In an attempt to encourage safer use of one of the most commonly taken medications, the U.S. Food and Drug Administration (FDA) has asked health care professionals to stop giving patients prescription combination drugs that contain more than 325 milligrams (mg) of acetaminophen per dose.

“By limiting the maximum amount of acetaminophen in prescription products to 325 mg per tablet, capsule, or other dosage unit, consumers will be less likely to overdose on acetaminophen if they mistakenly take too many doses of acetaminophen-containing products,” explains FDA spokesperson Eric Pahon.

Acetaminophen, which relieves mild to moderate pain and reduces fever, is an active ingredient in hundreds of prescription and over-the-counter (OTC) medications, including Tylenol and Excedrin. It’s a popular arthritis pain reliever because it doesn’t carry the stomach and heart risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs). But it is also present in sleep aids as well as cold, cough and allergy medicine – drugs that many people don’t associate with the popular painkiller. Too much acetaminophen can lead to liver toxicity.

The FDA’s action pertains to the category of drugs that combines acetaminophen with another pain medication, usually an opioid, such as Percocet, Vicodin and Ultracet. The agency says there is no data showing any benefit from taking more than 325 mg of acetaminophen per dose in these kinds of medications, but it says there are clear risks.

According to the FDA, in the U.S. inadvertent overdose from prescription combination drugs containing acetaminophen is the cause of nearly half of all cases of acetaminophen-related liver failure, which can lead to the need for a liver transplant or result in death. The agency says severe liver injuries related to acetaminophen generally occur when people:

  • Exceed the recommended maximum dose of 4,000 mg in a 24-hour period
  • Take more than one acetaminophen-containing product at a time
  • Drink alcohol while taking acetaminophen

In January 2011, the FDA asked makers of oral prescription combination drugs containing acetaminophen to voluntarily limit the maximum dose per tablet or capsule to 325 mg by January 14, 2014. The agency says more than half of manufacturers complied with that request, and it plans to take action against those that did not. It can withdraw drug approval so medications can’t be sold or marketed in the U.S.

Rheumatologist Robert Katz, MD, a professor of medicine at Rush Medical College in Chicago, says this announcement is intended to spur real clinical change.

“I think it alerts doctors that sometimes acetaminophen can be over-prescribed because it is also available over-the-counter. Some might take prescription acetaminophen and get it in over-the-counter medication without realizing they are doubling up,” Dr. Katz explains.

Dr. Katz believes people are more familiar with brand names like Tylenol than they are with the drug name “acetaminophen.” For that reason he says it’s important to make sure your doctors know about all the OTC medications you take. That way they can make sure you are within safe and recommended ranges when they give you a prescription combination drug.

“There can be liver toxicity with this medication and people need to know that,” Dr. Katz explains.

This FDA alert does not apply to OTC acetaminophen products. The agency says it will address that issue in a separate regulatory action sometime in the future.