Download Acetylcholinesterase Inhibitors for the Treatment of Mild to Moderate

SHARED CARE PROTOCOL AND INFORMATION FOR GPS
Acetylcholinesterase Inhibitors and Memantine
Clinical Indication: Treatment of Dementia in Alzheimer’s Disease
(AD)
Version: 3
Date Approved: June 2011
Review Date: June 2013
Acetylcholinesterase Inhibitors for the Treatment of Mild to Moderate
Dementia, and Memantine for the Treatment of Moderate to Severe
Dementia in Alzheimer’s disease(AD).
AREAS OF RESPONSIBILITY FOR THE SHARING OF CARE
This shared care agreement outlines suggested ways in which the responsibilities for managing the
prescribing of Acetylcholinesterase Inhibitors and Memantine can be shared between the specialist and
general practitioner in primary care. GPs are invited to participate. If the GP is not confident to undertake
these roles, then he or she is under no obligation to do so. In that case, the total clinical responsibility for the
patient for the diagnosed condition remains with the specialist. If a specialist asks the GP to prescribe
drugs for this treatment, the GP should reply to this request as soon as practicable.
Sharing of care assumes communication between the specialist, GP and patient. The intention to share care
should be explained to the patient or the patient’s carer (where appropriate) by the doctor initiating treatment.
It is important that patients are consulted about treatment and are in agreement with it.
The doctor who prescribes the medication legally assumes clinical responsibility for the drug and
the consequences of its use.
RESPONSIBILITIES and ROLES
Hospital specialist team responsibilities
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Ask the GP whether he or she is willing to participate in shared care, and agree with the GP as to who will
discuss the shared care arrangement with the patient.
Confirm diagnosis of Alzheimer’s dementia.
Assess the need for treatment and the patient’s fitness for medication.
Consideration of potential drug interactions.
Assessment of baseline mental state by testing and via the carer’s view.
Provision of relevant information to the GP in writing including diagnosis, treatment to date, treatment to
be undertaken by the GP review arrangements, possible side-effects of treatment, system for monitoring
and recording adverse effects.
Selection and initiation of treatment with Acetylcholinesterase inhibitors and/or Memantine, or recommend GP
to initiate treatment.
Review of the patient's compliance and response to treatment 6 months after initiation of treatment.
Evaluation of any adverse effects noted by the patient/ carer or GP.
Communicate promptly with the GP when any change of therapy occurs, such as change in dose, or if a
patient is intolerant of a drug, or when discontinuing therapy if there is no longer evidence of benefit of
treatment.
Patient review when requested by the GP.
Report adverse events to the MHRA via Yellow Card Scheme.
Ensure that clear backup arrangements exist for GPs to obtain advice and support.
The Consultant Psychiatrist is responsible for ensuring that an appropriate T2 or T3 is completed for patients
detained under the Mental Health Act, and is responsible for sending a copy of a new or updated T2 or T3 to
the GP.
Any queries relating to this Shared Care Protocol contact the Clinical Effectiveness Pharmacist (01592) 226915
Document approved by NHS Fife Area Drugs & Therapeutics Committee on behalf of NHS Fife.
Ishtiaq Mohammed Clinical Effectiveness Pharmacist
General Practitioner responsibilities
1 Reply to the request for shared care as soon as practicable.
2 Undertake baseline investigations – full blood count, urea & electrolytes, calcium, phosphate, liver function
tests, thyroid function tests, serum glucose
3 Prescribe and administer Acetylcholinesterase inhibitors and/ or Memantine at the dose recommended by the
hospital specialist team.
4 Adjust the dose as advised by the hospital specialist team.
5 Monitor patient for the emergence/ worsening of adverse effects, particularly bradycardia, asthma/COPD or
symptoms of peptic ulceration.
6 Report to and seek advice from the hospital specialist team on any aspect of patient care that is of concern and
may affect treatment.
7 Refer patient to the hospital specialist team if there is concern about ongoing benefit.
8 Stop treatment on the advice of the hospital specialist team, or immediately if an urgent need to stop treatment
arises.
9 Report adverse events to the hospital specialist, where appropriate, and to the MHRA via the Yellow Card
Scheme.
10 Responsible for adhering to prescribing psychotropic medication as specified in a T2 or T3 for patients detained
under the Mental Health Act.
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Patient's / Carer’s role
Report to the specialist or GP if he or she does not have a clear understanding of the treatment.
Share any concerns in relation to treatment.
Report any adverse effects to the specialist or GP.
BACK-UP ADVICE AND SUPPORT
Contact details
Telephone No.
Email address:
Specialist:
Dr Pound
Dr Thomas
01383
2606
623623
01383 674192
ext
[email protected]
[email protected]
SUPPORTING INFORMATION
Introduction
Alzheimer’s disease is the most common cause of dementia characterised by insidious onset of global
mental impairment, and normally slow deterioration. Symptoms begin with decline in short-term memory and
cognition and progress to disorientation, altered mood and behaviour then to severe dementia.
Donepezil, galantamine and rivastigmine are reversible inhibitors of acetylcholinesterase which have been
approved by the Scottish Medicines Consortium (SMC), SIGN (Guideline 86) and NICE (Technology
appraisal guidance 217) as treatment options for mild to moderate Alzheimer’s dementia.
Memantine is also licensed and approved for treating moderate to severe dementia in Alzheimer’s disease
and has been approved by NICE (Technology appraisal guidance 217) and NHS Quality Improvement
Scotland.
Licensed indications
Any queries relating to this Shared Care Protocol contact the Clinical Effectiveness Pharmacist (01592) 226915
Document approved by NHS Fife Area Drugs & Therapeutics Committee on behalf of NHS Fife.
Ishtiaq Mohammed Clinical Effectiveness Pharmacist
Acetylcholinesterase inhibitors are licensed and approved for the symptomatic treatment of mild to
moderately severe dementia in AD. They should be initiated by or on the advice of a Consultant in Old Age
Psychiatry or Care of the Elderly.
Rivastigmine capsules and oral solution are also licensed for the symptomatic treatment of mild to moderate
severe dementia in patients with idiopathic Parkinson’s Disease. Rivastigmine patches are not licensed for
this indication.
Memantine is licensed and approved for the treatment of moderate to severe Alzheimer’s disease.
Dosage and Administration
Donepezil is available as tablets or orodispersible tablets. It should be initiated at 5mg once daily at bedtime
and increased to 10mg once daily at bedtime after at least one month if clinically appropriate.
Galantamine is available as tablets, oral solution and modified release capsules. The tablets /solution
should be initiated at a dose of 4mg twice daily, preferably with morning and evening meals and increased to
8mg twice daily after at least 4 weeks. Normal maintenance dose is 8 - 12mg twice daily.
Galantamine MR capsules should be started at a dose of 8mg once daily in the morning, swallowed whole
after food, and increased to 16mg MR once daily in the morning after at least 4 weeks. Normal maintenance
dose is 16 - 24mg once daily. Adequate fluid intake should be maintained during therapy.
Rivastigmine is available as capsules, oral solution and patches. The tablets /solution should be started at
1.5mg twice daily and increased in increments of 1.5mg twice daily at intervals of at least two weeks
according to response and tolerance, to a maximum of 6mg twice daily. If therapy is interrupted by more
than several days the dose should be re-titrated from 1.5mg twice daily. Usual range is 3 - 6mg twice daily.
Rivastigmine transdermal patches should be started at a dose of 4.6mg/ 24 hours and increased to
9.5mg/ 24 hours if necessary after at least 4 weeks if well tolerated. This is the recommended daily
maintenance dose. If therapy is interrupted by more than several days the dose should be re-titrated from
4.6mg/24hours. Patches should be applied to sites on the upper or lower back, upper arm or chest but not to
the abdomen or thigh areas due to decreased bioavailability of rivastigmine when the transdermal patch is
applied to these areas of the body. The patch should be removed after 24 hours, and the replacement patch
sited on a different area (avoid using the same area for 14 days).Patients with a body weight of less than
50kg are more likely to experience adverse effects leading to treatment discontinuation.
Memantine is available as 5mg, 10mg, 15mg and 20mg tablets, and as a 5mg/pump oral solution.
The recommended starting dose is 5mg once daily at the same time each day, increased stepwise in 5mg
increments weekly to a maximum of 20mg daily.
Oral solution - each pump activation gives 5mg in 0.5ml of solution.
Memantine oral solution should be dosed onto a spoon or into a glass of water using the pump. It should not
be poured or pumped into the mouth directly from the bottle or pump.
See detailed instructions about administration of memantine oral solution in the Ebixa® (memantine)
Summary of Product Characteristics (SPC)..
DRUG
Donepezil (Aricept®)
(Aricept Evess®)
Galantamine (Reminyl®)
(Reminyl XL®)
Memantine ( Ebixa®)
PRODUCTS AVAILABLE
5mg tablets x 28
10mg tablets x 28
5mg orodispersible tablets x 28
10mg orodispersible tablets x 28
8mg tablets x 56
12mg tablets x 56
4mg/ml oral solution (100ml)
8mg modified release capsules x 28
16mg modified release capsules x 28
24mg modified release capsules x 28
10mg scored tablets x 28 or 56 or 112
20mg scored tablets x 28 or 56 or 112
Treatment initiation pack: 7x5mg, 7x10mg, 7x15mg, 7x20mg
Oral drops 5mg/actuation ( 50g or 100g)
Rivastigmine (Exelon®)
1.5mg capsules x 28 or 56
3mg capsules x 28 or 56
4.5mg capsules x 28 or 56
6mg capsules x 28 or 56
Any queries relating to this Shared Care Protocol contact the Clinical Effectiveness Pharmacist (01592) 226915
Document approved by NHS Fife Area Drugs & Therapeutics Committee on behalf of NHS Fife.
Ishtiaq Mohammed Clinical Effectiveness Pharmacist
2mg/ml oral solution (120ml)
4.6mg/24h transdermal patches x 30, 60 or 90
9.5mg/24h transdermal patches x 30, 60 or 90
Contraindications and precautions for use
Known hypersensitivity to ingredients
Breastfeeding
Galantamine – severe renal and hepatic impairment
Rivastigmine – severe hepatic impairment
Cautions
Anaesthesia, cardiac conduction abnormalities, glaucoma, seizures (rivastigmine and memantine); asthma
or COPD, susceptibility to GI ulceration, urinary retention (galantamine, rivastigmine); recent MI,
uncompensated congestive heart failure and uncontrolled hypertension, raised urine PH ( drastic changes in
diet, massive intake of alkalising gastric buffers, renal tubulary acidosis, severe proteus UTIs) ( memantine)
Memantine oral solution contains sorbitol, avoid in patients with fructose intolerance.
Renal impairment
Donepezil – no dose adjustment necessary.
Galantamine – no dose adjustment in mild to moderate renal impairment. Severe - contraindicated if
creatinine clearance is less than 9ml/min.
Rivastigmine start with low dose and titrate slowly according to tolerability.
Memantine – moderate impairment (creatinine clearance 30-49ml/min ) maximum dose 10mg daily, if well
tolerated after at least 1 week then dose can be increased to 20mg daily in steps using the usual titration
procedure.
Severe impairment ( creatinine clearance 5-29ml/min) maximum dose 10mg daily. Avoid if creatinine
clearance less than 5ml/min.
Hepatic impairment
Donepezil – titrate dose based on tolerability,
Galantamine – mild - no dose adjustment.
Moderate – immediate release preparations: commence with 4mg daily, preferably in the morning, for at
least 7 days, increasing to 4mg twice a day for at least for weeks, maximum dose of 16mg daily.
Modified release preparations: 8mg modified release on alternate days (preferably in the morning) for 1
week, then 8mg once daily for 4 weeks; maximum dose 16mg daily.
Severe – contraindicated
Rivastigmine – mild to moderate – use with caution; severe –contraindicated.
Patch - patients with clinically significant hepatic impairment may experience more adverse effects.
Memantine – mild to moderate – no dose adjustment required; severe – not recommended.
Patients with clinically significant hepatic impairment may experience more adverse effects.
Discontinuation
Treatment can be stopped quickly if the patient has an adverse drug reaction.
In late stage Alzheimer’s where there is doubt about ongoing efficacy, after consultation with the patient’s
Consultant, treatment doses could be reduced and symptoms observed. If there is deterioration then the
dose can be increased again, or if there is no difference or improvement then treatment can be discontinued.
Side Effects
Acetylcholinesterase inhibitors
Gastrointestinal side effects of nausea, vomiting, and diarrhoea are very common especially during initiation
of therapy and after dose increases. Less common are peptic ulceration and GI bleeding.
Syncope, fatigue, headache, dizziness, anorexia, muscle cramps are also common, and bradycardia,
insomnia and extrapyridamal side effects can also occur. Nausea, vomiting and weight loss are more
common in women taking rivastigmine.
Any queries relating to this Shared Care Protocol contact the Clinical Effectiveness Pharmacist (01592) 226915
Document approved by NHS Fife Area Drugs & Therapeutics Committee on behalf of NHS Fife.
Ishtiaq Mohammed Clinical Effectiveness Pharmacist
Rivastigmine patches – anxiety, pyrexia and delirium are more likely, but dizziness, agitation, somnolence,
tremor, confusion, sweating, insomnia and cardiac arrhythmia probably less likely than with rivastigmine
capsules.
Memantine - most common - dizziness, headache, constipation, somnolence, dyspnoea and hypertension.
Drug Interactions
More severe side effects of peptic ulceration and GI bleeding are more likely where an acetylcholinesterase
inhibitor is co-prescribed with an SSRI, a NSAID, aspirin, warfarin or oral steroids.
There is an increased potential for decreased heart rate where an acetylcholinesterase inhibitor is coprescribed with digoxin, amiodarone, rate limiting calcium channel blockers verapamil or diltiazem, and beta
blockers.
Acetylcholinesterase inhibitors interact with muscle relaxants, antimuscarinics, erythromycin, itraconazole
and fluconazole, fluoxetine and paroxetine, quinidine.
Donepezil – rifampicin, phenytoin and carbamazepine may reduce plasma levels of donepezil.
Galantamine – caution with other drugs that can potentially cause Torsade De Pointes.
Rivastigmine less potential for interactions and no interaction expected with digoxin, fluoxetine, paroxetine,
warfarin.
Memantine – avoid NMDA antagonists such as amantadine, ketamine and dextromethophan.Cimetidine,
ranitidine, quinine, quinidine and nicotine may increase levels of memantine; isolated cases of increased INR
with warfarin; effects of L-dopa, dopaminergic agonists and anticholinergics may be enhanced; effects of
barbiturates and neuroleptics may be reduced; dose adjustments of baclofen, antispasmodics and
dantrolene may be necessary.
Cost
Donepezil standard and orodispersible tablets are the same price.
Galantamine standard and modified release preparations are the same price.
All doses of rivastigmine tablets are the same price.
Oral solutions of galantamine and rivastigmine are more expensive than tablets/capsules and this cost
increases with higher doses.
Drug & daily dose
Donepezil 5mg
Donepezil 10mg
Galantamine 16mg
Galantamine 24mg
Galantamine M/R 8mg
Galantamine M/R 16mg
Galantamine M/R 24mg
Galantamine oral solution (4mg/ml) 24mg dose
Memantine 10mg
Memantine 20mg
Memantine titration pack
Memantine oral drops 20mg
Rivastigmine 6mg, 9mg or 12mg
Rivastigmine 4.6mg/24 hours or 9.5mg/24 hours
Rivastigmine oral solution ( 2mg/ml) 12mg dose
Rivastigmine Patch 4.6mg/24 hours or 9.5mg/24 hours
Cost per 28 days
£59.85
£83.89
£68.32
£84.00
£51.88
£64.90
£79.80
£201.60
£34.50
£69.01
£43.13
£69.00
£66.51
£77.97
£138.80
£72.77
(from BNF 61 March 2011)
References:
British National Formulary 61, March 2011.British Medical Association.
Electronic Medicines Compendium. Summary of product Characteristics for Donepezil (Aricept®),
Galantamine (Reminyl ®), Rivastigmine (Exelon®) and Memantine (Ebixa®).
National Institute for Clinical Excellence. (Technology appraisal guidance 217). March 2011.Donepezil,
galantamine. rivastigmine and memantine for the treatment of Alzheimer’s disease (review).
Scottish Intercollegiate Guidelines Network (Guideline 86). February 2006. Management of patients with
dementia.
Any queries relating to this Shared Care Protocol contact the Clinical Effectiveness Pharmacist (01592) 226915
Document approved by NHS Fife Area Drugs & Therapeutics Committee on behalf of NHS Fife.
Ishtiaq Mohammed Clinical Effectiveness Pharmacist
Any queries relating to this Shared Care Protocol contact the Clinical Effectiveness Pharmacist (01592) 226915
Document approved by NHS Fife Area Drugs & Therapeutics Committee on behalf of NHS Fife.
Ishtiaq Mohammed Clinical Effectiveness Pharmacist