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J P Schofield - One of the best experts on this subject based on the ideXlab platform.
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transdermal buprenorphine plus oral paracetamol vs an oral codeine paracetamol combination for osteoarthritis of hip and or knee a randomised trial
Osteoarthritis and Cartilage, 2011Co-Authors: P G Conaghan, C M Obrien, M Wilson, J P SchofieldAbstract:Summary Objective Low-dose transdermal opioids offer a new therapeutic option for osteoarthritis (OA). This study compared symptom relief obtained with buprenorphine patches plus oral paracetamol with that obtained with an oral codeine-paracetamol combination tablet (Co-Codamol) in older adults with OA. Method Two hundred and twenty people (aged ≥60 years) with OA hip and/or knee pain were randomised to treatment with 7-day buprenorphine patches plus oral paracetamol (5–25μg/h buprenorphine patches plus 1000mg oral paracetamol q.i.d. (4 times daily); n =110) or Co-Codamol tablets (two 8/500–two 30/500mg tablets q.i.d.; n =110). They entered a titration period of up to 10 weeks, during which their dose of study medication was adjusted until they reached optimum pain control. Patients who achieved optimum pain control entered a 12-week assessment period. The primary outcome was average daily pain scores recorded using the box scale-11 (BS-11) pain scale. Results Both treatments significantly reduced patient pain scores. The estimated treatment difference [95% confidence interval ( CI)] was −0.02 (−0.64, 0.60) for the per protocol (PP) population. The results were similar for the full analysis population. Patients receiving 7-day buprenorphine patches plus oral paracetamol needed significantly less escape medication (ibuprofen) than those receiving Co-Codamol tablets ( P =0.002; PP population). Less than 10% of patients in the 7-day buprenorphine patches plus oral paracetamol group were receiving the highest dose level at the end of the study, compared with 34% in the Co-Codamol group. Withdrawal rates were high in both groups. The incidence of adverse events (AEs) was comparable between the groups (86.4% of patients in the 7-day buprenorphine patches plus oral paracetamol group; 81.7% in the Co-Codamol group). Six serious AEs were reported in three patients (2.7%) in the 7-day buprenorphine patches plus oral paracetamol group and one (0.9%) in the Co-Codamol group. Conclusions 7-day buprenorphine patches plus oral paracetamol were non-inferior to Co-Codamol tablets with respect to analgesic efficacy in older adults with OA pain in the hip/knee. Clintrials.gov number: NCT00324038.
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Transdermal buprenorphine plus oral paracetamol vs an oral codeine-paracetamol combination for osteoarthritis of hip and/or knee: a randomised trial
Osteoarthritis and Cartilage, 2011Co-Authors: P G Conaghan, M Wilson, C.m. O’brien, J P SchofieldAbstract:Summary Objective Low-dose transdermal opioids offer a new therapeutic option for osteoarthritis (OA). This study compared symptom relief obtained with buprenorphine patches plus oral paracetamol with that obtained with an oral codeine-paracetamol combination tablet (Co-Codamol) in older adults with OA. Method Two hundred and twenty people (aged ≥60 years) with OA hip and/or knee pain were randomised to treatment with 7-day buprenorphine patches plus oral paracetamol (5–25μg/h buprenorphine patches plus 1000mg oral paracetamol q.i.d. (4 times daily); n =110) or Co-Codamol tablets (two 8/500–two 30/500mg tablets q.i.d.; n =110). They entered a titration period of up to 10 weeks, during which their dose of study medication was adjusted until they reached optimum pain control. Patients who achieved optimum pain control entered a 12-week assessment period. The primary outcome was average daily pain scores recorded using the box scale-11 (BS-11) pain scale. Results Both treatments significantly reduced patient pain scores. The estimated treatment difference [95% confidence interval ( CI)] was −0.02 (−0.64, 0.60) for the per protocol (PP) population. The results were similar for the full analysis population. Patients receiving 7-day buprenorphine patches plus oral paracetamol needed significantly less escape medication (ibuprofen) than those receiving Co-Codamol tablets ( P =0.002; PP population). Less than 10% of patients in the 7-day buprenorphine patches plus oral paracetamol group were receiving the highest dose level at the end of the study, compared with 34% in the Co-Codamol group. Withdrawal rates were high in both groups. The incidence of adverse events (AEs) was comparable between the groups (86.4% of patients in the 7-day buprenorphine patches plus oral paracetamol group; 81.7% in the Co-Codamol group). Six serious AEs were reported in three patients (2.7%) in the 7-day buprenorphine patches plus oral paracetamol group and one (0.9%) in the Co-Codamol group. Conclusions 7-day buprenorphine patches plus oral paracetamol were non-inferior to Co-Codamol tablets with respect to analgesic efficacy in older adults with OA pain in the hip/knee. Clintrials.gov number: NCT00324038.
P G Conaghan - One of the best experts on this subject based on the ideXlab platform.
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transdermal buprenorphine plus oral paracetamol vs an oral codeine paracetamol combination for osteoarthritis of hip and or knee a randomised trial
Osteoarthritis and Cartilage, 2011Co-Authors: P G Conaghan, C M Obrien, M Wilson, J P SchofieldAbstract:Summary Objective Low-dose transdermal opioids offer a new therapeutic option for osteoarthritis (OA). This study compared symptom relief obtained with buprenorphine patches plus oral paracetamol with that obtained with an oral codeine-paracetamol combination tablet (Co-Codamol) in older adults with OA. Method Two hundred and twenty people (aged ≥60 years) with OA hip and/or knee pain were randomised to treatment with 7-day buprenorphine patches plus oral paracetamol (5–25μg/h buprenorphine patches plus 1000mg oral paracetamol q.i.d. (4 times daily); n =110) or Co-Codamol tablets (two 8/500–two 30/500mg tablets q.i.d.; n =110). They entered a titration period of up to 10 weeks, during which their dose of study medication was adjusted until they reached optimum pain control. Patients who achieved optimum pain control entered a 12-week assessment period. The primary outcome was average daily pain scores recorded using the box scale-11 (BS-11) pain scale. Results Both treatments significantly reduced patient pain scores. The estimated treatment difference [95% confidence interval ( CI)] was −0.02 (−0.64, 0.60) for the per protocol (PP) population. The results were similar for the full analysis population. Patients receiving 7-day buprenorphine patches plus oral paracetamol needed significantly less escape medication (ibuprofen) than those receiving Co-Codamol tablets ( P =0.002; PP population). Less than 10% of patients in the 7-day buprenorphine patches plus oral paracetamol group were receiving the highest dose level at the end of the study, compared with 34% in the Co-Codamol group. Withdrawal rates were high in both groups. The incidence of adverse events (AEs) was comparable between the groups (86.4% of patients in the 7-day buprenorphine patches plus oral paracetamol group; 81.7% in the Co-Codamol group). Six serious AEs were reported in three patients (2.7%) in the 7-day buprenorphine patches plus oral paracetamol group and one (0.9%) in the Co-Codamol group. Conclusions 7-day buprenorphine patches plus oral paracetamol were non-inferior to Co-Codamol tablets with respect to analgesic efficacy in older adults with OA pain in the hip/knee. Clintrials.gov number: NCT00324038.
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Transdermal buprenorphine plus oral paracetamol vs an oral codeine-paracetamol combination for osteoarthritis of hip and/or knee: a randomised trial
Osteoarthritis and Cartilage, 2011Co-Authors: P G Conaghan, M Wilson, C.m. O’brien, J P SchofieldAbstract:Summary Objective Low-dose transdermal opioids offer a new therapeutic option for osteoarthritis (OA). This study compared symptom relief obtained with buprenorphine patches plus oral paracetamol with that obtained with an oral codeine-paracetamol combination tablet (Co-Codamol) in older adults with OA. Method Two hundred and twenty people (aged ≥60 years) with OA hip and/or knee pain were randomised to treatment with 7-day buprenorphine patches plus oral paracetamol (5–25μg/h buprenorphine patches plus 1000mg oral paracetamol q.i.d. (4 times daily); n =110) or Co-Codamol tablets (two 8/500–two 30/500mg tablets q.i.d.; n =110). They entered a titration period of up to 10 weeks, during which their dose of study medication was adjusted until they reached optimum pain control. Patients who achieved optimum pain control entered a 12-week assessment period. The primary outcome was average daily pain scores recorded using the box scale-11 (BS-11) pain scale. Results Both treatments significantly reduced patient pain scores. The estimated treatment difference [95% confidence interval ( CI)] was −0.02 (−0.64, 0.60) for the per protocol (PP) population. The results were similar for the full analysis population. Patients receiving 7-day buprenorphine patches plus oral paracetamol needed significantly less escape medication (ibuprofen) than those receiving Co-Codamol tablets ( P =0.002; PP population). Less than 10% of patients in the 7-day buprenorphine patches plus oral paracetamol group were receiving the highest dose level at the end of the study, compared with 34% in the Co-Codamol group. Withdrawal rates were high in both groups. The incidence of adverse events (AEs) was comparable between the groups (86.4% of patients in the 7-day buprenorphine patches plus oral paracetamol group; 81.7% in the Co-Codamol group). Six serious AEs were reported in three patients (2.7%) in the 7-day buprenorphine patches plus oral paracetamol group and one (0.9%) in the Co-Codamol group. Conclusions 7-day buprenorphine patches plus oral paracetamol were non-inferior to Co-Codamol tablets with respect to analgesic efficacy in older adults with OA pain in the hip/knee. Clintrials.gov number: NCT00324038.
Navneet Kapur - One of the best experts on this subject based on the ideXlab platform.
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relative toxicity of analgesics commonly used for intentional self poisoning a study of case fatality based on fatal and non fatal overdoses
Journal of Affective Disorders, 2019Co-Authors: Keith Hawton, David Gunnell, Anne E Ferrey, Deborah Casey, Claudia Wells, Alice Fuller, Clare Bankhead, Caroline Clements, Jennifer Ness, Navneet KapurAbstract:Abstract Background Analgesics are used most frequently in fatal and non-fatal medicinal self-poisonings. Knowledge about their relative toxicity in overdose is important for clinicians and regulatory agencies. Methods Using data for 2005–2012 we investigated case fatality (number of suicides relative to number of non-fatal self-poisonings) of paracetamol, aspirin, codeine, dihydrocodeine, tramadol, paracetamol with codeine (Co-Codamol), paracetamol with dihydrocodeine (co-dydramol), ibuprofen and co-proxamol (paracetamol plus dextropropoxyphene; withdrawn in the UK in 2008 due to high toxicity). Data on suicides obtained from the Office for National Statistics and on non-fatal self-poisonings from the Multicentre Study of Self-harm in England. Case fatality was estimated for each drug, using paracetamol as the reference category. Results Compared to paracetamol and based on single drug deaths the case fatality index of dihydrocodeine was considerably elevated (odds ratio (OR) 12.81, 95% Confidence Interval (CI) 10.19–16.12). Case fatality indices for tramadol (OR 4.05, 95% CI 3.38–4.85) and codeine (OR 2.21, 95% CI 1.81–2.70) were also significantly higher than for paracetamol. The results when multiple drug deaths were included produced similar results. The relative toxicity of co-proxamol far exceeded that of the other analgesics. Limitations Data on fatal self-poisonings were based on national data, whereas those for non-fatal poisonings were based on local data. Conclusions Dihydrocodeine and tramadol are particularly toxic in overdose and codeine is also relatively toxic. They should be prescribed with caution, particularly to individuals at risk of self-harm.
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Relative toxicity of analgesics commonly used for intentional self-poisoning: A study of case fatality based on fatal and non-fatal overdoses
Journal of Affective Disorders, 2019Co-Authors: Keith Hawton, David Gunnell, Anne E Ferrey, Deborah Casey, Claudia Wells, Alice Fuller, Clare Bankhead, Caroline Clements, Jennifer Ness, Navneet KapurAbstract:Abstract Background Analgesics are used most frequently in fatal and non-fatal medicinal self-poisonings. Knowledge about their relative toxicity in overdose is important for clinicians and regulatory agencies. Methods Using data for 2005–2012 we investigated case fatality (number of suicides relative to number of non-fatal self-poisonings) of paracetamol, aspirin, codeine, dihydrocodeine, tramadol, paracetamol with codeine (Co-Codamol), paracetamol with dihydrocodeine (co-dydramol), ibuprofen and co-proxamol (paracetamol plus dextropropoxyphene; withdrawn in the UK in 2008 due to high toxicity). Data on suicides obtained from the Office for National Statistics and on non-fatal self-poisonings from the Multicentre Study of Self-harm in England. Case fatality was estimated for each drug, using paracetamol as the reference category. Results Compared to paracetamol and based on single drug deaths the case fatality index of dihydrocodeine was considerably elevated (odds ratio (OR) 12.81, 95% Confidence Interval (CI) 10.19–16.12). Case fatality indices for tramadol (OR 4.05, 95% CI 3.38–4.85) and codeine (OR 2.21, 95% CI 1.81–2.70) were also significantly higher than for paracetamol. The results when multiple drug deaths were included produced similar results. The relative toxicity of co-proxamol far exceeded that of the other analgesics. Limitations Data on fatal self-poisonings were based on national data, whereas those for non-fatal poisonings were based on local data. Conclusions Dihydrocodeine and tramadol are particularly toxic in overdose and codeine is also relatively toxic. They should be prescribed with caution, particularly to individuals at risk of self-harm.
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Six-Year Follow-Up of Impact of Co-proxamol Withdrawal in England and Wales on Prescribing and Deaths: Time-Series Study
PLoS Medicine, 2012Co-Authors: Keith Hawton, Helen Bergen, Sue Simkin, Navneet Kapur, Claudia Wells, David GunnellAbstract: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. METHODS AND FINDINGS: 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. Please see later in the article for the Editors' Summary. Language: en
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effect of withdrawal of co proxamol on prescribing and deaths from drug poisoning in england and wales time series analysis
BMJ, 2009Co-Authors: Keith Hawton, Helen Bergen, Sue Simkin, Anita Brock, Clare Griffiths, Ester Romeri, Karen Smith, Navneet Kapur, David GunnellAbstract: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.
M Wilson - One of the best experts on this subject based on the ideXlab platform.
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transdermal buprenorphine plus oral paracetamol vs an oral codeine paracetamol combination for osteoarthritis of hip and or knee a randomised trial
Osteoarthritis and Cartilage, 2011Co-Authors: P G Conaghan, C M Obrien, M Wilson, J P SchofieldAbstract:Summary Objective Low-dose transdermal opioids offer a new therapeutic option for osteoarthritis (OA). This study compared symptom relief obtained with buprenorphine patches plus oral paracetamol with that obtained with an oral codeine-paracetamol combination tablet (Co-Codamol) in older adults with OA. Method Two hundred and twenty people (aged ≥60 years) with OA hip and/or knee pain were randomised to treatment with 7-day buprenorphine patches plus oral paracetamol (5–25μg/h buprenorphine patches plus 1000mg oral paracetamol q.i.d. (4 times daily); n =110) or Co-Codamol tablets (two 8/500–two 30/500mg tablets q.i.d.; n =110). They entered a titration period of up to 10 weeks, during which their dose of study medication was adjusted until they reached optimum pain control. Patients who achieved optimum pain control entered a 12-week assessment period. The primary outcome was average daily pain scores recorded using the box scale-11 (BS-11) pain scale. Results Both treatments significantly reduced patient pain scores. The estimated treatment difference [95% confidence interval ( CI)] was −0.02 (−0.64, 0.60) for the per protocol (PP) population. The results were similar for the full analysis population. Patients receiving 7-day buprenorphine patches plus oral paracetamol needed significantly less escape medication (ibuprofen) than those receiving Co-Codamol tablets ( P =0.002; PP population). Less than 10% of patients in the 7-day buprenorphine patches plus oral paracetamol group were receiving the highest dose level at the end of the study, compared with 34% in the Co-Codamol group. Withdrawal rates were high in both groups. The incidence of adverse events (AEs) was comparable between the groups (86.4% of patients in the 7-day buprenorphine patches plus oral paracetamol group; 81.7% in the Co-Codamol group). Six serious AEs were reported in three patients (2.7%) in the 7-day buprenorphine patches plus oral paracetamol group and one (0.9%) in the Co-Codamol group. Conclusions 7-day buprenorphine patches plus oral paracetamol were non-inferior to Co-Codamol tablets with respect to analgesic efficacy in older adults with OA pain in the hip/knee. Clintrials.gov number: NCT00324038.
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Transdermal buprenorphine plus oral paracetamol vs an oral codeine-paracetamol combination for osteoarthritis of hip and/or knee: a randomised trial
Osteoarthritis and Cartilage, 2011Co-Authors: P G Conaghan, M Wilson, C.m. O’brien, J P SchofieldAbstract:Summary Objective Low-dose transdermal opioids offer a new therapeutic option for osteoarthritis (OA). This study compared symptom relief obtained with buprenorphine patches plus oral paracetamol with that obtained with an oral codeine-paracetamol combination tablet (Co-Codamol) in older adults with OA. Method Two hundred and twenty people (aged ≥60 years) with OA hip and/or knee pain were randomised to treatment with 7-day buprenorphine patches plus oral paracetamol (5–25μg/h buprenorphine patches plus 1000mg oral paracetamol q.i.d. (4 times daily); n =110) or Co-Codamol tablets (two 8/500–two 30/500mg tablets q.i.d.; n =110). They entered a titration period of up to 10 weeks, during which their dose of study medication was adjusted until they reached optimum pain control. Patients who achieved optimum pain control entered a 12-week assessment period. The primary outcome was average daily pain scores recorded using the box scale-11 (BS-11) pain scale. Results Both treatments significantly reduced patient pain scores. The estimated treatment difference [95% confidence interval ( CI)] was −0.02 (−0.64, 0.60) for the per protocol (PP) population. The results were similar for the full analysis population. Patients receiving 7-day buprenorphine patches plus oral paracetamol needed significantly less escape medication (ibuprofen) than those receiving Co-Codamol tablets ( P =0.002; PP population). Less than 10% of patients in the 7-day buprenorphine patches plus oral paracetamol group were receiving the highest dose level at the end of the study, compared with 34% in the Co-Codamol group. Withdrawal rates were high in both groups. The incidence of adverse events (AEs) was comparable between the groups (86.4% of patients in the 7-day buprenorphine patches plus oral paracetamol group; 81.7% in the Co-Codamol group). Six serious AEs were reported in three patients (2.7%) in the 7-day buprenorphine patches plus oral paracetamol group and one (0.9%) in the Co-Codamol group. Conclusions 7-day buprenorphine patches plus oral paracetamol were non-inferior to Co-Codamol tablets with respect to analgesic efficacy in older adults with OA pain in the hip/knee. Clintrials.gov number: NCT00324038.
Keith Hawton - One of the best experts on this subject based on the ideXlab platform.
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relative toxicity of analgesics commonly used for intentional self poisoning a study of case fatality based on fatal and non fatal overdoses
Journal of Affective Disorders, 2019Co-Authors: Keith Hawton, David Gunnell, Anne E Ferrey, Deborah Casey, Claudia Wells, Alice Fuller, Clare Bankhead, Caroline Clements, Jennifer Ness, Navneet KapurAbstract:Abstract Background Analgesics are used most frequently in fatal and non-fatal medicinal self-poisonings. Knowledge about their relative toxicity in overdose is important for clinicians and regulatory agencies. Methods Using data for 2005–2012 we investigated case fatality (number of suicides relative to number of non-fatal self-poisonings) of paracetamol, aspirin, codeine, dihydrocodeine, tramadol, paracetamol with codeine (Co-Codamol), paracetamol with dihydrocodeine (co-dydramol), ibuprofen and co-proxamol (paracetamol plus dextropropoxyphene; withdrawn in the UK in 2008 due to high toxicity). Data on suicides obtained from the Office for National Statistics and on non-fatal self-poisonings from the Multicentre Study of Self-harm in England. Case fatality was estimated for each drug, using paracetamol as the reference category. Results Compared to paracetamol and based on single drug deaths the case fatality index of dihydrocodeine was considerably elevated (odds ratio (OR) 12.81, 95% Confidence Interval (CI) 10.19–16.12). Case fatality indices for tramadol (OR 4.05, 95% CI 3.38–4.85) and codeine (OR 2.21, 95% CI 1.81–2.70) were also significantly higher than for paracetamol. The results when multiple drug deaths were included produced similar results. The relative toxicity of co-proxamol far exceeded that of the other analgesics. Limitations Data on fatal self-poisonings were based on national data, whereas those for non-fatal poisonings were based on local data. Conclusions Dihydrocodeine and tramadol are particularly toxic in overdose and codeine is also relatively toxic. They should be prescribed with caution, particularly to individuals at risk of self-harm.
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Relative toxicity of analgesics commonly used for intentional self-poisoning: A study of case fatality based on fatal and non-fatal overdoses
Journal of Affective Disorders, 2019Co-Authors: Keith Hawton, David Gunnell, Anne E Ferrey, Deborah Casey, Claudia Wells, Alice Fuller, Clare Bankhead, Caroline Clements, Jennifer Ness, Navneet KapurAbstract:Abstract Background Analgesics are used most frequently in fatal and non-fatal medicinal self-poisonings. Knowledge about their relative toxicity in overdose is important for clinicians and regulatory agencies. Methods Using data for 2005–2012 we investigated case fatality (number of suicides relative to number of non-fatal self-poisonings) of paracetamol, aspirin, codeine, dihydrocodeine, tramadol, paracetamol with codeine (Co-Codamol), paracetamol with dihydrocodeine (co-dydramol), ibuprofen and co-proxamol (paracetamol plus dextropropoxyphene; withdrawn in the UK in 2008 due to high toxicity). Data on suicides obtained from the Office for National Statistics and on non-fatal self-poisonings from the Multicentre Study of Self-harm in England. Case fatality was estimated for each drug, using paracetamol as the reference category. Results Compared to paracetamol and based on single drug deaths the case fatality index of dihydrocodeine was considerably elevated (odds ratio (OR) 12.81, 95% Confidence Interval (CI) 10.19–16.12). Case fatality indices for tramadol (OR 4.05, 95% CI 3.38–4.85) and codeine (OR 2.21, 95% CI 1.81–2.70) were also significantly higher than for paracetamol. The results when multiple drug deaths were included produced similar results. The relative toxicity of co-proxamol far exceeded that of the other analgesics. Limitations Data on fatal self-poisonings were based on national data, whereas those for non-fatal poisonings were based on local data. Conclusions Dihydrocodeine and tramadol are particularly toxic in overdose and codeine is also relatively toxic. They should be prescribed with caution, particularly to individuals at risk of self-harm.
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Six-Year Follow-Up of Impact of Co-proxamol Withdrawal in England and Wales on Prescribing and Deaths: Time-Series Study
PLoS Medicine, 2012Co-Authors: Keith Hawton, Helen Bergen, Sue Simkin, Navneet Kapur, Claudia Wells, David GunnellAbstract: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. METHODS AND FINDINGS: 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. Please see later in the article for the Editors' Summary. Language: en
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effect of withdrawal of co proxamol on prescribing and deaths from drug poisoning in england and wales time series analysis
BMJ, 2009Co-Authors: Keith Hawton, Helen Bergen, Sue Simkin, Anita Brock, Clare Griffiths, Ester Romeri, Karen Smith, Navneet Kapur, David GunnellAbstract: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.