Methadone oral solution vs. mixture

Some information you might find useful.

There is a page on the Society’s website containing controlled drug FAQs. It can be viewed at: www.rpsgb.org/worldofpharmacy/useofmedicines/controlleddrugs.html#faqs . In particular there is one section on miscellaneous queries which can be viewed at: www.rpsgb.org/pdfs/cdfaqregsmisc.pdf . It contains the following:

“5. If a prescription is written for Methadone mixture, can I supply Methadone oral solution?
If a mixture was prescribed, as an oral solution is a type of mixture, this could be supplied.


6. If a prescription is written for Methadone oral solution, can I supply Methadone mixture?
If an oral solution is prescribed, a mixture could only be supplied if the product’s licence stated that its form was an oral solution.
If an oral solution is prescribed, a mixture must not be supplied where it is not an oral solution, e.g. where it is an oral suspension etc. “

The Society has received confirmation from the Home Office that the above information reproduced in the CD FAQs is acceptable.

The background information resulting in the publication of these FAQs was as follows:

An oral solution contains active ingredient(s) dissolved in a suitable vehicle, while a mixture contains active ingredient(s) dissolved, suspended or dispersed in a suitable vehicle. While all oral solutions can be described as mixtures, not all types of mixtures are oral solutions.

My understanding is that when methadone mixture was first formulated, it was a preparation which was a solution of methadone hydrochloride in the vehicle. I am not aware of any oral liquid form of methadone hydrochloride that is a suspension or a dispersion of the active in a vehicle. Those described as mixtures have always been solutions.

The original formula adopted for methadone mixture never had any official status in the UK, having never appeared in the British Pharmaceutical Codex or the British Pharmacopoeia. However, the formula was published in the Drug Tariff and became known as Methadone Mixture DTF (drug tariff formula). This accorded the formula a form of semi-official status and it was widely used in the extemporaneous preparation of methadone mixture, and was regarded at that time as the only formula to use.

With the inclusion of an official monograph in the British Pharmacopoeia for Methadone Oral Solution (1 mg per mL), this should be the term used to describe the preparation; the term methadone mixture 1 mg/mL appears to have been superseded and relates to a non-official preparation.

The Home Office’s view was sought and it was determined that the following advice could be given:

1) If an oral solution is prescribed, a mixture could be supplied only if the product’s licence stated that its form was an oral solution.

2) If an oral solution is prescribed, a mixture must not be supplied where it is not an oral solution, i.e. where it is an oral suspension etc.

3) If a mixture was prescribed, as an oral solution is a type of mixture, this could be supplied.

I trust you will find this information useful.

Yours sincerely

Mr A. Paschalides
Pharmacist Advisor

Fitness to Practise and Legal Affairs Directorate
Royal Pharmaceutical Society of Great Britain
1 Lambeth High Street
London
SE1 7JN
Telephone: 020-7735-9141
Direct Line:020-7572-2624
Email: Ambrose.Paschalides@rpsgb.org

I can therefore confirm that a prescription for methadone mixture can be dispensed using a product labelled methadone oral solution because methadone oral solution is a mixture.

I have contacted several manufacturers – although I have not heard back from them all yet, I was able to find out the following:

When a manufacturer updates the Summary of Product Characteristics (SPC) with the MHRA, who approve SPCs, the MHRA now insist that only “oral solution” or “oral suspension” are the terms that can be used. If a manufacturer wants to use the term mixture this is refused unless the product (in the case of methadone mixture DTF) has historically had a licence as a mixture.

This means that in time (if it has not already happened) that all SPCs for methadone 1mg per ml will be called methadone oral solution (because methadone is highly soluble and so would never be available as a suspension). Methadone oral solution can be dispensed against prescriptions requesting either methadone oral solution or methadone mixture (because a solution is a mixture).

However, if any product is labelled as methadone mixture and the prescription asks for methadone oral solution, then the prescription cannot be dispensed. This means that the prescription writing advice given in Drug Misuse and dependence – clinical guidelines 2007 is correct as the term “methadone mixture” is acceptable on a prescription.


Marion Walker
Clinical team pharmacist
National Treatment Agency
15th May 2008