Donepezil Brand Name– Aricept
What is Donepezil
Donepezil was the first piperidine-type reversible cholinesterase (ChE) inhibitor to receive approval by the FDA.
Donepezil is approved for the symptomatic management of mild to severe Alzheimer’s disease. Prior to approval of donepezil, tacrine, an acridine-type cholinesterase (ChE) inhibitor, was the only agent approved for this disease, however, the acridine-type ChEs are associated with hepatotoxicity. Donepezil has not been associated with hepatotoxicity.
However, unlike other cholinesterase inhibitors, donepezil is considered a drug with a known risk of QT prolongation, and the risk versus benefit of donepezil therapy should be determined in patients with risk factors for QT prolongation and Torsade de Pointes (TdP).
Donepezil has limited peripheral adverse reactions because of its greater affinity for CNS cholinesterase than tacrine.
The long elimination half-life of donepezil allows for once daily dosing versus other orally administered cholinesterase inhibitors which are typically dosed two to four times daily.
Clinical efficacy of donepezil in Alzheimer’s disease is similar to other available ChE inhibitors (e.g., rivastigmine and tacrine) based on the Clinical Global Impression of Change (CGIC) scale and the Alzheimer’s Disease Assessment Scale-Cognitive Subscale score (ADAS-cog).
Donepezil does not alter the long-term prognosis of Alzheimer’s disease, but delays the time until institutionalization of the patient, which may be cost-effective and increase the patient’s quality of life. In addition, one large multicenter study showed that the use of donepezil improved global function, cognition and behavior in those patients with moderate to severely advanced Alzheimer’s disease (i.e., sMMSE score of 5—17) who did not yet require total nursing care.
In addition to head-to-head studies against other ChE-inhibitors, phase III trials of donepezil for Lewy Body dementia (LBD) and mild cognitive impairment (MCI) are in progress. Other clinical trials are ongoing to establish the safety, efficacy, and tolerability of donepezil in vascular dementia. Efficacy in severe Alzheimer’s was established in a double-blind, controlled clinical trial involving 248 subjects.
Improvement in cognitive function compared to placebo was measured by the Severe Impairment Battery (SIB) instrument and overall function was measured by a caregiver assessment using the Modified Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory for Severe Alzheimer’s Disease (ADCS-ADL-severe).
In a separate study, donepezil 10 mg/day was significantly better than placebo in treating severe Alzheimer’s as assessed by the SIB and Clinician’s Interview Based Impression of Change (CIBIC) plus.
In the same study, the 5 mg/day dose was found statistically superior to placebo on the SIB but not the CIBIC plus. Donepezil was approved by the FDA for mild to moderate Alzheimer’s disease in November 1996.
In October 2004, a rapid disintegration tablet (Aricept ODT) and an oral solution were approved by the FDA. In October 2006, the drug received approval for severe Alzheimer’s disease dementia.
Indications
- Alzheimer’s disease
- dementia with Lewy bodies
- ischemic stroke
- vascular dementia
For the treatment of Alzheimer’s disease
for the treatment of mild to moderate Alzheimer’s disease
Side Effects
- abdominal pain
- abnormal dreams
- agitation
- anorexia
- arthralgia
- asthenia
- atopic dermatitis
- AV block
- back pain
- bleeding
- bradycardia
- chest pain (unspecified)
- cholecystitis
- confusion
- dehydration
- depression
- diarrhea
- dizziness
- drowsiness
- ecchymosis
- emotional lability
- fatigue
- fever
- hallucinations
- headache
- hemolytic anemia
- hepatitis
- hostility
- hyperlipidemia
- hypertension
- hyponatremia
- increased urinary frequency
- infection
- insomnia
- muscle cramps
- nausea
- neuroleptic malignant syndrome
- pancreatitis
- QT prolongation
- rash
- rhabdomyolysis
- seizures
- syncope
- torsade de pointes
- urinary incontinence
- vomiting
- weight loss
Monitoring Parameters
- laboratory monitoring not necessary
- neurologic function
- weight
Contraindications
- abrupt discontinuation
- apheresis
- asthma
- AV block
- bladder obstruction
- bradycardia
- breast-feeding
- cardiomyopathy
- celiac disease
- children
- chronic obstructive pulmonary disease (COPD)
- diarrhea
- females
- fever
- geriatric
- GI bleeding
- GI disease
- heart failure
- hepatic disease
- human immunodeficiency virus (HIV) infection
- hyperparathyroidism
- hypocalcemia
- hypokalemia
- hypomagnesemia
- hypotension
- hypothermia
- hypothyroidism
- infants
- long QT syndrome
- myocardial infarction
- neonates
- peptic ulcer disease
- pheochromocytoma
- pregnancy
- pulmonary disease
- QT prolongation
- rheumatoid arthritis
- seizure disorder
- seizures
- sick sinus syndrome
- sickle cell disease
- sleep deprivation
- stroke
- surgery
- syncope
- systemic lupus erythematosus (SLE)
- vomiting
Interactions
- Acebutolol
- Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
- Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
- Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine
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