New Study Links Signs of Possible Liver Damage to Lower Doses of Acetaminophen (TYLENOL), Supporting Previous Research

Healthy medical study participants given the maximum approved daily dose of the popular pain and fever reducer acetaminophen (TYLENOL) developed an early sign of possible liver damage, according to research published in the July 1 Journal of the American Medical Association.

The study, which was testing a new product combining the narcotic painkiller hydrocodone with acetaminophen, was shut down early because of the frequent occurrence and size of blood level increases of an enzyme known as alanine aminotransferase (ALT) in groups receiving acetaminophen versus the group receiving a placebo. ALT elevation is an early sign of potential liver damage.

The study involved 145 healthy male and female volunteers, ranging in age from 18 to 45. The volunteers randomly received one of five treatments. Four of these treatments included four grams of acetaminophen daily and the fifth was a placebo. The intended duration of the study was 14 days.

Overall, 41 of the volunteers (39 percent) experienced ALT elevations more than three times the upper limit of what is considered normal, while none of the volunteers receiving the placebo had ALT elevations of this level. There were 27 patients (25 percent) with ALT elevations of more than five times the upper limit of what is considered normal and eight patients (eight percent) with ALT values more than eight times the upper limit of what is considered normal.

The authors of the study commented that their review of previously published medical studies supports their observations that some healthy adult patients in clinical trials developed ALT elevations when repeatedly treated with four grams of acetaminophen daily.

The study was entirely funded by the producer of the new hydrocodone-acetaminophen combination, Purdue Pharma LP, headquartered in Stamford, CT. Purdue Pharma is the notorious manufacturer of the potent, frequently-misused, timed-release narcotic oxycodone (OXYCONTIN).

Previous studies show acetaminophen linked to possible liver damage

The researchers noted that the incidence of ALT elevations they observed was higher than those reported in similar published studies. They speculate that, in part, their results may be related to the relatively high proportion of Hispanic people in their study. Previous research suggests that people of Hispanic origin are at increased susceptibility to ALT elevations.

Whatever the reason, the results of this study are troubling.

In the February issue of Worst Pills, Best Pills News, we reported on a study published in the December 2005 issue of the medical journal Hepatology. The study found that the annual percentage of potentially fatal acute liver failure cases caused by acetaminophen rose from 28 percent in 1998 to 51 percent in 2003. The authors of this study concluded that liver damage caused by acetaminophen far exceeds other causes of drug-induced acute liver failure in the United States.

This research showed that unintentional overdoses were responsible for 48 percent of the acute liver failure cases. Intentional overdoses, or suicide attempts, accounted for 44 percent of episodes. In eight percent of the cases, the intent was unknown. Of the patients who overdosed unintentionally, 38 percent took two or more acetaminophen-containing products simultaneously, and 63 percent used narcotic combination painkillers that contained acetaminophen.

Acetaminophen is found in many commonly used drugs

The list of acetaminophen-containing prescription and over-the-counter (OTC) drug products is long. The table below lists the brand names of various painkillers and products widely promoted for colds and flu. The right-hand column lists the amount of acetaminophen contained in one dose of the product.

The amount of acetaminophen contained in OTC drugs is clearly listed on the label. Always read these labels before taking any OTC drug to make sure you are not taking acetaminophen in two or more products.

Prescription painkillers may be combinations of a narcotic drug with acetaminophen, such as LORTAB, PERCOCET, TYLOX, and DARVOCET. If you are prescribed a painkiller, ask your pharmacist if it also contains acetaminophen. Mixing various OTC drugs and prescription painkillers may result in the ingestion of too much acetaminophen.    

In addition, alcohol in combination with acetaminophen can increase the risk of liver toxicity. OTC acetaminophen products now have the following warning on their labels:

What You Can Do

There are two important points that you should always consider when using acetaminophen or any over-the-counter drug. One, just because a drug is sold over the counter does not mean that it is totally safe — acetaminophen is a prime example. Two, when using any OTC product, always use the lowest dose that helps your symptoms. See your physician if the symptoms persist.

You should read the labels on OTC drug products carefully.  If you are given a prescription painkiller, ask your pharmacist if it contains acetaminophen.

If you or a family member develop any of the following symptoms of potential liver toxicity, you should stop taking all acetaminophen-containing products and call your physician immediately:

• Pruritus (itchy skin)
• Jaundice (yellowing of the skin or whites of the eyes)
• Dark urine
• Upper right-sided abdominal tenderness (location of the liver)
• Unexplained flu-like symptoms