Cholinesterase Inhibitors

Clinical Use Parameters

• Diagnosis of mild-moderate AD or Lewy body dementia; MMSE=10-26
• Use in more severe dementia and in other disease states (vascular dementia, schizophrenia, multiple sclerosis) continues to be studied
• Assess and document baseline cognition, function, and behavioral or psychiatric symptom
  

• Active peptic ulcer disease
• Unstable asthma or COPD
• Cardiac conduction abnormalities e.g. sick sinus syndrome, heart block, sinus bradycardia, recent MI
  

• Concurrent NSAID use
• Hx of syncope or seizure
• Concurrent digoxin, b-blockers

• Tailor titration schedule to patient tolerability
• If treatment related GI adverse effects are observed, decrease the dose or dosing frequency for 7- 10 days, then attempt continued titration. Utilize antiemetics e.g. Emetrol® , if needed but avoid anticholinergic antispasmodics, such as dicyclomine.
• Donepezil given at hs may diminish GI effects
• Rivastigmine should be given with or after a meal; donepezil may also be given with food
• Galantamine is recommended to be given with food twice daily with morning and evening meals.
  
• Titrate to maximally tolerated dose if possible
• Currently available CHE-I have demonstrated linear dose-response relationships to varying degrees in clinical trials
• Donepezil titration: 5mg qhs x 4-6 weeks, then increase to 10mg qhs
• Rivastigmine titration: 1.5mg bid x 14 days, then 3mg bid x 14 days, then 4.5mg bid x 14 days, then 6mg bid
• Galantamine titration: 4 mg bid x 4 weeks, then 8 mg bid x 4 weeks, then if tolerated 12 mg bid (maximum total dose of 24 mg/day).
• For Razdyne ER™ start with 8 mg once a day. After at least 4 weeks on the starting dose (8 mg a day), the dose is increased to 16 mg a day; after at least another 4 weeks, the dose may be increased to 24 mg a day.

• Assess throughout titration period for adverse effects
• nausea/vomiting/diarrhea
• anorexia/weight loss
• dizziness
• leg cramps
• insomnia
• urinary incontinence

• Advise patient to discontinue CHE-I therapy in advance of major surgery (CHE-I may potentiate paralytic agents)

• Drug interactions
  • Donepezil and galantamine — monitor for increased incidence of cholinergic adverse effects in the presence of CYP450 2D6 inhibitors (e.g. paroxetine, etc.) or CYP450 3A4 inhibitors (e.g. nefazodone, etc.
  • Rivastigmine — no known drug interactions, drug undergoes extra-hepatic metabolism

• Assess 3 months after attaining maximum tolerated dose for effects on cognition, functioning and behavior and compare to baseline
• Improvement over baseline measures or no deterioration (stabilization) are positive outcomes
• Assess every 6 months thereafter for disease progression

• Intolerable adverse effects or lack of compliance with therapy
• Continued deterioration at pretreatment rate after 3-6 months
• Total functional dependence on caregivers, severe cognitive impairment
• Drug-free period (controversial) suggests drug is no longer effective

top of page