The painful truth about acetaminophen

Pain relievers can work wonders, allowing many people to carry on with their lives despite disabling arthritis, for instance, or recurrent headaches. But all pain relievers, prescription or over-the-counter (OTC), have potential risks, especially when taken in high dosages or for a long term. Recent events have raised concerns about these widely-used drugs, in particular the No. 1 non-prescription pain reliever, acetaminophen.

For a long time, acetaminophen, the active ingredient in Tylenol, has seemed to be the safe bet among the commonly available pain relievers. Although acetaminophen is one of the safest and most effective drugs on the market, this pain reliever can damage your liver when taken in too high a dose. In fact, acetaminophen overdoses are the No. 1 cause of acute liver failure in the United States. One key reason: So many medications contain acetaminophen that it’s easy to take too much of the drug without realizing it. Although the problem of accidental overdoses isn’t new, the issue became headline news last year when an advisory committee of the US Food and Drug Administration (FDA) put new restrictions on drugs containing acetaminophen. Here’s more of what you should know about acetaminophen and how to take it safely.

WHAT IS ACETAMINOPHEN?

Acetaminophen, which in other countries is called paracetamol, was first synthesized and used in patients in the late 19th century. But it was dropped in favor of a related drug, phenacetin, and fell into obscurity until it was rediscovered in the 1950s after phenacetin proved to have too many side effects. Acetaminophen did not catch on until the early 1980s, when it filled the void left by aspirin as the safe pain reliever and fever reducer for children after aspirin was linked to Reye’s syndrome, a rare but potentially fatal condition that affects the brain and the liver.

Today, although OTC acetaminophen is often associated with the brand-name drug Tylenol, it can be found in numerous other products designed to treat headaches, cold and flu symptoms, sinus problems, sleeplessness, arthritis pain, and even menstrual cramps. But that’s not all. The drug also is an active ingredient in some popular pain medications, such as Dolcet, and muscle relaxants, such as Norgesic Forte.

Acetaminophen is sometimes confused with nonsteroidal anti-inflammatory drugs (NSAIDs) which include aspirin, naproxen, ibuprofen, and others. That’s because these medications all belong to a class of pain-relieving drugs called analgesics and are readily available without a prescription. Acetaminophen, however, is usually put in its own category, separate from the NSAIDs, because it doesn’t have their anti-inflammatory effects. Some research shows that it does interfere with prostaglandin synthesis, like NSAIDs, but in a way that doesn’t produce widespread effect on inflammation.

However, in recent years, acetaminophen has often been recommended instead of aspirin as a day-to-day pain reliever because it’s much easier on the stomach and is considered safe when taken properly. In fact, new pain management guidelines released by the American Geriatric Society in 2009 highly recommend acetaminophen as an initial and ongoing therapy for common forms of muscle and bone pain in older adults.

SIDE EFFECTS

With NSAIDs, the main concern is stomach bleeding. This is especially true in adults who are over age 60, are taking prescription blood thinners, and have a history of stomach bleeding or ulcers. The regular use of NSAIDs also can raise blood pressure, damage kidneys, and cause cardiovascular complications in some adults. With acetaminophen, the main concern is liver damage which can cause everything from abnormalities in liver function tests to acute liver failure and even death.

To add insult to injury, acetaminophen may have deleterious effects beyond the liver. Harvard researchers have linked the drug to high blood pressure. Other researchers have identified a possible connection to asthma. These are preliminary findings, not proof of cause and effect. Still, they’re another reason the perception of acetaminophen as a harmless drug is changing.

DANGER TO 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. It also seems that heavy drinkers aren’t any more likely than nondrinkers to suffer liver damage from a single large dose of acetaminophen

The trouble starts when heavy drinkers take a lot of acetaminophen over a period of time several days, at least, and maybe longer. A drinking habit and a poor diet often go hand in hand. Multiple high doses of acetaminophen are more dangerous for drinkers partly because they don’t eat well.

However, early signs and symptoms of liver damage caused by acetaminophen, such as loss of appetite, nausea, and vomiting, can sometimes be difficult to spot. That’s because they may take time to appear or be mistaken for something else, such as the flu.

Within a few days, however, liver damage can progress to liver failure and produce more serious symptoms. If you or someone you know suddenly develops a yellowing of the eyes and skin, tenderness in the upper abdomen, disorientation, or confusion, seek medical attention immediately. Liver failure caused by acetaminophen overdose is life threatening. But it often can be treated with medications used to reverse poisoning.

HOW MUCH IS TOO MUCH?

It’s difficult to pinpoint the exact amount of acetaminophen that will result in a liver-damaging overdose. People’s reactions vary, depending on the health of their livers and may be some other unknown factors. Some sources say 12,000 mg. over a 24-hour period will have toxic effects on the liver (That’s taking 37 regular strength pills at 325 mg. each!)

But there’s evidence that much lower amounts can harm the liver. According to the FDA working group, the median daily dose associated with liver injuries recorded in the agency’s adverse event data base and in a large liver failure study was 5,000 to 7,000 mg. That’s uncomfortably close to 4,000 mg., the current daily limit for safe intake.

POSSIBLE RESTRICTIONS

Experts agree that the dangers associated with taking too much acetaminophen shouldn’t be downplayed. According to recent studies, acetaminophen overdoses cause 56,000 emergency room visits, 26,000 hospitalizations, and nearly 500 deaths each year in the United States.

That is why the FDA is currently considering several new measures to address the problem, including:

• Lowering the maximum daily dose. Currently, it is recommended that adults take no more than 4,000 mg. of acetaminophen a day. However, research suggests that taking this amount in a 24-hour period could be toxic in some adults. As a result, it’s been proposed that the maximum daily dose be lowered to 2,600 mg.

• Reducing dosage strengths. Many non-prescription acetaminophen products contain 500 mg. of the drug per single tablet or capsule, and it’s recommended that single doses not exceed 1,000 mg. To lower the chances of an overdose, it’s been suggested that maximum single doses be limited to 650 mg and that OTC pills or tablets contain no more than 325 mg.

• Eliminating combination prescription medications. It’s been proposed that acetaminophen and narcotic drugs be prescribed separately, rather than being combined in one medication.

SAFETY PRECAUTIONS

Whether or not new restrictions go into place, it’s important to be careful when using acetaminophen. To avoid overdose:

• Read labels. Look on the label or package insert for either the word acetaminophen or paracetamol or the abbreviation APAP.

• Follow dosing directions. Make sure you understand how much acetaminophen you can take at one time, how many hours you must wait between dosages, and how many doses you can safely take each day.

• Don’t take more than one medicine containing acetaminophen at a time.

• Talk to your doctor before taking acetaminophen if you have risk factors for liver damage. You’re at greater risk if you consume three or more alcoholic drinks every day or have existing liver damage.

The bottom line: Acetaminophen, when used correctly and within dosage guidelines, is still probably the safest nonprescription pain reliever available. But you should view it as a serious drug not something you can pop like candy!

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Sources: Overdoing Acetaminophen. Harvard Health Publications, August 2009. www.health.harvard.edu; Acetaminophen is safe when used correctly, www.HealthLetter. MayoClinic.com, December 2009