Published: October 2006

Publications

Dextropropoxyphene-Paracetamol Combination Products and Risk of Overdose

This article is more than five years old. Some content may no longer be current.

Prescriber Update 27(2): 21-22.
October 2006

Medsafe Pharmacovigilance Team

To enhance the safe use of dextropropoxyphene-paracetamol combination products, changes to the prescribing information have been made.  These combination products are now indicated only for the relief of chronic pain of moderate severity in patients who have not adequately responded to, or not tolerated, therapeutic doses of alternative analgesics.  The maximum daily dose is eight tablets but lower doses may be adequate for some patients.  Concurrent use of alcohol or other paracetamol-containing products is contraindicated, and patients should be counselled accordingly and also reminded not to exceed the recommended dose.

Safety reviewed by MARC

In 2005, Medsafe and the Medicines Adverse Reactions Committee (MARC) undertook a review of the risk of overdose with dextropropoxyphene-paracetamol combination products, such as Capadex^® and Paradex^®.  Fatalities have occurred following intentional and accidental overdose, even with low numbers of tablets, and when normal doses have been taken concurrently with alcohol or other CNS depressants.  The combination of paracetamol and dextropropoxyphene carries an overdose risk of rapid-onset respiratory arrest and cardiac arrhythmias due to the dextropropoxyphene component, as well as latent onset of paracetamol-induced hepatic necrosis.¹  In New Zealand, between January 2001 and December 2002, there were 92 deaths from opioid poisonings.  Sixteen of these involved dextropropoxyphene, of which six deaths were unintentional.²

Part of the MARC's review involved consultation with healthcare professionals and patient support organisations, which provided opinions that there is still perceived to be a clinical need for these products for some patients in the treatment of chronic pain.

Updated prescribing information to improve safety

As a result of the MARC's review, and in order to manage the risks associated with these products, significant changes have been made to the prescribing information for Capadex and Paradex.^3,4  These changes include:

• Narrowing of the indication to the "relief of chronic pain of moderate severity".
• Restriction to second-line therapy for patients who have inadequately responded to, or have not tolerated, therapeutic doses of alternative analgesics.
• Restriction of the recommended dose to 2 tablets up to every 4 hours, with a maximum daily dose of 8 tablets (this represents 2.6g of paracetamol).  The dosage should be reduced in patients with hepatic or renal impairment and in the elderly.

For some patients, the time interval between doses can be increased and the total daily dose reduced without compromising pain control.

Avoid concurrent use with alcohol or paracetamol-containing products

Prescribers are reminded that concurrent use of alcohol or other paracetamol-containing products is contraindicated.  Dextropropoxyphene-paracetamol combination products should not be prescribed for patients who are suicidal or prone to medicine dependence, and should be prescribed with caution for those patients taking anxiolytics or antidepressants.

Remind patients to adhere to usage instructions

Prescribers and pharmacists should inform patients who have been prescribed a dextropropoxyphene-paracetamol combination product not to exceed the recommended dose; to avoid alcohol; not to take other paracetamol-containing products; not to give their tablets to anyone else; and that unwanted tablets should be destroyed or returned to a pharmacy as soon as possible after completing treatment.

Medsafe and the MARC will continue to monitor the safety of these products.

Competing interests (authors): none declared.

References

1. Medicines and Healthcare products Regulatory Agency (MHRA), United Kingdom. Co-proxamol overdose 19 May 2005. www.mhra.gov.uk (accessed 26 Sept 2006).
2. Reith D, Fountain J, Tilyard M. Opioid poisoning deaths in New Zealand (2001-2002). NZMJ 2005;118(1209):1-8. www.nzma.org.nz/journal/118-1209/1293/\ (accessed 10 Oct 2006).
3. Pharmacy Retailing (NZ) Ltd. Capadex (dextropropoxyphene hydrochloride 32.5mg and paracetamol 325mg) capsules data sheet. 22 March 2006.
4. PSM Healthcare Ltd. Paradex (dextropropoxyphene napsylate 50mg and paracetamol 325mg) tablets data sheet. 6 April 2006.