What is the toxic adult dose for acetaminophen (paracetamol)?

From the Guidelines

The toxic adult dose for paracetamol is generally considered to be more than 10 gm/day, but severe liver injury can occur rarely when doses as low as 3-4 gm/day are taken. When considering the management of paracetamol overdose, it is crucial to prioritize morbidity, mortality, and quality of life as outcomes. According to the study by 1, acetaminophen hepatotoxicity is suggested by historic evidence for excessive ingestion, and most ingestions leading to acute liver failure exceed 10 gm/day. However, the study also notes that severe liver injury can occur rarely when doses as low as 3-4 gm/day are taken. Key points to consider in the management of paracetamol overdose include:

• The dose-related toxicity of paracetamol, with most ingestions leading to acute liver failure exceeding 10 gm/day [ 1 ]
• The potential for severe liver injury at doses as low as 3-4 gm/day [ 1 ]
• The importance of drawing acetaminophen levels in all patients presenting with acute liver failure, as acetaminophen is the leading cause of acute liver failure in the United States and Europe [ 1 ]
• The use of activated charcoal for gastrointestinal decontamination, which may be beneficial if given within 1-4 hours of ingestion [ 1 ]
• The administration of N-acetylcysteine as an antidote, which is most effective when given promptly after overdose.

From the FDA Drug Label

Warnings Liver warning This product contains acetaminophen Severe liver damage may occur if: an adult takes more than 6 doses in 24 hours, or greater than 4000 mg of acetaminophen, the maximum daily amount Overdose warning Taking more than the recommended dose (overdose) may cause liver damage.

The toxic adult dose for paracetamol is more than 4000 mg in 24 hours, as it may cause severe liver damage 2.

From the Research

Toxic Adult Dose for Paracetamol

• The toxic adult dose for paracetamol is generally considered to be around 12g or more for an acute overdose, before the risk of serious hepatotoxicity is of concern 3.
• However, the exact dose can vary depending on several factors, including the individual's weight, the formulation of the paracetamol, and the time of ingestion.
• For example, patients who ingest ≥ 10g or ≥ 200mg/kg of paracetamol (whichever is less) should receive a full course of acetylcysteine 4.
• Additionally, patients who ingest ≥ 30g or ≥ 500mg/kg of paracetamol should receive increased doses of acetylcysteine 4.
• It's also important to note that the nomogram of serum paracetamol concentration vs hours post-ingestion can assist in determining the risk of liver injury and the need for treatment 3.

Factors Affecting Toxicity

• The risk of hepatotoxicity from paracetamol overdose can be affected by various factors, including the individual's age, weight, and medical history.
• For example, patients with conditions such as alcoholism, isoniazid use, or prolonged fasting may be more susceptible to paracetamol toxicity 5.
• The formulation of the paracetamol can also affect the risk of toxicity, with modified release paracetamol overdoses requiring different management than immediate release paracetamol overdoses 4.

Treatment and Management

• The treatment and management of paracetamol overdose typically involve the administration of activated charcoal and N-acetylcysteine (NAC) 4, 5, 6, 7.
• NAC is generally well-tolerated when given intravenously, but can cause anaphylactoid reactions in some cases 3.
• The optimal dose and duration of NAC treatment are not well established, but it is generally recommended to give a full course of NAC to patients with paracetamol overdose 4, 6, 7.