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 dose 13-15
  lack of knowledge about the dangers of 'double-dipping' or taking two over-the-
counter medicines containing paracetamol 11,15
 perceived safety of paracetamol due to its over-the-counter status 13
 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 medicine 17

 an uncertainty around appropriate indications 16,17,19
 a lack of awareness of strengths and formulations 16,17
 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