What is the toxic dose of paracetamol (acetaminophen) in adults and children?

Toxic Dose of Paracetamol (Acetaminophen)

The toxic dose of paracetamol is generally 150 mg/kg or ≥10 grams in a single acute ingestion for adults, and ≥200 mg/kg for children under 6 years of age. 1

Acute Single Ingestion Toxicity Thresholds

Adults

• Ingestions exceeding 10 grams (10,000 mg) in a 24-hour period are considered potentially toxic and require immediate medical evaluation 1
• The threshold can also be expressed as 150 mg/kg, whichever amount is reached first 1
• Severe hepatotoxicity and mortality have been documented with ingestions ranging from 10-65 grams, with documented survival after massive 60-gram ingestions (1200 mg/kg) 1
• In adults, ingestion of less than 125 mg/kg is unlikely to lead to hepatotoxicity 2

Children

• Children under 6 years require emergency department referral if they ingest ≥200 mg/kg in a single acute ingestion 3
• Children 6 years or older should be referred if they ingest at least 10 g or 200 mg/kg (whichever is lower) 3
• Single ingestions of more than ten times the recommended dose (>150 mg/kg) are potentially toxic 4
• Higher doses may be tolerated by children without causing liver damage compared to adults 2

Repeated Supratherapeutic Ingestion (RSTI)

Repeated supratherapeutic ingestions carry a worse prognosis than acute single overdoses and account for approximately 30% of acetaminophen overdose admissions. 1, 5

Adults

• ≥10 grams or 200 mg/kg (whichever is less) over a single 24-hour period requires medical evaluation 1
• ≥6 grams or 150 mg/kg (whichever is less) per 24-hour period for 48 hours or longer is potentially toxic 1
• For high-risk individuals (chronic alcohol use, liver disease, prolonged fasting), the threshold is lower at >4 grams or 100 mg/kg per day 1, 3

Children

• Children under 6 years should be referred to emergency department if they have ingested:
  • ≥200 mg/kg over a single 24-hour period, OR 3
  • ≥150 mg/kg per 24-hour period for the preceding 48 hours, OR 3
  • ≥100 mg/kg per 24-hour period for 72 hours or longer 3
• Liver injury should be considered when a child has received >75 mg/kg/day for at least 2 days 6
• Exposures greater than 140 mg/kg/day for several days carry a risk of serious toxicity 4

High-Risk Populations with Lower Toxicity Thresholds

Certain patient populations develop toxicity at significantly lower doses than the general population.

Chronic Alcohol Users

• Severe hepatotoxicity has been documented with doses as low as 4-5 g/day in chronic alcohol users 1
• Multiple case series demonstrate severe hepatotoxicity and mortality (20-33%) in chronic alcoholics taking 2.5-16.5 g/day (median 6.4 g/day) 1
• Cases of severe hepatotoxicity with doses between 5-20 g/day have been documented in alcoholic patients, with a mortality rate of 33% 1

Patients with Pre-existing Liver Disease

• Pre-existing liver disease, including cirrhosis, significantly increases susceptibility to acetaminophen hepatotoxicity 1
• These patients should limit intake to 2000-3000 mg daily 5

Other Risk Factors

• Prolonged fasting increases susceptibility to toxicity 3
• Isoniazid use increases risk 3
• Even therapeutic doses of 4 g/day for 14 days can cause ALT elevations >3 times normal in 31-41% of healthy adults without risk factors 1, 5

Modified Release Formulations

• All potentially toxic modified release paracetamol ingestions (≥10 g or ≥200 mg/kg, whichever is less) should receive a full course of acetylcysteine 7
• Patients ingesting ≥30 g or ≥500 mg/kg should receive increased doses of acetylcysteine 7

Critical Clinical Pearls and Pitfalls

• Very high aminotransferase levels (AST/ALT >3,500 IU/L) are highly correlated with acetaminophen poisoning and should raise suspicion even without clear overdose history 1
• Low or absent acetaminophen levels do not rule out acetaminophen poisoning if the ingestion was remote, occurred over several days, or timing is uncertain 1
• The Rumack-Matthew nomogram should be used to assess risk when acetaminophen level is drawn 4-24 hours post-ingestion—levels above 200 mcg/mL at 4 hours or 50 mcg/mL at 12 hours indicate potential hepatotoxicity 1
• Acetaminophen levels drawn before 4 hours are unreliable and should be repeated at 4 hours 1
• Combination products containing acetaminophen (with opioids like hydrocodone or codeine) significantly increase the risk of unintentional overdose because patients may not realize they are taking acetaminophen from multiple sources 1

Treatment Urgency

• Treatment within 8 hours results in only 2.9% severe hepatotoxicity; this increases to 6.1% when treated within 10 hours and 26.4% when treated 10-24 hours post-ingestion 1
• N-acetylcysteine (NAC) treatment should be initiated immediately for any patient with acetaminophen levels above the treatment line on the nomogram 1
• NAC should also be initiated for any patient with suspected acetaminophen ingestion with signs of liver injury (elevated transaminases) 1