Alzepil

Alzepil is a reversible selective substance that slows down acetylcholinesterase activity (it is the main type of cholinesterase that is located inside the human brain).

When cerebral cholinesterase is slowed down, the breakdown of acetylcholine (under the influence of donepezil) occurs, which transmits neuronal excitation pulses to the inside of the central nervous system. The slowing down of AChE activity under the action of donepezil is more powerful more than a thousand times than under the influence of butyrylcholinesterase, which is located inside the structures, mostly determined outside the central nervous system.

[1], [2], [3]

Indications Alzepila

It is used as a cure for signs of dementia in individuals with a weak or moderate Alzheimer's variety.

Release form

The release of the therapeutic substance is produced in tablets - 14 pieces inside the blister pack. In the box - 2 or 4 such packs.

Pharmacodynamics

At 1-time use of drugs in a dosage of 5 or 10 mg, the rate of inhibition of AChE activity is assessed within erythrocyte membranes and reaches, respectively, 63.6%, as well as 77.3%.

The inhibition of ache activity inside the erythrocytes under the therapeutic influence of Alzepil correlates with the changes taking place on the spectrum of the ADAS-cog (the indicated spectrum evaluates the cognitive activity of individuals with Alzheimer's).

Pharmacokinetics

Intra-plasma Cmax values are determined after 3-4 hours from the moment of drug administration. The Cmax level and AUC values increase in line with the dosage increase. The term half-life is approximately 70 hours, so in the case of drug reuse 1-fold, equilibrium indicators are gradually achieved per day (during the 21st day since the start of the course). At equilibrium elevations, only insignificant changes in the plasma level of donepezil and corresponding therapeutic activity are observed during the day. The absorption of drugs does not change with food intake.

Protein intraplasma synthesis of the drug is 95%. The pattern of distribution of drugs within different tissues has been studied to a limited extent. In theory, the active element, together with the decay products, can retain activity within the body for about 10 days.

Exchange processes and excretion.

Donepezil hydrochloride is excreted unchanged along with urine and is transformed under the influence of the hemoprotein P450 structure (this produces a large number of metabolic components, some of which are impossible to establish).

When 1-time use of 5 mg of donepezil, which is labeled 14C, the following indications are noted:

• part of the unpowered plasma element is equal to 30% of the accepted portion;
• a part of the 6-O-desmethyldonepesil component - 11% (only he has drug activity similar to donepezil);
• part of the substance donepezil-cis-N-oxide - 9%;
• part of the element 5-O-desmethyldoneepesil - 7%
• part of the glucuron conjugate (component 5-O-desmethyldonepezil) - 3%.

About 57% of the used dosage is determined inside the urine (of which 17% is in the form of donepezil), and another 14.5% is in the feces. From this we can conclude that the primary pathways of drug excretion are biotransformation, as well as excretion with urine.

Dosing and administration

It is necessary to take medication orally, before bedtime.

Therapy begins with the introduction of 5 mg of the drug 1 time per day (taken according to this scheme should be for at least 1 month). After this month, the dosage of the drug can be increased to 10 mg with 1-fold use per day (this is the maximum daily dose).

Therapy is carried out under the strict supervision of the attending physician, who has experience in the field of diagnosis and treatment of dementia of the Alzheimer's type.

It is possible to begin treatment only if there are people who are able to care for the sick and constantly monitor that he takes the medicine in time.

The implementation of the maintenance treatment is carried out until the therapeutic effect remains (the effectiveness of the therapy is required to be constantly evaluated). In the absence of drug exposure, the attending physician should consider the appropriateness of the subsequent use of Alzepil.

[7], [8]

Use Alzepila during pregnancy

It is forbidden to prescribe medication during pregnancy, except in situations where treatment is vital.

There is no information as to whether the medicine can be excreted with mother's milk. When it is necessary to use it during HB, the attending physician may decide to suspend breastfeeding.

[4], [5], [6]

Contraindications

It is contraindicated to use the drug in case of intolerance towards its components.

Side effects Alzepila

Most often, the drug causes the development of side effects such as diarrhea, vomiting, fatigue, muscle cramps, nausea and insomnia. In addition, there is evidence of cold, pain, dizziness and headaches. Typically, these symptoms pass on their own, without requiring discontinuation of the medication.

In addition to the violations described above, Alzepila can cause: a runny nose, extrapyramidal signs, fainting, bradycardia and hallucinations, and in addition nightmares, anorexia, dyspepsia, aggressive behavior, rash, arousal, epidermal itching and incontinence.

Overdose

In case of drug poisoning, a cholinergic crisis develops, in which symptoms such as hyperhidrosis, vomiting and severe nausea, drooling, bradycardia, seizures, decreased blood pressure, collapse and respiratory depression are noted. In addition, there may be a strong weakness in the musculature.

General support procedures are performed. Atropine is used as an antidote: you need to inject it in / in the method in increasing portions (until the desired effect is obtained).

Interactions with other drugs

The active component of the drug, together with its metabolites, reduce the rate of metabolic processes of such elements as warfarin and theophylline with digoxin or cimetidine. Moreover, in the case of a combination with cimetidine or digoxin, the exchange processes of Alzepil will remain unchanged. In vitro testing demonstrated that the metabolism of donepezil is realized under the action of an enzyme such as ZA4 from the structure of the hemoprotein P450, and at the same time 2D6 (the intensity is lower).

When determining the drug interaction in the form of in vitro, it was found that quinidine together with ketoconazole (this, respectively, inhibitors of 2D6 with CYP3A4) slow down the exchange of donepezil. From this it can be concluded that these and other inhibitors of CYP3A4 activity (among them, erythromycin and itraconazole with it) and with them inhibitors of CYP2D6 activity (for example, fluoxetine) can also slow down the metabolic processes of donepezil. During testing, in which volunteers participated, ketoconazole raised the average level of Alzepil by approximately 30%.

Substances that induce the activity of enzymes (among them carbamazepine with rifampicin, as well as phenytoin and alcoholic beverages) are capable of lowering the indicators of donepezil. Due to the fact that the degree of indicators of inducing or inhibiting effect is not defined, such combinations of medicines should be used with extreme caution.

Donepezil has the potential to interact with drugs that have an anticholinergic effect.

In addition, there is a risk of mutual potentiation when combining Alzepil with succinylcholine and other neuromuscular blockers, and in addition with cholinergic agonists or β-blockers that can affect the processes of cardiac conduction.

Introduction together with other cholinomimetics and 4-tychny holinoliticheskie components (for example, glycopyrolate) can provoke atypical changes in heart rate indicators, as well as blood pressure.

[9], [10]

Storage conditions

Alzepil needs to be kept in the places closed from access of the small child. Temperature level - no more than + 30 ° C.

[11]

Shelf life

Alzepil is allowed to apply within a 5-year term since the sale of the drug substance.

[12]

Application for children

Alzepil should not be used in pediatrics (for persons under the age of 18).

Analogs

Analogues of drugs are medicines Arizil, Aricept with Alzamed, Divara with Almer, and in addition, Servonex and Donerum with Doenza-Sanovel and Jasnal with Palixid-Richter.