NICE guidance NG97 Dementia: assessment, management and support for people living with dementia and their carers (issued June 2018): includes sections on pharmacological interventions for Alzheimer’s disease and non-Alzheimer’s dementia. NG97 should be referred to for the full recommendations for use of acetylcholinesterase inhibitors and memantine in Alzheimer’s disease as this guidance includes a partial update to NICE TA217: Alzheimer's disease - donepezil, galantamine, rivastigmine and memantine

NICE guidance NG71 Parkinson’s disease in adults: includes recommendations for the use of acetylcholinesterase inhibitors for mild, moderate and severe Parkinson’s disease dementia. The guidance notes that oral formulations of rivastigmine are licensed for mild and moderate dementia in Parkinson’s disease; the use of rivastigmine patches, donepezil and galantamine is off-label for mild and moderate dementia in Parkinson’s disease; and the use of all acetylcholinesterase inhibitors is off-label for severe Parkinson’s disease dementia

Dementia with Lewy bodies: NICE guidance NG97 includes recommendations for acetylcholinesterase inhibitors and memantine for dementia with Lewy bodies and notes the use of these medicines is off-label for these indications.

Medicines which may cause cognitive impairment and managing non-cognitive symptoms of dementia is addressed in NICE guidance NG97.

Prescribing information:

• Prescribing for Alzheimer's disease
• Behavioural and Psychological Symptoms of Dementia (BPSD)

Other resources:

• Devon Partnership NHS Trust
  • Pharmacological management of Alzheimer's Dementia (PG15 February 2020)
  • Pharmacological Management of Severe Behavioural & Psychological Symptoms of Dementia (BPSD) (PG14 July 2019)

Oral solutions, orodispersible and patch preparations of drugs for dementia should not be used routinely but may occasionally be initiated by specialists for patients in whom tablets are not suitable.

Donepezil hydrochloride

• Tablet 5mg, 10mg (£1.23 = 10mg daily)
• Orodispersible tablets sugar free 5mg, 10mg (£87.31 = 10mg daily)

Indications

• Mild to moderate dementia in Alzheimer's disease

Dose

• Initially 5mg once daily, increased if necessary after one month to maximum 10mg daily
• Hepatic impairment: mild to moderate hepatic impairment: dose escalation according to individual tolerability. No data are available for patients with severe hepatic impairment.

Notes

1. Donepezil has a long half-life so short accidental omission unlikely to have serious consequences

Galantamine

• Modified release capsules 8mg, 16mg, 24mg (click here for preferred brand)
• Oral solution 4mg/ml (£120.00 = 100ml)

Indications

• Mild to moderate dementia in Alzheimer's disease

Dose

• Oral solution: initially 4mg twice daily for 4 weeks, increased to 8mg twice daily for 4 weeks; maintenance 8–12mg twice daily
  • Hepatic impairment: No dosage adjustment required for mild hepatic impairment. For moderately impaired hepatic function begin dosing at 4mg once daily (taken in morning) for at least one week. Thereafter, proceed with 4mg twice daily for four weeks. In these patients, daily doses should not exceed 8mg twice daily. Contraindicated in severe hepatic impairment due to lack of data
  • Renal impairment: Contraindicated in patients with creatinine clearance <9ml/min
• Modified release: initially 8mg once daily for 4 weeks increased to 16mg once daily for 4 weeks; maintenance 16–24mg daily
  • Hepatic impairment: No dosage adjustment required for mild hepatic impairment. For moderate hepatic impairment initially 8mg on alternate days (taken in morning) for 7 days, then 8mg once daily for four weeks. Maximum 16mg once daily. Contraindicated in severe hepatic impairment due to lack of data
  • Renal impairment: Contraindicated in patients with creatinine clearance <9ml/min

Notes

1. It is sensible to re-titrate galantamine from the initial dose in the event of a treatment break (this is not mentioned in the Summary of Product Characteristics)
2. Where a preferred brand is recommended for a particular presentation, prescribing by brand helps ensure cost-efficient use of local NHS resources (see preferred brand link above)

Memantine

• Tablet 10mg, 20mg (£1.31 = 20mg daily)
• Oral solution sugar free 10mg/ml (£18.90 = 50ml)

Indications

• Moderate Alzheimer's disease
  • monotherapy for those intolerant of or have a contra-indication to acetylcholinesterase inhibitors, or
  • in addition to an acetylcholinesterase inhibitor if the patient is already taking an acetylcholinesterase inhibitor (see note 1)
• Severe dementia in Alzheimer's disease
  • monotherapy, or
  • in addition to an acetylcholinesterase inhibitor if the patient is already taking an acetylcholinesterase inhibitor (see note 1)

Dose

• Initially 5mg once daily, at the same time of day, increased in steps of 5mg at weekly intervals to maximum 20mg daily (see note 2)
• Dose titration for oral solution:
  • Week one: 0.5ml solution (5mg) per day for 7 days
  • Week two: 1ml solution (10mg) per day for 7 days
  • Week three: 1.5ml solution (15mg) per day for 7 days
  • Week four: 2ml solution (20mg) per day (maintenance / maximum dose)
• Hepatic impairment: Not recommended in severe hepatic impairment due to lack of data
• Renal impairment: Mild renal impairment (creatinine clearance 50-80ml/min), no dose adjustment required. Moderate renal impairment (creatinine clearance 30-49ml/min) the daily dose should be 10mg (1ml solution). If tolerated well after at least 7 days, the dose could be increased up to 20mg/day (2mls solution) following the titration scheme. Severe renal impairment (creatinine clearance 5-29ml/min) the daily dose should be 10mg (1ml solution).

Notes

1. See Prescribing for Alzheimer’s disease for guidance on initiating memantine in patients already taking acetylcholinesterase inhibitors
2. Clinicians should consider the patient and the support available to them in deciding on the most appropriate option for dose titration on initiation of treatment. The Summary of Product Characteristics for 10mg tablets indicates these can be used for dose titration but this involves halving the tablet to achieve some doses. The titration packs are non-formulary due to their higher cost.
3. Ensure the person administering the oral solution pump is familiar with its safe usage

Rivastigmine

• Capsule 1.5mg, 3mg, 4.5mg, 6mg (£6.78 = 2 x 3mg twice daily)
• Oral solution sugar free 2mg/ml (£96.82 = 120ml)
• Patches 4.6mg/24 hours, 9.5mg/24 hours, 13.3mg/24 hours (click here for preferred brand)

Indications

• Mild to moderate dementia in Alzheimer's disease (oral or transdermal)
• Mild to moderate dementia in Parkinson's disease (oral) (see note 1)

Dose

• Oral, initially 1.5mg twice daily, increased in steps of 1.5mg twice daily at intervals of at least 2 weeks according to response and tolerance. Usual range 3-6mg twice daily; maximum 6mg twice daily. If treatment interrupted for more than three days, treatment should be re-titrated from 1.5mg twice daily
• Transdermal application:
  • Initially apply 4.6mg/24 hours patch, removing after 24 hours and siting a replacement patch on a different area. After at least 4 weeks, and if well tolerated, increase to usual maintenance dose of 9.5mg/24 hours patch daily
  • After a further 6 months if well tolerated and cognitive deterioration or functional decline are demonstrated, the dose can be increased to 13.3mg/24 hours patch daily (caution in patients with body weight less than 50 kg)
  • If treatment interrupted for more than three days, treatment should be re-titrated from 4.6mg/24 hours patch
• Hepatic and renal impairment: oral formulations and patches, no dose adjustment is necessary for mild to moderate hepatic or renal impairment - titrate according to individual tolerability. Follow closely as patients with clinically significant hepatic or renal impairment might experience more dose dependent reactions. Patients with severe hepatic impairment have not been studied. Particular caution should be exercised in titrating these patients.

Notes

1. NICE guidance NG71 Parkinson’s disease in adults: includes recommendations for the use of acetylcholinesterase inhibitors for mild, moderate and severe Parkinson’s disease dementia. The guidance notes that oral formulations of rivastigmine are licensed for mild and moderate dementia in Parkinson’s disease; the use of rivastigmine patches, donepezil and galantamine is off-label for mild and moderate dementia in Parkinson’s disease; and the use of all acetylcholinesterase inhibitors is off-label for severe Parkinson’s disease dementia
2. MHRA Drug Safety Update (December 2014): Rivastigmine transdermal patch: risk of medication errors
   1. Symptoms of rivastigmine overdose include nausea, vomiting, diarrhoea, hypertension, and hallucinations; bradycardia and/or syncope, associated with malaise or falls, may also occur.
   2. In case of suspected overdose, all rivastigmine patches should be removed immediately and no further patch should be applied for the next 24 hours
   3. It is important to instruct patients and caregivers on the proper use of the transdermal patch, particularly that:
      1. Only one patch should be applied per day to healthy skin on the upper or lower back, upper arm, or chest
      2. The patch should be replaced by a new one after 24 hours, and the previous day's patch must be removed before application of a new patch to a different skin location
      3. Application to the same skin location within 14 days should be avoided to minimise skin irritation
      4. The patch should not be cut into pieces
3. Where a preferred brand is recommended for a particular presentation, prescribing by brand helps ensure cost-efficient use of local NHS resources (see preferred brand link above)