Acetaminophen is the most widely used analgesic and antipyretic in the world and is found in a wide range of over-the-counter products.  It is a generally safe drug, but overconsumption can lead to significant harm, particularly to the liver.  It is the most common cause of acute liver failure and responsible for a significant fraction of all liver transplants.

Accidental acetaminophen overdose is more common among individuals who have low levels of health literacy and who do not recognize its prevalence in multiple products. 

• In early stages, acetaminophen has no readily observable toxidrome.  In the out-of-hospital environment, acetaminophen overdose is most likely diagnosed through history taking, both from the patient and collaterally.  Always consider the possibility of co-ingestion of other drugs or substances. 
• To the extent that acetaminophen toxicity offers signs and symptoms, they are generally non-specific: nausea and vomiting; malaise; lethargy; pallor; and diaphoresis, associated with right upper quadrant abdominal pain.  Patients with significant liver injury may remain asymptomatic for hours prior to their deterioration.
• Single ingestions greater than 250 mg/kg (or more than 12 g in 24 hours) are likely to cause toxicity, but injury can occur at lower doses.
• Individuals with pre-existing liver disease are at increased risk of acetaminophen toxicity and can experience significant liver dysfunction, even with doses of acetaminophen that are generally considered safe.
• Provide supportive care for patients.

• The specific antidote to acetaminophen, N-acetylcysteine, is a hospital-based therapy that requires diagnostic testing not available in the out-of-hospital environment.
• Administration of activated charcoal within four hours of ingestion may help reduce the need for N-acetylcysteine treatment and limit the degree of liver injury.  Paramedics and EMRs/FRs identifying an acetaminophen overdose should consider the timing of ingestion and strive to deliver these patients to a hospital in a timely fashion.

Because of its high potential for toxicity, as well as its delayed onset of symptoms, patients suspected of acetaminophen overconsumption should be conveyed to hospital.

• There are essentially no signs or symptoms that are unique to acetaminophen overdose.  Diagnosis is made on the basis of a history of ingestion combined with serum acetaminophen.