Donezepil: Common spelling variant of Donepezil for Alzheimer's dementia

Donezepil is a common spelling variant of the active ingredient Donepezil (with p in the middle) used in the population. Both terms refer to the same active ingredient, a reversible second generation acetylcholinesterase inhibitor used in the treatment of mild to severe Alzheimer's dementia. The correct spelling according to the International Nonproprietary Name (INN) is Donepezil. The detailed pillar page can be found at /wirkstoff/donepezil.

Donepezil was approved in 1996 and is today the most frequently prescribed acetylcholinesterase inhibitor in Germany and many other countries. Well-known brand names are Aricept (originator) and numerous generics. The medication has the advantage of once daily administration and an established safety profile, making it particularly practical for cognitively impaired patients.

Mechanism of action

In Alzheimer's dementia, cholinergic neurons in the nucleus basalis Meynert and other subcortical nuclei degenerate early. The resulting acetylcholine deficiency in the hippocampus and cortex correlates with deterioration of memory, attention, and activities of daily living.

Donepezil reversibly and selectively inhibits acetylcholinesterase in the synaptic cleft. Acetylcholine remains available longer and can more strongly stimulate postsynaptic muscarinic and nicotinic receptors. Unlike galantamine, donepezil does not additionally modulate nicotinic receptors. Unlike rivastigmine, donepezil inhibits exclusively acetylcholinesterase, not butyrylcholinesterase.

Pharmacokinetically, donepezil is orally absorbed with high bioavailability (approximately 100 percent), half-life approximately 70 hours, which permits once daily administration. Metabolism via CYP3A4 and CYP2D6, renal elimination after conjugation.

Indications

• Mild, moderate, and severe Alzheimer type dementia: primary indication, approved for all severity grades in Germany
• Mixed dementia with vascular component: off label, supported by subgroup analyses
• Lewy body dementia and Parkinson dementia: off label, often rivastigmine preferred
• Pure vascular dementia: not approved, efficacy uncertain

Dosage and administration

Initial dose: 5 mg once daily in the evening for 4 to 6 weeks, then increase to 10 mg with good tolerability. In severe dementia, the dose can be increased to 23 mg daily (not approved in Germany, available in the USA).

Administration: in the evening, before bedtime, with or without food. Evening administration reduces the perception of nausea and gastrointestinal effects and corresponds to often improved cognitive activity in the morning hours.

Renal insufficiency and hepatic insufficiency: usually no dose adjustment necessary, exercise caution with severe hepatic insufficiency.

Side effects

Very common to common: nausea, vomiting, diarrhea, loss of appetite, weight loss, fatigue, dizziness, headache, sleep disturbances, vivid dreams or nightmares, muscle cramps.

Occasional: bradycardia, AV block, syncope, falls with fracture risk, tremor, incontinence, worsening of depressive symptoms.

Rare: Stevens Johnson syndrome, acute generalized exanthematous pustulosis, seizures, hepatotoxicity, neuroleptic malignant syndrome.

Important: cholinergic effects can cause falls, incontinence, and bradycardia. An EKG should be considered before therapy initiation to identify pre-existing AV blocks. Slow dose titration significantly reduces gastrointestinal side effects.

Drug interactions

• Anticholinergics (oxybutynin, amitriptyline, diphenhydramine, tolterodine, solifenacin): largely counteract donepezil effect, should be avoided if possible
• Beta blockers and digoxin: additive bradycardia, risk of AV block
• Succinylcholine and other muscle relaxants: prolonged neuromuscular blockade, pre anesthetic consultation required
• CYP3A4 inhibitors (ketoconazole, erythromycin): increase donepezil levels
• CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion): similar level increase
• NSAIDs: increased risk of gastrointestinal ulcers due to enhanced acid secretion

Special precautions

Pregnancy and nursing: not approved, as Alzheimer's dementia is rare in women of childbearing age.

Anesthesia: patients and anesthesiologists must be informed of ongoing donepezil therapy, as depolarizing muscle relaxants may have prolonged effects.

Treatment goal and course: donepezil slows cognitive decline on average over six to twelve months, but cannot halt the course. Efficacy assessment is performed after three to six months using MMSE/MoCA, ADL scales, and subjective impression of family members.

Discontinuation: in case of deterioration despite therapy and in transition to very severe dementia, a switch to memantine or combination therapy is discussed. Gradual dose reduction over two to four weeks is customary to observe cognitive deterioration.

You might also be interested in

• Donepezil, detailed pillar page (correct spelling)
• Galantamine, alternative acetylcholinesterase inhibitor with nicotinic modulation
• Rivastigmine, further therapy also available as transdermal patch
• Memantine, NMDA receptor antagonist for moderate to severe dementia
• Acetylcholine, the central neurotransmitter

Frequently asked questions

Sources

• EMA, Aricept (Donepezil) EPAR
• AWMF S3 Guideline Dementias (DGN, DGPPN)
• Gelbe Liste, Donepezil active ingredient profile
• BfArM, Federal Institute for Drugs and Medical Devices