LIVER INJURY RISKS WITH ACETAMINOPHEN PRODUCTS

February 3, 2014

On Jan. 14, 2014, the Food and Drug Administration (FDA) advised health care professionals to stop prescribing and dispensing prescription medications containing high doses of acetaminophen (TYLENOL) combined with other active ingredients. Such combination products often contain another pain reliever, such as codeine, oxycodone or hydrocodone.

In January 2011, the FDA asked manufacturers within two years to stop making prescription combination drugs containing doses of acetaminophen exceeding 325 milligrams (mg) per tablet, capsule or other dosage unit, because the agency determined that there is no evidence to show that higher amounts of acetaminophen doses provide additional benefit that outweighs the added risks for liver injury. While more than half of manufacturers have voluntarily complied with the agency’s 2011 request, many have not.

Disturbingly, the FDA has not asked manufacturers to stop selling high-dose over-the-counter (OTC) acetaminophen products containing “extra strength” doses of 500 mg per tablet, despite the fact that these OTC versions pose the same risk of liver injury as prescription versions.

Health Research Group’s former Director Dr. Sidney Wolfe had issued a press statement in 2011 criticizing the FDA for failing to take action concerning OTC products, which remain a major source of acetaminophen consumption and, consequently, acetaminophen toxicity.

In June 2009, Dr. Wolfe was among members of an FDA advisory committee that voted 24 to 13 to limit the maximum single dose of acetaminophen to 650 mg, which would have effectively lowered the maximum size of OTC acetaminophen tablets from 500 to 325 mg per tablet or capsule (a standard adult dose is two tablets or capsules).Twelve of the committee members who voted in favor of lowering the dose also stated that they considered the action a high priority.

Now, more than four years after the committee recommended lowering the OTC dose, the FDA has taken no action to reduce the dose of these products. Acetaminophen remains widely used as an OTC pain and fever medication and is often combined with other ingredients, such as cough and cold ingredients. For example, there are 650 mg of acetaminophen in one dose of NYQUIL, a popular OTC combination product used to treat cold symptoms. Data from 2008 show that OTC medications make up nearly 80 percent of the U.S. market for acetaminophen.

The FDA stated that most of the cases of severe liver injury associated with acetaminophen occurred in patients who took more than the prescribed dose of an acetaminophen-containing product in a 24-hour period, took more than one acetaminophen-containing product at the same time or drank alcohol while taking acetaminophen products.

A study published in 2006 found that some adults developed early signs of liver toxicity after taking just 4 grams per day of acetaminophen, or just over eight "extra-strength" tablets of 500 mg acetaminophen in a day. The current recommended daily maximum dose is 3 grams per day, the amount in six 500 mg tablets.

Combination products containing acetaminophen may pose especially high risk in cases where patients fail to recognize that the products contain high doses of acetaminophen and take additional OTC products containing the drug. Before the FDA’s 2011 request to manufacturers, prescription combination products accounted for nearly half of all cases of acetaminophen-related liver failure in the U.S., many of which result in liver transplant or death.

Many manufacturers have voluntarily complied with the FDA’s request to lower the acetaminophen dose to 325 mg per tablet or capsule in prescription combination products. However, some higher-dose prescription combination products remain on the market. The FDA plans to withdraw approval for combination prescription products containing high-dose acetaminophen still on the market in the near future. However, the FDA has not announced any similar plans to ban OTC products with dangerously high doses of acetaminophen, nor has the agency warned consumers not to purchase these products.

What You Can Do

If you need a prescription or OTC product containing acetaminophen, you should only use those products that contain no more than 325 mg of this drug.

You should never drink alcohol when taking acetaminophen-containing products.

You should avoid consuming more than 3 grams (3,000 mg) of acetaminophen in a 24-hour period. When taking OTC cold and flu medicines, read the label to confirm whether the product contains acetaminophen and if so, how much.

To read the most recent FDA consumer alert, see http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm381650.htm.