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

Clinical and pharmacological group: & nbsp

M-, N-holinomimetiki, incl. anticholinesterase agents

Included in the formulation

Alzepyl®

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EGIS ZAO Pharmaceutical Plant Hungary

Arisept®

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Pfizer Inc. USA

Dementis

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Elpen Pharmaceutical Co. Ink Greece

Jasnal®

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KRKA, dd, Novo mesto, AO

АТХ:

N.06.D.A.02 Donepezil

Pharmacodynamics:

Selective and reversible inhibitor of acetylcholinesterase, which is the predominant type of cholinesterase in the brain. Donepezil inhibits this enzyme is more than 1000 times stronger than butyrylcholinesterase contained mainly outside the central nervous system.

After a single dose of donepezil in doses of 5 mg or 10 mg, the degree of inhibition of acetylcholinesterase activity (estimated in erythrocyte envelopes) was 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 motions.

Pharmacokinetics:

The connection with plasma proteins is 95% (there is no information for the active metabolite 6-O-desmethyldonepezil). Half-life - 70 hours.Biotransformation in the liver with cytochrome P450 with the formation of active metabolites. Elimination - 57% of the kidneys, of which 17% unchanged; 14.5% - with feces.

Indications:

Symptomatic treatment of dementia of the Alzheimer's type of mild or moderate severity.

ICD-10

VI.G30-G32.G30 Alzheimer's disease

V.F00-F09.F00 * Dementia in Alzheimer's disease (G30 .- +)

Contraindications:

Pregnancy; lactation period (breastfeeding); Children under 18 years of age (due to lack of clinical data); hypersensitivity to the components of the drug; increased sensitivity to donepezil and piperidine derivatives.

Carefully:

Use with caution in patients with obstructive pulmonary disease in history (including bronchial asthma), with heart rhythm disorders, in anesthesia, and in patients with an increased risk of developing an ulcer (for example, patients with a history of peptic ulcer disease or receiving concomitant therapy non-steroidal anti-inflammatory drugs), concomitantly with the administration of non-steroidal anti-inflammatory drugs, cholinergic blockers or other cholinesterase inhibitors.

Pregnancy and lactation:

The category of FDA recommendations is not defined. Adequate and well-controlled studies on humans and animals have not been conducted. In pregnancy, use is only possible when the expected benefit of therapy for the mother exceeds the potential risk to the fetus.

There is no information on the penetration into breast milk. Do not apply.

Dosing and Administration:

Adults (including elderly patients) are given an initial dose of 5 mg once a day. Admission in the initial dose is continued for at least 4-6 weeks to reach equilibrium concentrations of donepezil and determine the early clinical effect of therapy. After 1 month, the dose can be increased to 10 mg per day.

The maximum daily dose is 10 mg.

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

Side effects:

From the cardiovascular system: infrequently bradycardia; rarely - sinoatrial blockade, AV blockade.

From the nervous system: often - a syncope, increased fatigue, dizziness, headache, insomnia, hallucinations, agitation, aggressive behavior; infrequently - convulsive seizures; rarely - extrapyramidal symptoms.

From the digestive system: very often - diarrhea, nausea; often - vomiting, indigestion, anorexia, gastrointestinal disorders; infrequently - bleeding from the digestive tract, ulcers of the stomach and duodenum.

From the urinary system: often - urinary incontinence; rarely - a violation of the liver, including hepatitis.

Dermatological reactions: often - a rash, itchy skin.

Laboratory research: infrequently, a slight increase in the activity of the muscle fraction of creatine kinase in the blood serum.

Other: pain of different localization, flu-like syndrome, muscle cramps.

Overdose:

Symptoms: cholinergic crisis (severe nausea, vomiting, excessive salivation, sweating, bradycardia, lowering of blood pressure, respiratory depression, collapse and convulsions).

Treatment: symptomatic therapy. As an antidote, tertiary anticholinergics can be used, in particular atropine in the initial dose of 1-2 mg intravenously, 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, being an inhibitor of cholinesterase, can enhance the muscle relaxancy of succinylcholine type during anesthesia.

Inhibitors of cytochrome P450 (itraconazole, ketoconazole, fluoxetine, quinidine, erythromycin) provoke an increase in donepezil concentration in the blood serum.

Inductors of cytochrome P450 (carbamazepine, rifampicin, phenytoin, ethanol) reduce the concentration of donepezil in the blood serum.

Non-steroidal anti-inflammatory drugs and preparations for general anesthesia increase the likelihood of adverse reactions.

Holinoblokatory - weakening the effect.

Holinomimetiki - mutual enhancement of the effect.

Special instructions:

Treatment should be prescribed and conducted by a physician with experience in managing patients with Alzheimer's disease.

Supportive therapy can be continued as long as the therapeutic effect remains. If the therapeutic effect disappears, then donepezil should be canceled. After discontinuation of treatment, there is a gradual decrease in donepezil, there is no information on withdrawal syndrome in the event of a sudden discontinuation. It is impossible to predict an individual reaction to donepezil therapy.

The efficacy of donepezil in patients with severe dementia of the Alzheimer's type, other types of dementia, or other types of memory impairment (eg, age-related deterioration of cognitive function) has not been studied.

Cholinesterase inhibitors (including donepezil) can have a vagotonic effect on the heart rate (in particular, cause bradycardia). The potential for such an action may be important for patients with syndrome of weakness of the sinus node or other disorders of supraventricular conduction, such as sinoatrial or AV blockade.

It is believed that cholinomimetics are capable of causing generalized convulsions. However, the appearance of seizures during treatment with donepezil can also be a manifestation of Alzheimer's disease.

The safety and efficacy of donepezil in children has not been studied, so the drug is not recommended for this category of patients.

Dementia Alzheimer's type itself can be accompanied by a disruption in the ability to drive and use sophisticated technology. Besides, donepezil, 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 the use of donepezil to drive a car or use complicated equipment should be decided by the doctor after assessing the patient's individual response to treatment.

Instructions

Donepezil (Donepezilum)