title: Six-year follow-up of impact of co-proxamol withdrawal in England and Wales on prescribing and deaths: time-series study.
abstract: BACKGROUND
  The analgesic co-proxamol (paracetamol/dextropropoxyphene combination) has been widely involved in fatal poisoning. Concerns about its safety/effectiveness profile and widespread use for suicidal poisoning prompted its withdrawal in the UK in 2005, with partial withdrawal between 2005 and 2007, and full withdrawal in 2008. Our objective in this study was to assess the association between co-proxamol withdrawal and prescribing and deaths in England and Wales in 2005-2010 compared with 1998-2004, including estimation of possible substitution effects by other analgesics.
  
  
  RESULTS
  We obtained prescribing data from the NHS Health and Social Care Information Centre (England) and Prescribing Services Partneriaeth Cydwasanaethau GIG Cymru (Wales), and mortality data from the Office for National Statistics. We carried out an interrupted time-series analysis of prescribing and deaths (suicide, open verdicts, accidental poisonings) involving single analgesics. The reduction in prescribing of co-proxamol following its withdrawal in 2005 was accompanied by increases in prescribing of several other analgesics (co-codamol, paracetamol, codeine, co-dydramol, tramadol, oxycodone, and morphine) during 2005-2010 compared with 1998-2004. These changes were associated with major reductions in deaths due to poisoning with co-proxamol receiving verdicts of suicide and undetermined cause of -21 deaths (95% CI -34 to -8) per quarter, equating to approximately 500 fewer suicide deaths (-61%) over the 6 years 2005-2010, and -25 deaths (95% CI -38 to -12) per quarter, equating to 600 fewer deaths (-62%) when accidental poisoning deaths were included. There was little observed change in deaths involving other analgesics, apart from an increase in oxycodone poisonings, but numbers were small. Limitations were that the study was based on deaths involving single drugs alone and changes in deaths involving prescribed morphine could not be assessed.
  
  
  CONCLUSIONS
  During the 6 years following the withdrawal of co-proxamol in the UK, there was a major reduction in poisoning deaths involving this drug, without apparent significant increase in deaths involving other analgesics.
authors.affiliation: Centre for Suicide Research, University of Oxford Department of Psychiatry, Warneford Hospital, Headington, Oxford, UK. keith.hawton@psych.ox.ac.uk
authors.forename: Keith
authors.initials: K
authors.lastname: Hawton
authors.forename: Helen
authors.initials: H
authors.lastname: Bergen
authors.forename: Sue
authors.initials: S
authors.lastname: Simkin
authors.forename: Claudia
authors.initials: C
authors.lastname: Wells
authors.forename: Navneet
authors.initials: N
authors.lastname: Kapur
authors.forename: David
authors.initials: D
authors.lastname: Gunnell
mesh_terms: D000059:Accidents; D000082:Acetaminophen / Q000506:poisoning*; D000700:Analgesics / Q000506:poisoning*; D002423:Cause of Death; D011431:Dextropropoxyphene / Q000506:poisoning*; D004338:Drug Combinations; D062787:Drug Overdose / Q000401:mortality*; D004739:England; D005500:Follow-Up Studies; D009020:Morphine / Q000506:poisoning; D010098:Oxycodone / Q000506:poisoning; D010818:Practice Patterns, Physicians'; D055656:Prescriptions; D013405:Suicide / Q000706:statistics & numerical data*; D014852:Wales
chemical_list: D000700:Analgesics; D004338:Drug Combinations; D000082:Acetaminophen; C011800:acetaminophen, dextropropoxyphene, drug combination; D009020:Morphine; D010098:Oxycodone; D011431:Dextropropoxyphene