Paracetamol is one of the most commonly used over-the-counter analgesics but misuse and accidental overdose is of increasing concern. Toxicity can occur even at doses lower than the recommended daily maximum dose. Gaps in patient knowledge, particularly around the perceived safety of paracetamol, are contributing factors to paracetamol misuse and accidental overdose.
Confusion surrounding the appropriate indications, formulations, and dose for infants and children also contributes to dosing errors in infants and children younger than 12 years. GPs and pharmacists play a key role in educating patients and carers of infants and children on the safe use of paracetamol.
- Paracetamol is recommended as first-line therapy for management of mild acute pain or chronic pain that is not relieved by non-pharmacological approaches.
- Discuss the potential for liver damage with misuse and overdose of paracetamol with your patients.
- Educate patients on how to identify paracetamol as the active ingredient in single and combination medicines.
- Discuss hazards and risks of overdosing through simultaneous use of multiple paracetamol-containing medicines. Inform patients of the maximum total dose and number of tablets permitted in a 24-hour period.
- Encourage patients to follow directions for use of paracetamol-containing medicines.
- Encourage patients to discuss any questions they may have regarding paracetamol-containing medicines.
Misuse and overdose with paracetamol
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
Gaps in patient knowledge
Approximately half to two-thirds of overdose cases associated with paracetamol use are unintentional.11,12 Descriptive, cross-sectional studies have highlighted deficiencies in patient knowledge about paracetamol use.11,13-15 These deficiencies centred around:
- lack of recognition of paracetamol as the active ingredient in a multitude of generic and brand name medicines11,13,14
- uncertainty surrounding the maximum daily dose13-15
- lack of knowledge about the dangers of 'double-dipping' or taking two over-the-counter medicines containing paracetamol11,15
- perceived safety of paracetamol due to its over-the-counter status13
- lack of awareness of the potential for liver damage with misuse.11,13
Carer uncertainties on appropriate and safe use in infants and children
Of all accidental poisonings by pharmaceuticals resulting in hospital admissions reported in Australia during 2009–2010, around 3% occurred in children aged 0–4 years and were attributable to non-opioid analgesics, antipyretics and antirheumatics. Of these most were due to paracetamol, and non-steroidal anti-inflammatory medicines.2
Knowledge gaps in carers of young children may contribute to unintentional misuse and overdose of paracetamol.11,16,17 In a cross-sectional study performed in the USA, only 38% of participants correctly selected and measured the appropriate paracetamol dose for infants or children.18
Knowledge gaps with respect to paracetamol use in children included:
- the perception that paracetamol is a safe medicine17
- an uncertainty around appropriate indications16,17,19
- a lack of awareness of strengths and formulations16,17
- the methods used to measure the correct dose.16,17
Multivariate analysis demonstrated that limited literacy was a significant independent predictor of paracetamol overdose.14,15 Therefore, in addition to simple and effective package labelling, education on the appropriate and safe use of paracetamol in adults and children is an important contributor to safe use.
Information for patients
Ensure your patients are aware that:
- Paracetamol is the active ingredient in a number of pain and fever relief medicines and combination medicines (eg, for cold and flu).
- Overdose can occur when taking more than one paracetamol-containing medicine.
- The maximum daily dose of 4 g in any given 24 hour period should not be exceeded for adults and children aged > 12 years.
When recommending paracetamol for pain relief in children and infants less than 12 years of age, ensure carers know the following:
- Paracetamol comes in different formulations and strengths for different ages. It is important to choose the correct paracetamol product for the child's age.
- Always read the medicine label and packaging before use.
- Knowing the child's weight – the recommended dose of paracetamol for children is based on ideal body weight (15 mg/kg).a
- Never exceed the maximum recommended dosage for children of 15 mg/kg every 4–6 hours to a maximum of 1 g, and no more than 4 doses in a 24-hour period.
- It is important to measure liquid medicines accurately using the syringe or device provided.
- Keep track of all medicines given to the child, and when they were given.
- Store medicines out of reach of children.
a Children more than 20% above their ideal body weight should be dosed according to their lean body weight which can be estimated by determining their predicted weight for height.20
- Australian Institute of Health and Welfare. National drug strategy household survey detailed report. Canberra: Australian Institute of Health and Welfare, 2014. [Online] (accessed 27 April 2015).
- Tovell A, McKenna K, Bradley C, et al. Hospital separations due to injury and poisoning, Australia. Canberra: Australian Institute of Health and Welfare, 2012. [Online] (accessed 27 April 2015).
- Drug Free Australia. Australian Bureau of Statistics - Deaths collection. Broadview, South Australia: Drug free Australia, 2007. [Online] (accessed 27 April 2015).
- US Food and Drug Administration. New steps aimed at cutting risks from acetaminophen. Silver Spring, Maryland: US Food and Drug Administration, 2011. [Online] (accessed 27 April 2015).
- Medicines and Healthcare Products Regulatory Agency. Press release: More exact paracetamol dosing for children to be introduced. London: Medicines and Healthcare Products Regulatory Agency, 2011. [Online] (accessed 27 April 2015).
- US Food and Drug Administration. Acetaminophen information. Maryland: US Food and Drug Administration, 2015. [Online] (accessed 1 May 2015).
- Expert group for analgesic. Therapeutic guidelines: analgesic. Melbourne: Therapeutic Guidelines Ltd, 2015. [Online] (accessed 27 April 2015).
- Australian Medicines Handbook. Paracetamol. Adelaide: AMH Ltd, 2015. [Online] (accessed 27 April 2015).
- Therapeutic Goods Administration. Recommended paracetamol doses. Canberra: Therapeutic Goods Administration, 2013. [Online] (accessed 27 April 2015).
- Amar PJ and Schiff ER. Acetaminophen safety and hepatotoxicity--where do we go from here? Expert Opin Drug Saf 2007;6:341–55. [PubMed].
- King JP, Davis TC, Bailey SC, et al. Developing consumer-centered, nonprescription drug labeling a study in acetaminophen. Am J Prev Med 2011;40:593–8. [PubMed].
- Bower WA, Johns M, Margolis HS, et al. Population-based surveillance for acute liver failure. Am J Gastroenterol 2007;102:2459–63. [PubMed].
- Hornsby LB, Whitley HP, Hester EK, et al. Survey of patient knowledge related to acetaminophen recognition, dosing, and toxicity. J Am Pharm Assoc (2003) 2010;50:485–9. [PubMed].
- Shone LP, King JP, Doane C, et al. Misunderstanding and potential unintended misuse of acetaminophen among adolescents and young adults. J Health Commun 2011;16 Suppl 3:256–67. [PubMed].
- Wolf MS, King J, Jacobson K, et al. Risk of unintentional overdose with non-prescription acetaminophen products. J Gen Intern Med 2012;27:1587–93. [PubMed].
- Therapeutic Goods Administration. Labelling and packaging practices: A summary of some of the evidence. Canberra: Therapeutic Goods Administration, 2013. [Online] (accessed 27 April 2015).
- Graudins LV and Gazarian M. Promoting safe use of paracetamol in children. J Pharmacy Pract Res 2006;36:297–300. [Online].
- Hurwitz J, Sands S, Davis E, et al. Patient knowledge and use of acetaminophen in over-the-counter medications. J Am Pharm Assoc (2003) 2014;54:19–26. [PubMed].
- Walsh A, Edwards H and Fraser J. Over-the-counter medication use for childhood fever: a cross-sectional study of Australian parents. J Paediatr Child Health 2007;43:601–6. [PubMed].
- Beggs S. Paediatric analgesia. Australian Prescriber 2008;31:63–5. [Online].