Availability of Paracetamol Sold Over the Counter in Europe · paracetamol-related enquiries was found in countries without non-pharmacy outlet sales compared to those with such sales

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Availability of Paracetamol Sold Over the Counter in Europe

A Descriptive Cross-Sectional International Survey of Pack Size RestrictionMorthorst, Britt Reuter; Erlangsen, Annette; Nordentoft, Merete; Hawton, Keith; Hoegberg,Lotte Christine Groth; Dalhoff, Kim Peder

Published in:Basic & Clinical Pharmacology & Toxicology

DOI:10.1111/bcpt.12959

Publication date:2018

Document version:Accepted manuscript

Citation for pulished version (APA):Morthorst, B. R., Erlangsen, A., Nordentoft, M., Hawton, K., Hoegberg, L. C. G., & Dalhoff, K. P. (2018).Availability of Paracetamol Sold Over the Counter in Europe: A Descriptive Cross-Sectional International Surveyof Pack Size Restriction. Basic & Clinical Pharmacology & Toxicology, 122(6), 643-649.https://doi.org/10.1111/bcpt.12959

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Article Type: Original Article

Availability of Paracetamol Sold Over-the-Counter in Europe: A

Descriptive Cross-Sectional International Survey of Pack Size

Restriction

Britt Reuter Morthorst1,2, Annette Erlangsen2,3,4, Merete Nordentoft1,2, Keith Hawton5, Lotte Christine Groth Hoegberg6 and Kim Peder Dalhoff7 1Faculty of Medical and Health Science, University of Copenhagen, Copenhagen, Denmark 2Danish Research Institute for Suicide Prevention, Research Unit, Mental Health Centre Copenhagen, Copenhagen, Denmark 3Department of Mental Health, Johns Hopkins School of Public Health, Baltimore, MD, USA 4Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark 5Centre for Suicide Research, University Department of Psychiatry, Oxford University, Oxford, UK 6Department of Anaesthesiology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark 7Department of Clinical Pharmacology and Clinical Toxicology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark Author for correspondence: Britt Reuter Morthorst, Danish Research Institute for Suicide Prevention, Research

Unit, Mental Health Centre Copenhagen, Kildegaardsvej 28, 2900 Hellerup, Denmark (e-mail: [email protected]).

Keywords: Paracetamol; poisoning; pack size restrictions; Poisons Information Centres. (Received 22 August 2017; Accepted 27 December 2017) Acknowledgement The authors are grateful to the EAPCCT and especially their general secretary Mark Zammit for his professional handling of our request. This study would not have been possible without his dedicated collaboration. The authors would also like to thank all participating members of EAPCCT who provided data.

Abstract

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

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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 multicentre 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 grams). 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.

Suicidal behaviour constitutes a global health burden with close to one million deaths

annually and 10-40 times as many episodes of self-harm [1]. In European countries,

poisonings account for the major part of hospital-presenting deliberate self-harm, and

analgesics, especially paracetamol, are frequently used for intentional self-poisoning [2-5].

Mild analgesics including paracetamol are sold in all European countries with or without

prescription and often in large quantities. Yet, intentional and accidental self-poisoning with

especially paracetamol represents a significant healthcare problem [4,6,7]. The proportion

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of paracetamol-related poisonings related to all poisonings varies among European

emergency departments; ranging from 4.5 % as reported in Spain [8] to 12% in Norway [9]

and 40-44% in the UK over the past decades [10]. Poisons Information Centres (PICs) which

answer enquiries , including those related to paracetamol, are established in most European

countries [11]. A comparison of PICs worldwide showed that paracetamol was among the

20 most frequent agents for which enquiries were made [12]. However, the association

between paracetamol sold over-the-counter (OTC) in pharmacies and non-pharmacy

outlets and number of enquiries to PICs is sparsely described and with conflicting findings

[13,14]. A British report found no decrease of paracetamol-related enquiries when

comparing frequencies before and after implementation of the British pack size restriction

on paracetamol [15]. However, an Irish report showed a decrease in severity of paracetamol

poisonings and number of tablets taken, as recorded from paracetamol-related enquiries,

after the Irish pack size restriction had been introduced [16]. During 2010-2013, the Swedish

Medical Agency reported a marked increase in paracetamol-related enquiries, arguing that

this was related to the introduction of sales in non-pharmacy outlets in November 2009

[13]. This was supported by an earlier Swedish report that related a 158% increase (50%

within the first three years) in the number of paracetamol-related PIC enquiries to the same

legislative change [17].

Paracetamol may be hepatotoxic when ingested in doses exceeding daily recommendations

[7,18,19]. Gulmez and colleagues noted that a liver transplant was needed in 0 - 52% of ALF

cases due to overdose by paracetamol in a sample mainly from the UK and Ireland. The

same report revealed that nearly 97% of all ALF overdose cases were due to paracetamol

poisoning [20], though varying across Europe [21]. The relatively low case fatality rate is

partly explained through high standards in clinical practice [22], including treatment with

the antidote, N-acetylcysteine [23].

Suicidal behaviour is a complex phenomenon, with suicidal ideation and actions fluctuating

over time [24]. Impulsive suicidal behaviour, which is particularly prevalent among the

young, implies that the person would tend to use means available in close proximity, e.g.

agents available in the household [25,26]. One suicide preventive measure is to restrict

access to potentially toxic drugs like paracetamol [27-29] and restrictions on pack sizes of

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mild analgesics including paracetamol sold OTC have been introduced in several European

countries [30]. A structured overview of the availability of paracetamol tablets OTC and its

association with self-poisoning was published in 2000 for European countries [4]. However,

an update is due. The primary aim of the present study was to gain an updated overview of

restrictions on paracetamol sold OTC in pharmacy and non-pharmacy outlets in Europe.

Secondly, we wanted to investigate the association between frequency of paracetamol-

related enquiries to PICs and availability of the drug.

Methods

Design and setting

We conducted a European multicentre study in a cross-sectional design during 2015 and

2016 describing the availability status of paracetamol sold OTC in European pharmacies and

other retail outlets.

PICs in all European countries were contacted using the European Association of Poisons

Centres and Clinical Toxicologists (EAPCCT) member lists. The EAPCCT is a scientific

association with individual members rather than countries. Currently, it includes members

from 29 countries, covering all major countries in Europe.

Data

A detailed survey questionnaire was developed and distributed via email to all current

members by the EAPCCT secretary during March 2015 (see Appendix). Responses were

returned directly via e-mail to the corresponding author, and data were entered into an

electronic database. Responses were reviewed by two researchers or through follow-up

enquiries to the respective PIC in order to clarify unclear information. Where we received

several responses from the same country, responders were contacted with the aim of

settling potential differences. Responses with national level data were preferred.

The survey included questions regarding: description of PIC; national availability of

paracetamol tablets; pack size restrictions in pharmacies and non-pharmacy outlets;

number of tablets and grams sold OTC and presence of blister package products; services

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provided by the local PIC (calls, hotline, web contacts or ward activity); annual numbers of

paracetamol-related enquiries as well as total number of enquiries for the years 2011-2013;

risk assessment of poisoning enquiries using the standardized Poisoning Severity Score, as

introduced by EAPCCT in 1990 [31]; access to hospital records, discharge letters; and other

services, such as Ministry consultancy, educational activities or surveillance functions.

Missing data

A reminder was dispatched five months after the initial questionnaire by the EAPCCT

general secretary. PICs in non-responding countries were followed up with emails. Lastly,

aggregate data on enquiries to PICs were downloaded from the website of the UK National

Poison Information Services since no personal reply was achieved from the UK, and this

procedure was recommended by leading British toxicologists [32].

Analysis

Descriptive analysis was supplemented by non-parametric tests of differences. A normal

distribution could not be assumed with respect to mean proportions of paracetamol-related

enquiries of all poisonings to PICs due to significant outliers observed in data from two

countries. This meant that calculations were based on medians. This also applied to the

calculation of rates where a normal distribution of either observed or estimated means

could not be assumed; hence not supporting Poisson regressions. The Wilcoxon and Mann-

Whitney U test of differences, respectively, were applied to determine differences among

countries with and without pack size restrictions, as well as among those with and without

non-pharmacy outlet sales.

Ethical considerations

Ethical approval was not required as no person-level data were collected.

Results

In total, 21 European PICs or EAPCCT members responded. According to the EAPCCT

website, there are currently PICs in 29 European countries. Assuming that all members in

the possible 29 European countries had received the survey, the country-based response

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rate was 72.4%. We obtained responses from 18 PICs covering nationwide information,

while three PICs provided information at a sub-national level (Munich, Germany; Lodz,

Poland; and Moscow, the Russian Federation).

Pack size restrictions

In 14 (67%) of the responding countries, pack size restrictions had been implemented in

pharmacies (range: 8 to 30 grams in blister packages) (Table 1). Countries where pack size

restrictions had not been introduced were predominantly Eastern European (Slovakia,

Lithuania, Croatia, Czech Republic, Poland (Lodz) and the Russia Federation (Moscow)). In 12

(57%) countries, mild analgesics including paracetamol were not available in non-pharmacy

outlets. Respondents from all countries confirmed that larger quantities of paracetamol

were available to patients through prescription from their primary care doctor.

Enquiries to PICs about poisonings

Only countries where information on annual paracetamol-related enquiries and total

number of enquiries (n= 17) had been reported were included in further analyses. Rates of

enquiries per 100,000 inhabitants from the public were presented for the year 2013 for

countries providing these services (n=18) (Table 2).

Despite the fact that pack size restrictions have been implemented in the UK, Ireland and

Sweden, a larger proportion of paracetamol-related enquiries was noted in these countries

compared to others (Table 2). Yet, at the same time, mild analgesics including paracetamol

were available in non-pharmacy outlets. Most countries where paracetamol was sold in

non-pharmacy outlets had a proportionally higher percentage of annual mean number of

paracetamol-related enquiries when compared to countries with no such sales. France was

an exception to this. Two significant outliers regarding mean paracetamol-related enquiries

were identified (Table 2), leading to the necessity for using non-parametric tests of

differences for median proportions of paracetamol-related enquiries, presented in Table 3.

No significant difference in paracetamol-related enquiries were found among countries with

pack size restriction (range 1.1% to 16.1%) and countries without pack size restriction (range

1.7% to 5.6%); median difference 0.7%, p = 0.36. However, a significant difference was

noted for median proportions of paracetamol-related enquiries among countries with no

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non-pharmacy outlet sales (range 1.1% to 5.3%) and those with non-pharmacy outlet sales

(range 1.9% to 16.1%); median difference 2.2%, p = 0.02 (Table 3).

We found a shift in impact of paracetamol-related enquiries when calculated as rates per

100,000 inhabitants. The rates ranged between 1.1 in Croatia to 39.7 per 100,000

inhabitants in Sweden; implying that Sweden had the highest rate of enquiries. The non-

parametric test revealed that the mean rate of paracetamol-related enquiries to PICs was

higher in countries with pack size restrictions than in those with no pack size restrictions

(p=0.027) (Table 3). Also, a higher mean rate of paracetamol-related enquiries per 100,000

inhabitants was noted in countries with non-pharmacy outlet sales of paracetamol when

compared to those with no non-pharmacy outlet sales (p=0.019).

In three of 21 countries (Slovenia, The Netherlands and the UK), PIC services were provided

for clinicians only. In spite of the vast majority of countries providing services for both

clinicians and the public, we found large differences in rates of public enquiries among

countries (Table 2). The rates varied from 0.7 in Slovakia to 609.5 per 100,000 inhabitants in

Belgium. All responding PICs provided phone hotline services, while 11 (55%) offered

personal consultations and 13 (65%) supported web-based enquiries. Action cards (stepwise

information on risk assessment and treatment guidelines) were available from five of the

PICs (26%), while other services were supplied by 16 of the centres (80%). These covered:

special ward facility, insurance or Ministry consultancy, educational activities and

surveillance functions. Five centres (24%) were able to systematically access hospital

records, including information on diagnosis codes, while nine centres (43%) had access to

discharge letters. Routine risk assessment of the level of paracetamol poisoning was

performed by 17 of the PICs (77%), of which 8 (36%) applied the Poisoning Severity Score,

the severity grading scale suggested by the EAPCCT [31].

Discussion

This is, to our knowledge, the first study to examine the impact of pack size restrictions and

non-pharmacy availability of paracetamol in Europe based on data from European PICs. Pack

size restrictions on pharmacy sales of paracetamol have been implemented in two thirds of

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the examined countries. There was no difference in the proportion of population-based

paracetamol-related enquiries (per 100,000 inhabitants) to PICs among countries which had

and had not implemented pack size restrictions. However, there was a higher population-

based rate of paracetamol-related enquiries in countries where mild analgesics including

paracetamol were sold in non-pharmacy outlets.

The fact that level of enquiries seemingly did not depend on whether pack size restrictions

had been introduced might seem surprising, especially considering the strong evidence from

the UK that pack size restrictions were linked to substantial reductions in deaths from

paracetamol poisoning [33]. However, our findings may reflect a greater pressure to reduce

pack sizes in countries in which the incidence of paracetamol overdoses is high.

The finding that paracetamol-related enquiries are greater where non-pharmacy sales are

permitted is supported by a Czech study in 2004 where the number of enquiries concerning

pharmaceuticals including paracetamol and ibuprofen over a five-year period rose following

a legislative change allowing sales in non-pharmacy outlets [34]. In Norway, sale of

paracetamol in non-pharmacy outlets was introduced in 2003. A subsequent study showed

no difference in number of hospital contacts for paracetamol overdoses when comparing

the two years before and after the legislative change, although an increase in the number of

paracetamol-related enquiries to PICs was noted. However, the authors concluded that the

severity of paracetamol poisonings had decreased [14]. In Sweden, sales outside pharmacies

were introduced in 2009; during the following four years, a 40% increase in paracetamol-

related poisonings was noted using national register data on hospital admissions and causes

of death [35]. A similar increase in paracetamol-related enquiries to PICs was noted [13]. The

increase observed in Sweden was associated with the liberalisation and as a direct consequence of

this, sales of paracetamol as regular tablets were withdrawn from non-pharmacy outlets in

2015, leaving only effervescent tablets on the market (that were not associated with an

elevated toxicity risk) [13]. One should think that the Swedish approach of pack size

restrictions in pharmacies and no sales in non-pharmacy-outlets might ensure that

paracetamol are available in a safer and controlled manner. However, the total number of

PIC consultation related to paracetamol poisoning has continued to increase in Sweden [36].

Long-term studies are needed to determine the effect of the intervention, possibly using

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data on hospital admissions for poisonings. In Denmark, another legislative change prior to

pack size restriction was implemented in March 2011. This legislation prohibited sales of

mild analgesics including paracetamol to minors below 18 years of age. However, it is not

known if this had an impact on hospital contacts due to overdose.

We found that the PICs in the UK and Ireland had particularly high frequencies of

paracetamol-related enquires (16% and 15% of all inquiries, respectively) compared to the

other participating countries. This matches national reports stating that paracetamol

intoxication is the most common poisoning in the UK and Ireland [32,37]. It is also well

documented that rates of self-harm by overdose of paracetamol, recorded as hospital

contacts in the UK and Ireland are substantially higher [38] than in other European countries

[2].

Examination of the impact of paracetamol-related enquiries when based on population size

(rates per 100,000 inhabitants) changed the picture. The highest rates were then found in

Sweden, with a mean rate of 38.7 per 100,000. This finding is clearly in line with the above-

mentioned most recent legislative decision to withdraw sales of regular paracetamol tablets

from all non-pharmacy outlets [13]. Future Scandinavian studies investigating the impact of

the ban on sales from non-pharmacy outlets on population-based hospital and PIC data also taking

prescription patterns into account will provide important information for public health policy

makers.

One essential difference in PICs across Europe was the target group in that 18 (86%)

provided services for both clinicians and the public, whereas in the remaining three

countries PICs only provided services for clinicians. Typically the latter types of PICs will refer

public enquiries on to GPs. Among PICs which provided services to both clinicians and the

public, rates of public enquiries differed significantly possibly suggesting different levels of

public awareness. A steady increase in the number of public enquiries has been noted by

PICs [16,39]. Some PICs use public awareness campaigns and social media initiatives to

increase public awareness [40].

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We found that among the responding countries, it seemed that pack size restriction was

accepted as a suicide prevention strategy, in spite of very few national evaluations of this

initiative [4,41]. Evidence in favour of the pack size restriction has been reported through

significantly reduced paracetamol-related deaths and also referrals for liver transplantation

[41].

Strengths and Limitations

Data were provided by experts in the field of toxicology and representatives from European

PICs with access mainly to national level enquiry data. Due to the close collaboration with

EAPCCT, which distributed the questionnaire and e-mail reminders, an estimated response

rate of 72% was obtained. This contrasts previous investigations involving EAPCCT

members, which have reported response rates of less than 30% [4,12]. No uniform,

international data sources are available in this area; hence, the current data collection can

be viewed as unique.

Although a structured questionnaire was used, we obtained heterogeneous replies, and

answers from several PICs were incomplete. The lack of response from larger countries,

such as Spain and Portugal, is unfortunate. It was not possible to examine whether

legislative rules regarding number of packages allowed in single sales played a role due to

lack of responses. Availability in households of paracetamol-related drugs does not solely

depend on availability OTC; a substantial share of the population will have obtained the

drugs through prescription, which was not feasible to assess in this study.

It would have been preferred to have complete data on sales of paracetamol. However, this

would not have been feasible without having to compromise the number of reporting

countries.

The difference in service provision between accepting enquiries from clinicians only or from

both clinicians and the public is unfortunate when examining enquiries as a surrogate

outcome; we have met this limitation by calculating rates of enquiries from the public for

the year 2013 where data were obtained. Only three countries did not take public enquiries,

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namely Slovenia, The Netherlands and the UK. It could be argued that their enquiries might

be related to more severe cases; however, it was not feasible to address level of severity in

this survey, such as through a poisoning severity score.

The term ‘paracetamol-related enquiries’ might have been differently interpreted by

responders, ranging from mild poisonings to severe cases. It might also have been unclear

whether multi-drug poisonings should be included or not. This level of detail could

unfortunately not be addressed in the questionnaire. Although self-poisonings with

paracetamol is frequent in European countries, there is likely to be variation in self-harming

methods among countries [2,4]. Hence, it would be fair to state that not only restrictions

but also cultural habits may influence the pattern in methods used for self-harm. Future

analysis would benefit from national data on hospital admissions for poisonings as well as

other relevant clinical outcomes.

To conclude, in most European countries, clinicians and the public have access to treatment

advice on paracetamol-related poisonings through PICs. In the majority of examined

countries, pack size restrictions have been implemented for mild analgesics including

paracetamol sold OTC in pharmacies. Countries with no pack size restriction in pharmacies

and no sales in non-pharmacy outlets had fewer paracetamol-related enquiries to PICs. One

conclusion would be that pack size restriction has no influence on the number of

paracetamol poisoning, whereas not selling paracetamol OTC has. However, the lack of

significant difference in the proportion of enquiries among countries with no pack size

restriction and those with pack size restriction indicates a need for further research using

national data and toxicity-related outcomes. The higher rate of paracetamol-related

enquiries in countries where mild analgesics including paracetamol were available in non-

pharmacy outlets could suggest that more restrictive measures might be advisable.

Conflict of interest

None.

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[32] National Poison Information Servies in UK. Annual reports. 20-3-2016.

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[33] Hawton K, Simkin S, Deeks J, et al. UK legislation on analgesic packs: before and after study of

long term effect on poisonings. BMJ 2004;329:1076.

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Center. Ceska Slov Farm 2004;53(4):172-6.

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incidence of paracetamol poisoning: using laboratory data to increase validity of a population-

based registry study. Pharmacoepidemiol Drug Saf 2017;26:518-527.

[36] Giftinformationscentralen GIC; Annual report 2015. Läkemedelsverket Sweden . 18-12-2016.

Ref Type: Online Source. https://giftinformation.se/

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Beaumont Hospital, Dublin 9, Ireland. 24-1-2017.

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[38] Hawton K, Bergen H, Cooper J, et al. Suicide following self-harm: findings from the Multicentre

Study of self-harm in England, 2000-2012. J Affect Disord 2015;175:147-151.

[39] Bogevig S, Hogberg LC, Dalhoff KP, et al. Status and trends in poisonings in Denmark 2007-

2009. Dan Med Bull 2011;58:A4268.

[40] Pourmand A, Wang J, Mazer M. A survey of poison control centers worldwide. Daru

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[41] Hawton K, Bergen H, Simkin S, et al. Long term effect of reduced pack sizes of paracetamol on

poisoning deaths and liver transplant activity in England and Wales: interrupted time series

analyses. BMJ 2013;346:f403.

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Table 1 European PICs, their year of establishment, pack size restriction on paracetamol in

pharmacies, and sales in non-pharmacy outlets by country

PIC Year of

establis

hment

of PIC

Area of

coverage

OTC

Pharmacy

sales

(gram)

Non-

pharmacy

outlet sales

(gram)

Countries with

restriction (n=14)

Austria Poisons Information Center

Vienna 1975 National 30 No sale

Belgium Anti-Poison center of Belgium 1963 National 10 No sale

Denmark Information Center Danish

Poison 2006 National 10 5

France Toxic vigilance Coordination

Committee and Association of

French Poison Centers

1999 National 8 No sale

Finland Finnish Poison Center 1961 National 15 No sale

Germany/Munich Poison Information Center

Munich 1968 Regional 10 No sale

Iceland Iceland Poison Center 1994 National 15 No sale

Ireland National Poison Information

Center Ireland 1966 National 12 6

Italy Florence Poison Center & Pavia

Poison Control Center 1991 National 15 No sale

Norway Norwegian Poisons Information

Center National 10 5

Slovenia Poison Control Centre, Division of

Internal Medicine, Ljubljana 1973 National 10 No sale

Sweden Poison Information Center

Sweden 1960 National 10 No sale*

Switzerland Tox Info Suisse 1966 National 8 No sale

UK National Poison Information

Services England (Toxbase 1982) 1962

National 16 8

Countries without

restriction (n=7)

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Croatia Poison Control Center Zagreb 1970 National Unlimited No sale

Czech Republic Toxicological Information Center

of Czech Republic (TIC) 1964 National Unlimited 6

The Netherlands Dutch Poison Information Center 1959 National Unlimited No sales

Lithuania Poison Information Bureau 2012 National Unlimited No sale

Poland/Lodz Poison Information Center 1967 Regional Unlimited 6

Russian

Federation/Moscow

Research and Applied Toxicology

Center of Medical and Biological

Agency

1993 Regional Unlimited Unlimited

Slovakia Research and Applied Toxicology

Center of Medical and Biological

Agency

1968 National Unlimited No sale

* In 2015, Sweden withdrew sales of mild analgesics including paracetamol (10 g) from non-

pharmacy outlets sold as regular tablets leaving only effervescent tablets on the market.

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Table 2 Paracetamol-related enquiries to PICs according to pack size restrictions and sales through non-pharmacy outlets in Europe in the

period of 2011-2013

Country

Mean percent of

paracetamol-

related enquiries of

all poisonings (%)

Overall rate of

enquiries per 100,000

inhabitants and

(paracetamol-related

enquiries) 2011-2013

Rate of public

enquiries per 100,000

inhabitants in 2013

Pack size restriction

in pharmacy

Sales restricted to

pharmacies Italy 2.7 61.0 (1.66) 10.7

France 5.3 289.6 (15.45) 170.6

Belgium 2.6 ** 714.5 (12.55 **) 609.5

Slovenia¹ 3.9 ** 83.9 (3.23 **) Clinicians only

Austria 1.1 283.7 (3.06) 1

Iceland Missing **** Missing **** Missing ****

Switzerland 3.4 456.0 (15.39) 296.2

Germany (Munich) 2 Missing ***** Missing *****

Finland 3 566 (17.12) 14.5

Available in non-

pharmacy outlets Ireland 16.1 * 212.8 (34.14) 59.3

Norway 3.4 792.2 (27.03) 504.7

Sweden 4.7 854 (39.68) 606.4

UK¹ 14.9 * 64.9 (9.69) Clinicians only

Denmark 5.4 380.4 (20.67) 173.6

No pack size Sales restricted to Slovakia 3.4 77.7 (2.60) 0.7

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restriction in

pharmacy

pharmacies

Lithuania 1.7 77.5 (1.32) 45.5

Croatia 2.7 40.3 (1.08) 7.3

Available in non-

pharmacy outlets Czech Republic 2.7 153.3 (3.58) 61.6

Moscow (Russian

Federation) 1.9*** Missing ****** Missing ******

The Netherlands ¹ 5.6 264.3 (14.79) Clinicians only

Poland (Lodz) 5 Missing ***** Missing *****

* Significant outliers of mean frequencies

** Data only available for 2012 and 1013

*** Data only available for 2013

**** Data not available, hence Iceland not included in the analysis.

***** Only regional data available

****** Only city data available

¹ In Slovenia, The Netherlands and the UK PICs provide services for clinicians only

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Table 3 Differences in paracetamol-related enquiries to PICs according to pack size restrictions and sales through non-pharmacy outlets a

Median percent of

paracetamol-

related enquiries of

all poisonings 2011-

2013 (%) (range)

Median

difference

(%)

p-valueb

Rate of

paracetamol-

related

enquiries per

100,000

inhabitants

Mean difference

(95 % CI) p-valueb

Pack size restriction

in pharmacies

Yes (n = 13) 3.4 (1.1 – 16.1) 16.64

No (n = 7) 2.7 (1.7 – 5.6) 0.7 0.362 4.67 -11.97

(-21.25 to -2.68) 0.027*

Packages available

in non-pharmacy

outlets

Yes (n = 9) 4.9 (1.9 – 16.1) 21.37

No (n = 11) 2.7 (1.1 -5.3) 2.2 0.02* 7.35

-14.02

(-26.39 to -1.66)

0.019*

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a Based on countries where regional or national data were available. b Using the Wilcoxon test and Mann-Whitney U test, respectively

* Significance level 0.05

Documents

Availability of Paracetamol Sold Over the Counter in Europe · paracetamol-related enquiries was found in countries without non-pharmacy outlet sales compared to those with such sales