FDA panel backs cut in maximum Tylenol dosage

It is one of the world's most popular drugs, considered safe to treat fevers in children and aches and pains in pregnant women.

But yesterday, the U.S. Food and Drug Administration took action aimed at making consumers more aware that acetaminophen, best known as the Johnson & Johnson drug Tylenol, can be as hazardous as it is ubiquitous.

An FDA panel of outside experts voted, 21 to 16, to lower doses of acetaminophen because it can cause liver damage.

The advisory panel recommended decreasing the maximum daily dose to 2,600 milligrams from 4,000 milligrams. A single pill of a medication such as Extra Strength Tylenol is 500 milligrams.

The FDA cited research showing that acetaminophen overdoses led to 56,000 emergency-room visits, 26,000 hospitalizations, and 458 deaths from 1990 through 1998.

Some overdoses were suicide attempts, but many were accidental and happened because patients took more than one product containing acetaminophen, an ingredient in products ranging from NyQuil to Kosher Care Pain Relief.

The FDA panel also recommended banning the prescription painkillers Percocet and Vicodin, both of which contain acetaminophen.

Endo Pharmaceuticals Holdings Inc. of Chadds Ford makes Percocet. The company plans to work with the FDA to find a way to keep the drug, which brought in $129 million in sales last year, on the market, Endo spokesman Kevin Wiggins said.

Abbott Laboratories of Illinois makes Vicodin.

The FDA is not required to follow the advisory panel's advice, but it usually does. It is not clear when the agency will issue its final decision.

The panel also voted to make the 1,000-milligram dose of acetaminophen available only by prescription.

U.S. consumers spend $2.6 billion yearly on 28 billion doses of products containing acetaminophen, the FDA said, citing data from IMS Health.

McNeil Consumer Healthcare, the Fort Washington unit of Johnson & Johnson that makes Tylenol, said in a statement that it disagreed with the panel's decision.

In its statement, McNeil said it worried the vote would lead consumers to use other pain relievers, which have their own risks. Alternatives such as aspirin can cause gastrointestinal bleeding, for example.

"The safety and efficacy of acetaminophen has been established in over 150 clinical studies and is supported by over 50 years of clinical use," McNeil said.

Cesar Alaniz, a clinical pharmacist and associate professor at the University of Michigan, said that the drug was safe at recommended doses, but that his research showed that consumers were ignorant about how to use it safely. "The problem is that not enough of the public knows what a potential toxic dose is," he said.

He was coauthor of a study that looked at 128 adult patients who overdosed on acetaminophen. About 60 percent of those overdoses were intentional. Among those who took too much acetaminophen by accident, many had chronic back or migraine pain.

"They had debilitating pain and out of frustration take too much acetaminophen," Alaniz said.

In another study that he coauthored, 104 patients visiting a general internal-medicine clinic run by the University of Michigan Health System said they had used acetaminophen in the last six months, but almost none could identify the maximum daily dose of either regular or extra-strength preparations of the drug. Nearly 70 percent of patients underestimated maximum doses.

The FDA panel's recommendation to lower doses made sense, Alaniz said.

"You don't really ever know for sure whether you need to take higher doses," he said, "so if you can relieve a headache with one tablet, that's better than two."

The connection between acetaminophen and liver damage has been on the FDA's radar screen for years. The consumer-advocacy group Public Citizen has been pushing the FDA to reduce recommended doses of the drug since at least 2002.

Sidney Wolfe, director of Public Citizen Health Research Group and a member of the FDA panel that voted yesterday, said a similar panel first had recommended adding a warning about the risk of liver damage to labels of drugs containing acetaminophen 32 years ago.

The FDA finally insisted on those warnings in April, a precursor to yesterday's recommendation on dosage.

Wolfe said that he wasn't sure why the action had taken so long, but guessed that industry pressure on the FDA had played a role.