Palliative treatment of mild to moderate dementia of the Alzheimer’s type (Alzheimer’s disease, presenile or senile dementia).
Comparative studies have not been performed to date, but donepezil does not share the hepatotoxic potential of tacrine and may be preferable to tacrine as a first-line treatment because it can be administered once daily and does not require regular monitoring of liver function.
Dosage and Administration
Administration
Oral Administration
Administer conventional or orally disintegrating tablets orally once daily, usually at bedtime.
Administer with or without food.
Orally disintegrating tablets: Place on tongue and allow to dissolve; follow with water.
Donepezil hydrochloride orally disintegrating and conventional film-coated tablets are bioequivalent.
Dosage
Available as donepezil hydrochloride; dosage expressed in terms of the salt.
Adults
Alzheimer’s Disease
Oral
Initially, 5 mg daily.
Some data suggest the possibility of additional benefit with higher (10 mg daily) dosage in some patients; however, additional benefit with the 10-mg dosage has not been demonstrated in controlled clinical studies. Adverse cholinergic effects are more likely with the 10-mg dosage.
Daily administration of 10 mg should not be considered until patient has received 5 mg daily for 4–6 weeks, since occurrence of adverse effects may be influenced by the rate of increase in dosage.
Special Populations
Hepatic Impairment
No specific recommendation for dosage adjustment.
Cautions
Contraindications
Known hypersensitivity to donepezil or piperidine derivatives or any ingredient in the formulation.
Cholinesterase inhibitors may produce bradycardia or heart block via vagotonic effects on the sinoatrial or AV nodes. May occur in patients with or without known cardiac conduction abnormalities. Syncope reported in patients receiving donepezil.
GI Effects
Possible diarrhea, nausea, and vomiting, particularly at dosage of 10 mg daily.
Potential for increased gastric acid secretion.
Carefully monitor patients, especially those at increased risk for developing ulcers (e.g., those with history of peptic ulcer disease, those receiving concomitant NSAIA therapy), for symptoms of active or occult GI bleeding.
GU Effects
Although not reported in clinical studies with donepezil, cholinomimetic agents may cause bladder outflow obstruction.
Respiratory Effects
Use with caution in patients with a history of asthma or obstructive pulmonary disease.
Neurologic Effects
Cholinomimetic agents may have the potential to cause generalized seizures; however, seizures also may be a manifestation of Alzheimer’s disease.
Specific Populations
Pregnancy
Category C.
Lactation
Not known whether donepezil is distributed into milk. Not indicated for use in nursing women.
Pediatric Use
Safety and efficacy not established.
Geriatric Use
Dementia of the Alzheimer's type occurs principally in patients >55 years of age. The mean age of patients receiving donepezil in clinical studies was 73 years of age. No substantial differences in most adverse effects in patients ≥65 years of age relative to those <65 years of age.
Metabolized by CYP3A4 and CYP2D6. Unlikely to cause clinically important induction or inhibition of CYP3A4 or CYP2D6; not known whether donepezil has any enzyme-induction potential.
Drugs Highly Bound to Plasma Proteins
Pharmacokinetic interactions unlikely with drugs highly bound to plasma proteins.
Drugs Affecting or Metabolized by Hepatic Enzymes
Unlikely to alter clearance of drugs metabolized by CYP3A4 or CYP2D6.
Possible pharmacokinetic interaction (altered plasma donepezil concentrations) with CYP2D6 or CYP3A4 inducers or inhibitors.
Specific Drugs
Drug
Interaction
Comments
Anticholinergic agents
Possible interference with activity of anticholinergic agents
Pharmacokinetic interactions (including protein binding interactions) unlikely
Pharmacokinetics
Absorption
Bioavailability
Relative oral bioavailability is 100%.
Orally disintegrating and conventional film-coated tablets are bioequivalent.
Food
Food does not affect rate or extent of absorption when administered as conventional film-coated tablets. Effect of food on donepezil absorption after administration as orally disintegrating tablets has not been studied, but any effects are expected to be minimal; orally disintegrating tablets may be taken without regard to meals.
Distribution
Plasma Protein Binding
Approximately 96% (mainly albumin [75%] and alpha1-acid glycoprotein [21%]).
Elimination
Metabolism
Extensively metabolized to 4 major metabolites (2 known to be active) and a number of minor metabolites. Is metabolized by CYP2D6 and CYP3A4 and undergoes glucuronidation.
Elimination Route
Eliminated in urine and feces (57 and 15%, respectively, over 10 days, with 28% still unrecovered; about 17% of the dose recovered in urine as unchanged drug).
Half-life
About 70 hours.
Special Populations
In patients with stable alcoholic cirrhosis, clearance appears to be reduced by about 20%.
In patients with moderate to severe renal impairment (Clcr <22 mL/minute per 1.73 m2), clearance appears to be similar to that in healthy individuals.
Stability
Storage
Oral
Tablets and Orally Disintegrating Tablets
15–30°C.
Actions
Precise mechanism(s) of action in patients with dementia of the Alzheimer’s type not fully elucidated. Binds reversibly with and inactivates cholinesterases (e.g., acetylcholinesterase), thus inhibiting hydrolysis of acetylcholine and resulting in increased acetylcholine concentrations at cholinergic synapses.
Advice to Patients
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
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