Epidemiology
Paracetamol is the most widely used non-prescription analgesic in the world, and one of the most frequently used drugs in intentional overdoses.[4][5] In 2021, 4859 deaths related to drug poisoning were registered in England and Wales; 227 of these were related to paracetamol poisoning.[6]
Toxicity may occur during self-medication for pain or following intentional overdose.[4][7][8]
In 2021, the American Association of Poison Control Centers' National Poison Data System reported 61,632 exposure cases (where there is actual or suspected contact [e.g., ingestion, inhalation, absorption] reported with a substance) involving paracetamol alone (995 life-threatening or disabling; 109 fatal) and 12,690 involving paracetamol in combination with another drug (51 life-threatening or disabling; 2 fatal).[9]
A clinically significant proportion of emergency department patients over-use non-prescription analgesics, with dental pain appearing to be a particular risk factor.[10][11][12] The use of multiple brand-name products containing paracetamol in varying doses can lead to unintended overdose.
There are rare case reports relating to iatrogenic paracetamol poisoning following intravenous administration of paracetamol.[13][14]
Risk factors
Paracetamol is present either alone or in combination with other drugs in many non-prescription preparations. The use of multiple brand-name products containing paracetamol in varying doses can lead to unintended overdose. A clinically significant proportion of emergency department patients over-use non-prescription analgesics, with dental pain appearing to be a particular risk factor.[10][11][12]
Retrospective studies suggest that patients who have a frequent or repeated supratherapeutic ingestion pattern of misuse for pain relief have a disproportionate incidence of severe hepatotoxicity and the most deaths.[19][20][21]
Patients who have relatively low levels of glutathione are more at risk of liver damage following paracetamol overdose.[22] However, there is no reliable method to assess glutathione stores in patients.
Patients at risk of glutathione deficiency include those with malnourishment (e.g., not eating because of dental pain, fasting for more than a day), eating disorders (e.g., anorexia, bulimia), psychiatric disorders, chronic illness (e.g., HIV, cystic fibrosis), cachexia, and alcohol-use disorder.[1]
Long-term treatment with drugs that induce liver enzymes (cytochrome P450 inducers) may increase the risk of liver injury following paracetamol overdose. These include carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, rifabutin, efavirenz, nevirapine, and St John’s wort.[1]
Unintentional overdose of oral paracetamol has been reported in adult inpatients with low bodyweight (<50 kg).[2] Caution is advised when prescribing oral and intravenous paracetamol to these patients; dose should be adjusted.[2] British Hepatology Pharmacy Group: Prescribing weight-adjusted oral paracetamol in adults Opens in new window
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