From the Guidelines
Management of Tylenol (acetaminophen) overdose requires prompt administration of N-acetylcysteine (NAC), which is the specific antidote, as soon as possible, ideally within 8 hours of ingestion, though it may still be beneficial up to 24 hours post-ingestion, as recommended by the most recent study 1. For suspected overdose, immediate medical attention is crucial. Treatment begins with activated charcoal if the patient presents within 1-2 hours of ingestion.
Key Considerations
- The standard NAC protocol involves an initial loading dose of 150 mg/kg over 60 minutes, followed by 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours, as supported by previous studies 1.
- Serum acetaminophen levels should be measured at 4 hours post-ingestion or as soon as possible thereafter, and plotted on the Rumack-Matthew nomogram to determine the risk of hepatotoxicity, as suggested by earlier research 1.
- Liver function tests, coagulation studies, and kidney function should be monitored, and treatment should continue until acetaminophen levels are undetectable and liver enzymes are improving or normalized, in line with the recommendations from 1 and 1.
- NAC works by replenishing glutathione stores, which are depleted during acetaminophen metabolism, preventing the toxic metabolite NAPQI from causing liver damage.
Administration and Monitoring
- NAC should be administered intravenously, with an initial loading dose of 150 mg/kg over 15 minutes, followed by 50 mg/kg over 4 hours, and then 100 mg/kg over 16 hours, as outlined in 1.
- Patients should be closely monitored for signs of liver damage, such as elevated liver enzymes, coagulopathy, and encephalopathy, and for potential side effects of NAC, including nausea, vomiting, and allergic reactions, as noted in 1.
From the FDA Drug Label
The acute ingestion of acetaminophen in quantities of 150 mg/kg or greater may result in hepatic toxicity. HOWEVER, THE REPORTED HISTORY OF THE QUANTITY OF A DRUG INGESTED AS AN OVERDOSE IS OFTEN INACCURATE AND IS NOT A RELIABLE GUIDE TO THERAPY OF THE OVERDOSE THEREFORE, PLASMA OR SERUM ACETAMINOPHEN CONCENTRATIONS, DETERMINED AS EARLY AS POSSIBLE, BUT NO SOONER THAN 4 HOURS FOLLOWING AN ACUTE OVERDOSE, ARE ESSENTIAL IN ASSESSING THE POTENTIAL RISK OF HEPATOTOXICITY. IF AN ASSAY FOR ACETAMINOPHEN CANNOT BE OBTAINED, IT IS NECESSARY TO ASSUME THAT THE OVERDOSE IS POTENTIALLY TOXIC. INTERPRETATION OF ACETAMINOPHEN ASSAYS 1 When results of the plasma acetaminophen assay are available refer to the nomogram below to determine if plasma concentration is in the potentially toxic range. Values above the solid line connecting 200 mcg/mL at least 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.) 2. If the predetoxification plasma level is above the broken line continue with maintenance doses of acetylcysteine. 3 If the predetoxification plasma level is below the broken line described above, there is minimal risk of hepatic toxicity and acetylcysteine treatment can be discontinued.
Management of Tylenol overdose involves:
- Determining plasma or serum acetaminophen concentrations as early as possible, but no sooner than 4 hours following an acute overdose
- Using a nomogram to determine if the plasma concentration is in the potentially toxic range
- Administering acetylcysteine treatment, even if assay results are not available, and continuing with maintenance doses if the predetoxification plasma level is above the broken line
- Supportive treatment measures, such as maintaining fluid and electrolyte balance, treating hypoglycemia, and administering vitamin K1 or fresh frozen plasma as necessary 2
- Additional supportive treatment measures include:
- Maintaining fluid and electrolyte balance based on clinical evaluation of state of hydration and serum electrolytes
- Treating as necessary for hypoglycemia
- Administering vitamin K1 if prothrombin time ratio exceeds 1.5 or fresh frozen plasma if the prothrombin time ratio exceeds 3.0
- Avoiding diuretics and forced diuresis 2
From the Research
Management of Tylenol Overdose
- The management of Tylenol (acetaminophen) overdose involves several steps, including initial history, referral to an emergency department, and treatment with activated charcoal and antidotes such as acetylcysteine 3.
- The initial history should include the patient's age, intent, specific formulation and dose of acetaminophen, ingestion pattern, duration of ingestion, and concomitant medications 3.
- 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 3.
- Activated charcoal can be considered if local poison center policies support its prehospital use, a toxic dose of acetaminophen has been taken, and fewer than 2 hours have elapsed since the ingestion 3.
Treatment with Activated Charcoal
- Activated charcoal seemed to reduce the absorption of paracetamol, but the clinical benefits were unclear 4.
- Activated charcoal seemed to have the best risk:benefit ratio among gastric lavage, ipecacuanha, or supportive treatment if given within four hours of ingestion 4.
- Administration of activated charcoal in addition to standard N-acetylcysteine (NAC) therapy after acetaminophen overdose was associated with reduced incidence of liver injury 5.
- Activated charcoal does not reduce the efficacy of subsequent oral N-acetylcysteine therapy during acute acetaminophen overdose and may provide some additional hepatoprotective benefit 6.
Treatment with Acetylcysteine
- Acetylcysteine appeared superior to placebo and had fewer adverse effects when compared with dimercaprol or cysteamine 4.
- Acetylcysteine should be given to people at risk of toxicity including people presenting with liver failure 4.
- N-acetylcysteine (N-AC) significantly decreased the plasma acetaminophen levels, and the combined therapy with activated charcoal (AC) enhanced the efficacy of N-AC 7.