Class: Cholinesterase inhibitor
- Tablets 5 mg
- Tablets 10 mg
- Tablets 23 mg
- Tablets, orally disintegrating 5 mg
- Tablets, orally disintegrating 10 mg
Increases acetylcholine by inhibiting acetylcholinesterase, thereby increasing cholinergic function.
T max for the 10 and 23 mg tablets is approximately 3 and 8 h, respectively. C max is almost 2–fold higher for the 23 mg tablet compared with the 10 mg tablet. Steady state is reached in 15 days.
Vd is 12 to 16 L/kg (at steady state). Approximately 96% protein bound (75% to albumin and 21% alpha-1 acid glycoprotein)
Metabolized by CYP2D6 and CYP3A4, and undergoes glucuronidation to 4 major metabolites (2 active) and several minor metabolites.
The elimination half-life is approximately 70 h. Cl is 0.13 to 0.19 L/h/kg. Approximately 57% recovered in urine and 15% in feces; approximately 17% of dose is recovered unchanged in urine.
Special PopulationsRenal Function Impairment
Cl did not differ in patients with moderate to severe renal impairment.Hepatic Function Impairment
Cl decreased 20% in patients with stable alcoholic cirrhosis.Elderly
When compared with patients 65 y of age, patients 90 y of age have a 17% decrease in Cl, while patients 40 y of age have a 33% increase in Cl. This effect may not be clinically significant.Gender
Cl was not affected to any important degree.Race
Cl was not affected to any important degree by race (Japanese and white patients).Body weight
For body weight from 50 to 110 kg, Cl increased from 7.77 to 14.04 L/h, with a value of 10 L/h for 70 kg individuals.
Indications and Usage
Treatment of mild to severe dementia of the Alzheimer type.
Autism, traumatic brain injury, vascular dementia, poststroke aphasia, improvement in memory in multiple sclerosis patients.
Hypersensitivity to donepezil or piperidine derivatives.
Dosage and AdministrationMild to Moderate Alzheimer Disease
PO 5 mg once daily; may increase to 10 mg once daily after 4 to 6 wk.Severe Alzheimer Disease
PO Start with 5 mg once daily. Increase to 10 mg once daily after 4 to 6 wk. A dosage of 23 mg once daily may be given after the patient has been on 10 mg once daily for at least 3 months.
- Orally disintegrating tablets are bioequivalent to tablets.
- Administer in the evening, just prior to bedtime.
- May be taken without respect to food.
- Allow the oral disintegrating tablet to dissolve on the tongue and follow with water.
Store between 59° and 86°F.
Drug InteractionsAnticholinergic 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.
Hypertension (3%); hemorrhage, syncope (2%); abnormal ECG, atrial fibrillation, bradycardia, heart failure, hot flashes, hypotension, vasodilation (at least 1%); heart block (postmarketing).
Insomnia (14%); headache (10%); dizziness, fatigue (8%); abnormal dreams, depression, hallucinations, hostility, nervousness (3%); asthenia, confusion, emotional lability, personality disorder, somnolence (2%); abnormal crying, abnormal gait, aggression, agitation, anxiety, aphasia, ataxia, convulsions, delusions, increased libido, irritability, paresthesia, restlessness, tremor, vertigo, wandering (at least 1%); NMS (postmarketing).
Eczema (3%); diaphoresis, pruritus, rash, skin ulcer, urticaria (at least 1%).
Blurred vision, cataract, eye irritation, pharyngitis, sore throat (at least 1%).
Nausea (19%); diarrhea (15%); vomiting (9%); anorexia (8%); abdominal pain, bloating, constipation, dyspepsia, fecal incontinence, gastroenteritis, GI bleeding, epigastric pain (at least 1%); pancreatitis (postmarketing).
Urinary incontinence (3%); frequent urination (2%); cystitis, glucosuria, hematuria, nocturia, UTI (at least 1%).
Increased ALT/AST (at least 1%); cholecystitis, hepatitis (postmarketing).
Ecchymosis (5%); anemia (at least 1%); hemolytic anemia (postmarketing).
Weight decrease (5%); increased CPK (3%); dehydration, hyperlipemia (2%); edema, increased alkaline phosphatase and LDH, peripheral edema (at least 1%); hyponatremia (postmarketing).
Muscle cramps (8%); back pain (3%); arthritis (2%); bone fracture (at least 1%).
Bronchitis, dyspnea, increased cough, pneumonia (at least 1%).
Accident (13%); infection (11%); pain (various locations) (9%); chest pain, contusion, fever (2%); flu syndrome, fungal infection, 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 .
Undetermined. The molecular weight (approximately 416) and long plasma elimination half-life (approximately 70 h) suggest donepezil will be excreted into breast milk. The extensive protein binding (approximately 0.96%) should limit this excretion.
Safety and efficacy not established.
May have vagotonic effects on the sinoatrial and AV nodes.
Concomitant medical conditions
Increases cholinergic activity and, therefore, can affect other organ systems, possibly leading to bradycardia or heart block, bladder outflow obstruction, increased gastric acid secretion, generalized convulsions, or bronchoconstriction. Use with caution in patients susceptible to these reactions.
Diarrhea, nausea, and vomiting appear more frequently with higher doses and may last for 1 to 3 weeks. Because of increased cholinergic activity increasing gastric secretion, patients are at an increased risk of developing occult GI bleeding, especially those at increased risk for developing ulcers (eg, history of ulcer disease or those receiving concurrent NSAIDs).
Patients weighing less than 55 kg reported more nausea and vomiting and decreased weight compared with patients weighing 55 kg or more.
Cholinergic crisis (eg, bradycardia, collapse, convulsions, hypotension, muscle weakness, respiratory depression, salivation, severe nausea, sweating, vomiting).
- Advise patient or caregiver that this drug does not alter the Alzheimer process and that the effectiveness of the medication may lessen in time.
- Advise patient to take prescribed dose once daily in the evening just before bedtime.
- Advise patient that donepezil can be taken without regard to meals but to take with food if stomach upset occurs.
- Advise patient receiving orally disintegrating tablet to allow tablet to dissolve on tongue and then follow with water.
- Advise patient that if a dose is missed to skip that dose and take next dose at regularly scheduled time. Caution patient not to double the dose to catch up.
- Advise patient or caregiver not to discontinue drug or change dose unless advised by health care provider.
- Caution patient or caregiver not to increase the dose of donepezil if Alzheimer symptoms worsen or do not appear to be improving, but to notify health care provider.
- Advise patient or caregiver that diarrhea, nausea, and vomiting commonly occur, especially during the early phase of treatment with donepezil, but that these symptoms will usually go away within 1 to 3 wk with continued therapy.
- Advise patient to notify health care provider if any of the following occur: appetite loss; depression; fainting; persistent nausea, diarrhea, or vomiting; sleeplessness; any other unexplained change or symptoms.
- Caution patient that donepezil may cause drowsiness or dizziness, and to use caution while driving or performing other activities requiring mental alertness or coordination until tolerance is determined.
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