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acetylcholinesterase

acetylcholinesterase

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Published by: biochemi on Jan 29, 2011
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01/28/2013

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Acetylcholinesterase Inhibitors
[Developed, April 2006; Revised, January 2010]MEDICAID DRUG USE REVIEW CRITERIA FOR OUTPATIENT USEInformation on indications for use or diagnosis is assumed to be unavailable. All criteria may be appliedretrospectively; prospective application is indicated with [*].1.*
Dosage
 
 Adults
All available acetylcholinesterase inhibitors (ACIs) are
FDA-approved in adults
for the management of mild to moderate Alzheimer’s dementia,
while donepezil is also FDA-approved for management of severe Alzheimer’s disease. Additionally, rivastigmine (Exelon®) is FDA-approved for use in mild tomoderate dementia associated with Parkinson’s disease.
Alzheimer’s disease is associated withsignificant losses in cholinergic neurons and decreased concentrations of acetylcholine, a neurotransmittersignificantly involved in learning and memory processes. ACIs exert pharmacologic effects by increasingavailability of intrasynaptic acetylcholine in the presence of intact cholinergic neurons. Recommended
adult
dosages are summarized in Table 1.
Table 1Recommended Adult Dosages for ACIs
 
 Drug Name Maximum Recommended Dosage
Donepezil (Aricept®,
Aricept® ODT
)
tablets (5 mg, 10 mg)oral solution (1 mg/ml)orally disintegrating tablets (5 mg, 10 mg)
 10 mg/day, as a single doseGalantamine (Razadyne®)
immediate-release:tablets (4 mg, 8 mg, 12 mg)oral solution (4 mg/ml)extended-release:capsules, extended-release (8 mg, 16 mg, 24 mg)
 
immediate-release: 24 mg/day, in 2 divided dosesextended-release: 24 mg/day once daily
 Rivastigmine (Exelon®)
immediate-release:capsules (1.5 mg, 3 mg, 4.5 mg, 6 mg)oral solution (2 mg/ml)transdermal (extended-release):transdermal patch (4.6 mg/24 h, 9.5 mg/24 h)
 
immediate-release: 12 mg/day, in 2 divided dosesextended-release: 9.5 mg/24 h
 Tacrine (Cognex®)**
capsules (10 mg, 20 mg, 30 mg, 40 mg)
160 mg/day, in 4 divided doses
**This agent has largely been replaced with other available acetylcholinesterase inhibitors with more favorable dosage regimens and adverse event profiles.
Although not FDA-approved, ACIs have also been evaluated for use in vascular dementia, dementia withLewy bodies,
post stroke aphasia, and memory improvement in multiple sclerosis patients
.
 
 Pediatrics
 ACIs are not recommended for use in children, as adequate, well-controlled clinical trials have notdocumented safety and efficacy of these agents for any disease state in the pediatric population.
 
2.
Duration of Therapy
 ACIs do not alter the long-term progressive decline of Alzheimer’s disease, but have been shown todelay time to institutionalization, which may be cost-effective. ACI may be prescribed to stabilizedementia in Alzheimer’s patients, as determined by periodic assessment of functional and cognitiveability. ACIs should be discontinued when dementia becomes unresponsive to therapy andprogressively severe, as the efficacy of these agents diminishes due to loss of intact cholinergic neurons.3.*
Duplicative Therapy
 Combined use of two or more ACIs does not provide enhanced therapeutic benefit and may result inadditive adverse effects. Concurrent administration of two or more ACIs is not recommended and willbe reviewed.4.*
Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens which may result in clinicallysignificant drug-drug interactions.
Drug-drug interactions considered clinically relevant for ACIs are summarized in Table 2.
Onlythose drug-drug interactions classified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.

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