FDA Panel Recommends Acetaminophen Restrictions

An FDA advisory panel has recommended that the agency remove prescription drugs that combine acetaminophen and powerful painkillers -- such as Percocet, which is formulated with oxycodone, and Vicodin, which is formulated with hydrocodone -- from the market because of the risk of liver injury associated with misuse of the products. The panel also voted to lower dosage recommendations for over-the-counter, or OTC, acetaminophen products.

Gerald Dal Pan, M.D., M.H.S., director of the Office of Surveillance and Epidemiology in the FDA's Center for Drug Evaluation and Research, or CDER, said during a June 30 media briefing that the agency would review the discussions and votes from a two-day joint meeting of its Drug Safety and Risk Management, Nonprescription Drugs, and Anesthetic and Life Support Drugs advisory committees.

However, the FDA is not bound to accept the recommendations of its expert committees.

"Whatever we do on any of these options will affect how acetaminophen is prescribed or administered or purchased," Dal Pan said. "It will affect the whole health care system -- pharmacies, pharmacists, physicians. It's a systemwide issue."

The FDA has been working for years to reduce the incidence of liver injury associated with acetaminophen misuse through such venues as labeling changes and educational programs. Dal Pan said the agency reviewed the results of those initiatives in 2007 and determined that additional action was necessary.

According to the FDA, more than 28 billion doses of acetaminophen-containing products are purchased each year in the United States, and acetaminophen-hydrocodone combination products have been the most frequently prescribed products for the past 12 years.

The expert panel voted 20-17 to remove the prescription combination products from the market.

That decision got mixed reviews from physicians in widespread media coverage. Randy Wexler, M.D., an assistant professor of clinical family medicine at Ohio State University College of Medicine, Columbus, and a health policy expert, told AAFP News Now that although patient education and improved labeling are needed, the recommendation to eliminate the products went too far.

"It complicates treatment," he said, "and it doesn't educate the patient about what the problem is in the first place." If FDA officials accept the panel's recommendation, Wexler added, physicians will need to educate patients about their options.

"The first thing is we need to do is reassure the patient that medications will still be on the market that contain the same pain medications they have been taking -- minus the acetaminophen," he said. "The second thing is that acetaminophen can still be taken with it, and we can discuss the dose with them."

One suggestion Wexler offered to reduce the risk of overdose: Suggest patients use pill boxes or calendars.

The FDA panel recommended two options if the agency allows the combination prescription products to stay on the market. In a 27-10 vote, the panel recommended that "unit-of-use" packages be required, and in a 36-1 vote, it recommended the FDA require a boxed warning for such products.

The agency's panel also made several recommendations related to acetaminophen-containing OTC products. Among them:

Although the panel recommended eliminating prescription combination products, it voted 24-13 against eliminating OTC combination products. According to Dal Pan, that's because problems with combination prescription drugs clearly were more prevalent.

Sandra Kweder, M.D., deputy director of the Office of New Drugs at CDER, said if recommendations for changes in dosage are approved by the FDA, the agency will be required to go through the federal rule-making process. She noted that product manufacturers could make voluntary changes much faster than the agency could complete that process.

Manufacturers, however, might not be lining up to cooperate.

McNeil Consumer Healthcare, which markets Tylenol, posted a letter to health care professionals (1-page PDF; About PDFs) objecting to the panel's recommendations to reduce the maximum single dose of OTC acetaminophen to 650 mg and to make the 1,000 mg dose available only by prescription.

"Specifically, we believe the committee's recommendations, if implemented, will lead to serious and more frequent adverse events if patients shift to other OTC analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs)," says the letter. "As you know, and as the FDA stated in its own assessment, the risk of liver injury with acetaminophen is related to overdose, whereas risks associated with NSAIDs, such as gastrointestinal bleeding and renal injury, occur at recommended doses."

Wexler acknowledged that the FDA recommendations might lead some consumers to think that NSAIDs are safer than acetaminophen, which he said is not the case if acetaminophen is used properly.

Wexler agreed that aspirin and other NSAIDs can cause bleeding ulcers and kidney problems. He also said that patients who take daily "baby aspirin" for cardiovascular disease and who also have pain issues should not switch from acetaminophen to an NSAID unless advised to do so by their physicians.