Galantamine (Reminyl)

All acetylcholinesterase inhibitors are PBS listed for mild to moderately severe Alzheimer’s disease.

The clinical criteria for initiation are as follows:

1. Patients must have a baseline sMMSE of 10 or more
2. The diagnosis MUST be confirmed by, or in consultation with a specialist / consultant physician (including psychiatrist)
3. The treatment must be the sole PBS subsidized therapy for this condition

For patients with a sMMSE score of 9 or less, then 1 or more of the following criteria must be met:

1. Unable to communicate adequately because of lack of competence in English, in people of non-English speaking background
2. Limited education, defined by <6 years of education, or who are illiterate or innumerate
3. Aboriginal or Torres Strait Islanders who, by virtue of cultural factors, are unable to complete an S(sMMSE)
4. Intellectual disability
5. Significant sensory impairment despite best correction, which precludes completion of an S(sMMSE)
6. Prominent dysphasia, out of proportion to other cognitive and functional impairment

These patients will need to be assessed using the Clinicians Interview Based Impression of Severity (CIBIS) scale. This will require referral to CDAMS clinic for specialist review.

• Before prescribing, note the patients sMMSE score, weight, baseline BP, falls history over the past 12 months, and perform an ECG
• Choose to dose with the best meal. Dosing with food is recommended and considered more important to improve tolerance than night time dosing.
• Do not add anti-cholinergic agent for urgency symptoms
• Check for postural hypotension if patient presents with falls, dizziness or fainting
• Most adverse effects are dose and/or time (24-48 hours) related and can be minimised by slow titration of the dose.
• Omit 1 or more doses if adverse effects occur; reduce to previous well-tolerated dose if adverse effects persist
• If treatment is interrupted for several days, restart at initial dosage to minimise the risk of severe vomiting
• Transdermal Rivastigmine patch may be suitable for patients who cannot tolerate oral medications
• People who have been prescribed an acetylcholinesterase inhibitor or memantine should be reviewed within a short time (e.g., one month) for evaluation of adverse effects and dose titration within three months, to determine whether there is a clinically meaningful response to treatment. Review and consideration of de-prescribing is recommended at regular intervals including at the time of admission to residential care.
• Discontinuation due to significant adverse effects is common, particularly gastrointestinal symptoms
• If patients tolerate and appear to benefit from cognitive enhancing drugs then they should not be ceased until the patient is in an advanced state of dementia
• Acetylcholinesterase inhibitors should not be prescribed for people with mild cognitive impairment

Precautions

• Risk of aggravation with a history of seizure, heart block, bradyarrythmias, peptic ulcer disease, Parkinson’s disease, asthma, obstructive pulmonary disease
• GI or ureteric obstruction – contraindicated
• Active peptic ulcer – contraindicated
• Renal – reduced clearance in renal impairment, titrate to maximum tolerated dose. Contraindicated if CrCl <10ml/min

• Avoid treatment combination with anticholinergic agents – antagonizes therapeutic benefit
• Severe hepatic impairment – contraindicated (reduce dosage in moderate impairment)

Adverse effects

• Common but usually only lasts 24-48 hours - nausea, vomiting, diarrhea, anorexia, abdominal pain, dyspepsia, headache, insomnia, vivid dreams, depression, fatigue, drowsiness,
• Common (>1%) – weight loss, dizziness and falls, urinary incontinence and frequency, muscle cramps, tremor, sweating, hypertension, fainting
• Infrequent or rare - bradycardia, heart block, seizure, agitation, hallucination, confusion, GI hemorrhage, increased libido, hypersensitivity
• Rare – Severe skin reactions (Steven Johnson syndrome, Acute generalized exanthematous pustulosis, erythema multiforme), Neuroleptic Malignant Syndrome

Galantamine orally (Reminyl, Galantyl)

1. Initially 8mg prolonged release daily (morning) for a minimum of 4 weeks.
2. Increase to 16mg daily (morning) if tolerated.

Clinical criteria for continuing treatment are as follows:

1. Patient must have received six months of sole PBS-subsidised initial therapy with this drug
2. Patient must demonstrate a clinically meaningful response to the initial treatment between 3-6 months
3. Treatment must be the sole PBS subsidised therapy for this condition

Prior to continuing treatment, assess response by re-assessing cognitive, functional and behavioural responses. A repeat sMMSE and history from the patient, the patient’s family, or carer should be documented. The GP should use this information to establish agreement that treatment is continuing to produce worthwhile benefit.

Treatment should cease if there is no agreement of benefit as there is always the possibility of harm from unnecessary use.

Re-assessments for a clinically meaningful response are to be undertaken and documented every six months.

Clinically meaningful response to treatment is demonstrated in the following areas:

• The stabilisation, lack of significant decline, or slowing of decline
• Patient's quality of life including but not limited to level of independence and happiness
• Patient's cognitive function including but not limited to memory, recognition and interest in environment
• Patient's behavioural symptoms, including but not limited to hallucination, delusions, anxiety, marked agitation or associated aggressive behaviour
• Also consider the patients family’s perception of ongoing benefit