Paracetamol was the most commonly misused over-the-counter analgesic in Australia in 2013.1 In 2009–2010 around 14% of all accidental poisoning cases were due to non-opioid analgesics, antipyretics and antirheumatics, with the majority of these cases caused by paracetamol.2 Furthermore, between 1997 and 2005, paracetamol was implicated in around 5% of drug-related deaths in Australia.3
With the increasing concern over the risk of misuse and accidental overdose with over-the-counter paracetamol, changes to recommendations for use of paracetamol (eg, limiting dosage strengths, updating paediatric dosing instructions) have been made in the USA and UK.4-6 The TGA considered these changes in 2013 but to date has not made recommendations to change dosing.
In Australia, paracetamol is recommended as first-line therapy for mild acute or chronic pain that is not relieved by non-pharmacological approaches such as reassurance, rest, ice or heat packs.7 The maximum daily oral dosage of paracetamol in adults and children older than 12 years is 500 to 1000 mg every 4 to 6 hours, or 665 to 1330 mg modified-release paracetamol every 6 to 8 hours, with a maximum of 4 g in a 24-hour period.7-9 In children aged 1 month to 12 years the optimal oral paracetamol dosage is 15 mg/kg (lean body weight, up to a maximum of 1 g) every 4 to 6 hours with no more than four doses (or a total of < 4 g) in a 24-hour period.8,9
Narrow safety margins
Hepatotoxicity has been reported at doses within the therapeutic range of paracetamol (in some cases at doses less than the recommended 4 g/day), although why certain individuals may be at greater risk of toxicity is unclear.10 Toxicity can be influenced by age, comorbidities, alcohol use, nutritional status (eg, prolonged fasting), concurrent medicine use and genetics.10
In children with febrile illness the therapeutic margin for paracetamol may be particularly narrow.10