Davis's Drug Guide
donepezil
General
Genetic Implications:
Pronunciation:
doe-nep-i-zil
Trade Name(s)
- Adlarity
- Aricept
- Aricept ODT
Ther. Class.
anti-Alzheimers's agents
Pharm. Class.
(cholinesterase inhibitors)
Indications
Mild, moderate, or severe dementia/neurocognitive disorder associated with Alzheimer disease.
Action
Inhibits acetylcholinesterase, thus improving cholinergic function by making more acetylcholine available.
Therapeutic Effect(s):
- May temporarily lessen some of the dementia associated with Alzheimer disease.
- Enhances cognition.
- Does not cure the disease.
Pharmacokinetics
Absorption: Well absorbed after oral administration. Bioavailability of transdermal formulation comparable to that of oral tablets.
Distribution: Widely distributed to extravascular tissues.
Protein Binding: 96%.
Metabolism and Excretion: Partially metabolized by the liver (CYP2D6 and CYP3A4 isoenyzmes) and partially excreted by kidneys (17% unchanged). Two metabolites are pharmacologically active. The CYP2D6 enzyme system exhibits genetic polymorphism (~7% of population may be poor metabolizers and may have significantly ↑ donepezil concentrations and an ↑ risk of adverse effects).
Half-life: Oral: 70 hr. Transdermal: 91 hr.
TIME/ACTION PROFILE (improvement in symptoms)
| ROUTE | ONSET | PEAK | DURATION |
|---|---|---|---|
| PO | unknown | several wk | 6 wk† |
| Transdermal | unknown | several wk | 6 wk† |
Contraindication/Precautions
Contraindicated in:
- Hypersensitivity to donepezil or piperidine derivatives;
- History of allergic contact dermatitis with transdermal donepezil.
Use Cautiously in:
- Underlying cardiac disease, especially sick sinus syndrome or supraventricular conduction defects;
- History of ulcer disease or currently taking NSAIDs;
- History of seizures;
- History of asthma or obstructive pulmonary disease;
- OB: Safety not established in pregnancy;
- Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
- Pedi: Safety and effectiveness not established in children.
Adverse Reactions/Side Effects
CV: atrial fibrillation, hypertension, hypotension, vasodilation
Derm: allergic contact dermatitis (transdermal), ecchymoses
Endo: hot flashes
GI: diarrhea, nausea, anorexia, vomiting
GU: frequent urination
Metabolic: weight loss
MS: arthritis, muscle cramps
Neuro: headache, abnormal dreams, depression, dizziness, drowsiness, fatigue, insomnia, syncope
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Interactions
Drug-Drug
- Exaggerates muscle relaxation from succinylcholine.
- Interferes with the action of anticholinergics.
- ↑ risk of cholinergic effects with bethanechol.
- May ↑ risk of GI bleeding from NSAIDs.
- Quinidine and ketoconazole may ↑ levels and risk of toxicity.
- Rifampin, carbamazepine, dexamethasone, phenobarbital, and phenytoin may ↓ levels and effectiveness.
Drug-Natural Products:
Jimson weed and scopolia may antagonize cholinergic effects.
Route/Dosage
Mild to Moderate Alzheimer Disease
PO (Adults): 5 mg once daily; may ↑ to 10 mg once daily after 4–6 wk (dose should not exceed 5 mg/day in frail older women).
Transdermal (Adults): Apply one 5 mg/day transdermal system once weekly; may ↑ to one 10 mg/day transdermal system once weekly after 4–6 wk. Switching from oral to transdermal donepezil: If patient taking 5 mg/day of oral donepezil, switch to one 5 mg/day transdermal system applied once weekly; if receiving 5 mg/day of oral donepezil for ≥4–6 wk, can switch to one 10 mg/day transdermal system applied once weekly. If patient taking 10 mg/day of oral donepezil, switch to one 10 mg/day transdermal system applied once weekly.
Severe Alzheimer Disease
PO (Adults): 5 mg once daily; may ↑ to 10 mg once daily after 4–6 wk; after 3 mo, may then ↑ to 23 mg once daily.
Transdermal (Adults): Apply one 5 mg/day transdermal system once weekly; may ↑ to one 10 mg/day transdermal system once weekly after 4–6 wk. Switching from oral to transdermal donepezil: If patient taking 5 mg/day of oral donepezil, switch to one 5 mg/day transdermal system applied once weekly; if receiving 5 mg/day of oral donepezil for ≥4–6 wk, can switch to one 10 mg/day transdermal system applied once weekly. If patient taking 10 mg/day of oral donepezil, switch to one 10 mg/day transdermal system applied once weekly.
Availability (generic available)
Tablets: 5 mg, 10 mg, 23 mg
Orally disintegrating tablets: 5 mg, 10 mg
Transdermal patch (Adlarity): 5 mg/day, 10 mg/day
In Combination with: memantine (Namzaric). See combination drugs.
Assessment
- Assess cognitive function (memory, attention, reasoning, language, ability to perform simple tasks) periodically during therapy.
- Monitor HR periodically during therapy. May cause bradycardia or heart block.
- Monitor for nausea and vomiting, especially during therapy initiation and dose ↑.
Implementation
- Do not confuse Aricept with Aciphex or Azilect.
- PO Administer in the evening just before going to bed. May be taken without regard to food.
- Orally disintegrating tablets should be allowed to dissolve on tongue; follow with water.
- Swallow 23-mg tablet whole. DNC: Do not split, crush, or chew; may ↑ rate of absorption.
- Transdermal Take patch from refrigerator and allow to reach room temperature; do not use external heat source to warm. Do not apply a cold transdermal patch. Apply to back; avoid the spine or a site that may be rubbed by tight clothing. May use upper buttocks or upper outer thigh. Do not use same location for application site for ≥2 wk. Do not apply after cream, lotion, or powder has recently been applied. Do not apply to red, irritated, or open skin. Do not shave site. Press down firmly for 30 sec to ensure good contact with skin at edges of patch. May be worn while bathing or in hot weather. Avoid long exposure to external heat sources. If patch falls off or a dose is missed, apply a new patch immediately and then replace 7 days later to start a new 1-wk cycle.
Patient/Family Teaching
- Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy. Missed doses should be skipped and regular schedule returned to the next day. Do not take more than prescribed; higher doses do not ↑ effectiveness but may ↑ side effects.
- Inform patient/family that it may take weeks before improvement in baseline behavior is observed.
- Caution patient and caregiver that donepezil may cause dizziness and to avoid driving and other activities requiring alertness until response to medication is known.
- Advise patient and caregiver to notify health care professional if significant weight loss, inability to urinate, bronchospasm, or seizures occur.
- Advise patient and caregiver to notify health care professional if nausea, vomiting, diarrhea, or blood in stool occur or if noted symptoms ↑ in severity.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products.
- Advise patient and caregiver to notify health care professional of medication regimen before treatment or surgery.
- Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
- Emphasize the importance of follow-up exams to monitor progress.
- Transdermal Instruct patients or caregivers to fold the patch in half after use and discard it in the trash, out of the reach and sight of children and pets. Inform patients or caregivers that drug still remains in the patch after 7-day usage and that patches should not be flushed down the toilet.
Evaluation/Desired Outcomes
Improvement in cognitive function (memory, attention, reasoning, language, ability to perform simple tasks).
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