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Aricept®

Drug Indications

Aricept® tablets/ Aricept® Evess orodisperible tablets are indicated for the symptomatic treatment of mild, moderate and severe Alzheimer's dementia. Aricept® Tablets 5mg and 10mg are bioequivalent to Aricept Evess® 5mg and 10mg respectively.

Dose and Administration

  • Aricept® is available in 5mg and 10mg.

  • Orodispersible Tablets: for 5mg and 10mg, allow Aricept® orodispersible tablet to dissolve on the tongue and follow with water.

  • Aricept® should be taken in the evening, just prior to retiring.

  • Aricept® can be taken with or without food and should be swallowed whole with water.

  • Mild to Moderate Alzheimer’s disease 
    The higher dose of 10 mg did not provide a statistically significantly greater clinical benefit than 5 mg. There is a suggestion, however, based upon order of group mean scores and dose trend analyses of data from these clinical trials, that a daily dose of 10 mg of Aricept® might provide additional benefit for some patients. Accordingly, whether or not to employ a dose of 10 mg is a matter of prescriber and patient preference.

  • Severe Alzheimer's Disease 
    Aricept® has been shown to be effective in controlled clinical trials at a dose of 10 mg administered once daily.
    Evidence from the controlled trials in mild to moderate Alzheimer's Disease indicates that the 10 mg dose, with a one week titration, is likely to be associated with a higher incidence of cholinergic adverse events than 5 mg dose. In open label trial using a 6 week titration, the frequency of these same adverse events was similar between the 5 mg and 10 mg dose groups. Therefore, because steady state is not achieved for 15 days and because the incidence of untoward effects may be influenced by the rate of dose escalation, a dose of 10 mg should not be achieved until patients have been on a daily dose of 5 mg for 4-6 weeks.

  • Renal and hepatic impairment
    A similar dose schedule can be followed for patients with renal impairment, as clearance of donepezil hydrochloride is not affected by this condition. 
    Due to possible increased exposure in mild to moderate hepatic impairment, dose escalation should be performed according to individual tolerability. There are no data for patients with severe hepatic impairment.

Titration

A dose of 10mg once daily can be administered once patients have been on a daily dose of 5mg for 4 to 6 weeks. 

Contraindications

Patients with known hypersensitivity to donepezil hydrochloride or to piperidine derivatives.

Warnings and Precautions

  • Cholinesterase inhibitors are likely to exaggerate succinylcholine type muscle relaxation during anesthesia.

  • Cholinesterase inhibitors may have vagotonic effects on the sinoatrial and atrioventricular nodes manifesting as bradycardia or heart block.

Safety Profile

The most common adverse events, defined as those occurring at a frequency of at least 5% in patients receiving 10mg/day and twice the placebo rate, are largely predicted by Aricept® cholinomimetic effects. These include nausea, diarrhea, insomnia, vomiting, muscle cramp, fatigue and anorexia. These adverse events were often of mild intensity and transient, resolving during continued Aricept® treatment without the need for dose modification.

Clinical Studies

The effectiveness of Aricept® as a treatment for Alzheimer’s disease is demonstrated by the results of randomized, double-blind, placebo controlled clinical investigations.

1. Mild to Moderate Alzheimer’s Disease
Thirty-Week study (5mg, 10mg and placebo)

In a study of 30 weeks duration, 473 patients were randomized to receive single daily dose of placebo, 5mg/day or 10mg/day of Aricept®. The 30-week study was divided into a 24-week double-blind active treatment phase followed by a 6-week single-blind placebo washout period. The study was designed to compare 5mg/day or 10mg/day fixed doses of Aricept® to placebo. However, to reduce the likelihood of cholinergic effects, the 10mg/day treatment was started following an initial 7-day treatment with 5mg/day doses.

 

Effects on ADAS-cog: Figure 1 illustrates the time for change from baseline in ADAS-cog scores for all three dose groups over the 30 weeks. After 24 weeks of treatment, the mean difference in ADAS-cog change scores for Aricept® treated patients compared to placebo patients were 2.8 and 3.1 point for 5mg/day and 10mg/day treatments, respectively. These differences were statistically significant.

 

Following 6 weeks of placebo washout, scores on the ADAS-cog for both the Aricept® treatment groups were indistinguishable from those patients who had received only placebo for 30 weeks. This suggests the beneficial effects of Aricept® abate over 6 weeks following discontinuation of treatment and do not represent a change in the underlying disease. There was no evidence of a rebound effect 6 weeks after erupt discontinuation of therapy.

 

*ADAS-cog (Alzheimer’s Disease Assessment Scale-cognitive subscale) was designed to measure the severity of the most important symptoms of Alzheimer’s disease. ADAS-cog is the most popular cognitive testing instrument used in clinical trials of nootropics. It consists of 11 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities that are often referred to as the core symptoms of Alzheimer’s Disease.

2. Severe Alzheimer’s Disease
6 Month study (10mg)

The effectiveness of Aricept® as a treatment for severe Alzheimer’s disease is demonstrated by the results of a randomized, double-blind, placebo controlled clinical study. Alzheimer’s disease diagnosed by MMSE range 1-20. 248 patients with severe Alzheimer’s disease were randomized to Aricept® or placebo. For the patients randomized to Aricept®, treatment was initiated at 5mg once daily for 28 days and then increased to 10mg once daily.

 

*SIB- Severe Impairment Battery

*Mini Mental State Examination (MMSE)

MMSE is the most commonly used test for complaints of memory problems. It is used to help diagnose dementia and to help assess its progression and severity. The MMSE is a series of questions and tests with a maximum score of 30 points. The MMSE tests a number of different mental abilities, including a person’s memory, attention and language.

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Figure1. Time-course of the change from Baseline in ADAS-cog score for patients completing 24 weeks of treatment.

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Figure 2 shows the time course for the change from baseline in SIB score for the two treatment groups over the 6 months of the study. At 6 months of treatment, the mean difference in the SIB changes score from the Aricept® group as compared to placebo was 5.9 points. Aricept® treatment was statistically significantly superior to placebo.

For further product information kindly refer to the prescribing information.

 

Reference

 

Aricept® prescribing information.

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