Toxic Dose of Paracetamol (Acetaminophen)
The toxic dose of paracetamol is 150 mg/kg or 10 grams (whichever is less) in a single acute ingestion for adults, though severe hepatotoxicity can occur with repeated doses as low as 4-6 grams per day in high-risk individuals. 1
Acute Single Ingestion Thresholds
For adults, any single ingestion exceeding 10 grams (10,000 mg) in a 24-hour period is considered potentially toxic and requires immediate medical evaluation. 1
The 150 mg/kg threshold applies across age groups, though children may tolerate higher doses per kilogram without liver damage compared to adults. 2
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) when treated appropriately. 1
In therapeutic doses, ingestion of less than 125 mg/kg is unlikely to lead to hepatotoxicity in adults. 2
Repeated Supratherapeutic Ingestion (RSTI)
This is a critical pitfall—repeated "therapeutic" doses can be more dangerous than recognized:
Repeated ingestions totaling ≥10 grams or 200 mg/kg (whichever is less) over a single 24-hour period require medical evaluation. 1
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
Severe hepatotoxicity has been documented with doses as low as 4-5 grams per day when taken repeatedly, particularly in patients with risk factors. 1
Even therapeutic doses of 4 grams per day for 14 days caused ALT elevations >3 times normal in 31-41% of healthy adults without any risk factors. 1
High-Risk Populations with Lower Toxicity Thresholds
For patients with risk factors, the toxic threshold drops dramatically:
Chronic alcoholics: Multiple case series demonstrate severe hepatotoxicity and 20-33% mortality with doses of 2.5-16.5 grams/day (median 6.4 grams/day). 1, 3
For high-risk individuals (chronic alcohol use, pre-existing liver disease, malnutrition, fasting state), the toxic threshold is >4 grams or 100 mg/kg per day. 1
Patients with cirrhosis, active drinking, or malnutrition should have maximum doses limited to 3 grams per day even for therapeutic use. 3
Pre-existing liver disease and chronic alcohol consumption significantly increase susceptibility to hepatotoxicity at otherwise "therapeutic" doses. 1
Treatment Thresholds Using the Rumack-Matthew Nomogram
The nomogram is used for acute ingestions with known timing (4-24 hours post-ingestion): levels above 200 mcg/mL at 4 hours or 50 mcg/mL at 12 hours indicate potential hepatotoxicity requiring N-acetylcysteine treatment. 1
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
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
Modified Release and Massive Overdoses
All potentially toxic modified release paracetamol ingestions (≥10 grams or ≥200 mg/kg, whichever is less) should receive a full course of acetylcysteine. 4
Patients ingesting ≥30 grams or ≥500 mg/kg should receive increased doses of acetylcysteine due to the massive overdose. 4
Critical Pitfalls to Avoid
Combination products containing paracetamol (with opioids like hydrocodone or codeine) significantly increase the risk of unintentional overdose because patients may not realize they are taking paracetamol from multiple sources. 1
Low or absent paracetamol levels do not rule out poisoning if the ingestion was remote, occurred over several days, or timing is uncertain. 1
The maximum therapeutic dose is 4 grams per day for the general population, but should be limited to 2-3 grams per day for patients with liver disease or chronic alcohol use. 1