Products
Donepezil is commercially available in tablet and oral tablet form (Aricept, Aricept Evess, generics). It has been approved in many countries since 1997.
Structure and properties
Donepezil (C24H29NO3, Mr = 379.5 g/mol) is a piperidine derivative and a racemate. It is present in drugs as donepezil hydrochloride, a white crystalline powder that is soluble in water.
Effects
Donepezil (ATC N06DA02) is indirectly cholinergic, improving symptoms of the disease, but has no effect on the progression of dementia. Its effects are due to reversible and selective inhibition of acetylcholinesterase in the brain. This enzyme is responsible for the breakdown of the neurotransmitter acetylcholine into choline and acetic acid. The inhibition leads to an increase in the residence time and concentration of acetylcholine. The question of whether donepezil is actually clinically effective is controversial in the scientific literature.
Indications
Symptomatic treatment of Alzheimer-type dementia.
Dosage
According to the SmPC. The drug is taken once daily immediately before bedtime. The dose range is from 5 to 23 mg. If sleep disturbances occur, it may also be taken in the morning. Donepezil has a long half-life of approximately 70 hours.
Contraindications
- Hypersensitivity
- Decompensated cirrhosis of the liver
Full details of precautions and interactions can be found in the drug label.
Interactions
Donepezil is biotransformed primarily by CYP3A4 and to a lesser extent by CYP2D6. CYP3A4 inhibitors such as ketoconazole or CYP2D6 inhibitors such as quinidine may increase bioavailability, and inducers may decrease it. Other possible interactions include levodopa, anticholinergics, and suxamethonium chloride.
Adverse effects
The most common possible adverse effects include diarrhea, nausea, vomiting, other digestive disorders, headache, insomnia, psychiatric disorders, skin rash, pruritus, muscle cramps, urinary incontinence, fatigue, pain, transient loss of consciousness, and accidents. Rarely, severe side effects are possible, including seizures, AV block, gastrointestinal ulceration, and hepatitis.
