Opiate Replacement Therapy Prescribing Guidance

Opiate Replacement Therapy Prescribing Guidance Formerly contained within the Methadone Assisted Treatment (MAT) and Buprenorphine Assisted Treatment (BAT) Keyworker Guidelines Approved: May 2017 Version: 1 Date of First Issue: July 2015 Review Date: July 2017 Date of Issue: July 2015 EQIA: Group / Committee: Primary Care Drug & Therapeutics Committee Author / Contact: Dr P. Aveyard; Dr C. McIntosh; Jean B. Logan

Consultation and Change Record Contributing Authors: Dr Philippa Aveyard, Dr Claire McIntosh & Jean B. Logan Consultation Process: Integrated Substance Misuse Clinical Governance Group Primary Care Drug & Therapeutics Committee Area Drug & Therapeutics Committee Distribution: To be hosted on Clinical Governance Website Change Record Date Author Change Version 2015 PA/CM/JL Major review to develop 2 separate guidelines: 1 ORT Prescribing Guidance and the Substance Misuse Service Keyworkers Guideline Version 1 July 2015 Page 2 of 20

Contents Page 1. Introduction 4 2. Scope 4 3. Definitions 5 4. Pre-prescription Phase 6 5. Induction Phase 6 6. Maintenance Phase 8 7. Low threshold Phase 8 8. Reduction Phase 9 9. Aftercare 9 10. References 10 11. Appendices 11 11.1 Pre-prescription checklist 11.2 ORT Titration Form 11.3 Pregnancy and Breastfeeding 11.4 Relaxation and re-instatement of supervision 11.5 Intoxication & Missed Doses 11.6 Prescription discontinuation 11.7 Holiday Prescriptions Version 1 July 2015 Page 3 of 20

1. Introduction This guideline replaces the former The Methadone Assisted Treatment and Buprenorphine Assisted Treatment Keyworker s Guidelines which set out the policy and procedures for opiate replacement therapy (ORT) within Forth Valley Substance Misuse Treatment Services. This prescribing guideline represents a major policy update in line with the Independent Expert Review of Opioid Replacement Therapies in Scotland (2013). The report confirmed the strong evidence base for opioid replacement as an essential component of treatment for opiate dependency. It recommends that ORT should be delivered as part of a coherent, person centred recovery plan and based upon an assessment of individual recovery capital. This document should be read in conjunction with the Substance Misuse Service Keyworkers Guideline. This guideline has been developed from the following evidence sources: NICE Technology Appraisal Guidance TA114, Methadone and buprenorphine for management of opioid dependence. Drug Misuse and Dependence: UK guidelines on clinical management Guidance for the use of substitute prescribing in the treatment of opioid dependence in primary care. 2. Scope This guideline has been developed as a reference for prescribers of ORT within Forth Valley to support clinical decision making. This covers the use of substitute medication which can be an important element in the treatment of opiate dependent patients as part of their recovery orientated care plan. Version 1 July 2015 Page 4 of 20

3. Definitions The management of opiate dependence involves the following phases: Pre-prescription Phase Induction Phase: Maintenance Phase: Low threshold Phase Reduction Phase Aftercare The pre-prescription phase involves a comprehensive assessment of the patient to establish opiate dependence, engagement and the initiation of a recovery care plan. Induction is the process of starting a patient on opiate replacement therapy and optimising the dose once the pre-prescription phase is complete. The maintenance phase commences when the prescribed dose of replacement medication is considered by both client and keyworker to be adequate and comfortable. The low threshold phase of treatment should be considered for clients who would be at a higher identifiable risk by having ORT stopped entirely. A lower dose to retain engagement with the service and daily pharmacy contact may be beneficial for certain patients. Clients should be supported to consider reduction of ORT when agreed as part of their recovery care plan. Clients should be supported after discontinuation of the ORT by the service. Version 1 July 2015 Page 5 of 20

4. Pre-prescription Phase Before prescribing any substitute medication opioid dependence must first be confirmed by history and examination. Choice of treatment and choice between detoxification and maintenance regimes should be discussed and confirmed. See NHF Inform for a handy chart to help compare the treatments for opiate dependence. The prescriber should: Ensure pre-prescription checklist is completed (Appendix 1) Complete Clinical Opiate Withdrawal Scale (COWS) to confirm opiate withdrawal Review LFTs if appropriate complete the ORT Titration Form (Appendix 2) generate first prescription sign the Partnership Agreement. 5. Induction Phase Methadone and buprenorphine are both effective evidence-based medicines for the treatment of opioid dependence. Induction onto methadone and buprenorphine treatment is the process of starting a patient on a suitable dose of a substitute opioid and optimising the dose once the pre-prescription phase is complete. Induction should be monitored by a doctor or specialist drug worker. It may take several weeks (or more) to achieve an optimal dose with methadone, less with buprenorphine. Clinicians need to balance three competing pressures in prescribing for opiate-dependent drug misusers: To prescribe an effective and appropriate dose. To minimise the risks of overdose or precipitated withdrawal during induction onto appropriate medication. To rapidly respond to the patients needs for appropriate treatment in order to retain them in treatment and prevent harm from illicit drug misuse. The starting dose will be based on the assessment of opioid tolerance, frequency of use, route of administration and use of other substances including alcohol and benzodiazepines. The dose induction of the two medicines is very different. For ORT in pregnancy and lactation please refer to Appendix 3. Version 1 July 2015 Page 6 of 20

5.1 Methadone Target Dosing Methadone oral solution 1mg/1ml is the formulation usually prescribed. Sugar free methadone mixture should only be prescribed for diabetic patients. The first two weeks of methadone treatment is a time of increased risk of methadone toxicity. It is important to start low and go slow to prevent risk of overdose. The initial dose will usually be in the range of 10-40mg methadone daily. The target dose should be discussed with the patient and based on the history of use, previous treatment experience and monitored on a weekly basis by the key-worker. This should include ongoing monitoring of withdrawal symptoms and assessment of reduction in illicit use. Methadone increases of between 5mg and 10mg a day with a maximum of 30mg (specialist service clinic) dose increase each week for the first two weeks are recommended. (In practice increases tend to be in the order of up to 10mg up to twice weekly during induction). Doses should be titrated up to optimal levels, usually between 60-120mg daily. 5.2 Buprenorphine Target Dosing It is important to get the timing of the first dose of buprenorphine correct to avoid precipitated withdrawal. This typically means at least 8 and preferably 12 hours after last heroin use or 24-48 hours after last methadone use. Clients should present in marked opiate withdrawal as supported by a COWS score of 13 on the first day. Suboxone is the formulation of buprenorphine usually prescribed. For induction from methadone the dose of methadone should be reduced to 30mg or less. Clients on more than 30mg methadone daily are less likely to be able to tolerate a transfer to buprenorphine but this may be considered within the specialist service setting. Commence with an initial dose of 4mg buprenorphine under supervision. If no signs of precipitated withdrawal are identified, a second 4mg dose may be given at least 2 hours later. The next day the treatment dose, usually 8-16mg, should be given supervised in the pharmacy. The target dose should be discussed with the patients and based on the history of use, previous treatment experience and monitored on a weekly basis by the key-worker. This should include ongoing monitoring of withdrawal symptoms and assessment of reduction in illicit use. A common effective dose is between 12-24mg daily. Version 1 July 2015 Page 7 of 20

Buprenorphine should be prescribed with caution where LFTs are above the normal limits. I would be advisable to seek advice from consultant addiction psychiatrists at the specialist service and consultant hepatologists. 5.3 Supervision New clients prescribed methadone or buprenorphine should be required to take their daily doses under the direct supervision of a professional, usually the community pharmacist, for at least three months. There should be a clear pathway for communication with the designated pharmacy and GP. GPs and Pharmacists should be provided with a written summary of the ORT plan including details of the prescriber and key worker as described in the Substance Misuse Communication Guideline. See Relaxation & Re-instatement of Supervision (Appendix 4). 6. Maintenance Phase in Recovery The maintenance phase commences when the prescribed dose of replacement medication is considered by both client and keyworker to be adequate and comfortable; this is confirmed by a minimum of two appropriate drug tests. The role of the prescriber in this phase is to: Ensure a safe appropriate dose regime and dispensing arrangement. If small increases or reductions in dose are required the client will still be considered to remain in maintenance phase. Provide regular (minimum 6 monthly) review of progress in treatment. If the appointment is missed consideration should be given to withholding the substitute prescription to facilitate attendance at the next appointment. Ensure ECG monitoring for clients on doses of methadone over 100mg or those with additional cardiac risk factors Ensure compliance with anti-psychotic monitoring guidance Assess and refer for appropriate treatment of co-morbid psychiatric and physical disorder including Blood borne viruses and sexual health. Actively liaise and participate in the multi-agency care of the client. Participate in recovery reviews and ensure communication with partners as per Substance Misuse Communication Guideline. 7. Low Threshold Phase A low threshold phase of treatment should be considered for clients who would be at a higher identifiable risk by having methadone stopped entirely. A lower dose to retain engagement with the service and daily pharmacy contact may be beneficial for certain patients. Version 1 July 2015 Page 8 of 20

Previous treatment history, including reviews should be considered in making the decision to move into this phase e.g. have both ORT options been considered. The rationale for this decision should be clearly documented. A recovery review should be completed at entry to the phase to agree clear criteria and goals for remaining in treatment that are reviewed strictly on a 3 monthly basis by the keyworker. This should be done jointly with the prescriber initially in a joint appointment and consideration given whether further joint appointment is required or whether discussion in team meeting will suffice. If these goals are not realised prescribing should be reviewed and the appropriateness of remaining in this phase considered. Attempts to stabilise such clients should include review of: Methadone dose and dispensing regime. Psychosocial interventions and support Precipitants to continued drug use The risks of combining methadone with other drug use against the benefits of continued treatment. If the risks of combining ORT with other drug use outweigh the benefits to the client arrange gradual withdrawal from methadone. 8. Reduction Phase Clients should be supported to consider reduction of ORT when agreed goals have been achieved as detailed in the recovery care plan. A structured dose reduction should be agreed with the client within realistic timeframes and verified by the prescriber. For methadone the dose may be reduced by 10mg methadone 1mg/ml per fortnight till 60mg daily is reached. The rate of reduction may then be reduced to 5mg per fortnight/month till zero. Transfer to buprenorphine when a dose of 30mg methadone 1mg/ml is reached should be considered. For buprenorphine a common regime is to reduce by 2 to 4mg every two weeks. When the dose is reduced to 2mg daily, it is possible to change to smaller dose reductions using 400microgram tablets. 9. After-care Clients should be supported after discontinuation of the ORT by the service as described in the key workers guide Relapse during this phase will usually result in a reassessment process to consider re-induction on to substitute prescribing. Version 1 July 2015 Page 9 of 20

10. References Department of Health (England) and devolved administrations (2007): Drug Misuse and Dependence: Guidelines on Clinical Management. London: Department of Health (England), the Scottish Government, Welsh Assembly Government and Northern Ireland Executive. NICE (2007) Methadone and Buprenorphine for the Management of Opioid Dependence. NICE technology appraisal guidance 114. London: National Institute for Health and Clinical Excellence. NICE (2007) Opioid Detoxification. NICE clinical guideline 52. London: National Institute for Health and Clinical Excellence NICE (2007) Psychosocial Interventions. NICE clinical guideline 5i-. London: National Institute for Health and Clinical Excellence. Road to Recovery RCGP guidance for ORT 2011 Opiate Replacement Therapies Independent Expert Review (2013). Version 1 July 2015 Page 10 of 20

Appendix 1 Pre-prescription Checklist Patient details: (please check details are the same as on Prescription Top Sheet ) Name: DoB : CHI: Address: Pharmacy: Postcode: Keyworker: GP: Proposed Start Date: Treatment Choice: Methadone/Buprenorphine: Pharmacy Verified: Date of last dose prescribed ORT taken: Partnership Agreement Signed: BBV Status if known: Drug Tests x 2 appropriate: Significant Mental Health: Signification Physical Health: Pregnant: AOCB: LFT s checked: (Buprenorphine only) Keyworker checklist (to be completed with patient) Copy of titration clinic timetable given Explanation of need to demonstrate withdrawal in clinic Discussion of treatment options Opiate replacement therapy information given Discussion re risks and benefits of medication safe storage Harm reduction discussion Naloxone training complete Naloxone supply given Pregnancy and contraception discussion Driving DVLA responsibilities discussed Does patient have unsupervised contact with children CP1 completed (if required) Keyworker prompt: 2 x OFT results attached? LFT s x 1 attached? Copy of GP summary? Copy of GP prescribed medication? Copy of Keepwell Assessment? Tick List: Version 1 July 2015 Page 11 of 20

Prescription Folder Top Sheet attached? Appendix 2 FORTH VALLEY SUBSTANCE MISUSE SERVICES Patient details: Opiate Replacement Therapy Titration Form Name: DoB : CHI: Address: Pharmacy: Postcode: Keyworker: GP: History and Clinical Detail: Pharmacy Verified: Partnership Agreement Initiated: Drug Tests x 2 appropriate: LFT s checked: (Buprenorphine only) Treatment Options Discussed: Observed in opiate withdrawal scale completed Discussion of treatment options Opiate replacement therapy information, risks and benefits of medication safe storage Pregnancy and contraception Harm reduction - risk of overdose and naloxone Driving and employment Liaise with G.P document health problems and other medications BBV advice Conduct and attendance in service and pharmacy (as per Partnership Agreement) Mental Health enquiry CP1 completed (if required) Risk of precipitated withdrawals (buprenorphine only) Test dose start date:... Date: Drug: Dose/frequency: (e.g. 50mls daily or 5mg twice daily) Date: Date: Date: Date: Supervised: (Yes/No) Dispensing regime: (e.g. daily, 3 x week etc) Requested by: Date: Prescription Version Signed 1 by: July 2015 Date: Page 12 of 20

Appendix 3 Pregnancy & Breastfeeding Opiate Replacement Therapy (ORT) is recommended during pregnancy because it carries a lower risk to the foetus than continued use of illicit drugs. ORT for pregnant women: Enables stabilisation of drug use and lifestyle. Reduces or eliminates illicit opioid use and can stabilise the in utero environment. Facilitates access to comprehensive antenatal and postnatal care. Does not increase the risk of congenital abnormalities in the foetus. Choice of ORT in Pregnancy If a women is pregnant when she enters treatment the most appropriate choice of ORT for that individual should be considered and the United Kingdom Teratology Information Service* (UKTIS) contacted for advice. The UKTIS will request information on her current and past obstetric health then provide a risk:benefit analysis on a case by case basis. Women already prescribed ORT who become pregnant can be maintained on their current treatment and UKTIS should be consulted for specific advice. The bio availability of methadone is decreased in the later stages of pregnancy due to increased plasma volume, an increase in plasma proteins which bind methadone and placental metabolism of methadone. It may be necessary to either increase the dose of methadone or change to twice daily consumption (or a combination of both strategies) to prevent withdrawal symptoms from developing. Babies born to mothers on ORT may experience a withdrawal syndrome. Available evidence gives little support to a dose dependent relationship between maternal ORT dose at delivery and the severity of the neonatal withdrawal syndrome; its occurrence is unpredictable. The benefits of ORT for both the mother and baby outweigh any risks from neonatal withdrawal syndrome. Risks of dose reductions or detoxification during pregnancy Opioid withdrawal in the first trimester of pregnancy is thought to be associated with an increased risk of miscarriage while in the third trimester it may be associated with foetal distress and death. Therefore it is important that pregnant women are not exposed to withdrawal during these 2 trimesters. If dose reductions or detoxification are to be undertaken during pregnancy these should be implemented during the second trimester: Dose reductions should only occur if the pregnancy is stable. The magnitude and rate of reduction needs to be flexible and responsive to the symptoms of withdrawal that may be experienced by the client. Withdrawal symptoms should be avoided as much as possible as they cause considerable distress to the foetus. Version 1 July 2015 Page 13 of 20

Careful monitoring of the pregnancy and foetus should be undertaken during dose reduction. In most instances, dose reductions of 2.5 to 5mg methadone in the middle trimester can be considered these should be carefully discussed with the mother. If the mother requests it may be possible to continue reductions of methadone at the rate of 1 to 2mg weekly in the third trimester. Buprenorphine can be reduced at a rate of 1-2mg/week in the middle trimester. Breastfeeding An assessment of the risks associated with breastfeeding by an opioiddependent mother, in terms of sustaining successful breastfeeding and possible exposure of the infant to opioids, will need to be undertaken before considering the additional risks of exposing the infant to drugs used to treat the mother s dependence. Methadone is the mainstay of the treatment of opioid drug dependence and breastfeeding has benefits to an infant who has been exposed in utero to maternal opioids. There is less evidence and experience for the use of buprenorphine, which is considered compatible with breastfeeding for shortterm use. Monitor infants for drowsiness, adequate weight gain, respiratory problems and developmental milestones especially in younger (up to one month) exclusively breastfed infants. For further information contact the UK Drugs in Lactation Advisory Service. Methadone Small amounts in breast milk Infants exposed to methadone in utero should berastfeed normally after delivery if the mother is stable. Methadone in breast milk may decrease withdrawal symptoms if infant exposed in utero, but will be insufficient to allow dose reduction of any treatment of the infant Infants may experience withdrawal symptoms if the mother has an abrupt withdrawal of methadone or if the infant is weaned abruptly Infant monitoring advise, especially in young infants Buprenorphine Small amounts in breast milk Considered safe for short term Infant monitoring advised,especially in young infants *The United Kingdom Teratology Information Service (UKTIS) is a national service commissioned by the Health Protection Agency to provide information Version 1 July 2015 Page 14 of 20

on all aspects of the toxicity of drugs and chemicals in pregnancy. The UKTIS telephone number is: 0844 892 0909. All enquiries are confidential Appendix 4 Relaxation & Re-instatement of Supervision Relaxation of requirements for supervised consumption and for instalment dispensing should be a stepped process in which the client initially moves from supervision to daily dispensing. Decision on the supervision/dispensing regimen is a team decision. However the final decision (and responsibility) rests with the prescriber. Reasons for allowing take away doses should be clearly documented in the client s case notes. Normally, progression should be: daily dispensing three times weekly twice weekly weekly Indications to consider removal of supervision or relaxation of dispensing arrangements: Clear evidence of stability with appropriate drug testing available in last 12 weeks Highly motivated to move on to higher treatment goals Working or attending training/education Genuine practical or physical problems with daily attendance at pharmacy No problem use of alcohol Safe medicine storage available and utilised No child/vulnerable adult safety fears relating to safe storage Plan agreed by prescriber Reasons to consider re-instatement of supervision or tightening dispensing arrangements: Suspicion of diversion Reduction of stability: in terms of any of the following: o Illicit drug use (including use of Benzodiazepines) o Notification of a non-fatal overdose o Homelessness; resulting in unstable lifestyle o Relationships instability (especially if a drug using partner relapses) o Serious forensic issues o Deteriorating mental or physical health o Poor relationship with pharmacy / services o Child/vulnerable adult safety fears relating to safe storage o Problem drinking Version 1 July 2015 Page 15 of 20

Re-instatement of supervision This may be implemented directly or through a process of re-titration depending on the clinical assessment of risk. Where a decision is made to re-instate supervision directly the client must confirm in writing that they have been taking their whole dose and fully understand the consequences of taking this dose if they are not tolerant to it. Where there are concerns of safety or suspicion of diversion/non compliance with prescribed dose re-titration may be appropriate. Version 1 July 2015 Page 16 of 20

Appendix 5 Intoxication and missed doses If client presents intoxicated the pharmacist should withhold the dose of ORT and ask the client to return for reassessment later that day or the following day. Missed doses: After three days without their regular prescribed dose of opioid, patients may have lost their tolerance to the drug and may be at risk of overdose if the usual dose is taken. The risks of loss of tolerance are less with buprenorphine than methadone. If the ORT dose has not been collected for 3 or more consecutive days the pharmacist should withhold the dose until the client has been re-assessed by the prescriber. Dispensing or administration errors: Methadone dispensed in excess of that prescribed can lead to toxicity. The risk of overdose is particularly high during induction therefore extreme caution is required in the early stages of treatment. If an amount greater than the normal prescribed dose is dispensed and given to the client, either as supervised or take home, the pharmacist must inform the client and seek advice from the prescriber on the course of action. See Community Pharmacy Guidance for the Dispensing and Supervision of ORT. Version 1 July 2015 Page 17 of 20

Appendix 6 Prescription Discontinuation There are times in a client s recovery journey when the team may decide that continuing to prescribe substitute medication is not possible. Wherever possible a phased reduction is the preferred treatment. There are other occasions where prescriptions will require to be stopped without a phased reduction. Where possible this should occur through a team meeting, but these high risk cases should always be discussed with the prescriber. Clients should be offered ongoing care within Substance Treatment services with a view to re-establishing ORT where appropriate. At this point overdose awareness, naloxone training and supply should be reenforced for all clients and documented in the case note. Example of a phased reduction Day Dose: Methadone Oral Solution 1mg/ml 1-7 inclusive 60ml 8-14 inclusive 40ml 15-21 inclusive 20ml 22 Stop Version 1 July 2015 Page 18 of 20

Appendix 7 Holiday Prescriptions Supporting service users where appropriate by agreeing a holiday prescription may assist their recovery journey. There must be clear documented evidence that the service user is stable in treatment and risks have been assessed before facilitating a holiday prescription is considered. Cases will be considered on an individual basis. It is important to discuss all holiday prescriptions at the team meeting at the earliest opportunity. In exceptional circumstances if this is not possible the prescriber should be contacted. Patients should provide proof of flights/accommodation when requesting ORT supply for a holiday. If the holiday is in Britain, and the person is still supervised, a community pharmacy should be found near the holiday destination to continue the supervision. It is the client s responsibility to nominate the pharmacy. It is the keyworker s responsibility to make clear arrangements with the community pharmacy. If a person is travelling abroad for less than 3 months and carrying less than 3 months supply of prescribed controlled drugs a personal import or export license is not required by the Home Office. The service must issue a letter confirming the patient name, travel itinerary, names of prescribed controlled drugs, dosages and total amounts of each to be carried. It is a responsibility of both the service and patient to check the advisability of transportation of ORT when travelling abroad with the appropriate Embassy. The prescribed controlled medicine must be transported in the original, correctly labelled packaging. It should be carried in hnad luggage where airline regulations permit A minimum of 14 days notice is required to generate a prescription. Keyworkers must discuss the safe storage of ORT particularly in respect to child protection. Issue of a storage box is good practice. Version 1 July 2015 Page 19 of 20

Publications in Alternative Formats NHS Forth Valley is happy to consider requests for publications in other language or formats such as large print. To request another language for a patient, please contact 01786 434784. For other formats contact 01324 590886, text 07990 690605, fax 01324 590867 or e-mail - fv-uhb.nhsfv-alternativeformats@nhs.net Version 1 July 2015 Page 20 of 20