Therapeutic Goals

What are Cholinesterase Inhibitors (ChE-Is)?

ChE-Is are a group of drugs that are used as a part of the treatment plan for mild to moderate Alzheimer's disease. The three most commonly used ChE-Is are donepezil (Aricept, Eisai, Inc), rivastigmine (Exelon, Novartis Pharmaceuticals), and galantamine (Reminyl, Janssen Pharmaceuticals). Tacrine (Cognex, First Horizon Pharmaceutical Corp.) was the first ChE-I approved for treatment of dementia 3. However, it is not recommended for use anymore due to its negative effects on the liver. These medications can provide modest and temporary improvements in memory or slow down the rate of decline in memory, improve thinking (decision making), and improve behavior 4.

How ChE-I's work?

In Alzheimer's disease there is too little of acetylcholine in the brain; these drugs help build up acetylcholine in the brain 4.

Other Uses

ChE-Is are being tested in other conditions such as vascular dementia, lewy body dementia, Down's syndrome, and multiple sclerosis 6. This is not a complete list just some examples.

What does it mean for Caregivers: Improvement in memory leads to improvement in behavior and thinking and improves activities of daily living. This can decrease the time and the effort needed to care for the person.

Patient Caregiver
  • Slow the progression of disease
  • Cognitive Improvement: memory, decision making
  • Behavior improvement
  • Activities of Daily living improvement: toileting, washing, cleaning
  • Delay placement in the nursing home
  • Reduce Burden
  • Save Time

It is important to remember that Cholinesterase inhibitors are not a cure for Alzheimer's disease. Even if a person does not get better, it does not mean that they haven't slowed down the rate at which they are declining. Studies have shown that things like memory, thinking, and behavior may improve, get better in small ways or stay the same, or get worse over time, but slower than expected. If symptoms stay the same or get worse over time but slower than expected, it can still mean that the medication is working 2.

How does the doctor decide which ChE-I to use?

What does it mean for Caregivers: There is no way to decide which one will work better for the person you take care of. Thus, one may have to try using more than one drug. Dosing schedule may be important for caregivers; Aricept is the only one with once a day dosing.

Dosing and Side Effects

Symptom week 1 Titration week 6 Titration
Nausea 19% 6%
Vomiting 8% 3%
Diarrhea 15% 9%

* 7 Table taken from MD Consult, Aricept 10 mg

On the left, the three most common side effects, nausea, vomiting, and diarrhea, which people experience while starting cholinesterase inhibitors are listed. Week 1 titration refers to people whose Aricept dose was increased over 1 week period, while Week 6 titration refers to the group of people whose Aricept dose was slowly increased over a 6 week period. In week 1 titration, 19% of the people had nausea, while in week 6 titration group with a much slower increase in dose, only 6% reported having nausea. Similarly, the percent of people reporting vomiting also decreased from 8% to 3% from week 1 titration to a much slower week 6 titration schedule. And lastly, 15% of the patient complained of Diarrhea in week 1 titration, but in a slower titration over 6 weeks only 9% reported diarrhea.

More drug is not necessarily better. Make sure not to exceed the prescribed dose.

Drug Name and Manufacturer's Recommended Dosage and Titration Schedule 1,8

Aricept (donepezil)

  • Initial dose is 5mg once a day taken in the evening right before going to bed
  • Increase after 4-6 weeks to 10mg once a day if well tolerated.

Exelon (rivastigmine)

  • Initial dose is 1.5mg twice a day (3mg/day) taken with morning and evening meals
  • Increase dose as tolerated but no more than by 1.5 mg twice a day (3mg/day) every 2 weeks
  • Maximum titration can be done till 6mg twice a day (12mg/day) if well tolerated.

Liquid form also available in 2mg/mL solution

Reminyl (galantamine)

  • Initial dose is 4mg twice a day (8mg/day) taken with morning and evening meals for 4 weeks
  • Increase by 8mg/day after 4 weeks to 8mg twice a day (16mg/day) if well tolerated.
  • After another 4 weeks, increasing to 12mg twice a day (24mg/day) can be considered on individual basis, depending on clinical benefit and tolerability

Liquid form also available in 4mg/mL solution

* created using information from References 1, 3 & 8

Side Effects of Cholinesterase Inhibitors 3

Report to your prescriber or health care professional as soon as possible:

Usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):

Nausea/vomiting, Diarrhea, and indigestion can be severe especially when the medication is first started. These can be reduced if the medications are taken WITH food.

Drug Interactions

What does it mean for Caregivers: Do not start, stop, or change drug, dosage, or frequency without consulting the doctor of pharmacist. Before a new medication is started, always make sure the doctor is aware of all the other medications the person you take care of is taking. Even though over-the-counter medications and herbal supplements are available without prescription they still can interfere with the way prescription medications work. Always check with the pharmacist before taking any new over-the-counter medication and herbal supplement.

Cautions

Before starting a ChE-I, tell your doctor if the person you are caring for has any of the following conditions 3:

What does it mean for Caregivers: It is important to tell the health care provider of any of the above mentioned conditions because they may interfere with the way ChE-Is work or may cause harm to the one you are taking care of.

Starting, Interrupting or Switching ChE-Is

What does it mean for Caregivers: once diagnosis is made, start the treatment early.

Dosage Forms and Administration Recommendations 3, 8

What does it mean for Caregivers: If the person you are taking care of cannot swallow a tablet whole there are two options: Reminyl and Exelon are available in liquid formulation or Exelon capsule that can be sprinkled.

Using Cholinesterase Inhibitor with Namenda

What does it mean for Caregivers: Since Namenda works by a different mechanism than ChE-Is, when added to the treatment it can further improve memory than ChE-I alone. Improvement in memory can mean improvements in behavior and activities of daily living. This can further decrease the number of hours the caregivers work spend and the effort it takes for the caregivers.

References

1. Alzheimer's disease education & referral center. Available at www.alzheimers.org Accessed on November 8, 2004.

2. Aricept website. Available at www.aricept.com Accessed on November 8, 2004.

3. Clinical Pharmacology, Version 2.13. Gold Standard Multimedia. Copyright 2004.

4. Cummings JL, Cherry D, Kohatsu ND, et al. Guidelines for Managing Alzheimer's Disease: Part II. Treatment. Accessed from: www.aafp.org/afp Accessed on November 5, 2004.

5. Hartmann S, Mobius HJ. Tolerability of memantine in combination with cholinesterase inhibitors in dementia therapy. International Clinical Psychopharmacology. 2003;18:81-85.

6. Jones RW. Have cholinergic therapies reached their clinical boundary in Alzheimer's disease? International Journal of Geriatric Psychiatry. 2003;18: S7-S13.

7. MD Consult. Available at http://www.mdconsult.com/ Accessed on November 8, 2004.

8. Package Insert for Aricept , Reminyl , and Exelon

9. Tariot PN, Farlow MR, Grossberg GT et al. Memantine treatment in patients with moderate to sevre Alzheimer disease already receiving donepezil. Journal of American Medical Association. 2004;291(3):317-324.

10. Lacy CF, Armstrong LL, Goldman MP et al. Lexi-Comp's Drug Information Handbook. 12 th Edition.

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College of Public Health and Health Professions, University of Florida