Title: Unique Identifier: Replaces: Guidance for the use of buprenorphine and buprenorphine with naloxone for the treatment of opioid dependence in NHS Grampian NHSG/guid/bup/MGPG733 NHSG/prot/bup/MGPG518 Across NHS Boards Organisation Wide Directorate Clinical Service Sub Department Area Yes This controlled document shall not be copied in part or whole without the express permission of the author or the author s representative. Lead Author/Co-ordinator: Subject (as per document registration categories): Key word(s): Process Document: Policy, Protocol, Procedure or Guideline Document application: Purpose/description: Specialist Pharmacists in Substance Misuse Clinical Guidance Guidance, buprenorphine, naloxone, suboxone, subutex, opioid, dependence, OST Guidance NHS Grampian This guidance advises all staff, involved in prescribing for substance misuse patients, on the appropriate use of buprenorphine products in managing opioid dependence. Responsibilities for implementation: Organisational: Departmental: Area: Policy statement: Review: Management Teams Substance misuse management team General practitioner practices It is the responsibility of all staff to ensure that they are working to the most up to date and relevant policies, protocols procedures. This guidance will be reviewed in two years or sooner if current treatment recommendations change. UNCONTROLLED WHEN PRINTED Review Date: April 2017 Identifier: NHSG/guid/bup/MGPG733 - i -
This document is also available in large print and other formats and languages, upon request. Please call NHS Grampian Corporate Communications on (01224) 551116 or (01224) 552245. Responsibilities for review of this document: Responsibilities for ensuring registration of this document on the NHS Grampian Information/ Document Silo: Physical location of the original of this document: Job/group title of those who have control over this document: Responsibilities for disseminating document as per distribution list: Substance Misuse Pharmacists Pharmacy and Medicines Directorate Substance Misuse Pharmacist Office, Fulton Clinic Specialist Pharmacists in Substance Misuse Substance Misuse Pharmacists Revision History: Revision Date Previous Revision Date Summary of Changes (Descriptive summary of the changes made) Changes Marked* (Identify page numbers and section heading ) July 2014 July 2012 Transferred to new template. Whole document July 2014 July 2012 Removed reference to specific types of opioid receptors. Page 2, Section 2 July 2014 July 2012 Condensed 3.1 and 3.2 removing repetition. July 2014 July 2012 Removed Section 4. Suboxone now preferred over buprenorphine as a sole agent in pregnancy. July 2014 July 2012 Removed recommendation regarding suitability over methadone with enzyme enducers/inhibitors SPC amended to reflect potential for interaction. July 2014 July 2012 Removed duplication of maximum dose. Page3, Section 3.1 Page 3, Section 4 (Removed) Page 3,Section 4 Page 5, Section 5.10 UNCONTROLLED WHEN PRINTED Review Date: April 2017 Identifier: NHSG/guid/bup/MGPG733 - ii -
Revision Date Previous Revision Date Summary of Changes (Descriptive summary of the changes made) July 2014 July 2012 Removed repetition of partial agonistic effect. July 2014 July 2012 Amended naming of branded product to read near patient testing. July 2014 July 2012 Removed statement regarding more thorough review every 3 months. Current practice is for regular review dependent on patient progress. July 2014 July 2012 Clarified information on rate of reduction. July 2014 July 2012 Information regarding withdrawal on discontinuation moved forward in document. July 2014 July 2012 Removed information regarding pharmacies providing supervision of buprenorphine products. Majority of pharmacies who dispense methadone will also dispense buprenorphine. July 2014 July 2012 Removed information regarding Suboxone being contraindicated in pregnancy July 2014 July 2012 Amended advice regarding use in pregnancy as per changes to Suboxone SPC. July 2014 July 2012 Amended advice in breastfeeding section to reflect above change. July 2014 July 2012 Removed section regarding DVLA as this is not restricted to prescribing buprenorphine but more widely. December July 2012 Added estimated to 2014 calculation of opioid load. December July 2012 Added statements clinical 2014 appropriateness of buprenorphine vs methadone December 2014 July 2012 and patient choice. Reworded sections 5.1. and 5.3. Changes Marked* (Identify page numbers and section heading ) Page 5, Section 6.3 Page 5, Section 6.3 Page 6, Section 6.4 Page 6, Section 7.1 Page 6, Section 7.2 Page 7, Section 8.3 Page 7, Section 11 Page 7, Section 11.1 Page 7, Section 11.2. Page 9. Section 11.6 in previous document Page 3, Section 4.1 Page 3, Sections 4 Page 3-4, Sections 5.1 and 5.3 UNCONTROLLED WHEN PRINTED Review Date: April 2017 Identifier: NHSG/guid/bup/MGPG733 - iii -
Revision Date December 2014 December 2014 December 2014 Previous Revision Date July 2012 Summary of Changes (Descriptive summary of the changes made) Added statement regarding requirement for day 2 dosing during titration. Changes Marked* (Identify page numbers and section heading ) Page 5, Section 5.11 July 2012 Reworded section 6.3. Page 5, Section 6.3 July 2012 Added information on supervision for people previously on take home methadone. March 2015 July 2012 Added new doses of generic buprenorphine. April 2015 July 2012 Added info on receptor occupancy. Amended precipitated withdrawal to read symptoms of withdrawal. April 2015 July 2012 Added line re weighing up risks of illicit use vs risks of prescribing. April 2015 July 2012 Removed information regarding administration every 2/3 days. Not used in practice. Page 7, Section 8.2 Page 4, Section 5.6 Page 2, Section 2 Page 4, Section 5.4 Page 5,Section 5 April 2015 July 2012 Added section on missed Page 7, Section 9. doses. April 2015 July 2012 Change to Guidance from Throughout Protocol. May 2015 July 2012 Addition of electronic link. Page 6, Section 7.4 May 2015 July 2012 Precautions moved below CI. Page 7, Section 10. May 2015 July 2012 Addition of electronic link. Section 11, page 8 * Changes marked should detail the section(s) of the document that have been amended i.e. page number and section heading. UNCONTROLLED WHEN PRINTED Review Date: April 2017 Identifier: NHSG/guid/bup/MGPG733 - iv -
Guidance For The Use Of Buprenorphine And Buprenorphine With Naloxone For the Treatment of Opioid Dependence in NHS Grampian Contents Page No 1 Introduction... 2 2 Pharmacology... 2 3 Key Recommendations... 3 4 Which Patients May Be Considered Suitable For Treatment With A Buprenorphine Product?... 3 5 Initiation Of Therapy... 3 6 Maintenance... 5 7 Dosage Reduction... 6 8 Supervision Of Consumption... 6 9 Missed Doses... 7 10 Contraindications To Use Of Buprenorphine Containing Products... 7 11 Precautions For Buprenorphine Containing Products... 7 See Section 5.4.... 8 12 Side Effects... 8 13 Consultation... 9 14 References Sources Used To Provide The Information For This Document:... 9 UNCONTROLLED WHEN PRINTED Review Date: April 2017 Identifier: NHSG/guid/bup/MGPG733-1 -
Guidance For The Use Of Buprenorphine And Buprenorphine With Naloxone For The Treatment Of Opioid Dependence in NHS Grampian 1 Introduction This guidance applies to both buprenorphine with naloxone (Suboxone sublingual tablets) and buprenorphine (Subutex and generic sublingual tablets are available). Suboxone is currently the recommended product for use in Grampian. This document is designed as a guide to the use of buprenorphine products in the treatment of opioid dependency and is intended for use by all clinicians and health care professionals involved in the treatment of this patient group in Grampian. Treatment must only be commenced by or on the recommendation of a specialist clinician in substance misuse. This may include GPs with the appropriate knowledge and/or training. 2 Pharmacology Buprenorphine is a partial opioid agonist which produces a milder, less euphoric and less sedating effect than full opioid agonists such as heroin, morphine and methadone. Nevertheless, its activity is usually sufficient to diminish cravings for heroin, and prevent or alleviate opioid withdrawal in dependent heroin users. Buprenorphine exerts little effect when swallowed and thus is administered via the sublingual route. Buprenorphine can block the effects of other opioid drugs, both illicit and prescribed. Patients should be informed of this when discussing buprenorphine as a treatment choice. Clinicians should be aware of this where opioid pain relief is required. This may be an issue during both planned and emergency admissions to hospital. As it is a partial opioid agonist, a ceiling effect is exhibited where continued dose increases will not result in a proportionate increase in effect. This means that buprenorphine has a lower risk of overdose than full agonists if taken as prescribed. Overdose remains a risk with poly drug use. Studies have shown that, in most patients, little additional effect is gained at doses above 16mg. [1] At this dose, approximately 95% of receptors are occupied leaving little room for additional effect. Suboxone includes the opioid antagonist naloxone in a combined sublingual tablet. If injected, naloxone has a high bioavailability and is liable to result in symptoms of withdrawal in opioid dependent patients. When taken sublingually, as prescribed, naloxone has very low bioavailability and does not diminish the therapeutic effect of the buprenorphine. Therefore theoretically, Suboxone should be subject to less misuse than buprenorphine as a sole agent. UNCONTROLLED WHEN PRINTED Review Date: April 2017 Identifier: NHSG/guid/bup/MGPG733-2 -
3 Key Recommendations 3.1 UK guidance [2] recommends that, following assessment of the patient and where both methadone and buprenorphine containing products are deemed equally suitable, methadone should be prescribed as first choice. An exception to this may include patients who express a strong preference towards buprenorphine, where it is clinically appropriate and the patient is informed of all available treatment options. 3.2 Buprenorphine containing products are recommended for substitution treatment for opioid drug dependence within a framework of medical, social and psychological treatment. 3.3 Where a buprenorphine containing product is the appropriate choice for maintenance treatment and where there are no contraindications to its use, Suboxone should be prescribed in preference to buprenorphine as a sole agent. 4 Which Patients May Be Considered Suitable For Treatment With A Buprenorphine Product? 4.1 Patients currently consuming a total daily opioid dose estimated to be the equivalent to 30mg or less of methadone. Illicit opioids should be included in this calculation. 4.2 Opioid drug users for whom methadone treatment is deemed less appropriate, e.g. in QTc prolongation. 4.3 Opioid drug users for whom methadone treatment is no longer working, e.g. for those who struggle on a reducing methadone dose. Metabolism varies between individuals but many find that at lower doses of methadone the dose may not hold them for the full 24 hours. Buprenorphine has a longer half life and is not as prone to the same issue which may make dose reductions easier to tolerate. 4.4 Patients who are considered suitable candidates for a detoxification programme. 4.5 Younger patients (between 16 and 18 years) due to the decreased risk of overdose (see Section 11.4). 4.6 Patients whose alcohol and/or poly drug use puts them at increased risk of overdose. 5 Initiation Of Therapy 5.1 Opioid dependence must be diagnosed prior to commencing treatment. In patients who are not currently receiving methadone maintenance treatment, a comprehensive assessment should be undertaken which includes a minimum of 2 confirmatory supervised screens (urine or oral fluid). 5.2 Patients must be assessed on an individual basis by a specialist clinician in substance misuse to determine suitability of treatment. Where the specialist service UNCONTROLLED WHEN PRINTED Review Date: April 2017 Identifier: NHSG/guid/bup/MGPG733-3 -
has initiated treatment, care may be transferred to primary care on the agreement of all parties involved. (Specialist clinician, primary care clinician and patient). 5.3 A discussion of the available treatment options should be undertaken. Corporate patient information leaflets and a flip chart are available to support discussion with further patient information leaflets on buprenorphine for treatment of opioid dependence are available from http://patient.info/medicine/buprenorphine-foraddiction-treatment-prefibin-subutex. This may be useful for some patients but issues with literacy should be considered. 5.4 Patients who are positive for viral hepatitis, on concomitant medicinal products which may interact with buprenorphine and/or have existing liver dysfunction are at risk of accelerated liver injury. Regular monitoring of liver function is recommended in these patients. As the pharmacokinetics of buprenorphine containing products may be altered in patients with hepatic impairment, lower initial doses and careful dose titration in patients with mild to moderate hepatic impairment are recommended. Buprenorphine containing products are contraindicated in [4] [5] patients with severe hepatic dysfunction/impairment. Both methadone and buprenorphine can accumulate in patients with hepatic impairment. Clinicians should weigh up the risk of continued illicit drug use versus the risks associated with the prescribed drug. With its ceiling effect, buprenorphine may present less of a risk of over sedation and overdose. 5.5 Precipitated withdrawal may occur when buprenorphine is first administered to an opioid dependent patient due to its high affinity for opioid receptors. Buprenorphine displaces other opioids from the receptors but exhibits less intrinsic activity thus inducing symptoms of withdrawal. Precipitated withdrawal typically occurs within 1 to 3 hours after the first buprenorphine dose and peaks within 3 to 6 hours before subsiding. This should be discussed with all patients prior to commencing treatment with buprenorphine containing substances and they should be reassured that, should they experience precipitated withdrawal, symptoms will subside. In order to minimise the risk of precipitated withdrawal, the first dose of buprenorphine containing product should not be given until the patient has been assessed and displays signs of opioid withdrawal. This should be a minimum of 12 hours after last heroin use and 24 hours after last methadone use. Where the patient is already experiencing mild symptoms of withdrawal the first dose of Suboxone should give them some relief and they are more likely to continue with this treatment. 5.6 Suboxone is available as 2mg (2mg buprenorphine and 500micrograms naloxone) and 8mg (8mg buprenorphine and 2mg naloxone) sublingual tablets. Buprenorphine as a sole agent is available as 400micrograms, 1mg, 2mg, 4mg, 6mg and 8mg sublingual tablets. Clinicians should advise patients that the sublingual route is the only effective and safe route of administration for this drug. The active ingredient will generally be absorbed after 3-5 minutes however pulp may be present for 10-15 minutes after administration but will contain little buprenorphine. UNCONTROLLED WHEN PRINTED Review Date: April 2017 Identifier: NHSG/guid/bup/MGPG733-4 -
5.7 It is recommended that the administration of initial doses are supervised (see Section 8). The clinician should discuss intial dosage instructions with both the patient and the community pharmacist to ensure clarity in the details of the initial dosing regimen. 5.8 An initial dose of 4mg of buprenorphine which should be followed by a further dose of 4mg later on the same day if there is no precipitated withdrawal. A minimum gap of 3 hours is recommended before consuming the second dose to allow sufficient time for appearance of precipitated withdrawal should it occur. Where precipitated withdrawal occurs, the second dose should be delayed until symptoms of withdrawal begin to reduce. 5.9 The dose should be titrated according to patient response as per Table 1 below. 5.10 It is recommended that patients are seen prior to each dosage increase to monitor efficacy and establish whether further dose increases are required. Table 1 Dose expressed as mg buprenorphine Day 1 4mg followed by a further 4mg after minimum 3 hours (Section 5.8) Day 2* 8mg Day 3 or next Daily dose increased to 16mg if required appointment 5.11 *Patient may be increased to 16mg on Day 2 where clinically appropriate to do so according to patient response. The majority of patients will gain minimal additional benefit at doses above 16mg (Section 2) however doses of up to 24mg Suboxone are licensed. 5.12 When converting from methadone, the patient s total daily opioid load should be 30mg of methadone per day or lower. Higher doses may lead to precipitated withdrawal (see Section 5.5) or treatment failure in circumstances where buprenorphine is not strong enough to cover withdrawal symptoms from cessation of full agonist opioids. Illicit opioid use should be considered, and accounted for, when calculating a patient s total daily opioid load. 6 Maintenance 6.1 The effective maintenance dose of buprenorphine products will be up to 16mg in most patients. [1][3] Very occasionally doses up to 24mg may be required (the maximum licensed dose for Suboxone ). 6.2 Patients should be seen a minimum of once a fortnight initially and which may be extended to a minimum of once a month with positive progress. 6.3 Urine or oral fluid tests for drugs of misuse should be undertaken a minimum of four times a year as determined by the clinician and according to each individual patient s progress. Presence of an illicit drug in a sample should be used to guide treatment. NB: In Grampian, current laboratory urine screening does not identify UNCONTROLLED WHEN PRINTED Review Date: April 2017 Identifier: NHSG/guid/bup/MGPG733-5 -
buprenorphine (March 2015). Near patient testing, where available, may identify buprenorphine. 6.4 Co-existing physical, emotional social and legal problems as well as drug and alcohol misuse should be addressed. 3 rd sector agencies may be able to provide this additional support and patients should be signposted or referred accordingly. 7 Dosage Reduction 7.1 Once the buprenorphine dose is stabilised, or a patient has been maintained on buprenorphine the following may be used as an approximate guide to reducing dose. Although the reduction rate is presented as every 1 to 2 weeks in literature, patient response and ability to cope/continue with the reduction is key. If the patient begins to struggle with the rate of reduction, it should be halted and the patient stabilised on a dose where they feel comfortable until ready to continue. 7.2 Patients tend to experience withdrawal symptoms at the end of treatment irrespective of the length of detoxification and should be advised and supported accordingly. Table 2 [3] Daily buprenorphine dose Above 16mg 8mg to 16mg 2mg to 8mg Below 2mg Reduction rate 4mg every 1 to 2 weeks 2mg to 4mg every 1 to 2 weeks 2mg every 1 to 2 weeks 400-800 micrograms every 1 to 2 weeks 7.3 For detoxification regimens, more rapid reductions may be considered and can be achieved within a one to two week timeframe. Rapid reductions are only recommended for use by specialist clinicians in substance misuse and are not recommended in primary care settings. 7.4 A discussion with the patient around the feasibility of naltrexone post reduction may be introduced at this time. See NHS Grampian guidance. http://www.nhsgrampian.com/grampianfoi/files/naltrex_673_0914.pdf 8 Supervision Of Consumption 8.1 As a minimum, it is recommended that doses of buprenorphine containing products should be supervised whilst titrating and stabilising the dose. This will provide the patient with additional support and monitoring from the community pharmacist and ensure that prescribing is appropriate. Where patients are new to treatment with an opioid substitute, current recommendations [6] state that initial doses should be prescribed daily with consumption supervised by a community pharmacy for at least the first three months of treatment. After this point, relaxation of supervised consumption may be considered on an individual patient basis at the discretion of the prescriber. Relaxation of supervision may be considered appropriate where the patient is deemed to be stable and can demonstrate continued abstinence from illicit drug use and compliance with treatment. UNCONTROLLED WHEN PRINTED Review Date: April 2017 Identifier: NHSG/guid/bup/MGPG733-6 -
8.2 Where patients have previously been maintained on a take home methadone prescription and are switching to a buprenorphine product, a short period of supervision during the titration will allow better monitoring and support of the patient s response to the change in medication. 8.3 For those patients on maintenance regimens, it is recommended that each instalment consists of no more than one week supply of buprenorphine to minimise the risk of large quantities being diverted. Twice or three times a week dispensing should be prescribed as a first step. 9 Missed Doses If a patient misses 3 or more doses of a buprenorphine product it is advised that the clinician discuss with the patient what has happened during this period. If 3 or more doses have been missed, the patient should be re-titrated as described in Section 5. If they have taken any opioid drugs in the interim, precipitated withdrawal will be a risk when restarting medication. They should be advised to wait 12 hours for heroin or 24 hours for methadone and be feeling mild symptoms of withdrawal before taking the next dose of buprenorphine. 10 Contraindications To Use Of Buprenorphine Containing Products A full list of contraindications can be found in the Summary of product characteristics or the British National Formulary. http://www.emc.medicines.org.uk; https://www.medicinescomplete.com/mc/bnf/current/. i. Patient must be 16 years of age or over for Subutex, over 15 years for Suboxone and have no other contraindications. ii. Severe respiratory insufficiency. iii. Severe hepatic insufficiency. iv. Acute alcoholism or delirium tremens. v. Hypersensitivity to buprenorphine, naloxone or to any of the excipients. vi. Patients suffering chronic pain for which additional opioid analgesia is frequently required. 11 Precautions For Buprenorphine Containing Products 11.1 Pregnancy Specialist advice should be sought when treating this patient group. Methadone remains first line where initiating an opioid substitution therapy in pregnancy. Where methadone is not the preferred treatment option, a buprenorphine product may be considered if the benefits of prescribing outweigh perceived risk. Where a buprenorphine product is indicated, Suboxone should be prescribed in preference due to the decreased risk of misuse. 11.2 Breastfeeding For mothers stabilised on a buprenorphine product who wish to breastfeed, an individual risk-benefit analysis to inform decision making should be undertaken. Due UNCONTROLLED WHEN PRINTED Review Date: April 2017 Identifier: NHSG/guid/bup/MGPG733-7 -
to the lack of evidence of the effects of these drugs on breastfed infants, manufacturers advice is to avoid, although expert consensus opinion states that the effects of these medications on the breastfed infants is likely to be minimal and that breastfeeding is not contraindicated. [7] 11.3 Liver function See Section 5.4. 11.4 Overdose Buprenorphine is reported to be safer in overdose than full agonists, such as methadone [3], causing less respiratory depression. This being said, drug related deaths involving buprenorphine have been reported particularly when taken in combination with other sedative drugs such as alcohol or benzodiazepines. In the event of accidental overdose, medical advice should be sought. Standard procedures for reversing opioid-induced respiratory depression should be followed. [4][5] Naloxone should be initiated titrating upwards until adequate respiratory ventilation is achieved. It may be necessary to use more than the normal amount of naloxone. General supportive measures should be instituted including close monitoring of respiratory and cardiac status. If the patient vomits care must be taken to prevent aspiration of the vomitus. Further guidance can be found in the document Patient Group Direction For The Administration Of Naloxone Injection In Suspected Opioid Overdose For Patients Aged 12 Years And Over By Nurses And Midwives Working Within NHS Grampian available on the NHS Grampian intranet. http://www.nhsgrampian.com/grampianfoi/files/naloxone_656_0714.pdf 11.5 Concomitant use of CNS depressants As with methadone, concomitant use of buprenorphine with benzodiazepines, alcohol and other CNS depressant drugs may result in fatal overdose. Caution should be employed when initiating buprenorphine containing products in poly drug users. Consideration should be given to the potential illicit use of CNS depressants before initiating treatment. 12 Side Effects A full list of side effects and cautions can be found in the Summary of product characteristics or the British National Formulary. http://www.emc.medicines.org.uk https://www.medicinescomplete.com/mc/bnf/current/ The most common side effects of buprenorphine containing products include: constipation, headaches, sleeplessness, sickness and sweating. It should be noted that patients often report a clear head with buprenorphine containing products as opposed to the clouding effect often experienced with methadone or heroin. UNCONTROLLED WHEN PRINTED Review Date: April 2017 Identifier: NHSG/guid/bup/MGPG733-8 -
13 Consultation The document was sent to the following individuals/groups for consultation: Steve Beason Psychiatrist, NHSG Substance Misuse Service Carol Buchanan GP with Special Interest in Substance Misuse Lynne Crighton Specialist Pharmacist, Gastroenterology Bruce Davidson Consultant Psychiatrist, Clinical Lead NHSG Substance Misuse Service Richard Legg GP with Special Interest in Substance Misuse Stephen Lynch GP, Calsayseat Medical Group Alison Mearns GP with Special Interest in Substance Misuse Isobel Morison Specialist Pharmacist, Aberdeen Maternity Hospital Allen Robertson Quality Assurance Supervisor, NHSG Substance Misuse Service Lucy Skea Specialist Pharmacist in Substance Misuse CPN Clinical Leads NHSG Substance Misuse Service CPN Team Leads NHSG Substance Misuse Service Medical Team NHSG Substance Misuse Service NHS Grampian Mental Health Operational Medicines Management Group 14 References Sources Used To Provide The Information For This Document: [1] Greenwald MK, Johanson CE, Moody DE, Woods JH, Kilbourn MR, Koeppe RA, et al. Effects of buprenorphine maintenance dose on mu-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers. Neuropsychopharmacology. 2003; 28:2000 2009 [2] National Institute of Clinical Excellence. Methadone and buprenorphine for the management of opioid dependence. London: NICE technology appraisal guidance 114. January 2007. Cited 15/07/2014 [3].Ford, C. Halliday, K. Lawson, E. Browne, E. et al. Guidance for the use of substitute prescribing in the treatment of opioid dependence in primary care. London: January 2011. Cited 15/07/2014. www.smmgp.org.uk [4] Reckitt Benckiser Pharmaceuticals. Summary of Product Characteristics: Suboxone. Slough, UK. Cited 15/07/2014. www.medicines.org.uk. [5] Reckitt Benckiser Pharmaceuticals. Summary of Product Characteristics: Subutex. Slough, UK. Cited 15/07/2014. www.medicines.org.uk. [6] Department of Health (England) and the devolved administrations (2007). Drug Misuse and Dependence: UK Guidelines on Clinical Management. London: Department of Health (England), the Scottish Government, Welsh Assembly Government and Northern Ireland Executive. Cited 15/07/2014. [7] Whittaker, A. The Essential Guide to Problem Substance Use During Pregnancy. A Resource Book for Professionals. London: DrugScope. Updated edition 2011. UNCONTROLLED WHEN PRINTED Review Date: April 2017 Identifier: NHSG/guid/bup/MGPG733-9 -