FDA Panel Addresses Acetaminophen Toxicity

ADELPHI, MD. — Clinicians should educate their patients about the potential for hepatotoxicity with acetaminophen and make sure they understand acetaminophen is the active ingredient in Tylenol and is contained in many combination over-the-counter and prescription products, a Food and Drug Administration representative said at an advisory panel meeting on the topic.

During a briefing held after the meeting, Dr. Sandra Kweder, deputy director of the Office of New Drugs in the FDA's Center for Drug Evaluation and Research (CDER), said that there are multiple components to the problem and there is “probably not one [individual] thing that will reverse the trend of acetaminophen-related liver toxicity.”

The FDA convened the joint meeting of its Drug Safety and Risk Management Advisory Committee, Nonprescription Drugs Advisory Committee, and Anesthetic and Life Support Drugs Advisory Committee to seek input from a variety of specialists on different options proposed by the agency to address the ongoing problem of acetaminophen-induced liver injury.

At the meeting, the majority of the panel recommended major changes to acetaminophen-containing products, including lowering the maximum daily dose and single adult dose of acetaminophen in nonprescription products, limiting pediatric liquid formulations to only one concentration, and adding a boxed warning about the risk of liver damage to prescription acetaminophen combination products.

In other votes, the majority of the panel, in a 24-13 vote, did not support eliminating over-the-counter acetaminophen combination products.

But in a 20-17 vote, the panel narrowly voted to recommend the elimination of prescription products containing a combination of acetaminophen and other drugs such as oxycodone (Percocet) and hydrocodone. The hydrocodone-acetaminophen combination, which includes Vicodin, is the most commonly prescribed pain medication in the United States, and was identified as a common cause of acetaminophen-induced hepatotoxicity and the cause of many deaths related to liver failure.

Acetaminophen-induced hepatotoxicity is usually related to both unintentional and intentional ingestions of products containing acetaminophen that exceeds the maximum daily dose of 4 g/day, Dr. Gerald Dal Pan, director of CDER's Office of Surveillance and Epidemiology, said at the meeting.

Among the data from different speakers and sources presented at the meeting was a survey of emergency departments (EDs) that found that 50% (54,743) of acetaminophen-related visits to EDs in 2006-2007 were the result of “self-harm, of which almost half involved opioid-analgesic combinations, and 38% involved single-ingredient acetaminophen products. Almost 14,000 (10%) were for unsupervised ingestions among children under age 10, and about 13,000 (12%) were other types of unintentional overdoses.

Acetaminophen products account for about 640 cases of acute liver failure every year in the United States, according to the Centers of Disease Control and Prevention. In addition, 5% of calls to poison control centers in 2005 involved acetaminophen; 37% of those calls were in children under age 6 years, and 60% of the cases were unintentional.

In a 21-16 vote, the panel also recommended that the maximum daily dose of 4 g of acetaminophen recommended for nonprescription single-ingredient and combination products be reduced, and they voted 24-13 that the maximum nonprescription single adult dose be limited to 650 mg (two 325-mg tablets).

The panel voted 26-11 that the current acetaminophen OTC dosage—two doses of 500 mg—be switched to prescription status. Some panelists voting against this switch said it would create a barrier for some patients, particularly the elderly, to getting the medication, while some of those voting for the switch said it would provide an opportunity for direct discussion with patient about their pain.

The FDA usually follows its advisory panels' advice, which is not binding.

ADELPHI, MD. — Clinicians should educate their patients about the potential for hepatotoxicity with acetaminophen and make sure they understand acetaminophen is the active ingredient in Tylenol and is contained in many combination over-the-counter and prescription products, a Food and Drug Administration representative said at an advisory panel meeting on the topic.

During a briefing held after the meeting, Dr. Sandra Kweder, deputy director of the Office of New Drugs in the FDA's Center for Drug Evaluation and Research (CDER), said that there are multiple components to the problem and there is “probably not one [individual] thing that will reverse the trend of acetaminophen-related liver toxicity.”

The FDA convened the joint meeting of its Drug Safety and Risk Management Advisory Committee, Nonprescription Drugs Advisory Committee, and Anesthetic and Life Support Drugs Advisory Committee to seek input from a variety of specialists on different options proposed by the agency to address the ongoing problem of acetaminophen-induced liver injury.

At the meeting, the majority of the panel recommended major changes to acetaminophen-containing products, including lowering the maximum daily dose and single adult dose of acetaminophen in nonprescription products, limiting pediatric liquid formulations to only one concentration, and adding a boxed warning about the risk of liver damage to prescription acetaminophen combination products.

In other votes, the majority of the panel, in a 24-13 vote, did not support eliminating over-the-counter acetaminophen combination products.

But in a 20-17 vote, the panel narrowly voted to recommend the elimination of prescription products containing a combination of acetaminophen and other drugs such as oxycodone (Percocet) and hydrocodone. The hydrocodone-acetaminophen combination, which includes Vicodin, is the most commonly prescribed pain medication in the United States, and was identified as a common cause of acetaminophen-induced hepatotoxicity and the cause of many deaths related to liver failure.

Acetaminophen-induced hepatotoxicity is usually related to both unintentional and intentional ingestions of products containing acetaminophen that exceeds the maximum daily dose of 4 g/day, Dr. Gerald Dal Pan, director of CDER's Office of Surveillance and Epidemiology, said at the meeting.

Among the data from different speakers and sources presented at the meeting was a survey of emergency departments (EDs) that found that 50% (54,743) of acetaminophen-related visits to EDs in 2006-2007 were the result of “self-harm, of which almost half involved opioid-analgesic combinations, and 38% involved single-ingredient acetaminophen products. Almost 14,000 (10%) were for unsupervised ingestions among children under age 10, and about 13,000 (12%) were other types of unintentional overdoses.

Acetaminophen products account for about 640 cases of acute liver failure every year in the United States, according to the Centers of Disease Control and Prevention. In addition, 5% of calls to poison control centers in 2005 involved acetaminophen; 37% of those calls were in children under age 6 years, and 60% of the cases were unintentional.

In a 21-16 vote, the panel also recommended that the maximum daily dose of 4 g of acetaminophen recommended for nonprescription single-ingredient and combination products be reduced, and they voted 24-13 that the maximum nonprescription single adult dose be limited to 650 mg (two 325-mg tablets).

The panel voted 26-11 that the current acetaminophen OTC dosage—two doses of 500 mg—be switched to prescription status. Some panelists voting against this switch said it would create a barrier for some patients, particularly the elderly, to getting the medication, while some of those voting for the switch said it would provide an opportunity for direct discussion with patient about their pain.

The FDA usually follows its advisory panels' advice, which is not binding.

ADELPHI, MD. — Clinicians should educate their patients about the potential for hepatotoxicity with acetaminophen and make sure they understand acetaminophen is the active ingredient in Tylenol and is contained in many combination over-the-counter and prescription products, a Food and Drug Administration representative said at an advisory panel meeting on the topic.

During a briefing held after the meeting, Dr. Sandra Kweder, deputy director of the Office of New Drugs in the FDA's Center for Drug Evaluation and Research (CDER), said that there are multiple components to the problem and there is “probably not one [individual] thing that will reverse the trend of acetaminophen-related liver toxicity.”

The FDA convened the joint meeting of its Drug Safety and Risk Management Advisory Committee, Nonprescription Drugs Advisory Committee, and Anesthetic and Life Support Drugs Advisory Committee to seek input from a variety of specialists on different options proposed by the agency to address the ongoing problem of acetaminophen-induced liver injury.

At the meeting, the majority of the panel recommended major changes to acetaminophen-containing products, including lowering the maximum daily dose and single adult dose of acetaminophen in nonprescription products, limiting pediatric liquid formulations to only one concentration, and adding a boxed warning about the risk of liver damage to prescription acetaminophen combination products.

In other votes, the majority of the panel, in a 24-13 vote, did not support eliminating over-the-counter acetaminophen combination products.

But in a 20-17 vote, the panel narrowly voted to recommend the elimination of prescription products containing a combination of acetaminophen and other drugs such as oxycodone (Percocet) and hydrocodone. The hydrocodone-acetaminophen combination, which includes Vicodin, is the most commonly prescribed pain medication in the United States, and was identified as a common cause of acetaminophen-induced hepatotoxicity and the cause of many deaths related to liver failure.

Acetaminophen-induced hepatotoxicity is usually related to both unintentional and intentional ingestions of products containing acetaminophen that exceeds the maximum daily dose of 4 g/day, Dr. Gerald Dal Pan, director of CDER's Office of Surveillance and Epidemiology, said at the meeting.

Among the data from different speakers and sources presented at the meeting was a survey of emergency departments (EDs) that found that 50% (54,743) of acetaminophen-related visits to EDs in 2006-2007 were the result of “self-harm, of which almost half involved opioid-analgesic combinations, and 38% involved single-ingredient acetaminophen products. Almost 14,000 (10%) were for unsupervised ingestions among children under age 10, and about 13,000 (12%) were other types of unintentional overdoses.

Acetaminophen products account for about 640 cases of acute liver failure every year in the United States, according to the Centers of Disease Control and Prevention. In addition, 5% of calls to poison control centers in 2005 involved acetaminophen; 37% of those calls were in children under age 6 years, and 60% of the cases were unintentional.

In a 21-16 vote, the panel also recommended that the maximum daily dose of 4 g of acetaminophen recommended for nonprescription single-ingredient and combination products be reduced, and they voted 24-13 that the maximum nonprescription single adult dose be limited to 650 mg (two 325-mg tablets).

The panel voted 26-11 that the current acetaminophen OTC dosage—two doses of 500 mg—be switched to prescription status. Some panelists voting against this switch said it would create a barrier for some patients, particularly the elderly, to getting the medication, while some of those voting for the switch said it would provide an opportunity for direct discussion with patient about their pain.

The FDA usually follows its advisory panels' advice, which is not binding.