Aricept 5 mg Tablets

Brand Name

The medication is widely recognized under the trade name Aricept, a designation commonly used in clinical and commercial settings.

International Non-Proprietary Name

The active ingredient is identified globally as donepezil, adhering to international standards for pharmaceutical nomenclature.

Form of Release

This drug is available in multiple oral forms to suit varying patient needs. It comes as film-coated tablets in strengths of 5 milligrams, 10 milligrams, and 23 milligrams. Additionally, an orally disintegrating tablet option exists in 5-milligram and 10-milligram doses, designed to dissolve on the tongue for easier administration.

Composition

The primary active component is donepezil hydrochloride, a cholinesterase inhibitor responsible for its therapeutic effects. In the film-coated tablets, inactive ingredients include lactose monohydrate, corn starch, microcrystalline cellulose, hydroxypropyl cellulose, and magnesium stearate, which aid in stability and delivery. The orally disintegrating version contains similar excipients adjusted for its unique dissolution properties, ensuring effective release of the active substance.

Pharmacologic Properties

Pharmacodynamics

The medication functions by selectively inhibiting acetylcholinesterase, an enzyme that breaks down acetylcholine in the brain. Acetylcholine plays a critical role in memory, reasoning, and cognitive processes, which are often impaired in certain neurological conditions. By preventing its degradation, the drug enhances cholinergic transmission, temporarily improving cognitive function. This action does not halt disease progression but supports symptom management by boosting neurotransmitter availability at synaptic sites. Its specificity for acetylcholinesterase over other enzymes minimizes peripheral side effects, focusing its impact on central nervous system activity.

Clinical studies demonstrate measurable improvements in attention, memory retention, and daily functioning in affected individuals. The effect stems from increased acetylcholine levels in cerebral regions like the hippocampus and cortex, areas vital for cognitive processing. While the benefits are temporary and vary among patients, this mechanism offers a practical approach to alleviating cognitive decline symptoms.

Pharmacokinetics

After oral administration, the drug is well absorbed from the gastrointestinal tract, reaching peak plasma concentrations within three to four hours. Food intake does not significantly alter its absorption, providing flexibility in dosing schedules. It exhibits a bioavailability of nearly 100 percent, reflecting efficient uptake into the bloodstream.

Once absorbed, the substance distributes widely throughout the body, including the central nervous system, due to its ability to cross the blood-brain barrier. Approximately 96 percent binds to plasma proteins, primarily albumin, which influences its distribution and availability. The volume of distribution is about 12 liters per kilogram, indicating extensive tissue penetration.

Metabolism occurs predominantly in the liver via cytochrome P450 enzymes, specifically CYP2D6 and CYP3A4, producing several metabolites with minimal activity compared to the parent compound. This hepatic processing ensures the drug remains active for an extended period, with a half-life averaging 70 hours in adults. The prolonged half-life supports once-daily dosing, maintaining steady therapeutic levels.

Excretion happens mainly through urine, with about 57 percent eliminated as unchanged drug or metabolites, while the remainder exits via feces. Renal clearance is relatively low, suggesting that kidney function impacts elimination less than hepatic metabolism. This pharmacokinetic profile allows for consistent efficacy over time with proper administration.

Indications for Use

Conditions and Disorders

The medication is prescribed to manage dementia associated with Alzheimer’s disease, a progressive neurodegenerative disorder. It addresses symptoms in mild, moderate, and severe stages, helping patients maintain cognitive abilities and perform daily tasks longer. Indications include memory loss, impaired reasoning, and difficulty with language or problem-solving, common features of this condition. Though not a cure, it provides symptomatic relief, supporting quality of life for those affected.

Physicians may also consider it for off-label uses, such as managing cognitive deficits in other dementias or brain injuries, though evidence for these applications varies. Its primary approval remains tied to Alzheimer’s, where clinical trials have established efficacy across disease severity levels.

Contraindications

Conditions Prohibiting Use

Use is prohibited in individuals with known hypersensitivity to donepezil hydrochloride or piperidine derivatives, as allergic reactions could range from mild rashes to severe anaphylaxis. Patients with a history of severe reactions to similar compounds should avoid it entirely.

Other contraindications include active gastrointestinal bleeding or untreated ulcers, due to the drug’s potential to increase gastric acid secretion via cholinergic stimulation. Those with uncontrolled asthma or chronic obstructive pulmonary disease face heightened risks of bronchoconstriction, making its use inadvisable. Cardiac conditions like sick sinus syndrome or severe bradycardia also preclude administration, as the medication may exacerbate heart rate irregularities through vagotonic effects.

Method of Administration and Dosage

Administration Guidelines

The drug should be taken orally once daily, preferably in the evening before bedtime, to align with its pharmacokinetic profile and reduce daytime side effects. It can be consumed with or without food, offering flexibility based on patient preference or tolerance. Film-coated tablets must be swallowed whole with water, while orally disintegrating tablets should be placed on the tongue to dissolve, followed by a sip of water to ensure complete ingestion.

Dosage for Adults and Children

For adults with mild to moderate Alzheimer’s, the initial dose is 5 milligrams daily. After four to six weeks, if tolerated, this may increase to 10 milligrams daily, the maximum recommended dose for this stage. In moderate to severe cases, escalation to 23 milligrams daily is possible after at least three months on 10 milligrams, depending on physician assessment. Children lack approved dosing, as the drug’s safety and efficacy in pediatric populations remain unestablished.

Dose Adjustments for Specific Conditions

No specific adjustments are required for mild to moderate renal or hepatic impairment, given the drug’s primary clearance pathways and prolonged half-life. However, in severe liver dysfunction, cautious monitoring is advised, as metabolism may slow, potentially elevating plasma levels. Patients with reduced kidney function typically tolerate standard doses, but clinicians should evaluate individual responses to avoid accumulation risks.

Side Effects

Potential Adverse Reactions

Common reactions include gastrointestinal disturbances like nausea, diarrhea, and vomiting, often linked to cholinergic overstimulation. These effects tend to occur early in treatment or after dose increases, subsiding with continued use in many cases. Muscle cramps, fatigue, and insomnia also appear frequently, reflecting the drug’s impact on neuromuscular and central nervous systems.

Less common but serious effects involve cardiovascular changes, such as bradycardia or fainting, particularly in patients with underlying heart conditions. Seizures or worsening of asthma symptoms may occur rarely, necessitating immediate medical attention. Skin reactions like rashes signal possible hypersensitivity, while severe abdominal pain or black stools suggest gastrointestinal complications requiring urgent evaluation.

Overdose

Symptoms of Excessive Intake

Overdose manifests through exaggerated cholinergic effects, including severe nausea, vomiting, excessive salivation, sweating, and slowed heart rate. Muscle weakness, respiratory distress, and convulsions may follow, indicating a critical state. In extreme cases, collapse or coma could develop, posing life-threatening risks without prompt intervention.

First Aid Measures

Immediate cessation of the drug is essential, followed by contacting emergency services. Administering activated charcoal within an hour of ingestion may reduce absorption if the patient is conscious and cooperative. Atropine, a cholinergic antagonist, may be used under medical supervision to reverse severe symptoms like bradycardia or bronchospasm. Supportive care, including monitoring vital signs and maintaining airway patency, remains crucial until professional help arrives.

Drug Interactions

Effects on Other Medications

The medication can amplify the effects of other cholinergic agents, such as bethanechol, increasing risks of gastrointestinal or cardiac side effects. It may antagonize anticholinergics like atropine, reducing their efficacy in conditions requiring decreased acetylcholine activity. Concurrent use with nonsteroidal anti-inflammatory drugs heightens ulcer risk due to enhanced gastric acid secretion.

Inhibition of cytochrome P450 enzymes by drugs like ketoconazole or quinidine can elevate plasma concentrations, potentially intensifying side effects. Conversely, inducers like rifampicin may lower levels, reducing effectiveness. Caution is warranted with agents prolonging QT intervals, such as certain antidepressants, due to additive cardiac risks.

Compatibility with Alcohol and Food

Alcohol does not directly alter the drug’s pharmacokinetics but may exacerbate side effects like drowsiness or gastrointestinal upset, so moderation is advised. Food has negligible impact on absorption, allowing administration with meals if preferred for tolerability.

Special Precautions

Use During Pregnancy and Breastfeeding

Data on use during pregnancy are limited, with no clear evidence of harm or safety in humans. Animal studies suggest no teratogenic effects, but physicians should weigh benefits against potential fetal risks, reserving it for cases where necessity outweighs uncertainty. It is unknown whether the drug passes into breast milk, so breastfeeding mothers should consult healthcare providers, possibly suspending lactation during treatment.

Impact on Driving and Machinery Operation

The medication may cause dizziness, fatigue, or slowed reactions, particularly at higher doses or during initial therapy. Patients should assess their response before driving or operating heavy equipment, avoiding such activities if impairment occurs. Caregivers may need to monitor those with advanced disease for additional safety.

Considerations for Elderly and Pediatric Patients

Elderly individuals, the primary users due to Alzheimer’s prevalence, generally tolerate standard doses well, though age-related declines in liver or kidney function may necessitate closer observation. Dose escalation should proceed cautiously to minimize adverse reactions. Pediatric use lacks approval, as clinical trials have not established efficacy or safety in younger populations, restricting its application to adults.