What is the toxic dose of paracetamol (Acetaminophen) in adults?

Paracetamol Toxic Dose in Adults

The toxic dose of paracetamol in adults is generally 150 mg/kg or ≥10 grams in a single acute ingestion, though severe hepatotoxicity can occur with doses as low as 4 grams per day in high-risk populations such as chronic alcoholics or malnourished patients. 1, 2

Acute Single Ingestion Thresholds

For most adults, ingestions exceeding 10 grams (10,000 mg) in a 24-hour period are considered potentially toxic and require immediate medical evaluation. 1

• The FDA label warns that severe liver damage may occur if an adult takes more than 4,000 mg of acetaminophen in 24 hours, which represents the maximum daily therapeutic amount 3
• The standard toxic threshold is 150 mg/kg or 10 grams (whichever is less) for acute single ingestions 1, 4
• Documented cases of severe hepatotoxicity and mortality have occurred with ingestions ranging from 10-65 grams, with mean doses causing severe hepatotoxicity around 23 grams 2
• For adults weighing less than 70 kg, a 7-gram ingestion represents >100 mg/kg and places them at higher risk 5

Repeated Supratherapeutic Ingestion (RSTI)

Repeated ingestions totaling ≥10 grams or 200 mg/kg (whichever is less) over a single 24-hour period require medical evaluation, with lower thresholds for high-risk individuals. 1, 4

• 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, 4
• For high-risk individuals (chronic alcoholics, malnourished patients, those taking enzyme-inducing drugs), the threshold drops to >4 grams or 100 mg/kg per day 1, 4
• Severe hepatotoxicity has been documented with doses as low as 4-5 grams per day when taken repeatedly, particularly in patients with risk factors 2

High-Risk Populations with Lower Toxicity Thresholds

Chronic alcohol users, malnourished patients, and those with pre-existing liver disease develop toxicity at significantly lower doses than the general population. 5, 2

• Multiple case series demonstrate severe hepatotoxicity and mortality (20-33%) in chronic alcoholics taking 2.5-16.5 grams per day (median 6.4 grams per day) 2
• The FDA label specifically warns that liver damage may occur when paracetamol is taken with 3 or more alcoholic drinks every day 3
• For patients with risk factors for hepatotoxicity, the maximum daily dose should be limited to 2,000-3,000 mg 1
• Malnourished patients have depleted glutathione stores, making them more vulnerable to paracetamol toxicity even at therapeutic doses 5

Critical Clinical Context

Even therapeutic doses of 4 grams per day for 14 days can cause ALT elevations >3 times normal in 31-41% of healthy adults without risk factors. 5, 2

• Severe liver injury has been reported rarely with doses as low as 3-4 grams per day 1
• Very high aminotransferase levels (AST/ALT >3,500 IU/L) are highly correlated with paracetamol poisoning and should raise suspicion even without clear overdose history 1, 2
• The Rumack-Matthew nomogram is used to assess risk when paracetamol 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

Common Pitfalls and Caveats

• No absolute "lethal dose" exists—mortality critically depends on the time until treatment with N-acetylcysteine (NAC), not just the amount ingested 1
• Low or absent paracetamol levels do NOT rule out paracetamol poisoning if ingestion was remote, occurred over several days, or timing is uncertain 1
• Combination products containing paracetamol (such as those with opioids) significantly increase the risk of unintentional overdose because patients may not realize they are taking paracetamol from multiple sources 1
• Patients may present with elevated transaminases despite being stratified as "no risk" on the nomogram due to inaccurate history or increased susceptibility 5
• Extended-release formulations may show late increases in serum paracetamol concentration at 14 hours or beyond, requiring serial paracetamol levels 5