Blood thinners and acetaminophen
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Acetaminophen leading cause of acute liver failure

Found in over 100 preparations, Acetaminophen is truly not a pain reliever (doesn’t act upon nerves or reduce inflammation) and is commonly thought to be like an NSAID—which it isn’t!--jk

 

New Study Links Signs of Possible Liver Damage to Lower Doses of Acetaminophen (TYLENOL), Supporting Previous Research

     Worst Pills Best Pills Newsletter article September, 2006

From www.Worstpill.org 

Healthy medical study participants given the maximum approved daily dose of the popular pain and fever reducer acetaminophen (TYLENOL) developed an early sign of possible liver damage, according to research published in the July 1 Journal of the American Medical Association.

The study, which was testing a new product combining the narcotic painkiller hydrocodone with acetaminophen, was shut down early because of the frequent occurrence and size of blood level increases of an enzyme known as alanine aminotransferase (ALT) in groups receiving acetaminophen versus the group receiving a placebo. ALT elevation is an early sign of potential liver damage.

The study involved 145 healthy male and female volunteers, ranging in age from 18 to 45. The volunteers randomly received one of five treatments. Four of these treatments included four grams of acetaminophen (equivalent to eight extra-strength doses) daily and the fifth was a placebo. The intended duration of the study was 14 days.

Overall, 41 of the volunteers (39 percent) experienced ALT elevations more than three times the upper limit of what is considered normal, while none of the volunteers receiving the placebo had ALT elevations of this level. There were 27 patients (25 percent) with ALT elevations of more than five times the upper limit of what is considered normal and eight patients (eight percent) with ALT values more than eight times the upper limit of what is considered normal.

The authors of the study commented that their review of previously published medical studies supports their observations that some healthy adult patients in clinical trials developed ALT elevations when repeatedly treated with four grams of acetaminophen daily.

The study was entirely funded by the producer of the new hydrocodone-acetaminophen combination, Purdue Pharma LP, headquartered in Stamford, CT. Purdue Pharma is the notorious manufacturer of the potent, frequently-misused, timed-release narcotic oxycodone (OXYCONTIN).

Previous studies show acetaminophen linked to possible liver damage

The researchers noted that the incidence of ALT elevations they observed was higher than those reported in similar published studies. They speculate that, in part, their results may be related to the relatively high proportion of Hispanic people in their study. Previous research suggests that people of Hispanic origin are at increased susceptibility to ALT elevations.

Whatever the reason, the results of this study are troubling.

In the February issue of Worst Pills, Best Pills News, we reported on a study published in the December 2005 issue of the medical journal Hepatology. The study found that the annual percentage of potentially fatal acute liver failure cases caused by acetaminophen rose from 28 percent in 1998 to 51 percent in 2003. The authors of this study concluded that liver damage caused by acetaminophen far exceeds other causes of drug-induced acute liver failure in the United States.  {The real pisser is that acetaminophen has practically no therapeutic value, just product recognition. I also insist that the compound containing a pain killer contain aspirin, for all other NSAIDS increase significantly the rate of development of arteriosclerosis—jk.}

This research showed that unintentional overdoses were responsible for 48 percent of the acute liver failure cases. Intentional overdoses, or suicide attempts, accounted for 44 percent of episodes. In eight percent of the cases, the intent was unknown. Of the patients who overdosed unintentionally, 38 percent took two or more acetaminophen-containing products simultaneously, and 63 percent used narcotic combination painkillers that contained acetaminophen.

Acetaminophen is found in many commonly used drugs

The list of acetaminophen-containing prescription and over-the-counter (OTC) drug products is long. The table below lists the brand names of various painkillers and products widely promoted for colds and flu. The right-hand column lists the amount of acetaminophen contained in one dose of the product.

BRAND NAME

AMOUNT OF ACETAMINOPHEN
   PER DOSE

DRIXORAL PLUS

.500 grams

EXCEDRINE MIGRAINE

.250 grams

EXTRA STRENGTH TYLENOL

.500 grams

FIORICET

.325 grams

LORTAB

.500 grams

PERCOCET

.325 grams

REGULAR STRENGTH TYLENOL

.325 grams

TAVIST ALLERGY/
SINUS/HEADACHE

.500 grams

TYLENOL CAPLETS

.650 grams

TYLENOL GELTABS

.650 grams

TYLOX

.500 grams

VICKS DAYQUIL
MULTISYMPTOM COLD/
FLU RELIEF

.325 grams

VICKS NYQUIL

.500 grams

VICODIN

.500 grams

The amount of acetaminophen contained in OTC drugs is clearly listed on the label. Always read these labels before taking any OTC drug to make sure you are not taking acetaminophen in two or more products.  {There are more than 100 products containing acetaminophen.  Too often these products are taken in addition to products such as vicodin, often without the awareness of both products containing acetaminophen and the possibility of liver damage—jk.}

Prescription painkillers may be combinations of a narcotic drug with acetaminophen, such as LORTAB, PERCOCET, TYLOX, and DARVOCET. If you are prescribed a painkiller, ask your pharmacist if it also contains acetaminophen. Mixing various OTC drugs and prescription painkillers may result in the ingestion of too much acetaminophen.    

In addition, alcohol in combination with acetaminophen can increase the risk of liver toxicity. OTC acetaminophen products now have the following warning on their labels:

Warnings
Alcohol warning: If you consume three or more alcoholic drinks every day, ask your doctor whether you should take acetaminophen or other pain relievers/fever reducers. Acetaminophen may cause liver damage.

What You Can Do

There are two important points that you should always consider when using acetaminophen or any over-the-counter drug. One, just because a drug is sold over the counter does not mean that it is totally safe — acetaminophen is a prime example. Two, when using any OTC product, always use the lowest dose that helps your symptoms. See your physician if the symptoms persist.

You should read the labels on OTC drug products carefully.  If you are given a prescription painkiller, ask your pharmacist if it contains acetaminophen.

If you or a family member develop any of the following symptoms of potential liver toxicity, you should stop taking all acetaminophen-containing products and call your physician immediately:

• Pruritus (itchy skin)
• Jaundice (yellowing of the skin or whites of the eyes)
• Dark urine
• Upper right-sided abdominal tenderness (location of the liver)
• Unexplained flu-like symptoms

 

 

 

New paradigm identifies gene responsible for acetaminophen-induced liver injury

Posted May 12, 2009 at http://www.fiercebiotech.com/press-releases/new-paradigm-identifies-gene-responsible-acetaminophen-induced-liver-injury

New paradigm identifies gene responsible for acetaminophen-induced liver injury

Acetaminophen (Tylenol and generics) is one of the most commonly used over-the-counter drugs in the United States. While generally safe, acetaminophen is known to cause severe liver injury if taken in high doses. But likely due to genetics, even the recommended dose can induce serious liver damage in a significant number of people. In a study published online in Genome Research (www.genome.org), scientists have found a genetic marker linked to the risk of acetaminophen-induced liver injury, using a strategy that will help develop safer drugs in the future.

Acetaminophen is considered safe over long-term use, but recent studies have indicated that even over a relatively short period, the maximum allowable dose can induce elevated levels of the liver enzyme ALT in blood serum in approximately one third of healthy individuals, suggesting possible liver injury. It is possible that if given high doses, many of these individuals would be susceptible to acute liver failure. There is likely to be a genetic predisposition, but finding the variants by scanning human subjects alone can be very difficult, requiring large studies with many participants. But with a little help from mice, researchers can overcome these experimental hurdles.

In this study, a team of researchers led by Dr. David Threadgill of North Carolina State University utilized mouse genetics to aid the search for candidate genes linked to acetaminophen-induced liver injury in humans. "We approached the study from the perspective that drugs are used in very heterogeneous patient populations, and that drug-induced toxicities are likely the result of a person's genetic makeup," Threadgill explained. The group used a genetically diverse population of mice to model human genetic variation, taking advantage of the known genetic differences in these strains to find genes linked to variable responses to acetaminophen treatment.

Once Threadgill and colleagues narrowed their search to a few candidate genes in mouse, they sequenced the genetic code of the counterparts of the same genes in human patients exhibiting elevated levels of serum ALT in response to acetaminophen. They found that a single letter change to the DNA sequence in one of these candidate genes, called CD44, is significantly associated with elevated serum ALT in these patients. While the role of this gene in liver toxicity is not yet known, CD44 could serve as a potentially useful marker to identify people at risk for acetaminophen-induced liver damage.

Threadgill noted that in addition to the identification of a gene linked to acetaminophen-induced liver injury, this study has broader implications for drug testing, as up until now, genetic differences in humans has not been considered in pre-clinical tests using animal models. "If genetic differences are included in early safety testing, more accurate predictions of clinical response will be obtained," said Threadgill. "The end result will be safer drugs."

###

 

Scientists from the University of North Carolina (Chapel Hill, NC), the Genomics Institute of the Novartis Research Foundation (San Diego, CA), the Jackson Laboratory (Bar Harbor, ME), the National Institute of Environmental Health Sciences (Research Triangle Park, NC), Verto Institute Research Laboratories (New Brunswick, NJ), the Cancer Institute of New Jersey (New Brunswick, NJ), Purdue Pharma (Stamford, CT), and North Carolina State University (Raleigh, NC) contributed to this study.

This work was supported by the National Institutes of Health and the Environmental Protection Agency.

Media contacts: David Threadgill, Ph.D. (threadgill@ncsu.edu, +1-919-515-2292) is available for more information.

Interested reporters may obtain copies of the manuscript from Robert Majovski, Ph.D., Assistant Editor, Genome Research (majovski@cshl.edu).

About the article: The manuscript will be published online ahead of print on May 5, 2009. Its full citation is as follows: Harrill, A.H., Watkins, P.B., Su, S., Ross, P.K., Harbourt, D.E., Stylianou, I.M., Boorman, G.A., Russo, M.W., Sackler, R.S., Harris, S.C., Contractor, T., Wiltshire, T., Rusyn, I., and Threadgill, D.W. Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humans. Genome Res. doi:10.1101/gr.090241.108.

About Genome Research:

Launched in 1995, Genome Research (www.genome.org) is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.

About Cold Spring Harbor Laboratory Press:

Cold Spring Harbor Laboratory is a private, nonprofit institution in New York that conducts research in cancer and other life sciences and has a variety of educational programs. Its Press, originating in 1933, is the largest of the Laboratory's five education divisions and is a publisher of books, journals, and electronic media for scientists, students, and the general public.

Genome Research issues press releases to highlight significant research studies that are published in the journal.

For more go to http://www.nature.com/clpt/journal/v88/n3/abs/clpt2010164a.html

Donald Rumsfeld

 

From Public Citizen at http://www.citizen.org  

 

 

INCREASING NUMBER OF FATAL ACUTE
                  LIVER FAILURE CASES LINKED TO THE 
POPULAR PAINKILLER ACETAMINOPHEN (TYLENOL) 
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

                  
                  

THOUGH VOTED TO BE ELIMINATED, THIS WAS NOT CARRIED THROUGH.  THE FDA IS AN ARM OF PhARMA

 

http://www.msnbc.msn.com/id/31664450/ns/health-more_health_news/

FDA panel votes to eliminate Vicodin, Percocet

Deadly overdoses of acetaminophen, narcotics are cited in recommendation

updated 4:16 p.m. PT, Tues., June 30, 2009

ADELPHI, Md. - Government experts say prescription drugs like Vicodin and Percocet that combine a popular painkiller with stronger narcotics should be eliminated because of their role in deadly overdoses.

A Food and Drug Administration panel on Tuesday voted 20-17 that prescription drugs that combine acetaminophen with other painkilling ingredients should be pulled off the market.

The FDA has assembled a group of experts to vote on ways to reduce liver damage associated with acetaminophen, one of the most widely used drugs in the U.S.

Despite years of educational campaigns and other federal actions, acetaminophen remains the leading cause of liver failure in the U.S., according to the FDA.

Panelists cited FDA data indicating 60 percent of acetaminophen-related deaths are related to prescription products. Acetaminophen is also found in popular over-the-counter medications like Tylenol and Excedrin.

“We’re here because there are inadvertent overdoses with this drug that are fatal and this is the one opportunity we have to do something that will have a big impact,” said Dr. Judith Kramer of Duke University Medical Center.

Many opposed to recommendation
But many panelists opposed a sweeping withdraw of products that are so widely used to control severe, chronic pain.

“To make this shift without very clear understanding of the implications on the management of pain would be a huge mistake,” said Dr. Robert Kerns of Yale University.

In a separate vote, the panel voted overwhelmingly, 36-1, that if the drugs stay on the market they should carry a black box warning, the most serious safety label available.

The FDA is not required to follow the advice of its panels, though it usually does.

Prescription acetaminophen combination drugs were prescribed 200 million times last year, according to FDA data. Vicodin is marketed by Abbott Laboratories, while Percocet is marketed by Endo Pharmaceuticals. Both painkillers also are available in cheaper generic versions.

The FDA convened the two-day meeting to ask experts to discuss and vote on a slew of proposals to reduce overdoses with acetaminophen. The drug has been on the market for about 50 years and many patients find it easier on the stomach than ibuprofen and aspirin, which can cause ulcers.

Panel voted to lower maximum acetaminophen dose
Earlier in the day, panelists took aim at safety problems with Tylenol and dozens of other over-the-counter painkillers. In a series of votes, the panel endorsed lowering the maximum dose of those products.

FDA’s experts voted 21-16 to lower the current maximum daily dose of nonprescription acetaminophen, which is 4 grams, or eight pills of a medication like Extra Strength Tylenol.

The group was not asked to recommend an alternative maximum daily dose.

The panel also voted 24-13 to limit the maximum single dose of the drug to 650 milligrams. The current single dose of Johnson & Johnson’s Extra Strength Tylenol is 1,000 milligrams, or two tablets.

In a third vote, a majority of panelists said the 1,000-milligram dose should only be available by prescription.

However, panelists rejected a proposal to pull certain cold and cough medicines off the market because of their role in overdosing.

The drugs in question, such as Procter & Gamble’s NyQuil or Novartis’ Theraflu, combine acetaminophen with other ingredients that treat cough and runny nose.

The FDA says patients often pair the cold medications with pure acetaminophen drugs, like Tylenol, exposing themselves to unsafe levels of the drug.

But panelists cited FDA data that said the medications play a minor role in acetaminophen overdoses, with only 10 percent of acetaminophen-related deaths involving a cold and cough product.

“I don’t think we should be advocating a solution to a problem that really is not there,” said Dr. Osemwota Omoigui, of the Los Angeles pain clinic.

The panel voted 24-13 to keep the products on the market.

 

 

 

 

 

 

 
Research published in the December
                  2005 issue of the medical journal 
Hepatology found that the annual percentage of potentially fatal acute 
liver failure (ALF)
                  cases caused by acetaminophen (TYLENOL) rose from 28 
percent in 1998 to 51 percent in 2003.  The research was conducted by 
the Division of
                  Gastroenterology at the University of Washington
                  Medical 
Center, Seattle WA. 
                  The facility is part of the U.S. Acute Liver 
Failure Study Group (ALFSG), a consortium of 22 academic medical centers 
that monitor cases
                  of liver toxicity around the country. 
 
The ALFSG collected information on all cases of acute liver failure 
that occurred between
                  Jan. 1, 1998 and Dec.
                  31, 2003, including outcome 
information.  A careful history of each patient's acetaminophen use, 
including the total
                  dose, the type of product used, and the duration of 
use, was obtained where possible. 
 
The researchers identified a total of 662 patients during the six year 
study period who met the criteria
                  for acute liver failure. Of these 662 
patients, in 275 (42%) cases, liver failure was found to have resulted 
from acetaminophen-induced liver
                  toxicity. The fraction
                  rose from 28% 
in 1998 to 51% in 2003, almost doubling in five years. The median total 
dose of acetaminophen
                  taken by these patients was 24 grams, the 
equivalent of 48 extra-strength acetaminophen tablets.  Unintentional overdoses were responsible for 131 (48%) of the
                  acute liver failure cases. Intentional overdoses, or suicide attempts, accounted for 122 (44%) episodes. In 22 (8%) of the cases, the intent was unknown.
                  Of the 131 patients who overdosed unintentionally, 38% took two or more acetaminophen containing products simultaneously, and 63% used narcotic combination painkillers
                  that contained acetaminophen.  Overall, 178 (65%) of 275 patients identified as having acetaminophen-induced liver toxicity survived. Seventy-four
                  (27%) died without a liver transplantation, and 23 (8%) patients underwent a liver transplantation 
operation. 
 
The authors of the
                  study concluded: “...acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States.”  They also stated that efforts
                  to limit OTC package size and to restrict the prescription of narcotic-acetaminophen combinations (or to separate the narcotic
                  from the acetaminophen) may be necessary to reduce the incidence of this increasingly recognized but preventable cause of
                  ALF in the United States. Educational
                  programs for practicing physicians, pharmacists, and consumers, involving a full discussion of the hazards of this ubiquitous
                  pain reliever and the identification of susceptible groups, seems warranted. 
 
In testimony before an FDA advisory committee on
                  this topic more than 
three years ago, Health Research Group Deputy Director Dr. Peter Lurie 
made several similar
                  suggestions, as well as some others, to reduce the 
terrible toll of acetaminophen-induced liver failure. That testimony is 
available on our web site at http://www.citizen.org/publications/release.cfm?ID=7202. 
 
Drug induced injury or death is a tragedy because, as is the case with 
acetaminophen, most
                  of the time the toxicity of the drugs causing 
injury or death is known.  It is even more troubling when the drug-induced
                  
injury or death is unintentional. In the case of acetaminophen, this can 
occur in patients who are taking a prescription
                  narcotic combined with 
acetaminophen as directed by their physicians if they also take acetaminophen-containing over-the-counter
                  (OTC) products. This can happen even if these patients follow the instructions on the label of the product.  {What troubles me is the fact that acetaminophen has little if any
                  medicinal use—it is not an anti-inflamitory like the NSAIDs including aspirin, and it doesn’t dull pain like opiates. 
                  It is a dangerous placebo.—jk}   
 
The amount of acetaminophen contained in OTC drugs is clearly listed on 
the label. 
                  Always read these labels before taking any OTC drug to make 
sure you are not taking acetaminophen (or any other
                  drug) in more than 
one product.  If you are prescribed a prescription painkiller, it is 
likely that it is
                  a combination of a narcotic drug with acetaminophen.  
Lortab, Percocet, and Tylox are a few examples
                  of widely-prescribed 
acetaminophen-containing painkillers.  If you are prescribed a painkiller, 
ask your pharmacist
                  if it also contains acetaminophen.  Mixing OTC 
drugs and prescription painkillers may result in too much acetaminophen 
being taken.    
                  
 
Alcohol in combination with acetaminophen can increase the risk of 
liver toxicity. 
                  All OTC drugs that contain acetaminophen have the 
following warning on their labels: 
 
      Warnings  
       
      Alcohol
                  warning: If you consume 3 or more alcoholic drinks every 
day, ask your doctor whether you should take acetaminophen
                  or other 
pain relievers/fever reducers. Acetaminophen may cause liver damage. 
       
       
 
What You Can
                  Do 
 
To prevent acetaminophen overdose, you should carefully read the labels 
on all OTC drug
                  products to see if they contain acetaminophen. If you 
are prescribed a prescription painkiller, ask your pharmacist if it 
contains acetaminophen.
                  Do not take OTC products that contain acetaminophen 
if you are taking an acetaminophen-containing painkiller. Do not take 
more than one acetaminophen-containing
                  drug, prescription or otherwise.  
 
If you or a family member develop any of the symptoms of potential 
liver toxicity,
                  stop taking all acetaminophen-containing products and call 
your physician immediately. These symptoms are:
                  
 
* Pruritus (itchy skin)
* Jaundice (yellowing of the skin or whites of the eyes)
* Dark urine
* Upper right-sided
                  abdominal tenderness (location of the liver)
* Unexplained "flu-like" symptoms