donepezil ARICEPT
Class: Acetylcholinesterase InhibitorFDA Indications: Alzheimer's Dementia
Off-Label Use: Motor Symptoms Of Parkinson's Disease, Mild Cognitive Impairment
Prescribing
Forms: 5, 10mg tablet; 5, 10mg ODT; 23mg sustained-release, film-coated tabletDose Range: 5-10 mg/day
Starting: 5 mg daily for 4 weeks, then ↑ to 10 mg daily. Morning dosing may minimize insomnia and vivid dreams.
Precautions
Contraindications: Known hypersensitivity to a specific drug or its derivatives is the only true contraindication. Cautious administration of cholinesterase inhibitors is advised in patients who have a previous history of allergy or adverse reactions to prior cholinesterase inhibitors, severe liver disease, preexisting bradycardia, peptic ulcer disease, current alcoholism, asthma, or chronic obstructive pulmonary disease.Known Risk of TdP
Side Effects: diarrhea, nausea, insomnia, fatigue, agitation, vivid dreams, vomiting, muscle cramps, anorexia, syncope (2%)
Pharmacodynamics
1° MOA: Centrally acting, reversible, noncompetitive AChEI2° MOA: High affinity σ1 agonist
Target: AChE, σ1
Pharmacokinetics
t½: 70° TMAX: 3-5°Substrate of: 3A4; 2D6
Inhibits: ∅ ; Induces: ∅
Active Metabolites: 6-O-desmethyl donepezil
DDIs
- - AChEIs have the potential to interfere with the activity of anticholinergic medications
- - A synergistic effect may be expected with concomitant administration of succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists
- - 3A4 inhibitors can ↑ levels; likewise, 3A4 inducers can ↓ levels
Misc
- - a "nonclassical" cholinesterase inhibitor that binds to both AChE and butyrylcholinesterase
- - displays linear pharmacokinetics
- - has the best evidence for effectiveness in mild cognitive impairment of all cholinesterase inhibitors
- - GI side effects can be minimized by gradual dose increases, administration with food, adequate hydration, and judicious use of an antiemetic
- - package insert recommended QHS dosing to prevent the patient from experiencing side effects; however, QAM dosing may minimize insomnia and vivid dreams
Special Populations
Category C—No reports describing the use of donepezil in human pregnancy have been located. Because of its indication, such reports should be rare. Moreover, the animal data suggest that the risk to the embryo and/ or fetus is low. Therefore, inadvertent exposure to donepezil during pregnancy should not be a reason for pregnancy termination.
No reports describing the use of donepezil during human lactation have been located. The molecular weight of the parent compound and its long t½ suggest that donepezil, and possible the active metabolites, will be excreted into breast milk. The extensive protein binding (about 96%), however, should limit this excretion. The effects of this exposure on a nursing infant are unknown.
No dosage adjustment necessary.
Only a minimal dose decrease required in hepatic impairment.