Paracetamol poisoning

What it is

Paracetamol, also written acetaminophen, is a drug that injures the liver when too much is taken. Acetaminophen overdose is the most common cause of acute liver failure, and drug-induced liver injury is most commonly caused by paracetamol, antibiotics, particularly amoxicillin-clavulanate, and antiepileptic medications, phenytoin and valproate.

Peak plasma concentration comes 4 hours post ingestion, and the half life is generally around 2 hours. Paracetamol toxicity is the example given for drug-induced liver injury, and the classes named beside it are antibiotic, anti fungal, anti TB, anti epilepsy and anti arrhythmia. There the diagnosis is a history of ingestion of one of those drugs, and the treatment is to stop the associated drugs with supportive care.

Causes and risk

The maximum recommended daily dose is 75 mg/kg for children and 4 g for adults. The minimum hepatotoxic dose as a single acute ingestion is 150 mg/kg for a child, and 7.5-10 g, which is 15-20 tablets, for an adult.

Two things are asked at the first contact, and they drive everything that follows:

• Amount ingested: our pages do not agree on the adult amount. It is given as 7.5 g or more in one, as 7.5-10 g in another, and as a potentially hepatotoxic dose of 6-7g in a third, while 4 g is named elsewhere as the dose above which acute liver failure usually follows. In children the number is the same throughout: more than 150 mg/kg.
• Time since ingestion.

Repeated ingestion has its own thresholds, and they go by age. For patients under 6 years of age: 150 mg/kg/day or more for 2 days, or 100 mg/kg/day or more for 3 days or longer. For patients 6 years of age and older: 10 g or 200 mg/kg, whichever is less, over a single 24 hours period, or 6 g or 150 mg/kg, whichever is less, per 24-hour period for 48 hours or longer. For patients with alcoholism, chronic fasting, or on isoniazid (INH) therapy: 4 g or 100 mg/kg per 24 hours, whichever is less.

Acute liver failure is usually caused by acetaminophen ingestion above 4 g, but it can occur with lower doses in patients with alcoholism. There is increasing recognition of toxicity at therapeutic doses in malnourished patients and in alcoholics, called therapeutic misadventure, so these groups have a lower threshold for toxicity.