• Summary
• Introduction
• Regulations covering methadone manufacture
• Oral methadone preparations available
• Injectable methadone
• Pros and cons of the various oral preparations
  

Summary

• Methadone is a generic medicine – not a brand name.

• Methadone mixture 1mg/1mL is the treatment of choice when prescribing for opiate users.

• The majority of people on methadone are given oral methadone mixture DTF 1mg/1mL but there are a number of other products and formulation variants available, although these may be poorly accepted by clients.

• Different liquid formulations only alter the medium in which the methadone is dissolved and will therefore have the same effect on the client.

• There are a number of manufacturers producing methadone mixture and methadone concentrate.

• Methadone linctus is a much weaker preparation (2mg/5mL) that is seldom used in the treatment of dependence and should not be confused with methadone mixture 1mg/1mL.

• Prescribing methadone in tablet form is rarely justified and is best avoided if possible.

• Injectable methadone comes in a variety of strengths. It is usually prescribed only by specialist doctors and is designed for intra-muscular or subcutaneous use although it is often administered intravenously.

Introduction
Methadone can be made in liquid, tablet and injectable forms. This section looks at the law and regulations surrounding methadone and describes the different products that are available and their relative merits.

Regulations covering methadone manufacture
Methadone is usually prescribed as a generic medicine. This means that within the specified constraints of the:

• Drug
• Route of administration
• Concentration

Pharmacists can dispense a ready made product or make it up themselves. This is called ‘extemporaneous production’. In the case of methadone mixture this is done by mixing methadone concentrate and diluent.

Manufacture of methadone, as with all medicines, is covered by the Medicines Act. Before a manufacturer can make any claims about, or advertise, a medicine they must have a product licence. Some pharmaceutical companies can, under the terms of their Medicines Control Act manufacturing licence, produce products to be dispensed at the specific request of a doctor under what is called a ‘special licence’. Manufacturers of products with a special licence are not allowed to make any claims about their product or advertise them.

There are several companies with licences to manufacture methadone mixture, methadone concentrates and injectable methadone and several more manufacturing them under special licence.

Doctors can (and often do) prescribe drugs outside the terms of the product licence (such as the use of clonidine for opiate detox) or prescribe a drug which has no product licence. When prescribing such products the doctor takes full responsibility for the efficacy and safety of the drug rather than the company that manufactured it.

Oral methadone preparations available
Oral methadone comes in both liquid and tablet form.

Terminology
The terminology used to describe liquid preparations has been the source of much confusion among both workers and clients.

Methadone 1mg/1mL is not a linctus preparation (see below). Methadone 1mg/1mL is known and prescribed as:

• Methadone mixture DTF
• Methadone mixture
• Methadone oral solution
• Martindale methadone mixture.

Methadone mixture DTF1mg/1mL
The treatment of choice for illicit opiate users is methadone mixture 1mg/1mL.⁵⁰

There are several manufacturers making a green 1mg/1mL syrup based on the Drug Tariff Formulary (DTF) formulation:

• Methadone Hydrochloride (HCL) BP 1mg/1mL
• Glucose syrup
• Green S (E142)
• Tartrazine (E102)
• Sunset Yellow (E110)
• Parabens (preservative)
• Ethanol
• Trace chloroform water.

Until early 1995 most of the methadone mixture DTF 1mg/1mL was made by a single manufacturer, however since then a number of manufacturers have started producing DTF formulations. This means that, from time to time, the colour, flavour and/or consistency of the methadone dispensed may change.

If this occurs the reason should be explained to the clients to avoid them becoming anxious about the efficacy of their methadone (which is, of course, unaffected by the taste or consistancy of the liquids used to dissolve the methadone concentrate).

Doctors can prevent the dispensed formulation changing by prescribing methadone for their patients as the proprietary medicine ‘Martindale methadone mixture 1mg/1mL’.

Locally prepared methadone mixture1mg/1mL
Pharmacists preparing methadone 1mg/1mL extemporaneously commonly use formulae like the ones below:

Methadone mixture 1mg/mL per 5mL
Methadone HCL BP 5mg
Colourings
Unpreserved syrup 2.5mLs
Double strength chloroform to 5mLs

Methadone mixture 1mg/mL sugar free⁵¹
Methadone HCL BP 5mg
Concentrated chloroform water 0.1mL
Sorbitol syrup 2mLs
Distilled water to 5mLs

Sugar free and colouring free methadone mixture 1mg/1mL
There are a number of manufacturers making preparations that are:

• Sugar free
• Colouring free
• Sugar and colouring free.

Some of these have a product licence and some are made under special licence.

Methadone linctus 2mg/5mL
Methadone linctus is often confused with methadone mixture by both drug users and doctors. It is a generic medicine which is licensed in the UK for treating coughing in terminal disease but not drug dependence.

Wellcome’s methadone preparation ‘Physeptone Linctus’ is no longer available in the UK. Physeptone linctus is used for the treatment of drug dependence in the Republic of Ireland.

Methadone linctus is rarely used in the UK for the treatment of opiate dependence – and when it is it is often because it has been prescribed by mistake.

A typical formulation of methadone linctus would be:

• Methadone HCL BP 2mg/5mL
• Sucrose BP
• Glycerol BP
• Chloroform BP
• Ethanol
• Caramel BPC 1973
• Flavouring IFF 1831
• Purified water BP
• Benzoates (preservatives).

It is usually dispensed as a clear, brown syrup-based mixture from a 500mL bottle.

Methadone 5mg tablets
The 5mg tablet is most often prescribed under its trade name Physeptone. Physeptone tablets are not licensed for the treatment of opiate dependence. Several companies make generic 5mg tablets. The prescription of methadone in tablet form is discouraged because the tablets:

• Can be crushed and injected
• Have a higher illicit market value (because they can not be diluted)
• Are not as flexible in dose reductions as a liquid preparation.

Physeptone tablets contain:

• Methadone HCL 5mg
• Starch
• Magnesium stearate
• Glycerine.

Other tablet preparations will have similar ingredients. Physeptone tablets are a small, round, white tablet, scored and with ‘Wellcome 4LA’ written on them. They come in packs of 50.

Methadone suppositories
Methadone can be prepared as a suppository under the special licensing system. They are rarely used in the treatment of dependency. Although they would be expected to have a rapid onset of action the possible therapeutic benefits of this would probably be outweighed by the ease with which they dissolve in water and could thus be injected.

Injectable methadone
There is a range of injectable methadone preparations with a product licence for treatment of dependence. They come at a concentration of:

• 10mg per 1/mL (1%)

In the following ampoule sizes:

• 1mL (10mg)
• 2mL (20mg)
• 3.5mL (35mg)
• 5mL (50mg)

Under special licence other concentrations are made up to 50mg per mL.

The product licence for injectable methadone specifies that it is for intra-muscular or subcutaneous injection but it is usually prescribed and/or used intravenously.

There is fairly widespread anecdotal evidence of these preparations being painful to inject intravenously, especially at high concentrations. There is also anecdotal evidence of their leaving a bitter taste in the mouth following injection.

Pros and cons of the various oral preparations