30th October 2015, Volume 128 Number 1424

Nadia Freeman, Paul Quigley

Paracetamol is commonly used throughout the world as an effective form of mild pain relief.1 It is the first line analgesic recommended for the treatment of minor injury by the Accident Compensation Corporation.5 However, paracetamol also contributes to considerable financial cost to the health care system through hospital admissions, as paracetamol overdose is now the most common form of drug poisoning in many developed countries.1 While the demand for paracetamol as an effective pain reliever and anti-pyretic appears appropriate, strategies to reduce supply need to be considered to prevent misuse and overdose.

Methods

A dataset on paracetamol poisoning attendances at Wellington Hospital Emergency Department (ED) was extracted from audit data that had been collated through the Emergency Department Information System (EDIS). Data are captured in EDIS automatically for all patients attending with a primary diagnosis within the ICD10 code range T36 to T50 for drugs, medications and biological substances, and T51 to T65 for toxic effects of substances, chiefly non-medical. This dataset is used to provide information to the New Zealand Ministry of Health (MoH) on the cause of poisonings, and the age and sex of those poisoned. For this study, a subset of paracetamol overdoses or accidental poisoning was extracted for the period 2007 to 2012. To single out overdoses where paracetamol was the primary agent, a case-based audit of 2013 data was performed on all EDIS T391 codes with recordable paracetamol levels. All statistical analyses were conducted using Microsoft Excel for Mac 2011 14.6.4 (Microsoft Corporation, Redmond, WA, United States).

The MoH collects information on discharges from publicly-funded hospitals relating to poisonings across New Zealand for the National Minimum Dataset. For this study, data was obtained from the MoH on the number and associated costs of poisonings from 4-aminophenol derivatives subgroup—aminophenol derivatives are used in the synthesis of paracetamol—using the code T39 (of which paracetamol is the only available medication in New Zealand) and on T36–T50, the poisonings subgroup for drugs, medications and biological substances for 2012.

A search on the quantity of paracetamol per packet available for sale through online pharmacies was conducted on 24 February, 2014. New Zealand-operated online pharmacies were found by using online search engine Google, and the key words ‘New Zealand’ and ‘pharmacy’. Pharmacies that sold products online and were identifiable as New Zealand operated by their web address, physical address or retail name were selected.

Literature on effective strategies to reduce overdose rates was found through article databases Google Scholar, Scopus and general searches of a wide range of databases using the University of Otago library aggregator. Key word combinations of ‘paracetamol’, ‘overdose’, ‘self harm’, ‘suicide’, ‘acetaminophen’, ‘quantity’, ‘restriction’ and ‘supply reduction’ were used for these searches. Articles were selected if they described supply reduction strategies with the aim of reducing paracetamol overdose rates.

Results

There were 3,259 episodes of medication poisonings recorded in the Wellington Hospital EDIS from 2007 to 2012. Table 1 shows the frequency of agents used or associated with poisonings. The most common agent was paracetamol, used in 23% of all cases. All other medications accounted for between 3 and 9% of overdoses.

Table 1: The top nine most common medication misused or overdosed in Wellington Hospital Emergency Department presentations 2007–2012 

Agent

No. of Episodes

%

Paracetamol

747

23%

Zopiclone

308

9%

Quetiapine

237

7%

Codeine

158

5%

Ibuprofen

145

5%

Citalopram

134

4%

Clonazepam

133

4%

Fluoxetine

96

3%

Diazepam

93

3%

In 2013, 172 out of 879 (19.6%) overdose presentations to Wellington Hospital Emergency Department were for primary paracetamol poisoning, with serum positive paracetamol levels above the minimum threshold. Of these, 9.3% had paracetamol levels sufficiently high to require treatment (level >1,000 umol/L). The main cause of paracetamol overdose in 2013 was deliberate self-harm and attempted suicide, accounting for 86.2% of presentations, followed by accidental therapeutic overdose at 8.6% and paediatric accidental ingestions at 5.2%. Of the deliberate overdose presentations, 80% were female with a median age of 20, ranging from 13 years to 76 years old.

Data presented in Figure 1 demonstrates that 50% of cases occurred in patients under the age of 20 years. This group also had the highest number of cases that tested at levels above the minimum threshold for treatment than any other age group.

In 2012, aminophenol derivatives (ICD10 T39.1) accounted for 22.4% (1,712) of hospitalisations in New Zealand for poisonings related to drugs, medications and biological substances in (7,637).3 These had an average estimated cost of NZD$1,702.71 per hospitalisation.3

The online survey of New Zealand-operated online pharmacies found that 25 of the 27 sold paracetamol packets containing 100 tablets of 500 mg tablets (50 grams). The price of these packets ranged from NZ$9.99 to NZ$20.99. Sales pages were reviewed for each of the online pharmacy retailers; for each retailer, the only information required to complete the paracetamol product sales were payment and delivery details. No retailers required information on the purchaser’s age or medical history in order to complete the purchase.

Figure 1: Age distribution of deliberate self-harm patients who presented with paracetamol levels above the minimum threshold. 

c 

Paracetamol supply

There is a large body of evidence that both supports and questions the use of strategies that reduce access to large quantities of paracetamol.6,9-11,20,26 Many of these studies concern the effect of the legislative changes introduced to the UK in 1998. This legislation limited the maximum quantity of paracetamol available for purchase in pharmacies to 32, 500 mg tablets (16 g in total), and in all other outlets to 16, 500 mg tablets (8 g in total).12,13

Although several studies have found there were no changes to paracetamol-related suicides, or referrals to transplant units in Scotland,1,19,21 some studies have found strong indications of the legislations effectiveness across the UK, with evaluations reporting a 20% reduction in paracetamol-related overdoses, a 22% reduction in deaths and a 30% reduction in liver unit admissions.13

These findings have been challenged. A 2007 study by Morgan et al observed similar trends for deaths relating to anti-depressants, paracetamol compounds and aspirin.22 One weakness of this study is that aspirin was not a suitable control comparison, as it was subject to similar restrictions to paracetamol under the legislation.22,23 Despite that, Morgan’s findings raise doubt as to whether reductions in paracetamol-related deaths can be attributed to the UK’s legislation change, or may be related to an overall trend in all poisoning-related deaths.

To further investigate the effectiveness of the UK legislation, Hawton et al (2013), conducted an analysis of paracetamol-related deaths and liver transplant registrations, adjusting for potentially confounding trends in all drug poisoning and suicide-related deaths. The analysis observed a 43% reduction in paracetamol-related death and a 61% reduction in paracetamol-related registrations for liver transplants, after adjusting for non-paracetamol poisonings. In addition, both Morgan and Hawton found a significant downward step-change for paracetamol-related deaths immediately after the legislations commencement in 1998, which was not observed by other forms of poisoning.19

The variation in results may be best explained by a wide variation in legislative compliance amongst retailers, with many individuals who overdosed on paracetamol after 1998, reporting to have purchased quantities in excess of the legislative restrictions.23,24,25 This highlights the need to ensure adherence to regulations.

Both prescriptions and online pharmacies have also been found to be the source of unsafe quantities of paracetamol supply. Studies have found a significant proportion of prescribed paracetamol to be above the recommended dosage in both hospital and general practice settings.2,30,31 Likewise, surveys of online pharmacies have found that many fail to supply information on the pharmacy’s country of origin, accreditation, and appropriate use of medicine. A large number of online pharmacies did not collect key customer safety information; did not have systems to detect the accuracy of customer information; and some did not require prescriptions for prescription-only medications.27,28,29 Methods to ensure safety procedures are followed could aid in reducing paracetamol overdose rates.

Discussion

Paracetamol is the most common cause of overdose in many developed countries. Statistics from Wellington Hospital’s ED and the National Minimum Dataset demonstrate New Zealand is no exception to this rule, with paracetamol overdoses accounting for 22–23% of medication poisonings. Of these, poisonings were more common among young females under the age of 20 years.

Paracetamol is often selected for intentional overdose, as a method of self-harm and suicide because of its availability, affordability, known danger and potential to cause death.6-8 In 2012, the average estimated cost of hospitalisations for poisonings with aminophenol derivatives, according to data from public hospitals in New Zealand, was $1,702.71. If multiplied by the number of poisonings for that year (1,712), the total estimated cost of aminophenol poisonings from public hospitalisations in New Zealand in 2012 would have been $2,915,039.

New Zealand does not restrict the amount of paracetamol that can be purchased in pharmacies, and has a set limit of 10 g per packet for all other outlet types, with no limit on the number of packets that may be purchased. 16 This is comparably less secure than the United Kingdom, who have taken steps to restrict paracetamol sales to a maximum of 16 g per transaction in pharmacies and 8 g per transaction, for all other outlets.

In New Zealand, the New Zealand Food and Grocery Council have advocated to the Medicines Classification Committee of Medsafe that the maximum packet capacity should be increased to 12.5 g to align with Australia and free trade agreements.4,18 This is of concern, because acute ingestion of 10 g of paracetamol or more (or 200 mg/kg) within an eight-hour periodrequires hospitalisation and investigation for toxicity.17 This is the same quantity currently available in New Zealand in a single packet for general sale, providing little protection from the risk of overdose. Restricting the quantity to 8 g per sale to align with the United Kingdom may be a more suitable level of protection, in order to prevent potential overdoses.

In addition, the widespread availability of paracetamol in quantities of 50 g or more in pharmacies is cause for concern. This lack of restriction on packet size in pharmacies is compounded by the lack of professional supervision when paracetamol purchases are conducted through online pharmacies. While the survey conducted for the purpose of this article did not use systematic means to identify all online pharmacies in New Zealand, it did demonstrate there were numerous online outlets where paracetamol could be purchased in large quantities, with no measures in place to monitor the safety of consumers.

Due to the high proportion of toxic paracetamol overdose amongst those under the age of 20 years, further investigation into interventions that reduce supply and harm to this age group should be explored. This should include examining the potential benefits of a policy which places age restrictions on the purchase of paracetamol.

There are a number of factors that need to be considered before adopting restrictive strategies, including the potential to increase inequities by reducing access to affordable medication and restricting the free exchange of goods.6,14,15 However, a system similar to the UK’s legislation—to limit pharmacy sales to 16 grams, with a discretionary allowance of 50 grams—could be an effective overdose prevention strategy that provides a suitable level of flexibility for those with higher needs. 

Summary

Statistics on overdoses at Wellington Hospital Emergency Department from 2007-12, found that paracetamol is the most common form of drug poisoning. Examination for potential harm to the liver, is required if a minimum of 10 g of paracetamol is taken within eight hours. For this reason the United Kingdom has limited the sale of paracetamol to 8 g per sale (approximately 16 tablets). In New Zealand, some stores have a limit of 10 g per packet (approximately 20 tablets). But, pharmacies do not have to limit the amount sold in each packet, and there is also no limit on the amount of packets that can be purchased. This is of particular concern when considering online pharmacies, where there are few procedures in place to ensure customer safety.

Abstract

Aim

To examine statistics on paracetamol overdose in New Zealand and investigate options to reduce paracetamol overdose rates, through supply reduction strategies.

Method

Data was gathered from the Ministry of Health’s National Minimum Dataset and Wellington Hospital Emergency Department attendances. Twenty articles on supply reduction strategies were sourced through article database searches. A survey on paracetamol availability from online pharmacies within New Zealand was conducted by searching for New Zealand online pharmacies through Google.

Results

A five-year audit of data (2007–2012) from the Wellington Hospital Emergency Department revealed that paracetamol was the most common medication used for overdose (23%). National data on aminophenol derivatives accounted for 22.4% of poisonings in New Zealand’s public hospitals. An online search found that 25 out of 27 online pharmacies sold packets containing 50 grams of paracetamol. However, the literature supported restricting packets to the minimum threshold for an acute exposure (10 g).

Conclusion

Paracetamol poisoning is the most common form of drug overdose in many developed countries. Tightening restrictions on the quantity of paracetamol sold per packet, in all outlets in New Zealand, may be an effective strategy to reduce overdose rates. This includes online pharmacies where large quantities of paracetamol per packet are available for sale.

Author Information

Nadia Freeman, Public Health Advisor, Regional Public Health, Hutt Valley District Health Board, Wellington; Paul Quigley, Emergency Medicine Specialist, Department of Emergency Medicine, Wellington Hospital, Wellington

Correspondence

Paul Quigley, Emergency Medicine, Capital & Coast District Health Board, Private Bag 7902, Wellington, New Zealand.

Correspondence Email

paul.quigley@ccdhb.org.nz

Competing Interests

Nil

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