Long term effect of reduced pack sizes of paracetamol on poisoning deaths and liver transplant activity in England and Wales: interrupted time series analyses.

OBJECTIVE To assess the long term effect of United Kingdom legislation introduced in September 1998 to restrict pack sizes of paracetamol on deaths from paracetamol poisoning and liver unit activity. DESIGN Interrupted time series analyses to assess mean quarterly changes from October 1998 to the end of 2009 relative to projected deaths without the legislation based on pre-legislation trends. SETTING Mortality (1993-2009) and liver unit activity (1995-2009) in England and Wales, using information from the Office for National Statistics and NHS Blood and Transplant, respectively. PARTICIPANTS Residents of England and Wales. MAIN OUTCOME MEASURES Suicide, deaths of undetermined intent, and accidental poisoning deaths involving single drug ingestion of paracetamol and paracetamol compounds in people aged 10 years and over, and liver unit registrations and transplantations for paracetamol induced hepatotoxicity. RESULTS Compared with the pre-legislation level, following the legislation there was an estimated average reduction of 17 (95% confidence interval -25 to -9) deaths per quarter in England and Wales involving paracetamol alone (with or without alcohol) that received suicide or undetermined verdicts. This decrease represented a 43% reduction or an estimated 765 fewer deaths over the 11¼ years after the legislation. A similar effect was found when accidental poisoning deaths were included, and when a conservative method of analysis was used. This decrease was largely unaltered after controlling for a non-significant reduction in deaths involving other methods of poisoning and also suicides by all methods. There was a 61% reduction in registrations for liver transplantation for paracetamol induced hepatotoxicity (-11 (-20 to -1) registrations per quarter). But no reduction was seen in actual transplantations (-3 (-12 to 6)), nor in registrations after a conservative method of analysis was used. CONCLUSIONS UK legislation to reduce pack sizes of paracetamol was followed by significant reductions in deaths due to paracetamol overdose, with some indication of fewer registrations for transplantation at liver units during the 11 years after the legislation. The continuing toll of deaths suggests, however, that further preventive measures should be sought.

[1]  D. Gunnell,et al.  Six-Year Follow-Up of Impact of Co-proxamol Withdrawal in England and Wales on Prescribing and Deaths: Time-Series Study , 2012, PLoS medicine.

[2]  K. Hawton,et al.  Epidemiology and trends in non-fatal self-harm in three centres in England: 2000-2007. , 2010, The British journal of psychiatry : the journal of mental science.

[3]  D. N. Bateman Limiting paracetamol pack size: has it worked in the UK? , 2009, Clinical toxicology.

[4]  G. Auzinger,et al.  Intensive care management of acute liver failure , 2008, Current opinion in critical care.

[5]  A. Burroughs,et al.  Selection of patients for liver transplantation and allocation of donated livers in the UK , 2007, Gut.

[6]  Azeem Majeed,et al.  Interrupted Time-Series Analysis of Regulations to Reduce Paracetamol (Acetaminophen) Poisoning , 2007, PLoS medicine.

[7]  D. Gunnell,et al.  Does Restricting Pack Size of Paracetamol (Acetaminophen) Reduce Suicides? , 2007, PLoS medicine.

[8]  F. House,et al.  Legislation restricting paracetamol sales and patterns of self-harm and death from paracetamol-containing preparations in Scotland. , 2006, British journal of clinical pharmacology.

[9]  P. Dargan,et al.  Paracetamol availability and recent changes in paracetamol poisoning: is the 1998 legislation limiting availability of paracetamol being followed? , 2006, Postgraduate Medical Journal.

[10]  A. Majeed,et al.  Impact of paracetamol pack size restrictions on poisoning from paracetamol in England and Wales: an observational study. , 2005, Journal of public health.

[11]  S. Gottlieb Warnings issued over COX 2 inhibitors in US and UK , 2004, BMJ : British Medical Journal.

[12]  J. Deeks,et al.  UK legislation on analgesic packs: before and after study of long term effect on poisonings , 2004, BMJ : British Medical Journal.

[13]  H. Sørensen,et al.  Hospital discharges and 30-day case fatality for drug poisoning: a Danish population-based study from 1979 to 2002 with special emphasis on paracetamol , 2004, European Journal of Clinical Pharmacology.

[14]  Craig R Ramsay,et al.  INTERRUPTED TIME SERIES DESIGNS IN HEALTH TECHNOLOGY ASSESSMENT: LESSONS FROM TWO SYSTEMATIC REVIEWS OF BEHAVIOR CHANGE STRATEGIES , 2003, International Journal of Technology Assessment in Health Care.

[15]  W. Bernal Changing Patterns of Causation and the Use of Transplantation in the United Kingdom , 2003, Seminars in liver disease.

[16]  A K Wagner,et al.  Segmented regression analysis of interrupted time series studies in medication use research , 2002, Journal of clinical pharmacy and therapeutics.

[17]  T. MacDonald,et al.  Paracetamol pack size restriction: the impact on paracetamol poisoning and the over‐the‐counter supply of paracetamol, aspirin and ibuprofen , 2002, Pharmacoepidemiology and drug safety.

[18]  L. Appleby,et al.  Effects of legislation restricting pack sizes of paracetamol and salicylate on self poisoning in the United Kingdom: before and after study , 2001, BMJ : British Medical Journal.

[19]  K. Schapira,et al.  Open verdict v. suicide – importance to research , 2001, British Journal of Psychiatry.

[20]  D. Gunnell,et al.  Use of paracetamol (acetaminophen) for suicide and nonfatal poisoning: worldwide patterns of use and misuse. , 2000, Suicide & life-threatening behavior.

[21]  M. Hudson,et al.  Reduction in incidence of severe paracetamol poisoning , 2000, The Lancet.

[22]  P. Angus,et al.  Paracetamol overdose in a liver transplantation centre: An 8‐year experience , 1999, Journal of gastroenterology and hepatology.

[23]  S Simkin,et al.  Trends in deliberate self-harm in Oxford, 1985–1995 , 1997, British Journal of Psychiatry.

[24]  R. Garnier,et al.  Use of paracetamol for suicide and non-fatal poisoning in the UK and France: are restrictions on availability justified? , 1997, Journal of epidemiology and community health.

[25]  P. Reid,et al.  Changing patterns of self-poisoning in a UK health district. , 1996, QJM : monthly journal of the Association of Physicians.

[26]  K. Hawton,et al.  Paracetamol Self-Poisoning Characteristics, Prevention and Harm Reduction , 1996, British Journal of Psychiatry.

[27]  K. Hawton,et al.  Why patients choose paracetamol for self poisoning and their knowledge of its dangers , 1995, British medical journal.

[28]  D. Gunnell,et al.  What can be done to reduce mortality from paracetamol overdoses? A patient interview study. , 2012, QJM : monthly journal of the Association of Physicians.

[29]  William M. Lee,et al.  LIVER FAILURE AND LIVER DISEASE LIVER FAILURE Acetaminophen-Induced Acute Liver Failure: Results of a United States Multicenter, Prospective Study , 2005 .

[30]  R. Jenkins,et al.  Suicide deaths in England and Wales: trends in factors associated with suicide deaths. , 1993 .