Drugmakers May Limit Doses, Add Warnings for Tylenol (Update3)

By Catherine Larkin



May 27 (Bloomberg) -- Drugmakers should limit doses and strengthen warnings on Johnson and Johnson’s Tylenol and other medicines containing acetaminophen to reduce the risk of liver injury, according to a U.S. report.

The recommendations are part of a working group report posted today on the Food and Drug Administration’s Web site. Acetaminophen, used to reduce pain and fever, is sold under the brand name Tylenol, as a generic, and in combination products including Abbott Laboratories’ prescription painkiller Vicodin. The report recommends eliminating acetaminophen from over-the- counter combination products, such as Tylenol Cold.

Liver injury has been a known risk of acetaminophen since the late 1990s, and efforts to educate consumers and revise prescribing information have been unsuccessful, the FDA said. While the agency doesn’t want to discourage appropriate use, the proposed restrictions may prevent accidental overdose.

“We know patients will not always take drugs appropriately and according to directions,” members of the FDA working group wrote in their report, dated Feb. 26, 2008. “It is important, however, to initiate measures that could to the extent possible decrease the number of unintentional overdose cases.”

The agency has asked members of its advisory panels on drug safety, anesthetic and life-support drugs, and nonprescription drugs to meet June 29-30 in Adelphi, Maryland, to discuss the group’s recommendations on over-the-counter and prescription medicines containing acetaminophen and how they may be implemented. The internal report was released in conjunction with the meeting, said Karen Riley, an FDA spokeswoman.

J&J’s Tylenol Products

J&J, of New Brunswick, New Jersey, is the world’s biggest maker of health-care products. Its sales of over-the-counter drugs, including Tylenol, and nutritional products rose 15 percent to $5.9 billion last year. The company didn’t specify sales of its Tylenol family of products in its annual report.

J&J said Tylenol, taken properly, is safe for consumers and the company will continue to work with regulators to find ways to reduce the potential for taking too much acetaminophen, according to an e-mailed statement from its McNeil Consumer Healthcare unit.

“While we share the FDA’s mutual goal of preventing and decreasing the misuse and overdose of acetaminophen, we have concerns that some of the FDA recommendations could discourage appropriate use and are not necessary to addressing the root causes of acetaminophen overdose,” the company said in the statement.

Liver Failure

Acetaminophen overdose was linked to 458 deaths and 26,000 hospitalizations annually from 1990 to 2001, according to the FDA report. The drug is a leading cause of acute liver failure in the U.S., the agency said.

The Consumer Healthcare Products Association, a Washington- based trade group representing makers of over-the-counter drugs, said in an e-mailed statement it “looks forward to working with the FDA and other interested parties to further build awareness among consumers about how to safely and effectively use acetaminophen.”

The working group, made up of 12 top officials in the FDA’s Center for Drug Evaluation and Research, recommended lowering immediate-release tablet strength to no more than 325 milligrams from the current 500 milligrams and reducing the single adult dose to 650 milligrams, from 1,000 milligrams. They also urged decreasing the maximum daily dose of all acetaminophen to 3,250 milligrams from 4,000 milligrams.

Multiple Combinations

The recommendation on combination products would cut over- the-counter sales of acetaminophen by about half, according to the report. Consumers may not recognize acetaminophen in products without the Tylenol name and end up taking multiple combinations with the medicine, the working group said.

“Even though the percentage of cases of acute liver failure resulting from the use of two OTC products is relatively low, it is difficult to justify any cases because these products are available only for convenience.” they wrote.

The group also called for limiting liquid formulations of acetaminophen for children to one mid-strength concentration instead of multiple doses available now. They also advised adding more warnings about liver risks to drugs’ prescribing information, especially for alcohol users or people with liver disease.

To contact the reporter on this story: Catherine Larkin in Washington at clarkin4@bloomberg.net.