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Indications/Uses
Symptomatic treatment of mild, moderate & severe Alzheimer's disease, vascular dementia (associated w/ CV disease) & dementia w/ Lewy bodies (DLB).
Dosage/Direction for Use
Adults and Elderly: Initiated at 5 mg/day (once-a-day dosing). The 5 mg/day dose should be maintained for at least 1 month in order to allow the earliest clinical responses to treatment to be assessed and to allow steady-state concentrations of donepezil HCl to be achieved. Following a 4-6 weeks clinical assessment in patients who tolerated treatment at 5 mg/day, the dose of Aricept Evess can be increased to 10 mg/day (once-a-day dosing). The maximum recommended daily dose is 10 mg. Doses >10 mg/day have not been studied in clinical trials.
Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer's dementia. Diagnosis should be made according to accepted guidelines (eg, DSM IV, ICD 10). Therapy with donepezil should only be started if a caregiver who will regularly monitor drug intake for the patient is available. Maintenance treatment can be continued for as long as a therapeutic benefit for the patient exists. Therefore, the clinical benefit of donepezil should be re-assessed on a regular basis. Discontinuation should be considered when evidence of a therapeutic effect is no longer present. Individual response to donepezil cannot be predicted.
Upon discontinuation of treatment, a gradual abatement of the beneficial effects of Aricept Evess is seen.
Renal and Hepatic Impairment: A similar dose schedule can be followed for patients with renal impairment, as clearance of donepezil HCl is not affected by this condition.
Due to possible increased exposure in mild to moderate hepatic impairment (see Pharmacokinetics under Actions), dose escalation should be performed according to individual tolerability. There are no data for patients with severe hepatic impairment.
Aricept Evess should be taken orally in the evening, just prior to retiring. The tablet should be placed on the tongue and allow to disintegrate before swallowing with or without water, according to patient's preference.
Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer's dementia. Diagnosis should be made according to accepted guidelines (eg, DSM IV, ICD 10). Therapy with donepezil should only be started if a caregiver who will regularly monitor drug intake for the patient is available. Maintenance treatment can be continued for as long as a therapeutic benefit for the patient exists. Therefore, the clinical benefit of donepezil should be re-assessed on a regular basis. Discontinuation should be considered when evidence of a therapeutic effect is no longer present. Individual response to donepezil cannot be predicted.
Upon discontinuation of treatment, a gradual abatement of the beneficial effects of Aricept Evess is seen.
Renal and Hepatic Impairment: A similar dose schedule can be followed for patients with renal impairment, as clearance of donepezil HCl is not affected by this condition.
Due to possible increased exposure in mild to moderate hepatic impairment (see Pharmacokinetics under Actions), dose escalation should be performed according to individual tolerability. There are no data for patients with severe hepatic impairment.
Aricept Evess should be taken orally in the evening, just prior to retiring. The tablet should be placed on the tongue and allow to disintegrate before swallowing with or without water, according to patient's preference.
Overdosage
The estimated median lethal dose of donepezil HCl following administration of a single oral dose in mice and rats is 45 mg/kg and 32 mg/kg, respectively, or approximately 225 times and 160 times the maximum recommended human dose of 10 mg/day. Dose-related signs of cholinergic stimulation were observed in animals and included reduced spontaneous movement, prone position, staggering gait, lacrimation, clonic convulsions, depressed respiration, salivation, miosis, fasciculation and lower body surface temperature.
Overdosage with cholinesterase inhibitors can result in 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.
As in any case of overdose, general supportive measures should be utilized. Tertiary anticholinergics eg, atropine may be used as an antidote for donepezil HCl overdosage. Intravenous atropine sulfate titrated to effect is recommended: An initial dose of 1-2 mg IV with subsequent doses based upon clinical response. Atypical responses in blood pressure and heart rate have been reported with other cholinomimetics when co-administered with quaternary anticholinergics eg, glycopyrrolate. It is not known whether donepezil HCl and/or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis or hemofiltration).
Overdosage with cholinesterase inhibitors can result in 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.
As in any case of overdose, general supportive measures should be utilized. Tertiary anticholinergics eg, atropine may be used as an antidote for donepezil HCl overdosage. Intravenous atropine sulfate titrated to effect is recommended: An initial dose of 1-2 mg IV with subsequent doses based upon clinical response. Atypical responses in blood pressure and heart rate have been reported with other cholinomimetics when co-administered with quaternary anticholinergics eg, glycopyrrolate. It is not known whether donepezil HCl and/or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis or hemofiltration).
Administration
May be taken with or without food: Place tab on the tongue & allow to disintegrate then, swallow w/ or w/o water.
Contraindications
Known hypersensitivity to donepezil HCl, piperidine derivatives or to any of the excipients of Aricept Evess.
Use in pregnancy: Donepezil HCl is contraindicated in pregnancy.
Use in lactation: Donepezil is excreted in the milk of rats. It is not known whether donepezil HCl is excreted in human breast milk and there are no studies in lactating women. Therefore, women on donepezil should not breastfeed.
Use in pregnancy: Donepezil HCl is contraindicated in pregnancy.
Use in lactation: Donepezil is excreted in the milk of rats. It is not known whether donepezil HCl is excreted in human breast milk and there are no studies in lactating women. Therefore, women on donepezil should not breastfeed.
Special Precautions
The use of Aricept Evess in patients with other types of dementia and other types of memory impairment (eg, age-related cognitive decline) has not been investigated.
Anesthesia: Aricept Evess, as a cholinesterase inhibitor, is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia.
Cardiovascular Conditions: Because of their pharmacological action, cholinesterase inhibitors may have vagotonic effects on heart rate (eg, bradycardia). The potential for this action may be particularly important to patients with "sick sinus syndrome" or other supraventricular cardiac conduction conditions eg, sinoatrial or atrioventricular block.
There have been reports of syncope and seizures. In investigating such patients, the possibility of heart block or long sinusal pauses should be considered.
Gastrointestinal Conditions: Patients at increased risk for developing ulcers eg, those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) should be monitored for symptoms. However, the clinical studies with Aricept Evess showed no increase relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding.
Genitourinary: Although not observed in clinical trials of Aricept Evess, cholinomimetics may cause bladder outflow obstruction.
Neurological Conditions: Seizures: Cholinomimetics are believed to have some potential to cause generalized convulsions. However, seizure activity may also be a manifestation of Alzheimer's disease.
Cholinomimetics may have the potential to exacerbate or induce extrapyramidal symptoms.
Pulmonary Conditions: Because of their cholinomimetic actions, cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.
The administration of Aricept Evess concomitantly with other inhibitors of AChE, agonists or antagonists of the cholinergic system should be avoided.
Severe Hepatic Impairment: There are no data for patients with severe hepatic impairment.
Anesthesia: Aricept Evess, as a cholinesterase inhibitor, is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia.
Cardiovascular Conditions: Because of their pharmacological action, cholinesterase inhibitors may have vagotonic effects on heart rate (eg, bradycardia). The potential for this action may be particularly important to patients with "sick sinus syndrome" or other supraventricular cardiac conduction conditions eg, sinoatrial or atrioventricular block.
There have been reports of syncope and seizures. In investigating such patients, the possibility of heart block or long sinusal pauses should be considered.
Gastrointestinal Conditions: Patients at increased risk for developing ulcers eg, those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) should be monitored for symptoms. However, the clinical studies with Aricept Evess showed no increase relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding.
Genitourinary: Although not observed in clinical trials of Aricept Evess, cholinomimetics may cause bladder outflow obstruction.
Neurological Conditions: Seizures: Cholinomimetics are believed to have some potential to cause generalized convulsions. However, seizure activity may also be a manifestation of Alzheimer's disease.
Cholinomimetics may have the potential to exacerbate or induce extrapyramidal symptoms.
Pulmonary Conditions: Because of their cholinomimetic actions, cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.
The administration of Aricept Evess concomitantly with other inhibitors of AChE, agonists or antagonists of the cholinergic system should be avoided.
Severe Hepatic Impairment: There are no data for patients with severe hepatic impairment.
Adverse Reactions
The most common adverse events are diarrhea, muscle cramps, fatigue, nausea, vomiting and insomnia.
The incidence profile for adverse events for severe Alzheimer's disease is similar to that of mild to moderately severe Alzheimer's disease. Table 4 reflects the incidence of adverse events in patients receiving treatment with Aricept Evess for all stages of Alzheimer's disease.
Adverse reactions reported as more than an isolated case are listed by system organ class and by frequency. Frequencies are defined as: Very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000) and not known (cannot be estimated from available data).
The incidence profile for adverse events for severe Alzheimer's disease is similar to that of mild to moderately severe Alzheimer's disease. Table 4 reflects the incidence of adverse events in patients receiving treatment with Aricept Evess for all stages of Alzheimer's disease.
Adverse reactions reported as more than an isolated case are listed by system organ class and by frequency. Frequencies are defined as: Very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000) and not known (cannot be estimated from available data).
Drug Interactions
Donepezil HCl and/or any of its metabolites do not inhibit the metabolism of theophylline, warfarin, cimetidine or digoxin in humans. The metabolism of donepezil HCl is not affected by concurrent administration of digoxin or cimetidine. In vitro studies have shown that the cytochrome P-450 isoenzymes 3A4 and to a minor extent 2D6 are involved in the metabolism of donepezil. Drug interaction studies performed in vitro show that ketoconazole and quinidine, inhibitors of CYP3A4 and CYP2D6 respectively, inhibit donepezil metabolism. Therefore these and other CYP3A4 inhibitors eg, itraconazole and erythromycin, and CYP2D6 inhibitors eg, fluoxetine could inhibit the metabolism of donepezil. In a study in healthy volunteers, ketoconazole increased mean donepezil concentrations by about 30%. Enzyme inducers eg, rifampicin, phenytoin, carbamazepine and alcohol may reduce the levels of donepezil. Since the magnitude of an inhibiting or inducing effect is unknown, such drug combinations should be used with care. Donepezil HCl has the potential to interfere with medications having anticholinergic activity. There is also the potential for synergistic activity with concomitant treatment involving medications eg, succinylcholine, other neuromuscular blocking agents or cholinergic agonists or β-blocking agents which have effects on cardiac conduction.
Storage
Store at temperatures not exceeding 30°C. Protect from light.
Shelf-Life: 3 years.
Shelf-Life: 3 years.
Action
Pharmacotherapeutic Group: Drugs for dementia. ATC Code: N06DA02.
Pharmacology: Pharmacodynamics: Donepezil HCl is a specific and reversible inhibitor of acetylcholinesterase (AChE), the predominant cholinesterase in the brain. Donepezil HCl is in vitro over 1000 times more potent inhibitor of AChE than of butyrylcholinesterase, an enzyme which is present mainly outside the central nervous system.
Alzheimer's Dementia: Mild to Moderate Alzheimer's Disease: In patients with Alzheimer's dementia participating in clinical trials, administration of single daily doses of Aricept Evess 5 or 10 mg produced steady-state inhibition of AChE activity (measured in erythrocyte membranes) of 63.6% and 77.3%, respectively when measured post-dose. The inhibition of AChE in red blood cells by donepezil HCl has been shown to correlate to changes in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), a sensitive scale which examines selected aspects of cognition. The potential for donepezil HCl to alter the course of the underlying neuropathology has not been studied. Thus, Aricept Evess cannot be considered to have any effect on the progress of the disease. Efficacy of treatment of Alzheimer's dementia with Aricept Evess has been investigated in 4 placebo-controlled trials, 2 trials of 6-month duration and 2 trials of 1-year duration.
In the 6 months clinical trial, an analysis was done at the conclusion of donepezil treatment using a combination of 3 efficacy criteria: The ADAS-Cog (a measure of cognitive performance), the Clinician's Interview Based Impression of Change with Caregiver Input [(CIBIC), a measure of global function] and the Activities of Daily Living Subscale of the Clinical Dementia Rating Scale (a measure of capabilities in community affairs, home and hobbies, and personal care).
Patients who fulfilled the criteria listed as follows were considered treatment responders.
Response: Improvement of ADAS-Cog of at least 4 points; no deterioration of CIBIC and Activities of Daily Living Subscale of the Clinical Dementia Rating Scale.
Pharmacology: Pharmacodynamics: Donepezil HCl is a specific and reversible inhibitor of acetylcholinesterase (AChE), the predominant cholinesterase in the brain. Donepezil HCl is in vitro over 1000 times more potent inhibitor of AChE than of butyrylcholinesterase, an enzyme which is present mainly outside the central nervous system.
Alzheimer's Dementia: Mild to Moderate Alzheimer's Disease: In patients with Alzheimer's dementia participating in clinical trials, administration of single daily doses of Aricept Evess 5 or 10 mg produced steady-state inhibition of AChE activity (measured in erythrocyte membranes) of 63.6% and 77.3%, respectively when measured post-dose. The inhibition of AChE in red blood cells by donepezil HCl has been shown to correlate to changes in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), a sensitive scale which examines selected aspects of cognition. The potential for donepezil HCl to alter the course of the underlying neuropathology has not been studied. Thus, Aricept Evess cannot be considered to have any effect on the progress of the disease. Efficacy of treatment of Alzheimer's dementia with Aricept Evess has been investigated in 4 placebo-controlled trials, 2 trials of 6-month duration and 2 trials of 1-year duration.
In the 6 months clinical trial, an analysis was done at the conclusion of donepezil treatment using a combination of 3 efficacy criteria: The ADAS-Cog (a measure of cognitive performance), the Clinician's Interview Based Impression of Change with Caregiver Input [(CIBIC), a measure of global function] and the Activities of Daily Living Subscale of the Clinical Dementia Rating Scale (a measure of capabilities in community affairs, home and hobbies, and personal care).
Patients who fulfilled the criteria listed as follows were considered treatment responders.
Response: Improvement of ADAS-Cog of at least 4 points; no deterioration of CIBIC and Activities of Daily Living Subscale of the Clinical Dementia Rating Scale.
MedsGo Class
Neurodegenerative Disease Drugs
Features
Brand
Aricept Evess
Full Details
Dosage Strength
5mg
Drug Ingredients
- Donepezil
Drug Packaging
Orodispersible Tablet 1's
Generic Name
Donepezil
Dosage Form
Orodispersible Tablet
Registration Number
DR-XY35549
Drug Classification
Prescription Drug (RX)