FDA limits acetaminophen in combination products

Jan 12, 2011

The U.S. Food and Drug Administration (FDA) is asking manufacturers of prescription combination products that contain acetaminophen to limit the amount of acetaminophen to no more than 325 milligrams in each tablet or capsule.

The FDA is also requiring manufacturers to update labels of all prescription combination acetaminophen products to warn of the potential risk for severe liver injury.

Acetaminophen, also called APAP, is used in many prescription products in combination with other ingredients, usually opioids such as codeine (Tylenol with Codeine), oxycodone (Percocet), and hydrocodone (Vicodin).

"FDA is taking this action to make prescription combination pain medications containing acetaminophen safer for patients to use," said Sandra Kweder, MD, deputy director of the Office of New Drugs in FDA's Center for Drug Evaluation and Research (CDER), in a news release. "Overdose from prescription combination products containing acetaminophen account for nearly half of all cases of acetaminophen-related liver failure in the U.S., many of which result in liver transplant or death."

The elimination of higher-dose prescription combination acetaminophen products will be phased in over three years and should not create a shortage of pain medication. The FDA believes that prescription combination products containing no more than 325 mg of acetaminophen per tablet are effective for treating pain.

"There is no immediate danger to patients who take these combination pain medications, and they should continue to take them as directed by their healthcare provider," Dr. Kweder said. "The risk of liver injury primarily occurs when patients take multiple products containing acetaminophen at one time and exceed the current maximum dose of 4,000 mg within a 24-hour period."

Acetaminophen also is widely used as an over-the-counter (OTC) pain and fever medication and is combined with other OTC ingredients, such as cough and cold ingredients. The actions FDA is taking for prescription acetaminophen products do not affect OTC acetaminophen products.

Because of continued reports of liver injury, the FDA is proposing that boxed warnings, the agency's strongest warning for prescription drugs, be added to all acetaminophen prescription products.