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Paracetamol Overdose

NICE BNF Treatment summaries. Poisoning, emergency treatment. Paracetamol poisoning.

Article Last Updated: 13 November 2025

Background information added accordingly.

Date: 13 November 2025

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Background Information

Pathophysiology

Clinical Presentation

Time from ingestion	Clinical manifestation	Laboratory results
0-24 hours	Asymptomatic or mild non-specific symptoms Nausea / vomiting Anorexia Malaise Diaphoresis	Blood tests are generally normal ALT may be elevated
24-72 hours	Hepatic injury occurs at this point: RUQ pain Hepatomegaly	Deranged LFTs
72-96 hours	Maximal liver toxicity occurs at this point Jaundice Hepatic encephalopathy Coagulopathy Hypoglycaemia The most common stage for death to occur due to acute liver failure and subsequent multisystem organ failure	AST levels peak (>1,000 IU/L) Signs of acute liver failure (synthetic dysfunction) Hyperbilirubinaemia Prolonged PT / INR Hypoglycaemia Lactic acidosis Acute renal failure

Classification

Type	Definition
Acute overdose	Ingestion of all the paracetamol tablets within 1 hour
Staggered overdose	Ingestion of the paracetamol tablets over more than 1 hour
Therapeutic excess	Ingestion of potentially toxic paracetamol dose with the intent to treat pain / fever and without self-harm intent

Diagnosis

Investigation and Diagnosis

Management

Essential information to obtain from the history of ANY drug overdose cases:

Elicit the agent involved
Elicit the dose
Elicit the intent
Pattern of use (acute or staggered?)
Time of ingestion
Presence of co-ingestants
Presence of comorbid conditions or medications (e.g. Gilbert disease, alcohol use, antiepileptic drugs)

Antidote of choice for paracetamol overdose is N-acetylcysteine (standard 21-hour regimen, 3 consecutive IV infusions over 1 hour, 4 hours and 16 hours).

Prevents or reduces the severity of liver damage if given up to 24 hours after ingestion (possibly beyond 24 hours)
Most effective when given within 8 hours of ingestion, its effectiveness declines after

Guidelines regarding paracetamol overdose are complicated, therefore the author presented 2 approaches: 1) a list of indications to give N-acetylcysteine immediately, 2) management depending on the type of overdose. It is recommended to go over both and consolidate the content.

Indications to Give N-acetylcysteine Immediately

Management by Type of Overdose

Unknown Ingestion Timing

Staggered Overdose

Acute Overdose

Scenario	Management
Ingested <4 hours ago	Wait until 4 hours after ingestion, then measure serum paracetamol concentration, and Only give N-acetylcysteine if paracetamol level is on or above the treatment line
Ingested <8 hours ago	Give N-acetylcysteine immediately (without waiting for paracetamol concentration) if Dose >150 mg/kg, and There will be a delay of ≥8 hours in obtaining paracetamol levels
Ingested 8-24 hours ago	Give N-acetylcysteine immediately (without waiting for paracetamol concentration) if there is ANY of the following: Dose >150 mg/kg Unknown dose Symptomatic (jaundiced or RUQ tenderness)
Ingestion >24 hours	Give N-acetylcysteine if any of the following: >150 mg/kg Unknown dose Symptomatic (jaundiced or RUQ tenderness) Detectable paracetamol concentration
Biochemical tests suggest acute liver injury (e.g. ↑ ALT, INR >1.3 in the absence of other causes)	Give N-acetylcysteine (even if paracetamol concentration is BELOW the treatment line)

Therapeutic Excess

References

BNF Treatment summaries Poisoning emergency treatment

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Hepatitis	↑↑ AST and ALT levels (often >1,000 IU/L)
Liver synthetic dysfunction (from acute liver failure)	Prolonged INR / PT (the earliest and most sensitive marker of loss of hepatic synthetic function) ↑ Bilirubin Hypoglycaemia
Systemic / secondary effects	Lactic acidosis → high-anion-gap metabolic acidosis ↑ Urea and creatinine (from acute renal failure)