Stocks of paracetamol products stored in urban New Zealand households: A cross-sectional study.

BACKGROUND: Intentional self-harm is a common cause of hospital presentations in New Zealand and across the world, and self-poisoning is the most common method of self-harm. Paracetamol (acetaminophen) is frequently used in impulsive intentional overdoses, where ease of access may determine the choice of substance. OBJECTIVE: This cross-sectional study aimed to determine how much paracetamol is present and therefore accessible in urban New Zealand households, and sources from where it has been obtained. This information is not currently available through any other means, but could inform New Zealand drug policy on access to paracetamol. METHODS: Random cluster-sampling of households was performed in major urban areas of two cities in New Zealand, and the paracetamol-containing products, quantities, and sources were recorded. Population estimates of proportions of various types of paracetamol products were calculated. RESULTS: A total of 174 of the 201 study households (86.6%) had at least one paracetamol product. Study households had mostly prescription products (78.2% of total mass), and a median of 24.0 g paracetamol present per household (inter-quartile range 6.0-54.0 g). Prescribed paracetamol was the main source of large stock. Based on the study findings, 53% of New Zealand households had 30 g or more paracetamol present, and 36% had 30 g or more of prescribed paracetamol, specifically. CONCLUSIONS: This study highlights the importance of assessing whether and how much paracetamol is truly needed when prescribing and dispensing it. Convenience of appropriate access to therapeutic paracetamol needs to be balanced with preventing unnecessary accumulation of paracetamol stocks in households and inappropriate access to it. Prescribers and pharmacists need to be aware of the risks of such accumulation and assess the therapeutic needs of their patients. Public initiatives should be rolled out at regular intervals to encourage people to return unused or expired medicines to pharmacies for safe disposal.

A cluster randomized trial to measure the impact on nonsteroidal anti-inflammatory drug and proton pump inhibitor prescribing in Italy of distributing cost-free paracetamol to osteoarthritic patients.

BACKGROUND: Paracetamol is recommended as first-line treatment for pain control in osteoarthritis because it has fewer side effects than do other therapeutic options, including nonsteroidal anti-inflammatory drugs (NSAIDs). Prescribing proton pump inhibitors (PPIs) as gastric bleeding prophylaxis in chronic NSAID users is also common, although not recommended. In Italy, paracetamol is not reimbursed by the National Health System. The aim of this trial was to test whether the availability to osteoarthritis patients of free paracetamol would decrease their use of NSAIDs and, as a secondary objective, whether opioid and PPI consumption would also decrease. METHODS: Eight general practitioners (GPs) (59 patients) were randomized to usual care and 8 (58 patients) to the experimental arm, where prescribed paracetamol was directly distributed for free by the local hospital. After 6 months, paracetamol was also available for free in the control arm. The main outcome was the pre/post difference in average NSAID and PPI consumption. Differences between experimental and control arms in pre/post differences are reported, as registered by the drug prescription information system. RESULTS: Average NSAID consumption decreased non-significantly, from 6.79 to 2.16 defined daily dose (DDD) in the experimental arm and from 3.19 to 2.97 DDD in the control group (p = 0.067). No changes were observed for PPIs (from 11.27 to 14.65 DDD and from 9.74 to 12.58 DDD in experimental and control arms, respectively, p = 0.788) or opioids (from 1.61 to 1.14 DDD and from 1.41 to 1.56 DDD in experimental and control arms, respectively, p = 0.419). When the intervention was extended to the control arm, no decrease in NSAID consumption was observed (from 2.46 to 2.43 DDD, p = 0.521). CONCLUSIONS: Removing small economic barriers had small or no effect on the appropriateness of opioid or PPI prescribing to patients with osteoarthritis; a reduction in NSAID consumption cannot be ruled out. TRIAL REGISTRATION NUMBER: NCT02691754 (Approved February 24, 2016).

Availability and affordability of priority life-saving medicines for under-five children in health facilities of Tigray region, northern Ethiopia.

BACKGROUND: In developing countries, child health outcomes are influenced by the non-availability of priority life-saving medicines at public sector health facilities and non-affordability of medicines at private medicine outlets. This study aimed to assess availability, price components and affordability of priority life-saving medicines for under-five children in Tigray region, Northern Ethiopia. METHODS: A cross-sectional study was conducted in Tigray region from December 2015 to July 2016 using a standard method developed by the World Health Organization and Health Action International (WHO/HAI). Data on the availability and price of 27 priority life-saving medicines were collected from 31 public and 10 private sectors. Availability and prices were expressed in percent and median price ratios (MPRs), respectively. Affordability was reported in terms of the daily wage of the lowest-paid unskilled government worker. RESULTS: The overall availability of priority life-saving drugs in this study was low (34.1%). The average availabilities of all surveyed medicines in public and private sectors were 41.9 and 31.5%, respectively. The overall availability of medicines for malaria was found to be poor with average values of 29.3% for artemisinin combination therapy tablet, 19.5% for artesunate injection and 0% for rectal artesunate. Whereas, the availability of oral rehydration salt (ORS) and zinc sulphate dispersible tablets for the treatment of diarrhea was moderately high (90% for ORS and 82% for zinc sulphate). Medicines for pneumonia showed an overall percent availability in the range of 0% (ampicillin 250 mg and 1 g powder for injection and oxygen medicinal gas) to 100% (amoxicillin 500 mg capsule). The MPRs of 12 lowest price generic medicines were 1.5 and 2.7 times higher than the international reference prices (IRPs) for the private and public sectors, respectively. About 30% of priority life-saving medicines in the public sector and 50% of them in the private sector demanded above a single daily wages to purchase the standard treatment of the prevalent diseases of children. CONCLUSIONS: The lower availability, high price and low affordability of lowest price generic priority life-saving medicines in public and private sectors reflect a failure to implement the health policy on priority life-saving medicines in the region.

Use of analgesics in France, following dextropropoxyphene withdrawal.

BACKGROUND: In 2009, the European Medicines Agency recommended withdrawal of dextropropoxyphene (DXP); in March 2011 it was withdrawn from the market in France. Up until that time the combination dextropropoxyphene-paracetamol (DXP/PC) was widely used for analgesia. At withdrawal, French regulators recommended that DXP/PC be replaced by other step 2 analgesics, i.e. tramadol, codeine, or opium-containing drugs, or by PC for a weak level of pain. To investigate prescribing behaviours after DXP/PC withdrawal, dispensations of analgesics before and after withdrawal were analysed. METHODS: Aggregated dispensation data of analgesics prescribed between January 2009 and December 2012 in the Rhône-Alpes region were obtained from the general health insurance claims data; changes in analgesic dispensation over time were analysed with the ATC/DDD methodology. Pre (Jan-June 2009) and post-withdrawal (Jan-June 2012) changes of DDDs where computed for each analgesic step. RESULTS: The dispensations of DXP/PC experienced a two-step decrease until 2011. Over the withdrawal period 2009-2012, there was a 14% decrease in the overall use of analgesic (from 109 to 94 DDDs), while the use of step 2 analgesics declined by 46% (- 22 DDDs, from 47 to 25 DDDs). This latter decline included a cessation of use of DXP/PC (29 DDDs in 2009) that were only in part (+ 7 DDDs, from 18 to 25 DDDs) compensated by increased use of codeine, tramadol and opium, in monotherapy or combined with PC. For step 1 analgesics, use increased with 9%, mostly PC (+ 8 DDDs, from 31 to 39 DDDs). Step 3 analgesics dispensations remained largely unchanged over this period (around 3 DDDs). CONCLUSIONS: In the Rhône-Alpes region, DXP/PC withdrawal was accompanied in part by an increased use of same level analgesics, and in part by an increased use of PC in monotherapy. The extent of DXP/PC use before withdrawal, and the increased use of PC after DXP withdrawal, underline the complexity of pain management.

Availability of Paracetamol Sold Over the Counter in Europe: A Descriptive Cross-Sectional International Survey of Pack Size Restriction.

Due to the risk of hepatotoxicity when excessive amounts of paracetamol are consumed, Poisons Information Centers (PICs) frequently receive paracetamol-related enquiries. This study examined how widely pack size restrictions of paracetamol sold over the counter have been implemented in Europe and also availability of paracetamol through non-pharmacy outlets and their possible associations with frequency of poisoning enquiries. A cross-sectional European multi-centre questionnaire study was performed using a questionnaire to identify the extent and nature of paracetamol pack size restrictions, non-pharmacy outlet sales and the frequency of paracetamol-related enquiries to PICs. In total, 21 European countries participated. All PICs provided telephone hotline services. In 14 (67%) countries, pack size restrictions had been implemented in pharmacies (range: 8-30 g). No significant difference (median difference 0.7%, p-value = 0.36) was found when comparing median frequencies of paracetamol-related enquiries in countries with pack size restriction to countries without restrictions. A significantly lower median frequency of paracetamol-related enquiries was found in countries without non-pharmacy outlet sales compared to those with such sales (median difference 2.2%, p = 0.02). Pack size restrictions on pharmacy sales of paracetamol have been implemented in two-thirds of examined countries. There was no difference in the proportion of paracetamol-related enquiries to PICs among countries with and without pack size restrictions. However, a lower rate of paracetamol-related enquiries was noted in countries where paracetamol was not available in non-pharmacy outlets.

Increased availability of paracetamol in Sweden and incidence of paracetamol poisoning: using laboratory data to increase validity of a population-based registry study.

PURPOSE: To estimate the incidence trend and outcome of paracetamol poisoning, in relation to increased availability of paracetamol from non-pharmacy outlets in 2009. METHOD: Patients' serum paracetamol results over 14 years (2000-2013) from 20 (out of 21) regions in Sweden were linked to national registers of hospital care, cause of death, and prescriptions. Paracetamol poisonings were defined by serum paracetamol levels, hospital diagnoses, or cause of death. The change in incidence of poisonings following increased availability of paracetamol was analysed by using segmental regression of time series. RESULTS: Of the 12 068 paracetamol poisonings, 85% were classified as intentional self-harm. Following increased availability from non-pharmacy outlets, there was a 40.5% increase in the incidence of paracetamol poisoning, from 11.5/100 000 in 2009 to 16.2/100 000 in 2013. Regression analyses indicated a change in the trend (p < 0.0001) but not an immediate jump in the incidence (p = 0.5991) following the increased availability. Adjusting for trends in hospital episodes for self-harm, suicides, and the sales volume of paracetamol did not influence the result. All-cause mortality at 30 days (3.2%) did not change over time. CONCLUSIONS: The incidence of paracetamol poisoning in Sweden has increased since 2009, contrasting the decreased incidence in the period of 2007-2009. The change in trend was temporally associated with the introduction of availability of paracetamol from non-pharmacy outlets but did not appear to be related to sales volume of paracetamol or general trends in self-harm or suicides. © 2017 Commonwealth of Australia. Pharmacoepidemiology and Drug Safety © 2017 John Wiley & Sons, Ltd.

The impact of codeine re-scheduling on misuse: a retrospective review of calls to Australia's largest poisons centre.

BACKGROUND AND AIMS: Codeine is the most commonly used opioid in the world, and is available over the counter (OTC) in many countries, including Australia. Several countries are reconsidering codeine's OTC status due to concerns over addiction and misuse, with serious morbidity and mortality being reported. Australia's Therapeutic Goods Administration restricted codeine containing analgesics to 'Pharmacist Only' in 2010, and has recently been considering further up-scheduling to make codeine 'Prescription Only'. This paper estimated Australian trends of codeine misuse over the past 12 years, and examined whether trends changed following previous rescheduling efforts in 2010. DESIGN: A retrospective review of calls regarding codeine misuse made to the New South Wales Poisons Information Centre (NSWPIC, Australia's largest poisons centre), 2004-15. Joinpoint software was used to quantify the average annual change in calls, and whether there was a significant change in trend at any time, including following rescheduling. SETTING: Australia. PARTICIPANTS: Four hundred patients about whom a call was made to the NSWPIC. MEASURES: Calls per year, patient age, gender, tablets taken per day, formulation used, symptom disposition. FINDINGS: The NSWPIC database contained 400 cases of codeine combination analgesic misuse from 2004 to 2015. Joinpoint analysis showed that the frequency of cases increased significantly from 2004 to 2015, with an average annual percentage change (AAPC) of 19.5% [95% confidence interval (CI) = 13.8-25.5% P < 0.0001] for paracetamol/codeine and 17.9% (95% CI = 7.9-28.9%, P < 0.01) for ibuprofen/codeine. No significant change in trend was seen at any time, including following 2010 rescheduling. The median age of patients was 34 and 27 years for paracetamol/codeine and ibuprofen/codeine cases, respectively. Gender distribution was approximately equal. Clinical features reported were consistent with codeine, paracetamol and ibuprofen toxicity. CONCLUSIONS: Misuse of codeine combination products appears to be increasing in Australia. Limited rescheduling in 2010 failed to curb this increase.

How well are national guidelines relating to the general sales of aspirin and paracetamol, adhered to by retail stores: a mystery shopper study.

OBJECTIVE: To determine whether non-pharmaceutical retail outlets are aboding to the current Medicines and Healthcare products Regulatory Agency (MHRA) national guidelines for over-the-counter (OTC) sales of aspirin and paracetamol. METHODS: Stages 1 and 2 of the study deployed eight and four medical students, respectively, to undertake a mystery shopper style investigation. Stage 1: eight medical students attempted to buy ≥ 96 tablets/capsules aspirin or paracetamol in one transaction in 62 shops. Stage 2: four medical students attempted to purchase 32 paracetamol 500 mg along with a 'flu remedy preparation also containing paracetamol, in 54 shops. RESULTS: Stage 1 data revealed that 58% and 57% retailers sold more than the MHRA guidelines recommended for paracetamol and aspirin, respectively. We observed that 23% and 28% retailers were willing to sell ≥ 96 tablets of paracetamol or aspirin with no questions asked. Stage 2 results showed that 57% retailers sold 32 × 500 mg paracetamol in conjunction with a paracetamol-containing 'flu preparation; while 98% shops sold 16 × paracetamol 500 mg along with a paracetamol-containing 'flu remedy, with no questions asked of the shopper or advice given. DISCUSSION: MHRA national guidelines for OTC medicines sales appear to be poorly adhered to in non-pharmacy shops. Sales of aspirin and paracetamol OTC must be better regulated in the UK to ultimately reduce morbidity and mortality rates of deliberate and accidental overdoses.

Care versus convenience: Examining paracetamol overdose in New Zealand and harm reduction strategies through sale and supply.

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.

Internet survey of home storage of paracetamol by individuals in the UK.

AIM: Paracetamol (acetaminophen) is a common cause of liver failure due to overdose. Legislation introduced in the UK in 1998 to limit pack sizes of paracetamol has had limited impact on the overall number and severity of paracetamol overdoses. This may be because people have large amounts of paracetamol stored at home, but no previous studies have explored this question. METHODS: Individuals who regularly take part in market research surveys were invited to take part in an Internet survey. They were asked to supply demographic details, the frequency with which they use paracetamol and ibuprofen, and details of the amount and location of these drugs that they possessed. RESULTS: The mean age of respondents was 43.3 years (standard deviation 14.5 years), and 49.9% were female. People with both ibuprofen and paracetamol tended to have more packs and tablets of paracetamol (P < 0.001) and over a third had 32 or more paracetamol tablets. The most common pack size was 16 tablet packs (44.8% of all packs), which accounted for 39.4% of tablets. The most common site of paracetamol storage in the home was the kitchen (63.8% of people, 95% confidence interval 60.7, 66.7). CONCLUSION: This study suggests that pack size legislation in the UK has had limited effect on the amount of paracetamol that individuals have access to in the home. This may explain, at least in part, the limited impact of the pack size legislation on paracetamol overdoses in the UK.

What can be done to reduce mortality from paracetamol overdoses? A patient interview study.

BACKGROUND: Paracetamol (acetaminophen) is the most common self-poisoning agent in the UK and a leading cause of fatal hepatotoxicity. Following legislation in 1998 to limit pack sizes, beneficial effects on paracetamol-related mortality and morbidity were reported in England. However, there are still over 100 deaths a year and evidence of breaches of sales guidelines. AIM: To investigate characteristics of people taking larger paracetamol overdoses and compliance with sales guidelines, to inform possible further initiatives to reduce paracetamol fatalities. DESIGN AND METHODS: Interview study of 60 general hospital patients who took overdoses of over 16 paracetamol tablets (8 g). RESULTS: Half of all paracetamol overdoses involved over 16 tablets. Patients were predominantly young (three-quarters aged 16-40 years) and female (58.3%); over half (53.3%) had taken a previous paracetamol overdose. Three-quarters said they wanted to die. Half took the overdose within an hour of first thinking of it, half (53.3%) took tablets already in the home and 58.3% bought tablets specifically for the overdose. Ten people tried to buy more than 32 tablets in one transaction; four succeeded. Most knew that a paracetamol overdose could cause death or permanent damage (88.3%) and harm the liver (80.0%) but 70.0% thought they would lose consciousness. Warnings on packs had little deterrent effect. Media and internet influences were identified. Patients chose paracetamol because it was cheap and easily available. CONCLUSIONS: Further measures to reduce breaches of sales guidelines and the dangers of paracetamol overdose are required. Media and internet site producers should follow guidelines on reporting suicide.

Effect of withdrawal of co-proxamol on prescribing and deaths from drug poisoning in England and Wales: time series analysis.

OBJECTIVE: To assess the effect of the UK Committee on Safety of Medicines' announcement in January 2005 of withdrawal of co-proxamol on analgesic prescribing and poisoning mortality. DESIGN: Interrupted time series analysis for 1998-2007. SETTING: England and Wales. DATA SOURCES: Prescribing data from the prescription statistics department of the Information Centre for Health and Social Care (England) and the Prescribing Services Unit, Health Solutions Wales (Wales). Mortality data from the Office for National Statistics. MAIN OUTCOME MEASURES: Prescriptions. Deaths from drug poisoning (suicides, open verdicts, accidental poisonings) involving single analgesics. RESULTS: A steep reduction in prescribing of co-proxamol occurred in the post-intervention period 2005-7, such that number of prescriptions fell by an average of 859 (95% confidence interval 653 to 1065) thousand per quarter, equating to an overall decrease of about 59%. Prescribing of some other analgesics (co-codamol, paracetamol, co-dydramol, and codeine) increased significantly during this time. These changes were associated with a major reduction in deaths involving co-proxamol compared with the expected number of deaths (an estimated 295 fewer suicides and 349 fewer deaths including accidental poisonings), but no statistical evidence for an increase in deaths involving either other analgesics or other drugs. CONCLUSIONS: Major changes in prescribing after the announcement of the withdrawal of co-proxamol have had a marked beneficial effect on poisoning mortality involving this drug, with little evidence of substitution of suicide method related to increased prescribing of other analgesics.

Paracetamol availability in pharmacy and non-pharmacy outlets in Dublin, Ireland.

INTRODUCTION: In 2004, there were 11,092 presentations to Irish hospitals with deliberate self-harm, including 7,933 cases of drug overdose, of which 31% involved paracetamol. Limiting the availability of paracetamol reduces morbidity and mortality associated with paracetamol overdose. AIM: The present study aimed to determine the level of compliance with statutory regulations governing the sale of paracetamol in Ireland. METHODS: Researchers visited pharmacy (n = 20) and non-pharmacy outlets (newsagents, mini-markets and supermarkets) (n = 50) in Dublin city and attempted to purchase amounts of paracetamol that exceeded the statutory limits for a single transaction. RESULTS: Amounts of paracetamol in excess of statutory limits for a single transaction were purchased in 50.0% of pharmacies, 81.8% of newsagents/mini-markets and 20.0% of supermarkets. One year later, we again visited pharmacy (n = 20) and non-pharmacy outlets (n = 50) in Dublin city and purchased amounts of paracetamol in excess of statutory limits in 50.0% of pharmacies, 52.3% of newsagents/mini-markets and 10.0% of supermarkets. CONCLUSION: We recommend that (a) notwithstanding the improvement in compliance rates in newsagents/mini-markets, the sale of paracetamol in these outlets should be discontinued; (b) the sale of paracetamol in supermarkets should continue, although automated checkout tills should be appropriately re-programmed; and (c) there should be greater efforts to ensure compliance with statutory regulations in pharmacies.

Co-proxamol withdrawal has reduced suicide from drugs in Scotland.

AIM: To determine what effect the withdrawal of co-proxamol from the UK market has had on mortality from poisoning in Scotland. METHODS: This was a retrospective, observational study of mortality relating to poisoning by single agents in Scotland for the period 2000-2006. Mortality data were obtained from the General Register Office Scotland, and primary care prescribing data from the Information and Statistics Division of the Scottish Executive Health Department. RESULTS: A significant reduction in the proportion of poisoning deaths due to co-proxamol was observed following legislation [mean 2000-2004, 37 deaths (21.8% of total poisoning deaths); 2006, 10 (7.8%); P < 0.0001]. The most significant reduction was seen in male out-of-hospital deaths [mean 2000-2004, 17 (21.8%); 2006, two (2.9%); P < 0.0001]. This was associated with a decline in prescriptions by 60% within 6 months of legislation. The total number of poisoning deaths also fell, slightly earlier than the full impact on co-proxamol deaths (mean 2000-2004, 171.2; mean 2005-2006, 129.5; P = 0.005). CONCLUSIONS: Legislation has resulted in a major reduction in the number of deaths associated with co-proxamol poisoning in Scotland, with no compensatory rise in mortality from poisonings from other common analgesics. We estimate from this study that a minimum of 300 lives across the UK will have been saved by the withdrawal of co-proxamol.

Are N-of-1 trials an economically viable option to improve access to selected high cost medications? The Australian experience.

OBJECTIVE: To explore the economic viability of N-of-1 trials for improving access to selected high cost medications in Australia. METHODS: Cost and effectiveness estimates were derived from two N-of-1 trials conducted by The University of Queensland from 2003 to 2005-celecoxib versus sustained-release paracetamol for osteoarthritis in a general practice setting and gabapentin versus placebo for chronic neuropathic pain in a hospital setting. Effectiveness was determined by the proportion of responders to each medication. The costs of trials were offset against the savings generated by subsequent changes in prescribing. Decision analysis models with semi-Markov processes were used to compare different scenarios of N-of-1 trials versus usual care. RESULTS: The fixed cost of performing N-of-1 trials was approximately AUS$23,000 for each trial and the variable cost was approximately AUS$1300 per participant. Clinical outcomes favored celecoxib over paracetamol in 17% of participants and gabapentin over placebo in 24% of participants. Modeling these results showed that the cost-offsets from efficient use of medications were less than the cost of running a trial; however, the incremental costs per quality-adjusted life-year gained were AUS$6,896 and AUS$29,550 for the gabapentin/placebo and celecoxib/paracetamol trials, respectively, over a 5-year horizon. Key factors affecting the viability were the time horizon modeled, the variable cost per participant, the probability of response to the intervention medication, and rates of use in nonresponders and the usual care alternative. CONCLUSIONS: The N-of-1 strategy offers a realistic and viable option for increasing access to selected high cost medications where the medications are used for the symptomatic treatment of chronic disease, have rapid onset of action, and clinical response is unpredictable without a trial.

Paracetamol (acetaminophen) pack size restrictions and poisoning severity: time trends in enquiries to a UK poisons centre.

BACKGROUND AND OBJECTIVE: In September 1998, legislation was introduced in the United Kingdom to limit paracetamol pack sizes to 16 tablets of 500 mg at general sales outlets and 32 tablets of 500 mg at pharmacies. The effect of the regulations on severity of paracetamol poisoning is unclear. The aim of this study was to describe trends in the severity of paracetamol poisoning and to assess the impact of the 1998 Regulations on the enquiries to a UK poisons centre. METHODS: We extracted data about the age, sex and number of tablets or capsules of paracetamol ingested by patients notified to Guy's and St Thomas' Poisons Unit (London, UK) between 1996 and 2004. RESULTS AND DISCUSSION: During the study period, there were approximately 140 000 patients with suspected paracetamol poisoning, accounting for around 11% of all patients reported to the poisons unit. The median number of tablets fell from 25 to 20 for males and 20 to 16 for females after 1998. There was also a reduction in the proportion of patients who ingested 17-32 tablets (from 36% to 30%) and 33-100 tablets (from 25% to 19%). CONCLUSION: Following the 1998 Regulations there was a decline in the severity, but not frequency, of paracetamol poisoning cases reported to Guy's and St Thomas' Poisons Unit. It is unclear whether the decline in severity was a direct consequence of the regulations.

Impact of restricting paracetamol pack sizes on paracetamol poisoning in the United Kingdom: a review of the literature.

Paracetamol (acetaminophen) is the most common drug taken in overdose in the UK, accounting for 48% of poisoning admissions to hospital and being involved in an estimated 100-200 deaths per year. In 1998, the UK government introduced legislation that reduced the maximum pack size of all non-effervescent tablets and capsules containing aspirin (acetylsalicylic acid) or paracetamol that can be sold or supplied from outlets other than registered pharmacies from 25 to 16 tablets or capsules. This article reviews the literature to determine the effectiveness of the legislation, focusing specifically on paracetamol poisoning. Seventeen studies on this subject were identified. Three studies found reductions in mortality rates; one study found an increase in mortality rates, while one found an initial reduction followed by an eventual increase; three found no significant difference in mortality rates before and after introduction of the legislation. Five studies found reductions in admissions to liver units, three of these finding a reduction in liver transplantation rates; two further studies found no change in liver function tests and rates of paracetamol-induced acute liver injury or failure. Four studies found a sustained decrease in hospital admissions, while two found an initial decrease followed by an eventual increase. One study found a decline in admissions for paracetamol poisoning and an increase in admissions for non-paracetamol poisoning. Sales data are conflicting, with two studies finding no significant difference in paracetamol sales before and after the introduction of the legislation and one reporting a decline. The severity of overdose appears to have decreased since the maximum permitted packet size was reduced, with five studies reporting a reduction in the number of severe overdoses (measured by numbers of tablets ingested, serum paracetamol concentrations and usage of antidotes). Only two studies reported an increase in the number of severe overdoses.Paracetamol-associated mortality rates, admissions to liver units/liver transplants, hospital admissions and the severity of paracetamol overdose appear to have been decreasing since 1998. However, one study showed that the reductions in mortality and hospital admissions began in 1997; therefore, the contribution of the 1998 legislation to the observed changes is unclear. Most of the studies are based on short-term follow-up so it is difficult to draw any conclusions regarding long-term trends. Many of the studies were also restricted to relatively small areas of the UK; this, combined with a variety of outcome measures, makes it difficult to distinguish any conclusive trends. The studies also suffer from a lack of comparison and control groups. Some studies do not clearly differentiate between the paracetamol preparations covered by the legislation and those not. The limited number of studies to date, combined with a variety of outcome measures, make it difficult to determine with accuracy whether or not the legislation has been a success. More long-term studies are needed to fully assess the impact of the legislation.