Dosing and uses of Aricept (donepezil)
Adult dosage forms and strengths
tablet
- 5mg
- 10mg
- 23mg
tablet, oral disintegrating
- 5mg
- 10mg
Alzheimer's Disease
Dementia of the Alzheimer's type
Mild to moderate
- 5 mg PO qHS initially, may increase to 10 mg/day after 4-6 weeks if warranted
Moderate to severe
- 5 mg PO qHS initially, may increase to 10 mg qDay after 4-6 weeks; may further increase to 23 mg/day after 3 months if warranted
Administration
Take at bedtime before retiring
Take with or without food
ODT: Dissolve on tongue and follow with water
Dose Modification
Renal Impairment
- Not studied
Hepatic Impairment
- Not studied
Pediatric dosage forms and strengths
Not recommended
Aricept (donepezil) adverse (side) effects
>10%
Nausea (3-19%)
Diarrhea (5-15%)
Insomnia (2-14%)
Accident (7-13%)
Infection (11%)
1-10%
Headache (3-10%)
Vomiting (3-8%)
Cramping (3-8%)
Fatigue (3-8%)
Anorexia (2-8%)
Hypertension (3% )
Abnormal dreams (3%)
Hallucinations (3%)
Confusion (2%)
Syncope (2%)
Postmarketing reports
Abdominal pain, agitation, aggression, cholecystitis, convulsions, heart block (all types), hemolytic anemia, hepatitis, hyponatremia, neuroleptic malignant syndrome, pancreatitis, rash, rhabdomyolysis, QTc prolongation, Stevens Johnson syndrome toxic epidermal necrolysis and torsade de pointes
Warnings
Contraindications
Hypersensitivity to donepezil or to piperidine derivatives
Cautions
Risk of GI bleed, especially in patients with history of gastric ulcer or those on NSAIDs
Cholinesterase inhibitors are likely to exaggerate succinylcholine-type muscle relaxation during anesthesia
Cholinesterase inhibitors may have vagotonic effects on the sinoatrial and atrioventricular nodes manifesting as bradycardia or heart block
Can cause vomiting (higher risk with dose of 23 mg/day)
May cause anorexia and/or weight loss (dose dependent)
Cholinomimetics may cause bladder outflow obstructions
Cholinomimetics are believed to have some potential to cause generalized convulsions
Cholinesterase inhibitors should be prescribed with care with history of asthma or obstructive pulmonary disease
Use with caution in patients with history of seizure disorders, urinary tract obstruction, peptic ulcer disease, cardiac conduction abnormalities, or respiratory disease including COPD or asthma
May be associated with QT prolongation and torsades de pointes; use caution in patients at risk of cardiac repolarization
Rare cases of neuroleptic malignant syndrome reported; may consider discontinuing therapy if symptoms occur
Rare cases of rhabdomyolysis reported following few months of therapy or following therapy initiation; use caution in patients with risk factors rhabdomyolysis, including medications associated with rhabdomyolysis; consider discontinuing therapy if marked elevation of CPK levels or symptoms suggesting rhabdomyolysis occur
Low weight patients <55 kg may experience more weight loss, nausea, and vomiting than patients >55 kg
Pregnancy and lactation
Pregnancy category: C
Lactation: Excretion in breast milk unknown, use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Aricept (donepezil)
Mechanism of action
Acetylcholinesterase inhibitor that causes an increase in concentrations of acetylcholine, which in turn enhances cholinergic neurotransmission
Absorption
Bioavailability: 100%
Peak plasma time: 3-4 hr
Distribution
Protein bound: 96%
Vd: 12-16 L/kg
Metabolism
Hepatic P-450 enzymes CYP2D6, CYP3A4
Metabolites: 4 major metabolites, 2 active
Elimination
Half-life: 70 hr
Total body clearance: 0.13 L/hr/kg
Excretion: Urine (57%), feces (17%)
