DONEPEZILO

Use Alzheimer disease: Treatment of mild, moderate, or severe dementia of the Alzheimer
type
Use: Off-Label
Dementia associated with Parkinson disease; Lewy body dementia; Traumatic brain injury;
Vascular dementia

Mechanism of Action Alzheimer's disease is characterized by cholinergic deficiency in the

cortex and basal forebrain, which contributes to cognitive deficits. Donepezil reversibly and
noncompetitively inhibits centrally-active acetylcholinesterase, the enzyme responsible for
hydrolysis of acetylcholine. This appears to result in increased concentrations of acetylcholine
available for synaptic transmission in the central nervous system.
Pharmacodynamics/Kinetics
Absorption: Well absorbed

Distribution: Vdss: 12 to 16 L/kg

Protein binding: ~96%, primarily to albumin (75%) and alpha1-acid glycoprotein (21%)

Metabolism: Extensive hepatic metabolism via CYP2D6 and 3A4 and glucuronidation to four
major metabolites (two are active)

Half-life elimination: 70 hours; time to steady-state: 15 days

Time to peak, plasma: Tablet, 10 mg: 3 hours; Tablet, 23 mg: ~8 hours; Note: Peak plasma
concentrations almost twofold higher for the 23 mg tablet compared to the 10 mg tablet

Excretion: Urine (57%; 17% as unchanged drug); feces (15%)

Dosing: Adult
Alzheimer disease: Oral:

Mild-to-moderate: Initial: 5 mg once daily; may increase to 10 mg once daily after 4 to 6

weeks; effective dosage range in clinical studies: 5 to 10 mg/day

Moderate-to-severe: Initial: 5 mg once daily; may increase to 10 mg once daily after 4 to 6

weeks; may increase further to 23 mg once daily after ≥3 months; effective dosage range in
clinical studies: 10 to 23 mg/day

Dementia associated with Parkinson disease (off-label use): 5 mg once daily; may increase to
10 mg once daily after 4 to 6 weeks; may increase further to 23 mg once daily after the use of
10 mg once daily ≥3 months (APA [Rabins 2007]); Dubois 2012)

Lewy body dementia (off-label use): Initial: 2.5 mg once daily for 2 weeks, then increase to 5
mg once daily. After 4 weeks may further increase dose based on response and tolerability up
to 10 mg once daily (Ikeda 2013; Mori 2012)

Traumatic brain injury (off- label use): Initial: 5 mg once daily for 2 to 3 weeks, then increase to
10 mg once daily (Kim 2009; Zhang 2004).
Vascular dementia (with comorbid Alzheimer disease) (off-label use): See Alzheimer disease
dosing.

Dosing: Renal Impairment: Adult There are no dosage adjustments provided in the
manufacturer’s labeling. Limited data suggest severe renal impairment does not adversely
affect donepezil clearance.
Dosing: Hepatic Impairment: Adult There are no dosage adjustments provided in the
manufacturer’s labeling.
Dosing: Geriatric Refer to adult dosing. Note: The Canadian labeling recommends a maximum
dose of 5 mg once daily in elderly women (≥85 years of age) of low body weight.
Dosage Forms Excipient information presented when available (limited, particularly for
generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral, as hydrochloride:

Aricept: 5 mg, 10 mg, 23 mg

Generic: 5 mg, 10 mg, 23 mg

Tablet Disintegrating, Oral, as hydrochloride:

Aricept ODT: 10 mg [DSC]

Generic: 5 mg, 10 mg

Generic Equivalent Available (US) Yes

Administration Oral: Administer at bedtime without regard to food.
Aricept 23 mg tablet: Swallow whole with water; do NOT crush or chew due to an increased
rate of absorption. The 23 mg strength is provided in a unique film-coated formulation
different from the 5 mg or 10 mg tablet strengths, which results in an altered pharmacokinetic
profile.

Aricept ODT: Allow tablet to dissolve completely on tongue and follow with water.

Adverse Reactions
>10%:

Central nervous system: Insomnia (2% to 14%)

Gastrointestinal: Nausea (3% to 19%; dose related), diarrhea (5% to 15%; dose related)

Infection: Infection (11%)

Miscellaneous: Accidental injury (7% to 13%)

≥1% to 10%:

Cardiovascular: Hypertension (3%), chest pain (2%), syncope (2%), atrial fibrillation (≥1%),
bradycardia (≥1%), cardiac failure (≥1%), ECG abnormality (≥1%), edema (≥1%), hypotension
(≥1%), peripheral edema (≥1%), vasodilation (≥1%)
Central nervous system: Headache (3% to 10%), pain (3% to 9%), dizziness (2% to 8%), fatigue
(1% to 8%), abnormal dreams (3%), hallucination (3%), hostility (3%), depression (2% to 3%),
nervousness (1% to 3%), confusion (2%), drowsiness (2%), emotional lability (2%; including
crying), personality disorder (2%), abnormal gait (≥1%), aggressive behavior (≥1%), agitation
(≥1%), anxiety (≥1%), aphasia (≥1%), ataxia (≥1%), convulsions (≥1%), delusions (≥1%),
irritability (≥1%), paresthesia (≥1%), restlessness (≥1%), vertigo (≥1%), wandering (≥1%)

Dermatologic: Ecchymosis (4% to 5%), eczema (3%), dermal ulcer (≥1%), diaphoresis (≥1%),
pruritus (≥1%), skin rash (≥1%), urticaria (≥1%)

Endocrine & metabolic: Weight loss (3% to 5%; dose related), hyperlipidemia (2%),
dehydration (1% to 2%), glycosuria (≥1%), hot flash (≥1%), increased lactate dehydrogenase
(≥1%), increased libido (≥1%)

Gastrointestinal: Vomiting (3% to 9%; dose related), anorexia (2% to 8%), abdominal pain
(≥1%), bloating (≥1%), constipation (≥1%), dyspepsia (≥1%), epigastric pain (≥1%), fecal
incontinence (≥1%), gastroenteritis (≥1%), gastrointestinal hemorrhage (≥1%), sore throat
(≥1%), toothache (≥1%)

Genitourinary: Urinary incontinence (1% to 3%), urinary frequency (2%), cystitis (≥1%),
hematuria (≥1%), nocturia (≥1%), urinary tract infection (≥1%)

Hematologic & oncologic: Bruise (2%), hemorrhage (2%), anemia (≥1%)

Hepatic: Increased serum alkaline phosphatase (≥1%)

Infection: Fungal infection (≥1%), influenza (≥1%)

Neuromuscular & skeletal: Muscle cramps (3% to 8%), back pain (3%), increased creatine
phosphokinase (3%), arthritis (1% to 2%), weakness (1% to 2%), bone fracture (≥1%), tremor
(≥1%)

Ophthalmic: Blurred vision (≥1%), cataract (≥1%), eye irritation (≥1%)

Respiratory: Bronchitis (≥1%), dyspnea (≥1%), flu-like symptoms (≥1%), increased cough (≥1%),
pharyngitis (≥1%), pneumonia (≥1%)

Miscellaneous: Fever (2%)

≤1%, postmarketing, and/or case reports: Abnormal hepatic function tests, abnormal
lacrimation, abnormal vision, abscess, acute rhinitis, albuminuria, alopecia, angina pectoris,
apathy, arteritis, arthralgia, arthropathy, asthma, atelectasis, atrophic striae, benign prostatic
hypertrophy, blepharitis, breast fibroadenosis, cachexia, cardiomegaly, cellulitis, cerebral
hemorrhage, cerebral infarction, cerebral ischemia, cerebrovascular accident, chills,
cholecystitis, cholelithiasis, conjunctival hemorrhage, conjunctivitis, convulsions, decreased
libido, deep vein thrombosis, dementia, dermatitis, diabetes mellitus, diverticulitis, duodenal
ulcer, dysarthria, dysgeusia, dysphagia, dysphoria, dysuria, emotional disturbance,
eosinophilia, epigastric distress, epistaxis, eructation, erythema, erythrocytopenia, esophagitis,
euphoria, extrapyramidal reaction, facial edema, fasciculations, fibrocystic breast changes, first
degree atrioventricular block, flatulence, fungal dermatitis, gastritis, gastric ulcer, gingivitis,
glaucoma, goiter, gout, hearing loss, heart block, hemiplegia, hemolytic anemia, hemorrhoids,
hepatitis, hernia, herpes zoster, hiatal hernia, hirsutism, hyperbilirubinemia, hyperglycemia,
hyperkeratosis, hypersensitivity reaction, hypertonia, hypokalemia, hypokinesia,
hyponatremia, hypoproteinemia, hypoxia, increased appetite, increased blood urea nitrogen,
increased gamma-glutamyl transferase, increased post-void residual urine volume, increased
serum ALT, increased serum AST, increased serum creatinine, increased serum transaminases,
increased thirst, intestinal obstruction, intracranial hemorrhage, iron deficiency anemia,
irritable bowel syndrome, jaundice, leg cramps, leukocytosis, localized coldness, malaise,
mastitis, melena, motion sickness, muscle spasm, myalgia, myasthenia, myocardial infarction,
neuralgia, neurodermatitis, neuroleptic malignant syndrome, night sweats, nystagmus,
orthostatic hypotension, osteoporosis, otalgia, otitis externa, otitis media, pacing, pancreatitis,
paranoia, peptic ulcer disease, periodontal abscess, periodontitis, periorbital edema,
peripheral vascular disease, pernicious anemia, pleurisy, polydipsia, post nasal drip, prolonged
Q-T interval on ECG, psoriasis, pulmonary congestion, pyelonephritis, pyuria, rectal
hemorrhage, renal failure, retinal hemorrhage, rhabdomyolysis, rhinitis, seeing spots,
sensation of cold, sepsis, severe depression, sialorrhea, skin discoloration, sleep apnea,
snoring, supraventricular extrasystole, supraventricular tachycardia, thrombocythemia,
thrombocytopenia, tinnitus, tongue edema, tonic-clonic seizures, torsades de pointes,
transient ischemic attacks, urinary urgency, uterine hemorrhage, vaginitis, vasodilation,
ventricular premature contractions, ventricular tachycardia, vertigo, vesiculobullous
dermatitis, weight gain, wheezing, xeroderma, xerophthalmia, xerostomia