Acetaminophen and liver damage: Are you taking too much?

Many of my patients—even the very informed ones—don’t realize that acetaminophen, the active ingredient in Tylenol, can be dangerous if taken in large quantities. And don’t let the phrase “large quantities” fool you—it’s quite easy to take a dangerous amount of acetaminophen, especially if you’re taking multiple over-the-counter drugs that contain it. For instance, many cold and flu medicines contain acetaminophen, so if you take those and some Tylenol, you’re getting more acetaminophen than you might realize. This excerpt, from an article recently published in the Harvard Health Letter, explains the risks of taking too much acetaminophen, and how you can avoid doing so.

By some counts, tens of thousands of Americans are hospitalized each year for liver problems caused by acetaminophen, and several hundred die. Many of the overdoses are suicide attempts, but one important study found that nearly half were accidental.

And clear-cut overdoses may not be the only problem. Even supposedly safe amounts of acetaminophen—doses close to 4,000 milligrams (mg) per day, the current daily limit— may be quite toxic to the liver in a small number of people.

In 2009, a group of experts called the Acetaminophen Hepatotoxicity Working Group (hepatotoxicity means liver poisoning) made several recommendations to the FDA that would tighten up the rules for acetaminophen. As of July 2009, the FDA hadn’t decided which, if any, of the recommendations to implement, but some changes are likely.

Regardless of what the FDA decides to do, it makes sense to be careful about how much acetaminophen you take. But don’t overreact. Millions of people take acetaminophen every day with no bad side effects—and are in less pain because they do. Just because acetaminophen is capable of causing harm doesn’t mean it’s dangerous.

The liver and acetaminophen

Like many drugs, acetaminophen is broken down in the liver. A small percentage of the drug is changed into a compound that’s extremely harmful to liver cells, called NAPQI.

Usually, NAPQI combines with another compound in the liver, called glutathione. In this combination, NAPQI is harmless to the liver. But if there’s too much NAPQI or not enough glutathione to sop it up, then liver damage can occur. Too much NAPQI can occur if you take too much acetaminophen. Too little glutathione can happen if you haven’t eaten well or are malnourished.

How much is too much?

The current daily limit for safe intake is 4,000 mg. It’s difficult to pinpoint the amount of acetaminophen that will result in a liver-damaging overdose. People’s reactions vary, depending on the health of their livers, their glutathione levels, and maybe some genetic factors. Some sources say 12,000 mg over a 24-hour period will have toxic effects on the liver. To put that in perspective, you’d have to take 37 regular-strength pills (at 325 mg each) to hit the 12,000-mg mark.

But there’s evidence that much lower amounts will harm the liver. The average daily dose associated with the liver injuries recorded in an FDA database and in a large liver failure study was 5,000 mg to 7,500 mg. That’s uncomfortably close to the current daily limit for safe intake, so the working group recommended lowering it to 3,250 mg. Taking 10 regular-strength pills a day would get you to 3,250 mg.

Dangerous for chronic drinkers

If you drink a lot of alcohol in one session and take a normal dose of acetaminophen, you probably are not going to have liver problems. The trouble starts when heavy drinkers take a lot of acetaminophen over a period of time—several days, at least, and maybe longer. (In this context, heavy drinkers are defined as people who have three or more drinks a day.) 

One of the recommendations from the FDA’s working group is to set a lower daily limit for acetaminophen for people who routinely have three or more alcoholic drinks a day. How much lower was not specified.

“Hidden” sources

You may take more acetaminophen than you should without knowing it, because acetaminophen is an ingredient in so many medicines. The powerful prescription painkillers Darvocet, Percocet, and Vicodin contain anywhere from 350 to 650 mg in each pill. And it’s an ingredient in many over-the-counter medications: the cold and flu products like NyQuil and TheraFlu, Excedrin’s migraine headache products, and even some varieties of Alka-Seltzer. Acetaminophen from these sources can start to add up.

When researchers have compared accidental overdoses of acetaminophen with intentional ones, they’ve found something surprising: accidental overdoses tend to result in more serious liver damage than the intentional ones, even though the intentional overdoses were much larger.

Why? The initial symptoms of liver poisoning from acetaminophen are often vague—fatigue, some nausea. So people who take too much acetaminophen by mistake don’t go to the doctor or hospital because they don’t realize they’ve done damage to their liver. By the time the accidental overdose patient gets medical attention, the acetaminophen levels are high and the damage to the liver more extensive. Acetaminophen overdosing is treatable with a drug called acetylcysteine, but it’s important that it be caught early.

What you should do

For starters, what you should not do is throw out your acetaminophen. It’s an excellent drug with a good safety record. But you should view acetaminophen as a serious drug—not something you can pop like candy. Here are a few pointers:

• ·         Keep tabs on the amount of acetaminophen you are taking. Remember to include in your totals the amounts in over-the-counter medications.
• ·         Be especially careful if you are taking a heavy-duty prescription painkiller like Percocet or Vicodin. Each pill may contain as much as 650 mg of acetaminophen.
• ·         If you’re sick and not eating well, limit your daily intake of acetaminophen to about 3,000 mg.
• ·         If you regularly drink three or more servings of alcohol a day, you must limit your intake of acetaminophen if you’re taking the drug over several days.
• ·         If you have hepatitis or another liver disease, ask your doctor about whether it’s safe for you to take acetaminophen and, if so, how much.

How surprised are you by the facts of this article? Do you know anyone who has had liver problems due to taking too much acetaminophen? Are you going to do anything differently regarding how you take over-the-counter medications now?

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