Secret Ingredient: Acetaminophen

A popular, normally safe drug is all over the pharmacy shelves—and it could put your liver at risk.

As an associate clinical professor at UCSF, I start every semester by taking new nurse-practitioner students on a walk down the aisle of a local pharmacy. After spending an hour investigating the dozens of brands of Tylenol, the four brands of Benadryl, plus NyQuil/DayQuil, Contac, Midol, Theraflu and more than 100 other over-the-
counter products, we find a common denominator: All contain acetaminophen. Thirty-six percent of Americans take the drug, which is the active ingredient in Tylenol, in one form or another at least once a month.

Why is this important? Because a recent study in the medical journal Hepatology revealed that acetaminophen overdose is one of the leading causes for calls to poison-control centers and accounts for more than 56,000 emergency-room visits and 458 deaths a year. Twenty-one percent of all episodes of liver failure in the United States are due to unintentional overdoses of acetaminophen. About a third of those liver failures end in death.

You may be wondering how someone can accidentally overdose on Tylenol. Taking too many tablets is a danger that can be easily avoided: The product’s label warns users not to take more than 1,000 milligrams (the equivalent of two extra-strength tablets) at a time, and no more than 4,000 milligrams in a twenty-four-hour period. So if you have a terrible headache and take more than eight extra-strength pills in 24 hours, you know you’ve maxed out.

But many of the people in the Hepatology study were unknowingly taking multiple forms of acetaminophen—because so many different over-the-counter medicines contain it. For instance, say a person takes Tylenol for the pain of a sports injury, and then adds Benadryl for allergy symptoms. This person easily could be taking more than the maximum dose.

Think of the liver as a multipurpose facility: It’s a factory that makes protein and enzymes, a warehouse that stores carbohydrates for when the body needs them and a sanitation plant that disposes of waste products, including alcohol and drugs of any kind. Acetaminophen itself isn’t poisonous—in fact, huge numbers of people take it in moderation without any adverse effects. But the liver metabolizes acetaminophen via certain pathways, just as it does any drug. When the normal metabolic sequences for acetaminophen become overwhelmed by too much of the drug, a backup system kicks in, forming a very toxic metabolite with a horrendously long name—N-acetyl-p-benzo-quinone imine (NAPQI)—which can quickly poison the liver.