Guidelines on the use of Antidementia Drugs in People Living with Dementia
GUIDELINE VERSION 6 RATIFYING COMMITTEE Drugs and Therapeutics Group DATE FIRST RATIFIED April 26th, 2011.
Reviewed & updated: September 2012 February 2013 June 2016 July 2019
NEXT REVIEW DATE July 2022, or earlier if there is new national guidance GUIDELINE SPONSOR Chief Medical Officer ORIGINAL GUIDELINE Jed Hewitt – Chief Pharmacist, AUTHOR Governance & Professional Practice THIS VERSION REVIEWED BY Grant Salvage – Lead Pharmacist Mental Health (Chichester Locality)
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Guidelines on the use of Antidementia Drugs in People Living with Dementia
1. Pharmacological Management of Dementia
The following medications for dementia are available to prescribe on the Trust formulary: o The acetylcholinesterase inhibitors (AChEIs); donepezil, rivastigmine and galantamine. o The NMDA receptor antagonist; memantine.
Patients with mild to moderate Alzheimer’s disease should initially be offered treatment with an acetylcholinesterase inhibitor.
The initial acetylcholinesterase inhibitor offered should usually be donepezil tablets as these have the lowest ongoing cost, however it may be appropriate on an individual basis to offer an alternative choice after taking into account the adverse effect profile of the medications, concurrent medications and possible interactions, expected patient adherence and medication dosing regimens.
Patients with moderate Alzheimer’s disease who are intolerant or have contraindications to treatment with acetylcholinesterase inhibitors should be offered treatment with memantine.
Patients with severe Alzheimer’s disease should be offered treatment with the NMDA receptor antagonist memantine.
The decision to offer initial treatment of Alzheimer’s disease with either an acetylcholinesterase inhibitor or memantine should only be undertaken on the advice of a secondary care specialist (consultant, associated specialist, geriatrician, neurologist) or other healthcare professional who has expertise in diagnosing and treating Alzheimer’s Disease (GP, nurse consultant, advanced nurse practitioner).
Once a decision has been made to start an acetylcholinesterase inhibitor or memantine, the first prescription may be provided by primary care, but if a specialist is seeing the patient they should initiate treatment to avoid delay.
Patients with moderate Alzheimer’s disease who are already taking an acetylcholinesterase inhibitor should be considered for treatment with memantine in addition to their other treatment.
Patients with severe Alzheimer’s disease who are already taking an acetylcholinesterase inhibitor should be offered treatment with memantine in addition to their other treatment.
Where patients have an established diagnosis of Alzheimer’s disease and are already taking an acetylcholinesterase inhibitor, primary care prescribers may start treatment with memantine in addition to their other treatment without taking specialist advice.
The pharmacological treatment of Alzheimer’s disease should not be stopped on the basis of disease progression or disease severity only.
Patients with non-Alzheimer’s dementia should be offered the following treatments:
o Patients with mild to moderate dementia with Lewy bodies should be offered treatment with donepezil or rivastigmine, o Patients with severe dementia with Lewy bodies should be considered for treatment with donepezil or rivastigmine o Galantamine should only be offered in the treatment of dementia with Lewy Bodies if donepezil or rivastigmine are not tolerated. o If acetylcholinesterase inhibitors are not tolerated or are contraindicated, consider offering memantine in the treatment of dementia with Lewy bodies.
o Patients with mild to moderate Parkinson’s disease dementia should be offered treatment with an acetylcholinesterase inhibitor. o Patients with severe Parkinson’s disease dementia should be considered for treatment with an acetylcholinesterase inhibitor. o If acetylcholinesterase inhibitors are not tolerated or are contraindicated, consider offering memantine in the treatment Parkinson’s disease dementia.
o Patient with vascular dementia should only be offered treatment with acetylcholinesterase inhibitors or memantine if they have co-morbid Alzheimer’s disease, dementia with Lewy bodies or Parkinson’s disease dementia.
Patients with frontotemporal dementia should not be offered treatment with acetylcholinesterase inhibitors or memantine.
Patients with cognitive impairment caused by multiple sclerosis should not be offered treatment with acetylcholinesterase inhibitors or memantine.
Patients with mild cognitive impairment should not be offered treatment with acetylcholinesterase inhibitors as current evidence suggests they do not reduce the risk of developing dementia, and that they are ineffective in the treatment of mild cognitive impairment whilst also increasing the risk to the patient from adverse effects. There are no studies to support the prescribing of memantine in mild cognitive impairment.
2. Contra-indications and Cautions
Acetylcholinesterase inhibitors are contraindicated by the manufacturers where patients have a known hypersensitivity to the active pharmaceutical ingredient, piperidine derivatives, carbamate derivatives, or to any excipients present in the formulation. o Galantamine is additionally contraindicated in patients with severe renal and hepatic dysfunction o Rivastigmine is additionally contraindicated in patients with application site reactions suggestive of allergic contact dermatitis with rivastigmine patches, unless further allergy testing is negative. Patients who have become sensitised to rivastigmine may not be able to take rivastigmine in any form.
Acetylcholinesterase inhibitors must be used with caution in conditions which may be exacerbated by the increase in systemic acetylcholine caused by the treatment, this includes: o Patients with on-going gastro-intestinal disorders such as nausea, vomiting, and diarrhoea. o Patients experiencing weight loss. o Patients who are at high risk of developing torsade de pointes, for example those with uncompensated heart failure, recent myocardial infarction, bradycardia, hypokaelaemia, hypomagnesaemia, and prolonged QTc interval or concomitant use of medications known to prolong QTc interval. o Patients with sick sinus syndrome or conduction deficits. o Patients with active gastric or duodenal ulcers or patients predisposed to these conditions. o Patients with a history of asthma or chronic obstructive pulmonary disease. o Patients predisposed to urinary obstructions and seizures.
Memantine must be used with caution in the following situations: o Patients with epilepsy, history of convulsions, or patients with predisposing factors for epilepsy. o Concomitant use of NMDA receptor antagonists such as amantadine, ketamine or dextromethorphan, which may exacerbate incidence and severity of adverse effects. o Patients with raised urinary pH, as alkalinisation of urine may lead to the elimination of memantine being reduced by a factor of 7 to 9. o Patients with recent myocardial infarction, uncompensated heart failure, or uncontrolled hypertension.
3. Dosing Recommendations:
All acetylcholinesterase inhibitors and memantine must be prescribed by generic name.
Donepezil o 5mg once daily for 4 weeks, increasing to 10mg once daily if necessary.
Galantamine o Immediate release - 4mg twice daily for 4 weeks, increasing to 8mg twice daily for at least 4 weeks, the usual maintenance dose is 8 to 12 mg twice daily. o Modified release capsules – 8mg once daily for 4 weeks, increasing to 16mg once daily for at least 4 weeks. Usual maintenance dose is 16 to 24mg daily.
Rivastigmine o Capsules – 1.5mg twice daily for 2 weeks, increasing in steps of 1.5mg twice daily at intervals of at least 2 weeks according to tolerance. Usual maintenance dose is 3 to 6mg twice daily. o Transdermal patches – One 4.6mg/24 hour patch daily for at least 4 weeks, increased if tolerated to one 9.5mg/24 hour patch daily for a further 6 months, then increased if necessary to one 13.3mg/24 hour patch daily if well tolerated.
Memantine o 5mg once daily for 1 week, increasing in 5mg steps every week. Usual maintenance dose 20mg daily.
Doses may need to be adjusted according to renal and hepatic function, refer to product literature.
If patients suffer from intolerable adverse effects during treatment with acetylcholinesterase inhibitors, treatment should be discontinued and adverse effects allowed the time to resolve completely. Treatment can then either be restarted and titrated at a slower rate, or an alternative medication tried instead.
Where patents have been non-adherent with their medication, treatment may require re-titration to avoid dose related adverse effects such as those caused by systemic increases in acetylcholine with acetylcholinesterase inhibitors, as per when they were first initiated: o This is most evident with rivastigmine, whereby if 3 days of treatment is missed in a row it must be restarted from 1.5mg twice daily for the capsules or one 4.6mg/24 hours patch daily for the transdermal patches.
4. Monitoring and Review
GPs should be asked to review patients after a maintenance dose has been achieved and if treatment is well tolerated and there are no complications; continue the treatment long-term.
When reviewing patients with dementia, concomitant anticholinergic medications should also be reviewed and discontinued or switched to an alternative where possible. Anticholinergics with effects on cognition or the additive effect of multiple anticholinergic medications (anticholinergic burden) may worsen the symptoms of dementia, and counteract the potential benefits of acetylcholinesterase inhibitors.
5. Costs
DONEPEZIL Dose Cost for 28 day’s treatment 5mg tablets 5mg daily £0.87 10mg tablets 10mg daily £0.96 5mg orodispersible tablets 5mg daily £7.33 10mg orodispersible tablets 10mg daily £8.14 1mg/mL oral solution 5mg daily £50.99 1mg/mL oral solution 10mg daily £101.98 RIVASTIGMINE 1.5mg capsules 1.5mg twice daily £11.28 3mg capsules 3mg twice daily £11.90 4.5mg capsules 4.5mg twice daily £47.06 6mg capsules 6mg twice daily £58.36 4.6mg/24 hour patches 1 patch daily £77.97 9.5mg/24 hour patches 1 patch daily £19.97 13.3mg/24 hour patches 1 patch daily £77.97 GALANTAMINE 8mg modified release capsules 8mg daily £51.88 16mg modified release capsules 16mg daily £64.90 24mg modified release capsules 24mg daily £79.80 20mg/5mL oral solution 4mg twice daily £67.20 20mg/5mL oral solution 8mg twice daily £134.40 20mg/5mL oral solution 12mg twice daily £201.60 MEMANTINE 10mg tablets 5mg daily £0.64 10mg tablets 10mg daily £1.29 10mg tablets 15mg daily £1.93 20mg tablets 20mg daily £1.63 10mg orodispersible tablets 10mg daily £24.99 20mg orodispersible tablets 20mg daily £49.98 10mg/mL oral solution 5mg daily £15.42 10mg/mL oral solution 10mg daily £30.84 10mg/mL oral solution 15mg daily £46.26 10mg/mL oral solution 20mg daily £61.68 Initiation pack 5mg/10mg/15mg/20mg daily £43.13
6. References and background information:
1. NICE guidance NG97 – Dementia: assessment, management and support for people living with dementia and their carers; June 2018 https://www.nice.org.uk/guidance/ng97/ 2. NICE guidance NG71 - Parkinson’s disease in adults; July 2017 https://www.nice.org.uk/guidance/ng71 3. NICE technical appraisal TA217 - Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease (review). May 2016. https://www.nice.org.uk/guidance/ta217. 4. Clinical practice with anti-dementia drugs: a revised (third) consensus statement from British Association for Psychopharmacology; British Association of psychopharmacology; 2017 5. The Maudsley Prescribing Guidelines in Psychiatry; David Taylor, Thomas E Barnes, Allan Young; 13th Edition 2018 6. Donepezil Summary of Product Characteristics; https://www.medicines.org.uk/emc/product/3776/smpc; accessed 08/07/2019 7. Rivastigmine summary of product characteristics; https://www.medicines.org.uk/emc/product/4835/smpc ; https://www.medicines.org.uk/emc/product/8510/smpc ; accessed 08/07/2019 8. Galantamine summary of product characteristics; https://www.medicines.org.uk/emc/product/8620/smpc ; accessed 08/07/2019 9. Memantine summary of product characteristics; https://www.medicines.org.uk/emc/product/8222/smpc ; accessed 08/07/2019 10. BNF; NICE; https://bnf.nice.org.uk/ ; accessed 08/07/2019 11. Drug Tariff July 2019; https://www.nhsbsa.nhs.uk/pharmacies-gp-practices-and-appliance- contractors/drug-tariff; access 08/07/2019
Originally ratified April 2011. Updated in September 2012, February 2013 and June 2016, July 2019 Next review: June 2022.