Toxic Dose of Paracetamol
The toxic dose of paracetamol is 150 mg/kg or ≥10 grams in a single acute ingestion for adults, with this threshold requiring immediate medical evaluation and treatment consideration. 1, 2
Acute Single Ingestion Thresholds
For acute overdose, any ingestion of ≥150 mg/kg or ≥10 grams (whichever is less) is considered potentially toxic and mandates medical assessment. 1, 2 The FDA drug label explicitly states that acute ingestion of 150 mg/kg or greater may result in hepatic toxicity. 2
- In the case series literature, severe hepatotoxicity and mortality have been documented with ingestions ranging from 10-65 grams, with one case report describing survival after a massive 60-gram ingestion (1200 mg/kg). 3, 4
- The mean dose causing severe hepatotoxicity in intentional overdose patients was 23 g/day in one case series. 3
Repeated Supratherapeutic Ingestion (RSTI)
For repeated ingestions, toxicity thresholds are lower and depend on the duration of exposure:
- ≥10 grams or 200 mg/kg (whichever is less) over a single 24-hour period requires evaluation. 1
- ≥6 grams or 150 mg/kg (whichever is less) per 24-hour period for ≥48 hours is potentially toxic. 1
- Severe hepatotoxicity has been documented with doses as low as 4-5 g/day when taken repeatedly, particularly in patients with risk factors. 3, 1
High-Risk Populations
Patients with chronic alcohol use or other risk factors have significantly lower toxicity thresholds:
- The toxic threshold drops to >4 grams or 100 mg/kg per day in high-risk individuals. 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). 3
- One randomized controlled trial showed that even therapeutic doses of 4 g/day for 14 days caused ALT elevations >3 times normal in 31-41% of healthy adults without risk factors. 3, 1
Critical Clinical Considerations
The reported history of ingested quantity is often inaccurate and should not guide treatment decisions alone. 2 Plasma or serum paracetamol concentrations obtained no sooner than 4 hours post-ingestion are essential for risk assessment. 2
Common pitfall: Do not wait for assay results to initiate N-acetylcysteine treatment if the history suggests a potentially toxic ingestion. 2 If paracetamol levels cannot be obtained, assume the overdose is potentially toxic and treat accordingly. 2
For modified release formulations, all ingestions ≥10 grams or ≥200 mg/kg (whichever is less) should receive a full course of acetylcysteine, and ingestions ≥30 grams or ≥500 mg/kg require increased acetylcysteine dosing. 5