Mild to Moderate Alzheiner’s Disease
Severe Alzheimer’s Disease
Increases acetylcholine by inhibiting acetylcholinesterase, thereby increasing cholinergic function.
Use Cautiously in:
CNS: headache, abnormal dreams, depression, dizziness , drowsiness, fatigue, insomnia , syncope, sedation (unusual) .
CV: atrial fibrillation, hypertension, hypotension, vasodilation .
GI: diarrhea , nausea, anorexia, vomiting, weight gain (unusual).
GU: frequent urination.
Metab: hot flashes , weight loss.
MS: arthritis , muscle cramps.
Anticholinergic drugs (eg, atropine)
Possible reduction of anticholinergic effects. Monitor the clinical response and adjust treatment dose as needed.
Aspirin, NSAIDs (eg, ibuprofen, naproxen)
Donepezil increases gastric acid secretions caused by increased cholinergic activity. The risk of stomach ulcers may be increased. Therefore, monitor for active or occult GI bleeding.
Cholinesterase inhibitors/cholinomimetics (eg, bethanechol, succinylcholine)
Synergistic effects may occur. Monitor the clinical response and adjust treatment dose as needed.
CYP2D6 and CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin)
May increase donepezil rate of elimination, decreasing donepezil plasma concentrations. Monitor the clinical response and adjust the donepezil dose as needed.
CYP2D6 and CYP3A4 inhibitors (eg, ketoconazole, quinidine)
May inhibit donepezil metabolism, increasing donepezil plasma concentrations. Monitor the clinical response and adjust the donepezil dose as needed.
Therapeutic Classification: anti-Alzheimers’s agents
Pharmacologic Classification: cholinergics (cholinesterase inhibitors)
Absorption: Well absorbed after oral administration.
Protein Binding: 96%.
Metabolism/Excretion: Partially metabolized by the liver (CYP2D6 and CYP3A4 enyzmes) and partially excreted by kidneys (17% unchanged). Two metabolites are pharmacologically active.
Half-life: 70 hr.
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