What are the effects of an acetaminophen (Tylenol) overdose?

From the Guidelines

Tylenol (acetaminophen) overdose is a medical emergency requiring immediate attention, and the antidote N-acetylcysteine (NAC) should be administered within 8 hours of ingestion for best results. If you suspect an overdose, call poison control at 1-800-222-1222 or go to the emergency room immediately. A toxic dose is generally considered more than 4,000 mg in 24 hours for adults, as stated in the study by 1. Symptoms of overdose include nausea, vomiting, abdominal pain, and later, jaundice and liver failure. Acetaminophen overdose damages the liver by depleting glutathione, which normally detoxifies a harmful metabolite called NAPQI. NAC works by replenishing glutathione stores, as explained in the study by 1.

Treatment Approach

Treatment typically involves:

• Activated charcoal if the ingestion was recent, as mentioned in the study by 1
• NAC administration either orally or intravenously for 21 hours, as stated in the study by 1
• Blood tests to measure acetaminophen levels and liver function will be performed, as recommended in the study by 1

Prevention

To prevent overdose, always:

• Follow dosing instructions
• Avoid taking multiple acetaminophen-containing products simultaneously
• Be cautious with alcohol use, which increases toxicity risk, as noted in the study by 1

Key Considerations

• The Rumack-Matthew nomogram can be used to predict hepatotoxicity, but it has limitations, as discussed in the study by 1
• NAC can be effective even when administered more than 8 hours after ingestion, as shown in the study by 1
• Repeated supratherapeutic ingestions of acetaminophen can result in hepatotoxicity, hepatic failure, and even death, as reported in the study by 1

From the FDA Drug Label

ACETAMINOPHEN ASSAYS - INTERPRETATION AND METHODOLOGY The acute ingestion of acetaminophen in quantities of 150 mg/kg or greater may result in hepatic toxicity. IF AN ASSAY FOR ACETAMINOPHEN CANNOT BE OBTAINED, IT IS NECESSARY TO ASSUME THAT THE OVERDOSE IS POTENTIALLY TOXIC Values above the solid line connecting 200 mcg/mL at 4 hours with 50 mcg/mL at 12 hours are associated with a possibility of hepatic toxicity if an antidote is not administered. (Do not wait for assay results to begin acetylcysteine treatment.)

The treatment for a Tylenol overdose involves administering acetylcysteine as an antidote.

• The decision to treat should be based on plasma or serum acetaminophen concentrations determined as early as possible, but no sooner than 4 hours following an acute overdose.
• If an assay for acetaminophen cannot be obtained, it is necessary to assume that the overdose is potentially toxic.
• Treatment with acetylcysteine should not be delayed pending assay results. 2

From the Research

Tylenol Overdose Management

• The management of Tylenol (acetaminophen) overdose involves several strategies, including inhibition of absorption, removal from the vascular system, antidotes, and liver transplantation 3, 4.
• Activated charcoal can be used to reduce the absorption of acetaminophen, and it seems to have the best risk-benefit ratio compared to other methods such as gastric lavage and ipecacuanha 3, 4.
• N-acetylcysteine is a commonly used antidote for acetaminophen overdose, and it seems to be preferable to placebo/supportive treatment, dimercaprol, and cysteamine 3, 4.
• The use of activated charcoal before oral N-acetylcysteine does not reduce the efficacy of N-acetylcysteine therapy and may provide some additional hepatoprotective benefit 5.
• Administration of activated charcoal more than four hours after acetaminophen overdose may provide additional patient benefit over N-acetylcysteine therapy alone, as it was associated with reduced incidence of liver injury 6.

Patient Referral to Emergency Department

• Any patient with stated or suspected self-harm or who is the recipient of a potentially malicious administration of acetaminophen should be referred to an emergency department immediately regardless of the amount ingested 7.
• Patients less than 6 years of age should be referred to an emergency department if the estimated acute ingestion amount is unknown or is 200 mg/kg or more 7.
• Patients 6 years of age or older should be referred to an emergency department if they have ingested at least 10 g or 200 mg/kg (whichever is lower) or when the amount ingested is unknown 7.

Treatment Protocols

• The out-of-hospital management of extended-release acetaminophen or multi-drug combination products containing acetaminophen is the same as an ingestion of acetaminophen alone 7.
• The use of cimetidine as an antidote is not recommended 7.
• Liver transplantation has the potential to be life-saving in fulminant hepatic failure, but refinement of selection criteria for transplantation and long-term outcome reporting are required 3, 4.