Revised: 26 March 2010

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Questions and answers on the withdrawal of the dextropropoxyphene-containing medicines Capadex and Paradex

What are Capadex and Paradex?

Capadex and Paradex are the only medicines containing dextropropoxyphene that are approved for use in New Zealand. These medicines contain a combination of dextropropoxyphene and low dose paracetamol (325 milligrams). In comparison, most paracetamol-only tablets and capsules contain 500mg of paracetamol. Capadex and Paradex are used to treat long-term (chronic) pain of moderate severity.

Dextropropoxyphene is one of a group of medicines called opiates that are used to relieve pain. Other opioid medicines include codeine and morphine.

What is happening with Capadex and Paradex?

The consents to distribute Capadex and Paradex in New Zealand will be revoked.

When will Capadex and Paradex be withdrawn?

The consents to distribute Capadex and Paradex will be revoked on 1 August 2010 . This date, which was set following consultation with clinicians form the Royal New Zealand College of General Practitioners, is to allow sufficient time for patients to transfer safely onto alternative treatments. From this date it will no longer be legal to sell, distribute or advertise these medicines, unless exempted under the Medicines Act 1981.

How many patients will be affected by this withdrawal?

It is estimated that approximately 78,000 patients were prescribed Capadex or Paradex in 2009.

Are there alternative pain relieving medicines available in New Zealand?

There are a number of alternative pain relieving medicines approved for use in New Zealand. Experience in the United Kingdom1, where dextropropoxyphene-containing medicines were withdrawn in 2007, suggests that most patients were successfully changed to either full dose paracetamol alone, codeine alone, or paracetamol/codeine combination products. These medicines are all available in New Zealand.

Why was a statutory review of dextropropoxyphene undertaken?

The MARC first reviewed the use of dextropropoxyphene-containing medicines in 2005 after it was announced that these medicines were to be withdrawn from the United Kingdom (UK)2. The UK stated that deaths had occurred following intentional and accidental overdose, even with low numbers of tablets. These deaths had occurred primarily when the tablets were combined with alcohol or other medicines that can affect the brain, such as antidepressants and anti-anxiety medicines. The MARC was particularly concerned that death could occur rapidly (within 1 hour of ingestion) and prior to medical intervention being possible. In New Zealand between January 2001 and December 2002 there were 16 deaths involving dextropropoxyphene, of which six deaths were unintentional. The MARC considered that dextropropoxyphene-containing medicines were much more dangerous in overdose than alternative pain-relieving medicines. At that time the MARC concluded that the risks outweighed the benefits of use for the majority of patients.

However, after consultation with healthcare professionals and patient interest groups, the MARC accepted that there might be an unmet clinical need for these medicines in a select group of patients, in whom the benefits would outweigh the risks. The MARC recommended that prescribing restrictions be introduced to limit use of these medicines to this group of patients. These restrictions limited the use of Capadex and Paradex to patients with chronic (long term) pain conditions who had experienced inadequate pain relief from full doses of alternative analgesics3. The MARC also requested that a study be conducted to monitor the effect of the new restrictions.

In June 2009, the MARC reviewed the results of the study conducted for Paradex, This showed that less than half of the prescriptions issued were consistent with the new restrictions. In addition, a significant number of prescriptions were also issued to children. The MARC concluded that significant numbers of New Zealanders were still being exposed to a medicine in which the risks outweighed the benefits for the majority of patients. Therefore, the MARC recommended that a statutory review of the benefits and risks of these medicines be initiated under section 36 of the Medicines Act 1981.

What is Section 36 of the Medicines Act 1981?

Section 36 of the Medicines Act 1981 gives the Director General of Health the power to require a medicine sponsor (ie the New Zealand manufacturer or distributor of a medicine), to provide data on the safety and effectiveness of that medicine. If the Director General has concerns with the data provided, the medicine may be referred to the MARC. If assessment and analysis of the data provided by the company indicates that the risks outweigh the benefits, the MARC may recommend that the Minister of Health take action, which may include withdrawing the medicine from New Zealand.

Which information did the MARC consider in the statutory review?

The MARC considered data provided by the sponsors of Capadex and Paradex in support of the effectiveness and safety of their medicines. The MARC also reviewed a risk-benefit review provided by Medsafe, which included analysis of published literature, toxicology information, a review of adverse reactions (side effects) and data from the New Zealand Poisons Centre.

What are the conclusions of the MARC?

After analysis and discussion of the available data the MARC concluded that

  • Studies have demonstrated that these medicines are no more effective at relieving pain than paracetamol alone used at maximum recommended doses.
  • The available data on side effects (adverse reactions) experienced by patients taking these medicines showed that they have the potential to cause more side effects than paracetamol alone.
  • These medicines are more dangerous than other pain-relievers in overdose, particularly when combined with alcohol.
  • Prescribing restrictions introduced in 2006 have been ineffective at limiting the use of these medicines to the small group of patients in whom the benefits are likely to outweigh the risks.
  • Overall the benefits of these medicines do not outweigh the risks associated with their use. In addition, there are safer alternative pain relievers available in New Zealand.

The MARC considered that there were no further statutory restrictions that could be introduced to minimise the risks associated with these medicines. Therefore, in the interests of public safety, the MARC recommended that Capadex and Paradex be withdrawn from New Zealand. More information about the data that the MARC considered in their review can be found in the minutes of the 140th MARC meeting at www.medsafe.govt.nz/profs/adverse/Minutes140.htm

Capadex and Paradex have been around for a long time. Why is action being taken now?

The first medicines containing dextropropoxyphene was approved for use in New Zealand about 40 years ago. At that time the requirements for medicines approval were not as stringent as they are now.

The risks associated with the use of dextropropoxyphene-containing medicines only became apparent after they had been used by a large number of patients for many years. After this risk was identified, Medsafe and the MARC introduced prescribing restrictions in an attempt to restrict use to patients in whom the benefits were likely to outweigh the risks.

Sufficient time was given to allow these new restrictions to take effect before an audit was performed. In 2009, when evidence suggested that these prescribing restrictions had been ineffective, a statutory review of the risks and benefits of dextropropoxyphene-containing medicines was initiated.

If these medicines are unsafe, why not remove them from the market straight away?

Due to the significant usage of Capadex and Paradex in New Zealand the MARC considered it was important that there be sufficient time to allow patients to be safely and effectively transferred to alternative pain relievers before these medicines are finally withdrawn.

What actions have been taken in other countries?

Medicines containing dextropropoxyphene have already been withdrawn in the UK. In addition, medicines regulators in Europe and Singapore have also announced that these medicines will be withdrawn.

The United States Food and Drug Administration has chosen not to withdraw dextropropoxyphene-containing medicines from their market at this stage. However, the FDA has recently imposed further restrictions on their use.

What happened in the United Kingdom when dextropropoxyphene was removed from the market?

In the UK studies have shown that the majority of patients have been effectively changed to other pain relievers including paracetamol alone, codeine alone, or a codeine/paracetamol combination product.

I am currently taking dextropropoxyphene. What should I do?

You should talk with your doctor at your next appointment to have your pain relief medication plan reviewed.

For patients who are unable to change treatment there is provision under the Medicines Act which allows a medial practitioner to prescribe and supply medicines that are not approved for distribution in New Zealand. Further information is available at: www.medsafe.govt.nz/profs/riss/unapp.asp

Is it safe to stop Capadex/Paradex straight away?

If you have been taking these medicines continuously for a long time you should not stop taking them without talking to your doctor. You should talk with your doctor at your next appointment to have your pain relief medication plan reviewed.

For further information please refer to:

  1. Hawton K et al 2009.  Effect of withdrawal of co-proxamol on prescribing and deaths from drug poisoning in England and Wales:time series analysis.  BMJ 338:b2270. doi: 10.1136/bmj.b2270.
  2. Minutes of the 122nd MARC meeting June 2005 available at www.medsafe.govt.nz/profs/adverse/Minutes122.htm#3.1%20Dextropropoxyphene/paracetamol
  3. Medsafe Pharmacovigilance Team 2006. Dextropropoxyphene-Paracetamol Combination Products and Risk of Overdose. Prescriber Update 2006;27(2):21-22. www.medsafe.govt.nz/profs/PUarticles/dextro.htm
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