen per dosage unit that remain on the market.

RECOMMENDATION: FDA recommends that health care providers consider prescribing combination drug products that contain 325 mg or less of acetaminophen. FDA also recommends that when a pharmacist receives a prescription for a combination product with more than 325 mg of acetaminophen per dosage unit that they contact the prescriber to discuss a product with a lower dose of acetaminophen. A two tablet or two capsule dose may still be prescribed, if appropriate. In that case, the total dose of acetaminophen would be 650 mg (the amount in two 325 mg dosage units). When making individual dosing determinations, health care providers should always consider the amounts of both the acetaminophen and the opioid components in the prescription combination drug product.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm381650.htm

[lopburi3]

And that can be very misleading as it only applies to use in combination drugs and has been the recommendation for years so really only a making it official type thing. It does not change the normal usage of this drug or total daily allowed amount but will help to prevent excessive total intake for those normally using high levels for pain relief who may also be prescribed other drugs that contain as a secondary ingredient and might not be aware of this.

[TallGuyJohninBKK]

The unfortunate part of the FDA's advisory, as best as I can read it, is that it doesn't seem to say exactly what total acetaminophen dose is considered the maximum safe level for any 24 hour period.

They don't want any one pill or capsule to contain more than 325 mg. But then add that a two-tablet or caplet dose totaling 650 mg may be used. But I assume that means taken at once -- not as the total dose over a 24 hour period.

Meanwhile, how many years have the manufacturers of Tylenol and similar products been selling 500 and 650 mg tablets and capsules? And where was the FDA and the warnings about potential liver damage during all that time?

[bina]

old news. liver problems and tylenol is a know problem.as is inadvertant over dose.

[lopburi3]

As I said it does not change recommended daily max when using just that drug so 500mg or even two if adult is fine every six hours. It is only to limit additional exposure.

[Tywais]

(CNN) -- You're in pain after surgery, and your doctor prescribes you Vicodin, or maybe Percocet. But when you get home, the pain hasn't subsided and you decide to pop some Extra Strength Tylenol.

Unknowingly, you may have just taken more of the drug acetaminophen than is safe.

<snip>

The warning does not apply to over-the-counter drugs such as Tylenol, which contains acetaminophen. The FDA said it will address over-the-counter products in another regulatory action.

In 2011, the FDA asked manufacturers to limit the amount of acetaminophen in prescription combination drugs to 325 mg per capsule or tablet by January 2014. While more than half of the manufacturers agreed, some combination drugs with higher amounts of acetaminophen remain on the market.

CNN.com

[Sheryl]

And that can be very misleading as it only applies to use in combination drugs and has been the recommendation for years so really only a making it official type thing. It does not change the normal usage of this drug or total daily allowed amount but will help to prevent excessive total intake for those normally using high levels for pain relief who may also be prescribed other drugs that contain as a secondary ingredient and might not be aware of this.

+1

[harrry]

I seems to me they are trying to limit it's use to where it is knowingly prescribed or taken. They may be triying to stop people being prescribed a medicine without knowing it contains it and then taking more. A little like saying that sugar in softdrinks should be controlled though sugar may still be sold as people can then judge how much they take themselves as it is not hidden.

[Sheryl]

The unfortunate part of the FDA's advisory, as best as I can read it, is that it doesn't seem to say exactly what total acetaminophen dose is considered the maximum safe level for any 24 hour period.

They don't want any one pill or capsule to contain more than 325 mg. But then add that a two-tablet or caplet dose totaling 650 mg may be used. But I assume that means taken at once -- not as the total dose over a 24 hour period.

Meanwhile, how many years have the manufacturers of Tylenol and similar products been selling 500 and 650 mg tablets and capsules? And where was the FDA and the warnings about potential liver damage during all that time?

the earlier advisory in 2011 listed the maximum daily dosage at 4,000 mg http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm239871.htm

Note that this is for healthy people, use by anyone with impaired liver or kidney function would be another matter.

FDA warnings about liver damage go back more than 5 years.

[Sheryl]

P.S. relating this to Thailand, the usual dose of paracetemol in combination drugs here (of which there are many, including cold remedies and various pain relievers) is 500 mg.

[TallGuyJohninBKK]

the earlier advisory in 2011 listed the maximum daily dosage at 4,000 mg http://www.fda.gov/drugs/drugsafety/informationbydrugclass/ucm239871.htm

Note that this is for healthy people, use by anyone with impaired liver or kidney function would be another matter.

Thanks much for the link and info, Sheryl... I think it's unfortunate the FDA didn't reiterate or at least mention that issue/fact in their latest missive.

4000 mg is a 24-hour period certainly seems like A LOT!!! This below from the 2011 FDA info you linked above.

Q4. Will the new dosage limit affect the dosing directions for oral prescription acetaminophen combination products?

The new dosage limit will not affect other aspects of prescribing of prescription acetaminophen combination products. The total number of tablets, capsules, or other dosage units that may be prescribed and the time intervals at which they may be prescribed need not change as a result of the lower amount of acetaminophen per dosage unit.

For example, if a healthcare professional previously prescribed 1 or 2 tablets of an oral prescription acetaminophen combination product every 4 to 6 hours, these dosing instructions will not change. A prescription drug containing 325 mg of acetaminophen prescribed at a maximum dosage of 2 tablets every 4 hours will add up to a total daily dose of 3900 mg (3.9 grams), which is less than the 4000 mg recommended maximum daily dose of acetaminophen.

Of course, if someone was taking two 500 mg acetaminophen pills every six hours, they'd be right at the 4000 mg limit for a 24 hour period. And if they were taking two 500 mg pills every four hours, they'd be at 6000 mgs for a 24 hour period, which sounds like a big NO-NO.

[chubby]

I think it is funny, that from what I've read, one should not drink alcohol for 7 days, before using any acetaminophen, cause I've often used it with hangovers, which is when I need it .......

Also, the alternative is NSAIDs, which are probably more dangerous, for any ongoing use, I was gonna try to get some Voltaren (NSAID) topical for pain, myself, not sure if they have that in Tland?

[Sheryl]

Votaren (dicloflenic) and many other NSAIDs are readily available in Thailand, both topical and oral.

Be sure to take oral form on a full stomach.

Topical form will be more effective if you first apply heat until the area os pink in color, it promotes absorption.

[dddave]

Kind of scary for me to read this. I have arthritic knees and before going out every day will take a fairly heavy dose of an NSAID. I alternate between plain aspirin, Ibuprofin, Naproxin and Acetaminophen. I am 70 years old and otherwise in good health....knock wood!!

Foe one thing, I had no idea of the risks of alcohol consumption within a 7 day period. I am neither a regular or a binge drinker but I often meet friends for one to three beers, maybe once or twice a week.

Guess I've got some more studying to do. It's frustrating because there is so much conflicting information.

[chubby]

well mai mak-jai mak mak , i don't recall where the reference was i read, just risk/benefit like everything but i'd not use the aspirin , ibuprofen or any NSAIDs at age 70 , try the topical and the paracetoml and lots of ice and a knee sleeve IMHO

Pharmacotherapy. 2012 Sep;32(9):784-91. doi: 10.1002/j.1875-9114.2012.01122.x. Epub 2012 Jul 31.

Effect of therapeutic doses of acetaminophen (up to 4 g/day) on serum alanine aminotransferase levels in subjects consuming ethanol: systematic review and meta-analysis of randomized controlled trials.

Rumack B1, Heard K, Green J, Albert D, Bucher-Bartelson B, Bodmer M, Sivilotti ML, Dart RC.

Author information

Abstract

STUDY OBJECTIVE:

To quantify the effect of therapeutic doses of acetaminophen on serum alanine aminotransferase (ALT) levels in subjects who consumed ethanol.

DESIGN:

Systematic review of six randomized placebo-controlled trials, of which five were included in a meta-analysis.

SUBJECTS:

Subjects included in the meta-analysis were those who consumed ethanol and received acetaminophen in doses up to 4 g/day (551 subjects) or placebo (350 subjects).

MEASUREMENTS AND MAIN RESULTS:

A comprehensive literature search of the MEDLINE, EMBASE, and International Pharmaceutical Abstracts databases and the Cochrane Central Register of Controlled Trials was performed to identify randomized, placebo-controlled trials that enrolled subjects who consumed ethanol, received acetaminophen in therapeutic doses up to 4 g/day, and had serum ALT level measurements. A total of 184 articles were identified; six articles met all criteria. Five of the six articles reported ALT levels on study day 4 for both groups of subjects who receivedacetaminophen or placebo. Thus, for the meta-analysis, we used the primary outcome of mean change in serum ALT level from baseline to day 4 in the acetaminophen groups compared with the placebo groups. We found that the difference in mean change from baseline ALT levels between theacetaminophen and placebo groups on day 4 was 0.0 U/L (95% confidence interval -0.2-0.1 U/L). There were no reports of liver dysfunction, liver failure, or death in any of the trials.

CONCLUSION:

In randomized, placebo-controlled trials of subjects who consumed ethanol, no elevation of ALT level on study day 4 was noted when subjects ingested up to 4 g/day of acetaminophen.

© 2012 Pharmacotherapy Publications, Inc. All rights reserved.

[chubby]

on the other hand

http://www.webmd.com/mental-health/addiction/news/20131104/tylenol-and-alcohol-a-bad-mix-study-suggests

always thought it was more a liver risk, guess it's kidneys too

[Sheryl]

It is both.

Occasional use by people with no pre-existing liver or kidney impairment is no problem but regular use can be. Ditto NSAIDs.