July 2018
clinical initiatives, research and current updates in treatment
Paracetamol safety and risk of inadvertent toxicity Chris Henry, Epic Pharmacy
Paracetamol is the most commonly used over the counter analgesic in the world.1 For the majority of people who use this drug, it is safe and effective.2 However, paracetamol overdose due to accidental paediatric exposures, repeated supra-therapeutic intake (RSI) (i.e. above usual doses required for treatment) and deliberate selfpoisonings can lead to hepatic toxicity and is currently the leading drug responsible for calls to Poisons Information Centres in Australia and New Zealand. 1 Fortunately, due to the availability of an effective antidote, hepatic failure and death are uncommon outcomes. However, paracetamol remains the most important single cause of acute hepatic failure in developed countries. 1 Confusion surrounding the appropriate use and dose in children and infants combined with the availability of numerous paracetamol-containing formulations exposes many patients to the risk of inadvertent overdose. There are currently over 30 different formulations of paracetamol containing products listed on the Australian Register of Therapeutic Goods. 3
The potential for overdose also exists in healthcare facilities. Instances of duplicate orders on multiple drug charts; poorly written or illegible prescriptions and orders for multiple paracetamol containing products or formulations increases the risk of paracetamol toxicity for inpatients. Nurses, doctors and pharmacy staff play important roles in educating patients, carers and parents about the appropriate use, accurate dosing and potential harms of paracetamol both within healthcare facilities and in the community.
the kidneys. 2 However, when taken in larger amounts, the liver is forced to use a different group of enzymes to process paracetamol which results in the accumulation of a toxic metabolite called N-acetyl-p-benzoquinoneimine (NAPQI). 2 NAPQI accumulation results in damage to the liver cells which can progress to liver failure. Current guidelines for the management of paracetamol poisoning define the toxic thresholds for paracetamol ingestion below. 1
Doses considered toxic
Toxicology
Acute Single Ingestion
Despite its long-term use as an analgesic, the precise mechanism of action of paracetamol remains unknown. 2 Paracetamol is rapidly absorbed from the small intestine (after oral administration of the immediate-release tablet) and reaches peak plasma concentration within 1-2 hours (or within 30 minutes for liquid preparations). 1 Elimination half-life is typically 2-3 hours, however, this can be delayed in the elderly, neonates and patients with pre-existing liver disease. 2 At therapeutic doses, paracetamol is processed by liver enzymes to produce predominantly non-toxic metabolites which are excreted by
>200mg/kg or 10g (whichever is less)
Repeated Supra‑Therapeutic Ingestion (RSI) >150mg/kg or 6g (whichever is less) per 24 hours over a 48‑hour period >100mg/kg or 4g (whichever is less) per 24 hours over a period more than 48 hours Continued on page 2