What is the toxic dose of Tylenol (acetaminophen)?

Toxic Dose of Acetaminophen (Tylenol)

The toxic dose of acetaminophen is generally considered to be 150 mg/kg or greater in a single acute ingestion, which is approximately 10 grams or more for most adults. 1, 2

Acute Single Ingestion Toxicity

• For adults, ingestions exceeding 10 grams (10,000 mg) in a 24-hour period are considered potentially toxic and require medical evaluation 1, 2
• For children under 6 years, the toxic threshold is 200 mg/kg in a single ingestion 3
• For patients 6 years and older, toxicity risk exists at either 10 grams or 200 mg/kg, whichever is lower 3
• While most toxic ingestions exceed 10 grams, severe liver injury has been reported rarely with doses as low as 3-4 grams per day 1

Repeated Supratherapeutic Ingestion (RSTI)

• For adults, repeated ingestions totaling ≥10 grams or 200 mg/kg (whichever is less) over a single 24-hour period require medical evaluation 1, 3
• Repeated ingestions of ≥6 grams or 150 mg/kg (whichever is less) per 24-hour period for 48 hours or longer are potentially toxic 1, 3
• For high-risk individuals (alcoholism, isoniazid use, prolonged fasting), the threshold is lower at >4 grams or 100 mg/kg per day 1, 3

Risk Assessment and Monitoring

• Serum acetaminophen levels should be measured at least 4 hours post-ingestion to determine toxicity risk using the Rumack-Matthew nomogram 4, 1
• Values above the treatment line (starting at 150 μg/mL at 4 hours and declining to 4.7 μg/mL at 24 hours) indicate potential hepatotoxicity 4
• For extended-release formulations, an additional level 4-6 hours after the first measurement is recommended to capture delayed absorption 5
• Patients with very high aminotransferase levels (>3,500 IU/L) should be suspected of acetaminophen toxicity even without a clear history of overdose 1

Treatment Thresholds

• N-acetylcysteine (NAC) treatment should be initiated for any patient with:
  • Acetaminophen levels above the treatment line on the nomogram 1, 4
  • Unknown time of ingestion with detectable acetaminophen levels 1
  • Suspected acetaminophen ingestion with signs of liver injury (elevated transaminases) 1

Maximum Therapeutic Dose

• The traditional maximum daily therapeutic dose is 4,000 mg (4 grams) per day 6, 1
• Some manufacturers have voluntarily reduced recommended maximum daily doses to 3,000-3,250 mg per day 6
• For patients with risk factors for hepatotoxicity, the maximum daily dose should be limited to 2,000-3,000 mg 1

Clinical Pearls and Pitfalls

• Patient history regarding amount and timing of ingestion is often unreliable; laboratory testing is essential 4, 2
• The nomogram cannot be used for repeated supratherapeutic ingestions or when the time of ingestion is unknown 1
• Peak hepatotoxicity typically occurs 48-96 hours after ingestion, even when acetaminophen is no longer detectable in serum 2
• Activated charcoal is most effective when administered within 1-2 hours of ingestion 1, 3
• Extended-release acetaminophen formulations may have delayed absorption, requiring additional monitoring 5