Clinicians should only prescribe substitute medication as part of a locally agreed, multidisciplinary framework, having undergone additional training in such treatment, and supported by a specialist team for updates and supervision.

The Orange Book, Drug Misuse and Dependence: UK Guidelines on Clinical Management – this guidance is for clinicians treating people with drug problems. Treatment for drug misuse should always involve a psychosocial element, see NICE CG51- Drug misuse: psychosocial interventions (July 2007).

Selection of methadone or buprenorphine should be made on a case-by-case basis, but methadone should be prescribed if both drugs are equally suitable.

Supervised Consumption
The Orange Book states that the duration of supervised consumption should be dependent on assessed clinical need and should not be applied in an arbitrary way; however the NICE Technology appraisal guidance (TA114) published in 2007 states that methadone and buprenorphine should be administered daily, under supervision, for at least the first 3 months. Supervision should be relaxed only when the patient's compliance is assured. Both drugs should be given as part of a programme of supportive care.

Refer to your local Substance Misuse Prescribing Guidelines for further information:

Devon Partnership Trust

• Further information is available from the Clinical Management of Substance Misuse in Community policy (P09) and the Pharmacological Management of Substance Misuse prescribing guideline (PG20)

For the management of pain in substance misuse disorders, refer to formulary guidance here.

Opioid substitution therapy

Sublingual buprenorphine

• Sublingual tablets sugar free 400 micrograms, 2mg, 8mg (£49.08 = 8mg x 3 daily)

Indications

• Substitution treatment for opioid drug dependence
• Not to be used in primary care for the treatment of pain

Dose

• By sublingual administration, adult and adolescent over 16 years, initially, 0.8–4mg on day 1, adjusted if necessary by 2–4mg daily to usual dose of 12–24mg daily (maximum 32mg daily); withdraw gradually

Notes

1. Sublingual buprenorphine is not interchangeable with Espranor (below), as the bioavailability of products differ. Espranor has a higher bioavailability (25-30%) compared to Subutex.
2. Once the appropriate dose has been identified for a patient with a certain product (brand), the product cannot readily be exchanged with another product.
3. Sublingual tablets should be kept under the tongue until dissolved, which usually occurs within 5 to 10 minutes.
4. NICE TA114: Methadone and buprenorphine for the management of opioid dependence (January 2007)
   1. Methadone and buprenorphine (oral formulations), using flexible dosing regimens, are recommended as options for maintenance therapy in the management of opioid dependence
   2. The decision about which drug to use should be made on a case by case basis, taking into account a number of factors, including the person's history of opioid dependence, their commitment to a particular long-term management strategy, and an estimate of the risks and benefits of each treatment made by the responsible clinician in consultation with the person. If both drugs are equally suitable, methadone should be prescribed as the first choice
   3. Methadone and buprenorphine should be administered daily, under supervision, for at least the first 3 months. Supervision should be relaxed only when the patient's compliance is assured. Both drugs should be given as part of a programme of supportive care
5. Buprenorphine blocks the effect of illicit opioid use at doses of 12mg and above
6. Buprenorphine may be considered in the following circumstances:
   1. 1st episode of treatment for a low dose opioid user
   2. Short-term reduction over 2 - 3 weeks for a client stabilised on a low dose of methadone at the end of a "reduction to zero" regimen
   3. Patients who are unable to optimise management of their opioid misuse on methadone, or who have a preference for buprenorphine

Espranor

• Buprenorphine oral lyophilisates sugar free 2mg, 8mg (£152.40 = 8mg x 2 daily)

Indications

• Substitution treatment for opioid drug dependence
• Not to be used for the treatment of pain

Dose

• By oromucosal administration, adults and adolescents aged 15 years or over: Initially 2mg daily, an additional 2-4mg may be taken on day one if required. Adjust dose in steps of 2–6mg daily if required, consult the product literature for adjustment of dosing interval following stabilisation, maximum 18mg per day

Notes

1. Prescribing of Espranor should remain with the drug and alcohol service.
2. Espranor must be prescribed by brand.
3. Espranor is not interchangeable with other buprenorphine products, as the bioavailability of products differ. Espranor has a higher bioavailability (25-30%) compared to Subutex.
4. Once the appropriate dose has been identified for a patient with a certain product (brand), the product cannot readily be exchanged with another product.
5. Oral lyophilisates should be placed on the tongue and allowed to dissolve which usually occurs within 15 seconds. Patients should be advised not to swallow for 2 minutes and not to consume food or drink for at least 5 minutes after administration.
6. Buprenorphine blocks the effect of illicit opioid use at doses of 12mg and above
7. Buprenorphine may be considered in the following circumstances:
   1. 1st episode of treatment for a low dose opioid user
   2. Short-term reduction over 2 - 3 weeks for a client stabilised on a low dose of methadone at the end of a "reduction to zero" regimen
   3. Patients who are unable to optimise management of their opioid misuse on methadone, or who have a preference for buprenorphine
8. NICE TA114: Methadone and buprenorphine for the management of opioid dependence (January 2007)
   1. Methadone and buprenorphine (oral formulations), using flexible dosing regimens, are recommended as options for maintenance therapy in the management of opioid dependence
   2. The decision about which drug to use should be made on a case by case basis, taking into account a number of factors, including the person's history of opioid dependence, their commitment to a particular long-term management strategy, and an estimate of the risks and benefits of each treatment made by the responsible clinician in consultation with the person. If both drugs are equally suitable, methadone should be prescribed as the first choice
   3. Methadone and buprenorphine should be administered daily, under supervision, for at least the first 3 months. Supervision should be relaxed only when the patient's compliance is assured. Both drugs should be given as part of a programme of supportive care

Methadone

• Oral solution 1mg/ml (£15.96 = 14 days x 120mg daily)
• Sugar free oral solution 1mg/ml (£16.30 = 14 days x 120mg daily)

Indications

• For the treatment of opioid dependency, may only be prescribed with input from specialist services, and in line with local guidelines/enhanced service specification.
• For the treatment of pain in palliative care - only to be initiated following specialist advice from the palliative care team

Dose

• Opioid dependency: Initially 10–30mg daily, increased in steps of 5-10mg daily if required until no signs of withdrawal nor evidence of intoxication. Dose to be increased in the first week, then increased every few days as necessary up to usual dose. Maximum weekly dose increase of 30mg. If tolerance low or not known, initially 10-20mg daily. If tolerance high initially up to 40mg daily (under expert supervision only). Usual daily dose 60–120mg

Notes

1. NICE TA114: Methadone and buprenorphine for the management of opioid dependence (January 2007)
   1. Methadone and buprenorphine (oral formulations), using flexible dosing regimens, are recommended as options for maintenance therapy in the management of opioid dependence
   2. The decision about which drug to use should be made on a case by case basis, taking into account a number of factors, including the person's history of opioid dependence, their commitment to a particular long-term management strategy, and an estimate of the risks and benefits of each treatment made by the responsible clinician in consultation with the person. If both drugs are equally suitable, methadone should be prescribed as the first choice
   3. Methadone and buprenorphine should be administered daily, under supervision, for at least the first 3 months. Supervision should be relaxed only when the patient's compliance is assured. Both drugs should be given as part of a programme of supportive care
2. Evidence shows methadone is more effective than buprenorphine at retaining people in treatment and reducing heroin use.
3. Drug interactions can slow down or speed up methadone metabolism, or can potentiate toxicity. Prescribers should consult the BNF, individual product Summary of Product Characteristics (SPCs) and the Orange Book for further details.
4. Patients with any risk factors for QT-interval prolongation should be carefully monitored while taking methadone, including but not limited to: heart or liver disease, electrolyte abnormalities, or concomitant treatment with drugs that can prolong QT interval; patients requiring more than 100 mg daily should also be monitored. Clinicians, either at initial assessment or prior to induction, can consider use of an ECG where they have concerns. Clinicians should act according to local policy and the Orange Book

Adjunctive therapy and symptomatic treatment

Lofexidine

• 200 microgram tablets (£28.84 = 800 micrograms daily for 7 days)

Indications

• Management of the symptoms of opioid withdrawal (short-term use)

Dose

• Initially 800 micrograms daily in divided doses, increased as necessary in steps of 400–800 micrograms daily to maximum 2.4mg daily in divided doses; maximum single dose 800 micrograms; recommended duration of treatment 7–10 days if no opioid use (but longer may be required)

Notes

1. To be initiated by a Substance Misuse specialist only.
2. Lofexidine can cause hypotension. Patients should have their blood pressure monitored before and during treatment. Lofexidine should be discontinued gradually over 2-4 days to avoid rebound hypertension

Opioid-receptor antagonist

Naltrexone

• Tablets 50mg (£73.71 = 50mg daily)

Indications

• Relapse prevention in opioid dependence
• Relapse prevention in alcohol dependence

Dose

• Relapse prevention in opioid dependence, adult over 18 years (initiate in specialist clinics only): 25mg initially then 50mg daily; total weekly dose (350mg) may be divided and given on 3 days of the week for improved compliance (e.g. 100mg on Monday and Wednesday, and 150mg on Friday)
  • When using for post opioid abstinence treatment, patients should remain opioid-free for at least 7-10 days before naltrexone treatment is started
• Relapse prevention in alcohol dependence, adult and child over 16 years (unlicensed under 18 years): 25mg (unlicensed dose) on first day, increased to 50mg daily if tolerated

Notes

1. NICE TA115: Naltrexone for the management of opioid dependence (January 2007)
   1. Naltrexone is recommended as a treatment option in detoxified formerly opioid-dependent people who are highly motivated to remain in an abstinence programme
   2. Naltrexone should only be administered under adequate supervision to people who have been fully informed of the potential adverse effects of treatment. It should be given as part of a programme of supportive care
   3. The effectiveness of naltrexone in preventing opioid misuse in people being treated should be reviewed regularly. Discontinuation of naltrexone treatment should be considered if there is evidence of such misuse
2. NICE CG115: Alcohol use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence (February 2011). Naltrexone is supported by NICE following assisted withdrawal, or for harmful drinkers and people with mild alcohol dependence who have requested a pharmacological intervention in combination with an individual psychological intervention
3. Naltrexone should be initiated by a specialist in the field of substance misuse. However, it may be prescribed on an on-going basis by a primary care prescriber for the maintenance of abstinence from opioids or alcohol or for mild alcohol dependence following advice from a specialist practitioner.
4. Test for opioid dependence with naloxone (naloxone challenge) before starting treatment. This minimises the chance of a prolonged withdrawal syndrome being precipitated by naltrexone.
5. Liver function tests are required before and during treatment.
6. Patients should be warned that an attempt to overcome the blockage of opioid receptors by overdosing could result in acute opioid intoxication.
7. Patients should carry a medication warning card in case of opioid analgesia required in an emergency.