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 coproxamol 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. ConclusionsMajor changes in prescribing after the announcement of thewithdrawal of co-proxamol havehada marked beneficial effect on poisoning mortality involving this drug, with little evidence of substitution of suicide method related to increasedprescribingof other analgesics. INTRODUCTION For many years concerns have been expressed about the extent of fatal poisoningwith the analgesic co-proxamol (dextropropoxyphene in combination with paracetamol), especially its use for suicide. Death occurs largely because of the toxic effects of high levels of dextropropoxyphene on respiration and cardiac conduction. 4 The margin between therapeutic and potentially lethal concentrations is relatively narrow. Between 1997 and 1999 co-proxamol was the single drug used most frequently for suicide in England and Wales (766 deaths over the three year period), implicated in nearly a fifth of all suicides from drug related poisoning. 6 After the Medicines and Healthcare products Regulatory Agency reviewed the efficacy and safety profile of co-proxamol, theCommittee onSafety ofMedicines (CSM) advised in January 2005 that co-proxamol should be withdrawn from use in the UK, the final date of withdrawal being 31 December 2007. The committee also advised that during the intervening period efforts should be made to move patients to suitable alternatives, although patients for whom this was difficult could continue to receive the drug through normal prescribing. This announcement had a major effect during the withdrawal phase on prescribing in England and in Scotland, where there was a beneficial effect on suicides during 2005-6. We evaluated the effect of the announcement of coproxamol withdrawal on prescribing and mortality involving co-proxamol and other analgesics in England andWales.We investigateddeaths fromdrugpoisoning that received a verdict of suicide or an open verdict, and also those with a verdict of accidental death, some of which may have been suicidal acts. Substitution of method is a potential concern where a common means used for suicide becomes less available. We therefore investigated the possible effect of the withdrawal of coproxamol on the prescribing of other analgesics and on their use in suicide.Ourmethod takes account of underlying trends in prescribing and deaths before the committee’s announcement. METHOD Prescriptions We obtained data on prescriptions of co-proxamol and of co-codamol, codeine, co-dydramol, dihydrocodeine, Centre for Suicide Research, University of Oxford Department of Psychiatry, Warneford Hospital, Headington, Oxford OX3 7JX Office for National Statistics, London EC1R 1UW Centre for Statistics in Medicine, Wolfson College Annexe, University of Oxford, Oxford, OX2 6UD Centre for Suicide Prevention, University of Manchester, Manchester M13 9PL Department of Social Medicine, University of Bristol, Bristol BS8 2PR Correspondence to: K Hawton keith.hawton@psych.ox.ac.uk Cite this as: BMJ 2009;338:b2270 doi:10.1136/bmj.b2270 BMJ | ONLINE FIRST | bmj.com page 1 of 5 on 25 June 2009 bmj.com Downloaded from