FDA Limits Acetaminophen in Combo Prescription Products

Sets 325 mg maximum in order to lower risk of liver toxicity; also requesting boxed warning

15 jan 2011-- The U.S. Food and Drug Administration is requesting that manufacturers of prescription combination products containing acetaminophen limit the amount of acetaminophen to a maximum of 325 mg in each tablet or capsule to reduce the risk of liver toxicity. In addition, the agency is directing manufacturers to update labels of all prescription combination products to warn consumers of the possible risk for severe liver injury.

Combination prescription products that contain acetaminophen may also contain codeine (Tylenol with Codeine), oxycodone (Percocet), and hydrocodone (Vicodin). According to the FDA, the risk of severe liver injury appears to be highest among those who take more than the prescribed dose of an acetaminophen-containing product in a 24-hour period, take more than one acetaminophen-containing product at the same time, or consume alcohol while taking acetaminophen products. The current maximum dose is 4,000 mg within 24 hours.

Over the next three years, higher dose prescription products containing acetaminophen will be phased out, but this poses no threat of a shortage of pain medication, according to the FDA. The FDA is also proposing a boxed warning to be added to the label of acetaminophen prescription products. Acetaminophen is also available over-the-counter (OTC) alone or in combination with other OTC ingredients, such as cough and cold ingredients. The FDA action regarding prescription acetaminophen products is not intended to impact the use of OTC acetaminophen products.

"There is no immediate danger to patients who take these combination pain medications and they should continue to take them as directed by their health care provider," Sandra Kweder, M.D., deputy director of the Office of New Drugs in FDA's Center for Drug Evaluation and Research, said in a statement.

Research shows safe dosages of common pain reliever may help prevent conditions related to aging

HUNTINGTON, W.Va., 24 sept 2009 – Recent studies conducted by Dr. Eric Blough and his colleagues at Marshall University have shown that use of the common pain reliever acetaminophen may help prevent age-associated muscle loss and other conditions.

Their study examined how acetaminophen may affect the regulation of protein kinase B (Akt), an enzyme known to play an important role in regulation of cellular survival, proliferation and metabolism.

The researchers' data indicates that aging skeletal muscles experience a decrease in the proper functioning of the enzyme and that acetaminophen intervention in aged animals could be used to restore Akt activity to a level comparable to that seen in young animals. In turn, this improvement in Akt activity was associated with improvements in muscle cell size and decreased muscle cell death.

"Using a model that closely mimics many of the age-associated physiological changes observed in humans, we were able to demonstrate that chronic acetaminophen treatment in a recommended dosage is not only safe but might be beneficial for the treatment of the muscle dysfunction many people experience as they get older," said Blough, an associate professor in the university's Department of Biological Sciences.

The lab's work, which was published in the July 29 issue of the international research journal PLoS One, is the first study to show that acetaminophen ingestion, at least in animals, can be safely used for the treatment of age-related muscle loss. This finding could have far-reaching implications, given the fact that people age 65 and older make up the fastest-growing segment of the U.S. population.

Additional research in their laboratory, which was published in the March issue of the journal Diabetes/Metabolism Research and Reviews, demonstrates the medication may also be useful in diminishing the severity of age-associated hyperglycemia, commonly referred to as high blood sugar.

"It is thought that acetaminophen may exert its action by decreasing the amount of reactive oxygen species," explained Dr. Miaozong Wu, the lead author and a postdoctoral fellow in Blough's lab. "Given the finding that increases in reactive oxygen species may play a role in the development of several age-associated disorders, it is possible that acetaminophen could be used to treat many different types of conditions."

Dr. John Maher, vice president for research and executive director of the Marshall University Research Corporation, said, "These findings are yet another indication that Marshall's researchers are conducting vital research in areas of great importance to human health and safety. I could not be more pleased and wish Dr. Blough and his team continued success."

According to Blough, scientists in his lab will now turn their attention to examining other physiological systems, such as the heart and blood vessels, to see if acetaminophen therapy might have similar benefits for people with cardiovascular disease.

FDA group recommends acetaminophen liver warnings

NEW YORK, 28 may 2009 – A Food and Drug Administration report released Wednesday recommends stronger warnings and dose limits on drugs containing the painkiller acetaminophen, citing an increased risk of liver injury.

The recommendation covers both prescription doses and over-the-counter medication, of which Johnson & Johnson's Tylenol is the most well-known. Acetaminophen is also widely available as a generic over-the-counter drug.

"There is extensive evidence that hepatotoxicity (liver toxicity) caused by acetaminophen use may result from lack of consumer awareness that acetaminophen can cause severe liver injury," the working group report said.

The outside advisers will meet in June to discuss the report's findings. The recommendations include enhanced public information efforts, stronger labels warning of liver side effects, and dose limitations.

"Consumers may not be aware that acetaminophen is present in many over-the-counter combination products, so they may unknowingly exceed the recommended acetaminophen dose if they take more than one acetaminophen product without knowing that both contain acetaminophen," the report said.

The recommendations also call for limiting the maximum adult daily dose to no more than 3,250 milligrams. The current recommendation stands at 4,000 milligrams per day. Other recommendations include limiting tablet strength for immediate release formulations and limiting options in liquid formulations for children.