North Essex Partnership University Nhs Foundation Trust

POLICY DOCUMENT

Acetylcholinesterase (AChE) inhibitors and Document Title Memantine Prescribing and Treatment Continuing Care Guidelines

Medicines Management/ Shared & Continuing Care Reference Number Guideline

Policy Type Continuing Care Guideline

N:\\Pharmacy\ Policies & Guidelines/ Shared & Continuing Care Guideline/ Electronic File/Location Acetylcholinesterase ( AChE) Inhibitors & Memantine Continuing Care Guidelines

http://intranep/teamCentre/pharm/PublishedDocuments/ Intranet Location Acetylcholinesterase (AChE) Inhibitors & Memantine Continuing Care Guidelines.pdf

Status Final

Version No/Date Version 6 – July 2016

Dr Justin Marley – Consultant Psychiatrist Author(s) Responsible for Dr Shafalica Bhan-Kotwal – Consultant Psychiatrist Writing and Monitoring Helen Thurlow - Lead Pharmacist for North East

Approved By and Date Medicines Management Group – May 2016

Implementation Date July 2016

Review Date July 2019

© North Essex Partnership University NHS Foundation Trust (2016). All rights reserved. Not to Copyright be reproduced in whole or in part without the permission of the copyright owner. All matters or concerns regarding fraud or corruption should be reported to: Chris Rising, Senior Manager ([email protected] 07768 873701), Hannah Wenlock, LCFS Lead ([email protected] 07972 004257) Mark Trevallion, LCFS Lead ([email protected] 07800 718680) OR the National Fraud and Corruption Line 0800 028 40 60 https://www.reportnhsfraud.nhs.uk/

IntraNep / Clinical resources / Pharmacy / Shared & Continuing Care Guideline Implementation Date July 2016 Review Date July 2019 Page 1 of 17

Contents

Page Section Topic Number

1 Introduction

3 Scope

4 Reference to other standards, policies or procedures

5 Procedure

5.1 Indications for use of these medications

5.2 Referral for consideration of these medications

5.3 Specialist assessment

5.4 Initiation and on-going treatment by specialist service following appropriate diagnosis 5.5 Continuation of care by GP service

5.6 Withdrawal of Medication

5.7 Choice and cost of medication

5.8 Dosage and side effects

5.9 Adverse effects

5.10 Care in prescribing

5.11 Interactions

5.12 Contact details for consultants or other staff in North Essex

5.13 Advice and useful information

6 References

Appendices

Algorithm for the use of cholinesterase inhibitors or 1 memantine for the treatment of Alzheimer’s disease

SUMMARY OF CHANGES

Page Date Summary of Changes Number(s) March 2016 All Reformatted into new template March 2016 4 Introduction shortened Removed references to older adult services and working age March 2016 All adult services as now age inclusive teams March 2016 Medication cost information removed March 2016 13 & 14 Contact details updated March 2016 15 Appendix 1 reformatted and simplified March 2016 Appendix 2 removed as not used in practice

Compliance Monitoring

Compliance with this procedure will be against the Trust’s agreed minimum requirements/standards as detailed within the Auditable Standards and Monitoring Arrangements.

Acetylcholinesterase (AChE) Inhibitors & Memantine Prescribing and Treatment Continuing Care Guidelines

1. INTRODUCTION

This guidance is based on the NICE Technology Appraisal 217: Donepezil, Galantamine, Rivastigmine and Memantine for the Treatment of Alzheimer’s disease (2011, but updated May 2016), and the NICE Clinical Guideline 42: Dementia (2006, but updated May 2016). It is acknowledged that medications are part of a wide range of support and treatments which should be offered to those with dementia, but non- pharmacological strategies are outside the scope of this guidance. This document applies to those with Alzheimer’s disease.

2. AIM

To provide continuing care guidelines and treatment information to healthcare professionals working in North Essex Partnership University NHS Foundation Trust (NEP) and General Practitioners working in North Essex when prescribing Acetylcholinesterase (AChE) inhibitors and Memantine.

3. SCOPE

This policy applies to all healthcare professionals working in North Essex Partnership University NHS Foundation Trust (NEP) and General Practitioners working in North Essex prescribing under the continuing care guideline

4. REFERENCES TO OTHER STANDARDS, POLICIES OR PROCEDURES

NEP Medicine Management Policies – available on the IntraNep. http://intranep/TeamCentre/pharm/PublishedDocuments/Forms/PolicyTabs.aspx

5. PROCEDURE

5.1 Indi c a ti o n s f o r u s e of these medications

5.1.1 The three AChE inhibitors are recommended as options for managing mild to moderate Alzheimer’s disease. The AChE inhibitor with the lowest acquisition cost (Drug tariff prices) should be first choice. Alternatives may be considered if there is an adverse event profile, adherence issues, medical comorbidity, possibility of drug interactions and dosing profiles.

5.1.2 Memantine is recommended as an option for managing Alzheimer’s disease for people with either moderate Alzheimer’s disease if they are intolerant or have a contra-indication to AChE inhibitors or severe Alzheimer’s disease.

5.1.3 Treatment with the AChE inhibitors or Memantine should be under the following conditions:

 Initiation of treatment must be by specialists in the care of dementia. It is recommended that neurologists, and physicians specialising in the care of older people should not initiate these medicines if they or the GP are unable to carry out the 6-monthly monitoring required by the NICE TA 217.  Carers views on the patient’s condition at baseline, and during follow up should be sought.  Treatment should be continued ONLY when it is considered to be having worthwhile effect on cognitive, global, functional or behavioural symptoms.  Patients who continue on treatment should be reviewed regularly using cognitive, global, functional and behavioural assessment.  Treatment should be reviewed by an appropriate specialist team, unless there are locally agreed protocols for shared (continuing) care.

5.1.4 There is no recommendation to use Memantine to augment the effects of AChE inhibitors.

5.2 Referral fo r c o n s i d e r a t i o n o f th es e m e d i c a t i on s

5.2.1 By GP or other secondary care consultant, for diagnosis by a Psychiatrist specialising in dementias.

N O T E:

Neurologists and physicians specialising in the care of the elderly may not have the facility to do the monitoring required by the NICE TA 217.

5.2.2 Referral should be for patients of any age with dementias which require a specialist opinion. He/she should have shown a persistent and progressively declining memory problem for more than 6 months.

N O T E:

Delirium should be excluded

5.2.3 People who have a MMSE score of less than 10, who are not taking one of these medications, and who are settled need not be referred unless there is a change in behaviour.

5.2.4 Provide FBC, serum B12 and folate, serum calcium, liver function, thyroid function, U&Es, random blood glucose, and also urinalysis results if indicated.

5.2.5 The results of an MRI scan should be included or CT scan if MRI is not appropriate.

5.2.6 Risk factors and a printout of the patient history should be included.

5.2.7 Provide a recent report of physical examination, and ECG.

5.2.8 Provide written information on background, life, psychiatric and physical

history, and current medication.

5.2.9 Advise patient and carer that referral is for assessment only initially. The assessment may need to be repeated several times, and medications may not be offered.

5.2.10 Arrange that a relative/friend/carer attends with the patient to receive and provide information.

N O T E: This is frequently crucial to accurate diagnosis

5.3 Specialist Assessment

5.3.1 In accordance with NICE guidelines include:

 Relevant history (with NOK/carer)  MRI or CT scan if it has not been done already. NEP will arrange as soon as the referral is received.  Mini-Mental State Examination MMSE (30-point, or equivalent)

o Mild Alzheimer’s disease: MMSE 21-26 o Moderate Alzheimer’s disease: MMSE 10- 20 o Moderately severe Alzheimer’s disease: MMSE 10-14 o Severe Alzheimer’s disease: MMSE less than 10

N O T E:

The accuracy of this test may vary for several reasons: for example, English as a foreign language, educational attainment, and sensory impairment. It may not be the most significant parameter in assessment

for all individuals. In these circumstances the clinician should have the flexibility to prescribe based on their clinical judgement.

 Assessment of mood/other psychopathology  Investigations, including further blood tests, CT or MRI scan, EEG if indicated.  The ability to live independently and a significant improvement in quality of life should also be considered.  Specific assessments will be used for people with learning disabilities. Details of these alternative assessments should be included in correspondence with primary care colleagues who may need to this for monitoring purposes.

5.4 Ini t ia t io n a n d o n - g oi ng t r ea t m en t b y s pe ci a l i s t s e r v i c e f ol l o w i n g app r o p r i a t e di a gno s is

5.4.1 Please note as per NICE Guidance:

When assessing the severity of Alzheimer's disease and the need for treatment, healthcare professionals should not rely solely on cognition scores in circumstances in which it would be inappropriate to do so (e.g. language or communication difficulties). In these cases alternative methods of assessment are to be used, and these should be communicated to primary care to ensure they have full monitoring records.

5.4.2 Treatment with AChE inhibitors will be initiated if the MMSE score averages between 10 and 26 points and/or the other assessments and investigations provide evidence that cholinesterase inhibitors will be an effective treatment. Donepezil, Galantamine and Rivastigmine are llicensed for mild-moderate Alzheimer’s Disease.

5.4.3 Treatment with memantine will be initiated if the MMSE score is below 20 for those who cannot be treated with AChE inhibitors or below 10, and/or the other assessments and investigations provide evidence that memantine will be an effective treatment. Memantine is licensed for the treatment of moderate-severe Alzheimer’s Disease.

5.4.4 The assessment should be repeated on two occasions 2-4 weeks apart.

5.4.5 The patient and carer will be provided with written and verbal information about the medication, including advice about when the medication will be discontinued.

5.4.6 The carer will be advised to attend all specialist clinic appointments where possible.

5.4.7 The carer’s views on the patient’s condition should be sought at each appointment.

5.4.8 The GP will be informed of treatment initiation.

5.4.9 In West Essex the GP will carry out the 6-monthly checks after the patient has been stabilised. In Mid and North East Essex the patient will be followed up by the local memory monitoring service for subsequent reviews- including MMSE, global, functional and behavioural assessment.

5.4.10 The patient will be referred to a specialist clinic for appointments at baseline (when treatment commences) one month, and 3 months. All prescriptions will be through specialist care at this point.

5.4.11 At 3 months, treatment must be reassessed and only continued if there is evidence of improvement, or lack of deterioration in MMSE score, OR EQUIVALENT recorded in the notes. Treatment should be continued when it is considered to be having a worthwhile effect on cognitive, global, functional or behavioural symptoms as assessed by the specialist team.

5.4.12 The specialist service must continue to prescribe until the dose/patient is stabilised, then agree continuing care with the GP. Thereafter the specialist may advise the GP to make minor changes in treatment, according to an agreed care plan. IntraNep / Clinical resources / Pharmacy / Shared & Continuing Care Guideline Implementation Date July 2016 Review Date July 2019 Page 9 of 17

5.4.13 The GP will be provided with contact details of specialist staff and will be provided with details of the assessments (including scores) in correspondence.

5.4.14 The specialist staff will provide a rapid response to GP concerns. See contact details section for relevant points of contact..

5.4.15 Treatment can be reassessed if the patient’s circumstances change (for example, a move to an enhanced care facility or residential home)

5.4.16 Patients who are already living in a care setting will be reviewed regularly.

5.4.17 If the specialist service changes the dose they will advise the GP of the change.

5.4.18 Treatment will be reviewed by the specialist service

• If there is no evidence of improvement with the medication • If the MMSE falls below 10 (or other parameters) for cholinesterase inhibitors, or memantine is no longer considered to be useful. Please note other specialist assessments may indicate it is appropriate to continue treatment as the patient’s behavioural and psychological issues may still require treatment • At the point where the patient scores less than 10 points on the MMSE (or equivalent if using alternative scales- ie the patient is moving from a diagnosis of ‘moderate’ Alzheimer’s Disease to ‘severe’ Alzheimer’s Disease) consideration should be given to the clinical appropriateness for continuation of the cholinesterase inhibitor. There should be a discussion with the MDT, and if necessary a clinical review with the patient by an appropriate member of the clinical team. Donepezil, Rivastigmine and Galantamine are not licensed to treat severe Alzheimer’s Disease so at this point the prescription of these drugs becomes ‘off-licence’. IntraNep / Clinical resources / Pharmacy / Shared & Continuing Care Guideline Implementation Date July 2016 Review Date July 2019 Page 10 of 17

• If there is a significant decline in cognitive state or deterioration in behaviour • If side effects outweigh advantages • If concordance is too poor to continue. • The patient will be seen during dose reduction and at 4-6 weeks after discontinuation. Therapy may be restarted after reassessment if clinically indicated.

5.4.19 If a patient moves area the specialist service should notify the new Trust, but the responsibility for referral will lie with the GP for discontinuation and/or ingoing care.

5.5 C on t in u at i o n o f c a re b y G P s e r v i c e

5.5.1 The GP will be informed that treatment has commenced and that medication will be provided initially by the specialist service.

5.5.2 When the patient is stable (minimum 3 months) the specialist service will ask the GP to prescribe, and provide a care plan to include prescribing. In Mid and NE.Essex it should also state the plans for 6 monthly reviews.

5.5.3 The GP will be advised by the specialist service of subsequent changes in treatment if memory services are to be used.

5.5.4 The GP should notify the specialist care service of any severe/unusual side effects or any concerns requiring a reassessment or cessation of treatment, including the patient moving from home into a care facility.

5.5.5 The GP or the carer(s) should notify the specialist service if they wish to discontinue the medication at any time.

5.5.6 The GP may make dose changes or discontinue the medication if IntraNep / Clinical resources / Pharmacy / Shared & Continuing Care Guideline Implementation Date July 2016 Review Date July 2019 Page 11 of 17

necessary. In this case the GP must notify the specialist service.

5.5.7 Patients who have moved to a new GP from a different area should be referred to specialist services as necessary when they register.

5.5.8 Care homes and GPs should ensure that new residents with symptoms of dementia are referred to specialist services.

5.6 Withdrawal of Medication

5.6.1 Reasons for withdrawal include: Marked deterioration in behaviour and mental state, a decline in MMSE to less than 10, peptic ulcer, physical illness, major side effects, poor concordance, the wishes of the patient or carer(s). Please note decline in MMSE score does not always necessitate withdrawal of the medication as the patient’s behavioural and psychological demands may require treatment. This should be assessed by the specialist team.

5.6.2 The medication should be withdrawn following advice of the specialist service, They are responsible for ensuring that support and advice are given to the patient and carer(s).

5.6.3 Withdrawal should be gradual if possible, to lessen the impact on the patient and carer(s).

5.6.4 If the GP stops therapy the specialist service should be informed.

5.7 C hoi c e a n d c o s t o f m edi c atio n

5.7.1 The least expensive medication should be first line treatment: however the additional carer cost for a twice daily dosage should be taken into consideration. Other considerations include adverse events profile, expectation of concordance, medical co-morbidity, drug interactions, dosing profiles, need for soluble or liquid form, carer support.

5.7.2 Generic preparations of these medications are available but patches and

liquid formulations can be more expensive.

5.7.3 Galantamine tablets prescribed twice-daily (BD) are non-formulary in North Essex to reduce the risk of prescribing errors

5.8 D o s ag e an d s id e e ff e c t s

5.8.1 See the BNF ww w . b n f .o rg , or Summaries of Product Characteristics (SPCs) for each preparation for full and up to date details w w w . m edi ci ne s .o r g . u k .

5.8.2 If treatment is interrupted for 3 days or more, reintroduce with initial dose and increase gradually. Contact specialist services if further advice is needed.

5.9 Adverse effects

5.9.1 See individual Summary of Product Characteristics

5.10 C a re i n p r e sc r i b in g

5.10.1 AChE inhibitors : Hepatic or renal impairment, sick sinus syndrome, other supraventricular abnormalities, asthma, obstructive airways disease, patients at risk of developing gastric or duodenal ulcers, history of seizures, bladder outflow impairment, pregnancy.

5.10.2 Memantine : Hepatic or renal impairment, history of convulsions

5.11 Interactions

• Galantamine levels increased by erythromycin, paroxetine, ketoconazole • Anticholinesterase effects reduced by antimuscarinics. • Suxamethonium effects may be increased by anticholinesterases. Rivastigmine and donepezil can antagonise the effects of non-depolarising muscle relaxants • Increased risk of CNS toxicity if memantine is given with ketamine, dextromethorphan, amantidine.

• Memantine possibly enhances warfarin, antimuscarinics, dopaminergics and selegiline. • Memantine possibly reduces effects of primidone, antipsychotics and barbiturates. • Memantine possibly modifies effects of baclofen and dantrolene.

 C onta c t de t a i l s f o r c on s ult a nt s o r ot h e r s ta f f i n N o r t h Ess e x

Wes t E s s ex :  Memory Clinics: St Margaret’s Hospital, Epping and Latton Bush, Harlow

C on s u l t a n ts: o Dr Z Walker 01279 827893 o Dr T Stevens 01279 827488 o Dr K Suresh 01279 827167 o Dr T Dannhauser 01279 827260 o Learning disabilities Dr E Da Costa 01279 827470

No r t h E as t E s se x

 Memory Clinics: King’s Wood Centre, Colchester and Landemere Centre, Clacton  Team telephone number (Dementia ‘help-line’): 01206 228970/75

C on s u l t a n ts: o Dr J Marley 01206 228928 o Dr S Bhan-Kotwal o Learning disabilities Dr Opute 01206 366653 X235 or 363268

M id E ss e x

 Memory Assessment Support Services, Crystal Unit, Chelmsford. Clinics are also held in Braintree and Maldon  Telephone contact number: 01245 515377  Medication monitoring team: 01245 515385

C on s u l t a n ts o Dr Leontis: Lead Consultant (Chelmsford) 01245 515377 o Learning disabilities Dr Fernando 01376 308741 IntraNep / Clinical resources / Pharmacy / Shared & Continuing Care Guideline Implementation Date July 2016 Review Date July 2019 Page 15 of 17

5.13 A d v i c e an d u s e f u l in f o r m atio n

• NICE technology appraisal guidance 217 w w w . n i c e . o r g . u k/ T A 21 7 • NICE clinical guideline 42 November 2006 ww w . n i c e . o r g . u k/ C G 04 2 • NICE Public Health Guideline 16 w w w . n i c e . o r g . u k/P H G 01 6 • ww w . med i c i ne s. o r g . u k . • ww w . bn f. o r g . u k • For patient information leaflets and comparison of treatments ww w .c ho i c eand m ed i c a t i on . o r g . u k / ne p ft • NEP Pharmacy 01245 315 500

6 References  NICE Technology Appraisal 217: Donepezil, Galantamine, Rivastigmine and Memantine for the Treatment of Alzheimer’s disease (2011, but updated May 2016)  NICE Clinical Guideline 42: Dementia (2006, but updated May 2016).  Choice and Medication Website: www.choiceandmedication.org.uk/nepft accessed 12/7/2016

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