Acetaminophen

Acetaminophen is one of the most common pain relievers (analgesics) and fever reducers (antipyretics) available over the counter. It is generally regarded as safe. However, it is also the most common cause of toxic hepatitis in North America and Europe and one of the most common poisonings from either accidental or intentional overdose.

Acetaminophen is primarily processed (metabolized) by the liver. In therapeutic doses, the liver is able to process the drug safely without any harmful effects. When a large dose is ingested and/or when doses exceed the recommended amount over a period of time, however, the liver may be overwhelmed and may not process the excessive amount of drug. As a result, a toxic intermediate form of the drug can build up in the liver and cause damage to liver cells. If treatment is not given soon enough, liver failure may result.

For this reason, acetaminophen can be harmful or even fatal if not taken correctly and children in particular are at risk if caregivers do not follow dosing instructions carefully. Often, people do not realize that acetaminophen is one of the ingredients in many combination medications such as cold and flu preparations. If two or more of these medications are taken together, levels of acetaminophen may exceed safe limits.

Acetaminophen preparations come in varying strengths and several different forms, including tablets, capsules and liquid.

• For adults, the typical maximum daily limit for acetaminophen is 4000 milligrams (mg). Consuming more than 4000 mg in a 24-hour period is considered an overdose, while ingesting more than 7000 mg can lead to a severe overdose reaction unless treated promptly.
• For children, the amount that is considered an overdose depends on their age and body weight. (For more on this, see the MayoClinic webpage Acetaminophen and children: Why dose matters.)

If it is known or suspected that someone has ingested an overdose of acetaminophen, it is recommended to take the person to the emergency room. If a health practitioner determines that an overdose has occurred, treatment may include an antidote, N-acetylcysteine (NAC), which can help minimize damage to the liver, especially if given within 8 to 12 hours after an overdose. Though NAC is ideally administered within this timeframe, people who seek treatment more than 12 hours after ingestion may still be given the antidote.

Until recently, NAC for people who visit healthcare providers later than 24 hours after acetaminophen ingestion was not the standard of care for acetaminophen overdose management in the United States. However, study data from England suggest that NAC may be beneficial for acetaminophen-induced liver failure more than 24 hours after ingestion.

How is it used?

The test for acetaminophen is used to measure the level of drug in the blood in order to establish a diagnosis of overdosage, to assess the risk of liver damage, and to help decide on the need for treatment. Prompt diagnosis and treatment are important for a positive outcome.

Since high levels of acetaminophen can be toxic to the liver, health practitioners may also order tests such as AST and ALT to detect liver damage. A PT may be used to detect impaired liver function. A health practitioner might also order serum salicylate levels or a urine drug screen for unconscious patients or those for whom there is a suspicion of ingestion of other substances. Other possible tests include blood gases, lactate level, and metabolic panel with creatinine. These are used to monitor severity of liver failure and, in cases of severe overdose, determine whether an overdose patient would benefit from liver transplantation.

Women of childbearing age who have suspected acetaminophen overdose may get human chorionic gonadotropin (hCG) tests to determine if they are pregnant because the drug crosses the placenta and can harm the fetus.

When is it ordered?

Health practitioners may order acetaminophen levels beginning at 4 hours after ingestion or possible ingestion and then every 4 to 6 hours to monitor whether the drug level is increasing or decreasing. Samples collected too soon after ingestion may not accurately reflect the amount absorbed from the stomach into the blood.

Testing may be ordered when a person has signs and symptoms of an overdose. These can appear as early as 2 to 3 hours after ingestion or may not occur for 12 or more hours. Some of these include:

• Nausea, vomiting, diarrhea
• Loss of appetite
• Abdominal pain or cramping
• Irritability
• Sweating

If untreated, toxicity can progress within 3 to 4 days to include jaundice, liver and kidney failure, convulsions, coma and death. If treatment is received within 8 hours of the overdose, however, there is a very good chance of recovery.

For children who have taken acetaminophen in liquid form, a treatment decision may be made as soon as 2 hours after ingestion since the drug is absorbed more rapidly in this form.

What does the test result mean?

The table below summarizes some results that may be seen:

Acetaminophen Level	Result Interpretation
10-20 mcg/mL	Therapeutic levels
Less than 150 mcg/mL 4 hours after ingestion	Low risk of liver damage
Greater than 200 mcg/mL 4 hours after ingestion Or Greater than 50 mcg/mL 12 hours after ingestion	Associated with toxicity and liver damage

The levels discussed above typically apply to a single ingestion of a toxic amount of the drug. They do not necessarily apply to cases in which the recommended amount of acetaminophen has been exceeded over a period of time (chronic overdose ingestion). However, a health practitioner may take acetaminophen levels into account along with clinical signs and symptoms and liver tests to determine the risk and/or presence of liver damage in chronic overdose cases.