Post by unlawflcombatnt on Jul 4, 2009 10:49:09 GMT -6
from Yahoo News
FDA panel recommends smaller doses of painkillers
By MATTHEW PERRONE,
"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% of acetaminophen-related deaths are related to prescription products.
[This suggests that 60% of those deaths are from a combination of acetaminophen with another drug, such as codeine, hydrocodone, oxycodone, or hydromorphone. The significance to this is that many people are addicted to the opiate that comes in combination with acetaminophen, and ingest toxic amounts of the acetaminophen by trying take in more of the opiate it's combined with.]
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.
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 2-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."
[Vicoprofen is one example of a drug that contains ibuprofen instead of acetaminophen, in combination with the opiate hydrocodone. This is one way to avoid any chance of acetaminophen liver toxicity.]
"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....."
[It was previously believed that it took >10 grams/day of acetaminophen to cause liver toxicity. Liver toxicity is rarely reported with daily doses of acetaminophen of less than 10 grams.]
"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 3rd 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."
[Yes, and they may deliberately take too much of BOTH medications. However, this situation pails in comparison to those who take too much because of its being taken in combination with opiates.]
"But panelists cited FDA data that said the medications play a minor role in acetaminophen overdoses, with only 10% of acetaminophen-related deaths involving a cold and cough product.
[Again, that's because the largest number of overdoses occur from opiate addicts--who take acetaminophen in combination with codeine, hydrocodone, oxycodone, and hydromorphone.]
"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 "problem" is that there are a lot of doctor-created opiate addicts out there, who're getting acetaminophen toxicity by taking excessive doses of the opiate its combined with.]
The panel voted 24-13 to keep the products on the market."
------------------------------------------
A brief note on Acetaminophen toxicity.
Acetaminophen is metabolized by the liver via 2 metabolic pathways. The 1° pathway for hepatic metabolism produces non-toxic metabolites. The 2° pathway, however, produces hepatotoxic metabolites. The 1° pathway metabolizes acetaminophen almost exclusively, until a certain threshold level is reached, when that metabolic pathway becomes saturated. Once the 1° pathway is saturated, metabolism begins occurring in the 2° (and toxic) pathway. The 1° pathway's saturation level was previously put at 10 grams (10,000 mg.) per day. Below the threshold level, however, there is thought to be absolutely 0 toxicity.
Acetaminophen toxicity is like falling off a cliff. There's no problem, regardless of how close you get to the cliff. It's only when you get far enough out to fall off that you have a problem.
The point is that acetaminophen is not toxic at all below the threshold level. It does not cause cumulative damage to take 3 grams of Tylenol per day for 10, 20, or 100 years. It's only toxic when its daily threshold level is exceeded. (regardless of what that level has been determined to be.)
Patients should not live in fear of taking too much Tylenol/Acetaminophen over time. The effects are not cumulative. It's still unlikely that hepatotoxicity will occur below a level of 10,000 mg. day, even if you take it every day for the rest of your life. If you don't saturate the 1° pathway, you do absolutely no damage to your liver.
news.yahoo.com/s/ap/20090630/ap_on_he_me/us_tylenol_safety_fda
FDA panel recommends smaller doses of painkillers
By MATTHEW PERRONE,
"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% of acetaminophen-related deaths are related to prescription products.
[This suggests that 60% of those deaths are from a combination of acetaminophen with another drug, such as codeine, hydrocodone, oxycodone, or hydromorphone. The significance to this is that many people are addicted to the opiate that comes in combination with acetaminophen, and ingest toxic amounts of the acetaminophen by trying take in more of the opiate it's combined with.]
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.
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 2-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."
[Vicoprofen is one example of a drug that contains ibuprofen instead of acetaminophen, in combination with the opiate hydrocodone. This is one way to avoid any chance of acetaminophen liver toxicity.]
"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....."
[It was previously believed that it took >10 grams/day of acetaminophen to cause liver toxicity. Liver toxicity is rarely reported with daily doses of acetaminophen of less than 10 grams.]
"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 3rd 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."
[Yes, and they may deliberately take too much of BOTH medications. However, this situation pails in comparison to those who take too much because of its being taken in combination with opiates.]
"But panelists cited FDA data that said the medications play a minor role in acetaminophen overdoses, with only 10% of acetaminophen-related deaths involving a cold and cough product.
[Again, that's because the largest number of overdoses occur from opiate addicts--who take acetaminophen in combination with codeine, hydrocodone, oxycodone, and hydromorphone.]
"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 "problem" is that there are a lot of doctor-created opiate addicts out there, who're getting acetaminophen toxicity by taking excessive doses of the opiate its combined with.]
The panel voted 24-13 to keep the products on the market."
------------------------------------------
A brief note on Acetaminophen toxicity.
Acetaminophen is metabolized by the liver via 2 metabolic pathways. The 1° pathway for hepatic metabolism produces non-toxic metabolites. The 2° pathway, however, produces hepatotoxic metabolites. The 1° pathway metabolizes acetaminophen almost exclusively, until a certain threshold level is reached, when that metabolic pathway becomes saturated. Once the 1° pathway is saturated, metabolism begins occurring in the 2° (and toxic) pathway. The 1° pathway's saturation level was previously put at 10 grams (10,000 mg.) per day. Below the threshold level, however, there is thought to be absolutely 0 toxicity.
Acetaminophen toxicity is like falling off a cliff. There's no problem, regardless of how close you get to the cliff. It's only when you get far enough out to fall off that you have a problem.
The point is that acetaminophen is not toxic at all below the threshold level. It does not cause cumulative damage to take 3 grams of Tylenol per day for 10, 20, or 100 years. It's only toxic when its daily threshold level is exceeded. (regardless of what that level has been determined to be.)
Patients should not live in fear of taking too much Tylenol/Acetaminophen over time. The effects are not cumulative. It's still unlikely that hepatotoxicity will occur below a level of 10,000 mg. day, even if you take it every day for the rest of your life. If you don't saturate the 1° pathway, you do absolutely no damage to your liver.
news.yahoo.com/s/ap/20090630/ap_on_he_me/us_tylenol_safety_fda