INDICES> UK to remove dextropropoxyphene combination from the market

[hamis@iafrica.com]

Indices: UK to remove dextropropoxyphene combination from the market


Cross posted from Druginfo: thanks to Andy Grey:

Earlier the MHRA had indicated that it was reviewing the registration of
what they call "Co-proxamol" - the combination of paracetamol and
dextropropoxyphene. The CSM has now decided that:

"*  In relation to safety, there is evidence that fatal toxicity may occur
with a small multiple of the normal therapeutic dose and a proportion of
fatalities are
caused by inadvertent overdose. Pharmacokinetic and pharmacodynamic
interactions with alcohol further reduce the threshold for fatal toxicity.
* There is no robust evidence that efficacy of this combination product is
superior to full strength paracetamol alone in either acute or chronic use.
*  It has not been possible to identify any patient group in whom the
risk:benefit may be positive.
* Co-proxamol products should be withdrawn altogether over the next 6-12
months.
* During the withdrawal phase, interim restrictions and warnings regarding
the use of co-proxamol should be introduced to the product information."

It noted that "Each year there are 300-400 fatalities following deliberate
or accidental drug overdose involving co-proxamol in England and Wales
alone." - are there arny comparable data for SA? This is a widely used
product.

The Q&A fromj the MHRA site is below - here's the advice:

"Indications:
* For the treatment of mild to moderate pain in adults where first line
analgesics have proved ineffective or are inappropriate. Co-proxamol should
not be used for any acute pain indication.
* Co-proxamol therapy should not be initiated in new patients.
* Co-proxamol should not be used in patients aged <18 years

Co-proxamol is contraindicated in:
* Patients who are alcohol-dependent or who are likely to consume alcohol
whilst taking co-proxamol.
* Patients who are suicidal or addiction-prone.

Special warnings to give your patients:
* never exceed the recommended dose.
* never consume alcohol while taking a course of co-proxamol
* Dispose of any unused supplies of co-proxamol (through a pharmacist) as
soon as possible after completing treatment."

Should this be followed immediately by an MCC review? The other combination
that is probably overused in SA is paracetamol+meprobamate. Should that also
be reviewed?

~~

http://www.mhra.gov.uk/news/january/co-proxamol_q&a.pdf
Question and Answer Document
CO-PROXAMOL: OUTCOME OF THE REVIEW OF RISKS AND BENEFITS

1 What is co-proxamol?

Co-proxamol is a prescription only medicine used to treat mild to moderate
pain. It contains a combination of a low dose of paracetamol (325 milligrams
per tablet) and a painkiller called dextropropoxyphene (DXP). (Ordinary
paracetamol tablets normally contain 500 milligrams). Several pharmaceutical
companies market it as 'Co-proxamol' and it is also marketed under the brand
names Distalgesic, Cosalgesic and Dolgesic.

2 What is the problem with co-proxamol?

There is little evidence that co-proxamol is more effective in treating pain
than normal paracetamol in the recommended dose. Around 300-400
self-poisoning deaths each year, of which around a fifth are accidental,
involve co-proxamol. Prescribers are aware of the serious risks to patients
who exceed the recommended dose on co-proxamol. The MHRA has conducted a
review of the risks and benefits of co-proxamol and the Committee on Safety
of Medicines (CSM) has advised that the balance of risks and benefits of
co-proxamol is unfavourable.

3 What was the outcome of the review of the use of co-proxamol and
request for information on risk: benefit?

The CSM, the independent expert body which advises the government on
medicines, has considered the responses to the public request for further
information on the risks and benefits of co-proxamol. After careful
consideration, the CSM has advised that co-proxamol should be withdrawn from
the market on the grounds that the benefits of taking co-proxamol are not
considered to outweigh the risks.

4 If co-proxamol has been available for over 40 years, why has action only
been taken now? Co-proxamol has been marketed since the 1960's, and was
firmly established as a treatment for mild to moderate pain before modern
standards of clinical research. Current evidence is that previous advice in
1985 to strengthen warnings about co-proxamol overdose has not impacted on
the problem.

5 When will co-proxamol be withdrawn from the market?

Co-proxamol will be phased out of the market place gradually over 6 - 12
months to give patients time to discuss their treatment with their doctor
and change to a suitable alternative. There is no need for panic or concern
and if patients havebeen taking co-proxamol continuously for a long time
they should not stop without consulting their doctor.

6 How will patients who use co-proxamol now treat their conditions?

There are a number of options for managing painful conditions and CSM has
recently issued advice. There is no need for urgent medical advice -
patients taking co-proxamol can have the management of their treatment
reviewed at their next routine check.

7 If the CSM has advised that co-proxamol should be withdrawn from the
market why is it not being done immediately - is it safe for me to carry on
taking medicines containing co-proxamol until it is no longer available?

The CSM advised that co-proxamol should be phased out over a period of time
rather that withdrawn from the market immediately, to give patients
currently taking the medicine time to discuss their medication with their
doctor and move to a suitable alternative. No medicine is absolutely free of
possible side-effects. It is important that you:

* Only take the medicine if it has been prescribed for you
* Always read the patient information leaflet supplied with your medicine
and follow the instructions carefully
* Do not take more than the recommended dose
* Never take it with alcohol, sedatives, tranquillisers or other medicines
containing paracetamol
* Store your medicine out of the sight and reach of children and adolescents
* Destroy any unused tablets or return them to your pharmacist as soon as
possible

8 Is it safe to stop co-proxamol straight away? What else can I take?

If you have been taking co-proxamol continuously for a long time, you should
not stop without consulting your doctor. If you only take co-proxamol
intermittently, there is no problem with stopping straight away. Remember to
destroy any unused supplies or return them to the pharmacist as soon as
possible. There are other medicines available with or without prescription
that do not contain the ingredient dextropropoxyphene (DXP). Your pharmacist
or doctor can advise you on the choice available.

9 How can I get further information?

For further information call: NHS Direct on 08 45 46 47.

MHRA
January 2005

~~~~~~~~~~~~~~~~~~~
Andy Gray MSc(Pharm) FPS
* Senior Lecturer
Dept of Therapeutics and Medicines Management
* Study Pharmacist
Centre for the AIDS Programme of Research
in South Africa (CAPRISA)
Nelson R Mandela School of Medicine
University of KwaZulu-Natal
PBag 7 Congella 4013
South Africa
Tel: +27-31-2604334/4298 Fax: +27-31-2604338
email: graya1@ukzn.ac.za or andy@gray.za.net

--
To send a message to Indices, write to: indices@healthnet.org
To subscribe or unsubscribe, write to: majordomo@healthnet.org
in the body of the message type: subscribe indices OR unsubscribe indices
To contact a person, send a message to: indices-help@healthnet.org
Information and archives: http://www.essentialdrugs.org/indices/