What Are the Symptoms of Paracetamol Overdose?
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Symptoms and Management of Acetaminophen (Paracetamol) Toxicity

Published on Oct 28, 2022 and last reviewed on Nov 02, 2022   -  4 min read


Acetaminophen (Paracetamol) toxicity occurs due to the excessive use of Paracetamol. This article explains Acetaminophen toxicity and its treatment.


Acetaminophen toxicity is one of the most common causes of liver failure worldwide. It is caused by the excessive use of Paracetamol and other Acetaminophen-containing medications used for relieving pain and fever. These medications are easily available at a low cost in the market, and most of the population considers them safe compared to other drugs. Acute Acetaminophen toxicity will cause immediate symptoms and later on cause multiple organ failures, especially in the liver. Hepatotoxicity (liver toxicity) is the most important side effect of Acetaminophen toxicity and is the most important reason for liver transplantation in the world.

What Is Acetaminophen?

Acetaminophen (otherwise known as Paracetamol) is a drug used for the treatment of fever and pain (mild to moderate). It is the most commonly used oral antipyretic (reduce fever) and analgesic (pain killer) drug. Acetaminophen belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs). They act by inhibiting cyclooxygenase (COX) present in the brain and prevent the production of prostaglandins, which are responsible for fever and pain. It also acts directly on the hypothalamus and produces its antipyretic effects (reducing fever).

What Are the Uses of Acetaminophen?

Acetaminophen is used for the following purposes.

What Is Acetaminophen Toxicity?

Acetaminophen toxicity is caused by the enormous use of Paracetamol and N-acetyl-P-aminophenol (APAP), the most commonly used medications for relieving fever and pain. It can occur due to accidental ingestion of large doses of Acetaminophen or purposeful consumption as a part of suicidal attempts. The maximum recommended daily dosage of Acetaminophen in adults is four grams per day, and in children, it is 90 milligrams per kilogram per day. An excessive dose of Acetaminophen in the human body causes immediate side effects within 24 hours and later progresses to liver damage. Hepatotoxicity is the most important effect of Acetaminophen overdose. It occurs due to the toxic metabolites released from Acetaminophen in the body. N-acetyl-P-benzoquinone imine (NAPQI) is a toxic intermediate produced from Acetaminophen. N-acetyl-P-benzoquinone imine (NAPQI) causes damage to liver cells and reduces the levels of antioxidants present in the liver (glutathione). People with a history of chronic alcohol use, malnutrition, and underlying liver diseases are at increased risk of developing hepatotoxicity and liver damage.

What Are the Symptoms of Acetaminophen Toxicity?

Acetaminophen toxicity will result in an immediate body response within a few hours. These symptoms can be divided into three based on the severity and time of onset.

It includes the following:

  • First Phase - It occurs within a few hours after the overdose. Initial symptoms include vomiting, sweating, nausea, and a pale appearance. Some patients develop only mild symptoms within 24 hours of poisoning.

  • Second Phase - These symptoms will develop within 24 to 72 hours after Acetaminophen toxicity. During this phase, Acetaminophen is converted to toxic metabolites, which causes liver cell damage. Individuals may experience pain in the right upper portion of the abdomen. During this phase, there will be a rapid increase in the levels of biochemical markers for liver function, including alanine transaminase (ALT), aspartate transaminase (AST), and international normalized ratio (INR). Acetaminophen toxicity may also cause acute kidney failure due to multiple organ dysfunction syndromes and hepatorenal syndrome (kidney failure in individuals with liver damage).

  • Third Phase - It occurs three to five days after Acetaminophen toxicity. It consists of multiple organ damage and associated complications. This final stage includes liver necrosis (cell death), low blood sugar, blood coagulation defects, brain swelling, hepatic encephalopathy, septicemia, multiple organ damage, and death.

How Can We Manage Acetaminophen Toxicity?

1. Gastric Decontamination - It can be used as a treatment option only when the patient is admitted within two hours of Acetaminophen overdose. Gastrointestinal absorption of Acetaminophen occurs within two hours. Gastric decontamination is performed within two hours to prevent the gastric absorption of Acetaminophen and reduce toxicity. It can be done in two ways. It includes:

  • Gastric Irrigation or Lavage (Stomach Pumping) - It is performed within one hour after ingestion. Gastric lavage involves cleaning the contents present in the stomach to eliminate toxic substances.

  • Activated Charcoal - It can be used to reduce the gastrointestinal absorption of Paracetamol. Activated charcoal helps in gastrointestinal decontamination by adsorbing Paracetamol and reducing toxicity. It is given within 30 minutes to two hours for better gastric decontamination.

2. N-acetylcysteine (NAC) -Toxic metabolites produced from Acetaminophen will cause liver damage by inhibiting glutathione (antioxidant). Acetylcysteine reduces Acetaminophen toxicity by restoring glutathione. It is most effective when given within eight hours of overdose and poisoning. Acetylcysteine can be administered orally or intravenously, but the intravenous route of administration shows greater effectiveness. Certain patients will develop allergic reactions after administration (anaphylactic reaction). Proper allergic history and test dose must be taken before administration.

3. Liver Transplantation - Acute liver failure after Acetaminophen toxicity is treated with liver transplantation to avoid death. The diseased liver is replaced with another healthy liver from a donor. The criteria for liver transplant include the following:

  • Arterial blood pH lower than 7.3, even after fluid replacement.

  • Grade III or grade IV hepatic encephalopathy.

  • Prothrombin time more than 100 seconds.

  • Serum creatinine levels of more than 300 mmol/L in 24 hours.


Acetaminophen (Paracetamol) toxicity happens due to excessive levels of Acetaminophen in our body. Acetaminophen is commonly used for relieving pain and reducing fever. In low doses, it is safe for consumption and relieves pain, and reduces fever. Accidental ingestion of larger doses or suicidal attempts by consuming Paracetamol tablets will cause toxicity and adverse health effects. Hepatotoxicity is the most important and dangerous effect produced by Acetaminophen toxicity. Early medical management and proper medications can reduce the progression of adverse health effects and prevent multiple organ failures causing death.

Frequently Asked Questions


What Are the Signs of Acetaminophen Toxicity?

Abdominal pain, irritability, vomiting, loss of appetite, sweating, and unexplained fatigue are the first signs of an Acetaminophen overdose. Other signs associated with Acetaminophen toxicity include diarrhea, generalized weakness, convulsions, blurred vision, confusion, dark urine, and jaundice.


What Are the Serious Health Effects of Acetaminophen Toxicity?

The most severe and fatal side effect of Acetaminophen overdose is liver damage. When a person consumes more Acetaminophen than the recommended daily dose  (4,000 milligrams), liver damage may result; however, some persons have been known to experience liver damage with even lower doses. A liver transplant may be the only way to reverse acute liver failure caused by Acetaminophen toxicity.


What Is the Daily Recommended Dose of Acetaminophen?

Generally, 4,000 milligrams of Acetaminophen per day is considered the maximum dose for adults. Children should not take more than 90 milligrams per kilogram per day. Within 24 hours of taking an excessive amount of Acetaminophen, a person will experience side effects, eventually leading to liver damage.


Can One Take 1500 Milligrams of Acetaminophen in a Single Dose?

A single dose of 1500 milligrams of Acetaminophen is dangerous. The Maximum recommended single dose of Acetaminophen in a healthy adult is 1000 milligrams. However, adults can typically take between 650 milligrams to 1,000 milligrams of Acetaminophen every four to six hours.


What Are the Treatment Options for Acetaminophen Toxicity?

Stabilization, decontamination, and administration of N-acetylcysteine, a specific antidote, may be used to treat an Acetaminophen-poisoned patient. Gastric lavage is the process of cleaning the contents of the stomach to eliminate toxic substances. In addition, liver transplantation is usually done to treat acute liver failure following acetaminophen poisoning.


Can Acetaminophen Toxicity Cause Liver Damage?

When taken in excess, Acetaminophen has a direct hepatotoxic potential that can result in severe liver damage and death from acute liver failure. Toxic metabolites of Acetaminophen induce liver damage by inhibiting glutathione (antioxidant). For example, N-acetyl-P-benzoquinone imine (NAPQI) produced from Acetaminophen damages liver cells and reduces the number of antioxidants in the liver leading to liver damage.


What Are the Tests Used to Confirm Acetaminophen Toxicity?

Diagnostic tests, such as Acetaminophen levels (blood), renal function tests, electrolytes, amylase, liver function tests, lipase, complete blood counts, and coagulation factors, are typically used to confirm a diagnosis of Acetaminophen toxicity. Blood tests like the Acetaminophen level test determine the amount of Acetaminophen in the blood.


How Much Acetaminophen Can a Healthy Adult Take In Two Hours?

The maximum amount of Acetaminophen for healthy adults is one gram (1,000 milligrams) per dose and four grams (4,000 milligrams) per 24 hours. Therefore, adults can take one or two 500 milligrams of Acetaminophen up to four times in 24 hours. Always wait at least four hours between doses. Acetaminophen overdoing can cause serious side effects.

Last reviewed at:
02 Nov 2022  -  4 min read




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