Dementis pills 5mg, 28pcs

Composition

1 tablet contains:

Active ingredient:

Donepezil Hydrochloride (Tsipla Ltd, India) 5.00 mg

Auxiliary substances:

Lactose monohydrate 91.75 mg, corn starch 20.00 mg, microcrystalline cellulose 15.00 mg, hydroxypropylcellulose 3.00 mg, magnesium stearate 0.25 mg (tablet core weight 135.00 mg); shell (sepifilm 752 white): hypromellose 2.00 mg, microcrystalline cellulose 1.60 mg, macrogol stearate 0.40 mg, titanium dioxide E 171 1.00 mg (theoretical weight 140.00 mg).

Pharmacological action

Pharmacological group: Cholinesterase inhibitor.

Pharmacodynamics

Donepezil is a selective, reversible inhibitor of the enzyme acetylcholinesterase, which is the 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.

By inhibiting cholinesterase in the brain, donepezil blocks the breakdown of acetylcholine, which carries out the transmission of arousal in the central nervous system (CNS). After a single dose of donepezil in doses of 5 mg or 10 mg, the degree of suppression of acetylcholinesterase activity (estimated on a model of red blood cell membranes) was 63.6 and 77.3%, respectively. Inhibition of acetylcholinesterase in red blood cells under the action of donepezil correlates with changes in the ADAS-cog scale (cognitive function assessment scale in Alzheimer’s disease). 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.

Pharmacokinetics

Suction

The maximum concentration (Cmax) of donepezil in plasma is reached approximately 3-4 hours after oral use. The plasma concentration and area under the concentration-time curve (AUC) increase in proportion to the dose. The half-life of T 1/2 is approximately 70 hours, so the systematic use of single doses leads to a stable concentration, which is reached within approximately 3 weeks after the start of therapy. The steady-state plasma concentration of donepezil and its associated pharmacodynamic effects change very little during the day. Food intake does not affect the absorption of donepezil.

Distribution

Approximately 95% of donepezil binds to plasma proteins. There are no data on binding to plasma proteins of its active metabolite 6-Q-desmethyldonepezil. The distribution of donepezil in various body tissues has not been sufficiently studied. In distribution studies on healthy male volunteers, it was found that after taking a single dose of 5 mg labeled 14C-donepezil hydrochloride, approximately 28% of the dose was detected in the body 240 hours after use. This indicates that donepezil and / or its metabolites may persist in the body for more than 10 days.

Metabolism and elimination

Donepezil is excreted by the kidneys both unchanged and in the form of numerous metabolites formed by cytochrome P 450 enzymes, not all of which have been identified. After a single dose of 5 mg labeled 14C-donepezil hydrochloride, the concentration of unchanged donepezil in plasma was 30% of the dose taken,6 — O-desmethyldonepezil-11% (the only metabolite with similar activity to donepezil hydrochloride), donepezil — cis-N-oxide-9%,5 — O-desmethyl-donepezil-7% and 5 — O‑desmethyl‑donepezil conjugate glucuronide. desmethyldonepezil — 3%. Approximately 57% of the administered dose was detected in the urine (17% — unchanged) and 14.5% – in the feces, on the basis of which it was concluded that biotransformation and renal excretion are the primary route of elimination. There are no data confirming enterohepatic recirculation of donepezil and / or its metabolites.

The half-life of donepezil is approximately 70 hours.

Gender, ethnicity, and smoking do not significantly affect the plasma concentration of donepezil. The pharmacokinetics of donepezil have not been formally studied in healthy elderly patients, nor in patients with Alzheimer’s-type dementia or vascular dementia. However, the mean plasma concentration of donepezil in these patients corresponded to that of healthy volunteers.

Patients with mild to moderate hepatic impairment may experience elevated steady-state plasma concentrations of donepezil.

Indications

Symptomatic treatment of mild or moderate Alzheimer’s dementia.

Use during pregnancy and lactation

Pregnancy

There is no experience of using the drug in humans during pregnancy and lactation. Animal studies did not reveal a teratogenic effect of donepezil, however, peri – and postnatal toxicity was established. The potential risk to humans is unknown.

Therefore, the drug should not be used during pregnancy, except in cases where treatment is absolutely necessary.

Breast-feeding period

In rats, donepezil is excreted in milk. It is not known whether the drug is excreted in human breast milk, such studies have not been conducted. If it is necessary to take the drug during lactation, it is necessary to decide whether to stop breastfeeding.

Contraindications

-Individual hypersensitivity to any component of the drug or piperidine derivatives;

– Lactose intolerance, lactase deficiency or glucose-galactose malabsorption (since the drug contains lactose monohydrate);

– Children under 18 years of age (safety and efficacy of the drug have not been studied).

With caution

Use with caution in patients with a history of obstructive pulmonary diseases (including bronchial asthma), with cardiac arrhythmias (possible vagotonic effect on the heart rate, in particular bradycardia), with an increased risk of developing ulcers (a history of peptic ulcer or concomitant therapy with nonsteroidal anti-inflammatory drugs), during general anesthesia, while taking with cholinesterase blockers or other cholinesterase inhibitors, in patients with a high risk of developing ulcers. patients with a history of seizures and convulsions, hepatitis or other liver diseases, difficulty passing urine, or moderate kidney disease.

Side effects

The most common adverse events are diarrhea, muscle cramps, fatigue, nausea, vomiting, and insomnia. Dizziness, headaches, pain, accidents, and colds have also been reported. In most cases, these phenomena pass and do not require discontinuation of the drug.

Side effects are listed below in descending order of frequency according to the organ classification: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (

Infections and parasitic diseases: common: runny nose.

Metabolic and nutritional disorders: common: anorexia nervosa.

Mental disorders: common: hallucinations**, agitation**, aggressive behavior**, abnormal dreams, nightmares**.

Nervous system disorders: common: syncope*, dizziness, insomnia; uncommon: convulsive seizures*; rare: extrapyramidal disorders; very rare: neuroleptic malignant syndrome.

Cardiac disorders: infrequently: bradycardia; rarely: sinoatrial and atrioventricular block.

Gastrointestinal disorders: very common: diarrhea, nausea; common: vomiting, dyspepsia; uncommon: gastrointestinal bleeding, stomach and duodenal ulcers.

Liver and biliary tract disorders: rare: impaired liver function, including hepatitis***.

Skin and subcutaneous tissue disorders: common: rash, itchy skin.

Musculoskeletal and connective tissue disorders: common: muscle spasms; very rare: rhabdomyolysis****.

From the side of the kidneys and urinary tract: often: urinary incontinence.

General disorders and disorders at the injection site: very often: headache; often: fatigue, pain of various localization.

Influence on the results of laboratory and instrumental studies: infrequently: slight increase in the concentration of muscle creatine kinase in the blood serum.

Injuries, intoxications, and manipulation complications: common: accidents.

Interaction

When prescribing donepezil, it is necessary to take into account the risk of previously unknown interactions with other drugs.

Donepezil and / or its metabolites do not inhibit the metabolism of theophylline, warfarin, cimetidine or digoxin in humans. Simultaneous use of digoxin or cimetidine does not affect the metabolism of donepezil.

In vitro studies have shown that cytochrome P 450 isoenzymes 3A4 and to a small extent 2D6 are involved in the metabolism of donepezil. In vitro studies of the drug show that ketoconazole and quinidine, inhibitors of CYP3A4 and 2D6, respectively, inhibit the metabolism of donepezil. Thus, these and other CYP3A4 inhibitors, such as itraconazole and erythromycin, and CYP2D6 inhibitors, such as fluoxetine, can inhibit the metabolism of donepezil. In studies on healthy volunteers, ketoconazole increased donepezil concentrations by approximately 30%. Enzyme inducers such as rifampicin, phenytoin, carbamazepine, and ethanol can reduce the concentration of donepezil in the blood. Since the magnitude of the inhibitory or inducing effect is unknown, such drug combinations should be used with extreme caution.

Donepezil may affect the activity of drugs with anticholinergic activity. Donepezil may show synergistic activity against drugs such as succinylcholine, other neuromuscular blockers, or cholinergic agonists or beta-blockers that affect the cardiac conduction system.

How to take, course of use and dosage

Inside.

Take in the evening (before going to bed), with a sufficient amount of water (100 ml).

Adults / Seniors

The initial dose is 5 mg once a day (at night). A dose of 5 mg / day should be taken for at least 1 month before reaching steady-state plasma concentrations of donepezil and evaluating the clinical effect. After a month, if necessary, the dose can be increased to 10 mg once a day.

The maximum daily dose is 10 mg. The duration of therapy is determined by the doctor.

If the next dose is missed, the next dose is taken at the usual time (do not take two doses at the same time). If you repeatedly miss taking the drug (a break of more than 1 week), you should consult your doctor.

Treatment should be prescribed and carried out by a specialist doctor who has experience in managing patients with Alzheimer’s dementia. The diagnosis should be made in accordance with generally accepted criteria (for example, DSM IV — Diagnostic and Statistical Manual of Mental Disorders fourth revision, ICD 10 — International Classification of Diseases Tenth revision). Treatment can only be carried out if there are people caring for the patient who are able to regularly monitor the use of the drug. Treatment is carried out as long as there is a therapeutic effect, which should be regularly evaluated. In the absence of a therapeutic effect, discontinuation of treatment should be considered.

After discontinuation of the drug, there may be a gradual decrease in the beneficial effect of treatment.

There is no information about the “withdrawal syndrome” in case of abrupt discontinuation of donepezil.

Patients with impaired renal and hepatic function

Patients with impaired renal function do not need to change the treatment regimen, as this condition does not affect the clearance of donepezil.

Due to the possible increase in exposure with mild or moderate hepatic impairment, dose increases should be made taking into account individual tolerability.

There are no data on the use of the drug in patients with severe hepatic impairment.

Children and teenagers

The drug is not intended for the treatment of children and adolescents.

Overdose

Overdose with donepezil can lead to a cholinergic crisis.

Symptoms: cholinergic crisis (severe nausea, vomiting, excessive salivation, sweating, bradycardia, low blood pressure, respiratory depression, loss of consciousness, convulsions). Increasing myasthenia gravis is possible, which can lead to death if the respiratory muscles are affected.

Treatment: in cases of suspected overdose, symptomatic therapy is indicated. As an antidote, you can use tertiary anticholinergic agents, in particular atropine sulfate in an initial dose of 1-2 mg intravenously, followed by titration of the dose-depending on the effect. It is not known whether donepezil and/or its metabolites are removed during dialysis (hemodialysis, peritoneal dialysis, or hemofiltration).

Special instructions

The individual response to donepezil therapy cannot be predicted. The efficacy of donepezil in patients with severe Alzheimer’s-type dementia, other types of dementia, or other types of memory impairment (such as age-related cognitive decline) has not been studied.

Anesthesia: As a cholinesterase inhibitor, donepezil may enhance succinyl-type muscle relaxation during anesthesia.

Cardiovascular diseases: donepezil may have a vagotonic effect on the heart rate (in particular, cause bradycardia). The potential for such an action may be important for patients with sinus node weakness syndrome or other supraventricular conduction disorders, such as sinoatrial or atrioventricular block.

Gastrointestinal disorders: as a cholinomimetic, donepezil may increase the secretion of acid in the stomach, so patients at risk of developing ulcers (for example, patients with a history of peptic ulcer disease or receiving nonsteroidal anti-inflammatory drugs) should be closely monitored. At the same time, placebo-controlled studies of donepezil did not show an increase in the incidence of peptic ulcers or gastrointestinal bleeding.

Genitourinary system: as a cholinomimetic, donepezil may cause difficulty in the outflow of urine.

Neurological disorders: as a cholinomimetic, donepezil can cause generalized seizures, but the appearance of seizures can also be a manifestation of Alzheimer’s disease. As a cholinomimetic, donepezil may increase or cause extrapyramidal disorders.

Impaired lung function: cholinesterase inhibitors should be used with caution in patients with a history of asthma or obstructive pulmonary disease due to their pharmacological effects.

Concomitant use of donepezil and other acetylcholinesterase inhibitors, as well as cholinergic system agonists or antagonists, should be avoided.

Severe hepatic impairment: there are no data on use in patients with severe hepatic impairment.

Neuroleptic malignant syndrome: This is a potentially life-threatening disorder characterized by hyperthermia (fever), muscle rigidity, autonomic nervous system disorders, altered consciousness, and elevated serum creatinine phosphokinase levels. Additional symptoms may include myoglobinuria (rhabdomyolysis) and acute renal failure.

There are very rare reports of the development of neuroleptic malignant syndrome associated with the use of donepezil, especially in patients who are also receiving concomitant therapy with antipsychotic drugs.

If the patient develops signs and symptoms of neuroleptic malignant syndrome or has an unexplained high fever without additional clinical manifestations, treatment should be discontinued.

Mortality in vascular dementia clinical trials: Three 6-month clinical trials were conducted in patients who met the NINDS-AIREN criteria for possible or probable vascular dementia (DM). The NINDS-AIREN criteria are designed to identify patients in whom dementia can only be associated with vascular causes, and exclude patients with Alzheimer’s disease.

In the first study, the incidence of death was 2/198 (1%) in the 5 mg donepezil hydrochloride group,5/206 (2.4%) in the 10 mg donepezil hydrochloride group, and 7/199 (3.5%) in the placebo group. In the second study, the incidence of death was 4/208 (1.9%) in the 5 mg donepezil hydrochloride group,3/215 (1.4%) in the 10 mg donepezil hydrochloride group, and 1/193 (0.5%) in the placebo group. In the third study, the incidence of death was 11/648 (1.7%) in the 5 mg donepezil hydrochloride group and 0/326 (0%) in the placebo group.

The incidence of death in all groups receiving donepezil hydrochloride in the three DM studies (1.7%) was numerically higher than in the placebo group (1.1%), but this difference was not statistically significant. Most of the deaths of patients taking donepezil hydrochloride or placebo occurred as a result of various vascular disorders that are expected in this population of elderly people with concomitant vascular lesions. Analysis of all serious non-fatal and fatal vascular disorders did not show a difference in the frequency of their occurrence in the groups receiving donepezil hydrochloride and placebo.

In the combined data from Alzheimer’s disease studies (n=4146), as well as the same Alzheimer’s disease studies with the addition of vascular dementia studies (total number of patients 6888), the mortality rates in the placebo groups are numerically higher than in the groups treated with donepezil hydrochloride.

The drug contains lactose, so it is not recommended for people suffering from lactase deficiency, galactosemia or glucose/galactose malabsorption syndrome.

Influence on the ability to drive motor vehicles and manage mechanisms

The drug has an effect on psychophysical abilities. Alzheimer’s dementia itself can be accompanied by a violation of the ability to drive a car and use complex equipment. In addition, the drug may cause fatigue, dizziness, muscle cramps (especially at the beginning of treatment or when the dose is exceeded). The patient’s ability to drive a car or use complex equipment should be evaluated by the doctor.

Form of production

Film-coated tablets 5 mg

14 tablets each in PVC/PVDC is an aluminum blister. 2 or 7 blisters together with the instructions for use are placed in a cardboard box.

Storage conditions

At a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 3 years. The drug should not be used after the expiration date indicated on the package.

Active ingredient

Donepezil

Conditions of release from pharmacies

By prescription

Dosage form

Tablets