Alzepil, pills 10mg, 28pcs

Composition

1 tablet contains:

Active ingredient:

donepezil hydrochloride monohydrate-10.42 mg (corresponds to donepezil hydrochloride-10 mg) 

Auxiliary substances:

microcrystalline cellulose-192 mg,

low-substituted hydroxypropylcellulose (L-HPC B1) – 48 mg,

magnesium stearate-2 mg.

Composition of the film shell:

 opadray Y-1-7000 white (hypromellose-3.75 mg, titanium dioxide-1.875 mg, macrogol 400-0.375 mg) – 6 mg

Pharmacological action

Selective and reversible inhibitor of acetylcholinesterase, which is the main predominant type of cholinesterase in the brain. In vitro, donepezil inhibits this enzyme more than 1000 times more strongly than butyrylcholinesterase, an enzyme that is mainly found outside the central nervous system.

A single dose of 5 mg or 10 mg at steady state is accompanied by inhibition of cholinesterase activity (estimated on the model of erythrocyte membranes) by 63.6% and 77.3%, respectively. The ability of donepezil hydrochloride to inhibit the activity of red blood cell cholinesterase correlates with changes in the results of the ADAS-cog scale, which is a sensitive tool for assessing changes in cognitive function. The ability of donepezil hydrochloride to alter the course of concomitant neurological changes has not been studied. Thus, donepezil cannot be considered to affect the progression of the disease.

The efficacy of donepezil was evaluated in four placebo-controlled trials, two six-month and two one-year studies.

In a six-month clinical trial, the analysis was performed using three efficacy criteria after completion of donepezil use. We used the ADAS-Cog scale (an indicator of cognitive function); a scale of clinician’s impressions of changes based on interviews and data obtained from patient caregivers (an indicator of the overall level of function); a subscale of daily activity of the clinical dementia assessment scale (an indicator of the patient’s ability to participate in society, perform household chores, favorite activities, and serve themselves).

Patients who met the criteria listed below were considered to have responded to treatment.

Response = improvement on the ADAS-Cog scale of at least 4 points, no deterioration on the CIBIC scale, no deterioration on the daily activity subscale of the clinical dementia assessment scale.

* p<0.05, **p<0.01

Donepezil hydrochloride caused a dose-dependent, statistically significant increase in the percentage of patients who were found to respond to treatment.

Indications

Symptomatic treatment of mild or moderate Alzheimer’s disease

Contraindications

• hypersensitivity (including to piperedine derivatives);
• pregnancy (see “Use during pregnancy and lactation”);
• lactation period (see “Use during pregnancy and lactation”);
• children under 18 years of age (due to the lack of clinical data).

With caution:  chronic obstructive pulmonary disease, bronchial asthma, cardiac arrhythmias, general anesthesia, gastric and duodenal ulcers, concomitant use of NSAIDs, cholinesterase blockers or other cholinesterase inhibitors.

Side effects

Nausea, diarrhea, headache, fainting spells, dizziness, insomnia, fatigue, hallucinations, agitation, aggressive behavior (which stops after reducing the dose or discontinuing the drug), vomiting, upset stomach, urinary incontinence, rash, pruritus, muscle spasms, anorexia, colds, pain of various localization, slight increase in the concentration of muscle cretininphosphokinase in the blood serum, bradycardia, convulsive seizures, gastrointestinal bleeding, gastric and duodenal ulcers, sinoatrial and atrioventricular block, extrapyramidal symptoms, liver dysfunction, including hepatitis.

Interaction

Alzepil and / or its metabolites do not inhibit the metabolism of theophylline, warfarin, cimetidine or digoxin. When used concomitantly with digoxin or cimetidine, the metabolism of donepezil hydrochloride does not change. Ketoconazole and quinidine, inhibitors of CYP3A4 (itraconazole, erythromycin) and 2D6 (fluoxetine), inhibit the metabolism of donepezil. In a study in healthy volunteers, ketoconazole increased average donepezil concentrations by about 30%. Enzyme inducers (rifampicin, phenytoin, carbamazepine, and ethanol) may reduce donepezil levels. However, the extent of this inhibitory or inducing effect is not known, so such drug combinations should be used with caution. Alzepil may interact with drugs that have anticholinergic activity. Also, Alzepil has a synergistic effect when taken simultaneously with succinylcholine, other muscle relaxants or antagonists of cholinergic receptors and beta-blockers, which affect the conduction of the heart. Atypical changes in blood pressure and heart rate have been reported when Alzepil is co-administered with other cholinomimetics and quaternary anticholinergic drugs, such as glycopyrrolate.

How to take, course of use and dosage

Alzepil is used strictly as prescribed by a doctor!The drug should be taken orally in the evening before bedtime. For adults and elderly patients, the drug is prescribed at an initial dose of 5 mg once a day. The initial dose of 5 mg should be continued for 1 month to assess the early clinical effect of therapy and reach the equilibrium concentration of donepezil. After a month, if necessary, you can increase to 10 mg per day (in 1 reception). The recommended maximum daily dose is 10 mg. Clinical studies with a dosage of more than 10 mg / day have not been conducted. No dose adjustment is required in patients with impaired liver and kidney function. Due to the possible increase in exposure with mild or moderate hepatic impairment, dose increases should be made taking into account individual tolerability.

Overdose

Symptoms:  cholinergic crisis (severe nausea, vomiting, drooling, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions). It is possible to increase muscle weakness, which, if the respiratory muscles are affected, can lead to death. Treatment:  general supportive care should be given. As an antidote, tertiary anticholinergic drugs are used, for example, atropine at an initial dose of 1-2 mg intravenously, then the dose is selected depending on the clinical effect. There are no data on the elimination of donepezil hydrochloride and / or its metabolites by dialysis (hemodialysis, peritoneal dialysis, or hemofiltration).

Special instructions

Treatment should be prescribed and carried out by a specialist doctor who has experience in managing patients with Alzheimer’s dementia. The diagnosis of the disease should be made in accordance with generally accepted criteria (for example, DSM IV, ICD 10). Treatment can only be carried out if there is a person who is able to control the intake of medicines. Treatment is carried out as long as there is a therapeutic effect, which should be regularly evaluated. In the absence of a therapeutic effect, the drug should be discontinued. The individual response to Alzepil therapy cannot be predicted. After the drug is discontinued, its effect gradually and slowly disappears. There is no information about the withdrawal syndrome in case of abrupt discontinuation of the drug. The efficacy of Alzepil has not been established in patients with severe Alzheimer’s-type dementia, other types of dementia, or memory impairment (for example, with age-related cognitive decline). As a cholinesterase inhibitor, Alzepil can enhance the succinylcholine type of muscle relaxation during general anesthesia. It can also have a vagotonic effect on the heart rate (cause bradycardia). The possibility of such an action should be considered if the sinus node is weak or other supraventricular conduction disorders, such as sinoatrial or atrioventricular block. Fainting and convulsions have been reported. When examining such patients, it is necessary to take into account the possibility of blockage or prolonged sinus arrest. Caution should be exercised in patients with an increased risk of developing ulcers (for example, patients with a history of peptic ulcer disease or taking nonsteroidal anti-inflammatory drugs (NSAIDs)). However, clinical trials of donepezil compared with placebo did not show an increase in the incidence of peptic ulcers or gastrointestinal bleeding. Cholinomimetics can cause obstruction of the mouth of the bladder, although in clinical studies conducted with the use of donepezil hydrochloride, such information is not available. It is suggested that cholinomimetics can cause generalized seizures, but seizures can also be a manifestation of Alzheimer’s disease. Cholinomimetics may worsen or reduce extrapyramidal disorders.Special care should be taken when prescribing the drug to patients with bronchial asthma or a history of obstructive pulmonary diseases. Do not take Alzepil concomitantly with other acetylcholinesterase inhibitors, agonists or antagonists of the cholinergic system. There are no data on the use of the drug in patients with severe hepatic impairment. Discontinuation of Alzepil should be considered in patients with liver function disorders of unknown etiology. The safety and efficacy of Alzepil in children has not been studied, so the drug is not recommended for this category of patients.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C.

Shelf life

5 years

Active ingredient

Donepezil

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Alzheimer ‘s Disease