Download Management of patients receiving Cholinesterase Inhibitors

SH CP 58
Shared Care Guideline:
Management of patients receiving
Cholinesterase Inhibitors
(Donepezil tablets; Rivastigmine (twice daily capsules and once daily patch);
Galantamine (twice daily tablets and once daily XL capsules)
Version: 3
Summary:
Guidelines for patients receiving cholinesterase
inhibitors
Keywords (minimum of 5):
(To assist policy search engine)
Cholinesterase, cholinesterase inhibitor, donepezil,
rivastigmine, galantamine, shared care guidelines
Target Audience:
Medical Staff, Nursing Staff working in Clinical areas,
MHPs, Medicines Management Team.
Next Review Date:
April 2020
Approved and ratified by:
Date issued:
Medicines Management
Committee
Portsmouth and South
East Hampshire Area
Prescribing Committee
April 2017
Author:
Dr Raja Badrakalimuthu
Sponsor:
Dr Lesley Stevens, Medical Director.
Date of meeting.
18 June 2014
17 October 2014
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Management of patients receiving cholinesterase inhibitors
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Version Control
Change Record
Date
1/14
04/16
03/17
Author
Dr Raja
Badrakalimuthu
Dr Raja
Badrakalimuthu
Dr Raja
Badrakalimuthu
Version
2
2
3
Page
Reason for Change
Through
out
Policy review. Removed the need for once yearly review of
medication
Policy review – no changes. Review date extended to
2019
Policy review – no changes. Review date extended to
2020
Reviewers/contributors
Name
OPMH consultants
Medicines Management Committee
Basingstoke, Southampton and
Winchester DPC
Portsmouth and SE Hampshire APC
Medicines Management Committee
Position
Version Reviewed & Date
July 2014
August 2014
December 2014
October 2014
September 2016
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Management of patients receiving cholinesterase inhibitors
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CONTENTS
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Introduction
Status of Cholinesterase Inhibitors
Indications and Dose
Referral Criteria
Patient Selection
Safety Issues
Role of Secondary Care Team
Role of GP
Responsibilities of the Carer
Cessation of treatment
References
A1
Appendices
Acetylcholinesterase Inhibitors for Dementia
Page
4
4
4
5
6
6
8
8
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Management of patients receiving Cholinesterase Inhibitors
(Donepezil tablets; Rivastigmine (twice daily capsules and once daily patch);
Galantamine (twice daily tablets and once daily XL capsules)
1.
Introduction
1.1
This shared care guideline has been produced to support the seamless transfer of
prescribing and patient monitoring from secondary to primary care, and provides an
information resource to support clinicians providing care to the patient. It does not
replace discussion about sharing care on an individual patient basis.
1.2
This guideline was prepared using information available at the time of preparation,
but users should always refer to the manufacturer’s current edition of the Summary
of Product Characteristics (SPC or “data sheet”) for more details.
2.
Status of Cholinesterase Inhibitors (Donepezil, Rivastigmine and
Galantamine)
2.1
Donepezil, Rivastigmine, Galantamine and Memantine are ‘amber’ drugs using our
local traffic light system. This means that treatment will usually be initiated in
secondary care and may be transferred to primary care if the initial response is
good. The key principle is that the GP is provided with comprehensive information
about the patient in particular about behavioural and psychological symptoms,
issues around care and risk at the time of transfer back to primary care.
3.
Indications and Dose
3.1
Cholinesterase Inhibitors (Donepezil; Rivastigmine or Galantamine) are licensed for
the treatment of Alzheimer’s Disease specifically for mild to moderate disease.
Rivastigmine capsules are licensed for the treatment of mild to moderate
Parkinson’s Disease Dementia. Memantine is licensed for the treatment of
moderate to severe Alzheimer’s Disease. Following NICE review of guidance
TA217 cholinesterase inhibitors are recommended for the treatment of mild to
moderate Alzheimer ’s Disease; Memantine is recommended for moderate
Alzheimer’s Disease in patients who are intolerant or have a contraindication to a
cholinesterase inhibitor or have severe Alzheimer’s Disease. Neither
cholinesterase inhibitors nor memantine should be used for the treatment of
Vascular Dementia.
3.2
A commonly used assessment of severity is the mini-mental state examination
(MMSE) score (mild Alzheimer’s Disease MMSE 21-26; moderate MMSE 10-20;
severe <10 points). However, when using assessment scales to determine severity
of Alzheimer’s Disease, healthcare professionals should take into account any
physical, sensory or communication difficulties or learning disabilities that could
affect the results and make any adjustments they consider appropriate. This
includes the use of alternative assessments that do not rely solely on a cognitive
score.
 Therapy should be initiated with a drug of the lowest acquisition cost. However,
an alternative acetylcholinesterase inhibitor can be prescribed where it is
considered appropriate having regard to adverse event profile, expectations
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around concordance, medical comorbidity, possibility of drug interactions and
dosing profiles.
 Based on a clinical and financial assessment Donepezil is recommended as the
first drug of choice; Rivastigmine patches should only be used as a second or
third line treatment option.
Dose:
Donepezil tablets
The usual starting dose is 5mg (to minimise the risk of side effects) which may be
increased to 10mg after one month, if there are no problems with tolerability. If
there are problems of tolerability at 10mg then consider reducing the dose to a
maintenance dose of 5mg instead.
Galantamine b.d. tablets or Galantamine once daily XL capsules
The usual starting dose is 4mg twice a day(or 8mg o.d. XL capsules) for four
weeks, increased to 8mg twice daily (or 16mg o.d. XL capsules) for 4 weeks. This
may be increased to 12mg twice a day (or 24mg o.d. XL capsules) taken with food.
Rivastigmine capsules
The starting dose is 1.5mg twice daily, increased in steps of 1.5mg twice daily at
intervals of at least 4 weeks, according to response and tolerance. This is slower
than the current manufacturer’s advice but reduces incidence of side effects. Usual
dosage ranges from 3 to 6mg twice daily swallowed whole.
Rivastigmine patch (should be used after a trial of capsules)
Initially apply 4.6 mg/24 hours patch to clean, dry, non-hairy, non-irritated skin on
back, upper arm, or chest, removing after 24 hours and siting a replacement patch
on a different area (avoid using the same area for 14 days); if well tolerated
increase to 9.5 mg/24 hours patch daily after no less than 4 weeks; if patch not
applied for more than 4 days, treatment should be restarted with 4.6 mg/24 hours
patch. When switching a patient from oral to transdermal therapy, patients taking 36 mg daily should be prescribed the 4.6 mg/24 hours patch; patients taking 9 mg
daily who do not tolerate the dose well should be prescribed the 4.6 mg/24 hours
patch, while those taking 9 mg daily who tolerate the dose well should be
prescribed the 9.5 mg/24 hours patch; patients taking 12 mg daily should be
prescribed the 9.5 mg/24 hours patch. The first patch should be applied on the day
following the last oral dose. Rivastigmine patches are generally better tolerated
than capsules but are associated with an application site reaction, hence need for
rotation between sites.
4.
Referral Criteria
4.1
Patients with a suspected or established dementia can be referred from a primary
care clinician following a pre-treatment assessment (Sect 5.5a) for assessment by
a secondary care clinician that includes those specialising in old age psychiatry;
learning disability, neurology and elderly medicine. The secondary care clinician
will, after establishing the patient selection criteria below, consider initiating
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treatment with Donepezil tablets, Rivastigmine (capsules or patch), Galantamine
(twice daily tablets or once daily capsules).
5.
Patient Selection
5.1
Patients with mild to moderate Alzheimer’s Disease (ICD-10) may be prescribed
cholinesterase inhibitors.
5.2
Patients with mild to moderate Parkinsons Disease Dementia may be prescribed
Rivastigmine capsules.
5.3
Patients with moderate Alzheimer’s disease who are intolerant or have a
contraindication to a cholinesterase inhibitor may be prescribed Memantine.
5.4
Diagnosis is made by a specialist team according to standard diagnostic criteria
5.5
There has been an assessment of compliance
5.6
Treatment with a cholinesterase inhibitor should continue whilst the patient’s
cognitive, global, functional and behavioural condition remains at a level where the
drug is considered to be having a worthwhile effect. When a patient has reached a
level of severe dementia the patient should be reviewed by the GP with the aim of
stopping the cholinesterase inhibitor.
5.7
Once the patients reach stable treatment dose (usually by 3 months), prescribing
and monitoring can be transferred as a routine to primary care, with the facility to
review by secondary care if there is an unexpected change in condition as
requested by the patient, carer or primary care clinician.
5.8
When patients on cholinesterase inhibitors are presenting with behavioural
problems leading to risk of self-neglect, aggression, falls and wandering, they will
need a care co-ordinator who will review the management of behavioural
symptoms and risk until the time the there is stability and an effective care is
organised.
6.
Safety Issues
6.1
Contra-indications (see BNF or SPC)
a) Cholinesterase Inhibitors
 Pregnancy and breast feeding
 Galantamine is contraindicated in severe renal and hepatic impairment and
metabolic disorders of galactose metabolism
 Rivastigmine is contraindicated in severe hepatic impairment.
6.2
Cautions (see BNF or SPC)
a) All Cholinesterase Inhibitors
 Cardiovascular disease: may cause bradycardia. Special care in sick sinus
syndrome and supraventricular conduction disorders.
 Gastrointestinal disorder: may enhance pre-disposition to peptic ulceration,
avoid in gastrointestinal obstruction.
 Pulmonary disorders: may cause broncho constriction. Caution in asthma
and chronic obstructive airway disease.
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 May exacerbate extrapyramidal symptoms including worsening of Parkinsons
Disease.
 Bladder outflow problems may be exaggerated. Avoid in urinary retention or
history of prostatic condition.
 Renal impairment: Rivastigmine dose should be modified according to
patient’s tolerability.
 Hepatic impairment – Donepezil, rivastigmine. Galantamine reduce dose in
moderate impairment.
 Anaesthesia is likely to exaggerate succinyl-type muscle relaxants.
6.3
Common Side Effects
(See BNF or SPC)
6.4
Drug Interactions
(See BNF or SPC)
6.5
Pre-treatment Assessment
a) GP
 Medical history to include BP; pulse and cardiac assessment, with ECG if
clinically indicated, to exclude cardiac problems. Review of vision and
hearing to exclude sensory problems, in particular ear wax and cataracts. If
there is a diagnosis of Down syndrome a review of musculoskeletal system to
exclude atlanto-axial instability, (for example, pain behind the ear or neck
pain elsewhere; abnormal head posture; deterioration of gait, manipulative
skills, or bowel/bladder control).
 Cognitive examination e.g. MMSE or 6-CIT
 Availability of care giver to monitor compliance
 Full blood count. ESR. B12 and Folate, Urea and Electrolyte, blood glucose,
TFT’s, liver function, bone profile, creatinine tests. Urinalysis for infections
and glucose. In female patients with Learning disabilities a sex hormone
profile to determine menopausal status.
b) Secondary care
 Cognitive function e.g. MMSE, ACE-R
 Activities of daily living
 Behaviour and psychiatric symptoms
 Carer burden
 Availability of carer to supervise medication and ensure compliance
 Counselling of patient and carer about implications of diagnosis.
 Including written information about signs and symptoms; course and
prognosis and treatments; local care and support groups; financial and legal
advice.
 Brain imaging if indicated
If clinically appropriate treatment is initiated.
6.6
Routine Safety Monitoring
Parameter
Compliance checks
Adverse effects
Check for drug interactions
By Whom
Primary and Secondary care
Primary and Secondary care
Primary and Secondary Care
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7.
Role of Secondary Care Team
a) To assess the suitability of the patient for the drugs and counsel patient and
carer about implications of diagnosis
b) To carry out secondary investigations
c) To give the patient the appropriate drug information leaflets
d) To explain the possible side effects of the medication to the patient
e) To emphasise the need for the carer to supervise medication and ensure
compliance
f) To initiate and titrate cholinesterase inhibitor treatment until a maintenance dose
has been reached. The initiation and titration period will be for a minimum of 3
months (12 weeks) but may be longer if there is difficulty reaching a
maintenance dose.
g) To liaise with primary care and document preferred follow up arrangements after
reaching maintenance dose and for reassessment and monitoring as
appropriate. Follow up beyond the twelve weeks can be in secondary care if
there are:1. Complex behavioural and psychological symptoms
2. Challenges in setting up appropriate care to meet the needs of the
individual
3. Risks such as self-neglect, wandering, aggression or accidents, which
require CMHN input to monitor and manage.
In the absence of these complexities, patients will be routinely transferred to
follow-up by GP with access to services such as Dementia Advisors,
Alzheimer’s Society, Age Care UK and other local agencies involved in
supporting patients and carers with dementia.
h) If the follow-up is by secondary care, the patient should be allocated to a care
co-ordinator to formulate a care plan to address the complex issues along with
the involvement of other agencies including Adult Social Care.
8.
Role of GP
1. To provide prescriptions of the drug once a maintenance dose has been
achieved (usually takes 3 months).
2. To monitor for compliance.
3. To monitor for side-effects
4. To monitor for progress of dementia using general history taking of activities of
daily living and support required during opportunistic or scheduled consultations.
6-CIT or MMSE, can be used as a formal measure of cognition.
5. To be aware of drug-interactions whilst changing medications.
6. To refer back to secondary care if there is deterioration in mental state after
ruling out delirium, emergence of behavioural and psychological symptoms,
change in care needs, when considering cessation of treatment due to poor
compliance, lack of efficacy, adverse consequences or if the patient asks to
stop.
9.
Responsibilities of the Carer
a) To assist in completion of carer burden assessment
b) Ensure compliance
c) Report any side effects
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10.
Cessation of treatment
Cessation of cholinesterase inhibitor treatment may be recommended if:
 Evidence of poor compliance with no available strategies to improve compliance
 Major adverse effects
 Patient asks to stop
It is important to be aware that recent literature evidence suggests that continuing
treatment in the severe phases of the illness is associated with benefit in managing
BPSD.
Shared care protocol guidelines once patients progress to severe dementia
severity whilst taking a cholinesterase inhibitor.
None of the cholinesterase inhibitors are licensed for the treatment of severe
dementia in the UK. Thus, although there is randomised controlled trial evidence of
efficacy in patients with MMSE 1-10a, prescribing a cholinesterase inhibitor to
Alzheimer’s disease patients with severe dementia is off licence and shared care
guidelines are no longer valid. Continuation of a cholinesterase inhibitor after this
point should be based on an individual patient basis dependent on a consensus
view by the GP; senior specialist doctor, community nurse; patient and carer.
The following procedure should be followed once patients reach a level of severe
dementia (typically MMSE score < 10 points):
1. It is good practice, when first starting patients on cholinesterase inhibitors, to
point out that treatment of patients with severe Alzheimer’s Disease with a
cholinesterase inhibitor is outside NICE guidance and any need for continuation
would need to be reviewed.
2. Patient and carer informed that the continued treatment with the cholinesterase
inhibitor is no longer licensed in the UK.
3. The patient and carers views on discontinuation should be obtained.
4. In certain situations where there are complex behavioural and psychological
symptoms and risks about the time the medication is being considered for being
stopped, the patient can be re-referred to mental health services for specialist
advice.
11.
References
a) Winbald et al. Lancet 2006: 367; 1057-65.
b) Doody et al. Arch Neurol 2001: 58; 427-33
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Appendix A
Acetylcholinesterase Inhibitors for Dementia – Abridged GP
Summary as part of Shared Care Agreement
This guideline was prepared using information available at the time of preparation, but users should always
refer to the manufacturer’s current edition of the Summary of Product Characteristics (SPC or “data sheet”) for
more details. For further information please refer to the full Shared Care Guideline
Licensed indications
Donepezil (Aricept; Aricept Evess), Galantamine (Reminyl; Reminyl XL; Galsya XL),
Rivastigmine (Exelon) are licensed for use in the treatment of Alzheimer’s disease,
specifically for mild to moderate disease. Rivastigmine is also licensed for mild to
moderate dementia associated with Parkinson’s disease. Following NICE review of
guidance TA217 cholinesterase inhibitors are recommended for the treatment of mild to
moderate Alzheimer’s disease.
Patient Selection by OPMH consultant



Patients with mild to moderate Alzheimer’s disease (ICD-10) may be prescribed
cholinesterase inhibitors.
Patients with mild to moderate Parkinson’s disease Dementia may be prescribed
Rivastigmine capsules.
A commonly used assessment of severity is the mini-mental state examination
(MMSE) score (mild Alzheimer’s Disease MMSE 21-26; moderate MMSE 10-20;
severe <10 points). However, when using assessment scales to determine severity
of Alzheimer’s disease, healthcare professionals should take into account any
physical, sensory or communication difficulties or learning disabilities that could
affect the results and make any adjustments they consider appropriate. This
includes the use of alternative assessments that do not rely solely on cognitive
scores.
Contra-indications
• Pregnancy and breast feeding.
• Galantamine is contraindicated in
severe renal and hepatic impairment
and metabolic disorders of galactose
metabolism.
• Rivastigmine is contraindicated in
severe hepatic impairment.
Cautions
• Cardiovascular disease: may cause bradycardia.
Special care in sick sinus syndrome and
supraventricular conduction disorders.
• Gastrointestinal disorder: may enhance predisposition to peptic ulceration, avoid in
gastrointestinal obstruction.
• Pulmonary disorders: may cause broncho
constriction. Caution in asthma and chronic
obstructive airway disease.
• May exacerbate extrapyramidal symptoms
including worsening of Parkinson’s Disease.
• Bladder outflow problems may be exaggerated.
Avoid in urinary retention or history of prostatic
condition.
• Renal impairment: Rivastigmine dose should be
modified according to patient’s tolerability (do they
mention eGFR here?)
• Hepatic impairment – Donepezil, Rivastigmine.
Galantamine reduce dose in moderate
impairment.
• Anaesthesia is likely to exaggerate succinyl-type
muscle relaxants.
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Role of GP
 To provide prescriptions of the drug once a maintenance dose has been achieved
(usually takes 3 months).
 To monitor for compliance.
 To monitor for side-effects (listed in appendix)
 To monitor for progress of dementia using 6-CIT or MMSE, behavioural and
psychological problems and change in activities of daily living.
 To be aware of drug-interactions (listed in appendix) whilst changing medications.
 To refer back to secondary care if there is deterioration in mental state after ruling
out delirium, emergence of behavioural and psychological symptoms, change in
care needs, when considering cessation of treatment due to poor compliance, lack
of efficacy, adverse consequences or if the patient asks to stop.
GP Quick Reference Guide: Acetylcholinesterase inhibitors
Usual Dose:
Donepezil: 10mg (Unless recommended by secondary care at a dose of 5mg)
Galantamine: 8-12 mg twice daily (or 16-24mg XL)
Rivastigmine: oral: 3-6mg twice daily patch: 9.5mg/ 24 hours
Contraindications:
Galantamine is contraindicated in severe renal and hepatic impairment and metabolic
disorders of galactose metabolism.
Rivastigmine is contraindicated in severe hepatic impairment.
Monitoring:
To monitor for progress of dementia, behavioural and psychological problems and
change in activities of daily living.
To be aware of drug-interactions (listed in appendix) whilst changing medications.
Renal function and hepatic function can be monitored on a yearly basis.
Interactions:
All drugs: enhance effect of suxamethonium-type muscle relaxant; with NSAIDs may
increase risk of ulcers; ketoconazole can increase plasma level of acetylcholinesterase
inhibitors
Rivastigmine: Syncope with atenolol
Galantamine: Bradycardia with beta-blockers and digoxin; erythromycin and paroxetine
increase plasma levels.
Main side effects (refer to BNF or SPC for full list):
All drugs: Nausea, vomiting, diarrhoea, weight loss, dizziness, head ache, fatigue,
bradycardia
Donepezil: muscle cramps, pain, hallucinations, aggressive behaviour, insomnia, rash,
pruritus, insomnia
Rivastigmine: somnolence, asthenia, abdominal pain, dyspepsia, tremor, confusion,
agitation, sweating, malaise
Galantamine: somnolence
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