Drugs for cognitive loss and dementia

Clinical Studies – The results of a 3-year randomized, double-blind trial comparing donepezil 10 mg/day or vitamin E 2000 IU/day with placebo in 769 patients with MCI did not show any si

Treatment Guidelines

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IN THIS ISSUE (starts on next page)

Drugs for Cognitive Loss and Dementia p 95

Drugs for Cognitive Loss and Dementia

Tables

1 FDA-Approved Drugs for Alzheimer’s Disease Page 97

Treatment Guidelines

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Volume 11 (Issue 134) October 2013

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Take CME exams

Alzheimer’s disease (AD) is the most common cause

of dementia, but cognitive loss is also associated with

other neurological conditions such as Parkinson’s

dis-ease, dementia with Lewy bodies, and vascular

dementia Mild cognitive impairment (MCI) is

gener-ally defined as cognitive decline greater than expected

for an individual’s age and educational level, but not

interfering with activities of daily living; it may be a

transitional state between the cognitive changes of

normal aging and dementia.1

Treatment of reversible dementia due to drug toxicity,

infections, or metabolic disorders is not included here

ACETYLCHOLINESTERASE INHIBITORS

Cognitive loss in AD is associated with depletion of

acetylcholine, which is involved in learning and

mem-ory Acetylcholinesterase inhibitors increase the

con-centration of acetylcholine and may have beneficial

effects on the symptoms of dementia, but can also

cause adverse cholinergic effects such as nausea,

vom-iting, and diarrhea Bradycardia and syncope can occur, and an increased incidence of hip fracture has been reported in elderly patients taking these agents.2

Concurrent use of drugs with anticholinergic effects, including first-generation antihistamines, such as

diphenhydramine (Benadryl, and others), drugs for overactive bladder, such as oxybutynin (Ditropan, and

others), or tricyclic antidepressants, such as imipramine

(Tofranil, and others), may decrease the activity of

acetylcholinesterase inhibitors All three of the acetyl-cholinesterase inhibitors in Table 1 are approved by the FDA for treatment of mild to moderate AD dementia; donepezil and transdermal rivastigmine are also approved for treatment of severe AD dementia Rivastigmine is the only acetylcholinesterase inhibitor approved for treatment of mild to moderate dementia associated with Parkinson’s disease

DONEPEZIL — Donepezil (Aricept, Aricept ODT,

and generics) is a centrally active, reversible inhibitor

of acetylcholinesterase with little peripheral activity.3

It is approved for treatment of mild, moderate, or severe AD dementia

Pharmacokinetics – Donepezil is rapidly absorbed

from the gastrointestinal tract, reaching peak plasma concentrations in 3-4 hours with the 10-mg tablet and

in about 8 hours with the 23-mg tablet It is metabo-lized primarily by CYP2D6 and 3A4 and is excreted

in urine Donepezil has a half-life of about 70 hours, allowing once-daily administration

Clinical Studies – The results of a 3-year randomized,

double-blind trial comparing donepezil 10 mg/day or vitamin E 2000 IU/day with placebo in 769 patients

with MCI did not show any significant differences in

the probability of progression from MCI to AD, except during the first year of the study when the donepezil group had a significantly lower rate of progression to

AD.4Another placebo-controlled trial in 821 patients

The drugs currently available for the treatment of

Alzheimer’s disease and other dementias can provide

limited symptomatic improvement The

acetyl-cholinesterase inhibitors donepezil, rivastigmine, and

galantamine and the NMDA-receptor antagonist

memantine have produced modest but apparently

persistent improvements in cognition, activities of

daily living, and behavior in patients with disease

severity ranging from mild to severe Among the

acetylcholinesterase inhibitors, transdermal

rivastig-mine causes fewer gastrointestinal side effects than

the oral formulation Whether adding memantine to

an acetylcholinesterase inhibitor is more effective

than an acetylcholinesterase inhibitor alone remains

to be established; clinical trial results have been

mixed None of these agents have been shown to stop

or reverse the underlying neurodegenerative process

For further information call: 800-211-2769

Related article(s) since publication

Drugs for Cognitive Loss and Dementia

Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 134) • October 2013

with MCI followed for 48 weeks showed that

donepezil had a small but significant effect on

cogni-tion, but no effect on global function.5

FDA approval of donepezil for treatment of severe AD

dementia was based on 2 studies One randomized,

placebo-controlled, double-blind 24-week trial in 248

patients with severe AD dementia living in nursing homes

found improvements in activities of daily living,

cogni-tion, and global function with donepezil, but no difference

in behavior.6In the second study, a 24-week randomized,

double-blind, placebo-controlled trial in 343 ambulatory

outpatients with severe AD dementia, donepezil was

more effective than placebo on measures of cognition and

global function.7Discontinuation of donepezil in patients

with moderate to severe AD dementia has been

associat-ed with cognitive and functional decline.8 A trial of

donepezil for treatment of agitation in 272 patients with

AD dementia failed to show improvement.9

The results of some small, short-term (10-26 weeks)

placebo-controlled trials have suggested a modest

improvement in cognition, global function, and

activi-ties of daily living with donepezil in patients with

dementia associated with Parkinson’s disease and in

those with dementia associated with Lewy bodies.10,11

In patients with vascular dementia treated with

donepezil, some randomized, double-blind,

placebo-con-trolled 24-week trials have shown statistically significant

improvements in cognition and global functioning.12,13

Dosage – The initial dosage of donepezil is 5 mg once

daily for at least 4-6 weeks The dose can then be

increased to 10 mg once daily Donepezil 5 mg per day

has been safe and well tolerated in patients with

impaired hepatic or renal function It is also available

as 23-mg tablets marketed for patients with a

subopti-mal response to lower doses, but the larger dose has

marginal benefits at best and causes a substantial

increase in gastrointestinal side effects.14,15

Adverse Effects – The most common adverse effects

of donepezil have been nausea, vomiting, and diarrhea,

particularly when the drug is started or the dose is

increased Urinary incontinence, vivid dreams,

brady-cardia, and syncope have also occurred Fatigue and

muscle cramps have been reported Higher plasma

lev-els of the drug and possibly a higher incidence of

adverse effects might occur in the 7% of the population

who are CYP2D6 poor metabolizers

Drug Interactions – In addition to interactions with

drugs that have anticholinergic or cholinergic effects,

donepezil could potentially interact with inhibitors or

inducers of CYP3A4 or 2D6.16

96

GALANTAMINE — Galantamine (Razadyne,

Razadyne ER, and generics) is a reversible, competitive

inhibitor of acetylcholinesterase It also acts on nico-tinic acetylcholine receptors; the clinical significance

of its nicotinic activity remains to be established Galantamine is FDA-approved for treatment of mild to moderate AD dementia

Pharmacokinetics – Galantamine is rapidly absorbed

from the gastrointestinal tract Serum concentrations of the immediate-release (IR) formulation peak in about one hour without food and in about 2.5 hours with food The median time to peak (Tmax) with the extended-release (ER) formulation is 4.5-5 hours Galantamine is metabolized in the liver by CYP2D6 and 3A4 to metabolites that have little anticholinesterase activity

Clinical Studies – In short-term (5-6 months) trials in patients with mild to moderate AD dementia,

galan-tamine showed some benefits in cognitive and clinical global measures compared to placebo.17

In two 2-year randomized, placebo-controlled trials in

2048 patients with MCI, there was no difference in the

rate of progression to AD dementia between the placebo- and galantamine-treated groups.18

Several trials (6-12 months) in AD dementia patients

with vascular dementia have shown significant

improvement in cognition, behavior, and activities of daily living with galantamine treatment.19,20

Dosage – The initial dose of galantamine is 8 mg daily

with food, taken either as 4 mg twice daily of the IR formulation or 8 mg once daily of the ER formulation The dose can then be increased to 16 mg per day after

4 weeks and then to 24 mg after another 4 weeks The maximum dose should be limited to 16 mg/day in patients with moderate hepatic or renal impairment; the drug should be avoided in patients with severe hepatic or renal impairment If treatment is interrupted for >3 days, galantamine should be restarted at the lowest daily dose

Adverse Effects – The most common adverse effects

of galantamine are nausea, vomiting, diarrhea, dizzi-ness, anorexia, and weight loss, reported mostly during rapid dose escalation and less commonly during main-tenance treatment Bradycardia and syncope can occur Depression, fatigue, and somnolence have been

report-ed In one study in patients with MCI, more deaths occurred with galantamine treatment than with

place-bo, probably due to an unusually low mortality rate in the placebo group.18 A higher incidence of death has not been reported in patients with AD dementia treated with galantamine Higher plasma levels of the drug

and possibly a higher incidence of adverse effects

might occur in the 7% of the population who are

CYP2D6 poor metabolizers

Drug Interactions – In addition to interactions with

drugs that have anticholinergic or cholinergic effects,

galantamine could potentially interact with drugs that

inhibit or induce CYP2D6 or 3A4

RIVASTIGMINE — Rivastigmine (Exelon, and

gener-ics; Exelon Patch) is a carbamate-based, slowly

reversible, non-competitive cholinesterase inhibitor

with good penetration into the central nervous system.21

The drug is FDA-approved for treatment of mild to

moderate dementia associated with AD or Parkinson’s

disease; the transdermal patch is also approved for

severe AD dementia

Pharmacokinetics – The oral formulation of

rivastig-mine is rapidly absorbed from the gastrointestinal

tract, reaching peak plasma concentrations in about 1

hour without food and in about 2.5 hours with food

The drug binds weakly to plasma proteins and has a

short life in plasma (1.5 hours), but it has a

half-life for cholinesterase inhibition in the central nervous

system of about 10 hours, which permits twice-daily

dosing Rivastigmine is metabolized mainly through

hydrolysis by esterases and is excreted in urine

Clinical Studies – A review of 9 double-blind,

ran-domized, placebo-controlled trials involving 4775

patients with mild to moderate AD dementia found

that oral rivastigmine 6-12 mg per day slowed the rate

of decline in cognitive function, improved activities of daily living, and decreased the severity of dementia.22

In a 24-week study in 1195 patients with severe AD dementia, a rivastigmine 9.5 mg/24 hours patch was

as effective as the highest dose of capsules, with about three times fewer reports of nausea and vomiting.23 In another 24-week double-blind trial, 716 patients with severe AD dementia were randomized to receive rivastigmine patches containing 4.6 or 13.3 mg/24 hours At the end of the study, the mean decline from baseline on assessments of cognition and overall func-tion was significantly less with the 13.3 mg patch.24

A randomized, double-blind, placebo-controlled 24-week trial found statistically significant improvements

in attention and cognition with rivastigmine in 541

patients with dementia associated with Parkinson’s disease.25A double-blind, placebo-controlled 20-week

trial of rivastigmine in 120 patients with dementia with Lewy bodies found clinically and statistically

signifi-cant improvement in behavior in the treatment group.26

Dosage – The usual starting dosage of oral

rivastig-mine is 1.5 mg twice daily with food The dose can be

Drug Formulations Usual Dosage Starting Dose/Titration Cost 1

Acetylcholinesterase Inhibitors

Donepezil – generic 5, 10, 23 mg tabs 5-10 mg once/d 5 mg once/d; after 4-6 wks $9.00 Aricept (Eisai/Pfizer) increase to 10 mg once/d; if 353.00 orally disintegrating – generic 5, 10 mg orally suboptimal response to 10 mg 50.00 Aricept ODT (Eisai/Pfizer) disintegrating tabs after 3 months, can consider 353.00

increasing to 23 mg Galantamine – generic 4, 8, 12 mg tabs; 16-24 mg divided 8 mg/d divided bid; after 4 wks 146.00 Razadyne 2 (Janssen) 4 mg/mL soln bid with meals increase to 16 mg/d, then 241.00

after 4 wks more to 24 mg/d extended-release – generic 8, 16, 24 mg ER caps 16-24 mg once/d 8 mg once/d; after 4 wks 140.00 Razadyne ER (Janssen) with meals increase to 16 mg/d, then 241.00

after 4 wks more to 24 mg/d Rivastigmine – generic 1.5, 3, 4.5, 6 mg caps 9-12 mg divided 3 mg/d divided bid; increased 164.00 Exelon (Novartis) 1.5, 3, 4.5, 6 mg caps; bid with meals in increments of 3 mg/d q 2 wks 3 285.00

2 mg/mL soln to 12 mg/d transdermal

Exelon Patch (Novartis) 4.6 mg/24 hours, 9.5 mg/24 hours 4.6 mg/24 hours; after 4 wks 296.00

9.5 mg/24 hours, increase to 9.5 mg/24 hours;

13.3 mg/24 hours after an additional 4 wks

increase to 13.3 mg/24 hours

NMDA-Receptor Antagonist

Memantine – 5, 10 mg tabs; 10 mg bid 5 mg once/d; increase in

Namenda (Forest) 2 mg/mL soln increments of 5 mg q wk 265.00

to 20 mg/d divided bid extended-release

Namenda XR (Forest) 7, 14, 21, 28 mg ER caps 28 mg once/d 7 mg once/d; increase to 28 mg/d 252.00

in increments of 7 mg q wk

ODT = orally disintegrating tablet; ER = extended release

1 Approximate cost for 30 days’ treatment with the lowest usual dosage Source: $ource® Monthly (Selected from FDB MedKnowledge™) September 5, 2013 Reprinted with permission by FDB, Inc All rights reserved ©2013 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher.

2 Formerly Reminyl.

3 Every 4 weeks for dementia associated with Parkinson’s disease.

Table 1 FDA-Approved Drugs for Alzheimer’s Disease

Drugs for Cognitive Loss and Dementia

Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 134) • October 2013

increased in 1.5-mg increments at 2-week intervals, up

to a maximum daily dose of 12 mg No dosage

adjust-ments are required for renal or hepatic impairment If

treatment is interrupted for several days, rivastigmine

should be restarted at the lowest daily dose

The transdermal formulation, which requires daily

applications of a rivastigmine patch, may be a more

reliable method of administration in demented

patients.27 The initial dose is one 4.6 mg/24 hours

patch, placed in rotation around the back, chest, or

upper arm After one month, the dose can be

increased to 9.5 mg/24 hours; subsequent escalation

after another 4 weeks to a 13.3 mg/24 hours patch

may provide additional benefit.28 If treatment is

inter-rupted for >3 days, it should be restarted with the

lowest-dose patch

Adverse Effects – Oral rivastigmine causes a high

inci-dence of nausea, vomiting, and diarrhea, which can be

reduced if titration is slow and the drug is taken with

food These effects appear to be substantially less

fre-quent with the transdermal formulation Bradycardia

and syncope can occur

Drug Interactions – Except for interactions with

drugs that have anticholinergic or cholinergic effects,

rivastigmine has no well-documented drug

interac-tions It is not metabolized by CYP450 isozymes

CHOICE OF DRUG — Donepezil, galantamine, and

rivastigmine appear to have similar efficacy and similar

adverse effects, however independent comparative

tri-als among the acetylcholinesterase inhibitors are

lack-ing Transdermal rivastigmine may be better tolerated

than the oral formulation Both donepezil and

rivastig-mine have documented efficacy in vascular dementia

and dementia associated with Parkinson’s and Lewy

body disease Galantamine has documented efficacy in

vascular dementia

NMDA-RECEPTOR ANTAGONIST

MEMANTINE — An N-methyl-D-aspartate

(NMDA)-receptor antagonist, memantine (Namenda) is approved

by the FDA for treatment of moderate to severe AD

dementia.29 Its mechanism of action in AD is unclear; it

may reduce glutamatergic overstimulation at the NMDA

receptor, which could have symptomatic benefits.30

Pharmacokinetics – Memantine is well absorbed

fol-lowing oral administration, with peak plasma

concen-trations achieved in about 3-7 hours The terminal

elimination half-life is between 60-80 hours

Memantine is excreted primarily in urine

98

Clinical Studies – In 252 patients with moderate to severe AD dementia, a 28-week double-blind trial

found that memantine treatment resulted in modest, but statistically significant, benefits in global, func-tional, and cognitive scores, compared to placebo.31

One placebo-controlled study in patients with moder-ate to severe AD dementia already receiving donepezil found that adding memantine led to

signif-icantly better outcomes on measures of cognition, behavior, activities of daily living, and global improvement.32Addition of extended-release meman-tine to a cholinesterase inhibitor in patients with mod-erate to severe AD dementia also led to significantly better outcomes, compared to adding a placebo, on measures of cognition and global improvement.33

However, in a double-blind, placebo-controlled trial

in 295 patients with moderate to severe AD dementia already receiving donepezil, adding memantine did not result in significantly better scores on measures of cognition and activities of daily living compared to continuing donepezil alone.8 In a prospective,

double-blind 24-week study in 433 patients with mild to moderate AD dementia already taking a cholinesterase inhibitor, adding memantine was no

more effective than adding placebo.34

Memantine 20 mg/day has been reported to improve

cognition in patients with mild to moderate vascular dementia35,36and may be effective in dementia with Lewy bodies.37

Dosage – The initial dosage of memantine is 5 mg

once daily The dose can be titrated up in weekly incre-ments of 5 mg to a final dose of 20 mg daily, usually given as 10 mg twice a day The once-daily ER formu-lation is started at a dose of 7 mg and titrated up in increments of 7 mg weekly to a target dose of 28 mg daily No dosage adjustments are needed for patients with mild to moderate renal impairment; for those with severe renal impairment, the maximum recommended dose is 5 mg twice daily or one 14-mg ER tablet daily

Adverse Effects – Memantine is usually well

tolerat-ed Adverse effects have included dizziness, confusion, insomnia, hallucinations, and delusions

Drug Interactions – Memantine does not affect the

inhibition of acetylcholinesterase by cholinesterase inhibitors Amantadine, which is used to treat Parkinson’s disease, is also an NMDA-receptor antag-onist and theoretically might have an undesirable additive effect if used concurrently Memantine does not appear to interact with drugs metabolized by CYP450 isozymes

Although not approved for such use by the FDA,

antipsychotic drugs are widely used to treat agitation

and other behavioral symptoms in elderly patients,

especially those with dementia.38 Second-generation

antipsychotics used in low doses have generally been

preferred because they have fewer extrapyramidal

effects than the first-generation drugs

Efficacy in AD Dementia – Although many clinicians

believe that use of second-generation antipsychotics

such as aripiprazole (Abilify), quetiapine (Seroquel),

risperidone (Risperdal), or olanzapine (Zyprexa) to

calm agitated or aggressive patients with dementia is

beneficial, controlled-trial evidence for the efficacy of

antipsychotic medications in dementia is limited One

placebo-controlled 36-week trial in 421 outpatients

with AD dementia found some benefit from

antipsy-chotics for behavioral symptoms such as anger,

aggres-sion, and paranoid ideation, but no improvement in

functioning, care needs, or quality of life.39

Adverse Effects – Common adverse effects of

antipsychotic drugs include somnolence, gait changes,

and extrapyramidal effects One study in 421 patients

with AD dementia found that cognitive function

declined more in patients receiving antipsychotics than

in those given a placebo.40 The FDA has reported that

elderly patients with dementia treated with

second-generation antipsychotics in randomized, controlled

trials had a 1.6-1.7 times higher mortality rate than

those receiving placebo Most of the deaths were due

to cardiovascular or infectious causes The FDA

requires manufacturers of antipsychotics to include a

warning in the labeling about an increased risk of death

among elderly patients with dementia

The FDA also requires all manufacturers of

second-generation antipsychotics to include product-label

warnings about the risk of hyperglycemia and diabetes

Some second-generation drugs, particularly clozapine

(Clozaril, and others) and olanzapine, probably cause

more weight gain than first-generation drugs.41 The

second-generation drugs are less likely to cause

extrapyramidal symptoms, tardive dyskinesia, and

neuroleptic malignant syndrome Extrapyramidal

effects of antipsychotics have been reported to increase

in patients also taking an acetylcholinesterase

inhibitor.42 QTc prolongation has been reported,

partic-ularly with ziprasidone (Geodon).

GINKGO BILOBA

The dietary supplement Ginkgo biloba has been used

worldwide and is heavily promoted in the US for

pre-vention of dementia and other indications Double-blind, randomized trials have found that it was not effective in preventing or treating dementia or for pre-venting cognitive decline in older adults.43,44,45

MEDICAL FOODS

Two “medical foods”, Axona and CerefolinNAC, are

currently marketed for use in AD Their effectiveness remains to be established and their long-term safety is unknown.46,47

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4 RC Petersen et al Vitamin E and donepezil for the treatment of mild cognitive impairment N Engl J Med 2005; 352:2379.

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6 B Winblad et al Donepezil in patients with severe Alzheimer’s disease: double-blind, parallel-group, placebo-controlled study Lancet 2006; 367:1057.

7 SE Black et al Donepezil preserves cognition and global function in patients with severe Alzheimer disease Neurology 2007; 69:459.

8 R Howard et al Donepezil and memantine for moderate-to-severe Alzheimer’s disease N Engl J Med 2012; 366:893.

9 RJ Howard et al Donepezil for the treatment of agitation in Alzheimer’s disease N Engl J Med 2007; 357:1382.

10 M Rolinski et al Cholinesterase inhibitors for dementia with Lewy bod-ies, Parkinson’s disease dementia and cognitive impairment in Parkinson’s disease Cochrane Database Syst Rev 2012; (3):CD006504.

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choliner-gic approaches in the symptomatic treatment of Alzheimer’s disease.

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Copyright 2013 ISSN 1541-2792

Treatment Guidelines from The Medical Letter®

EDITOR IN CHIEF: Mark Abramowicz, M.D.

EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical

School

EDITOR: Jean-Marie Pflomm, Pharm.D.

ASSISTANT EDITORS, DRUG INFORMATION: Susan M Daron, Pharm.D., Corinne Z Morrison, Pharm.D.

CONSULTING EDITORS: Brinda M Shah, Pharm.D., F Peter Swanson, M.D CONTRIBUTING EDITORS:

Carl W Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons Vanessa K Dalton, M.D., M.P.H., University of Michigan Medical School Eric J Epstein, M.D., Albert Einstein College of Medicine

Jane P Galiardi, M.D., M.H.S., F.A.C.P., Duke University School of Medicine Jules Hirsch, M.D., Rockefeller University

David N Juurlink, BPhm, M.D., PhD, Sunnybrook Health Sciences Centre Richard B Kim, M.D., University of Western Ontario

Hans Meinertz, M.D., University Hospital, Copenhagen Sandip K Mukherjee, M.D., F.A.C.C., Yale School of Medicine Dan M Roden, M.D., Vanderbilt University School of Medicine Esperance A K Schaefer, M.D., M.P.H., Harvard Medical School

F Estelle R Simons, M.D., University of Manitoba Neal H Steigbigel, M.D., New York University School of Medicine Arthur M.F Yee, M.D., Ph.D., F.A.C.R, Weill Medical College of Cornell University SENIOR ASSOCIATE EDITOR: Amy Faucard

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Questions start on next page

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Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 134) • October 2013

1 The most common cause of dementia is:

a Parkinson’s disease

b Alzheimer’s disease

c dementia with Lewy bodies

d vascular dementia

2 Acetylcholinesterase inhibitors:

a increase concentrations of acetylcholine

b have been shown to improve symptoms of dementia

c interact with drugs that have anticholinergic effects

d all of the above

3 Which one of the following has been shown to reverse the

under-lying neurodegenerative process of Alzheimer’s disease?

a ginkgo biloba

b memantine

c donepezil

d none of the above

4 An 82-year-old woman with Alzheimer’s disease dementia

recent-ly started taking rivastigmine 3 mg oralrecent-ly twice dairecent-ly and has been

experiencing significant nausea, vomiting and diarrhea You could

tell the patient and her daughter that:

a rivastigmine is available as a transdermal patch that is less

likely to cause gastrointestinal adverse events

b other cholinesterase inhibitors do not cause any

gastroin-testinal adverse events

c quickly increasing the dose should alleviate these adverse

events

d none of the above

5 Donepezil:

a is approved for mild, moderate or severe Alzheimer’s disease

dementia

b is taken once daily

c is available generically

d all of the above

6 Adverse effects of acetylcholinesterase inhibitors include:

a nausea

b vomiting

c diarrhea

d all of the above

7 The FDA requires manufacturers to include a warning in the label-ing about an increased risk of death among elderly patients with dementia on all:

a acetylcholinesterase inhibitors

b NMDA-receptor antagonists

c antipsychotics

d ginkgo biloba products

8 Which of the following have been shown to produce modest improvements in cognition, activities of daily living, and behavior

in patients with Alzheimer’s disease dementia?

a donepezil

b memantine

c galantamine

d all of the above

9 Memantine:

a interferes with the action of acetylcholinesterase inhibitors

b is FDA-approved for treatment of moderate to severe Alzheimer’s disease dementia

c is the preferred initial treatment for patients with mild cogni-tive impairment

d all of the above

10 Adverse effects of memantine include:

a dizziness

b hallucinations

c delusions

d all of the above

11 A 68-year-old man who requires treatment for moderate dementia associated with Parkinson’s disease comes to your office Which

of the following is true?

a rivastigmine is FDA-approved for treatment of mild to moder-ate dementia associmoder-ated with Parkinson’s disease

b the use of medical foods has been proven to be safe and effective for treatment of Parkinson’s disease dementia

c the most common side effect of memantine is vomiting

d all of the above

12 Which of the following would not be affected by concurrent use of

a CYP2D6 inhibitor?

a rivastigmine

b donepezil

c galantamine

d none of the above

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Issue 134 Questions

ACPE UPN: 0379-0000-13-134-H01-P; Release: September 2013, Expire: September 2014