Drugs used for opioid dependence not listed below:

• Dihydrocodeine (see 4.7.2 Opioid analgesics)

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.

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:

Livewell Southwest

• Full guidance for the prescribing of drugs used in the treatment of opioid dependence is available from the Substance Misuse (including alcohol misuse) Prescribing Policy.

Devon Partnership Trust

• Further information is available from the Clinical Management of Substance Misuse in Community policy and the Pharmacological Management of Substance Misuse prescribing guideline.

Addaction (Kernow patients)

• Guidelines are available from the Addaction website.

Opioid substitution therapy

Sublingual buprenorphine

• Sublingual tablets sugar free 400micrograms, 2mg, 8mg (£36.72 = 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 aged 16 years or over: 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. Buprenorphine blocks the effect of illicit opioid use at doses of 12mg and above.
5. 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" regime
   3. Patients who are unable to optimise management of their opioid misuse on methadone, or who have a preference for buprenorphine.
6. 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.

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 2 mg daily, followed by 2–4 mg if required on day one, adjusted in steps of 2–6 mg daily if required, for adjustment of dosing interval following stabilisation, consult product literature; maximum 18 mg per day

Notes

1. Espranor must be prescribed by brand
2. Espranor is not interchangeable with other buprenorphine products, as the bioavailability of products differ. Espranor has a higher bioavailability (25-30%) compared to Subutex.
3. Once the appropriate dose has been identified for a patient with a certain product (brand), the product cannot readily be exchanged with another product.
4. 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.
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" regime
   3. Patients who are unable to optimise management of their opioid misuse on methadone, or who have a preference for buprenorphine.
7. 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.

Buprenorphine / naloxone

• Sublingual tablets sugar free; buprenorphine 2mg / naloxone 500micrograms, buprenorphine 8mg / naloxone 2mg (£228.57 = 8mg/2mg x 3 daily)

Indications

• Substitution treatment for opioid drug dependence

Dose

• Expressed as buprenorphine, adult and child over 15 years, initially 2–4mg once daily (an additional dose of 2–4mg may be administered on day 1 depending on the individual patient's requirement), increased in steps of 2–8mg according to response; maximum 24mg daily; total weekly dose may be divided and given on alternate days or 3 times weekly (but maximum 24mg daily)

Notes

• Buprenorphine/naloxone is indicated as a second line treatment to buprenorphine alone if there is a significant risk of diversion or illicit injection.

Methadone

• Oral solution sugar free 1mg/1ml (£7.81 = 14 days x 60mg daily)
• Oral solution 1mg/1ml (£7.56 = 14 days x 60mg daily)
• Tablets 5mg (£16.50 = 50 tablets) (see notes below)

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. In some exceptional circumstances, may be considered for a holiday prescription following a suitable risk assessment (see Livewell Southwest prescribing policy for the management of substance misuse and see notes below)
• Cough in terminal disease
• For the treatment of chronic pain (secondary care only), treatment must be initiated solely by the pain clinic or palliative care team. In exceptional circumstances, and with ongoing input from the pain clinic or palliative care team, treatment may be continued in primary care

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. Methadone should only be supplied as the mixture; any prescribing of methadone tablets, for example prescriptions for patients going on holiday, should be in accordance with local Prescribing Policies.
3. Methadone tablets are only licensed for use as an analgesic for moderate to severe pain, not for the treatment of opioid dependency.
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

• Tablets 200micrograms

Indications

• Management of symptoms of opioid withdrawal

Dose

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

Notes

• Only to be initiated by a substance misuse specialist.
• 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 (£91.76 = 50mg x 28 tablets)

Indications

• Adjunct to prevent relapse in formerly opioid-dependent patients (who have remained opioid-free for at least 7–10 days)
• Adjunct to prevent relapse in formerly alcohol-dependent patients (section 4.10.1)
• Treatment should be initiated and supervised by an appropriate specialist

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 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.
2. 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.
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.