Alzepil

Alzepil is a reversible selective substance that inhibits the activity of acetylcholinesterase (it is the main type of cholinesterase that is found inside the human brain). [ 1 ]

When cerebral cholinesterase is slowed down, the breakdown of acetylcholine (under the influence of donepezil), which transmits impulses of neuronal excitation into the CNS, is blocked. The slowing down of AChE activity under the influence of donepezil is more than a thousand times more powerful than under the influence of butyrylcholinesterase, which is located inside structures that are mostly determined outside the CNS.

[ 2 ]

Indications Alzepila

It is used as a treatment for signs of dementia in people with mild to moderate Alzheimer's disease.

Release form

The therapeutic substance is released in tablets - 14 pieces inside a blister pack. In a box - 2 or 4 such packs.

Pharmacodynamics

With a single use of the drug in a portioned dosage of 5 or 10 mg, the rate of suppression of AChE activity is estimated within erythrocyte membranes and reaches, respectively, 63.6% and 77.3%. [ 3 ]

Inhibition of AChE activity inside erythrocytes under the therapeutic influence of Alzepil correlates with changes occurring on the ADAS-cog spectrum (this spectrum evaluates cognitive activity in individuals with Alzheimer's). [ 4 ]

Pharmacokinetics

Intraplasmic Cmax values are determined after 3-4 hours from the moment of drug administration. Cmax level and AUC values increase in accordance with the increase in dosage. The half-life term is approximately 70 hours, therefore, in case of repeated use of the drug once a day, equilibrium values are gradually achieved (over the 21st day from the start of the course). At equilibrium marks, only an insignificant change in the plasma level of donepezil and the corresponding therapeutic activity during the day is observed. Absorption of the drug does not change with food intake.

Protein intraplasmic synthesis of the drug is 95%. The scheme of drug distribution in different tissues has been studied to a limited extent. In theory, the active element together with decay products can remain active in the body for about 10 days.

Metabolic processes and excretion.

Donepezil hydrochloride is excreted unchanged in the urine and is transformed under the influence of the structure of hemoprotein P450 (in this case, a large number of metabolic components are formed, some of which cannot be identified).

With a single use of 5 mg of donepezil, which is labeled with 14C, the following indications are noted:

• the portion of intraplasmic unchanged element is equal to 30% of the accepted portion;
• part of the component 6-O-desmethyldonepezil – 11% (only it has a medicinal activity similar to donepezil);
• part of the substance donepezil-cis-N-oxide – 9%;
• part of the element 5-O-desmethyldonepezil – 7%;
• part of the glucuronic conjugate (component 5-O-desmethyldonepezil) – 3%.

About 57% of the dose used is recovered in urine (17% of which is in the form of donepezil) and another 14.5% in feces. This suggests that the primary routes of drug excretion are biotransformation and urinary excretion.

Dosing and administration

The medication must be taken orally, before bedtime.

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

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

Treatment can only be started if there are people who can care for the patient and constantly monitor that he takes the medication on time.

Maintenance treatment is performed until the therapeutic effect is maintained (the effectiveness of therapy must be constantly assessed). In the absence of drug effect, the attending physician should consider the advisability of further use of Alzepil.

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Use Alzepila during pregnancy

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

There is no information yet on whether the drug can be excreted in breast milk. If it is necessary to use it during breastfeeding, the attending physician may decide to stop breastfeeding.

[ 5 ], [ 6 ]

Contraindications

It is contraindicated to use the medicine if you are intolerant to any of its components.

Side effects Alzepila

Most often, the drug causes the development of such side effects as diarrhea, vomiting, fatigue, muscle cramps, nausea and insomnia. In addition, there are reports of colds, pain, dizziness and headaches. Usually, such symptoms go away on their own, without requiring discontinuation of the medication.

In addition to the above-described disorders, taking Alzepil can provoke: runny nose, extrapyramidal symptoms, fainting, bradycardia and hallucinations, as well as nightmares, anorexia, dyspepsia, aggressive behavior, rash, a feeling of excitement, epidermal itching and urinary incontinence.

Overdose

In case of poisoning with the drug, a cholinergic crisis develops, which is characterized by symptoms such as hyperhidrosis, vomiting and severe nausea, salivation, bradycardia, convulsions, decreased blood pressure, collapse and respiratory depression. In addition, severe weakness in the muscular area may be observed.

General supportive procedures are performed. Atropine is used as an antidote: it must be administered intravenously in increasing doses (until the desired effect is achieved).

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. At the same time, in the case of a combination with cimetidine or digoxin, the metabolic processes in Alzepil will remain unchanged. In vitro testing has shown that the metabolism of donepezil is realized under the action of an enzyme of the 3A4 type from the structure of hemoprotein P450, and also 2D6 (lower intensity).

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

Substances that induce enzyme activity (including carbamazepine with rifampicin, as well as phenytoin and alcoholic beverages) can reduce donepezil levels. Since the extent of the inducing or inhibiting effects has not been determined, such combinations of medications should be used with extreme caution.

Donepezil has the potential to interact with medications that have anticholinergic effects.

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

Administration together with other cholinomimetics and 4-aryl anticholinergic components (eg, glycopyrrolate) can provoke atypical changes in heart rate and blood pressure.

[ 8 ], [ 9 ]

Storage conditions

Alzepil should be stored in places closed to small children. Temperature level – no more than +30°C.

Shelf life

Alzepil can be used within a 5-year period from the date of sale of the medicinal substance.

Application for children

Alzepil cannot be used in pediatrics (in persons under 18 years of age).

Analogues

The analogs of the drug are the medications Arizil, Arisept with Alzamed, Divare with Almer, and in addition Servonex and Donerum with Doenza-Sanovel and Yasnal with Palixid-Richter.