Trade Names:Aricept- Tablets 5 mg- Tablets 10 mg- Tablets, orally disintegrating 5 mg- Tablets, orally disintegrating 10 mgAricept RDT (Canada)
Increases acetylcholine by inhibiting acetylcholinesterase, thereby increasing cholinergic function.
Bioavailability is 100%. T max is 3 to 4 h.
Vd is 12 L/kg (at steady state). Approximately 96% protein bound (75% to albumin and 21% alpha-1 acid glycoprotein)
Metabolized by CYP2D6 and 3A4, and undergoes glucuronidation to 4 major metabolites (2 active) and several minor metabolites.
The t ½ is approximately 70 h. Cl is 0.13 L/h/kg. Approximately 57% recovered in urine and 15% in feces; approximately 17% of dose recovered unchanged in urine.
Cl decreased 20% in patients with stable alcoholic cirrhosis.
Treatment of mild to severe dementia of the Alzheimer type.
Hypersensitivity to donepezil or piperidine derivatives.
PO 5 mg once daily; may increase to 10 mg once daily after 4 to 6 wk, depending on prescriber and patient preference.Severe Alzheimer DiseaseAdults
PO Start with 5 mg once daily. Increase to 10 mg once daily after 4 to 6 wk.
Store at 59° to 86°F.
Possible reduction of anticholinergic effects.Cholinesterase inhibitors/cholinomimetics
Synergistic effects may occur.CYP2D6 and CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin)
May increase donepezil rate of elimination.CYP2D6 and CYP3A4 inhibitors (eg, ketoconazole, quinidine)
May inhibit donepezil metabolism.Succinylcholine
Muscle relaxation may be exaggerated.
None well documented.
The 10 mg dose, with 1-wk titration, is likely to be associated with a higher incidence of cholinergic adverse reactions than the 5 mg dose. With 6-wk titration, the frequency of these same adverse reactions was similar between 5 and 10 mg dosing. The following adverse reactions are based on 6-wk titration.
Hypertension (3%); hemorrhage, syncope (2%); abnormal ECG, atrial fibrillation, bradycardia, heart failure, hot flashes, hypertension, hypotension, vasodilation (at least 1%); heart block (postmarketing).
Headache (10%); insomnia (9%); dizziness (8%); fatigue, nervousness (5%); abnormal dreams, depression, hallucinations, hostility (3%); confusion, emotional lability, personality disorder, somnolence (2%); abnormal crying, abnormal gait, aggression, agitation, anxiety, aphasia, asthenia, ataxia, convulsions, delusions, increased libido, irritability, paresthesia, restlessness, tremor, vertigo, wandering (at least 1%); hallucinations, neuroleptic malignant syndrome (postmarketing).
Eczema (3%); diaphoresis, pruritus, skin rash, ulcer, urticaria (at least 1%).
Blurred vision, cataract, eye irritation, pharyngitis, sore throat (at least 1%).
Nausea (11%); diarrhea (10%); anorexia, vomiting (8%); abdominal pain, bloating, constipation, dyspepsia, fecal incontinence, gastroenteritis, GI bleeding, epigastric pain (at least 1%); pancreatitis (postmarketing).
Frequent urination, urinary incontinence (2%); cystitis, glucosuria, hematuria, nocturia, UTI (at least 1%).
Cholecystitis, hepatitis (postmarketing).
Ecchymosis (5%); anemia (at least 1%); hemolytic anemia (postmarketing).
Increased CPK, weight decrease (3%); dehydration, hyperlipemia (2%); edema, increased alkaline phosphatase and LDH, peripheral edema (at least 1%); hyponatremia (postmarketing).
Muscle cramps (6%); back pain (3%); arthritis (2%); bone fracture (at least 1%).
Bronchitis, dyspnea, increased cough, pneumonia (at least 1%).
Accident (13%); pain (9%); chest pain, fever (2%); flu syndrome, fungal pain, toothache (at least 1%).
Evaluate patient's mental status, cognitive function, and activities of daily living prior to initiation of therapy and periodically thereafter during prolonged treatment. Monitor for signs and symptoms of GI bleed.
Category C .
Safety and efficacy not established.
May have vagotonic effects on the sinoatrial and AV nodes.
Increases cholinergic activity and, therefore, can affect other organ systems, possibly leading to bradycardia, bladder outflow obstruction, increased gastric acid secretion, generalized convulsions, or bronchoconstriction. Use drug with caution in patients susceptible to these reactions.
Cholinergic crisis (eg, bradycardia, collapse, convulsions, hypotension, muscle weakness, respiratory depression, salivation, severe nausea, sweating, vomiting).
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