Information for Prescribing Anti-dementia Drugs
November 2012
The aim of this document is to provide information about the prescribing of
anti-dementia medication for adult patients with dementia following an
assessment and stabilisation of treatment in the memory clinic.
The information will ensure there is a consistent rationale for prescribing in
memory clinics across the Health Board and that GPs will have sufficient
information to enable them to safely undertake ongoing prescribing of anti-
dementia medication.
NICE Recommendations
This information is based on the National Institute for Clinical Excellence
Technology Appraisal 217: donepezil, rivastigmine and galantamine and
memantine for the treatment of Alzheimer’s disease in March 2011.
http://guidance.nice.org.uk/TA217
In summary, the review advises that:
• The three acetylcholinesterase (AChE) inhibitors, donepezil,
galantamine and rivastigmine are recommended as options for the
treatment of mild to moderate Alzheimer’s disease (AD).
• Memantine is recommended as an option for people with moderately
severe to severe Alzheimer’s disease
• The medication with the lowest acquisition cost should be initiated
however, if this is not suitable for the patient, another medication could
be prescribed.
Choice of treatment
All anti-dementia medication will be prescribed by the approved name, not by
proprietary (brand) name.
A generically available preparation of donepezil, galantamine or rivastigmine
(chosen according to current acquisition cost and specialist preference /
experience), will be considered for patients with mild to moderate Alzheimer’s
disease, unless contra-indicated.
A patient with Alzheimer’s disease may be offered one of the other two drugs
if the first is not tolerated or due to lack of clinical efficacy.
Prescribing Information Anti-dementia Drugs
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November 2012
Donepezil Hydrochloride
Licensed indications: symptomatic treatment of mild to moderately severe
Alzheimer’s dementia.
Pharmacology: Reversible inhibitor of acetylcholinesterase.
Preparations available: 5mg and 10mg tablets. Orodispersible tablets are
available for those patients with swallowing difficulties.
Recommended dosage and administration
Initial dose: 5 mg once daily, increased if necessary after one month to 10mg
once daily.
Usual maintenance dose: 5mg to 10mg once daily.
Maximum dose: 10mg once daily.
* Orodispersible tablets should be placed on the tongue, allowed to disperse and
swallowed.
Contra-indications: Patients with a known hypersensitivity to donepezil (or
other piperidine derivatives), or to any of the excipients used in the
formulations. Breastfeeding.
Cautions: Sick sinus syndrome or other supraventricular conduction
abnormalities; susceptibility to peptic ulcers; asthma, chronic obstructive
pulmonary disease, pregnancy.
Hepatic impairment: caution in mild to moderate impairment, no information
available for severe impairment.
Drug interactions: Check current BNF Appendix 1 before co-prescribing
other drugs. Acetylcholinesterase inhibitors act as parasympathomimetics
• Antimuscarinics - Effects of Acetylcholinesterase inhibitors antagonised
by antimuscarinics.
• Muscle Relaxants – Acetylcholinesterase inhibitors can also enhance
the effect of the depolarising muscle relaxants and antagonise the
effects of non-depolarising muscle relaxants.
• Ketoconazole, quinidine, itraconazole, erythromycin, fluoxetine inhibit
donepezil metabolism (in vitro studies).
• Rifampicin, phenytoin, carbamazepine and alcohol may reduce the
levels of donepezil (in vitro studies).
Adverse effects: most common – diarrhoea, muscle cramps, fatigue,
nausea, vomiting, headache and insomnia.
** If the patient develops seizures, pancreatitis, cardiac, gastrointestinal
or ophthalmological disorders withhold drug and discuss with the
specialist team
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November 2012
Galantamine
Licensed indications: symptomatic treatment of mild to moderately severe
dementia of the Alzheimer type.
Pharmacology: competitive and reversible inhibitor of acetylcholinesterase,
and also an enhancer of the intrinsic action of acetylcholine on nicotinic
receptors.
Preparations available: 8mg and 12mg galantamine tablets, 8mg, 16mg and
24mg modified release capsules and oral solution.
The modified release preparations are now initiated first line however an oral
solution is available for those patients with swallowing difficulties.
Recommended dosage and administration
Initial dose:
Galantamine XL Capsules: 8mg once daily for 4 weeks, increased to 16mg
once daily for 4 weeks.
Galantamine Oral solution: 4mg twice daily for 4 weeks, increased to 8mg
twice daily for 4 weeks.
Usual maintenance dose:
Galantamine XL Capsules: 16 to 24mg once daily.
Galantamine Oral solution: 8 to 12mg twice daily.
Maximum dose:
Galantamine XL Capsules: 24mg once daily.
Galantamine Oral solution: 12mg twice daily.
Contra-indications: Patients with a known hypersensitivity to galantamine (or
other carbamate derivatives) or to any of the excipients used in the
formulations. Breastfeeding.
Avoid in urinary retention, gastro-intestinal obstruction, and while recovering
from bladder or gastro-intestinal surgery.
Severe hepatic (Child –Pugh score >9) and severe renal (creatinine clearance
< 9ml/min).
Hepatic impairment:
•
for immediate-release preparations in moderate impairment, initially
4 mg once daily (preferably in the morning) for at least 7 days, then
4 mg twice daily for at least 4 weeks; max. 8 mg twice daily; avoid in
severe impairment.
•
for modified-release preparations in moderate impairment, initially 8 mg
on alternate days (preferably in the morning) for 7 days, then 8 mg
once daily for 4 weeks; max. 16 mg daily; avoid in severe impairment.
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(Galantamine continued)
Cautions: Cardiac disease (including sick sinus syndrome or other
supraventricular conduction abnormalities), unstable angina, congestive heart
failure); electrolyte disturbances; susceptibility to peptic ulcers; asthma,
chronic obstructive pulmonary disease, pulmonary infection; history of
seizures, pregnancy.
Drug interactions: Check current BNF Appendix 1 before co-prescribing
other drugs. Acetylcholinesterase inhibitors act as parasympathomimetic:
• Antimuscarinics - Effects of Acetylcholinesterase inhibitors
antagoinsed by antimuscarinics.
• Muscle Relaxants – Acetylcholinesterase inhibitors can also enhance
the effect of the depolarising muscle relaxants and antagoinse the
effects of non-depolarising muscle relaxants. Galantamine enhances
the effects of suxamethonium.
• Erythromycin - can increase plasma concentration of galantamine.
• Ketoconazole - can increase plasma concentration of galantamine.
• Paroxetine - can increase plasma concentration of galantamine.
Adverse effects: Most common - nausea, vomiting, diarrhoea, abdominal
pain, dyspepsia, anorexia, fatigue, dizziness, headache, somnolence and
weight decrease.
** If the patient develops seizures, pancreatitis, cardiac, gastrointestinal
or ophthalmological disorders withhold drug and discuss with the
specialist team
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November 2012
Rivastigmine
Licensed indications: symptomatic treatment of mild to moderately severe
Alzheimer’s dementia.
*Rivastigmine capsules (not the transdermal patches) are also licensed for the
treatment of mild to moderately severe dementia in Parkinson's disease.
Pharmacology: Pseudo-irreversible acetylcholinesterase inhibitor.
Preparations available: 1.5mg, 3mg, 4.5mg and 6mg capsules, 2mg in 1ml
oral solution and patches of 4.6mg / 24hour 9.5 mg / 24hour.
Recommended dosage and administration
Initial dose:
Rivastigmine capsules / oral solution: 1.5mg twice daily, increased in steps of
1.5mg twice daily at intervals of at least 2 weeks according to response and
tolerance.
Rivastigmine patches: 4.6mg/24 hours; if well tolerated increase to 9.5mg/24
hours patch daily after at least 4 weeks.
Usual maintenance dose:
Rivastigmine capsules / oral solution: 3 to 6mg twice daily. If treatment is
interrupted for more than several days, treatment should be retitrated from
1.5mg twice daily.
Rivastigmine patches: 4.6 to 9.5mg/24 hours; if patch not applied for more
than several days, treatment should be restarted with 4.6mg/24 hours patch.
Maximum dose:
Rivastigmine capsules / oral solution: 6mg twice daily.
Rivastigmine patches: 9.5mg/24 hours.
Note - When switching from oral to transdermal therapy, patients taking 3–
6 mg by mouth daily should initially switch to 4.6 mg/24 hours patch (then
titrate as above); patients taking 9–12 mg by mouth daily should switch to
9.5 mg/24 hours patch. The first patch should be applied on the day following
the last oral dose.
Contra-indications: Patients with a known hypersensitivity to rivastigmine (or
other carbamate derivatives) or to any of the excipients used in the
formulations. Breastfeeding.
Previous application site reactions suggestive of allergic contact dermatitis
(for patches).
Patients with severe hepatic impairment (no studies in theses patients).
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November 2012
(Rivastigmine continued)
Cautions: Gastric or duodenal ulcers (or susceptibility to ulcers); monitor
body-weight; sick sinus syndrome, conduction abnormalities; history of
asthma or chronic obstructive pulmonary disease; history of seizures; bladder
outflow obstruction.
Hepatic and renal impairment: use with caution as patients may experience
more adverse reactions.
Drug interactions: Check current BNF Appendix 1 before co-prescribing
other drugs. Acetylcholinesterase inhibitors act as parasympathomimetics:
• Muscle Relaxants – rivastigmine antagoinse the effects of non-
depolarising muscle relaxants.
• Suxamethonium – rivastigmine enhances the effects of
suxamethonium.
• Antimuscarinics - Effects of Acetylcholinesterase inhibitors antagonised
by antimuscarinics.
Adverse effects: most common – nausea, vomiting, diarrhoea, dyspepsia,
anorexia, weight loss, increased salivation, abdominal pain, bradycardia,
dizziness, headache, drowsiness, malaise, agitation, anxiety, tremor,
confusion, insomnia, extrapyramidal symptoms (and worsening of Parkinson’s
disease), sweating. Female patients were found to be more susceptible to
nausea, vomiting, loss of appetite and weight loss.
Note - Transdermal administration less likely to cause gastro-intestinal
disturbance.
Note - Treatment should be interrupted if gastro-intestinal side-effects occur
and withheld until their resolution - retitrate dose if necessary.
** If the patient develops seizures, pancreatitis, cardiac, gastrointestinal
or ophthalmological disorders withhold drug and discuss with the
specialist team
Prescribing Information Anti-dementia Drugs
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November 2012
Memantine
Licensed indications: symptomatic treatment of patients with moderate to
severe Alzheimer's disease.
Pharmacology: Memantine acts as an antagonist at N-methyl-D-aspartate
(NMDA) receptors, an action which, in theory, may be neuroprotective and
thus disease modifying.
Preparations available: 10mg and 20mg film coated tablets, a Treatment
Initiation pack containing 5mg, 10mg, 15mg and 20mg tablets and an oral
solution 5mg per actuation (10mg in 1ml).
Recommended dosage and administration:
Initial dose (adult): Memantine is initially given as 5 mg once daily and then
increased in steps of 5 mg at weekly intervals to a maximum of 20 mg daily.
Usual maintenance dose: 20mg once daily.
Maximum dose: 20mg once daily.
Contra-indications: Patients with a known hypersensitivity to memantine or
to any of the excipients used in the formulations. Breast feeding.
Cautions: patients with epilepsy, former history of convulsions or patients
with predisposing factors for epilepsy. Concomitant use of N-methyl-D-
aspartate (NMDA)-antagonists such as amantadine, ketamine or
dextromethorphan should be avoided. These compounds act at the same
receptor system as memantine, and therefore adverse drug reactions (mainly
CNS-related) may be more frequent or more pronounced.
Risk in pregnancy is unknown therefore should be avoided unless absolutely
necessary.
Hepatic impairment: in patients with mild or moderate hepatic impaired
function no dosage adjustment is needed. There is no data available on the
use of memantine in patients with severe hepatic impairment. Avoid in severe
hepatic impairment.
Renal impairment: reduce dose to 10 mg daily if eGFR 30-
49 mL/minute/1.73 m2, if well tolerated after at least 7 days dose can be
increased in steps to 20 mg daily; reduce dose to 10 mg daily if eGFR 5–
29 mL/minute/1.73 m2; avoid if eGFR less than 5 mL/minute/1.73 m2.
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(Memantine continued)
Drug interactions:
• Amantadine - increased risk of CNS toxicity when memantine given
with amantadine (manufacturer of memantine advises avoid
concomitant use).
• Antimuscarinics - memantine possibly enhances effects of
antimuscarinics.
• Antipsychotics - memantine possibly reduces effects of antipsychotics.
• Baclofen - memantine possibly modifies effects of baclofen.
• Barbiturates - memantine possibly reduces effects of barbiturates.
• Dantrolene - memantine possibly modifies effects of dantrolene.
• Dextromethorphan - increased risk of CNS toxicity when memantine
given with dextromethorphan (manufacturer of memantine advises
avoid concomitant use).
• Dopaminergics - memantine possibly enhances effects of
dopaminergics.
• Ketamine - increased risk of CNS toxicity when memantine given with
ketamine (manufacturer of memantine advises avoid concomitant use).
• Selegiline - memantine possibly enhances effects of selegiline.
• Warfarin – memantine possibly enhances anticoagulant effect of
warfarin.
Adverse effects: most common – constipation, hypertension, dyspnoea,
headache, dizziness and drowsiness.
Prescribing Information Anti-dementia Drugs
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November 2012
NOTES for all medication
** If the patient develops seizures, pancreatitis, cardiac, gastrointestinal
or ophthalmological disorders withhold drug and discuss with the
specialist mental health team
• Please report adverse events to the CSM using the yellow card
system.
www.mhra.gov.uk/Safetyinformation/Reportingsafetyproblems/index.htm
• Please refer to the SPC for full prescribing information (available at
www.medicines.org.uk).
Date of Preparation: November 2012
Review Date: November 2014
References:
BNF 64 September 2012
Maudsley Prescribing Guidelines in Psychiatry 11th edition
SmPCs accessed via www.medicines.org 15.11.2012
Contact Details for Memory Clinics
Clinic
Telephone Number
Fax Number
Carmarthen
Medical Secretary: 01267
674042
01267 674040
Memory Clinic Nurse
Margaret Tooby
Consultant Psychiatrist
Dr Graham O’Connor
Llanelli
Medical Secretary:
01554 779310
01554 779312
Memory Clinic Nurse
Ann Pearce
Consultant Psychiatrist
Dr Toyin Adeyemo
Ammanford
Medical Secretary : 01267
674034
01267 674039
Memory Clinic Nurse
Barbara Davies
Consultant Psychiatrist
Dr Apparao Biradar
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November 2012
Aberystwyth
Medical Secretary
Enilli Unit
01970 635844/ 635842
01970 635931
Memory Clinic Nurse
Clive Thomas
xxxxxxx.xxxxxxx@xxxxx.xxx.xx
Dr Anke Cupok
xxxx.xxxxx@xxxxx.xxx.xx
Consultant Psychologist
Becci Dow
xxxxxxx.xxx@xxxxx.xxx.xx
Cardigan
Medical Secretary
Cardigan Hospital
01970 635844/ 635842
01970 635931
(Monthly)
Memory Clinic Nurse
Clive Thomas
Dr Anke Cupok
Consultant Psychologist
Becci Dow
Pembrokeshire Memory Medical Secretary
Clinic
01437 772828
01437 773057
Bro Cerwyn Centre
Memory Clinic Nurse
Clinic
Helen Goodchild
01437 772844
Consultant
Dr C James
Pembrokeshire
Medical Secretary
Older Adults CMHT
01437 772828
01437 773057
Bro Cerwyn Centre
CMHT Co-ordinator
Clinic
Judith Radbourne
01437 772844
Consultant Psychiatrist
Dr Pansari
Prescribing Information Anti-dementia Drugs
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November 2012
ANTI-DEMENTIA MEDICATION PRESCRIPTION REQUEST FORM
Part A: To be completed by Specialist Memory Assessment Service
Dear Dr.........................................................................................
GP Practice……………………………………………………………
Patient’s name
Date of birth
Address
The above patient has been assessed by the specialist memory service and
has been stabilised on the following treatment for their dementia.
I am requesting your agreement to continue prescribing this medication
Medication, dose and frequency
Date of most recent issue of
medicine(s)
Date next issue is due
Date of next Memory Clinic
Review appointment
Name of consultant
Date:
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November 2012
Part B: To be completed by GP Practice
ACKNOWLEDGEMENT OF TRANSFER OF PRESCRIBING
Patient’s name
Date of birth
Address
Medication, dose and frequency
Date of Next Issue
I AGREE / DO NOT AGREE TO CONTINUING THE PRESCRIPTION OF
THE ABOVE MEDICATION TO THIS PATIENT (PLEASE INDICATE)
Signed……………………………………………………………………
Print Name………………………………………………………………
Date………………………………………………………………………
GP Practice……………………………………………………………….
Please return to
Eileen Richards
Mental Health Pharmacy
Glangwili Hospital
Carmarthen
SA31 2AF
Tel: 01267 227367
Or FAX to SAFE HAVEN FAX on 01267 227720
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