donepezil

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/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‡

‡Return to baseline after discontinuation.

Contraind./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.

Adv. 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

Metab: weight loss

MS: arthritis, muscle cramps

Neuro: headache, abnormal dreams, depression, dizziness, drowsiness, fatigue, insomnia, syncope

Interactions ⬆ ⬇

Drug-drug:

Exaggerates muscle relaxation from succinylcholine.
Interferes with the action of anticholinergics.
↑cholinergic effects of bethanechol.
May ↑ risk of GI bleeding from NSAIDs.
Quinidine and ketoconazole↓ metabolism of donepezil.
Rifampin, carbamazepine, dexamethasone, phenobarbital, and phenytoin induce the enzymes that metabolize donepezil and may ↓ its effects.

Drug-Natural Products:

Jimson weed and scopolia may antagonize cholinergic effects.

Route/Dosage ⬆ ⬇

Mild to Moderate Alzheimer's 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, elderly females).
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's 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 Appendix [not included in this PDA edition].

Assessment ⬆ ⬇

Assess cognitive function (memory, attention, reasoning, language, ability to perform simple tasks) periodically during therapy.
Monitor heart rate periodically during therapy. May cause bradycardia.

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.
- Oral 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 increase rate of absorption.
Take patch from refrigerator and allow to reach room temperature; do not use external heat sources to warm. Do not apply a cold transdermal system. Recommended application site is the back, avoiding the spine or a site that would be rubbed by tight clothing. May use the upper buttocks or the upper outer thigh. Do not use same location for application site for at least 2 weeks (14 days). Do not apply to an area where medication, cream, lotion, or powder has recently been applied. Do not apply to red, irritated, or cut skin. Do not shave site. Press down firmly for 30 sec to ensure good contact with skin at edges of transdermal system. May be worn while bathing or in hot weather. Avoid long exposure to external heat sources (excessive sunlight, saunas, solariums, heating pads). If patch falls off or a dose is missed, apply a new transdermal system immediately and then replace this transdermal system 7 days later to start a new 1-week cycle.

Patient/Family Teaching ⬆ ⬇

Emphasize the importance of taking donepezil daily, as directed. Missed doses should be skipped and regular schedule returned to the following day. Do not take more than prescribed; higher doses do not increase effects but may increase 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. Advise patient to avoid driving and other activities requiring alertness until response to medication is known.
Advise patient and caregiver to notify health care professional if nausea, vomiting, diarrhea, or changes in color of stool occur or if new symptoms occur or previously noted symptoms increase 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.
Advise females 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.
Instruct patients or caregivers to fold the transdermal system 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 transdermal system after 7-day usage and that used transdermal systems should not be flushed down the toilet.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇