Aricept: Clinically Proven Treatment for Alzheimer's Dementia
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Synonyms
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Aricept (donepezil hydrochloride) is a reversible acetylcholinesterase inhibitor specifically developed for the treatment of dementia of the Alzheimer’s type. As a first-line therapeutic agent, it works by increasing acetylcholine concentrations in the cerebral cortex through slowing the degradation of acetylcholine released by still-intact cholinergic neurons. This mechanism of action targets the core cholinergic deficit associated with Alzheimer’s disease, making it a cornerstone in the pharmacological management of mild to moderate, and subsequently severe, dementia symptoms. Its well-established efficacy profile and generally favorable tolerability have made it one of the most widely prescribed medications in its class globally.
Features
- Active Ingredient: Donepezil hydrochloride
- Available Formulations: Film-coated tablets in 5 mg and 10 mg strengths; Orally disintegrating tablets (ODT)
- Pharmacological Class: Acetylcholinesterase inhibitor (central)
- Half-life: Approximately 70 hours, allowing for once-daily dosing
- Metabolism: Hepatic, primarily via CYP2D6 and CYP3A4 isoenzymes
- Excretion: Primarily renal, with some fecal elimination
- Bioavailability: High and not significantly affected by food
Benefits
- Cognitive Enhancement: Demonstrated improvement in scores on standardized assessment tools like the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Mini-Mental State Examination (MMSE).
- Functional Improvement: Helps maintain activities of daily living (ADLs), potentially prolonging patient independence and reducing caregiver burden.
- Global Function: Shown to have a positive effect on overall clinical function as rated by clinicians using the Clinician’s Interview-Based Impression of Change plus caregiver input (CIBIC-plus).
- Behavioral Symptom Management: May help ameliorate certain neuropsychiatric symptoms often associated with Alzheimer’s dementia, such as apathy and agitation.
- Progression Delay: While not a cure, treatment can slow the symptomatic progression of the disease, potentially delaying the need for higher levels of care.
- Well-Tolerated Profile: Extensive clinical experience supports a manageable side effect profile for most patients, facilitating long-term treatment adherence.
Common use
Aricept is indicated for the treatment of dementia of the Alzheimer’s type. It is approved for use in mild, moderate, and severe stages of the disease. Its primary use is to manage the core cognitive symptoms—such as memory loss, confusion, and problems with reasoning—that characterize Alzheimer’s disease. It is used as a chronic therapy, with treatment initiation typically occurring after a formal diagnosis has been established by a qualified healthcare professional using standard diagnostic criteria. It is not indicated for other forms of dementia (e.g., vascular dementia, Lewy body dementia) unless specifically evaluated and deemed appropriate by a specialist, though evidence for other types is less robust.
Dosage and direction
The recommended starting dosage for Aricept is 5 mg administered once daily, preferably at bedtime. This may help mitigate potential cholinergic side effects that are often more noticeable upon initiation. After a minimum of 4 to 6 weeks, and upon clinical assessment confirming good tolerability, the dose may be increased to 10 mg once daily, which is the maximum recommended dose. The 10 mg dose has been shown to provide a greater efficacy effect in many patients.
The tablets should be swallowed whole with water and can be taken with or without food. The orally disintegrating tablet (ODT) should be placed on the tongue, where it will dissolve rapidly and be swallowed with saliva; no water is needed. Dosage adjustment is not routinely required for elderly patients or those with renal or mild to moderate hepatic impairment. Use in patients with severe hepatic impairment is not recommended. Treatment should be initiated and supervised by a physician experienced in the diagnosis and management of Alzheimer’s dementia.
Precautions
Aricept should be used with caution in patients with a history of cardiac conduction abnormalities (e.g., sick sinus syndrome, supraventricular conduction conditions), as cholinesterase inhibitors may have vagotonic effects on heart rate. Patients with a history of asthma, COPD, or other significant respiratory diseases should be monitored, as increased bronchial secretions and potential bronchoconstriction are possible. Due to its cholinergic activity, Aricept should be prescribed with care to patients at risk for gastrointestinal ulcers or those with a history of ulcer disease, as it may increase gastric acid secretion. It may also cause bladder outflow obstruction. Caution is advised in patients with a history of seizures. Cholinesterase inhibitors have been associated with weight loss in clinical trials; patient weight should be monitored during therapy.
Contraindications
Aricept is contraindicated in patients with known hypersensitivity to donepezil hydrochloride, piperidine derivatives, or to any excipients used in the formulation. Its use is also contraindicated in patients with severe hepatic impairment.
Possible side effect
The majority of adverse reactions are mild, cholinergic in nature, and often transient. The most common side effects are nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, and anorexia. These events are more common during the dose-escalation phase and often diminish with continued treatment. Less frequent side effects can include bradycardia, syncope, headache, dizziness, agitation, aggressive behavior, nightmares, gastrointestinal bleeding, and urinary incontinence. There have been rare reports of neuroleptic malignant syndrome and rhabdomyolysis. Extrapyramidal symptoms and seizures have also been reported in association with this class of drugs.
Drug interaction
Due to its metabolism via CYP450 isoenzymes, Aricept has the potential for pharmacokinetic interactions. Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole) or CYP2D6 inhibitors (e.g., quinidine) may increase donepezil concentrations. It may potentiate the effects of succinylcholine-type muscle relaxants during anesthesia. As a cholinergic agent, it may interfere with the activity of anticholinergic medications (e.g., oxybutynin, tolterodine). Theoretical potential exists for synergistic effects with other cholinergic agents, potentially increasing the risk of side effects. Beta-blockers may exacerbate bradycardia. Caution is advised when used concomitantly with NSAIDs due to the increased risk of gastrointestinal bleeding.
Missed dose
If a dose is missed, it should be taken as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped, and the regular dosing schedule resumed. Patients and caregivers should be instructed not to double the dose to make up for a missed one.
Overdose
An overdose would be expected to produce severe cholinergic crisis, characterized by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Due to the long half-life of donepezil, supportive medical care and monitoring may be required for a prolonged period. General supportive measures should be instituted. Tertiary anticholinergics such as atropine may be used as an antidote; intravenous atropine sulfate titrated to effect is recommended. It is critical to manage respiratory and cardiovascular function.
Storage
Aricept tablets should be stored at room temperature, between 20°C to 25°C (68°F to 77°F), in a tightly closed container. The medication must be kept out of reach of children and pets. Protect from light and moisture. Do not use after the expiration date printed on the bottle or blister pack.
Disclaimer
This information is intended for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The information provided is based on the manufacturer’s prescribing information and may not encompass all possible uses, directions, precautions, or adverse effects.
Reviews
Clinical trials and extensive post-marketing surveillance over decades have established Aricept as a well-studied and effective agent for the symptomatic management of Alzheimer’s disease. In large-scale, randomized, double-blind, placebo-controlled studies, Aricept consistently demonstrated statistically significant benefits in cognitive function, activities of daily living, and global clinical state compared to placebo over periods of 6 months to 1 year. Many clinicians report that a noticeable subset of patients experience a meaningful stabilization or modest improvement in cognitive and functional abilities, which can significantly impact quality of life for both the patient and their caregivers. The once-daily dosing regimen is frequently cited as a major advantage for adherence in an elderly population. While not all patients respond, and the magnitude of effect varies, it remains a fundamental first-choice therapy in treatment guidelines worldwide.