FDA Recommends Tougher Standards for Acetaminophen

Recommended by health care professionals worldwide, acetaminophen has become one of the most commonly used drugs for treating everything from headache, colds and fever to muscle aches and arthritis. It is contained in more than 100 products, including many prescription drugs administered by pharmacies. Much of its popularity hinges on the fact that, when taken at recommended doses, acetaminophen does not cause stomach discomfort or bleeding, unlike other drugs commonly used to reduce pain and fever, such as aspirin, ibuprofen and naproxen. However, when taken over the maximum amount of 4 grams per day, acetaminophen can cause liver damage, ranging from abnormalities in blood tests used to assess liver function to acute liver failure (ALF), and even death; a problem not caused by other over-the-counter painkillers.

Despite efforts since the early 1990s to reduce the incidence of acetaminophen-related liver damage, liver injury from acetaminophen overdose remains a serious public health problem. In fact, acetaminophen toxicity has replaced viral hepatitis as the most common cause of acute hepatic failure in the United States, and is the second most common cause of liver failure requiring transplantation in the U.S.; concerns that have an advisory group to the Food and Drug Administration (FDA) recommending stronger labels warning of liver side effects, dose limitations and enhanced public information efforts.

“There is extensive evidence that hepatoxicity (liver toxicity) caused by acetaminophen use may result from lack of consumer awareness that acetaminophen can cause severe liver injury,” the group’s report said. “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 calls for limiting the maximum adult daily dose to no more than 3,250 milligrams, with a lower daily maximum for those who consume three or more alcoholic drinks per day while using acetaminophen products. It also recommends limiting the tablet strength for immediate-release formulations to a maximum of 325 milligrams, and the single adult dose to a maximum of 650 milligrams. Other recommendations include:

• limiting pediatric liquid formulations to one mid-strength concentration instead of the multiple dose strengths available now;
• requiring a measuring device and dosing instruction for children under 2 years of age be included in each package, if accurate dosing instructions can be determined and adequate efficacy data exist to support dosing;
• eliminate acetaminophen from all OTC combination medications;
• identify currently existing research or consider conducting further research to address important issues that do not appear to have been adequately addressed previously.

These recommendations are scheduled for discussion at a joint meeting of the Drug Safety and Risk Management Advisory Committee, the Nonprescription Drugs Advisory Committee, and the Anesthetic and Life Support Drugs Advisory Committee to be convened on June 29 and 30 in Adelphi, Maryland.

Last month, the FDA announced that many over-the-counter pain relievers and fever reducers will be required to carry new warnings  on the potential danger of liver damage and stomach bleeding. Medications containing acetaminophen must warn of hepatoxicity risks and increased risk of liver damage in those who drink three or more alcoholic beverages daily. Medications containing non-steroidal anti-inflammatory drugs, commonly known as NSAIDs, must warn of the risks of gastrointestinal bleeding and the symptoms. Manufacturers of medications containing these ingredients have been given until April 2010 to comply.