NPC Archive Item: EMEA recommends withdrawal of co-proxamol

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2nd July 2009

The EMEA has recommended that the marketing authorisations for dextropropoxyphene-containing medicines are withdrawn across the European Union (EU) because their benefits do not outweigh their risks. Co-proxamol is the only medicine affected in the UK by this announcement. About 73,000 co-proxamol items were dispensed in England in the first quarter of 2009, a large reduction since 2005.

This does not change current practice within the UK as the MHRA cancelled co-proxamol’s marketing authorisation at the end of 2007. The pain control of most patients taking co-proxamol should already have been reviewed, and their prescriptions should have been changed to more suitable and licensed alternatives, where possible. Patients who are still taking co-proxamol should continue to be reviewed. Unlicensed co-proxamol is still available to prescribe for a small number of patients under a “named-patient” basis. However, prescribers take full clinical responsibility. A previous MeReC Bulletin discusses alternative analgesics for managing mild-to-moderate pain.

What is the background to this?
The MHRA announced in January 2005 that co-proxamol would be withdrawn in the UK at the end of 2007 following a phased withdrawal. This decision was reached after a safety review of the risks and benefits of co-proxamol concluded that the “efficacy of co-proxamol is poorly established and the risk of toxicity in overdose, both accidental and deliberate, is unacceptable”.

In June 2009, the EMEA’s Committee for Medicinal Products for Human Use (CHMP) reviewed data on dextropropoxyphene-containing medicines from both the manufacturer’s and published literature. They recommended that the marketing authorisations for dextropropoxyphene-containing medicines are withdrawn across the EU, after concluding that:

  • dextropropoxyphene-containing medicines are weak pain killers. The available evidence suggests that co-proxamol is no more effective than other widely used painkillers, such as paracetamol or ibuprofen, at normal doses
  • dextropropoxyphene has a ‘narrow therapeutic index’. Co-proxamol is extremely dangerous in overdose as only a small overdose can be fatal, and death can occur very rapidly – before medical attention can be sought. Many fatal overdoses have been accidental
  • a significant number of deaths have been associated with overdose in patients taking dextropropoxyphene
  • the benefits of dextropropoxyphene-containing medicines do not outweigh their risks.

The MHRA has advised that there is still provision for the prescription of unlicensed co-proxamol for a small number of patients who find it very difficult to change from co-proxamol, or where other analgesics are ineffective or unsuitable. However, prescribers, who can judge the risks and benefits in consultation with the patient, take full clinical responsibility for this.

What has been the effect of co-proxamol withdrawal in the UK?
A time series analysis reported in the British Medical Journal (BMJ) has shown that, after the announcement of withdrawal of co-proxamol in January 2005, there was a steep reduction in co-proxamol prescriptions for England and Wales during 2005-2007 compared with that expected from the data for 1998-2004. This equated to 59% fewer prescriptions and significant increases in prescriptions for other analgesics (co-codamol, paracetamol, co-dydramol and codeine) were seen. The decrease in co-proxamol prescribing was also associated with a 62% reduction in deaths from suicide related to co-proxamol, or an estimated 295 fewer deaths over the three years (349 fewer deaths when accidental deaths were included.) There was no evidence of an increase in deaths involving other analgesics during this period. This evidence, along with similar findings for Scotland (see previous MeReC Rapid Review Blog) suggests that the UK withdrawal of co-proxamol has been beneficial.

We have previously shown a substantial reduction in co-proxamol prescribing between January 2005 and May 2008. Prescribing data from the NHS Business Services Authority (NHSBSA) shows that 73,617 prescriptions for co-proxamol were still dispensed in England in the first quarter of 2009. Although this represents a reduction from 493,191 in the last quarter of 2005, patients still taking co-proxamol may benefit from a review of their pain control. In 2008, a MeReC Stop Press Blog reported that the price of co-proxamol had increased dramatically since its withdrawal. Therefore, even though co-proxamol prescribing has reduced, the cost in England has increased from just under £1.3million in the last quarter of 2005 to just under £1.9million in the first quarter of 2009.

MeReC Bulletin Vol 16 No. 4 discusses alternative analgesics for managing mild-to-moderate pain in the light of co-proxamol withdrawal. More information on pain control can be found on the pain management section of NPC.

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