Upcoming Changes to Paracetamol Scheduling

The scheduling of paracetamol will change on 1 February 2025, affecting pack sizes and how paracetamol-containing products can be accessed. These changes are intended to minimise harm related to intentional paracetamol overdose while also maintaining appropriate access for therapeutic use.

The upcoming changes are summarised in Table 1. These restrictions apply to all paracetamol-containing products, including combination products with additional active ingredients (e.g. paracetamol-containing cold and flu tablets).

Table 1. Summary of changes to paracetamol scheduling

* Poisons regulations governing the storage and display of Schedule 2 medicines differ slightly in Queensland and Western Australia. In these states, the maximum pack size available for self-selection in a pharmacy will be 16 tablets or capsules; packs of 16 to 100 will be stored behind the counter.

Implementation of changes

Non-pharmacy retailers must comply with these new pack limits from 1 February 2025. They are also encouraged to restrict sales to a single pack at a time.

Pharmacies will also need to implement these changes for the storage and supply of paracetamol products from 1 February 2025. Manufacturers have already begun to supply wholesalers with products that are compliant with the new restrictions in terms of pack size and updated labelling. However, pharmacies have been granted a 12-month labelling exemption. During this period, pharmacies may continue to supply paracetamol-containing products with the existing labelling as long as they comply with the new storage and supply conditions.

Why are these changes being made?

While paracetamol has an excellent safety profile when used therapeutically, it is hepatotoxic and potentially fatal in overdose. Given the ready availability of paracetamol, it is perhaps not surprising to know that it is commonly involved in overdoses. Recent Australian evidence shows that paracetamol is:

• The most common cause of severe acute liver injury;
• The most common reason for calls to Poisons Information Centres;
• One of the most common medications involved in deliberate self-poisoning;
• Involved in a large percentage of accidental paediatric exposures; and
• Involved in a significant number of overdoses with therapeutic intent.

The Therapeutic Goods Administration (TGA) estimate that around 225 people are hospitalised with liver injury, and 50 people die from paracetamol overdose each year in Australia.

The final decision to make these changes was the result of a lengthy consultation period. This included an independent expert report examining the incidence of serious injury and death from intentional paracetamol overdose; advice from the Advisory Committee on Medicines Scheduling (ACMS); and submissions from individuals, and organisations representing consumers, healthcare practitioners, and industry.

The Independent expert report on the risks of intentional self-poisoning with paracetamol was commissioned by the TGA to examine the reasons for the increasing rate of intentional paracetamol overdoses. In particular, the report focussed on the rising prevalence in young people involving paracetamol sourced from non-pharmacy settings (i.e. supermarkets and convenience stores).

This report found that the majority of paracetamol self-poisonings are impulsive but with suicidal intent. This was true across all age groups. The paracetamol taken was present in the home in more than half of all cases, with only around 10% of individuals reporting a recent paracetamol purchase. Where purchases were made, one or two packs were typically bought. The pack sizes most commonly involved were 20/24s and 96/100s; unscheduled products were involved in between 25% and 30% of events.

The largest pack size available is often consumed in an intentional self-poisoning. Therefore, the idea of reducing pack sizes is often suggested as a harm minimisation strategy. Evidence shows that the introduction of reduced pack sizes is associated with reduced harm from self-poisoning. For example, the United Kingdom made changes to the scheduling of paracetamol in 1998. This has been associated with a 43% reduction in paracetamol-related deaths, a 61% reduction in registration for liver transplants due to paracetamol-induced hepatotoxicity, and a reduction in the median number of tablets taken in an intentional overdose (from 50 to 20 tablets for males and from 20 to 16 tablets for females). However, while there has been a significant reduction in the severity of paracetamol poisonings, the frequency of reported cases has not decreased.

Treatment of paracetamol overdose

While paracetamol overdose is common, severe liver injury and death are not common outcomes. This is due to the efficacy of therapies, although this is dependent upon the time to initiation of therapy.

The management of a paracetamol overdose will depend upon the context. For example:

• Overdose involving immediate-release compared to modified-release products;
• Unintentional overdoses in children younger than six years; and
• Unintentional overdose with therapeutic intent (also referred to as repeated supratherapeutic ingestion [RSTI]).

For example, activated charcoal may be used for gastrointestinal decontamination in patients presenting early (i.e. within two hours of ingesting immediate-release preparations and four hours for modified-release). However, this would not be useful in RSTI, where the paracetamol ingestion occurs over a long period.

Acetylcysteine:

Acetylcysteine is a paracetamol antidote used for patients at risk of hepatotoxicity. It is highly effective when given early, particularly within eight hours of ingestion. The therapeutic effect of acetylcysteine occurs via several mechanisms.

When administered in therapeutic quantities, paracetamol is primarily metabolised via glucuronidation and sulfation. Less than 5% is oxidised by cytochrome P450 to generate the toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Glutathione present in the liver can normally detoxify the small amounts of NAPQI produced, thereby preventing cellular injury. This occurs via irreversible conjugation of NAPQI to the sulfhydryl groups of glutathione.

However, when excessive amounts of paracetamol are taken, the glucuronidation and sulfation pathways become saturated. Metabolism via the CYP450 pathway then increases with a greater quantity of NAPQI produced. This leads to the depletion of glutathione reserves and the accumulation of toxic metabolites, which are the causes of hepatic injury.

Acetylcysteine is a sulfhydryl donor which can directly conjugate with NAPQI to prevent hepatic injury. Other possible mechanisms include providing cysteine (an essential precursor of glutathione) and increasing blood flow and oxygen delivery to the liver.

The Updated Guidelines for the Management of Paracetamol Poisoning in Australia and New Zealand provide details of the protocols recommended for various clinical situations. Expert advice is recommended in the following cases as the risk of hepatotoxicity and complications is greater:

• Overdoses involving more than 50g or 1g/kg (whichever is less);
• High paracetamol levels (>3 times the nomogram line);
• Overdoses involving IV paracetamol;
• Hepatotoxicity (i.e. ALT > 100 IU/L); and
• Neonatal poisonings.

Advice can be sought from a clinical toxicologist or from a Poisons Information Centre (13 11 26).

Summary

These changes to paracetamol scheduling are intended to minimise the harm related to intentional overdoses. There have been no changes to treatment guidelines or dosing recommendations. Patients can be assured that paracetamol remains a safe medication when used appropriately.

Additional steps that can be taken to minimise paracetamol-related harm include:

• Encouraging patients to avoid stockpiling medication;
• Encouraging patients to store all medicines out of the reach of children;
• Educating patients to be aware of the active ingredients in the medications they use. This can avoid inadvertent overdosing from taking more than one paracetamol-containing product at the same time; and
• Educating patients on the correct dose and dosing interval for paracetamol.