Alzepil - instructions for use, dose, side effects, contraindications

Active substanceDonepezilDonepezil

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Alzepyl®

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EGIS ZAO Pharmaceutical Plant Hungary

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Dosage form: & nbspfilm coated tablets

Composition:

Active substance:

donepezil hydrochloride monohydrate 5.21 mg or 10.42 mg in one tablet (corresponding to 5 mg or 10 mg of donepezil hydrochloride);

Excipients:

cellulose microcrystalline 96 mg / 192 mg,

hydroxypropyl cellulose with a low degree of substitution (L-HPC B1) 24 mg / 48 mg, magnesium stearate 1 mg / 2 mg,

opedraj Y-1-7000 white 3 mg / 6 mg:

hypromellose 1,875 mg / 3,75 mg, titanium dioxide 0,9375 mg / 1,875 mg, macrogol 400 0,1875 mg / 0,375 mg.

Description:

Tablets 5 mg: white or almost white, round, biconvex tablets, film-coated, engraved "E 381" on one side, odorless or almost odorless.

Tablets 10 mg: white or almost white, round, biconvex tablets, film-coated, engraved "E 382" on one side, odorless or almost odorless.

Pharmacotherapeutic group:Cholinesterase inhibitor

ATX: & nbsp

N.06.D.A.02 Donepezil

Pharmacodynamics:

Donepezil is a selective and reversible inhibitor of acetylcholinesterase, which is the main predominant type of cholinesterase in the brain. Donepezil inhibits this enzyme more than 1000 times stronger than butyrylcholine esterase, an enzyme that is located mainly outside the central nervous system.

A single dose of 5 mg or 10 mg in an equilibrium state is accompanied by inhibition of cholinesterase activity (estimated in erythrocyte envelopes) by 63.6 and 77.3%, respectively. Slows down the progression of Alzheimer's disease, reduces the severity of cognitive symptoms, in some cases restores the daytime activity of patients and facilitates the care of them. Corrects behavioral disorders, reduces apathy, hallucinations and unreasonable repetitive movements.

Pharmacokinetics:

Suction

The maximum concentration (Cmah) donepezil in the blood plasma after oral administration are reached after about 3-4 hours. The concentrations in the plasma and the area under the curve AUC increase in proportion to the dose. The half-life of T1 / 2 is approximately 70 hours, so the systematic use of single doses leads to the achievement of an equilibrium state, which is achieved within 2-3 weeks after the initiation of therapy. In the equilibrium state, donepezil concentration in plasma and the correspondingPharmacodynamic activity varies slightly during the day. The intake of food does not affect the absorption of donepezil.

Distribution

The connection with plasma proteins is 95%. The connection with plasma proteins of the active metabolite - 6-O-des-methyldonepezil is unknown. The distribution was not studied. Donepezil and / or its metabolites can persist in the body for more than 10 days.

Metabolism and excretion

Donepezil is metabolized in the liver and is excreted, as well as its metabolites formed by the cytochrome P450 system, mainly in kidneys in unchanged form: approximately 57% of the administered dose was detected in urine (17% unchanged) and 14.5% in - stool .

After a single dose of 5 mg, the concentration of unmodified donepezil in plasma is 30% of the dose taken, 6-O-desmethyldonepezil is 11% (the only metabolite having similar activity with donepezil hydrochloride), donepezil-cis-N9%, 5-0-desmethyldonepezil - 7%, and 5-O-desmethyldonepezil glucuronic conjugate - 3%. The half-life of donepezil is about 70 hours.

Sex, race and smoking have no significant effect on the concentration of donepezil in plasma.

In patients with mild or moderate impairment of liver function, elevated equilibrium concentrations of donepezil in blood plasma can be observed.

Indications:

Symptomatic treatment of dementia of the Alzheimer's type of mild, moderate and severe.

Contraindications:

Hypersensitivity (including the derivatives of piperidine).

Pregnancy and lactation (see "Pregnancy and lactation period")

Children under 18 years of age (due to lack of clinical data)

Carefully:Chronic obstructive pulmonary disease, bronchial asthma, heart rhythm disorders, general anesthesia, peptic ulcer and duodenal ulcer, simultaneous use of NSAIDs, holinoblockers or other cholinesterase inhibitors.

Pregnancy and lactation:

Experience in the use of the drug during pregnancy and during lactation there. It is not known whether the drug is excreted in breast milk. Therefore, the use during pregnancy is contraindicated, if necessary, the drug during lactation, it is necessary to resolve the issue of stopping breastfeeding.

Dosing and Administration:

Inside. The drug is recommended in the evening before bedtime.

Treatment begins with taking 5 mg once a day and continues for at least 4 weeks to reach equilibrium concentrations of donepezil and assess the early clinical effect of therapy.

After 1 month, the dose of Alzepyl can be increased to 10 mg once a day, which is the maximum recommended daily dose.

Supportive therapy can be continued as long as the therapeutic effect remains, which should be evaluated regularly.

Patients with impaired hepatic and renal function

Patients with impaired liver function of mild and moderate severity, as well as with impaired renal function, do not need to change the treatment regimen, because these conditions do not affect the clearance of donepezil.

Side effects:

Depending on the frequency, side effects are defined as follows: very frequent (≥ 1/10), frequent (≥ 1/100 - <1/10), infrequent (≥ 1/1000 - <1/100), rare (≥ 1 / 10000 - <1/1000), very rare (<1/10000).

From the cardiovascular system: infrequently: bradycardia, rarely: sinoatrial block, atrioventricular block.

From the central nervous system and the peripheral nervous system: often: fainting *, fatigue, dizziness, headache, muscle cramps, insomnia, hallucinations, agitation, aggressive behavior, infrequent: convulsive attacks *, rarely: extrapyramidal symptoms.

From the gastrointestinal tract: very frequent: diarrhea, nausea, frequent: vomiting, dyspepsia, anorexia, gastrointestinal disorders, infrequent: bleeding from the gastrointestinal tract, stomach and duodenal ulcers.

From the kidneys, urinary and liver organs: often: urinary incontinence, rarely: a violation of the liver, including hepatitis.

From the skin and subcutaneous tissue: frequent: rash, itchy skin.

Laboratory studies: infrequently: a slight increase in the activity of the muscle isoform of creatine phosphokinase in the blood serum.

Other: pain of different localization, "cold".

* When examining patients with syncope or convulsive seizures, the possibility of cardiac blockade should be considered.

Overdose:

Symptoms: cholinergic crisis (pronounced nausea, vomiting, drooling, increased sweating, bradycardia, lowering of blood pressure, respiratory depression, collapse, convulsions). Possible myasthenia gravis, which can lead to a fatal outcome in the event of injury to the respiratory muscles.

Treatment: Symptomatic therapy. As an antidote can be used atropine IV in the initial dose of 1-2 mg, then the dose is selected depending on the effect. It is not known whether the donepezil and / or its metabolites in dialysis (hemodialysis, peritoneal dialysis or hemofiltration).

Interaction:

Donepezil and / or its metabolic products do not inhibit the metabolism of theophylline, warfarin, cimetidine, digoxin, thioridazine, risperidone and sertraline. Simultaneous reception of digoxin, cimetidine, thioridazine, risperidone and sertraline does not affect the metabolism of donepezil.

The use of donepezil simultaneously with levodopa / carbidopa for 21 days had no effect on the concentrations of these drugs in the blood.

The metabolism of donepezil involves cytochrome P450 - 3A4 isoenzyme and, to a lesser extent, 2D6. Ketoconazole and quinidine, which are inhibitors CYP3A4 and 2D6 respectively, suppress the metabolism donepezil. Consequently, these and other inhibitors CYP3A4, such as itraconazole and erythromycin, and inhibitors CYP2D6, such as fluoxetine, can inhibit donepezil metabolism. In healthy volunteers ketoconazole increased mean concentrations of donepezil by approximately 30%.The simultaneous use of donepezil does not affect the pharmacokinetics of ketoconazole.

Inductors of enzymes, such as rifampicin, phenytoin, carbamazepine and ethanol can cause a decrease in donepezil levels. However, the extent of such inhibitory or inducing action is not known, so use such agents in combination with donepezil should be used with caution.

Donepezil has an effect on the effect of drugs that have anticholinergic activity. In addition, with simultaneous application, donepezil can enhance the action of suxamethonium bromide, other muscle relaxants or agonists of cholinergic receptors and beta-adrenoblockers that affect the conductivity of the heart.

With simultaneous use of donepezil and agonists of cholinergic receptors, quaternary anticholinergics such as glycopyrronium bromide, cases of atypical changes in blood pressure and heart rate are described.

Special instructions:

Supportive therapy can be continued as long as the therapeutic effect remains. In this regard, the effect of donepezil should be regularly evaluated.If the drug ceases to function, it should be discarded. After discontinuation of treatment there is a gradual decrease in Alzepyl's action, information about the "withdrawal" syndrome in the event of a sharp discontinuation of the drug is not available. Donepezil can not predict an individual response to therapy.

Donepezil can enhance expression of neuromuscular blockade induced by depolarizing muscle relaxants during general anesthesia.

Cholinesterase inhibitors can have a vagotonic effect on the heart rate (in particular, cause bradycardia). The potential for such action may have important implications for patients with sick sinus syndrome or other supraventricular conduction disturbances, such as atrioventikulyarnaya or sinoatrial block.

In the period of treatment should be carefully monitored patients who are at risk of developing gastric and duodenal ulcers, for example, patients with gastric ulcer or a history of patients receiving nonsteroidal anti-inflammatory drugs, as Cholinomimetics can increase the secretion of hydrochloric acid in the stomach.At the same time, clinical studies showed no increase in the incidence of peptic ulcers or gastrointestinal bleeding compared with placebo.

Cholinesterase inhibitors can cause urinary retention, although this effect was not found in clinical studies.

It is believed that cholinesterase inhibitors can, to some extent, cause generalized convulsions, but convulsive activity may also be a manifestation of Alzheimer's dementia.

Given the cholinomimetic effect of cholinesterase inhibitors, they should be administered with caution to patients with bronchial asthma or obstructive pulmonary disease in anamnesis.

Effect on the ability to drive transp. cf. and fur:Dementia Alzheimer's type itself can be accompanied by a violation of the ability to drive and use sophisticated technology. In addition, the drug, mainly at the beginning of treatment or with increasing doses, can cause fatigue, dizziness and muscle cramps. The question of the ability of a patient with Alzheimer's dementia during taking donepezil to drive a car or use complicated equipment should be decided by the doctor after evaluating the individual reactionpatient for treatment.

Form release / dosage:Tablets film-coated 5 mg and 10 mg.

Packaging:

For 14 tablets in a blister of polyamide / al. foil / PVC / / al. foil or from PVC / PVDC / / al. foil. 2 or 4 blisters are packed together with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 30 ° C. Keep out of the reach of children.

Shelf life:5 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000228

Date of registration:16.02.2011

The owner of the registration certificate:EGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Manufacturer: & nbsp

EGIS PHARMACEUTICALS, Plc Hungary

Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Information update date: & nbsp25.11.2015

Illustrated instructions

Instructions

Alzepyl® (Alzepil®)