High doses of donepezil or memantine may be the next step in achieving better results than standard pharmacologic treatments for AD. However, these dosages are associated with only modest beneficial effects in managing cognitive deterioration in patients with moderate to severe dementia. Recently, the FDA approved higher daily doses of donepezil 23 mg and memantine 28 mg for moderate to severe AD on the basis of positive phase III trial results. Donepezil is a selective, reversible ChEI believed to enhance central cholinergic function. Rationale for higher doses.

We present a patient who developed cholinergic toxicity from donepezil after starting fluoxetine. K is a 65 yo male with schizoaffective disorder, bipolar type. He was admitted to an inpatient psychiatric unit due to increased agitation, fecal incontinence, and new behaviors of smearing feces and repeatedly placing his fingers in his rectum. Physical exam was notable for excessive salivation, lacrimation, and fecal incontinence. Complete blood count and chemistry panel were within normal limits. The patient was restarted on all of his outpatient medications including fluoxetine 20mg daily and donepezil 10mg nightly. Due to concern for a cholinergic toxidrome, donepezil and fluoxetine were discontinued.

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The plan was a new 23 mg dose of Aricept Aricept 23 that could not be reached by combining the soon to be generic and less expensive 5 mg and 10 mg doses. This scheme would ensure three more years of exclusivity and sole marketing rights for the pharmaceutical companies, along with a continued revenue stream, for the new 23 mg dose. With this approval, Pfizer and Eisai revved up a relentless marketing and advertising campaign that continues to this day, the core of which is to misrepresent the safety and efficacy of the clever new dose, and prey on a vulnerable elderly patient population, their families and caregivers, who are desperate to try anything to help their loved ones. Aricept is the best-selling drug in the world to treat symptoms of AD. The drug is co-marketed in the United States with Pfizer, Inc. It is a blockbuster drug that has generated billions of dollars in revenue for Pfizer and Eisai since its approval in the United States. Aricept was first approved by the FDA on November 25, for the treatment of mild to moderate AD, at a dose of 5 mg or 10 mg once a day. On October 13, Aricept was approved for severe AD at a dose of 10 mg once a day. On July 23, just a few months before patent expiration in November, Aricept 23 was approved for moderate to severe AD.

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Higher doses of donepezil, if safe and well tolerated, might provide further benefits for patients with AD. No patients withdrew from the study and there were no serious adverse events or deaths. Frequently asked questions. My Bibliography Add to Bibliography. Generate aricept 20mg file for use with external citation management software.

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Mechanism of Action Current theories on the pathogenesis of the cognitive signs and symptoms of Alzheimer's disease attribute some of them to a deficiency of cholinergic neurotransmission. The 23 mg tablet should not be split, crushed or chewed because this may increase its rate of absorption. 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 compared to the 5 mg dose. In open-label trials using a 6 week titration, the type and frequency of these same adverse events were similar between the 5 mg and 10 mg dose groups. Therefore, because ARICEPT steady state is achieved about 15 days after it is started and because the incidence of untoward effects may be influenced by the rate of dose escalation, a dose of 10 mg should not be administered until patients have been on a daily dose of 5 mg for 4 to 6 weeks.

Background: Cholinesterase inhibitors are approved to treat patients with mild to moderate Alzheimer disease, and are also often used to treat other types of dementia. Their potential for side effects such as bradycardia may be underestimated because initial clinical trials tended to exclude patients with certain cardiovascular disorders. Hernan-dez and colleagues studied the relationship aricept 20mg cholinesterase inhibitor therapy and bradycardia. Over a two-year period, the incidence of bradycardia was assessed among patients using one of three cholinesterase inhibitors i. Patients were excluded from the study if they had preexisting bradycardia, sinus syncope, or a pacemaker.

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From: Epilepsy and Brain Tumors, Three of the human metabolites of donepezil have not undergone extensive safety tests in animals. These comprise two O -demethylated derivatives and an N -oxidation product. The rate of metabolism of donepezil is slow and does not appear to be saturable. Pharmacokinetic studies also demonstrated that the metabolism of donepezil is not affected by concurrent administration of digoxin or cimetidine. Morning dosing of donepezil is recommended to minimize insomnia.

Alzheimer disease is devastating to the patient and the family. We all wish for a good treatment option. Aricept 20mg Aricept has tried to fill this void, but does donepezil in any dose actually benefit patients? And, is the new dosage of 23 mg per day superior to the standard dosage of 10 mg per day? Mark: This is a randomized, double-blind, week trial comparing 23 mg with 10 mg of donepezil in 1, patients 45 to 90 years of age. Those with controlled hypertension, diabetes mellitus, coronary artery disease, and hypothyroidism were eligible.

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